Effects of glibenclamide and nicorandil on cardiac function during ischemia and reperfusion in isolated perfused rat hearts.

Abstract

We examined influences of a blocker (glibenclamide) and an opener (nicorandil) of the ATP-sensitive potassium (KATP) channel on extracellular K concentration [( K+]e), as well as the myocardial function and metabolites during global ischemia and reperfusion in Langendorff-perfused rat heart preparation. In control hearts, [K+]e began to rise 20 s after the onset of ischemia up to an initial peak (8.3 +/- 0.3 mM) at 2.5 +/- 0.7 min, then fell to 6.0 +/- 0.8 mM after 8.2 +/- 0.7 min, and then rose progressively to 14.6 +/- 0.8 mM at the end of 30 min of ischemia. Glibenclamide (50 microM) reduced the initial peak of [K+]e to 7.2 +/- 0.3 mM (P less than 0.01), and nicorandil (200 microM) increased it to 9.4 +/- 0.6 mM (P less than 0.01). There were no significant differences in [K+]e values among all groups at the end of ischemia. During ischemia, nicorandil decreased the time to mechanical arrest from 1.9 +/- 0.1 min to 1.5 +/- 0.1 min, whereas it was increased by glibenclamide to 2.7 +/- 0.4 min. In control hearts, the time to onset of ischemic contracture was 14.7 +/- 1.8 min. Nicorandil delayed onset of contracture and glibenclamide accelerated it. Thus we have confirmed that some part of the early increase in [K+]e during ischemia is attributable to K+ efflux through the KATP channel in our model, and opening of the KATP channel may contribute to a rapid reduction of the contractility of the ischemic myocardium that subsequently protects the myocardium against further ischemic injury.

• Authors: A Mitani, K Kinoshita, K Fukamachi, M Sakamoto, K Kurisu, Y Tsuruhara, F Fukumura, A Nakashima, K Tokunaga
• Journal: The American journal of physiology (Am J Physiol) Vol. 261 Issue 6 Pt 2 Pg. H1864-71 (Dec 1991) ISSN: 0002-9513 [Print] United States
• PMID: 1836311 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channels
• Niacinamide
• Nicorandil
• Adenosine Triphosphate
• Potassium
• Glyburide

Topics

• Adenosine Triphosphate (pharmacology)
• Animals
• Coronary Disease (physiopathology)
• Glyburide (pharmacology)
• Heart (drug effects, physiopathology)
• Kinetics
• Male
• Myocardial Contraction (drug effects)
• Myocardial Reperfusion
• Niacinamide (analogs & derivatives, pharmacology)
• Nicorandil
• Potassium (metabolism)
• Potassium Channels (drug effects, physiology)
• Rats
• Rats, Inbred Strains
• Ventricular Function, Left