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Ischemic-reperfused isolated working mouse hearts: membrane damage and type IIA phospholipase A2
L J De Windt1, J Willems, T H Roemen
1Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands.
Abstract:
For the murine heart the relationships between ischemia-reperfusion-induced loss of cardiac function, enzyme release, high-energy phosphate (HEP), and membrane phospholipid metabolism are ill-defined. Accordingly, isolated ejecting murine hearts were subjected to varying periods of ischemia, whether or not followed by reperfusion. On reperfusion, hemodynamic function was almost completely restored after 10 min of ischemia [83 +/- 14% recovery of cardiac output (CO)], but was severely depressed after 15 and 20 min of ischemia (40 +/- 24 and 31 +/- 24% recovery of CO, respectively). Reperfusion was associated with partial recovery of HEP stores and enhanced degradation of phospholipids as indicated by the accumulation of fatty acids (FA). Myocardial FA content and enzyme release during reperfusion were correlated (r = 0.70), suggesting that membrane phospholipid degradation and cellular damage are closely related phenomena. To investigate the role of type IIA secretory phospholipase A2 (sPLA2) in this process, hearts from wild-type and sPLA2-deficient mice were subjected to ischemia-reperfusion. Postischemic functional recovery, ATP depletion, enzyme release, and FA accumulation were not significantly different between wild-type and sPLA2- deficient hearts. These findings argue against a prominent role of type IIA sPLA2 in the development of irreversible cell damage in the ischemic-reperfused murine myocardium.
Insights
Ischemia-reperfusion injury in murine hearts impairs cardiac function and causes cell damage. Type IIA secretory phospholipase A2 (sPLA2) does not appear to play a significant role in this process.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Molecular Biology
Background:
- The mechanisms linking ischemia-reperfusion injury to cardiac dysfunction, enzyme release, high-energy phosphate (HEP) levels, and membrane phospholipid metabolism in murine hearts remain unclear.
- Understanding these relationships is crucial for developing therapeutic strategies against myocardial infarction.
Purpose of the Study:
- To investigate the functional, biochemical, and metabolic changes in murine hearts subjected to ischemia-reperfusion.
- To determine the specific role of type IIA secretory phospholipase A2 (sPLA2) in mediating ischemia-reperfusion injury.
Main Methods:
- Isolated ejecting murine hearts were subjected to varying durations of ischemia, with or without reperfusion.
- Hemodynamic function, high-energy phosphate (HEP) levels, enzyme release, and fatty acid (FA) accumulation were measured.
- Experiments were conducted using both wild-type and sPLA2-deficient mice.
Main Results:
- Cardiac function recovery was significantly impaired after 15 and 20 minutes of ischemia, with partial recovery of HEP stores and increased FA accumulation upon reperfusion.
- Myocardial FA content correlated with enzyme release, suggesting a link between phospholipid degradation and cellular damage.
- No significant differences in functional recovery, ATP depletion, enzyme release, or FA accumulation were observed between wild-type and sPLA2-deficient hearts.
Conclusions:
- Membrane phospholipid degradation is closely associated with cellular damage during ischemia-reperfusion in murine hearts.
- Type IIA secretory phospholipase A2 (sPLA2) does not appear to be a major contributor to irreversible myocardial damage in this model.