Academic literature on the topic 'Frequency of cardiac reductions'

We studied the effects of synchronous cardiac cycle-specific high-frequency jet ventilation (HFJV) in pentobarbital-anesthetized, splenectomized, closed-chest dogs to test the hypothesis that phasic inspiratory increases in intrathoracic pressure (ITP) selectively timed to specific periods of the cardiac cycle have different hemodynamic effects during both hypovolemia (acute hemorrhage, 20 ml/kg) and neurogenic vasomotor shock (hexamethonium, 10 mg/kg) than those observed during normovolemic control conditions. Ventricular stroke volumes (SV) were measured by electromagnetic flow probes. The influence of changes in venous return (VR) on the subsequent hemodynamic response to synchronous HFJV was analyzed using instantaneous VR curves (M. R. Pinsky, J. Appl. Physiol. 56:765–771, 1984). During hemorrhage the VR curve was shifted leftward with concomitant reductions in apneic SV (15.4 +/- 3.8 to 11.2 +/- 3.6 ml, mean +/- SD), (P less than 0.01) that were accentuated by HFJV (P less than 0.01), except when the phasic inspiratory increases in ITP during HFJV were timed to occur during late diastole (-4% apneic SV, NS). SV was greater with late diastolic pulses than with other timed synchronous ITP pulses during hypovolemia (P less than 0.01). During ganglionic blockade, arterial pressure decreased (139 +/- 14 to 76 +/- 18 Torr, P less than 0.001), but VR was preserved at control levels, and no significant cardiac cycle-specific HFJV effects occurred. We conclude that SV reductions associated with positive-pressure ventilation during acute hypovolemia are minimized by HFJV synchronized to late diastole but that this effect is preload dependent.

BackgroundCreatine kinase (CK) testing in the setting of suspected cardiac injury is commonly performed yet rarely provides clinical value beyond troponin testing. We sought to evaluate and reduce CK testing coupled with troponin testing by 50% or greater.MethodsWe performed root cause analysis to study prevailing processes and patterns of CK testing. We developed new institutional guidelines, removed CK from high-volume paper and electronic order bundles and conducted academic detailing for departments with highest ordering frequency. We evaluated consecutive patients at Sunnybrook Health Sciences Centre between 1 January 2018 and 31 March 2020 who had either a CK or troponin level measured. We prespecified successful implementation as a reduction of 50% in total CK orders and a decrease in the ratio of CK-to-troponin tests to one-third or less. We retained additional data beyond our study period to assess for sustained reductions in testing.ResultsTotal CK tests decreased over the study period from 3963 to 2111 per month, amounting to a 46.7% reduction (95% CI 33.2 to 60.2; p<0.001) equalling 61 fewer tests per hospital day. Troponin testing did not significantly change during the intervention. Ratio of CK-to-troponin tests decreased from 0.91 to 0.49 (p<0.001). The reduction coincided with changes to order-sets, was observed across all clinical units and was sustained during additional months beyond the study period. These reductions in testing resulted in a projected annual cost savings of C$28 446.ConclusionsWe demonstrate that a low-cost and feasible quality improvement initiative may lead to significant reduction in unnecessary CK testing and substantial savings in healthcare costs for patients with suspected cardiac injury.

The exact mechanisms for the decrease in R-R interval (RRI) during acute physiological hyperinsulinemia with euglycemia are unknown. Power spectral analysis of RRI and microneurographic recordings of muscle sympathetic nerve activity (MSNA) in 16 normal subjects provided markers of autonomic control during 90-min hyperinsulinemic/euglycemic clamps. By infusing propranolol and insulin ( n = 6 subjects), we also explored the contribution of heightened cardiac sympathetic activity to the insulin-induced decrease in RRI. Slight decreases in RRI ( P < 0.001) induced by sevenfold increases in plasma insulin could not be suppressed by propranolol. Insulin increased MSNA by more than twofold ( P < 0.001), decreased the high-frequency variability of RRI ( P< 0.01), but did not affect the absolute low-frequency variability of RRI. These results suggest that reductions in cardiac vagal tone and modulation contribute at least in part to the reduction in RRI during hyperinsulinemia. Moreover, more than twofold increases in MSNA occurring concurrently with a slight and not purely sympathetically mediated tachycardia suggest regionally nonuniform increases in sympathetic activity during hyperinsulinemia in humans.

Objective The present study aimed to assess the effects of exercise with dietary restriction on cardiac autonomic activity, arterial stiffness, and cardiovascular biomarkers in obese individuals. Methods Seventeen obese adults completed an 8-week exercise and dietary program. Anthropometry, body composition, and multiple biochemical markers were measured. We used carotid-femoral pulse wave velocity (cfPWV), brachial-ankle pulse wave velocity (baPWV), central blood pressure, and augmentation index (AIx) to assess arterial stiffness. To determine cardiac autonomic activity, heart rate variability (HRV) was analyzed by standard deviation of normal-to-normal intervals (SDNN), square root of the mean squared differences of successive normal-to-normal intervals (RMSSD), total power (TF), low-frequency power in normalized units (LFnu), high-frequency power in normalized units (HFnu), and low-frequency power/high-frequency power (LF/HF). Results Following the exercise and diet intervention, obese subjects had significant reductions in body weight, body mass index, body fat percentage, brachial systolic blood pressure, and resting heart rate, and they had shown improvements in blood chemistry markers such as lipid profiles, insulin, and high-sensitivity C-reactive protein. There was a significant reduction in both cfPWV and baPWV following the intervention when compared to baseline levels. Moreover, the AIx and aortic systolic blood pressure were significantly reduced after the intervention. The diet and exercise intervention significantly increased cardiac autonomic modulation (determined by improved SDNN, RMSSD, TP LF, HF, and LF/HF), which was partly due to changes in heart rate, insulin resistance, and the inflammatory pattern. Furthermore, we observed a correlation between enhanced cardiac autonomic modulation (LF/HF) and decreased arterial stiffness, as measured by central cfPWV and systemic baPWV. Discussion An 8-week combined intervention of diet and exercise is effective in improving cardiac autonomic function in obese adults, with an associated decrease in central and systemic arterial stiffness.

