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Optimizing the oxygen balance during initial reperfusion with 2,3-butanedione monoxime attenuates cardiac reperfusion
H Habazettl1, J Voigtländer, D Mühlbayer
1Institute for Surgical Research, University of Munich, Germany.
Abstract:
The effect of 20 mmol/L butanedione monoxime on myocardial ischemia/reperfusion damage was studied in isolated guinea pig hearts. Three groups of hearts (n = 8) were perfused in the Langendorff mode and cardioplegic arrest was induced with St. Thomas Hospital II solution (STS) at 37 degrees C for 50 min. Myocardial oxygen demand, recovery of myocardial function, and creatine kinase release during 30 min of reperfusion were monitored. Preservation of myocardial ultrastructure was determined by electron microscopy. Control (C) hearts underwent cardioplegic arrest and reperfusion without treatment. BDM was added during cardioplegic arrest in BDMSTS hearts, or to the initial (20 min) reperfusate in BDMREP hearts. BDM during initial reperfusion markedly reduced O2 demand and prevented creatine kinase release from cardiac myocytes, resulting in improved recovery of myocardial function and attenuation of myocardial ultrastructural damage after washout of the drug. In contrast, addition of BDM to the cardioplegic solution provided no protection from ischemic or reperfusion injury.
Insights
Butanedione monoxime (BDM) administered during reperfusion, not cardioplegic arrest, significantly reduced myocardial ischemia/reperfusion injury. This protective effect improved cardiac function and ultrastructure in isolated guinea pig hearts.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Myocardial ischemia/reperfusion (I/R) injury is a significant clinical challenge.
- Cardioplegic arrest is used to protect the heart during surgery, but I/R injury can still occur.
- Butanedione monoxime (BDM) is a myosin ATPase inhibitor with potential cardioprotective properties.
Purpose of the Study:
- To investigate the effect of butanedione monoxime (BDM) on myocardial ischemia/reperfusion (I/R) damage.
- To determine if BDM administration during cardioplegic arrest or reperfusion offers protection.
- To assess the impact of BDM on myocardial oxygen demand, function, and cellular integrity.
Main Methods:
- Isolated guinea pig hearts were subjected to cardioplegic arrest using St. Thomas Hospital II solution.
- BDM was administered either during cardioplegic arrest (BDMSTS) or during initial reperfusion (BDMREP).
- Myocardial function, oxygen demand, creatine kinase release, and ultrastructure were evaluated.
Main Results:
- BDM administered during initial reperfusion (BDMREP) markedly reduced oxygen demand and prevented creatine kinase release.
- BDMREP treatment led to improved recovery of myocardial function and attenuated ultrastructural damage.
- BDM added to the cardioplegic solution (BDMSTS) provided no protection against I/R injury.
Conclusions:
- Butanedione monoxime (BDM) demonstrates significant cardioprotection when administered during the reperfusion phase of ischemia/reperfusion.
- The timing of BDM administration is critical for its protective effects against myocardial I/R injury.
- BDM may be a potential therapeutic agent for mitigating cardiac damage during reperfusion events.