Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo.

Abstract

The mechanisms responsible for changes in myocardial contractility during regional ischemia are unknown. Since changes in high-energy phosphates during ischemia are sensitive to reductions in myocardial blood flow, it was hypothesized that myocardial function under steady-state conditions of graded regional ischemia is closely related to changes in myocardial high-energy phosphates. Therefore, phosphorus-31 nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements4 of regional subendocardial blood flow, high-energy phosphates, pH, and myocardial segment shortening were made during various degrees of regional ischemia in which subendocardial blood flow was reduced by 16-94%. During mild reductions in myocardial blood flow (subendocardial blood flow = 83% of nonischemic myocardium), only the ratio of phosphocreatine to inorganic phosphate (PCr/P1), Pi, and [H'I were significantly changed from control. PCr, ATP, and PCr/ATP were not significantly reduced from control with mild reductions in blood flow. Changes in myocardial segment shortening were most closely associated with changes in PCr/ Pi (r = 0.94). Pi and [H'I were negatively correlated with segment shortening (r = -0.64 and -0.58, respectively) and increased over twofold when blood flow was reduced by 62%.Thus, these data demonstrate that PCr/P; is sensitive to reductions in myocardial blood flow and closely correlates with changes in myocardial function. These data are also consistent with a role for Pi or H' as inhibitors of myocardial contractility during ischemia. (J. Clin. Invest. 1990. 85:706-713.) high-energy phosphates -magnetic resonance spectroscopy * myocardial ischemia * phosphocreatine

Diminished Myocardial Function Precedes Tissue Acidosis during Coronary Hypoperf usion

“…Our data agree with the work of Clark [II] and Schafer et al [12] who have demonstrated in animal models of acute ischemia that hydrogen ion concentration was the slowest changing variable, lagging far behind functional changes. However, acidosis affects every step in the excitation-contraction coupling pathway including both the delivery of calcium to the myofilaments and the response of the myofilaments to calcium.…”

Low- and high-blood flow regions in the normal pig heart are equally vulnerable to ischaemia during partial coronary stenosis

“…by 30% for a 60% reduction in regional flow in pig heart [27]. However, even if regional blood flow in pig myocardium is reduced by 90%, leading to a reduction of PCr by some 80%, the ATP content is still not reduced and apparently is still buffered well by PCr [27]. This is in agreement with theoretical considerations of the creatine kinase and adenylate kinase high-energy phosphate buffering system which show that ATP is virtually constant until PCr drops below 10% of its normal level.…”

“…by 30% for a 60% reduction in regional flow in pig heart [27]. However, even if regional blood flow in pig myocardium is reduced by 90%, leading to a reduction of PCr by some 80%, the ATP content is still not reduced and apparently is still buffered well by PCr [27].…”

Taurine detected using high-resolution magic angle spinning 1H nuclear magnetic resonance: A potential indicator of early myocardial infarction

“…It has previously been shown that Cre levels, belonging to the myocardial energy index, are related to myocardial functional performance under ischemic conditions in animal hearts in vivo (37). In 31 P-MRS, PCr and ATP represent the level of myocardial energy.…”