Nrf2protects the lung from adverse responses to oxidants, including 100% oxygen (hyperoxia) and airborne pollutants like particulate matter (PM) exposure, but the role ofNrf2on heart rate (HR) and heart rate variability (HRV) responses is not known. We hypothesized that genetic disruption ofNrf2would exacerbate murine HR and HRV responses to severe hyperoxia or moderate PM exposures.Nrf2-/-andNrf2+/+mice were instrumented for continuous ECG recording to calculate HR and HRV (low frequency (LF), high frequency (HF), and total power (TP)). Mice were then either exposed to hyperoxia for up to 72 hrs or aspirated with ultrafine PM (UF-PM). Compared to respective controls, UF-PM induced significantly greater effects on HR (P<0.001) and HF HRV (P<0.001) inNrf2-/-mice compared toNrf2+/+mice.Nrf2-/-mice tolerated hyperoxia significantly less thanNrf2+/+mice (~22 hrs;P<0.001). Reductions in HR, LF, HF, and TP HRV were also significantly greater inNrf2-/-compared toNrf2+/+mice (P<0.01). Results demonstrate thatNrf2deletion increases susceptibility to change in HR and HRV responses to environmental stressors and suggest potential therapeutic strategies to prevent cardiovascular alterations.

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this “deconditioning response” could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of −6° head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15–0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate × stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05–0.15 Hz) power of systolic BP variability decreased after bed rest (−22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

Low-frequency (less than 0.15 Hz) fluctuations of heart rate are increased by maneuvers, such as standing or hemorrhage, that increase sympathetic outflow to the heart and vasculature. To test the hypothesis that low-frequency heart rate fluctuations provide an index of sympathetic efferent activity, we compared power spectral measures of heart rate variability with two measures of sympathetic outflow, peroneal nerve sympathetic activity and antecubital vein plasma norepinephrine concentrations. Autonomic outflow was varied with graded stepwise infusions of nitroprusside and phenylephrine, which lowered or raised average diastolic pressures by approximately 15 mmHg. Before vasoactive drug infusions, no spectral measure of heart rate variability correlated significantly with muscle sympathetic activity, plasma norepinephrine concentration, average heart rate, or arterial pressure. During increases of muscle sympathetic activity and probable reductions of cardiac vagal activity induced by nitroprusside, the fraction of heart rate spectral power at low frequencies, but not the absolute value, correlated significantly with muscle sympathetic activity and plasma norepinephrine. However, during reductions of muscle sympathetic activity and probable elevations of cardiac vagal activity induced by phenylephrine, no measure of heart rate variability correlated significantly with muscle sympathetic activity. These findings can be explained by a model of heart rate control in which low-frequency heart rate fluctuations result from changing levels of both the sympathetic and parasympathetic inputs to the sinoatrial node.

The present study investigated the effects of long-duration exercise on heart rate variability [as a marker of cardiac vagal tone (VT)]. Heart rate variability (time series analysis) was measured in mongrel dogs ( n = 24) with healed myocardial infarctions during 1 h of submaximal exercise (treadmill running at 6.4 km/h at 10% grade). Long-duration exercise provoked a significant (ANOVA, all P < 0.01, means ± SD) increase in heart rate (1st min, 165.3 ± 15.6 vs. last min, 197.5 ± 21.5 beats/min) and significant reductions in high frequency (0.24 to 1.04 Hz) power (VT: 1st min, 3.7 ± 1.5 vs. last min, 1.0 ± 0.9 ln ms2), R-R interval range (1st min, 107.9 ± 38.3 vs. last min, 28.8 ± 13.2 ms), and R-R interval SD (1st min, 24.3 ± 7.7 vs. last min 6.3 ± 1.7 ms). Because endurance exercise training can increase cardiac vagal regulation, the studies were repeated after either a 10-wk exercise training ( n = 9) or a 10-wk sedentary period ( n = 7). After training was completed, long-duration exercise elicited smaller increases in heart rate (pretraining: 1st min, 156.0 ± 13.8 vs. last min, 189.6 ± 21.9 beats/min; and posttraining: 1st min, 149.8 ± 14.6 vs. last min, 172.7 ± 8.8 beats/min) and smaller reductions in heart rate variability (e.g., VT, pretraining: 1st min, 4.2 ± 1.7 vs. last min, 0.9 ± 1.1 ln ms2; and posttraining: 1st min, 4.8 ± 1.1 vs. last min, 2.0 ± 0.6 ln ms2). The response to long-duration exercise did not change in the sedentary animals. Thus the heart rate increase that accompanies long-duration exercise results, at least in part, from reductions in cardiac vagal regulation. Furthermore, exercise training attenuated these exercise-induced reductions in heart rate variability, suggesting maintenance of a higher cardiac vagal activity during exercise in the trained state.

