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Updated: Aug 15, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA
Steve J Schomisch1, Deborah G Murdock, Nasim Hedayati
1Division of Cardiothoracic Surgery, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio 44106-5011, USA.
Insights
Hyperkalemic cardioplegia preserves heart gene expression during ischemia, maintaining energy conservation and cytoprotective pathways. This reveals an additional mechanism of myocardial protection beyond established effects.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Proteomics and Genomics
Background:
- Hyperkalemic cardioplegia protects the heart during ischemia via energy conservation and calcium homeostasis.
- Previous research suggests cytoprotective signaling pathways are activated by cardioplegia, contributing to reduced injury.
- This study investigated the transcriptional response of the heart to cardioplegia-protected ischemia.
Purpose of the Study:
- To investigate the transcriptional response of the heart to cardioplegia-protected ischemia compared to ischemia alone.
- To identify cytoprotective pathways activated by cardioplegia during ischemic events.
- To elucidate the molecular mechanisms underlying cardioplegia-induced cardioprotection.
Main Methods:
- Isolated perfused rat hearts subjected to global ischemia with or without St. Thomas cardioplegia.
- Gene expression profiling using Affymetrix microarrays.
- Protein expression analysis via immunoblotting.
Main Results:
- Cardioplegia preserved gene expression involved in energy metabolism (carbohydrate, fatty acid, glycolysis, electron transport) and calcium homeostasis (sodium-calcium exchanger, ryanodine receptor).
- Expression of multiple cytoprotective molecules (e.g., protein-tyrosine kinase, calcineurin B, p38 MAPK, HSP70, MnSOD) was maintained by cardioplegia.
- Ischemia alone led to decreased expression of these protective genes and proteins.
Conclusions:
- Cardioplegia maintains a gene expression profile similar to non-ischemic hearts, preserving energy conservation, calcium homeostasis, and cytoprotective pathways.
- Ischemia alone significantly alters the transcriptional profile, leading to reduced expression of protective genes.
- Understanding these transcriptional differences offers insight into an additional mechanism of cardioplegia-induced cardioprotection.
Background:
Energy conservation and calcium homeostasis contribute to myocardial protection provided by hyperkalemic cardioplegia during ischemia. Complimenting these established mechanisms of protection, previous work suggested that activation of cytoprotective signaling pathways also contributes to reduced injury with cardioplegia. We proposed that cardioplegia would recruit cytoprotective pathways and investigated the transcriptional response of the heart after cardioplegia-protected ischemia compared with that after ischemia alone.
Methods:
Isolated perfused rat hearts underwent 40 minutes of global ischemia alone or with St Thomas cardioplegia, followed by 120 minutes of reperfusion. The expression profiles of isolated RNA were determined by using Affymetrix microarrays and assessed by comparing cardioplegia-protected hearts and hearts undergoing unprotected ischemia with time-matched control hearts. The content of selected proteins was assessed by means of immunoblotting.
Results:
Cardioplegia preserved the expression of multiple genes involved in carbohydrate and fatty acid metabolism, glycolysis, and electron transport compared with ischemia alone. The expression of the sodium-calcium exchanger and ryanodine receptor was preserved in line with the ability of cardioplegia to decrease calcium overload. The expression of multiple cytoprotective molecules, including protein-tyrosine kinase, calcineurin B, p38 mitogen-activated protein kinase, voltage-dependent anion channel, protein kinase C , heat shock protein 70, and manganese superoxide dismutase all showed decreased expression in ischemia but were preserved to near nonischemic levels by cardioplegia.
Conclusion:
Cardioplegia during ischemia maintained an expression profile similar to that seen in nonischemic hearts for genes involved in energy conservation, calcium homeostasis, and cytoprotective pathways, whereas ischemia alone did not. Exposing the transcriptional differences in cytoprotective genes during untreated and cardioplegia-treated ischemia provides valuable insight into an additional mechanism of cardioprotection induced by cardioplegia.
