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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of cicletanine, a novel furopyridine antihypertensive drug was compared with that of nitrendipine, a dihydropyridine slow calcium channel blocker, on cardiac function and reperfusion-induced ventricular arrhythmias in isolated working rat hearts subjected to 10-min ischemia induced by ligation of the left main coronary artery followed by 10-min reperfusion. Before ischemia, cicletanine and nitrendipine, perfused at concentrations of 3 x 10(-5), 6 x 10(-5), 10(-4), and 2 x 10(-4) or 10(-8) M, respectively, did not influence heart rate (HR), LV developed pressure (LVDP), its first derivative (LVdP/dtmax), and LV end-diastolic pressure (LVEDP), whereas aortic flow (AF) was decreased by 2 x 10(-4) M cicletanine only. Coronary flow (CF) remained unchanged by various cicletanine concentrations but was slightly increased by nitrendipine. In the concentration range of 3 x 10(-5)-10(-4) M, cicletanine improved AF either in ischemia or during reperfusion, whereas 2 x 10(-4) M had no such effect. Nitrendipine slightly attenuated ischemia/reperfusion-induced decrease in AF. Cicletanine and nitrendipine enhanced LVDP during ischemia. Ischemia-induced deterioration of LVdP/dtmax was reduced by cicletanine, during reperfusion, but this parameter was reduced by nitrendipine and the highest cicletanine concentration. Cicletanine decreased LVEDP significantly during ischemia and reperfusion, but nitrendipine had no such effect. All cicletanine concentrations reduced the incidence of irreversible ventricular fibrillation (VF) during reperfusion, an effect roughly concentration dependent in the range of 3 x 10(-5)-10(-4) M, whereas nitrendipine had no influence on arrhythmias.
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PMID:Cicletanine improves myocardial function deteriorated by ischemia/reperfusion in isolated working rat hearts. 137 86

Pinacidil is a member of the new antihypertensive drug family possessing an action that involves an increased potassium efflux in vascular and cardiac muscle. We investigated the contribution of opening of ATP-sensitive potassium channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na+, K+, Ca2+, and Mg2+ in isolated rat hearts. After 30 min of normothermic global ischemia, pinacidil with 1 to 60 mumol/l failed to reduce the incidence of reperfusion-induced arrhythmias, even on the postischemic/reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (the duration of ischemia was reduced to 25 min), pinacidil treatment was associated with a greater incidence of reperfusion-induced arrhythmias (100%) as compared to the control value (50%). These proarrhythmic effects of pinacidil were also reflected in a maldistribution of myocardial ion contents both in nonischemic and ischemic/reperfused hearts. Cicletanine, a furopyridine antihypertensive agent that has no effect on coronary resistance, reduced the incidence of reperfusion arrhythmias, and its antiarrhythmic effect was antagonized by pinacidil. The same observation was made in relation to myocardial ion content, e.g., pinacidil-induced K+ loss and Ca2+ gain were antagonized by cicletanine, both in nonischemic and ischemic/reperfused hearts. It is hypothesized that the increased tendency to develop reperfusion-induced ventricular fibrillation is associated with the pinacidil-induced K+ efflux. The present study does not attempt to address the question of specific ionic currents; however, it has been suggested that proarrhythmic and antiarrhythmic effects of pinacidil and cicletanine, respectively, may relate to same receptor sites in which the latter may reflect a specific blockade of the outward K+ ion current via ATP-sensitive K+ channels. If this is so, the use of K+ channel openers as antihypertensive agents may be of particular concern in that population of postinfarction patients who are known to be at high risk of sudden coronary death.
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PMID:Reperfusion-induced arrhythmias and myocardial ion shifts: a pharmacologic interaction between pinacidil and cicletanine in isolated rat hearts. 141 6