BACKGROUND: Acute myocardial infarction places additional demands on an already compromised myocardium. Relaxing music can induce a relaxation response, thereby reversing the deleterious effects of the stress response. OBJECTIVES: To compare the effects of relaxing music; quiet, uninterrupted rest; and "treatment as usual" on anxiety levels and physiological indicators of cardiac autonomic function. METHODS: A 3-group repeated measures experimental design was used. Forty-five patients, 15 per group, with acute myocardial infarction were assigned randomly to 20 minutes of (1) music in a quiet, restful environment (experimental group); (2) quiet, restful environment without music (attention); or (3) treatment as usual (control). Anxiety levels and physiological indicators were measured. RESULTS: Immediately after the intervention, reductions in heart rate, respiratory rate, and myocardial oxygen demand were significantly greater in the experimental group than in the control group. The reductions in heart rate and respiratory rate remained significantly greater 1 hour later. Changes in heart rate, respiratory rate, and myocardial oxygen demand in the attention group did not differ significantly from changes in the other 2 groups. The 3 groups did not differ with respect to systolic blood pressure. Increases in high-frequency heart rate variability were significantly greater in the experimental and attention groups than in the control group immediately after the intervention. State anxiety was reduced in the experimental group only; the reduction was significant immediately and 1 hour after the intervention. CONCLUSIONS: Patients recovering from acute myocardial infarction may benefit from music therapy in a quiet, restful environment.

Patients with Type 2 Diabetes (T2D) are at risk of developing macrovascular (cardiac, cerebrovascular, peripheral arterial disease) and microvascular (nephropathy, neuropathy, retinopathy) complications. Glycemic control improves only microvascular outcomes. However, some SGLT-2 inhibitors and GLP1-R agonists have proven beneficial in macrovascular conditions. Canagliflozin is an SGLT2 inhibitor that provides sustained reductions in HbA1c, blood pressure and weight. Remarkably, as CANVAS program and CREDENCE trial demonstrated, canagliflozin promotes significant reductions in the frequency of atherosclerotic cardiovascular events, hospitalizations for heart failure and renal outcomes. In addition, real-world studies have confirmed the results of clinical trials in clinical practice. Therefore, canagliflozin should be considered a first-line therapy in the management of T2D patients in order to reduce both micro- and macrovascular complications.

The mechanisms responsible for maintenance of AF remain poorly understood. This thesis examines the frequency domain characteristics of AF in order to gain further insights into this arrhythmia. Through a series of studies involving patients undergoing catheter ablation for atrial fibrillation, intra-cardiac electrograms of AF were collected and analysed using Fast Fourier Transform to derive frequency domain parameters of dominant frequency (DF) and organization index (OI). It was found that intravenous flecainide reduced DF of AF, but only an associated increase in OI was predictive of successful return to sinus rhythm. In another study of patients having catheter ablation for persistent AF, a higher OI post-ablation was found to be associated with medium-term freedom of AF, suggesting that OI may be a useful guide to determine the extent of radiofrequency ablation needed. The effects of vagal blockade with atropine were also studied and compared with that of catheter ablation using a stepwise strategy of isolating the pulmonary veins, linear ablation and complex fractionated electrogram ablation, without deliberately targeting ganglionated plexi. This showed that atropine reduced DF and increased OI of AF electrograms, while decreasing mean RR intervals, standard deviation of RR intervals and 5th percentile of RR intervals. The directional changes of all the above parameters mirrored that of catheter ablation, suggesting that vagal blockade and catheter ablation not deliberately aimed at autonomic tissue can have similar effects on the frequency spectrum of AF, probably mediated through modulation of the autonomic tone. The relationship of regional DF and electrogram complexity as assessed by automated measurement of complex fractionated electrogram – mean (CFE-mean) were also compared, pre and post-ablation of the left atrium. There appeared to be only a modest correlation between the two and this was further weakened following ablation, suggesting that these are possibly separate substrate entities.

Accurate knowledge of the spatial and temporal temperature distribution within the myocardium would be of value in predicting lesion size and shape during radio frequency (RF) catheter ablation. Finite difference solutions of the Laplace equation, which models power delivery by the RF catheter, and the Bioheat equation, which predicts temperature rise within the myocardium, were developed to accurately model lesion generation during RF ablation. This model included the effects of tissue and electrode heat conduction, tissue perfusion, and the convective losses within the heart chamber. Results indicated that the convective effects of blood flow within the heart chamber over the catheter were significant. More power could be applied before reaching 100°C when these convective cooling effects were included than without them. Electrodes of higher thermal conductivity were determined, by both numerical simulations and in vitro experiments, to promote more heat flux away from the electrode-tissue interface. Consequently, more power could be delivered resulting in larger lesions. The effects of tissue perfusion on intramyocardial temperatures and lesion size were investigated. Perfusion was found to decrease both of these compared to non-perfused tissue. This was particularly evident with longer energy delivery times. The power density model was used to characterize the power density relationship for both single and arrays of multiple catheter electrodes. The results from this model were used to design and implement a multipolar ablation technique. In vitro and in vivo experiments proved this technique was useful for generating longer, deeper lesions than traditional techniques and holds promise for treating atrial fibrillation and flutter. This technique may offer insight into the effects of thermal transfer properties on lesion formation. Furthermore, this model may be useful as a tool to design more effective catheters and energy delivery procedures to produce lesions of desired size and shape.

