Increased diastolic chamber stiffness during demand ischemia: response to quick length change differentiates rigor-activated from calcium-activated tension.
BACKGROUND
Increased diastolic chamber stiffness (increased DCS) during angina (demand ischemia) has been postulated to be generated by increased diastolic myocyte calcium concentration.


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
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Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
Eberli
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Apstein
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D000818:Animals; D002118:Calcium / Q000502:physiology*; D003971:Diastole; D004195:Disease Models, Animal; D004562:Electrocardiography; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D010101:Oxygen Consumption; D011817:Rabbits
D002118:Calcium