Mark G. Zyvoloski

Determination of Experimental myocardial infarct size

Myocardial infarction was produced in anesthetized dogs by a 2-hr occlusion and 30-min reperfusion of the left anterior descending cornary artery. A balloon-reservoir perfusion system was used for reperfusion and delineation of perfusion bed size (area at risk) with Patent blue dye. Infarct mass was determined by a histochemical staining technique with triphenyl tetrazolium chloride. Regional myocardial perfusion in infarcted, ischemic, and normal regions was measured with radioactive microspheres. Infarct size was 8.5 +/- 1.6 g and accounted for irreversible damage in 9.2 +/- 1.9% and 32.5 +/- 4.8% of the left ventricle and area at risk, respectively. Regional myocardial blood flow within infarcted regions was constant over the 2-hr occlusion period (0.10 +/- 0.03 to 0.11 +/- 0.02 ml/min/g). Following reperfusion, these areas demonstrated significantly lower flow than did normal regions, Ischemic but noninfarcted tissue also had no change in flow over the occlusion period, but flow returned to normal following reperfusion. This study describes reliable methodology for production and determination of infarct size with simultaneous measurement of several factors involved in the relative extent of irreversible tissue damage.

Experimental Studies of Brain and Neck Injury

Static and dynamic axial tension loads were applied to the intact and isolated cervical column of the monkey and human cadaver. Radioactive microspheres were used to evaluate brain and spinal cord perfusion in the monkey. To determine neural pathway damage, somatosensory evoked potentials were recorded with stimulation of sensorimotor cortex, and in spinal cord with stimulation of cauda equina. The evoked potential amplitude decreased prior to heart rate and blood pressure changes presumably due to brainstem distention. The preliminary studies show, 1) the brain and spinal cord were well perfused as measured with the microspheres when the evoked potentials decreased, 2) the cervical isolated cadaveric monkey spinal column ligaments failed statically at approximately 1/2 to 1/3 the force required for dynamic disruption, 3) in the intact monkey, the cervical ligaments failed statically at approximately 1/2 the dynamic failure force, 4) the isolated human cervical ligaments failed at loads approximately three times those observed in the isolated monkey cervical column.

Beneficial effects of the dihydropyridine calcium antagonist, FR 34235, in a chronic coronary occlusion model☆

Administration of FR 34235 reduced aortic blood pressure and increased cardiac output in anesthetized dogs with an ameroid-induced coronary artery occlusion. Following FR 34235, there was an increase in perfusion within normal myocardium and ischemic subepicardium. Ischemic zone flow to subepicardium and subendocardium were both significantly increased when aortic pressure was held at control levels. The data demonstrate marked enhancement in oxygen supply to an area distal to a chronic coronary occlusion by a new calcium antagonist, FR 34235.

The slow-channel calcium blocking agent, nitrendipine, and coronary collateral blood flow.

The effects of a new dihydropyridine slow-channel calcium blocking agent, nitrendipine, on hemodynamics and myocardial blood flow in normal and ischemic areas distal to either an acute or chronic coronary artery occlusion were studied in anesthetized dogs. Nitrendipine produced significant and dose-related decreases in mean aortic blood pressure and increases in flow through the nonobstructed coronary artery. In acute coronary artery occlusion experiments, only small changes in perfusion of the ischemic zone were observed following nitrendipine. On the other hand, in dogs with a chronic coronary artery occlusion and well-developed collateral circulation, nitrendipine produced significant and dose-related increases in subepicardial perfusion within the central ischemic zone. No change in subendocardial blood flow during drug-induced hypotension was observed, but when aortic pressure was held constant, there was an increase in subepicardial, subendocardial, and overall transmural myocardial perfusion. The data demonstrate that nitrendipine improves oxygen supply to collateral-dependent myocardium via an increase in coronary collateral blood flow in a model of chronic coronary occlusion.

Importance of Retrograde Coronary Flow in the Prediction of Experimental Myocardial Infarct Size

The relationship between myocardial infarct size (measured by a histochemical stain) and coronary collateral blood flow (measured via retrograde flow and by use of radioactive microspheres) was studied in anesthetized dogs with high, moderate and low retrograde flows undergoing a 2-hour occlusion and 30-min reperfusion of the left anterior descending coronary artery. The results demonstrate that experimental myocardial infarct size is closely related to native coronary collateral blood flow, and the large variability in collateral perfusion amongst dogs is a source of variability in the mass of myocardium undergoing irreversible damage following acute coronary occlusion. Results also demonstrate that the variability in experimental infarct size can be reduced and ultimate infarct size predicted prior to irreversible tissue injury by initial measurement of retrograde coronary blood flow.