In mammalian hearts, initiation of the heartbeat occurs in a region of specialised pacemaker cells known as the sinoatrial node (SAN). The SAN is a highly complex spatially distributed structure which displays considerable cellular heterogeneity and is subject to complex electrotonic interactions with the surrounding atrial tissue. In this study, biophysically detailed ionic models of central and peripheral SAN pacemaker cells are described. These models are able to accurately reproduce experimental recordings of the membrane potential from central and peripheral SAN tissue. These models are used to investigate frequency synchronisation of electrically coupled cardiac pacemaker cells. Based on simulation results presented, it is proposed that cellular heterogeneity in the SAN plays an important role in achieving rhythm coordination and possibly contributes to the efficient activation of the surrounding atrial myocardium. This represents an important, previously unexplored, mechanism underlying pacemaker synchronisation and cardiac activation in vivo. A spatial-gradient model of action potential heterogeneity within the SAN is then formulated using a large-scale least squares optimisation technique. This model accurately reproduces the smooth spatial variation in action potential characteristics observed in the SAN. One and two dimensional models of the intact SAN are then formulated and three proposed models of SAN heterogeneity are investigated: 1) the discrete-region model, in which the SAN consists of a compact central region surrounded by a region of transitional pacemaker cells, 2) the gradient model, in which cells of the SAN exhibit a smooth variation in properties from the centre to the periphery of the SAN, and 3) the mosaic model, in which SAN and atrial cells are scattered throughout the SAN region with the proportion of atrial cells increasing towards the periphery. Simulation results suggest that the gradient model achieves frequency entrainment more easily than the other models of SAN heterogeneity. The gradient model also reproduces action potential waveshapes and a site of earliest activation consistent with experimental observations in the intact SAN. It is therefore proposed that the gradient model of SAN heterogeneity represents the most plausible model of SAN organisation.

In this study we evaluated the validity of well-known human electrocardiographic markers of myocardial pathology in Dorper sheep. These markers are all properties of PVC`s, namely the duration of the QRS complex of PVC`s, the presence of notching of the QRS complex of PVC`s and change in the ST segment of PVC`s. It was shown that these three electrocardiographic phenomena correlate with myocardial pathology in the hearts of Dorper sheep. We also described a new electrocardiographic indicator of myocardial pathology in the hearts of Dorper sheep, namely an increase in the frequency of cardiac memory T waves, induced by PVC`s, as a new electrocardiographic surrogate for myocardial pathology. This study was possible, because we knew from a pilot study that our specific method of inducing right ventricular PVC`s is known to induce structural alterations in the myocardium of Dorper sheep. The guidewire was situated in the right ventricle and we examined the histological appearance of only the left ventricle, in order to exclude any possible changes caused by the wire itself. Although this study was not designed to answer the question of whether PVC`s can be a cause of, rather than a consequence of, structural myocardial disease, it is an important method, because in this way every wether serves as it`s own histological control for electrocardiographic changes. We started with normal Dorper wethers, induced right ventricular PVC`s and these PVC`s had certain characteristics, as described in chapter 3. We know what the normal histological appearance of Dorper wethers are and the electrocardiographic appearance of PVC`s in the normal heart. At the end of the study certain changes appeared in the PVC`s, namely the QRS duration increased, notching appeared and the ST segment disappeared. Furthermore, at this stage the histological appearance of the left ventricle resembled that of myocarditis. At the end of the study (abnormal myocardial histology) we also noted an increase of 42 % in the incidence of cardiac memory T waves following PVC`s, when compared to the beginning of the study (normal myocardial histology). What might the reason be for the abnormal left ventricular histology ? As this study was not designed to answer that question this is open to debate. It might be the anaesthetic, the wire itself or the PVC`s. As already discussed we induced right ventricular PVC`s and afterwards we examined the left ventricles, therefore these histological alterations cannot be a direct consequence of the guidewire itself. It is suggested that it will be worthwhile to explore the possibility that PVC`s may be a cause of myocardial disease and that it is not always a consequence of established myocardial disease.
Thesis (PhD (Human Physiology))--University of Pretoria, 2006.
Physiology
unrestricted

In the monograph the literature information about the nature of stochastic processes and their participation in the work of the brain and human behavior. Established that the real cognitive processes and mental functions associated with the procedural side of external events and the stochastic properties of the internal dynamics of brain systems in the form of fluctuations of their parameters, including cardiac rhythm generation and sensorimotor reactions. Experimentally proved that the dynamics of the measured physiological processes is in the range from chaotic regime to a weakly deterministic — fractal mode. Fractal mode determines the maximum order and organization homeostasis of cognitive processes and States, as well as high adaptive ability of the body systems with fractal properties. The fractal-chaotic dynamics is a useful quality to examine the actual physiological and psychological systems - a unique numerical identification of the order and randomness of the processes through calculation of fractal indices. The monograph represents the results of many years of experimental studies of the reflection properties of stochastic sensorimotor reactions, as well as stochastic properties of heart rate in children, Teens and adults in the age aspect in the speech activity and the perception of different kinds of music with its own frequency-spectral structure. Designed for undergraduates, graduate students and researchers that perform research and development on cognitive psychology and neuroscience.

