Increased diastolic chamber stiffness during demand ischemia: response to quick length change differentiates rigor-activated from calcium-activated tension.

Abstract

BACKGROUND: Increased diastolic chamber stiffness (increased 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 increased DCS (isovolumic left ventricular end-diastolic pressure [LVEDP] increased 10 mm Hg, P<0. 001, n=38). To determine the mechanism of increased 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 increased 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.