Arrhythmias In Anesthetized Rats Research Articles

Neutrophil ablation with anti-serum does not protect against phase 2 ventricular arrhythmias in anaesthetised rats with myocardial infarction

Arrhythmias, including ventricular fibrillation (VF), occur in two phases after coronary obstruction, the first during the reversible stage of acute myocardial ischaemia (phase 1) and the second during evolution of the infarct (phase 2). We tested the hypothesis that phase 2 arrhythmias are mediated by actions of neutrophils accumulating within the infarct. Male rats (n=10 per group) were randomized to receive 2 ml/kg i.p. of either rabbit anti-rat neutrophil anti-serum or normal rabbit serum. After 17 h, single stage left coronary artery ligation was performed under pentobarbitone anaesthesia, and ischaemia was maintained for 240 min. Anti-serum pretreatment caused almost total neutropenia, reducing neutrophils in circulating blood from 2096+/-274x10(3) to 8+/-8x10(3) per ml (p<0.05). It also blocked neutrophil accumulation in the infarct, reducing cardiac myeloperoxidase activity from 74.7+/-27.4 to 9+/-3 mU per mg protein (p<0.05). Despite this, there was no significant difference between control and anti-serum-treated rats in the incidence of phase 2 VF (30% in each group) tachycardia (VT; 60% vs 80%) or number of ventricular premature beats (VPBs). Neutrophil accumulation within the evolving myocardial infarct does not mediate phase 2 VF.

The role of nitric oxide in modulating ischaemia-induced arrhythmias in rats.

The effect of a nitric oxide (NO) donor and the influence of endogenous NO in modulating ischaemia-induced arrhythmias was assessed in anaesthetised rats. The nitric oxide donor C87-3754 (1 mg/kg) caused a significant reduction in arterial blood pressure before coronary artery ligation but did not influence the incidence or severity of ventricular arrhythmias during a 30-min period of myocardial ischaemia [60 and 58% incidence of ventricular fibrillation (VF) in control and treated rats, respectively]. When the hearts were preconditioned by a short (3 min) coronary artery occlusion before the 30-min period of ischaemia, there was a marked reduction in both the number of ventricular ectopic beats (260 +/- 65 vs. 812 +/- 256 beats/min in controls; p < 0.05) and the incidence of ventricular fibrillation (9 vs. 67% in controls; p < 0.05). Neither NG-nitro-L-arginine methyl ester (L-NAME; 10-100 mg/kg) nor methylene blue (1-50 mg/kg) attenuated this marked antiarrhythmic effect of preconditioning. L-NAME caused a significant increase in blood pressure with all doses used, whereas methylene blue did not increase blood pressure. Both L-NAME and methylene blue attenuated ventricular arrhythmias in non-preconditioned hearts. L-NAME reduced the number of ventricular ectopic beats (from 812 +/- 256 to 318 +/- 81 beats/min at 10 mg/kg; p < 0.05), whereas methylene blue decreased the incidence of VF from 67 to 20% at a dose of 50 mg/kg (p < 0.05). These findings suggest that neither endogenous nor exogenously administered NO reduces ischaemic arrhythmias in anaesthetised rats. Furthermore, the antiarrhythmic effect of preconditioning in this species appears to be independent of NO. The antiarrhythmic effects seen with both methylene blue and L-NAME may be the result of actions other than inhibition of the production or actions of NO.

Effect of hypertrophy induced by pressure overload or volume overload on reperfusion induced arrhythmias in anaesthetised rats

The aim was to determine the effect of myocardial hypertrophy on the incidence and severity of arrhythmias following reperfusion after experimental coronary artery occlusion, and to establish if the effect differed between pressure overload hypertrophy and volume overload hypertrophy. The experiments were performed in rats. Pressure overload hypertrophy was induced by aortic banding, and volume overload hypertrophy by perforation of the aortic valve. Four weeks after surgery, coronary artery occlusion and reperfusion experiments were performed. Both pressure and volume overloaded hearts exhibited a similar degree of left ventricular hypertrophy of about 45% weight gain compared to control animals. The total number of ventricular premature beats during reperfusion was not significantly increased in either model of hypertrophy. In contrast to volume overload, the incidence of reperfusion induced ventricular fibrillation was significantly increased in pressure overloaded hearts. Furthermore, there was a significant correlation between number of ventricular premature beats and degree of left ventricular hypertrophy, as well as between duration of ventricular tachycardia and degree of hypertrophy in the pressure overloaded group. Such correlations were not observed in hypertrophy due to volume overload. Neither volume nor pressure overload hypertrophy significantly increased mortality from ventricular fibrillation. An increase in cardiac mass per se does not necessarily aggravate reperfusion arrhythmias. The susceptibility to arrhythmias in this model seems to be critically dependent on the nature of the stimulus triggering left ventricular hypertrophy.