Cancer therapeutics may induce cardiac damage in the left and the right ventricle. Radiotherapy most frequently induces valvular damage, carotid stenosis, and coronary artery disease. Pericardial disease may be due to both chemo- and radiotherapy. The manifestations of both chemo- and radiotherapy can develop acutely but also become overt years after their performance, in particular after radiotherapy. The main cardiac damage of cancer therapeutics-related cardiac dysfunction (CTRCD) corresponds to the reduction of left ventricular (LV) systolic function. The Expert Consensus document from ASE and EACVI has defined CTRCD as a decrease in LV ejection fraction (LVEF) of greater than 10 percentage points, to a value less than 53%. The accurate calculation of LVEF at baseline and during follow-up is extremely important. The assessment of LV longitudinal function, in particular of speckle tracking-derived global longitudinal strain (GLS), can provide additional information, allowing early, subclinical detection of CTRCD. The ideal strategy could be to compare the measurements of GLS obtained during chemotherapy, with the one obtained at baseline. An integrated approach with the use of echocardiography at standardized, clinical preselected intervals with biomarker (ultrasensitive troponin) assessment prior to each chemotherapy cycle could be suggested in patients at high risk of CTRCD. Follow-up after therapy should depend on the type of chemotherapy/radiotherapy and the presence/absence of on-therapy CTRCD. Long-term follow-up should be planned after radiotherapy.

The past 20 years have seen significant changes in both the demographics and natural history of many cardiovascular diseases. Important reductions in case-fatality rates (such as in acute coronary syndromes) have resulted from improved diagnostics and treatment options and better understanding of natural history. For others (such as infective endocarditis), improvements have been limited and disappointing. While advances in therapy and the scientific evidence underpinning treatments have been crucial, the importance of accurate diagnosis has remained a key element for progress. Many of the principles needed for diagnosis are constant: the pre-eminence of a focused, accurate history, complete physical examination, and timely and relevant investigation endures. It is essential to have a secure knowledge of the strengths and limitations of interpretation of a frequently bewildering array of tests. Progress in this field has been rapid; advances in ultrasound, scintigraphy, and cardiac magnetic resonance stand out at the interface between structure and function central to good patient care.

Admission to ICU with severe limb weakness, or the occurrence of a respiratory or motor deficit, and failure to wean from mechanical ventilation while in the intensive care unit are common presentations of a neuromuscular disease. Neuromuscular diseases include neuronopathies, neuropathies, myasthenic syndromes, and myopathies. An accurate neurological examination and complementary investigations are necessary for both diagnosis and for evaluating the severity of the disease. Assessment of respiratory muscle function is a key step in deciding the need for mechanical ventilation and subsequently its weaning. Hypercapnia often indicates an impending respiratory arrest, but normocapnia, which can be seen in a patient with severe reduction in vital capacity is not reassuring. Hypoxaemia can be due to hypercapnia, pulmonary injury (atelectasis or pneumonia), or pulmonary embolism. Cardiac evaluation is important as cardiomyopathies are frequent in myopathies.

Preload modulates contractile performance, and is determined by end-diastolic volume (EDV) and ventricular compliance. Compliance falls with increasing preload, muscle stiffness or ventricular hypertrophy, making central venous pressure (CVP) a poor surrogate for EDV. Responsiveness to fluid loading can be identified by seeking a change in stroke volume (SV) with changes in cardiac loading. Afterload, the force to be overcome before cardiac muscle can shorten to eject blood, rises with transmural pressure and end-diastolic radius, and inversely with wall thickness. Afterload, being the tension across the ventricular wall, is influenced by pleural pressure. Reductions in afterload increase SV for any cardiac work, as do reductions in vascular resistance. Resistance is modified by changes in arteriolar cross-sectional area. A rise in resistance increases blood pressure and microvascular flow velocity. Increased resistance may reduce CO if cardiac work cannot be augmented sufficiently. Flow autoregulationis the ability of vascular beds to maintain constant flow across varied pressures by adjusting local resistance.

An evolutionary suggests that health interventions can reduce not only the frequency of infectious disease but also the harmfulness of the causal organisms. Interventions that may accomplish this dual goal include hygienic investments such as vector proofing of housing, provisioning of safe water supplies, infrastructure that blocks transmission of durable propagules, the prevention of attendant-borne transmission in hospitals and reductions in the potential for sexual transmission. Vaccines can also reduce the frequency of infection and the harmfulness of the target organisms if they are designed to inhibit selectively the harmful variants in the target population. These approaches should help suppress the evolution of antimicrobial resistance because benign variants causing mild or asymptomatic infections will be less exposed to antimicrobial treatment, reducing the strength of selection for antimicrobial resistance. The interventions should improve health at low cost, which would be especially important for low-income populations.

We use high-frequency data on fine particulate matter air pollution (PM 2.5) at the locality level to study the effects of high pollution on labor supply decisions and hospitalizations for respiratory disease in the metropolitan area of Mexico City. We document a negative, non-linear relationship between PM 2.5 and same-day labor supply, with strong effects on days with extremely high pollution levels. On these days, the average worker experiences a reduction of around 7.5% of working hours. Workers partially compensate for lost hours by increasing their labor supply on days that follow high-pollution days. Informal workers reduce their labor supply less than formal workers on high-pollution days and also compensate less on the following days. This suggests that informal workers may experience greater exposure to high pollution and greater reductions in labor supply and income. We provide evidence that reductions in labor supply due to high pollution are consistent with avoidance behavior and that income constraints may play an important role in workers' labor supply decisions.

