The role of platelets in contributing to occlusive coronary artery thrombus formation remains unresolved. A large number of studies have utilized in vitro techniques to study platelet aggregation. This report describes a model of spontaneous in vivo thrombus formation which involves application of current in the left circumflex coronary artery of the dog. Changes in mean coronary blood flow velocity (50% above control) are used to predict the point at which current can be discontinued without interrupting the ongoing process of thrombus formation. Thrombus formation proceeds to total vessel occlusion within 62 +/- 18 minutes after discontinuation of current. Coronary sinus plasma serotonin concentrations are used as an in vivo index of platelet aggregation during thrombus formation. Plasma serotonin levels increased only slightly above baseline levels during initial thrombus formation. Coronary sinus serotonin levels rose markedly after cessation of current, reaching a peak just prior to total vessel occlusion. The marked increase in serotonin concentration observed in the latter stages of thrombus formation strongly suggests that platelet aggregation is a significant factor in the evolution of an occlusive coronary thrombus.

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For an adequate evaluation of mitochondria from diseased hearts, basic characteristics of isolation, storage, media, ultrastructure and type of assay were first determined using mitochondria from normal animals. A proteinase procedure yielded mitochondria from small laboratory animals, with low respiratory control and marked permeability changes. The isolation medium yielding the most stable mitochondria with the highest respiratory control contained 0.18M KC1, 10mM EDTA, and 0.5% to 1% bovine serum albumin at pH 7.2. Heart failure in guinea pigs and rabbits was produced by varying degrees of stenosis of the ascending aorta. An aberration in respiratory control was found in mitochondria from hearts in severe failure. The quantitative differences between normal and experimental respiratory control values were greatest when the highest possible normal respiratory control levels were obtained. The difference between mitochondria prepared by a proteinase method from control and failing hearts was minimal. No changes in oxidative phosphorylation were noted in mitochondria from hearts arrested by nitrogen, suggesting that acute hypoxia does not irreversibly damage energy-liberating reactions. It is concluded that severe heart failure is characterized by defects in mitochondria] oxidative phosphorylation, and that techniques of isolation or assay or both are probably not causing the abnormalities.ADDITIONAL KEY WORDS hypoxia energy production cardiac mitochondria respiratory control cardiac arrest guinea pig rabbit B The cellular and molecular events characteristic of congestive heart failure are still largely unknown. During the past 10 years, two general and opposing concepts of energetics in heart failure have evolved, one implicating an aberration in energy-liberatingFrom the

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