Oxidative Phosphorylation in Mitochondria Isolated from Chronically Stressed Dog Hearts

Abstract

Oxidative and phosphorylative activities were measured polarographically in mitochondria isolated from the right and left ventricles of normal and chronically stressed dog hearts. Chronic myocardial stress was produced experimentally by surgical procedures (combined tricuspid insufficiency and pulmonary stenosis, pulmonary insufficiency, aortic stenosis, aortic insufficiency, Potts's anastomosis) and by inducing thyrotoxicosis. Experimental stress periods ranged from 332 to 608 days. Some of the dogs had overt symptoms of congestive heart failure at the time they were killed.Mitochondria isolated from the stressed hearts had abnormally high values for oxidative activity and respiratory control ratios when incubated in the presence of malate-pyruvate. In the presence of succinate, they had either normal or slightly elevated values for oxidative activity and respiratory control ratios. No differences were found between mitochondria from normal and stressed hearts with regard to the efficiency (ADP/O) of oxidative phosphorylation. Estimates of mitochondrial protein per gram of myocardial tissue indicated that the stressed hearts contained normal amounts of mitochondria. The results of this study suggest that the mitochondrial oxidative and phosphorylative capabilities of the chronically stressed myocardium are not impaired.ADDITIONAL KEY WORDS mitochondrial function mitochondrial respiration mitochondrial respiratory control experimental chronic congestive heart failure mitochondrial metabolism• Chronic stress on the heart often results in a gradual deterioration of myocardial performance as evidenced clinically by congestive heart failure. Although this deterioration has long been considered to be a reflection of a biochemical abnormality in the myocardium, positive identification of this abnormality has not been achieved. The present report describes a search for biochemical abnormalities in mitochondria isolated from chronically stressed dog hearts, some of which appeared to be in chronic failure.From the Heart Biochemistry Research Laboratory of the Cardiovascular Service, Division of Thoracic Surgery, and Departments of Surgery and Physiological Chemistry, Ohio State University College of Medicine, Columbus, Ohio 43210. These studies were supported by U. S. Public Health Service Research Grant HE 05273-06 from the National Heart Institute.Accepted for publication May 20, 1968. The results of previous studies on the condition of mitochondria in the chronically stressed or failing heart are conflicting. Mitochondrial function was reported to be normal in some of these studies (1-4), whereas in others a reduction in oxidative activity (5-7), respiratory control ratios (6) and efficiency of oxidative phosphorylation (5-7) was observed. The factors responsible for these divergent results have not been clear. To test the possibility that some of the conflict in these reports is due to differences in the means by which myocardial stress was produced, we have measured oxidative activity, respiratory control...

Hypertrophied Non-Failing Rat Heart: PARTIAL BIOCHEMICAL CHARACTERIZATION

“…There is considerable controversy in the literature regarding what happens to heart mitochondria in cardiac hypertrophy (1,6,(8)(9)(10)(11)(12)(13)(14)(15). Wollenberger and his co-workers (8)(9)(10) have reported that there is a decrease in the ratio of mitochondrial to lnyofibrillar area, a 50% disappearance of mitochondrial cristae, a significantly reduced capacity to carry out oxidative phosphorylation, and a diminished level of malate dehydrogenase activity in hypertrophied, non-failing canine hearts.…”

“…It appeared possible that a similar response might occur in heart muscle subjected to an increased work load. The published results of studies relating to this question are conflicting (1,6,(8)(9)(10)(11)(12)(13)(14)(15). A considerable portion of the present study was, therefore, devoted to obtaining biochemical information, using a number of independent approaches, regarding the response of heart mitochondria to cardiac hypertrophy.…”

Heart Mitochondrial Function in Acute and in Chronic Hyperthyroidism in Rats

“…The rat is a more susceptible species than the dog. In the latter no decreases in efficiency of oxidative phosphorylation have been observed following treatment for as long as 6 months to 2 years (3,5).…”

“…Studies to date suggest that a biochemical lesion in the area of oxidative phosphorylation is not involved in the heart as in other tissues. Neither sarcosomal function (3)(4)(5) nor myocardial levels of the end products of oxidative phosphorylation, phosphorylcreatine and adenosine triphosphate (ATP) (3,4,6) were decreased in acute or chronic hyperthyroid animals. Nevertheless, the reduced myocardial resistance to anoxia (7) and the increased oxygen consumption (3,8) in the hyperthyroid heart would appear to reflect involvement of energy production in the mitochondria.…”

A Toxic Cardiomyopathy Caused byCassia occidentalis. II. Biochemical Studies in Poisoned Rabbits

“…In view of the morphological evidence of mitochondrial damage, the function of mitochondria isolated from the hearts of rabbits poisoned by coffee senna was studied using polarographic techniques to evaluate the status of mitochondrial respiration [5,20]. These techniques have been used by others in the study of various cardio-myopathies [2,[15][16][17]28,33,39]. The studies were combined with examination of several enzymes of the glycolytic and citric acid cycles, and with assays of glycogen and lactate.…”