Effect of the blood supply to the normal noninfarcted myocardium on the incidence and severity of early postocclusion arrhythmias in dogs

Background and purpose: Exogenous peroxynitrite from nanomolar to micromolar concentrations exerts cardioprotection. Here, we have assessed its effects on ischaemia-and reperfusion-induced ventricular arrhythmias in vivo and a possible role for mitochondrial K ATP channels in these effects, using the channel inhibitor 5-hydroxydecanoate (5-HD). Experimental approach: Chloralose-urethane-anaesthetized dogs were treated twice for 5 min with peroxynitrite (100 nM, by intracoronary infusions) in both the absence and presence of 5-HD (150 mg kg À1 min À1 ), and then subjected to 25 min occlusion of the left anterior descending coronary artery. The severity of ischaemia and of arrhythmias, as well as the levels of nitrotyrosine were assessed and compared with a group of control dogs, subjected only to a 25 min occlusion and reperfusion insult. Key results: Compared with controls, infusion of peroxynitrite markedly suppressed the number of ventricular premature beats (388 ± 88 vs 133 ± 44), the incidence of ventricular fibrillation both during occlusion (50% vs 10%) and reperfusion (100% vs 44%), and increased survival (0% vs 50%; all Po0.05). The severity of ischaemia (epicardial ST-segment changes, inhomogeneity of electrical activation) during occlusion and nitrotyrosine levels on reperfusion were significantly less in the peroxynitrite-treated dogs than in the controls. 5-HD did not modify the cardioprotective effects of peroxynitrite. Conclusion and implications: Exogenous peroxynitrite provided antiarrhythmic protection in vivo, which might have been on account of a reduction in endogenous peroxynitrite formation. This protection seemed not to be mediated through mitoK ATP channels.

Section: Discussionsupporting

confidence: 61%

Section: Methodsmentioning

confidence: 99%

Peroxynitrite decreases arrhythmias induced by ischaemia reperfusion in anaesthetized dogs, without involving mitochondrial K_ATP channels

Kiss

Juhász

Huliák

et al. 2008

“…A thoracotomy was performed at the fifth intercostal space and the anterior descending branch of the left coronary artery (LAD) prepared for occlusion just proximal to the first main diagonal branch. Epicardial ST-segment changes and the degree of inhomogeneity of activation were measured from the left ventricular wall distal to the proposed coronary artery occlusion with unipolar electrodes and a 'composite electrode' previously described (Vegh et al, 1987). This gives a summarised recording of R-waves from 30 epicardial measuring points.…”

Section: Methodsmentioning

confidence: 99%

“…Epicardial ST-segment changes and the degree of inhomogeneity of activation were measured from the left ventricular wall distal to the proposed coronary artery occlusion with unipolar electrodes and a 'composite electrode' previously described (Vegh et al, 1987 The protocols were as follows:-(1) Group I (controls) These 15 animals served as controls and were allowed to stabilize after surgery for 1 h; the LAD coronary artery was then occluded for 25 min, after which the ischaemic area was reperfused.…”

Section: Methodsmentioning

confidence: 99%

Preconditioning of the ischaemic myocardium; involvement of the l‐arginine nitric oxide pathway

Végh

Szekeres

Parratt

1992

238

150

1 Short periods of coronary artery occlusion protect the heart against the effects of a subsequent prolonged period of ischaemia. This phenomenon is known as preconditioning of the ischaemic myocardium. 2 In mongrel, chloralose-urethane anaesthetized open-chest dogs, within a restricted body weight range, two 5 min periods of occlusion of the anterior descending branch of the left coronary artery markedly reduced the severity of the early ischaemic arrhythmias resulting from a prolonged (25 min) occlusion of the same coronary artery starting 20 min later. Thus, the number of ventricular premature beats (VPBs) was reduced from 528 ± 140 in controls to 78 ± 27 in preconditioned dogs, the incidence of ventricular fibrillation (VF) was reduced from 47% to 0% and the incidence of ventricular tachycardia (VT) from 100% to 20%. ST-segment elevation recorded from electrodes within the ischaemic area, and the degree of inhomogeneity of conduction within the ischaemic area were markedly reduced in these preconditioned dogs. 3 The incidence of VF following reperfusion of the ischaemic myocardium at the end of the 25 min occlusion period was reduced in the preconditioned dogs from 100% to 60%; there was thus a 40% survival from the combined ischaemia-reperfusion insult compared with 0% in the controls. 4 NG-nitro-L-arginine methyl ester (L-NAME) an inhibitor of the L-arginine nitric oxide pathway, given in a dose of 10 mg kg-' intravenously on two occasions, both before the initial preconditioning occlusion and then again before the prolonged occlusion, partially attenuated the protective effects of preconditioning. There were more VPBs (220 ± 75), a higher incidence of VT (60%) and more episodes of VT (11.5 ± 6.0 compared to 0.7 ± 0.3 episodes in the preconditioned dogs not given L-NAME); none of the animals survived reperfusion (incidence of VF 100%). The improvement in the severity of the degree of inhomogeneity which resulted from preconditioning was abolished by L-NAME administration. 5 L-NAME itself elevated blood pressure (from 96 ± 5 mmHg diastolic to 119 ± 7 mmHg), reduced heart rate (from 155 ± 7 to 144 ± 4 beats min-') but did not change LVEDP, LVdP/dt,,,,, coronary blood flow, ST-segment elevation or the degree of inhomogeneity of conduction. When given 10 min before the prolonged coronary artery occlusion in dogs not subjected to preconditioning, L-NAME had no significant effect on the severity of arrhythmias except for more periods of VT (a mean of 11.7 ± 4.7 episodes per dog). 6 It is concluded from these studies that the generation of nitric oxide contributes to the marked antiarrhythmic effects of preconditioning in the canine myocardium, probably through elevation of cyclic GMP.

“…was catheterized for the intracoronary infusion of bradykinin or saline. Epicardial ST-segment changes and the degree of inhomogeneity of conduction were measured in the area distal to the occlusion with the composite electrode described by Vegh et al (1987). In some of the experiments coronary blood flow was measured on either the LAD or on the left circumflex coronary artery (or both) with an electromagnetic flow probe (Statham SP 2202; 2.0 mm) and/or a 2.4mm Doppler flow probe (Triton Technology, San Diego, U.S.A.).…”

mentioning

confidence: 99%

Local intracoronary infusions of bradykinin profoundly reduce the severity of ischaemia‐induced arrhythmias in anaesthetized dogs

Végh

Szekeres

Parratt

1991

110

Bradykinin in a dose (25 ng kg-min 1) which did not alter coronary flow, or saline, were infused into a small branch of the left anterior descending coronary artery in dogs anaesthetized with chloralose and urethane, for 10 min prior to coronary artery occlusion and throughout the 25 min occlusion period. The degree of inhomogeneity of conduction and epicardial ST-segment changes were measured in the ischaemic zone with a composite electrode. In control dogs, coronary artery occlusion led to severe arrhythmias with an incidence of ventricular fibrillation of 47% and tachycardia of 80% and with a mean of 528 + 140 ventricular premature beats. In marked contrast, those dogs administered bradykinin had no ventricular fibrillation or tachycardia and the number of premature beats was significantly less (53 + 19). ST-segment changes were also much less in these dogs. These results raise the possibility that bradykinin might contribute to the protective effects of preconditioning and acts as an 'endogenous myocardial protective substance'.