No attenuation of ischaemic preconditioning by the calcium antagonist nisoldipine.
In anaesthetized dogs, intracoronary infusion of calcium prior to a prolonged ischaemic period reduced infarct size, thereby mimicking the protective effects of ischaemic preconditioning and suggesting that an increase in the intracellular calcium concentration might be an important mechanism underlying this phenomenon. The aim was to determine whether pretreatment with the calcium antagonist nisoldipine attenuates the reduction in infarct size achieved by ischaemic preconditioning. In 10 enflurane-anaesthetized pigs serving as controls (group 1), the inflow 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 cycle of 10 min of low-flow 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 identical to that of groups 1 and 2, respectively. Subendocardial blood flow was measured with radiolabelled microspheres. Infarct size (% area at risk) was determined by triphenyltetrazolium staining in all pigs after 120 min of reperfusion. Subendocardial blood flow in the area at 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 reduction in infarct size following nisoldipine treatment (group 3: 10.2 +/- 7.1%, group 4: 1.6 +/- 2.8%, P = 0.01). Thus administration of nisoldipine in pigs tended to decrease infarct size, and did not abolish the cardioprotection afforded by ischaemic preconditioning.
Wallbridge
D R
DR
Department of Pathophysiology, Universitätsklinikum Essen, Germany.
Schulz
R
R
Braun
C
C
Post
H
H
Heusch
G
G
D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D016014:Linear Models; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy; D009206:Myocardium / Q000378:metabolism; D015737:Nisoldipine / Q000494:pharmacology*; D013552:Swine; D013556:Swine, Miniature
D002121:Calcium Channel Blockers; D015737:Nisoldipine