Metabolic and functional effects of carbachol and ischaemic preconditioning in rat isolated heart

1. Metabolic and functional effects of ischaemic preconditioning (IP), pret reatment with carbachol (Ch) and combined interventions were studied in rat isolated working hearts subjected to 20 min global ischaemia (37 degrees C ) and 40 min reperfusion. Prior to the ischaemic period, hearts were either perfused according to Langendorff (control group), ischaemically precondit ioned by 5 min global ischaemia and 5 min reperfusion (IP group), perfused with 0.1 mu mol/L Ch for 5 min and then with Gh-free Krebs'-Henseleit buffe r for 5 min (Ch group) or perfused with 0.1 mu mol/L Ch for 5 min and then subjected to IP (Ch + IP group). 2. Although Ch exerted slight negative chronotropic and inotropic effects d uring pre-ischaemic Langendorff perfusion, it did not affect myocardial con tents of ATP and phosphocreatine (PCr) prior to sustained ischaemia. At the end of final reperfusion, the IP and Ch groups showed similar recovery of aortic output (67.5+/-5.0 and 56.8+/-5.4%, respectively), cardiac output (6 5.4+/-5.4 and 63.5+/-5.7%, respectively) and stroke volume (73.4+/-7.5 and 67.0+/-6.7%, respectively) expressed as a percentage of steady state values . These indices were higher than those in the control group (42.8+/-4.7, 53 .8+/-4.3 and 56.1+/-5.6%, respectively; P < 0.05). The Ch + IP group exhibi ted complete recovery of all indices of pump function, including cardiac wo rk, expressed as the cardiac output-mean aortic pressure (CO-MAP) product. 3. There were no differences in ATP recovery between the groups after reper fusion: the ATP content was, on average, 73.1+/-3.5% of the initial ATP con tent. However, all treated groups had enhanced PCr recovery and better pres ervation of total creatine (Sigma Cr = PCr + Cr), an index of cell membrane integrity, than control. Metabolic efficacy of the pre-ischaemic intervent ions can be ranked as follows: IP less than or equal to Ch < Ch + IP. In al l groups, myocardial content of Sigma Cr was positively correlated with per centage recovery of the CO-MAP product at the end of reperfusion (r = 0.79, P < 0.05). 4. The results demonstrate that Ch treatment combined with IP provides sign ificantly greater postischaemic myocardial salvage. The similarity of the m etabolic and functional effects of Ch treatment and IP strongly suggests mu scarinic M-2 acetylcholine receptor involvement in acute adaptation of rat heart to ischaemia/reperfusion stress.