OXYGEN FREE-RADICAL INJURY AND GS MEDIATED SIGNAL TRANSDUCTION IN THE STUNNED PORCINE MYOCARDIUM

Objective: The aim was to investigate involvement of oxygen free radicals and any changes in the Gs mediated beta-adrenergic signalling system of stunned porcine myocardium. Methods: Myocardial stunning was induced in eight pentobarbitone anaesthetised pigs by brief occlusions of the distal left anterior descending coronary artery for periods of up to 10 min. Segment length function was measured in the ischaemic region and in a control region supplied by the circumflex artery. Left ventricular biopsies were obtained from the two regions 1 h artery the last occlusion for ultrastructural and biochemical studies. Timolol was been used to prevent arrhythmia during ischaemia. Results: At the time when biopsies were obtained, percent systolic shortening was reduced to 58% in the region subjected to ischaemia and was only minimally reduced in the control region. In the biopsies from the stunned region: (1) electron microscopy showed mild and reversible intracellular changes in the stunned myocardium; (2) the activities of superoxide dismutase and glutathione peroxidase were decreased by 66% and 52%. respectively: (3) the content of malondialdehyde was increased by 49%; (4) neither density nor affinity of beta-adrenoceptors showed any changes: (5) there were no alterations in messenger RNA encoding for the alpha-subunit of the stimulatory guanine nucleotide binding protein (Gs), demonstrated by northern and dot-blot hybridisations: (6) ELISA technique utilising a specific antipeptide antibody showed no quantitative change in Gs; (7) the activity of adenyl cyclase was unchanged. Conclusions: Even though the stunned porcine myocardium showed substantial evidence of free radical injury, the beta-adrenergic signalling system was intact.