The general research objective was to increase herd pregnancy rates by enhancing corpus luteum (CL) function and optimizing follicle development, in order to increase conception rate and embryo survival. The specific objectives were: to determine the effect of the duration of the preovulatory LH surge on CL function; to determine the function of LH during the postovulatory period on CL development; to optimize CL differentiation and follicle development by means of a biodegradable GnRH implant; to test whether optimization of CL development and follicle dynamics in timed- insemination protocols would improve fertility in high-yielding dairy cows. Low fertility in cattle results in losses of hundreds of millions of dollars in the USA and Israel. Two major causes of low fertility are formation of a functionally impaired CL, and subsequent enhanced ovarian follicle development. A functionally impaired CL may result from suboptimal LH secretion. The two major causes of low fertility in dairy cattle in US and Israel are negative energy status and summer heat stress; in both situations, low fertility is associated with reductions in LH secretion and impaired development of the ovulatory follicle and of the CL. In Florida, the use of 450-mg deslorelin (GnRH analogue) implants to induce ovulation, under the Ovsynch protocol resulted in a higher pregnancy rates than use of 750-mg implants, and pregnancy losses tended to decrease compared to controls, due probably to decrease in follicular development and estradiol secretion at the time of conceptus signaling to maintain the CL. An alternative strategy to enhance progesterone concentrations involved induction of an accessory CL by injection of hCG on day 5 after the cows were inseminated. Treatment with hCG resulted in 86% of the cows having two CLs, compared with 23% of the control cows. Conception rates were higher among the hCG-treated cows than among the controls. Another approach was to replace the second injection of GnRH analogue, in a timed-insemination protocol, with estradiol cypionate (ECP) injected 24 h after the injection of PGF₂ₐ Pregnancy rates were comparable with those obtained under the regular Ovsynch (timed- AI) program. Use of ECP induced estrus, and cows inseminated at detected estrus are indeed more fertile than those not in estrus at the time of insemination. Collectively, the BARD-supported programs at the University of Florida have improved timed insemination programs. In Ohio, the importance of the frequency of LH episodes during the early stages of the estrous cycle of cattle, when the corpus luteum is developing, was studied in an in vivo experiment in which cows were subjected to various episodic exposures to exogenous bovine LH. Results indicate that the frequent LH episodes immediately following the time of ovulation are important in development of the corpus luteum, from the points of view of both size and functionality. In another study, rates of cell proliferation and numbers of endothelial cells were examined in vitro in CLs collected from cows that received post-ovulation pulsatile LH treatment at various frequencies. The results indicate that the corpora lutea growth that results from luteal cell proliferation is enhanced by the episodes of LH release that occur immediately after the time of ovulation in cattle. The results also show that luteal endothelial cell numbers did not differ among cows treated with different LH doses. In Israel. a longer duration of the preovulatory LH surge stimulated the steroidogenic capacity of granulosa-derived luteal cells, and might, thereby, contribute to a higher progesterone output from the bovine corpus luteum. In an in vivo study, a subgroup of high-yielding dairy cows with extended estrus to ovulation interval was identified. Associated with this extended interval were: low plasma progesterone and estradiol concentrations and a low preovulatory LH surge prior to ovulation, as well as low post- ovulation progesterone concentration. In experiments based on the above results, we found that injection of GnRH at the onset of estrus increased the LHpeak, prevented late ovulation, decreased the variability between cows and elicited high and uniform progesterone levels after ovulation. GnRH at estrus onset increased conception rates, especially in the summer, and among primiparous cows and those with low body condition. Another study compared ovarian functions in multiparous lactating cows with those in nulliparous non-lactating heifers. The results revealed differences in ovarian follicular dynamics, and in plasma concentrations of steroids and gonadotropins that may account for the differences in fertility between heifers and cows.

