Reduction of myocardial infarction by postischemic administration of the calpain inhibitor A-705253 in comparison to the Na(+)/H(+) exchange inhibitor Cariporide in isolated perfused rabbit hearts.

Abstract

The calpain inhibitor A-705253 and the Na(+)/H(+)-exchange inhibitor Cariporide were studied in isolated perfused rabbit hearts subjected to 60 min occlusion of the ramus interventricularis of the left coronary artery (below the origin of the first diagonal branch), followed by 120 min of reperfusion. The inhibitors were added to the perfusion fluid solely or in combination at the beginning of reperfusion. Hemodynamic monitoring and biochemical analysis of perfusion fluid from the coronary outflow were performed. Myocardial infarct size and area at risk (transiently not perfused myocardium) were determined from left ventricular slices after a special staining procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted area (dead myocardium) was 72.7+/-4.0% of the area at risk in untreated controls, but was significantly smaller in the presence of the inhibitors. The largest effect was seen with 10(-6) m A-705253, which reduced the infarcted area to 49.2+/-4.1% of the area at risk, corresponding to a reduction of 33.6%. Cariporide at 10(-6) m reduced the infarct size to the same extent. The combination of both inhibitors, however, did not further improve cardioprotection. No statistical difference was observed between the experimental groups in coronary perfusion, left ventricular pressure, heart rate, and in the release of lactate dehydrogenase and creatin kinase from heart muscle.

• Authors: Christiane Neuhof, Verena Fabiunk, Maria Speth, Achim Möller, Fritz Fritz, Harald Tillmanns, Heinz Neuhof, Ali Erdogan
• Journal: Biological chemistry (Biol Chem) Vol. 389 Issue 12 Pg. 1505-12 (Dec 2008) ISSN: 1431-6730 [Print] Germany
• PMID: 18844452 (Publication Type: Journal Article)

Chemical References

• A-705253
• Anti-Arrhythmia Agents
• Benzamides
• Guanidines
• Sodium-Hydrogen Exchangers
• Sulfones
• cariporide
• Calpain
• Potassium

Topics

• Animals
• Anti-Arrhythmia Agents (therapeutic use)
• Benzamides (therapeutic use)
• Blood Pressure (drug effects)
• Calpain (antagonists & inhibitors)
• Coronary Circulation (physiology)
• Female
• Guanidines (therapeutic use)
• Heart (drug effects)
• Heart Rate (drug effects)
• In Vitro Techniques
• Male
• Myocardial Infarction (pathology, prevention & control)
• Myocardium (pathology)
• Potassium (metabolism)
• Rabbits
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)
• Sulfones (therapeutic use)
• Ventricular Function, Left (drug effects)