Demand ischemia in isolated rabbit hearts increased left ventricular end-diastolic pressure from 15 to 27 mm Hg (P<0.001), which was reversed by a quick-stretch-release maneuver.
What is the mechanism underlying increased diastolic chamber stiffness during demand ischemia in isolated rabbit hearts?
Increased diastolic chamber stiffness during demand ischemia appears to be primarily driven by a rigor force rather than calcium-generated tension.
Absolute Event Rate: 27% vs 15%
p-value: p=<0.001
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.
Varma et al. (Tue,) conducted a other in Demand ischemia (n=38). Pacing tachycardia during global low coronary blood flow and quick-stretch-release maneuver vs. Pretachycardia baseline was evaluated on Isovolumic left ventricular end-diastolic pressure (LVEDP) (p=<0.001). Demand ischemia in isolated rabbit hearts increased left ventricular end-diastolic pressure from 15 to 27 mm Hg (P<0.001), which was reversed by a quick-stretch-release maneuver.