1.1 Macroeconomic summary Economic recovery has consistently outperformed the technical staff’s expectations following a steep decline in activity in the second quarter of 2020. At the same time, total and core inflation rates have fallen and remain at low levels, suggesting that a significant element of the reactivation of Colombia’s economy has been related to recovery in potential GDP. This would support the technical staff’s diagnosis of weak aggregate demand and ample excess capacity. The most recently available data on 2020 growth suggests a contraction in economic activity of 6.8%, lower than estimates from January’s Monetary Policy Report (-7.2%). High-frequency indicators suggest that economic performance was significantly more dynamic than expected in January, despite mobility restrictions and quarantine measures. This has also come amid declines in total and core inflation, the latter of which was below January projections if controlling for certain relative price changes. This suggests that the unexpected strength of recent growth contains elements of demand, and that excess capacity, while significant, could be lower than previously estimated. Nevertheless, uncertainty over the measurement of excess capacity continues to be unusually high and marked both by variations in the way different economic sectors and spending components have been affected by the pandemic, and by uneven price behavior. The size of excess capacity, and in particular the evolution of the pandemic in forthcoming quarters, constitute substantial risks to the macroeconomic forecast presented in this report. Despite the unexpected strength of the recovery, the technical staff continues to project ample excess capacity that is expected to remain on the forecast horizon, alongside core inflation that will likely remain below the target. Domestic demand remains below 2019 levels amid unusually significant uncertainty over the size of excess capacity in the economy. High national unemployment (14.6% for February 2021) reflects a loose labor market, while observed total and core inflation continue to be below 2%. Inflationary pressures from the exchange rate are expected to continue to be low, with relatively little pass-through on inflation. This would be compatible with a negative output gap. Excess productive capacity and the expectation of core inflation below the 3% target on the forecast horizon provide a basis for an expansive monetary policy posture. The technical staff’s assessment of certain shocks and their expected effects on the economy, as well as the presence of several sources of uncertainty and related assumptions about their potential macroeconomic impacts, remain a feature of this report. The coronavirus pandemic, in particular, continues to affect the public health environment, and the reopening of Colombia’s economy remains incomplete. The technical staff’s assessment is that the COVID-19 shock has affected both aggregate demand and supply, but that the impact on demand has been deeper and more persistent. Given this persistence, the central forecast accounts for a gradual tightening of the output gap in the absence of new waves of contagion, and as vaccination campaigns progress. The central forecast continues to include an expected increase of total and core inflation rates in the second quarter of 2021, alongside the lapse of the temporary price relief measures put in place in 2020. Additional COVID-19 outbreaks (of uncertain duration and intensity) represent a significant risk factor that could affect these projections. Additionally, the forecast continues to include an upward trend in sovereign risk premiums, reflected by higher levels of public debt that in the wake of the pandemic are likely to persist on the forecast horizon, even in the context of a fiscal adjustment. At the same time, the projection accounts for the shortterm effects on private domestic demand from a fiscal adjustment along the lines of the one currently being proposed by the national government. This would be compatible with a gradual recovery of private domestic demand in 2022. The size and characteristics of the fiscal adjustment that is ultimately implemented, as well as the corresponding market response, represent another source of forecast uncertainty. Newly available information offers evidence of the potential for significant changes to the macroeconomic scenario, though without altering the general diagnosis described above. The most recent data on inflation, growth, fiscal policy, and international financial conditions suggests a more dynamic economy than previously expected. However, a third wave of the pandemic has delayed the re-opening of Colombia’s economy and brought with it a deceleration in economic activity. Detailed descriptions of these considerations and subsequent changes to the macroeconomic forecast are presented below. The expected annual decline in GDP (-0.3%) in the first quarter of 2021 appears to have been less pronounced than projected in January (-4.8%). Partial closures in January to address a second wave of COVID-19 appear to have had a less significant negative impact on the economy than previously estimated. This is reflected in figures related to mobility, energy demand, industry and retail sales, foreign trade, commercial transactions from selected banks, and the national statistics agency’s (DANE) economic tracking indicator (ISE). Output is now expected to have declined annually in the first quarter by 0.3%. Private consumption likely continued to recover, registering levels somewhat above those from the previous year, while public consumption likely increased significantly. While a recovery in investment in both housing and in other buildings and structures is expected, overall investment levels in this case likely continued to be low, and gross fixed capital formation is expected to continue to show significant annual declines. Imports likely recovered to again outpace exports, though both are expected to register significant annual declines. Economic activity that outpaced projections, an increase in oil prices and other export products, and an expected increase in public spending this year account for the upward revision to the 2021 growth forecast (from 4.6% with a range between 2% and 6% in January, to 6.0% with a range between 3% and 7% in April). As a result, the output gap is expected to be smaller and to tighten more rapidly than projected in the previous report, though it is still expected to remain in negative territory on the forecast horizon. Wide forecast intervals reflect the fact that the future evolution of the COVID-19 pandemic remains a significant source of uncertainty on these projections. The delay in the recovery of economic activity as a result of the resurgence of COVID-19 in the first quarter appears to have been less significant than projected in the January report. The central forecast scenario expects this improved performance to continue in 2021 alongside increased consumer and business confidence. Low real interest rates and an active credit supply would also support this dynamic, and the overall conditions would be expected to spur a recovery in consumption and investment. Increased growth in public spending and public works based on the national government’s spending plan (Plan Financiero del Gobierno) are other factors to consider. Additionally, an expected recovery in global demand and higher projected prices for oil and coffee would further contribute to improved external revenues and would favor investment, in particular in the oil sector. Given the above, the technical staff’s 2021 growth forecast has been revised upward from 4.6% in January (range from 2% to 6%) to 6.0% in April (range from 3% to 7%). These projections account for the potential for the third wave of COVID-19 to have a larger and more persistent effect on the economy than the previous wave, while also supposing that there will not be any additional significant waves of the pandemic and that mobility restrictions will be relaxed as a result. Economic growth in 2022 is expected to be 3%, with a range between 1% and 5%. This figure would be lower than projected in the January report (3.6% with a range between 2% and 6%), due to a higher base of comparison given the upward revision to expected GDP in 2021. This forecast also takes into account the likely effects on private demand of a fiscal adjustment of the size currently being proposed by the national government, and which would come into effect in 2022. Excess in productive capacity is now expected to be lower than estimated in January but continues to be