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Calcium overload during reperfusion is accelerated in isolated hypertrophied rat hearts
M F Allard1, J D Flint, J C English
1Cardiovascular Research Laboratory, St. Paul's Hospital, Vancouver, BC, Canada.
Insights
Hypertrophied hearts experience greater calcium overload during reperfusion, leading to impaired left ventricular systolic function. This dysfunction is linked to calcium overload, not increased ischemic injury, suggesting other mechanisms are involved.
Area of Science:
- Cardiovascular Physiology
- Cardiac Metabolism
Background:
- Cardiac hypertrophy, a common condition, can alter heart function during ischemic events.
- Understanding the mechanisms of post-ischemic dysfunction in hypertrophied hearts is crucial for therapeutic development.
Purpose of the Study:
- To compare calcium overload and myocardial injury during reperfusion in hypertrophied versus normal rat hearts.
- To investigate the relationship between calcium overload, left ventricular dysfunction, and ischemic injury severity.
Main Methods:
- Isolated rat hearts (hypertrophied vs. control) were subjected to global ischemia and reperfusion.
- Left ventricular function, end-diastolic pressure, and calcium overload were measured.
- Myocardial injury was assessed morphologically using antimyosin antibody and glutaraldehyde fixation.
Main Results:
- Hypertrophied hearts showed significantly increased left ventricular end-diastolic pressure and reduced systolic function recovery post-reperfusion.
- Calcium overload during reperfusion was 2.5 times greater in hypertrophied hearts and correlated with dysfunction.
- Morphological assessment revealed no significant difference in ischemic myocardial injury severity between the groups.
Conclusions:
- Calcium overload during reperfusion significantly contributes to post-ischemic left ventricular dysfunction in hypertrophied hearts.
- The accelerated calcium overload is not explained by increased ischemic injury, indicating alternative underlying mechanisms.
Abstract:
In this study, calcium overload during reperfusion and the severity of morphologically evident ischemic myocardial injury were compared in hypertrophied and normal hearts. Hypertrophied hearts isolated from rats where a clip had been placed on the proximal thoracic aorta for 6 weeks were compared to those from sham-operated rats in an isolated state perfused with Krebs-Henseleit buffer containing 3% albumin, 1.2 mM palmitate and 11 mM glucose. The isolated hearts were exposed to global, no-flow, normothermic ischemia following potassium arrest and were reperfused. Following ischemia and reperfusion, left ventricular end diastolic pressure was increased (39 +/- 7 v 13 +/- 2 mmHg, P < 0.05), and percentage recovery of left ventricular systolic function was decreased (34.4 +/- 8.9 v 77.1 +/- 6.3% P < 0.05), in hypertrophied hearts compared to control hearts. Calcium overload during reperfusion was two and one-half times greater in the hypertrophied hearts than in the control hearts and showed significant relationships with recovery of left ventricular systolic function (r = -0.86, P < 0.001) and left ventricular end diastolic pressure (r = 0.78, P < 0.005). Myocardial energy charge did not differ between the two groups at the end of reperfusion. Ischemic myocardial injury was quantitated morphologically by point counting techniques in a comparable series of control and hypertrophied hearts. After ischemia, hearts were either exposed to a monoclonal antimyosin antibody to identify and measure irreversibly injured myocardium by light microscopy or fixed by perfusion with 2.5% glutaraldehyde to quantitate the morphologic changes ultrastructurally. Control and hypertrophied hearts were not significantly different in severity of myocardial injury due to ischemia as assessed morphologically. Thus, the data suggest that calcium overload during reperfusion plays a significant role in post-ischemic left ventricular dysfunction of the hypertrophied heart. The accelerated calcium overload that occurs in the hypertrophied rat heart during reperfusion cannot be explained by differences in severity of myocardial injury during ischemia which indicates that other mechanisms are responsible.