Effects of an Angiotensin II Antagonist on Reperfusion Arrhythmias in Dogs

Abstract

Losartan, an angiotensin II receptor antagonist with no bradykinin potentiating property, provides the opportunity to study the consequences of blocking angiotensin II. The objective of this study was to evaluate the antiarrhythmic responses of reperfusion arrhythmia to losartan in dogs. The effects of losartan on ventricular tachyarrhythmias induced during occlusion and reperfusion of the left anterior descending coronary artery were investigated in 30 dogs. The animals were randomized to receive either losartan (n = 15) or saline (n = 15). The VF inducing threshold was measured before occlusion and after reperfusion. Losartan (50 micrograms/kg per min) or saline was intravenously administered 5 minutes before occlusion and continued throughout the entire study period. The incidence of ventricular tachyarrhythmias during reperfusion was lower in the losartan group than in the control group (4/15 vs 6/15). There was no significant change in VF inducing threshold between the period before occlusion and during reperfusion in the losartan group [10.9 +/- 5.7 vs 11.1 +/- 5.7 mA, P = NS), whereas there was a significant decrease in the control group (15.5 +/- 4.4 vs 7.7 +/- 3.9 mA, P < 0.01). Blockade of the angiotensin II receptor has beneficial effects on reperfusion arrhythmias.

Angiotensin II Type 1a Receptor Is Involved in the Occurrence of Reperfusion Arrhythmias

“…Consistent with our findings, an AT1 antagonist, losartan, has been recently reported to attenuate ventricular tachyarrhythmias during reperfusion. 17 Finally, there was no significant difference in the incidence of arrhythmias between AT1 antagonist-treated WT mice and KO mice. In addition, in spite of the highly activated renin-angiotensin system in AT1a KO mice, fewer arrhythmias were observed in KO mice than in control mice during reperfusion, suggesting that AT1b may not play a major role in the induction of reperfusion arrhythmias.…”

Angiotensin II Antagonist Prevents Electrical Remodeling in Atrial Fibrillation

“…[1][2][3][4][5] However, the effect of these drugs on atrial fibrillation has not been thoroughly examined.…”

“…[21][22][23][24] Previous studies have reported the reduction of reperfusion ventricular arrhythmias by AT 1 receptor antagonist and ACEI. [3][4][5] It has been shown that Ang II increases the intracellular calcium concentration significantly more in atrial myocytes than in ventricular myocytes in the rat heart. 25 Moreover, the density of Ang II receptor in atria is generally higher than that in ventricles.…”

“…t has been shown that angiotensin-converting enzyme inhibitor (ACEI) and the angiotensin II (Ang II) type 1 (AT 1 ) receptor antagonist have beneficial effects on ventricular function and ventricular arrhythmias [1][2][3][4][5] ; however, little is known about how they affect atrial pathophysiology or electrophysiology.…”

Reperfusion-Induced Arrhythmias Are Suppressed by Inhibition of the Angiotensin II Type 1 Receptor

“…Both ACEI and AT 1 antagonist have been reported to suppress IR-induced ventricular arrhythmias in rats in vivo [8]and in vitro [13], in dogs in vivo [14], and in mice in vivo [9]. In addition, reperfusion arrhythmias were not observed in AT 1a knockout mice, in contrast to the wild-type mice [9].…”