The effects of beta-blocking agents on mitochondrial function in ischemic myocardium

We investigated the protective effects of beta-adrenergic blocking agents on ischemia-induced mitochondrial dysfunction in 42 anesthetized mongrel dogs. The animals, divided into 6 groups of 7 dogs each, were premedicated with either saline for the controls, or D, L-propranolol (0.5 mg/kg), D-propranolol (0.5 mg/kg), D, L-acebutolol (2.5 mg/kg), D, L-pindolol (0.1 mg/kg), or L-isoproterenol (0.2 microgram/kg/min, for 10 min). Myocardial mitochondria were prepared from both the normal and the ischemic areas after 30 min of coronary ligation. The concentration of long-chain acyl-CoA was measured enzymatically. Respiratory control index, ADP/O, and the rate of oxygen consumption in State III of mitochondria were also measured. In the control group, acyl-CoA in ischemic mitochondria increased significantly compared with that in normal mitochondria, and mitochondrial dysfunction was observed. Administration of L-isoproterenol further increased acyl-CoA level and accelerated the dysfunction, whereas premedication with beta-blocking agents reduced the elevation of acyl-CoA level and prevented the dysfunction. Premedication with D-propranolol had no effect on mitochondria. Since the accumulation of acyl-CoA interferes with normal mitochondrial function, these results suggest that the protective effects of beta-blocking agents are based, at least in part, on the prevention of the accumulation of acyl-CoA esters.