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

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... erum 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-liberating From the