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Published on: August 6, 2015
Paradoxical toxicity of cardioplegic compounds on ischemic cardiomyocyte using optimal design strategy
René Ferrera1, Pierre Michel, Michel Ovize
1INSERM, Institut National pour la Santé et la Recherche Médicale, EMI-U 0226, Lyon, France. ferrera@lyon.inserm.fr
Background:
The aim of this study was to evaluate the effects of major components of cardioplegic solutions on myocardial tissue submitted to prolonged cold ischemia.
Methods:
Our methodology was based on the simultaneous testing in the same series of experiments of many compounds (19 in number), which were included in the composition of 20 established solutions. All the experiments were performed by a matricial-predefined protocol that allows the evaluation of the protective or toxic effects of each of these 19 compounds. Pig hearts were removed and left ventricular myocardiums were cut into 320 pieces. For each solution tested, 8 pieces of myocardial tissue were incubated at 4 degrees C for 24 hours and 8 other pieces were incubated for 72 hours. At the end of incubation period, tissue injury was assessed by measuring the leakage of myocardial enzymes(glutamic-oxaloacetic transaminase, lactate dehydrogenase, creatine phosphokinase) into the incubation medium. Initially, the effects of each solution were evaluated, and then a mathematical analysis was performed and the effects of each compound deduced.
Results:
After the 24-hour incubation period, pyruvate (5 mmol/liter), polyethylene glycol (5 mmol/liter), Ala-Gln (20 mmol/liter), and reduced glutathione (3 mmol/liter) showed toxic effects, whereas ethanol (1%) and calcium chloride (2 mmol/liter) seemed to be protective. After 72 hours' incubation, similar data were obtained; dextran 70 (0.57 mmol/liter) was also found to be deleterious.
Conclusions:
The results revealed surprising myocardial toxicity (enzymatic release) from components included in cardioplegic solutions. Some components would induce metabolic activation during prolonged hypothermic ischemia, which may be inappropriated and which may perhaps exacerbate damages by increasing membrane ruptures. This concept confirms eventual discrepant effects of preservative compounds on cardiomyocyte membrane during deep hypothermia, according to the metabolic state of the cell.
Insights
Some cardioplegic solution components can harm myocardial tissue during cold ischemia. Ethanol and calcium chloride showed protective effects, while others like pyruvate were toxic, impacting cell membranes.
Area of Science:
- Cardiology
- Biochemistry
- Cell Biology
Background:
- Cardioplegic solutions are crucial for myocardial protection during cardiac surgery.
- Prolonged cold ischemia can lead to myocardial injury.
- Understanding the effects of individual components is vital for optimizing cardioplegic solutions.
Purpose of the Study:
- To evaluate the impact of individual components found in cardioplegic solutions.
- To assess the effects of these components on myocardial tissue subjected to prolonged cold ischemia.
Main Methods:
- Simultaneous testing of 19 compounds within 20 established cardioplegic solutions.
- Utilized a predefined protocol for evaluating protective or toxic effects.
- Assessed myocardial injury by measuring enzyme leakage (AST, LDH, CPK) after 24 and 72 hours of cold incubation (4°C) in pig heart tissue.
Main Results:
- Pyruvate, polyethylene glycol, Ala-Gln, and reduced glutathione exhibited toxicity after 24 hours.
- Ethanol and calcium chloride demonstrated protective effects.
- Dextran 70 was found to be deleterious after 72 hours of incubation.
Conclusions:
- Certain cardioplegic solution components can induce unexpected myocardial toxicity during prolonged hypothermic ischemia.
- Metabolic activation by some components may exacerbate cellular damage through membrane rupture.
- The effect of preservative compounds on cardiomyocyte membranes during hypothermia is dependent on the cell's metabolic state.
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