In vivo human cardiac shortening and lengthening velocity is region-dependent and not coupled with heart rate

New Findings •What is the central question of this study? Regulation of cardiac function is typically achieved by changes in heart rate (HR) and cardiac shortening velocity (strain rate; SR), but their interdependence in vivo remains poorly understood. •What is the main finding and its importance? Using resistance exercise to increase heart rate and arterial resistance physiologically in humans and measuring regional cardiac SR (at the base and apex), we found that HR and SR were not strictly coupled because SR at the base and apex responded differently, despite the same HR. Importantly, our data show that the region-averaged ‘longitudinal’ SR, which is currently popular in the clinical setting, markedly underestimates the contribution of the apex. The fundamental importance of cardiac shortening and lengthening velocity (i.e. strain rate; SR) has been demonstrated in vitro. Currently, the interdependence between in vivo SR and HR is poorly understood because studies have typically assessed region-averaged ‘longitudinal’ strain rate, which is likely to underestimate the apical contribution, and have used non-physiological interventions that may also have been influenced by multicollinearity caused by concomitant reductions in arterial resistance. Resistance exercise acutely raises HR, blood pressure and arterial resistance and transiently disassociates these cardiovascular factors following exercise. Therefore, we measured SR, HR, blood pressure and arterial resistance in nine healthy men (aged 20 ± 1 years) immediately before, during and after double-leg-press exercise at 30 and 60% of maximal strength. Resistance exercise caused a disproportionate SR response at the left ventricular base and apex (interaction effect, P < 0.05). Consequently, associations between HR and regional peak SR were inconsistent and mostly very weak (r2 = 0.0004–0.24). Likewise, the areas under the curve for systolic and diastolic SR and their relationship with systolic and diastolic duration were variable and weak. Importantly, region-averaged ‘longitudinal’ SR was identical to basal SR, thus, markedly underestimating the apical contribution. In conclusion, in vivo HR and SR are not strictly coupled in healthy humans, which is explained by the region-specific responses of SR that are not captured by ‘longitudinal SR’. This novel observation emphasizes the independent role of in vivo SR in overall cardiac function during stress and may cause a ‘revival’ of SR as a marker of regional left ventricular (dys)function

Zum Nachweis des Kohlenoxyd-H�moglobins

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Regulation of Coronary Blood Flow

The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery. © 2017 American Physiological Society. Compr Physiol 7:321-382, 2017

Silicon central pattern generators for cardiac diseases

Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronisation but not heart failure, which affects millions of patients worldwide. This paper reviews recent advances in biophysics and mathematical engineering that provide a novel technological platform for addressing heart disease and enabling beat-to-beat adaptation of cardiac pacing in response to physiological feedback. The technology consists of silicon hardware central pattern generators (hCPGs) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPGs). We discuss the limitations of present CPGs and appraise the advantages of analog over digital circuits for application in bioelectronic medicine. To test the system, we have focused on the cardio-respiratory oscillators in the medulla oblongata that modulate heart rate in phase with respiration to induce respiratory sinus arrhythmia (RSA). We describe here a novel, scalable hCPG comprising physiologically realistic (Hodgkin–Huxley type) neurones and synapses. Our hCPG comprises two neurones that antagonise each other to provide rhythmic motor drive to the vagus nerve to slow the heart. We show how recent advances in modelling allow the motor output to adapt to physiological feedback such as respiration. In rats, we report on the restoration of RSA using an hCPG that receives diaphragmatic electromyography input and use it to stimulate the vagus nerve at specific time points of the respiratory cycle to slow the heart rate. We have validated the adaptation of stimulation to alterations in respiratory rate. We demonstrate that the hCPG is tuneable in terms of the depth and timing of the RSA relative to respiratory phase. These pioneering studies will now permit an analysis of the physiological role of RSA as well as its any potential therapeutic use in cardiac disease

Silicon central pattern generators for cardiac diseases

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Determination of histamine in human plasma: the European external quality control study 1988

There is an increasing interest in measuring human plasma histamine levels in various clinical conditions. A variety of 'old' and newly developed techniques are applied to meet this demand. However, the discrepancy between reported reference values for histamine in human plasma measured using this variety of techniques, suggests the existence of a certain degree of inaccuracy and imprecision. We therefore organized an external quality control study on the reliability of current histamine determinations in European laboratories. Three lyophilized plasma quality control samples, in duplicate, covering the normal and pathological range of histamine concentrations (0-45 nmol/l), two different aqueous histamine standard samples and one solvent sample were sent to 10 laboratories for the analysis of their histamine content. The following methods were used: gas chromatography-mass spectrometry (n = 2), enzymatic single isotopic assay (n = 1), fluorometric-fluoroenzymatic assay (n = 3), radioimmunoassay (n = 3) and high performance liquid chromatography (n = 2). The study was performed and evaluated according to the approved recommendations (1983) of the International Federation of Clinical Chemistry (IFCC). The target values +/- s.d. of the three plasma samples were: 39.5 +/- 4.6 nmol/l (CV = 11.6%), 2.3 +/- 2.2 nmol/l (CV = 96%) and 8.9 +/- 1.5 nmol/l (CV = 17%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS