ABSTRACT
These experiments were designed to explore the possibility that a K+ channel opener which also donates nitric oxide to the myocardium (nicorandil) may modify ischaemia-induced ventricular arrhythmias in a large animal model. In mongrel dogs anaesthetised with chloralose-urethane and thoracotomised, a side branch of the left anterior descending artery was catheterised for the local intracoronary infusion of nicorandil (2.5 micrograms kg-1 min-1 for 20 min prior to coronary artery occlusion and then continuing throughout the 25 min occlusion period). In this dose, nicorandil had no haemodynamic effects, increased coronary blood flow by up to 16% and significantly reduced the severity of ischaemia-induced arrhythmias (e.g. from nearly 500 ventricular premature beats in the controls to 160 +/- 60 in the nicorandil group). There was a significant reduction in the number of episodes of ventricular tachycardia during the ischaemic period and a reduced incidence of ventricular fibrillation following reperfusion resulting in a 42% survival from the combined ischaemia-reperfusion insult (cf. 0% in the control; P < 0.05). The marked changes that occurred in ST-segment elevation (mapped with epicardial electrodes) and in the inhomogeneity of electrical activation within the ischaemic area in control dogs was markedly reduced in those dogs administered nicorandil. We conclude that the local intracoronary administration of nicorandil reduces the severity of both ischaemia and the life-threatening arrhythmias that result from an abrupt reduction in coronary blood flow in this canine model. Possible mechanisms include an increase in coronary blood flow, a reduction in the severity of myocardial ischaemia and an ability of the compound to "donate' nitric oxide to the ischaemic area.
Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Arrhythmias, Cardiac/drug therapy , Myocardial Ischemia/physiopathology , Niacinamide/analogs & derivatives , Vasodilator Agents/therapeutic use , Animals , Anti-Arrhythmia Agents/pharmacology , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/physiopathology , Blood Pressure/drug effects , Coronary Circulation/drug effects , Dogs , Electrocardiography , Female , Heart Rate/drug effects , Male , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/physiopathology , Myocardium/metabolism , Niacinamide/pharmacology , Niacinamide/therapeutic use , Nicorandil , Nitric Oxide/metabolism , Vascular Resistance/drug effects , Vasodilator Agents/pharmacologyABSTRACT
Organophosphates are the most widely used pesticides throughout the world. The considerable amount brought out to the environment poses a risk on the whole population. As organophosphates are neurotoxic substances and their residues can persist in the environment for several weeks, their influence on the nervous system of humans and animals is of principal interest. In the present study, we investigated the alterations induced by dichlorvos, a common pesticide substance, in parameters of somatosensory evoked potentials and hippocampal evoked population spikes of rats. The changes of the cortical vs. hippocampal evoked responses were opposite and only hippocampal effects could be directly explained through an increased cholinergic activity.
