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The purpose of this study was to document early structural changes in the human heart after the initial administration of doxorubicin. Endomyocardial biopsies were performed at baseline and at 4 and 24 hours after doxorubicin administration to 13 patients. Morphometric analysis of electron micrographs (x 31,200) quantitated mitochondrial and tubular sizes (sarcoplasmic reticulum and T tubules). The mitochondrial size increased from 0.25 +/- 0.01 mu 2 (mean +/- SE) at baseline to 0.27 +/- 0.03 mu 2 (not significant [NS]) at 4 hours and 0.30 +/- 0.03 mu 2 (NS) at 24 hours. The tubular size increased from 2.24 +/- 0.13 x 10(4) nm2 at baseline to 2.60 +/- 0.26 x 10(4) nm2 (P less than 0.05) at 4 hours and 2.46 +/- 0.29 x 10(4) nm2 (NS) at 24 hours. Micrographs analyzed for nuclear changes showed nucleolar contraction and segregation of granular and fibrillar components. These changes were noted in five of ten patients at 4 hours and in eight of 13 patients at 24 hours. Serial echocardiographic and systolic time interval determinations of left ventricular function demonstrated a significant improvement at both 4 and 24 hours. In conclusion, doxorubicin has its most significant effect on tubular structures. Left ventricular function improved during this time despite these findings.

The role of myocardial infarction was investigated in 121 cases of sudden death with atherosclerotic heart disease. In addition to supporting other reports which have demonstrated the importance of chronic occlusion of the coronary vessels in relation to the high rate of infarctions found in such cases, the authors presented evidence which showed differences in occurrence in the sites of remote and recent infarctions, a lack of concordance between the sites of recent infarctions, and acute thrombosis in coronary vessels proximal to these lesions. No relationship between patient age or prior symptoms could be associated with the occurrence of infarction. Evidence was also presented which discounted the possible role of transmural infarction in the formation of acute thrombosis. These pathological observations support the concept that sudden cardiac deaths are results of functional instability of the myocardium produced by advanced coronary atherosclerosis.

A case of endomyocardial fibrosis with intramyocardial calcification was characterized by symptoms of restrictive cardiomyopathy resembling constrictive pericarditis. Pathological findings were typical of those found in classical Davies' disease, originally encountered and described in Uganda.

The histopathologic features of nonischemic congestive cardiomyopathy (CCM) include diffuse and focal fibrosis, vacuolar degeneration, and myofiber hypertrophy. Eleven patients with CCM and five controls were studied. Fibrosis and degree of vacuolization were quantified by means of stereologic techniques; myocardial cell diameter was measured with an ocular micrometer. Five levels of the left ventricular free wall were examined. Area I was immediately subepicardial, and area 5 was immediately subendocardial. In all areas, fibrosis, vacuolization, and fiber diameter were significantly greater in the experimental group than in the control group (P less than 0.05). In addition, fibrosis and vacuolization had an umbrella distribution, which peaked in area 4, the area adjacent to the subendocardium (P less than 0.01). The distributions of fibrosis and vacuolar degeneration suggest compromised blood flow to the inner myocardial layers, with relative sparing of the immediate subendocardial region owing to its proximity to the left ventricular cavity.

Left-ventricular heart muscle and pectoralis major muscle of the rat were studied to determine the intracellular localization of lactic dehydrogenase (LDH) isoenzymes. Fixation of tissue for 2 hr in 2% buffered formaldehyde provided the best preservation of the ultrastructure and enzyme activity. Total LDH activity was found diffusely in the ground substance of the sarcoplasm and in the mitochondria of the heart muscle. In skeletal muscle a strong reaction was noted in the sarcoplasmic reticulum, and moderate activity was seen in the ground substance of the sarcoplasm and in the mitochondria. Differentiation of the isoenzymes of LDH was accomplished by addition of 4 M urea or application of heat. Heart-type isoenzymes were mainly localized in the mitochondria and sarcoplasm, whereas muscle-type isoenzymes were localized mainly in the sarcoplasmic reticulum of the skeletal muscle. It is speculated that the sarcoplasmic reticulum of the skeletal muscle is the site of anaerobic glycolysis and that the sarcoplasm and mitochondria are involved primarily in aerobic metabolism of pyruvate.

Employing an isolated perfused rat heart preparation, we investigated the contribution of anaerobic metabolic energy to the performance, recoverability, and ultrastructure of the heart perfused at 32 degrees C in 5% albumin in Krebs-Ringer Bicarbonate solution. During exposure to anoxia for 30 min, inclusion in the perfusate of the anaerobic substrate, glucose, resulted in marked improvement in electrical and mechanical performance of the heart and in enhanced recovery during the subsequent period of reoxygenation. Lactate production was fivefold greater in the glucose-supported anoxic heart than in the anoxic heart without glucose. Electron microscope sections of the hearts exposed to anoxia in the absence of glucose revealed alterations in mitochondrial morphology and dilatation of the longitudinal tubules. These morphologic changes during anoxia were averted by inclusion of glucose in the perfusion fluid. The data are consistent with the hypothesis that anaerobic energy generation plays a significant role in preserving myocardial function and structure and in promoting recoverability of the anoxic mammalian heart.