Biochemical dysfunction in heart mitochondria exposed to ischaemia and reperfusion.
Myocardial ischemia was produced in dogs by occluding the descending coronary artery. NAD decreased in the ischemic tissue taken 2 h after the arterial ligature, and an equivalent amount of nicotinamide was detected instead. A further breakdown occurred when fragments of ischemic and nonischemic tissue were incubated at 37 degrees C. In contrast, NAD concentration remained unchanged for as long as 60 min in incubated fragments from normal heart. When normal tissue was homogenized, an immediate hydrolysis of NAD was observed with the formation of stoichiometric amounts of nicotinamide. An excess of nicotinamide completely inhibited the NAD degradation. The NAD glycohydrolase activity assayed in vitro was similar in normal, ischemic, and nonischemic cardiac homogenates. The conclusions are that the NAD loss in the ischemic heart is due to the tissue NAD glycohydrolase activity and that the cell disorganization provoked by the occlusion of the coronary artery seems to facilitate the reaction between the substrate and the enzyme.