Frequency-dependent contractile response of isolated cardiac trabeculae under hypo-, normo-, and hyperthermic conditions

Abstract

The body is from time to time exposed to nonnormothermic conditions; both hypo- and hyperthermia can occur as a result of external (environment) or internal (pathogens, allergens) stressors. To preserve life under hypo- and hyperthermic conditions, adequate perfusion of vital organs is mandated. Although cardiac output regulation under hyperthermic conditions has been studied, the mechanical response of basic contractile function of the myocardium itself is incompletely understood. Accordingly, we set out to test mechanical output of isolated myocardium under hyperthermic conditions and to compare the results with the hypo- and normothermic response in the same tissue. We observed that, in absence of a frequency change, developed force decreased markedly. At a physiological normal stimulation rate of 6 Hz, developed force decreases to 67.2 +/- 2.6% at 42 degrees C compared with 37 degrees C. In addition, twitch timing characteristics also accelerate, allowing for a faster relaxation; time from peak tension to 50% relaxation is approximately 23% faster (from 31.4 +/- 2.6 to 24.4 +/- 1.7 ms). Although this faster relaxation in turn prevents a steep increase in diastolic tension at high frequencies, the very fast calcium kinetics now prevent a more complete activation of the myofilaments, resulting in a lower twitch-force maximum at hyperthermic conditions. Even at maximal beta-adrenergic stimulation, developed force is well below levels reached at physiological temperature.

Determinants of frequency-dependent contraction and relaxation of mammalian myocardium

“…Thus, as temperature increases, the frequency at which maximum active tension is developed shifts to the right (higher frequency) on the spectrum. Whereas the active force development in rat myocardium is maximal at around 2 Hz at room temperature, it will shift to 4 or 6 Hz at 30 °C, to 8 Hz at body temperature, and even above that under hyperthermic conditions [10], that can occur in vivo during a fever. When at non-physiological temperature one measures force at various frequencies, the results do not necessarily reflect the FFR, or processes underlying physiological frequency-dependent activation as they occur in vivo.…”

Heat Acclimation, Epigenetics, and Cytoprotection Memory

“…Accelerated fatigue could also be associated with metabolic inhibition of muscle contraction because ATP turnover is faster at high temperatures (170). Similarly, hyperthermia depresses cardiac contractility (negative inotropism), increases the oxygen cost of contractile response and may reduce Ca 2+ sensitivity (68,182). Nielsen et al (154) and Nielsen (151) in a review on 'Heat stress and acclimation' stated that "It was the rise in core temperature to about 40…”

“…Increased O 2 consumption and decreased contractile efficiency which may lead to working muscle fatigue in hyperthermic nonacclimated hearts may explain the detrimental effects in the nonacclimated hearts (68,182). Studies on hearts of trained animals do not demonstrate alterations in myosin isoform distribution (192).…”

Quantifying inter‐species differences in contractile function through biophysical modelling

“…† Measured data for rat at 37°C, based on data from Janssen et al (2002), Hiranandani et al (2006), Monasky et al (2008) and Monasky & Janssen (2009). ‡ Measured data for human at 37°C (Land et al 2012b) used to fit the contraction model parameters, based on data from Land (2013).…”