NO ATTENUATION OF ISCHEMIC PRECONDITIONING BY THE CALCIUM-ANTAGONIST NISOLDIPINE

In anaesthetized dogs, intracoronary infusion of calcium prior to a pr olonged ischaemic period reduced infarct size, thereby mimicking the p rotective effects of ischaemic preconditioning and suggesting that an increase in the intracellular calcium concentration might be an import ant mechanism underlying this phenomenon. The aim was to determine whe ther pretreatment with the calcium antagonist nisoldipine attenuates t he reduction in infarct size achieved by Ischaemic preconditioning. In 10 enflurane-anaesthetized pigs serving as controls (group 1), the in flow into the cannulated left anterior descending coronary artery was reduced (low-flow ischaemia) to achieve a 90% reduction in an anterior myocardial work index (sonomicrometry) for 90 min. In 11 pigs (group 2), a cylcle of 10 min of low-now ischaemia and 15 min of reperfusion (preconditioning) preceded the prolonged ischaemia. In groups 3 (n=9) and 4 (n=7), nisoldipine was administered by intravenous infusion (500 ng/kg/min) starting 40 min prior to and then throughout a protocol id entical to that of groups 1 and 2, respectively. Subendocardial blood flow was measured with radiolabelled microspheres. Infarct size (% are a at risk) was determined by triphenyltetrazolium staining in all pigs after 120 min of reperfusion. Subendocardial blood flow in the area a t risk was similar in all four groups (group 1: 0.09 +/- 0.04 ml/min/g ; group 2: 0.05 +/- 0.03: group 3: 0.09 +/- 0.03; group 4: 0.07 +/- 0. 03). Group 2 had reduced infarct size when compared with group 1 (2.6 +/- 3.0% v 12.4 +/- 8.7%, P=0.004), and there was a trend for a reduct ion in infarct size following nisoldipine treatment (group 3: 10.2 +/- 7.1%, group 4: 1.6 +/- 2.8%, P=0.01). Thus administration of nisoldip ine in pigs tended to decrease infarct size, and did not abolish the c ardioprotection afforded by ischaemic preconditioning. (C) 1996 Academ ic Press Limited