phosphocreatine and Tachycardia--Ventricular

Although both clinical and animal studies have shown that ischemic tolerance is reduced in the senescent myocardium, it has not been clarified when myocardium becomes more vulnerable to ischemia. Preconditioning protects the hearts of young adult animals of various species, but its effects are not identical in human studies. We investigated whether ischemic tolerance and the effect of preconditioning decreased in isolated hearts of middle-aged rats.. The hearts of young adult rats (12 weeks old: group Y, n = 44) and middle-aged rats (50 weeks old: group M, n = 44) were subjected to global ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also subjected to preconditioning and then to 20 (group Y, n = 22) or 15 (group M, n = 22) minutes of ischemia followed by reperfusion. Left ventricular developed pressure (LVDP) was decreased by 40% to 60%, and the level of ATP was decreased by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (% LVDP, 40.5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14.1; creatine phosphate, 17.0 to 23.1 mumol/g dry wt) and reduced left ventricular end-diastolic pressure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to 132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca2+ release after ischemia in group Y. Preconditioning exerted opposite effects in group M (% LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 mumol/g dry wt; and CK release, 176 to 332 U/g dry wt). Preconditioning was associated with increases in the incidence of reperfusion-induced ventricular fibrillation (0% to 62.5%) and the rate of sarcoplasmic reticulum Ca2+ release in group M.. These results indicate that hearts became more vulnerable to ischemia with age and that the beneficial effects of preconditioning were reversed in middle-aged rat hearts.

Topics: Adenosine Triphosphate; Age Factors; Animals; Calcium; Creatine Kinase; Energy Metabolism; Heart; Ischemic Preconditioning, Myocardial; Male; Myocardial Reperfusion; Myocardium; Phosphocreatine; Rats; Rats, Inbred F344; Sarcoplasmic Reticulum; Tachycardia, Ventricular; Ventricular Function, Left

At constant pressure work there was an increase in the oxygen consumption of the dog heartlung preparation after tachycardia due to auricular stimulation and a far greater increase in consumption after ouabain-induced ventricular tachycardia, as compared with control hearts beating at their own sinus rhythm. In neither condition was the increase in coronary flow greater than the spontaneous increase in the controls. It is suggested that an increase in oxygen demand, under certain circumstances, may be met primarily by an increased desaturation of coronary blood. "Therapeutic" doses of ouabain did not improve the mechanical efficiency of the preparation. "Toxic" doses of ouabain which gave rise to ventricular tachycardia did not decrease the phosphocreatine or labile nucleotide phosphorus content of the heart provided there was no hypoxia of the heart muscle.

Topics: Animals; Dogs; Heart; Myocardium; Ouabain; Oxygen Consumption; Phosphocreatine; Strophanthins; Tachycardia; Tachycardia, Ventricular