Comparison of the protective effects of ischemic preconditioning and the Na+/H+ exchanger blockade.

Abstract

The protective effects of ischemic preconditioning (IP) and Na+/H+ exchanger blockade (NHEb) by two blockers [ethylisopropylamiloride (EIPA) and HOE 642] were compared in the isovolumic perfused rat heart. The impairment in systolic and diastolic function detected in control ischemic hearts (C) exposed to 20 min of ischemia and 30 min of reperfusion was diminished in similar extent by IP and by NHEb with EIPA and HOE 642. At the end of the reperfusion period +dP/dtmax values were 57+/-9% in C hearts and 94+/-6%, 82+/-6% and 104+/-6% after IP and NHEb with EIPA and HOE 642, respectively. A depletion of ATP levels detected in C hearts after reperfusion (from 20.2+/-0.8 micromol/g dry weight before ischemia to 6.9+/-0.7 micromol/g dry weight) was partially prevented by both IP and NHEb with EIPA (9.2+/-0.7 micromol/g dry weight and 11.1+/-0.5 micromol/g dry weight, respectively). The ischemic contracture (IC), assessed by the left ventricular end diastolic pressure (LVEDP), observed in C hearts (35+/-4 mmHg) was not decreased by IP (40+/-4 mmHg) but it was prevented by NHEb (18+/-4 mmHg and 10+/-3 mmHg with EIPA and HOE 642, respectively). The ATP levels at the end of the ischemic period were similar in C and IP hearts (4.1+/-0.2 micromol/g dry wt vs. 3.3+/-0.4 micromol/g dry wt) but they were significantly higher after NHEb with HOE 642 (7.0+/-1.0 micromol/g dry wt). PKC inhibition by chelerythrine abolished the protection induced by IP after reperfusion although not the improvement induced by NHEb with EIPA. According to the present results, we can conclude that despite the fact that IP and NHEb are protecting the postischemic function in a similar magnitude, both interventions are different in terms of modifying IC that develops during the ischemic period. IC was prevented by NHEb whereas it was not by IP. Furthermore, IP protection and not that obtained by NHEb is abolished by PKC.

• Authors: S M Mosca, H E Cingolani
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 362 Issue 1 Pg. 7-13 (Jul 2000) ISSN: 0028-1298 [Print] Germany
• PMID: 10935527 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Enzyme Inhibitors
• Guanidines
• Sodium-Hydrogen Exchangers
• Sulfones
• Amiloride
• cariporide
• Adenosine Triphosphate
• Protein Kinase C
• ethylisopropylamiloride

Topics

• Adenosine Triphosphate (metabolism)
• Amiloride (analogs & derivatives, pharmacology)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Blood Pressure (drug effects)
• Enzyme Inhibitors (pharmacology)
• Guanidines (pharmacology)
• In Vitro Techniques
• Ischemic Preconditioning, Myocardial
• Myocardial Contraction (drug effects)
• Myocardium (enzymology, metabolism)
• Protein Kinase C (antagonists & inhibitors)
• Rats
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)
• Sulfones (pharmacology)
• Ventricular Function, Left