Benefit of Heart Rate Reduction in Heart Failure

# The Author(s) 2010. This article is published with open access at Springerlink.co

Effects of the NO donor sodium nitroprusside on oxygen consumption and energetics in rabbit myocardium

Nitric oxide (NO) has influence on various cellular functions. Little is known of the influence of NO on myocardial energetics. In the present study oxygen consumption and mechanical parameters of isometrically contracting rabbit papillary muscles (1 Hz stimulation frequency) were investigated at varying interventions while maintaining physiological conditions (37°C; 2.5 mM Ca2+) to study the effects of NO on energetics. The NO donor sodium nitroprusside (SNP) showed a negative inotropic effect. SNP decreased the maximal force in normal rabbit muscle strips by 30%, the force time integral (FTI) by 40% and the relaxation time by 20%. In addition the oxygen consumption decreased by 60%, a notably disproportional decrease compared to the mechanical parameters. Consequently, the economy as a ratio of FTI and oxygen consumption is significantly increased by SNP. In contrast the negative inotropic effect due to a reduction in extracellular Calcium (Ca2+) from 2.5 to 1.25 mM reduced FTI and oxygen consumption proportionally by 40% and did not change economy. The effect of NO on force and oxygen consumption could be reproduced by the application of the cyclic guanosine monophosphate (cGMP) analogue 8-bromo-cGMP. In summary, NO increased the economy of isometrically contracting papillary muscles. The improvement in contraction economy under NO seems to be mediated by cGMP as the secondary messenger and maybe due to alterations of the crossbridge cycle

Summative assessments are more powerful drivers of student learning than resource intensive teaching formats

BACKGROUND: Electrocardiogram (ECG) interpretation is a core clinical skill that needs to be acquired during undergraduate medical education. Intensive teaching is generally assumed to produce more favorable learning outcomes, but recent research suggests that examinations are more powerful drivers of student learning than instructional format. This study assessed the differential contribution of teaching format and examination consequences to learning outcome regarding ECG interpretation skills in undergraduate medical students. METHODS: A total of 534 fourth-year medical students participated in a six-group (two sets of three), partially randomized trial. Students received three levels of teaching intensity: self-directed learning (two groups), lectures (two groups) or small-group peer teaching facilitated by more advanced students (two groups). One of the two groups on each level of teaching intensity was assessed in a formative, the other in a summative written ECG examination, which provided a maximum of 1% credit points of the total curriculum. The formative examination provided individual feedback without credit points. Main outcome was the correct identification of ≥3 out of 5 diagnoses in original ECG tracings. Secondary outcome measures were time spent on independent study and use of additional study material. RESULTS: Compared with formative assessments, summative assessments increased the odds of correctly identifying at least three out of five ECG diagnoses (OR 5.14; 95% CI 3.26 to 8.09), of spending at least 2 h/week extra on ECG self-study (OR 4.02; 95% CI 2.65 to 6.12) and of using additional learning material (OR 2.86; 95% CI 1.92 to 4.24). Lectures and peer teaching were associated with increased learning effort only, but did not augment examination performance. CONCLUSIONS: Medical educators need to be aware of the paramount role of summative assessments in promoting student learning. Consequently, examinations within medical schools need to be closely matched to the desired learning outcomes. Shifting resources from implementing innovative and costly teaching formats to designing more high-quality summative examinations warrants further investigation

Slow breathing reduces sympathoexcitation in COPD

Neurohumoral activation has been shown to be present in hypoxic patients with chronic obstructive pulmonary disease (COPD). The aims of the present study were to investigate whether there is sympathetic activation in COPD patients in the absence of hypoxia and whether slow breathing has an impact on sympathoexcitation and baroreflex sensitivity. Efferent muscle sympathetic nerve activity, blood pressure, cardiac frequency and respiratory movements were continuously measured in 15 COPD patients and 15 healthy control subjects. Baroreflex sensitivity was analysed by autoregressive spectral analysis and the alpha-angle method. At baseline, sympathetic nerve activity was significantly elevated in COPD patients and baroreflex sensitivity was decreased (5.0+/-0.6 versus 8.9+/-0.8 ms.mmHg(-1)). Breathing at a rate of 6 breaths.min(-1) caused sympathetic activity to drop significantly in COPD patients (from 61.3+/-4.6 to 53.0+/-4.3 bursts per 100 heartbeats) but not in control subjects (39.2+/-3.2 versus 37.5+/-3.3 bursts per 100 heartbeats). In both groups, slow breathing significantly enhanced baroreflex sensitivity. In conclusion, sympathovagal imbalance is present in normoxic chronic obstructive pulmonary disease patients. The possibility of modifying these changes by slow breathing may help to better understand and influence this systemic disease

