Short preconditioning periods of myocardial ischaemia protect the myocardium against the arrhythmogenic effects of a more prolonged occlusion. The optimum time for this preconditioning occlusion in rats is 3 min and protection is still apparent 30 min later. In dogs, the protective effect is especially clear with two short (5 min) coronary artery occlusions. The protection in this species lasts for less than 1 h.

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.

Background: Autoactivation of initiator proteases of complement is a two-step process. Results: Autoactivation and possible cross-activation steps of complement lectin pathway proteases were quantified. Conclusion: Only MASP-1 can autoactivate rapidly, and MASP-2 is activated by MASP-1. Significance: The determined kinetic data are helpful to interpret activation scenarios for the lectin pathway, and the presented strategy can be used to quantify autoactivation of other proteases.

Uncoupling of GJs prior to ischaemia either by PC or CBX preserves the electrical coupling of cells and results in an antiarrhythmic effect during a subsequent ischaemic insult, indicating that a partial closure of gap junctions may play a trigger role in the protection. In contrast, when CBX is administered in PC dogs the protection both against GJ uncoupling and arrhythmias is markedly attenuated, suggesting that the antiarrhythmic protection, at least in part, is mediated through GJs.

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Dogs were paced, via a pacing electrode in the right ventricle, for four 5 min periods at a rate of 220 beats min-'. On the following day they were reanaesthetized, thoracotomized and the left anterior descending coronary artery occluded for 25 min. Pacing markedly reduced the severity of ischaemiainduced arrhythmias (e.g. reduction in VF from 45% in unpaced dogs to 10% in paced dogs; P<0.05), an effect reversed by dexamethasone (4 mg kg' i.v., 45 min prior to pacing). This protection may be due to the induction of nitric oxide synthase or cyclo-oxygenase. Keywords: Ischaemic preconditioning; second window of protection; rapid cardiac pacing; ventricular arrhythmias; antiarrhythmic effect of cardiac pacing; dexamethasone; nitric oxide Introduction Brief periods of either regional or global

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'.

Short, preconditioning periods of myocardial ischaemia protect the myocardium against the arrhythmogenic effects of a more prolonged occlusion. That this protection is lost if the cyclo-oxygenase pathway is blocked suggests a protective role for prostanoids, most likely prostacyclin, as endogenous myocardial protective substances.