Related Experiment Videos
Inhibitors of bradykinin-inactivating enzymes decrease myocardial ischemia/reperfusion injury following 3 and 7 days
J A Schriefer1, E P Broudy, A H Hassen
1Department of Pharmacology, West Virginia School of Osteopathic Medicine, Lewisburg, West Virginia 24901, USA. jschriefer@wvsom.edu
The Journal of Pharmacology and Experimental Therapeutics
|August 16, 2001
Summary
Inhibiting bradykinin (BK)-inactivating enzymes protects the heart from injury during reperfusion. This study shows these inhibitors offer long-lasting protection against myocardial ischemia/reperfusion injury by preserving BK levels.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Biochemistry
Background:
- Bradykinin (BK) inactivation is crucial for managing myocardial ischemia/reperfusion (I/R) injury.
- Short-term protection from BK-inactivating enzyme inhibitors does not guarantee long-term myocardial viability.
Purpose of the Study:
- To investigate the chronic effects of angiotensin-converting enzyme (ACE) inhibitors and endopeptidase inhibitors on myocardial I/R injury.
- To assess the impact of these inhibitors on bradykinin (BK) levels and infarct size over extended reperfusion periods.
Main Methods:
- A rabbit model of myocardial I/R injury was established with a 30-minute left descending coronary artery occlusion.
- Animals received saline, ramiprilat (ACE inhibitor), or endopeptidase inhibitors (EP24.11, EP24.15) post-occlusion, with some receiving HOE140 (BK2 receptor antagonist).
- Infarct size was determined after 3 or 7 days of reperfusion; BK tissue levels were measured after 2 hours.
Main Results:
- Ramiprilat and endopeptidase inhibitors significantly reduced infarct size at both 3 and 7 days.
- Combined inhibition further reduced infarct size at 3 days but not at 7 days.
- Endopeptidase inhibitor protection was abrogated by HOE140, and BK levels increased with ramiprilat and cFP-F-pAB treatment.
Conclusions:
- Inhibition of BK-inactivating enzymes preserves endogenous BK, providing sustained protection against myocardial I/R injury.
- While effective acutely, a single treatment does not prevent infarct expansion between 3 and 7 days post-reperfusion.