Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

Abstract

IntroductionThe purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. (6), aortic stenosis (7), dilated cardiomyopathy in the Syrian hamster (8), uninephrectomy plus steroid treatment (9), or the spontaneously hypertensive rat (10). The purpose of the present work was, therefore, to define performance, oxygen consumption, and parameters of energy reserve, i.e., tissue contents of ATP and creatine phosphate (CP), creatine kinase (CK) activity and isoenzyme distribution, and phosphoryl transfer rates via CK (using 3P-magnetization transfer), in normal rat heart and in residual intact myocardium after MI. Using these measurements, we directly tested whether changes in energy metabolism can contribute to contractile dysfunction in post-MI heart. MethodsAnimals and experimental MI. Infarcts or sham operations were carried out in 12-wk-old Wistar rats, kept in a 12-h light-dark cycle. Left anterior descending coronary artery (LAD) ligation was performed by a previously described technique (1, 11). Briefly, a left thoracotomy was performed under ether anesthesia and positive pressure ventilation. The heart was rapidly exteriorized by applying gentle pressure on both sides of the thorax. The LAD was ligated between the pulmonary outflow tract and the left atrium. The heart was then replaced into the thorax, lungs were inflated by increasing positive end-expiratory pressure, and the wound was closed immediately. Sham operation was performed using an identical procedure except that the suture was passed under the coronary artery without ligation. Mortality rate of infarcted rats for the first 24 h after the operation was 40-50%. Surviving rats were kept on commercial rat chow and water ad libitum. All procedures conformed to the guiding principles of the American Physiological Society. Isolated rat heart preparation. 8 wk after LAD ligation or sham operation, rats were anesthetized by injecting 20 mg pentobarbital sodium intraperitoneally. After thoracotomy, the heart was rapidly excised and immersed in ice-cold buffer. The aorta was dissected free and mounted onto a cannula attached to a perfusion apparatus, as described previously (12). Retrograde perfusion of the heart was started in the 1092Neubauer et al.J. Clin. Invest.C) The

Chronic Phosphocreatine Depletion by the Creatine Analogue β-Guanidinopropionate Is Associated With Increased Mortality and Loss of ATP in Rats After Myocardial Infarction

“…15,16 The mortality rate of infarcted rats for the first 24 hours after the operation was 40% to 50%. The investigation conforms with the Revised Guide for the Care and Use of Laboratory Animals.…”

“…15 Perfusion of the heart with phosphate-free Krebs-Henseleit buffer was started in the Langendorff mode at 37°C and a coronary perfusion pressure of 100 mm Hg. Coronary flow (CF) was measured by an ultrasonic flow probe (Transonic Systems Inc).…”

“…CF per gram viable tissue was calculated assuming a scar weight of 14% of the myocardium. 15 For measurement of cardiac performance, a water-filled latex balloon was inserted into the LV. 15 LV pressure-volume curves were obtained by stepwise (⌬0.05 mL) increases in balloon volume until maximum LVDP was reached or until LV end-diastolic pressure exceeded 50 mm Hg.…”

“…15 For measurement of cardiac performance, a water-filled latex balloon was inserted into the LV. 15 LV pressure-volume curves were obtained by stepwise (⌬0.05 mL) increases in balloon volume until maximum LVDP was reached or until LV end-diastolic pressure exceeded 50 mm Hg. Thereafter, end-diastolic pressure was set to 10 mm Hg for the duration of the MR measurements.…”

“…15 Sections were stained with picrosirius red, and the lengths of scar and noninfarcted muscle were measured. The average ratios of endocardial and epicardial surfaces defined the infarct.…”