Effects of N-dimethyl propranolol (UM-272) on isolated cardiac mitochondria and microsomes.

N-dimethyl propranolol (UM-272) has been shown to protect the heart from injury produced by ischemia. In the present study we examined the effects of UM-272 on the function of isolated rabbit cardiac mitochondria and microsomes. Concentrations of 13 micrometers or below were without effect on these organelles. UM-272 (130 micrometers) significantly decreased respiratory control of mitochondria utilizing glutamate plus malate, or succinate, as substrates. At 1.3 mM, UM-272 increased the initial rate of basal oxygen consumption, and decreased the rate of ADP-stimulated respiration. UM-272 was slightly more potent than d,1-propranolol. At a concentration of 1.3 mM, UM-272 significantly decreased the rate and maximum amount of 45CaCl2 accumulated by microsomes in the presence of ATP and oxalate. Concentrations of drug that suppress cellular metabolism are close to those required to prevent ischemic injury. We suggest that sarcolemmal and intracellular actions of the drug which help to depress oxygen demand and ATP utilization may account for part of the drug's protective effects.