Increased Diastolic Chamber Stiffness During Demand Ischemia

Abstract

Background —Increased diastolic chamber stiffness (↑DCS) during angina (demand ischemia) has been postulated to be generated by increased diastolic myocyte calcium concentration. Methods and Results —We reproduced demand ischemia in isolated isovolumically contracting red-cell–perfused rabbit hearts by imposing pacing tachycardia during global low coronary blood flow (32% of baseline). This increased lactate production without increasing oxygen consumption and resulted in ↑DCS (isovolumic left ventricular end-diastolic pressure [LVEDP] increased 10 mm Hg, P <0.001, n=38). To determine the mechanism of ↑DCS, we assessed responses to a quick-stretch-release maneuver (QSR), in which the intraventricular balloon was rapidly inflated and deflated to achieve a 3% circumferential muscle fiber length change. QSR was first validated as an effective method of discriminating between calcium-driven and rigor-mediated ↑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 any component of calcium-generated tension. Conclusions —A rigor force, possibly resulting from high-energy phosphate depletion and/or an increase in ADP, appears to be the primary mechanism underlying increased DCS in this model of global LV demand ischemia.