Effective protection by NHE-1 inhibition in ischemic and reperfused heart under preconditioning blockade.

Abstract

We compared the protective effects of ischemic preconditioning (IPC) and the Na(+)/H(+) exchanger-1 (NHE-1) inhibitor cariporide in isolated rat hearts subjected to global ischemia (45 or 90 min) and 30-min reperfusion and determined the protective effects of cariporide under IPC blockade with the mitochondrial ATP-sensitive K(+) channel blocker 5-hydroxydecanoate (5-HD). With 45-min ischemia, both IPC and cariporide equally increased maximum recovery of left ventricular developed pressure twofold (P < 0.05), although recovery was significantly greater with cariporide for the first 15 min of reperfusion. 5-HD almost completely blocked the protective effects of IPC on recovery but had no influence on the salutary effects of cariporide. With 90-min ischemic control, recovery was only 3% of preischemia and was unaffected by IPC, although cariporide increased recovery to approximately 30% (P < 0.05). This was associated with a 37% preservation of viable cardiac cells, whereas no structurally intact cells were found in either IPC or control hearts. Our study shows that NHE-1 inhibition is a more effective cardioprotective strategy than IPC in this model, possibly because of enhanced myocyte salvage, and because protection by NHE-1 inhibition is completely unaffected by IPC blockade with 5-HD.

• Authors: James V Haist, Claire N Hirst, Morris Karmazyn
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 284 Issue 3 Pg. H798-803 (Mar 2003) ISSN: 0363-6135 [Print] United States
• PMID: 12578812 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Decanoic Acids
• Guanidines
• Hydroxy Acids
• Potassium Channel Blockers
• Sodium-Hydrogen Exchangers
• Sulfones
• growth factor-activatable Na-H exchanger NHE-1
• 5-hydroxydecanoic acid
• cariporide

Topics

• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Decanoic Acids (pharmacology)
• Diastole (drug effects, physiology)
• Guanidines (pharmacology)
• Heart (drug effects, physiopathology)
• Hydroxy Acids (pharmacology)
• In Vitro Techniques
• Ischemic Preconditioning, Myocardial
• Male
• Myocardial Ischemia (pathology, physiopathology, prevention & control)
• Myocardial Reperfusion
• Myocardium (pathology)
• Potassium Channel Blockers (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects)
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)
• Sulfones (pharmacology)
• Time Factors
• Ventricular Function, Left (drug effects)