Does Cl-/HCO3- exchange play an important role in reperfusion arrhythmias in rats?

The protective effects of Cl(-)/HCO(3)(-) exchange inhibitors, 4,4'-diisothiocyano-stilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'isothiocyanato-stilbene-2,2'-disulfonic acid (SITS), against reperfusion-induced arrhythmias were investigated in anesthetized rats. Rats were subjected to 5-min occlusion of the left coronary artery followed by 10-min reperfusion. All drugs were intravenously administered 5 min before the onset of occlusion. DIDS (75 mg/kg) reduced the incidence of ventricular fibrillation and mortality to 0%, whereas SITS (75 mg/kg) only decreased these parameters to 60%. DIDS simultaneously decreased the mean blood pressure and heart rate, and prolonged PQ and QRS intervals, whereas SITS produced a weaker effect on these parameters and no change in QRS interval. Mexiletine (5 mg/kg), which had been demonstrated to suppress the arrhythmias and reduce the heart rate and mean blood pressure in this model, was shown to prolong PQ and QRS intervals. Verapamil (0.5 mg/kg) or diltiazem (0.4 mg/kg) suppressed the arrhythmias, simultaneously decreasing the heart rate and mean blood pressure and prolonging PQ interval. The results indicate that the protective effect of DIDS on reperfusion arrhythmias in the anesthetized rats is unlikely to be attributed to the inhibitory action on Cl(-)/HCO(3)(-) exchange, but possibly mediated by its blocking effects on cardiac ion channels, such as Na(+) or Ca(2+) channels.

Restored atrial excitability after late recanalization in a patient with atrial standstill and acute myocardial infarction.

Atrial standstill is electrophysiologically characterized by the loss of spontaneous excitation in atrial muscle and the inability to cause action potential firing upon electrical stimulation. Clinical diagnosis of transient standstill of the right atrium was made in a patient with acute occlusion of the right coronary artery and acute renal failure. Percutaneous coronary intervention, performed 5 days after the onset, restored the coronary blood flow and resulted in full recovery of electrical activity and regular sinus rhythm.

Inhibitory effects of pre-ischemic and post-ischemic treatment with FR 168888, a Na+/H+ exchange inhibitor, on reperfusion-induced ventricular arrhythmias in anesthetized rat.

Effects of pre-ischemic and post-ischemic treatment with FR 168888 (5-hydroxymethyl-3-(pyrrol-1-yl) benzoylguanidine methanesulfonate), a Na+/H+ exchange inhibitor, on reperfusion-induced ventricular arrhythmias were examined in an ischemia/reperfusion model of anesthetized rat. FR 168888 (0.3 mg/kg) significantly reduced the incidence of ventricular fibrillation (VF) and mortality induced by reperfusion following 5-min coronary occlusion, when it was intravenously administered 5 min before coronary artery occlusion. Post-ischemic treatment with FR 168888 (0.3-10 mg/kg), i.e. given 3 min after the start of occlusion, reduced the incidence of VF and mortality. In order to examine the optimal time of administration, FR 168888 (3 mg/kg) was administered 1 or 3 min after the start of occlusion or immediately before reperfusion. There was no significant difference in the reduction of VF and mortality among the three post-ischemic treatment groups. FR 168888 (3 and 10 mg/kg) significantly increased the blood pressure during ischemia without affecting the heart rate. These results indicate that FR 168888 has antiarrhythmic effects on reperfusion-induced arrhythmias even administered after coronary occlusion.