significant and affected by high levels of uncertainty, as reflected in the wide forecast intervals. The possibility of new waves of the virus (of uncertain intensity and duration) represents a significant downward risk to projected GDP growth, and is signaled by the lower limits of the ranges provided in this report. Inflation (1.51%) and inflation excluding food and regulated items (0.94%) declined in March compared to December, continuing below the 3% target. The decline in inflation in this period was below projections, explained in large part by unanticipated increases in the costs of certain foods (3.92%) and regulated items (1.52%). An increase in international food and shipping prices, increased foreign demand for beef, and specific upward pressures on perishable food supplies appear to explain a lower-than-expected deceleration in the consumer price index (CPI) for foods. An unexpected increase in regulated items prices came amid unanticipated increases in international fuel prices, on some utilities rates, and for regulated education prices. The decline in annual inflation excluding food and regulated items between December and March was in line with projections from January, though this included downward pressure from a significant reduction in telecommunications rates due to the imminent entry of a new operator. When controlling for the effects of this relative price change, inflation excluding food and regulated items exceeds levels forecast in the previous report. Within this indicator of core inflation, the CPI for goods (1.05%) accelerated due to a reversion of the effects of the VAT-free day in November, which was largely accounted for in February, and possibly by the transmission of a recent depreciation of the peso on domestic prices for certain items (electric and household appliances). For their part, services prices decelerated and showed the lowest rate of annual growth (0.89%) among the large consumer baskets in the CPI. Within the services basket, the annual change in rental prices continued to decline, while those services that continue to experience the most significant restrictions on returning to normal operations (tourism, cinemas, nightlife, etc.) continued to register significant price declines. As previously mentioned, telephone rates also fell significantly due to increased competition in the market. Total inflation is expected to continue to be affected by ample excesses in productive capacity for the remainder of 2021 and 2022, though less so than projected in January. As a result, convergence to the inflation target is now expected to be somewhat faster than estimated in the previous report, assuming the absence of significant additional outbreaks of COVID-19. The technical staff’s year-end inflation projections for 2021 and 2022 have increased, suggesting figures around 3% due largely to variation in food and regulated items prices. The projection for inflation excluding food and regulated items also increased, but remains below 3%. Price relief measures on indirect taxes implemented in 2020 are expected to lapse in the second quarter of 2021, generating a one-off effect on prices and temporarily affecting inflation excluding food and regulated items. However, indexation to low levels of past inflation, weak demand, and ample excess productive capacity are expected to keep core inflation below the target, near 2.3% at the end of 2021 (previously 2.1%). The reversion in 2021 of the effects of some price relief measures on utility rates from 2020 should lead to an increase in the CPI for regulated items in the second half of this year. Annual price changes are now expected to be higher than estimated in the January report due to an increased expected path for fuel prices and unanticipated increases in regulated education prices. The projection for the CPI for foods has increased compared to the previous report, taking into account certain factors that were not anticipated in January (a less favorable agricultural cycle, increased pressure from international prices, and transport costs). Given the above, year-end annual inflation for 2021 and 2022 is now expected to be 3% and 2.8%, respectively, which would be above projections from January (2.3% and 2,7%). For its part, expected inflation based on analyst surveys suggests year-end inflation in 2021 and 2022 of 2.8% and 3.1%, respectively. There remains significant uncertainty surrounding the inflation forecasts included in this report due to several factors: 1) the evolution of the pandemic; 2) the difficulty in evaluating the size and persistence of excess productive capacity; 3) the timing and manner in which price relief measures will lapse; and 4) the future behavior of food prices. Projected 2021 growth in foreign demand (4.4% to 5.2%) and the supposed average oil price (USD 53 to USD 61 per Brent benchmark barrel) were both revised upward. An increase in long-term international interest rates has been reflected in a depreciation of the peso and could result in relatively tighter external financial conditions for emerging market economies, including Colombia. Average growth among Colombia’s trade partners was greater than expected in the fourth quarter of 2020. This, together with a sizable fiscal stimulus approved in the United States and the onset of a massive global vaccination campaign, largely explains the projected increase in foreign demand growth in 2021. The resilience of the goods market in the face of global crisis and an expected normalization in international trade are additional factors. These considerations and the expected continuation of a gradual reduction of mobility restrictions abroad suggest that Colombia’s trade partners could grow on average by 5.2% in 2021 and around 3.4% in 2022. The improved prospects for global economic growth have led to an increase in current and expected oil prices. Production interruptions due to a heavy winter, reduced inventories, and increased supply restrictions instituted by producing countries have also contributed to the increase. Meanwhile, market forecasts and recent Federal Reserve pronouncements suggest that the benchmark interest rate in the U.S. will remain stable for the next two years. Nevertheless, a significant increase in public spending in the country has fostered expectations for greater growth and inflation, as well as increased uncertainty over the moment in which a normalization of monetary policy might begin. This has been reflected in an increase in long-term interest rates. In this context, emerging market economies in the region, including Colombia, have registered increases in sovereign risk premiums and long-term domestic interest rates, and a depreciation of local currencies against the dollar. Recent outbreaks of COVID-19 in several of these economies; limits on vaccine supply and the slow pace of immunization campaigns in some countries; a significant increase in public debt; and tensions between the United States and China, among other factors, all add to a high level of uncertainty surrounding interest rate spreads, external financing conditions, and the future performance of risk premiums. The impact that this environment could have on the exchange rate and on domestic financing conditions represent risks to the macroeconomic and monetary policy forecasts. Domestic financial conditions continue to favor recovery in economic activity. The transmission of reductions to the policy interest rate on credit rates has been significant. The banking portfolio continues to recover amid circumstances that have affected both the supply and demand for loans, and in which some credit risks have materialized. Preferential and ordinary commercial interest rates have fallen to a similar degree as the benchmark interest rate. As is generally the case, this transmission has come at a slower pace for consumer credit rates, and has been further delayed in the case of mortgage rates. Commercial credit levels stabilized above pre-pandemic levels in March, following an increase resulting from significant liquidity requirements for businesses in the second quarter of 2020. The consumer credit portfolio continued to recover and has now surpassed February 2020 levels, though overall growth in the portfolio remains low. At the same time, portfolio projections and default indicators have increased, and credit establishment earnings have come down. Despite this, credit disbursements continue to recover and solvency indicators remain well above regulatory minimums. 1.2 Monetary policy decision In its meetings in March and April the BDBR left the benchmark interest rate unchanged at 1.75%.