|
Introduction: Hydrogen sulfide is produced endogenously in response to myocardial ischemia and thought to be
cardioprotective. The mechanism underlying this protection has yet to be fully elucidated, but it may be related to
sulfide’s ability to limit inflammation. This study investigates the cardioprotection provided by exogenous hydrogen
sulfide and its potential anti-inflammatory mechanism of action.
Methods: The mid left anterior descending coronary artery in 14 Yorkshire swine was acutely occluded for 60
minutes, followed by reperfusion for 120 minutes. Controls (n ј 7) received placebo, and treatment animals (n ј
7) received sulfide 10 minutes before and throughout reperfusion. Hemodynamic and functional measurements
were obtained. Evans blue and triphenyl tetrazolium chloride staining identified the area at risk and infarction.
Coronary microvascular reactivity was assessed. Tissue was assayed for myeloperoxidase activity and proinflammatory
cytokines.
Results: Pre-ischemia/reperfusion hemodynamics were similar between groups, whereas post-ischemia/reperfusion
mean arterial pressure was reduced by 28.7 5.0 mm Hg in controls versus 6.7 6.2 mm Hg in treatment
animals ( P ј .03). Positive first derivative of left ventricular pressure over time was reduced by 1325 455 mm
Hg/s in controls versys 416 207 mm Hg/s in treatment animals (P ј .002). Segmental shortening in the area at
risk was better in treatment animals. Infarct size (percent of area at risk) in controls was 41.0 % 7.8% versus
21.2 %2.5%in the treated group (P ј.036). Tissue levels of interleukin 6, interleukin 8, tumor necrosis factoralpha,
and myeloperoxidase activity decreased in the treatment group. Treated animals demonstrated improved
microvascular reactivity.
Conclusions: Therapeutic sulfide provides protection in response to ischemia/reperfusion injury, improving
myocardial function, reducing infarct size, and improving coronary microvascular reactivity, potentially through
its anti-inflammatory properties. Exogenous sulfide may have therapeutic utility in clinical settings in which ischemia/
reperfusion injury is encountered.
| 
