Abstract | OBJECTIVE: We investigate the impact of different regimens of parenteral hydrogen sulfide (H2S) administration on myocardium during ischemia-reperfusion (IR) and the molecular pathways involved in its cytoprotective effects. METHODS: Eighteen male Yorkshire pigs underwent 60 minutes of mid-left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion. Pigs received either placebo (control, n = 6) or H2S as a bolus (bolus group, n = 6, 0.2 mg/kg over 10 seconds at the start of reperfusion) or as an infusion (infusion group, n = 6, 2 mg.kg.h initiated at the onset of ischemia and continued into the reperfusion period). Myocardial function was monitored throughout the experiment. The area at risk and myocardial necrosis was determined by Monastral blue/triphenyl tetrazolium chloride staining. Apoptosis and the expression pattern of various intracellular effector pathways were investigated in the ischemic territory. Coronary microvascular reactivity to endothelium-dependent and endothelium-independent factors was measured. RESULTS: CONCLUSIONS: This study demonstrates that infusion of H2S is superior to a bolus alone in reducing myocardial necrosis after IR injury, even though some markers of apoptosis and autophagy were affected in both H2S-treated groups. Thus, the current results indicate that infusion of H2S throughout IR may offer better myocardial protection from IR injury.
|
Authors | Robert M Osipov, Michael P Robich, Jun Feng, Yuhong Liu, Richard T Clements, Hilary P Glazer, Neel R Sodha, Csaba Szabo, Cesario Bianchi, Frank W Sellke |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 54
Issue 4
Pg. 287-97
(Oct 2009)
ISSN: 1533-4023 [Electronic] United States |
PMID | 19620880
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cardiotonic Agents
- Troponin I
- Hydrogen Sulfide
|
Topics |
- Animals
- Apoptosis
(drug effects)
- Cardiotonic Agents
(administration & dosage, blood, therapeutic use)
- Cell Survival
(drug effects)
- Coronary Circulation
(drug effects)
- Disease Models, Animal
- Hydrogen Sulfide
(administration & dosage, blood, therapeutic use)
- In Situ Nick-End Labeling
- Infusions, Intravenous
- Injections, Intravenous
- Male
- Microcirculation
(drug effects)
- Myocardial Infarction
(etiology, pathology, physiopathology, prevention & control)
- Myocardial Reperfusion Injury
(complications, drug therapy, pathology, physiopathology)
- Myocardium
(pathology)
- Swine
- Troponin I
(blood)
- Ventricular Function, Left
(drug effects)
|