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Superoxide dismutase plus catalase improve contractile function in the canine model of the "stunned myocardium"
Insights
Free radical scavengers, superoxide dismutase plus catalase, improved cardiac function after ischemia-reperfusion injury in dogs. However, this did not restore high energy phosphate levels or prevent blood pressure drops.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Myocardial stunning, a post-ischemic contractile dysfunction, occurs despite the absence of necrosis.
- Oxygen-derived free radicals are implicated in ischemia-reperfusion injury.
- Superoxide dismutase (SOD) and catalase are key enzymes that neutralize reactive oxygen species.
Purpose of the Study:
- To investigate if administering free radical scavengers (SOD + catalase) can attenuate myocardial stunning after coronary artery occlusion and reperfusion.
- To assess the impact of SOD + catalase on contractile function and high-energy phosphate content in stunned myocardium.
Main Methods:
- Anesthetized, open-chest dogs underwent 15 minutes of left anterior descending coronary artery occlusion followed by reperfusion.
- Free radical scavengers (SOD + catalase) were administered before, during occlusion, and throughout reperfusion in the treatment group.
- Segment shortening, wall thickening, high-energy phosphate content (ATP), and regional blood flow were measured.
Main Results:
- Dogs treated with SOD + catalase showed significantly improved segment shortening and wall thickening during reperfusion compared to controls.
- Contractile function recovery in treated dogs reached 56% of pre-infusion values, versus 10% in controls.
- ATP levels in the previously ischemic myocardium were not significantly different between treated and control groups.
- Blood flow during occlusion and reperfusion was unaffected, but blood pressure decreased in the treated group.
Conclusions:
- Administration of superoxide dismutase plus catalase can improve contractile function in stunned myocardium following ischemia-reperfusion.
- The beneficial effects on contractility are not mediated by increased ATP stores.
- Further research is needed to understand the mechanisms and potential side effects, such as hypotension, associated with free radical scavenger administration.
Abstract:
Fifteen minutes of coronary occlusion followed by reperfusion does not result in myocardial necrosis; however, the contractile function and high energy phosphate content of the previously ischemic myocardium remains depressed or "stunned" for several hours to days after reperfusion. Oxygen-derived free radicals have been implicated in ischemia and reperfusion-induced injury in a variety of tissues. We wished to determine whether administration of free radical scavengers superoxide dismutase plus catalase before and during occlusion, and throughout reperfusion, could attenuate the "stunning" produced by 15 minutes of left anterior descending coronary artery occlusion in anesthetized, open-chest dogs. Segment shortening in the previously ischemic zone recovered to within only +/- 10% of preinfusion values in the control group during 3 hours of reperfusion, while, in the treated dogs, segment shortening returned to a maximum of 56 +/- 16% of preinfusion at 1 1/2 hours post-reperfusion (P less than 0.0003 compared to controls). Similarly, superoxide dismutase + catalase-treated dogs exhibited improved wall thickening during reperfusion (+30% to +70% of preinfusion values), compared to controls (0% to +10%). However, this improvement in contractile function in the treated group was not accompanied by increased adenosine triphosphate stores in the previously ischemic zone (31.8 +/- 0.8 vs. 28.2 +/- 2.2 nmol/mg protein for control vs. treated groups). Infusion of superoxide dismutase + catalase did not influence blood flow during occlusion or reperfusion. However, the treated group did exhibit a significant decrease in blood pressure during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
