The relationships of high energy phosphates, tissue pH, and regional blood flow to diastolic distensibility in the ischemic dog myocardium

Abstract

Myocardial ischemia due to increased oxygen demand (pacing tachycardia plus critical coronary stenoses) alters diastolic distensibility and relaxation more than ischemia of comparable duration due to coronary occlusion. To investigate the relationship between myocardial diastolic function and metabolism, we compared myocardial high energy phosphate content, tissue pH, and regional blood flow for these two types of ischemia in anesthetized open-chest dogs. Myocardial biopsies were done with a high-speed air-turbine biopsy drill, permitting, rapid (<1-second) freezing of tissue samples from both nonischemic and ischemic areas, while myocardial pH was measured with a hydrogen ion-selective polymer membrane implanted in the subendocardium. After 3 minutes of pacing tachycardia in dogs with critical coronary stenoses (demand-type ischemia, n = 14), regional systolic function (% segment shortening by ultrasonic crystals) was mildly depressed (from 19 ± 2% control to 13 ± 2% post-pacing, P < 0.01), while left ventricular diastolic pressure-segment length relations shifted upward, indicating decreased distensibility of the ischemic myocardial segment. Associated with these changes in function, subendocardial adenosine triphosphate decreased (from 31.3 ± 1.5 to 27.9 ± 1.0 nmol/mg protein, P < 0.01), as did creatine phosphate (53.8 ± 2.1 to 39.6 ± 2.5 nmol/mg protein, P < 0.01), while myocardial pH declined slightly (ΔpH = -0.14 ± 0.02, P < 0.01). In contrast, at 3 minutes of coronary artery occlusion (primary ischemia, n = 14), regional segment shortening was replaced by systolic bulging (% shortening decreased from 17 ± 2% to -2 ± 1% during occlusion, P < 0.01), while left ventricular pressure-segment length relations were not shifted upward, and there was no decrease in diastolic distensibility of the ischemic segment. With coronary artery occlusion, subendocardial adenosine triphosphate declined slightly (33.2 ± 0.5 to 29.2 ± 2.0 nmol/mg, P < 0.05), while creatine phosphate decreased substantially (51.1 ± 2.3 to 7.8 ± 1.4 nmol/mg protein, P < 0.01). Myocardial pH fell strikingly (ΔpH = -0.33 ± 0.03, P < 0.01), and the decline was 236% of that seen with demand-type ischemia. Regional myocardial blood flow (microsphere technique) showed a decreased endocardial:epicardial (endo:epi) ratio (1.04 ± 0.04 control vs. 0.40 ± 0.05 during pacing, P < 0.01) and absolute subendocardial flow (1.02 ± 0.47 to 0.47 ± 0.05 ml/min per g, P < 0.01) with demand-type ischemia. However, subendocardial blood flow in demand-type ischemia was still much greater than flow during coronary artery occlusion (0.10 ± 0.03 ml/min per g, P < 0.01). In summary, diastolic dysfunction was prominent during ischemia caused by increased oxygen demand, but was minimal during ischemia due to primary coronary flow reduction of equal duration. The diastolic dysfunction could not be explained simply by adenosine triphosphate depletion, which was modest and similar with both types of ischemia. Protection against diastolic dysfunction in primary ischemia may reflect the combined effects of hydrogen ion accumulation, loss of coronary vascular turgor, and repeated systolic stretch of the ischemic segment.