SR 33589, a new amiodarone-like agent: Effect on reperfusion-induced arrhythmias in anaesthetised rats

SR 33589, a new amiodarone-like agent: Effect on reperfusion-induced arrhythmias in anaesthetised rats

The effects of drugs interacting with opioid receptors on the early ventricular arrhythmias arising from myocardial ischaemia

1. The effects of a range of opioid receptor agonists and antagonists with differing opioid receptor selectivities on ischaemia-induced arrhythmias in anaesthetised rats was investigated. 2. Naloxone was antiarrhythmic only at doses expected to antagonise kappa- and delta-receptors in addition to mu-receptors. 3. The opioid receptor antagonist Mr 2266, which is twice as potent at kappa-receptors as at mu-receptors dose-dependently reduced the incidence and severity of the arrhythmias resulting from coronary artery occlusion. 4. The opioid receptor antagonist M 8008 (1 mg kg-1), which is twice as potent at delta-receptors as at mu-receptors but has very little affinity for the kappa-receptor, did not exhibit any beneficial antiarrhythmic properties. 5. MrZ 2593, a quarternary complex of naloxone which does not readily cross the blood brain barrier, was antiarrhythmic which implies that the antiarrhythmic actions of opioid receptor antagonists may be mediated via peripheral opioid receptors. 6. The agonists, diamorphine, [Leu] enkephalin and U-50,488H exhibited no significant arrhythmogenic effects under the present experimental conditions. 7. It is tentatively suggested that blockade of peripheral kappa-receptors during acute myocardial ischaemia may result in an antiarrhythmic effect.

Effects of Alterations in Sympathetic Nervous Activity on the Severity of Reperfusion-Induced Arrhythmias in Anaesthetised Rats

The effects of a number of interventions influencing sympathetic nervous activity on the severity of coronary artery reperfusion-induced arrhythmias in anaesthetised rats have been examined. Noradrenaline (0.1 microgram kg-1 min-1) reduced the mortality that usually occurred as a consequence of ventricular fibrillation. Isoprenaline (5 micrograms kg-1) did not significantly affect the severity of reperfusion-induced arrhythmias, although arrhythmias occurring during the 5-min period of ischaemia were exacerbated. The alpha-adrenoceptor antagonist nicergoline (0.25 and 0.5 mg kg-1 min-1) markedly suppressed both the ventricular tachycardia and fibrillation occurring upon release of the occlusion, whereas prazosin (1.0 mg kg-1) only slightly reduced the incidence of ventricular tachycardia. The beta-adrenoceptor antagonists atenolol and timolol did not significantly modify the severity of these reperfusion-induced arrhythmias. Pretreatment with reserpine (0.1 mg kg-1) or 6-hydroxydopamine (20 mg kg-1), which depleted myocardial catecholamine concentrations by 90%, had no effect on the indices of arrhythmic activity. Similarly, administration of L-thyroxine (1 mg kg-1) or propylthiouracil (50 mg kg-1) on 7 consecutive days prior to coronary artery occlusion did not alter the incidence of arrhythmias occurring upon reperfusion. Taken as a whole, these results do not suggest an important role for sympathetic nervous activity in the genesis of reperfusion-induced arrhythmias in anaesthetised rats.

Antiarrhythmic and Electrophysiological Effects of ICS 205-930, an Antagonist of 5-Hydroxytryptamine at Peripheral Receptors

We assessed the antiarrhythmic activity of ICS 205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester], a selective antagonist at neuronal 5-hydroxytryptamine M-receptors, against the arrhythmias that occur following occlusion of the left main coronary artery in anaesthetised rats and subsequent release (reperfusion). The incidence of reperfusion-induced ventricular fibrillation and ventricular tachycardia was significantly reduced by pretreatment with ICS 205-930 (0.3 and 1.0 mg kg-1 i.v. and 10 and 30 mg kg-1 p.o.). The arrhythmias that occurred during 30 min of coronary artery occlusion were also less severe in animals given ICS 205-930 (1.0 and 5.0 mg kg-1 i.v.). Arterial blood pressure was not altered by the drug, and heart rate was only slightly reduced by the highest intravenous dose. In vitro, ICS 205-930 reduced the maximum rate of rise of phase 0 of normal sheep Purkinje fibre action potentials in concentrations from 0.5 to 5.0 mg L-1. Action potentials depressed by superfusion with a physiological salt solution modified to mimic the conditions occurring during mild ischaemia were similarly affected by ICS 205-930. The highest drug concentration studied under these conditions was 1.5 mg L-1 since, in combination with the modified physiological salt solution, this rendered some of the Purkinje fibres inexcitable. These results indicate that ICS 205-930 possesses marked antiarrhythmic activity against ischaemia-induced arrhythmias in anaesthetised rats and that a direct electrophysiological effect of the drug may, at least in part, underlie its protective action.

The effects of high blood pressure and chronic low level lead pretreatment, aloneand in combination, on the severity of ischaemia induced arrhythmias in anaesthetised rats

The effects of high blood pressure and chronic low level lead pretreatment, aloneand in combination, on the severity of ischaemia induced arrhythmias in anaesthetised rats