Cell Cycle–Mediated Cardiac Regeneration in the Mouse Heart

Purpose of Review Many forms of heart disease result in the essentially irreversible loss of cardiomyocytes. The ability to promote cardiomyocyte renewal may be a promising approach to reverse injury in diseased hearts. The purpose of this review is to describe the impact of cardiomyocyte cell cycle activation on cardiac function and structure in several different models of myocardial disease. Recent Findings Transgenic mice expressing cyclin D2 (D2 mice) exhibit sustained cardiomyocyte renewal in the adult heart. Earlier studies demonstrated that D2 mice exhibited progressive myocardial regeneration in experimental models of myocardial infarction, and that cardiac function was normalized to values seen in sham-operated litter mates by 180 days post-injury. D2 mice also exhibited markedly improved atrial structure in a genetic model of atrial fibrosis. More recent studies revealed that D2 mice were remarkably resistant to heart failure induced by chronic elevated afterload as compared with their wild type (WT siblings), with a 6-fold increase in median survival as well as retention of relatively normal cardiac function. Finally, D2 mice exhibited a progressive recovery in cardiac function to normal levels and a concomitant reduction in adverse myocardial remodeling in an anthracycline cardiotoxicity model. Summary The studies reviewed here make a strong case for the potential utility of inducing cardiomyocyte renewal as a means to treat injured hearts. Several challenges which must be met to develop a viable therapeutic intervention based on these observations are discussed

Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium

Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of spontaneous circulation (ROSC) and contributes to hemodynamic instability and low survival rates after cardiac arrest. Mild hypothermia for 24 h after ROSC has been shown to significantly improve neurologic recovery and survival rates. In the present study we investigate the influence of therapeutic hypothermia on hemodynamic parameters in resuscitated patients and on contractility in failing human myocardium. We analyzed hemodynamic data from 200 cardiac arrest survivors during the hypothermia period. The initial LVEF was 32.6 ± 1.2% indicating a significantly impaired LV function. During hypothermia induction, the infusion rate of epinephrine could be significantly reduced from 9.1 ± 1.3 μg/min [arrival intensive care unit (ICU) 35.4°C] to 4.6 ± 1.0 μg/min (34°C) and 2.8 ± 0.5 μg/min (33°C). The dobutamine and norepinephrine application rates were not changed significantly. The mean arterial blood pressure remained stable. The mean heart rate significantly decreased from 91.8 ± 1.7 bpm (arrival ICU) to 77.3 ± 1.5 bpm (34°C) and 70.3 ± 1.4 bpm (33°C). In vitro we investigated the effect of hypothermia on isolated ventricular muscle strips from explanted failing human hearts. With decreasing temperature, the contractility increased to a maximum of 168 ± 23% at 27°C (n = 16, P < 0.05). Positive inotropic response to hypothermia was accompanied by moderately increased rapid cooling contractures as a measure of sarcoplasmic reticulum (SR) Ca2+ content, but can be elicited even when the SR Ca2+ release is blocked in the presence of ryanodine. Contraction and relaxation kinetics are prolonged with hypothermia, indicating increased Ca2+ sensitivity as the main mechanism responsible for inotropy. In conclusion, mild hypothermia stabilizes hemodynamics in cardiac arrest survivors which might contribute to improved survival rates in these patients. Mechanistically, we demonstrate that hypothermia improves contractility in failing human myocardium most likely by increasing Ca2+-sensitivity

Venous lactate improves the prediction of in-hospital adverse outcomes in normotensive pulmonary embolism

Background: Arterial lactate is an established risk marker in patients with pulmonary embolism (PE). However, its clinical applicability is limited by the need of an arterial puncture. In contrast, venous lactate can easily be measured from blood samples obtained via routine peripheral venepuncture. Methods: We investigated the prognostic value of venous lactate with regard to in-hospital adverse outcomes and mortality in 419 consecutive PE patients enrolled in a single-center registry between 09/2008 and 09/2017. Results: An optimised venous lactate cut-off value of 3.3 mmol/l predicted both, in-hospital adverse outcome (OR 11.0 [95% CI 4.6?26.3]) and all-cause mortality (OR 3.8 [95%CI 1.3?11.3]). The established cut-off value for arterial lactate (2.0 mmol/l) and the upper limit of normal for venous lactate (2.3 mmol/l) had lower prognostic value for adverse outcomes (OR 3.6 [95% CI 1.5?8.7] and 5.7 [95% CI 2.4?13.6], respectively) and did not predict mortality. If added to the 2019 European Society of Cardiology (ESC) algorithm, venous lactate Conclusion: Venous lactate above the upper limit of normal was associated with increased risk for adverse outcomes and an optimised cut-off value of 3.3 mmol/l predicted adverse outcome and mortality. Adding venous lactate to the 2019 ESC algorithm may improve risk stratification. Importantly, the established cut-off value for arterial lactate has limited specificity in venous samples and should not be used.Peer reviewe