Increased diastolic chamber stiffness during demand ischemia - Response toquick length change differentiates rigor-activared from calcium-activated tension

Background-Increased diastolic chamber stiffness (up arrow DCS) during angi na (demand ischemia) has been postulated to be generated by increased diast olic myocyte calcium concentration. Methods and Results-We reproduced demand ischemia in isolated isovolumicall y contracting red-cell-perfused rabbit hearts by imposing pacing tachycardi a during global low coronary blood flow (32% of baseline). This increased l actate production without increasing oxygen consumption and resulted in up arrow DCS (isovolumic left ventricular end-diastolic pressure [LVEDP] incre ased 10 mm Hg, P<0.001, n=38). To determine the mechanism of up arrow DCS, we assessed responses to a quick-stretch-release maneuver (QSR), in which t he intraventricular balloon was rapidly inflated and deflated to achieve a 3% circumferential muscle fiber length change. QSR was first validated as a n effective method of discriminating between calcium-driven and rigor-media ted up arrow DCS. QSR imposed during demand ischemia when DCS had increased (LVEDP pretachycardia versus posttachycardia, 15+/-1 versus 27+/-2 mm Hg, P<0.001, n=6) reduced DCS to pretachycardia values (LVEDP post-QSR, 15+/-1 mm Hg, P<0.001), ie, elicited a response characteristic of rigor, without a ny component of calcium-generated tension. Conclusions-A rigor force, possibly resulting from high-energy phosphate de pletion and/or an increase in ADP, appears to be the primary mechanism unde rlying increased DCS in this model of global LV demand ischemia.