L-Name Enhances Microcirculatory Congestion and Cardiomyocyte Apoptosis During Myocardial Ischemia-Reperfusion in Rats
Autor: | Peitan Liu, Baohuan Xu, Lloyd J Forman, Carl E. Hock, Rocco V. Carsia |
---|---|
Rok vydání: | 2002 |
Předmět: |
Male
medicine.medical_specialty Necrosis Myocardial Ischemia Ischemia Hemodynamics Apoptosis Blood Pressure Cytochrome c Group Enzyme-Linked Immunosorbent Assay Myocardial Reperfusion DNA Fragmentation Nitric Oxide Critical Care and Intensive Care Medicine Microcirculation Rats Sprague-Dawley Afterload Internal medicine Animals Medicine Nitrites Nitrates business.industry Myocardium Heart Stroke volume medicine.disease Rats NG-Nitroarginine Methyl Ester medicine.anatomical_structure Anesthesia Emergency Medicine Cardiology medicine.symptom business Reperfusion injury Artery |
Zdroj: | Shock. 17:185-192 |
ISSN: | 1073-2322 |
DOI: | 10.1097/00024382-200203000-00005 |
Popis: | Besides necrosis, apoptosis is the other major mode of cardiomyocyte loss in ischemic cardiovascular disease. In the present study, we examined the hypothesis that nitric oxide (NO) protects myocardial function by improving myocardial microcirculation and attenuating cardiomyocyte apoptosis in a rat model of myocardial ischemia/reperfusion (MI/R). The left main coronary artery of anesthetized male rats was ligated for 40 min, followed by 4 h reperfusion. Four groups of animals were studied: sham operated control + saline; sham operated control + N(W)-nitro-L-arginine methyl ester (L-NAME); MI/R + saline; MI/R + L-NAME (10 mg/kg, iv, 10 min prior to reperfusion). Results show that MI/R caused a decrease in mean arterial blood pressure (MABP), cardiac index (CI), and stroke volume index (SVI). Inhibition of NO synthesis by L-NAME attenuated plasma NO levels, but increased MABP and SVR in sham control rats and rats subjected to MI/R, and further depressed left ventricular function in rats subjected to MI/R as indicated by decreased CI and SVI. Furthermore, administration of L-NAME to rats subjected to MI/R enhanced cardiomyocyte apoptosis as indicated by a significant increase in DNA fragmentation compared to rats with MI/R alone. Histological study revealed that L-NAME caused arterial constriction and congestion of red blood cells in arteries and capillaries in the peri-ischemic areas of the hearts in rats subjected to MI/R and, interestingly, also in the sham control rats. Data suggest that the mechanism of increased reperfusion injury may be attributable to a "no-reflow" phenomenon induced by L-NAME, resulting in increased cardiomyocyte apoptosis secondary to ischemia and enhanced cytochrome-c release from mitochondria. In addition, cardiac injury may be increased due to the augmented oxygen consumption of cardiomyocytes caused by the increased SVR and afterload. These results suggest that endogenous NO may act to improve myocardial microvascular perfusion, reduce SVR, and limit cardiomyocyte apoptosis, thereby, attenuating myocardial dysfunction induced by MI/R. |
Databáze: | OpenAIRE |
Externí odkaz: |
načítá se...