Isolated hearts from normotensive (NT) and spontaneously hypertensive (SH) rats, subjected to normothermic global ischemia, were used to study whether cicletanine (a new antihypertensive drug) treatment exerts an antiarrhythmic effect against reperfusion-induced arrhythmias. The effect of the drug on myocardial ion contents (Na+, K+, Ca2+, and Mg2+) during ischemia and reperfusion was also determined. Using the optimal doses of cicletanine (30 and 100 mg/kg orally for 14 days), the incidence of reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT) was reduced from their control values of 91 and 100% (after 30 min of ischemia) to 41 (p less than 0.05), 50 (p less than 0.05) and 41 (p less than 0.05), 58% in the NT group, while the corresponding value in the SH group for VF and VT were 17 (p less than 0.001), 33 (p less than 0.01) and 17 (p less than 0.001), 25% (p less than 0.001), respectively. The results obtained indicate that the cardioprotective effect of cicletanine was greater in the SH group than in the NT group. Cicletanine significantly reduced the ischemia- and reperfusion-induced myocardial Na+ and Ca2+ gains and inhibited the loss of myocardial K+ and Mg2+ in both NT and SH groups. The antiarrhythmic effect of cicletanine appears to be correlated with the preservation of myocardial Na+, K+, Ca2+, and Mg2+ contents via an ion transport modulation.
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PMID:Effect of cicletanine on reperfusion-induced arrhythmias and ion shifts in isolated rat hearts. 168 16

Isolated hearts, excised from spontaneously hypertensive male rats treated orally with cicletanine, a new furopyridine anti-hypertensive drug, were subjected to 30 min of global ischemia followed by 10 min of reperfusion. The effect of cicletanine on reperfusion-induced arrhythmias in relation to 6-keto-PGF1 alpha and thromboxane (TXB2) release was studied. After 30 min of global ischemia, the incidence (total) of ventricular fibrillation (VF) and ventricular tachycardia (VT) was reduced by 2-week pretreatment of the rats with 30 and 100 mg/kg of cicletanine (VF, 33% at 30 mg/kg and 25% at 100 mg/kg vs. 91% in untreated rats; VT, 42% at 30 mg/kg and 42% at 100 mg/kg vs. 100% in untreated rats), while lower doses of cicletanine (3 and 10 mg/kg) failed to reduce the incidence of reperfusion-induced rhythm disturbances. Reperfusion of the ischemic myocardium resulted in a fivefold increase of 6-keto-PGF1 alpha and TXB2 release in the perfusion effluent of fibrillated hearts but not in the perfusion effluent of nonfibrillated hearts. Cicletanine failed to influence the reperfusion-stimulated release of 6-keto-PGF1 alpha and TXB2. These results indicate that the anti-arrhythmic effect of cicletanine in the reperfused myocardium is not related to PGI2 and thromboxane A2 release.
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PMID:Effect of cicletanine on reperfusion-induced arrhythmias and its relation to 6-keto-PGF1 alpha and thromboxane B2 release. 205 11

Terfenadine, a histamine H(1) receptor antagonist, has been associated with clinical ventricular arrhythmias and in vitro excitation-conduction blocks, whereas anti-ischemic and antiarrhythmic effects have been shown with cicletanine, a prostacyclin generation stimulator. We aimed at determining in vitro if cicletanine can protect the ischemic myocardium from excitation-conduction blocks and specifically those induced by terfenadine. In a double-chamber bath, isolated guinea pig ventricular strips were partly exposed to normoxia and partly to ischemic, then reperfused, conditions, in the presence of 10 microM terfenadine, 10 microM indomethacin (prostacyclin generation blocker) or the solvent (dimethylsulfoxide 1:100, control) randomly allocated, and thus either in the absence (n=20) or presence (n=21) of 10 microM cicletanine during the total protocol duration. The multivariate Cox's model was used to predict the excitation-conduction block events and to assess the estimated survival of preparations (excitation-conduction block-free rate). Cicletanine protected the preparations (relative risk=0.08, t=-3.28) from the ischemia-induced excitation-conduction blocks (estimated survival=0.83 versus 0.30 in control), and this effect was abolished by indomethacin (estimated survival=0.35). Terfenadine enhanced 3. 58-fold the risk of occurrence of excitation-conduction blocks during ischemia (t=2.10) and this effect was inhibited by cicletanine pretreatment (estimated survival=0.40 versus 0.10 in untreated preparations). In conclusion, these in vitro findings have provided evidence for (1) protective effects of cicletanine against ischemia-induced excitation-conduction blocks, possibly related to its stimulating activity on local prostacyclin generation, and (2) efficacy of cicletanine to prevent excitation-conduction blocks induced by terfenadine in ischemic cardiac tissue.
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PMID:Cicletanine prevents the excitation-conduction blocks induced by terfenadine in ischemic myocardium. 1055 70