Levosimendan as a Rescue Drug in Experimental Propranolol-Induced Myocardial Depression: A Randomized Study
Received 23 December 2008; received in revised form 6 March 2009, 9 April 2009 and 30 April 2009; accepted 24 June 2009. published online 22 September 2009.
Study objective
Severe β-blocker intoxication remains a clinical challenge despite a variety of treatment options. Because of its unique mechanism of action, the new calcium sensitizer levosimendan may provide more prominent cardiac support compared with current medications used to reverse negative inotropy. We hypothesize that levosimendan could reverse propranolol-induced severe negative inotropy in a porcine model of β-blocker intoxication.
Methods
Twenty-four pigs were anesthetized and monitored. After severe propranolol intoxication was completed, animals were randomized into 3 groups. With a double-blind procedure, 9 animals received a 1.25-mg levosimendan bolus, followed by saline solution infusion, 9 animals received mean arterial pressure–targeted dobutamine infusion after saline solution bolus, and 6 animals received a saline solution bolus followed by saline solution infusion. Hemodynamic and laboratory data were collected during a follow-up period of 120 minutes.
Results
All 9 pigs in the levosimendan group survived. In contrast, 4 of 6 (67%) and 7 of 9 (78%) pigs died during the experiment in the placebo and the dobutamine groups, respectively. The levosimendan group showed improved change in the maximum positive slope of the left ventricular pressure, cardiac output, stroke volume, and mean arterial pressure compared with the dobutamine and the placebo groups.
Conclusion
Levosimendan improved hemodynamic function and survival in this animal model of severe propranolol intoxication. The potential clinical application of levosimendan in propranolol intoxication warrants further investigation.
aDepartment of Intensive Care, Kuopio University Hospital, Kuopio, Finland
bDepartment of Anaesthesia, Tampere University Hospital, Tampere, Finland
Address for correspondence: Kurola Jouni, MD, PhD, Department of Intensive Care, Kuopio University Hospital, PO Box 1777, 70211 Kuopio, Finland; 358-40-5677189, fax 358-17-173443
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. Financial support provided by Orion Pharma Inc.
Supervising editor: Richard C. Dart, MD, PhD
Author contributions: HL, ER, LL, and JK designed the study and obtained research funding. HL, JR, and JK performed the study. HL, VK, and JK performed statistical analysis. HL, ER, LL, and JK prepared the article. JK takes responsibility for the paper as a whole.
Reprints not available from the authors.
Publication date: Available online September 19, 2009.
ABSTRACT