title: Structural and metabolic correlates of cell injury in the hypertrophied myocardium during valve replacement.
abstract: To characterize the ultrastructural and metabolic changes occurring in the hypertrophied ventricle during cardiac operations in man, we studied 36 patients with valvular heart disease undergoing valve replacement, during which multiple doses of cold potassium cardioplegic solution were administered (Group I). Each patient had substantial ventricular hypertrophy according to measurements made of left ventricular mass, with a mean of 232.1 +/- 19.8 gm/m2 (normal: 92 +/- 16 gm/m2). Serial biopsy specimens were obtained from the left ventricular apex at the initiation of bypass, during the cross-clamp interval, and during reperfusion. Each specimen was scored from 0 to 4 according to ischemic changes in nuclear chromatin, mitochondrial swelling, myofibrillar edema, glycogen depletion, and overall cell morphology. Myocardial pH and temperature were measured continuously in the left ventricular free wall. During the cross-clamp period, ischemic injury was evidenced by changes in nuclear chromatin (0.38 +/- 0.10 to 1.25 +/- 0.21, p less than 0.0001), intracellular edema (0.43 +/- 0.06 to 0.97 +/- 0.14, p less than 0.002), overall cell morphology (0.37 +/- 0.06 to 0.97 +/- 0.14, p less than 0.001), and mitochondria (0.10 +/- 0.05 to 0.19 +/- 0.07, p less than 0.0001). During reperfusion, mitochondrial swelling increased further (0.19 +/- 0.07 to 0.35 +/- 0.08, p less than 0.0001) and glycogen stores were depleted (0.63 +/- 0.13 to 0.96 +/- 0.17, p less than 0.02), while the other structures remained unchanged. Myocardial pH declined during ischemic arrest from 6.89 +/- 0.04 to 6.40 +/- 0.04 (p less than 0.001). The changes in myocardial pH in Group I were compared to changes in myocardial pH in 10 patients (Group II) with no left ventricular hypertrophy undergoing isolated coronary bypass graft operations with the same protective techniques. In contrast to Group I, myocardial pH did not fall in Group II during ischemic arrest (6.98 +/- 0.06 to 6.94 +/- 0.05, p = not significant). Thus, with the use of current myocardial protective techniques, ultrastructural and metabolic changes indicative of ischemia are produced in the hypertrophied myocardium. The structural alterations consist of changes in nuclear chromatin and intracellular edema during the ischemic phase and by mitochondrial swelling during reperfusion.
mesh_terms: D000328:Adult; D000368:Aged; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D001026:Coronary Artery Bypass; D006324:Heart Arrest, Induced; D006349:Heart Valve Diseases / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D006350:Heart Valve Prosthesis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*