Preconditioning also markedly reduced the incidence, during prolonged occlusion of the LAD, of the more malignant arrhythmias such as VT (Figure 4) and VF (Figure 5). Whereas in the control group 90% of the dogs exhibited VT and the number of episodes ofVT per dog was 7.6±2.1, in the preconditioned group the incidence of VT was only 32% and the number of episodes ofVT per dog was 1.1±0.5 episodes. The incidence and number of episodes of VT were still reduced when meclofenamate and L-NAME were given before the prolonged occlusion (incidence of VT 50%, number of episodes of VT 2.6±2.2) but they were markedly increased when the two inhibitors were administered before the preconditioning occlusions (incidence ofVT 100%, number of episodes of VT 17.5±4.5; Figure 4).
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Figure 4 Incidence and number of episodes of ventricular tachycardia (VT) during a 25 min occlusion of the left anterior descending coronary artery in anesthetized dogs that were preconditioned (PC), in dogs that were also PC but then given a combination of sodium meclofenamate (MF) and NG-nitro-L-arginine methyl ester (L-NAME) before occlusion, in dogs given MF and L-NAME before PC and in control dogs not subjected to any treatment or to PC. PC markedly reduced the incidence ofVT (and the number of episodes); this protection was completely lost when both pathways were blocked (MF + L-NAME + PC)
Figure 5 Incidence of ventricular fibrillation (VF) during occlusion (open bars) and reperfusion (shaded bars) during and after a 25 min occlusion of the left anterior descending coronary artery in anesthetized dogs. There were no survivors in the control group, but a significant reduction in VF (especially during occlusion) and an increased survival in preconditioned (PC) dogs. This protection was markedly attenuated by inhibiting both the L-arginine-nitric oxide and the cyclooxygenase pathways. *P<0.05. MF Sodium meclofe-namate; L-NAME NG-nitro-L-arginine methyl ester