This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Varma, N. Articles by Apstein, C. S. Search for Related Content PubMed PubMed Citation Articles by Varma, N. Articles by Apstein, C. S. Related Collections Animal models of human disease

(Circulation. 2000;101:2185.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Increased Diastolic Chamber Stiffness During Demand Ischemia

Response to Quick Length Change Differentiates Rigor-Activated From Calcium-Activated Tension

Niraj Varma, MRCP; Franz R. Eberli, MD; Carl S. Apstein, MD

From the Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass.

Correspondence to Niraj Varma, MRCP, Cardiac Muscle Research Laboratory X720, Boston University School of Medicine, 650 Albany St, Boston MA 02118.

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.

Key Words: diastole • angina • rigor

This article has been cited by other articles:

				N. Varma, J. P. Morgan, and C. S. Apstein Mechanisms underlying ischemic diastolic dysfunction: relation between rigor, calcium homeostasis, and relaxation rate Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H758 - H771. [Abstract] [Full Text] [PDF]

				D. A. Brenner, C. S. Apstein, and K. W. Saupe Exercise Training Attenuates Age-Associated Diastolic Dysfunction in Rats Circulation, July 10, 2001; 104(2): 221 - 226. [Abstract] [Full Text] [PDF]

				N. Varma, F. R. Eberli, and C. S. Apstein Left ventricular diastolic dysfunction during demand ischemia: rigor underlies increased stiffness without calcium-mediated tension. Amelioration by glycolytic substrate J. Am. Coll. Cardiol., June 15, 2001; 37(8): 2144 - 2153. [Abstract] [Full Text] [PDF]