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Reversibly injured, postischemic canine myocardium retains normal contractile reserve
1Max-Planck-Institute/Kerckhoff Institute, Department of Experimental Cardiology, Bad Nauheim, Federal Republic of Germany.
Insights
Transient coronary occlusion causes stunned myocardium, a temporary contractile dysfunction. This study found that stunned heart muscle retains normal contractile reserve in response to calcium, indicating calcium
Area of Science:
- Cardiovascular Physiology
- Myocardial Ischemia and Reperfusion
Background:
- Transient coronary occlusion leads to stunned myocardium, characterized by prolonged contractile dysfunction without irreversible injury.
- The underlying mechanisms of stunned myocardium are debated, with hypotheses including impaired energetics, altered excitation-contraction coupling, or damaged contractile filaments.
Purpose of the Study:
- To evaluate the contractile reserve of reperfused myocardium to elucidate the mechanisms of postischemic contractile dysfunction.
- To test whether impaired calcium responsiveness contributes to stunned myocardium.
Main Methods:
- Regional subendocardial segment function was assessed using sonomicrometry in dogs.
- Dose-response curves to intracoronary calcium infusion were generated before and after 15 minutes of coronary occlusion and 30 minutes of reperfusion.
- Contractile reserve was measured as the change in segment shortening (%SS) in response to calcium.
Main Results:
- Following 15 minutes of ischemia and reperfusion, myocardial segment shortening was significantly depressed.
- Intracoronary calcium infusion in reperfused myocardium restored contractile function, with %SS reaching pre-ischemic levels at higher doses.
- Calcium-induced increases in segment shortening were sustained and did not cause further dysfunction.
Conclusions:
- Stunned myocardium in this model demonstrates a normal contractile reserve in response to calcium.
- These findings suggest that impaired calcium responsiveness is unlikely to be the primary mechanism underlying postischemic contractile dysfunction.
- The results implicate calcium handling or signaling as a key factor in the development of stunned myocardium.
Abstract:
Transient coronary occlusion (15 minutes) does not result in irreversible myocardial injury but is associated with a depression of contractile function sustained for several hours to days ("stunned myocardium"). The defect in the contractile process responsible for this phenomenon has been suggested to be causally related to a reduced energetic state, altered excitation or excitation-contraction coupling, or damaged contractile filaments. The purpose of this study was to attempt to exclude one or more of these hypotheses by evaluating the contractile reserve of reperfused myocardium. Regional subendocardial segment function was measured (sonomicrometry) in a control region and in an area (treatment region) perfused by a carotid artery to anterior descending coronary artery bypass in 13 chloralose-anesthetized dogs. Dose-response curves were constructed from changes in segment shortening (%SS) in response to intracoronary calcium infusion before ischemia and following 5 or 15 minutes of occlusion and reperfusion (30 minutes). Calcium infusion before ischemia resulted in dose-dependent increases in %SS in the treatment area to a maximum value of 36.6% from a preinfusion value of 25.5% (p less than 0.01), in the absence of changes in control region shortening (23.7%). After 15 minutes of occlusion and reperfusion, treatment area %SS had fallen to a depressed but stable level (46% of preischemic values; p less than 0.01). Subsequent calcium infusion at the same doses as in the preischemic trial produced increases in treatment segment function with return of shortening to control levels at an intermediate dose. At the highest dose, %SS was 35.4%, which was not different from the maximal value found in the preischemic trial. Alterations in heart rate and left ventricular systolic and diastolic pressures during calcium infusion were minor and similar before and after ischemia. Calcium-induced increases in regional segment shortening above control levels (113% of control) in reperfused myocardium were sustained with continuous infusion (30 minutes) without deleterious effects on subsequent function. These results demonstrate that stunned myocardium in this model retains a normal contractile reserve in response to calcium, suggesting that the mechanism responsible for postischemic contractile dysfunction involves calcium.