Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

Abstract

The relationships between contractile function, myocardial oxygen consumption, and tissue high energy phosphate and lactate content were investigated during partial coronary flow disruption. The experimental preparation was an isolated, isovolumic retrograde blood-perfused rabbit heart. Both developed pressure (r = 0.94) and dp/dt (r = 0.95) exhibited strong linear correlations with myocardial oxygen consumption that were stable for up to 45 min after blood flow reduction. In contrast, tissue high energy phosphate content exhibited nonlinear relationships with both developed pressure and oxygen consumption such that systolic mechanical function and oxidative metabolism declined to 20 and 30% of control values, respectively, before significant abnormalities in myocardial high energy phosphate stores were observed. Similarly, developed pressure and oxygen consumption decreased to 36 and 48% of control, respectively, before abnormal tissue lactate content was detected. The results of this study indicate that: (a) mechanical function is closely related to the rate of oxidative energy production during partial coronary flow disruption, and (b) despite the development of significant contractile dysfunction, tissue high energy phosphate content remains at normal levels except under the most severely flow-deprived conditions. The preservation of tissue energy stores can be explained by the apparent coupling of contractile performance to oxidative energy production, which could function to maintain myocardial energy balance during partial coronary flow restriction.

Cardiac contractile dysfunction during mild coronary flow reductions is due to an altered calcium-pressure relationship in rat hearts.

“…4 a) (8) showed a relationship between decreases in coronary perfusion pressure and a fall of PCr/Pi in the perfused rat heart. However, several perfused heart studies have suggested that the fall in contractility associated with mild coronary flow reductions occurs without changes in cardiac energy phosphates (6,7,14,15 The present study, which demonstrates a significant increase of Pi at a coronary flow to 75% of control, differs in several ways from the aforementioned reports. The signal/ noise ratio of the 3"P-MRS spectra was substantially improved by acquiring data over 10-min steady state periods of mild coronary flow reductions.…”

“…Although the increase of Pi was relatively small at this level ofcoronary flow reduction, it was ofa magnitude that has been associated with marked reductions of force and an alteration of the calcium-force relationship in skinned myofiber studies ( 12,13). In contrast, previous perfused heart studies (6,7,14,15) reported no change in energy phosphates as measured by 31P magnetic resonance spectroscopy (31P-MRS) during mild coronary flow reductions (i.e., 50-99% of 1. Abbreviations used in this paper: ACa., cytosolic free calcium transient amplitude; dCah, diastolic calcium; F385/F454, ration of Indo-l fluorescence intensities at emission wavelengths of 385 and 454 nm; 5F-BAPTA, 5,5'-difluoro derivative of l,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; MPA, methylphosphonic acid; Pi, inorganic phosphate; 3'P-MRS, 3'P magnetic resonance spectroscopy.…”

“…Factors thought to play a causal role in ischemic contractile dysfunction are (a) a decrease of Preliminary results of this study were presented at the 64th Scientific Session of the American Heart Association, Anaheim, CA, 1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] No- To assess the role of cytosolic free calcium in depressing contractility during reductions of coronary flow, several investigators have measured the cytosolic free calcium transient during ischemia (1)(2)(3)(4). However, these studies have yielded conflicting results.…”

A single myocardial stretch or decreased systolic fiber shortening stimulates the expression of heat shock protein 70 in the isolated, erythrocyte-perfused rabbit heart.

“…We used an isolated, isovolumic, working red cell-perfused heart preparation that was developed in our laboratory based on the work of Marshall (8) and has been described previously in detail (6,7,9 (10) and has been previously reported (1 1). The heart was then placed in a water-jacketed constant temperature chamber and submerged in saline.…”

“…A red cell perfusate as previously described (7,8) RNA isolation and Northern blot analysis. At the completion of nonischemic perfusion protocols the left ventricle was flushed with saline to remove the blood, dissected from the right ventricle, and then frozen in liquid nitrogen.…”