Streptozotocin-induced diabetes prolongs twitch duration without affecting the energetics of isolated ventricular trabeculae

Abstract

BackgroundDiabetes induces numerous electrical, ionic and biochemical defects in the heart. A general feature of diabetic myocardium is its low rate of activity, commonly characterised by prolonged twitch duration. This diabetes-induced mechanical change, however, seems to have no effect on contractile performance (i.e., force production) at the tissue level. Hence, we hypothesise that diabetes has no effect on either myocardial work output or heat production and, consequently, the dependence of myocardial efficiency on afterload of diabetic tissue is the same as that of healthy tissue.MethodsWe used isolated left ventricular trabeculae (streptozotocin-induced diabetes versus control) as our experimental tissue preparations. We measured a number of indices of mechanical (stress production, twitch duration, extent of shortening, shortening velocity, shortening power, stiffness, and work output) and energetic (heat production, change of enthalpy, and efficiency) performance. We calculated efficiency as the ratio of work output to change of enthalpy (the sum of work and heat).ResultsConsistent with literature results, we showed that peak twitch stress of diabetic tissue was normal despite suffering prolonged duration. We report, for the first time, the effect of diabetes on mechanoenergetic performance. We found that the indices of performance listed above were unaffected by diabetes. Hence, since neither work output nor change of enthalpy was affected, the efficiency-afterload relation of diabetic tissue was unaffected, as hypothesised.ConclusionsDiabetes prolongs twitch duration without having an effect on work output or heat production, and hence efficiency, of isolated ventricular trabeculae. Collectively, our results, arising from isolated trabeculae, reconcile the discrepancy between the mechanical performance of the whole heart and its tissues.

Mitochondrial inefficiencies and anoxic ATP hydrolysis capacities in diabetic rat heart

“…in the LV thickness-to-heart weight ratio (Table 1) was apparent, and this is consistent with published data for STZ-induced diabetic rat hearts, which progressively show depressed pumping capacities (52), most likely through decreasing LV compliance (4). We note that contemporaneous work found decreased pumping efficiencies at elevated afterloads in rats from the same source as those used in the present study (39). A significant decrease in heart rate (15%) and increase in systolic duration (24%) also occur in 8-wk STZ-diabetic Wistar rats (52) and have been reported in diabetic men and women (22).…”

Experimental and modelling evidence of shortening heat in cardiac muscle

“…The parameter governing the dependence of crossbridge detachment on the shortening velocity (σ p = 0.1) was modified to ensure that the enthalpy-load relationship was positive, as is observed in cardiac muscle (Gibbs et al 1967;Han et al 2012Han et al , 2014Tran et al 2016). The model assumes a 1:1 stoichiometry between the rate of cross-bridge cycling and the rate of ATP hydrolysis, i.e.…”

Sex differences in the mechano‐energetic effects of genistein on stunned rat and guinea pig hearts

“…Whole‐heart on‐line calorimetry has been used extensively to study the energetics of Ca 2+ homeostasis in the stunned heart after a transient ischemia, and the cardioprotection of cardioplegic solutions of high [K + ]o or pyruvate (Pyr), and the effects of hyperthyroidism . Microcalorimetry has also been performed by other authors using a more sensitive device to estimate the energetics of the tension‐dependent heat of superfused trabeculae in diabetes . Nevertheless, the physiologically perfused whole heart is the only preparation capable of simulating ischemia by flow cessation and reperfusion.…”