© 2006 European Society of Cardiology
Progressive left ventricular hypertrophy after withdrawal of long-term ACE inhibition following experimental myocardial infarction
a Department of Clinical Pharmacology, University Medical Center Groningen A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
b Department of Cardiology, University Medical Center Groningen The Netherlands
c Department of Internal Medicine Erasmus MC, Rotterdam, the Netherlands
* Corresponding author. Tel.: +31 50 363 2724; fax: +31 50 363 2812. E-mail address: b.westendorp{at}med.rug.nl
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Abstract |
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Background: Although discontinuation of chronic ACE inhibitor (ACEi) therapy after myocardial infarction (MI) is common in clinical practice, some clinical studies reported an increased incidence of ischemia-related events after withdrawal. To further address this issue, we assessed hemodynamic, neurohormonal and vascular consequences of withdrawing long-term ACEi treatment after experimental MI.
Methods: Rats were subjected to coronary ligation to induce MI, and received quinapril (15 mg/kg/day) from 2 weeks to 14 months post-MI. Subsequently, surviving rats were randomized to sacrifice at 0, 4, and 6 weeks after ACEi withdrawal. Rats were studied for signs of heart failure, hemodynamics and cardiac function, neurohormones, and vascular edothelial function.
Results: After discontinuation of ACEi treatment, plasma aldosterone levels increased between 0—4 weeks without further increment thereafter, suggesting persistent RAAS activation. Acetylcholine-induced aortic relaxation was impaired at 4 and 6 weeks, indicating rapid and sustained development of endothelial vasodilator dysfunction after withdrawal. Moreover, 24% of the rats developed heart failure signs (edema, dyspnea), and 3 rats died, all within 4 weeks after withdrawal. Significantly increased N-ANP levels and lung weights at 4, but not at 6 weeks suggest a transient volume overload. Finally, LV/body weight ratios significantly increased between 0—4 as well as 4—6 weeks, indicating progressive LV hypertrophy.
Conclusions: The observed alterations after withdrawing long-term post-MI quinapril treatment in the present study may account for an increased risk for ischemic events. Thus, our findings highlight the potentially harmful effects associated with abrupt discontinuation of long-term post-MI ACE inhibition, and imply careful clinical consideration in this matter.
Key Words: Withdrawal • ACE inhibition • Myocardial infarction
Received February 8, 2005; Accepted April 26, 2005
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