Andries J. Brink

Effect of ethanol on metabolism and function of perfused rat heart

Abstract The effect of ethanol (100 and 200 mm.) was studied on the metabolism and function of isolated, perfused rat hearts from control and ethanol-treated rats. Ethanol (200 mm.) increased incorporation of palm tate-C 14 uptake into tissue lipids, while C 4 O 2 formation was decreased, indicating a shift from exogenous to endogenous fuel. Long-term administration of ethanol resulted in a significant change in the pattern of myocardial palmitate metabolism as shown by the increased incorporation of palmintate-C 14 into tissue lipids. Ethanol depressed work performance and tension development of control rat hearts. Long-term administration of ethanol had no effect on the work performance of the perfused rat heart, but an increase in t-PH was suggestive evidence of an impairment in contractility.

Work Performance of the Isolated Perfused Beating Heart in the Hereditary Myocardiopathy of the Syrian Hamster

The work performance of the isolated beating heart of control Syrian hamsters and hamsters suffering from an inbred myocardiopathy was studied in a system using a myographic differential force transducer. A stretch force of either 3.75 or 8.75 g was applied to the hearts. Myocardial metabolism of pyruvate-3-14C and palmitate-1-14C was studied with and without a stretch force. A definite reduction in work performance of the myopathic heart could be demonstrated. Peak height of contraction, tension-time index, tension time per minute and heart rate were significantly lower. The progressive myocardial fiber lengthening, caused by the stretch force, was less in the myopathic hearts. No difference was observed between the uptake and oxidation of pyruvate-3-14C and palmitate-1-14C by control and myopathic hearts. The presence of a stretch force affected metabolism of both hearts in a similar manner. Two mechanisms for explaining the reduction in work performance by the myopathic heart were observed, namely, a reduction in heart rate and a relative inability of the myopathic muscle fibers to lengthen. The depressed mechanical performance could not be related directly with altered substrate metabolism or with reduction in total muscle mass.

Effect of propranolol on the metabolism and function of the rat heart

Abstract The effect of propranolol, a beta-adrenergic blocking agent, was studied on the metabolism and function of the isolated, perfused rat heart. Propranolol (20 μ m ) depressed the oxygen consumption, coronary flow rate, palmitate uptake and oxidation as well as the high energy phosphate contents of the perfused heart. Propranolol significantly reduced heart rate while the time to peak height of developed tension period was increased. The effect of propranolol was also studied on the metabolism of heart muscle slices and the sarcosomal oxidative phosphorylation process. With pyruvate or glucose as substrate, propranolol stimulated the respiration and metabolism of heart slices, while it depressed oxidative phosphorylation. In order to eliminate the effect of the reduction in heart rate on substrate metabolism in the perfused heart, additional studies were performed in which the effect of propranolol was studied in hearts driven at a controlled heart rate, by a pacemaker. The results showed that the chronotropic effect of propranolol had a significant effect on the reduction in substrate metabolism.

Protein synthesis in myocardial ischaemia and infarction

Abstract Protein synthesis, as indicated by the in vitro and in vivo incorporation of isotopic amino acids into myocardial proteins, was determined at various time intervals after ligation of the left coronary artery. The results show that the in vitro incorporation of l -[4,5- 3 H]leucine and l -[U- 14 C]lysine into the soluble protein and actomyosin fractions of heart muscle slices was normal up to 6 h after the onset of ischaemia. The rate of amino acid incorporation was significantly higher 12 h after occlusion of the left coronary artery and remained elevated for at least 2 months. After 3 months, the rate of amino acid incorporation into both protein fractions returned to normal. Protein synthesis was elevated in both the uninfarcted and infarcted areas of the myocardium. Studies on the in vivo incorporation of l -[4,5- 3 H]leucine into total myocardial proteins also showed that protein synthesis was normal up to 6 h after occlusion of the left coronary artery.

The Baboon (Papio ursinus) Heart (Coronary Blood Supply, Muscle Function and Metabolism)

The sub-human primate baboon (Papio ursinus) was subjected to cardiac catheterisation studies and pathologic injection techniques with a view to establishing baseline values pertaining to coronary artery morphology, coronary blood flow and myocardial energetics and metabolism. The similarities to the human situation (and minor differences) are considered in the light of possible extrapolation to clinical conditions in contemplated future experimental studies of myocardial physiology.

Effect of a high fat diet on the metabolism and mechanical behaviour of the isolated rat heart

Abstract The effects of a high fat, atherogenic diet was studied on the metabolism and mechanical behaviour of the isolated perfused rat heart. Palmitate and pyruvate metabolism were similar in control and fat-fed perfused hearts. Glucose uptake was lower in the fat-fed perfused heart, but the percentages of glucose converted to 14CO2 and glycogen were similar for the two groups. Explanations for the differences in glucose uptake are discussed. Fat-fed perfused hearts, with glucose as substrate, had significantly lower values for spontaneous rate, stress relaxation and tension time per minute than control hearts. With palmitate as substrate, the fat-fed perfused hearts had decreased coronary flow rates and a greater rate of tension increase on contraction. Contraction characteristics were different when hearts were perfused with glucose, compared with palmitate, in both dietary groups.

Nucleic acid synthesis in myocardial ischaemia and infarction

The rate of in vivo and in vitro labelling of DNA and RNA in left and right ventricles were studied at various time intervals after right coronary artery ligation. The RNA concentration of both left and right ventricles were significantly higher than the controls 7 days after ligation and remained elevated for at least 14 days. The DNA concentration remained significantly higher for one month. In vitro as well as in vivo labelling of myocardial RNA, were unaffected by coronary artery ligation. In vitro labelling of DNA was unchanged during ischaemia and infarction, while in vivo DNA labelling was significantly increased.