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Updated: Oct 2, 2026
Murine Isolated Heart Model of Myocardial Stunning Associated with Cardioplegic Arrest
Published on: August 6, 2015
Inhibition of Na(+)/H(+) isoform-1 exchange protects hearts perfused after 6-hour cardioplegic cold storage
David F Stowe1, James S Heisner, Jianzhong An
1Department of Anesthesiology Research Laboratories, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. dfstowe@mcw.edu
Insights
Inhibiting the Na(+)/H(+) isoform-1 exchanger protected guinea pig hearts during cold storage. This approach enhances the protective effects of cardioplegic solutions, reducing cellular injury and improving cardiac function post-reperfusion.
Area of Science:
- Cardiovascular Physiology
- Cellular Biology
- Pharmacology
Background:
- Cardiac ischemia-reperfusion injury involves Na(+)/H(+) exchange, leading to Na(+) and Ca(2+) overload.
- This overload contributes to cellular damage and impaired cardiac function.
Purpose of the Study:
- To investigate if inhibiting the Na(+)/H(+) isoform-1 exchanger (NHE-1) enhances heart protection during cold storage.
- To evaluate the additive protective effects of NHE-1 inhibition combined with acidic cardioplegic solutions.
Main Methods:
- Isolated guinea pig hearts were perfused and stored in acidic St. Thomas solution (STS) for 6 hours at 3.4°C.
- Hearts were divided into four groups: sham control, eniporide (EPR) administered intravenously (IV), intracoronary (IC), or both IV and IC.
- EPR is an inhibitor of the Na(+)/H(+) isoform-1 exchanger.
Main Results:
- Eniporide administration, particularly combined IV and IC, significantly improved left ventricular pressure and cardiac efficiency post-reperfusion compared to sham controls.
- Intracoronary EPR showed the highest preservation of coronary flow.
- Combined IV and IC EPR administration markedly reduced infarct size (6% +/- 2% vs. 35% +/- 3% in sham).
Conclusions:
- Na(+)/H(+) isoform-1 exchanger inhibition provides additional protection to hearts subjected to long-term cold storage in acidic cardioplegic solutions.
- Optimal protection was achieved with eniporide given both intravenously before isolation and intracoronary during cooling and rewarming.
Objectives:
Cardiac ischemia-reperfusion activates Na(+)/H(+) exchange; excess Na(+) and the resulting Ca(2+) overload, through reverse Na(+)/Ca(2+) exchange, cause cellular injury and cardiac dysfunction. We postulated that inhibiting the Na(+)/H(+) isoform-1 exchanger would add to the protection of hearts after long-term cold storage in acidic cardioplegic solution.
Methods:
Guinea pig hearts were isolated and perfused at 37 degrees C with Krebs-Ringer's solution (KRS) and then switched to an acidic St. Thomas solution (STS) at 25 degrees C. Perfusion was stopped at 10 degrees C, and hearts were stored for 6 hours in STS at 3.4 degrees C. On reperfusion to 25 degrees C, hearts were perfused with KRS for 60 minutes. Hearts were divided into 4 groups: sham control (SHAM); eniporide (EPR, EMD96785) IV, 1 mg/kg given IV over 15 minutes before heart isolation; EPR intracoronary, 1 micromol/liter in STS given intracoronary after heart isolation; and EPR IV and intracoronary.
Results:
Values at 60 minutes reperfusion (the percentage of control [100%] before cold storage) are given, respectively, for EPR IV, EPR intracoronary, and EPR IV and intracoronary vs drug-free SHAM (SEM, *p < 0.05 vs SHAM): 72% +/- 3%*, 65% +/- 3%*, and 81% +/- 2%* vs 55% +/- 3% for left ventricular pressure; 94% +/- 3%*, 96% +/- 5%*, and 102% +/- 2%* vs 81% +/- 3% for coronary flow; 60% +/- 2%, 58% +/- 3%, and 74%* +/- 3% vs 58% +/- 4% for cardiac efficiency; 106% +/- 2%*, 108% +/- 3%*, and 107% +/- 2%* vs 116% +/- 4% for percentage of O(2) extraction. Infarct size as percentage of ventricular weight was 20% +/- 3%*, 31% +/- 3%, and 6% +/- 2%* vs 35% +/- 3% (SHAM) after 60 minutes of reperfusion.
Conclusions:
Na(+)/H(+) isoform-1 exchanger inhibition, particularly if given IV before storage and intracoronary during cooling and rewarming, adds to the protection of cardioplegic solutions.
