The role of L-arginine in ameliorating reperfusion injury after myocardial ischemia in the cat.
Open accessAbstract
BACKGROUND: Myocardial ischemia followed by reperfusion results in endothelial dysfunction characterized by a reduced release of endothelium-derived relaxing factor (EDRF). Because EDRF has been characterized as nitric oxide, we examined the ability of L-arginine, the substrate for nitric oxide synthesis, to protect in a feline model of myocardial ischemia plus reperfusion. METHODS AND RESULTS: The effects of L-arginine were investigated in a 6-hour model of myocardial ischemia and reperfusion in pentobarbital-anesthetized cats. A bolus administration (30 mg/kg) of L-arginine, or its enantiomer D-arginine, was given followed by a continuous infusion of 10 mg/kg/min for 1 hour starting 10 minutes before reperfusion. Myocardial ischemia plus reperfusion in cats receiving D-arginine resulted in severe myocardial injury and endothelial dysfunction characterized by marked myocardial necrosis, high cardiac myeloperoxidase activity in ischemic cardiac tissue, and loss of acetylcholine- and A-23187-induced endothelium-dependent relaxation in coronary artery rings. In contrast, myocardial ischemia plus reperfusion cats treated with L-arginine exhibited a reduced area of cardiac necrosis (16 +/- 2% versus 41 +/- 5% of area at risk, p less than 0.01), lower myeloperoxidase activity in the ischemic region (0.3 +/- 0.08 versus 0.8 +/- 0.10 units/100 mg tissue, p less than 0.05), and significant preservation of acetylcholine- (p less than 0.01) and A-23187- (p less than 0.01) induced endothelial-dependent relaxation. CONCLUSIONS: These results demonstrate the ability of L-arginine to reduce necrotic injury in a cat model of myocardial ischemia plus reperfusion, and this reduction in infarct size is associated with the preservation of endothelial function and attenuation of neutrophil accumulation in ischemic cardiac tissue.
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Data point toward mitochondria as central targets for the molecular mechanisms behind nitrate effects.
“The molecular mechanisms behind these remarkable effects of nitrate have not been determined in detail, but data point toward the mitochondria as the central targets.132”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [132]
The discussion passage describes possible cardioprotective mechanisms of L-arginine and nitric oxide, including reduced neutrophil adherence and superoxide quenching. Searches for mitochondrial targets and nitrate effects found no passage in our copy addressing the claim. (LLM, conf=0.75)
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Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care
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- Authors
- Weyrich, A. S., Ma, X. L., & Lefer, A. M.
- Affiliations
- Thomas Jefferson University (US)
- Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa. 19107-6799.
- ORCID
- Weyrich, A S
- Venue
- Circulation
- Published
- 1992-07
- Volume
- 86
- Issue
- 1
- Pages
- 279-288
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2061897451
- Cited by
- 320
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2018: 3 · 2016: 3 · 2015: 1 · 2014: 3 · 2013: 7 · 2012: 1
- FWCI
- 19.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Circulation
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-08507, F32HL008507)
- National Institute of General Medical Sciences (GM-45434, R01GM045434)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- L-arginine, myocardial ischemia-reperfusion injury, nitric oxide, endothelial dysfunction, D-arginine, myocardial necrosis, infarct size, neutrophil accumulation, myeloperoxidase, endothelium-dependent relaxation, coronary arteries, cardioprotection
- MeSH terms
- Animals, Arginine, Cats, Cell Adhesion, Cell Movement, Coronary Disease, Coronary Vessels, Electrophysiology, Endothelium, Vascular, Heart, Hemodynamics, Male, Peroxidase, Neutrophils, Myocardial Reperfusion, Myocardial Reperfusion Injury
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