Effects of angiotensin converting enzyme inhibitor and angiotensin II receptor blocker on ventricular defibrillation threshold

Background: Angiotensin converting enzyme (ACE) inhibitors and Angiotensin II (AII) receptor blockers have previously been shown to be beneficial in treating patients with not only hypertension but also with cardiovascular diseases. Therefore, such drugs may potentially be used in patients with an implantable cardioverter defibrillator (ICD) who show cardiac dysfunctions. Objective: This study aimed to determine effects of short-term administration of the ACE inhibitor (CV-3317) and the AII receptor blocker (CV-11974, an active form of candesartan) on internal defibrillation threshold (DFT) in anesthetized canine hearts. Methods: DFTs were evaluated using a "hot can" defibrillation lead system in: (a) seven dogs following three intravenous administrations of 20 cc saline; (b) 11 dogs that received intravenous CV-3317 doses of 1 mg/kg, 10 mg/kg, and 50 mg/kg; and in (c) 10 dogs that were intravenously given 0.1 mg/kg, 1 mg/kg, and 10 mg/kg CV-11974. DFTs were determined using a "down-up down-up" protocol. Results: Mean DFT delivered energies at baseline and following three consecutive intravenous saline injections were 16.4 +/- 9.3 J, 15.3 +/- 7.5 J, 15.9 +/- 7.1 J, and 15.5 +/- 5.6 J, respectively. Those at baseline and following 1 mg/kg, 10 mg/kg, and 50 mg/kg intravenous CV-3317 were 12.9 +/- 6.4 J, 12.2 +/- 6.4 J, 11.0 +/- 6.6 J, and 11.9 +/- 6.6 J, respectively. Similarly, those at baseline and after 0.1 mg/kg, 1 mg/kg, and 10 mg/kg CV-11974 were 13 +/- 6.6 J, 12.5 +/- 6 J, 12.9 +/- 5.8 J, and 13.2 +/- 6.6 J, respectively. There were no significant differences between DFT at baseline and the others in each treatment group. Conclusions: Since an ACE inhibitor and an AII receptor blocker did not alter DFT, such drugs may be useful in ICD patients without a decrease in safety margins.