Effects of cicletanine on haemodynamics, arrhythmias and extent of necrosis during coronary ligation in rabbits

Abstract

1 The effects of cicletanine on arrhythmias, haemodynamics and extent of necrosis during myocardial ischaemia were investigated in rabbits subjected to coronary ligation. 2 Cicletanine increased cardiac output prior to coronary occlusion (P<0.01) but had no other significant haemodynamic effects at this time and did not significantly alter heart rate, blood pressure or cardiac output during 30 min of ischaemia or 30 min of reperfusion. 3 Ventricular fibrillation and mortality were greater in control (65% and 60% respectively) than treated animals (15.4% and 15.4%, P<0.01). 4 The extent of myocardial necrosis expressed as a percentage of the area at risk was also reduced by cicletanine from 61 ± 8% in controls to 37 ± 6% (P<0.05). 5 These findings indicate that cicletanine attenuates arrhythmias and preserves myocardium in the early phase of ischaemia and this effect appears to be independent of an established antihypertensive action.

Cicletanine for the Treatment of Pulmonary Arterial Hypertension

“…Furthermore, there are several animal studies showing favorable cardiac effects, including reversal of cardiac hypertrophy 17 and reduction in extent of ischemia-induced myocardial infarction. 18,19 The greater than 50% reduction in N-terminal probrain natriuretic peptide level in our patient, along with her marked clinical improvement as evidenced by a decrease in supplemental oxygen requirements and increased walking distance, is consistent with the hypothesis that cicletanine had a beneficial effect on both pulmonary vascular resistance and right ventricular function in this patient with severe idiopathic PAH. This in turn is consistent with the view that cicletanine directly treats endothelial dysfunction, which is thought to be a principal driver both in pulmonary hypertension and cardiac failure.…”

Beneficial Cardiac Effects of Cicletanine in Conscious Rabbits With Metabolic Syndrome

“…Numerous studies have been performed illustrating either the antiarrhythmic or the antiischemic effect of the drug in in vitro and ex vivo models 7,31 or whole animals, 10,11 but to the best of our knowledge, this is the first work, which demonstrates the cardioprotective action of CIC in a preclinical model, which exposes several leading symptoms (ie, insulin resistance, dyslipidemia, hypertension) of MS. Moreover, the animals were conscious throughout the entire set of experiments; therefore, the examined effects of CIC were influenced neither positively nor negatively by the untoward actions of drugs applied for anesthesia induction and maintenance.…”

“…[7][8][9] On the other hand, very few studies concerning CIC's antiarrhythmic action were carried out under in vivo conditions. 10,11 Moreover, in these latter experiments, arrhythmias were induced exclusively by the method of ischemia/reperfusion, not programmed electrical stimulation (PES).…”