K(ATP) channel opening is an endogenous mechanism of protection against the no-reflow phenomenon but its function is compromised by hypercholesterolemia.

Abstract

OBJECTIVE:

This study aimed to clarify the role of adenosine triphosphate-sensitive K(+) (K(ATP)) channels in the no-reflow phenomenon and in its extension by hypercholesterolemia.

BACKGROUND:

The no-reflow phenomenon is an important target of therapy in patients with acute myocardial infarction, but its mechanism remains unclear.

METHODS:

The left circumflex coronary artery was occluded for 30 or 60 min and reperfused in rabbit hearts in situ. The no-reflow zone, area at risk, and infarct size were determined by thioflavin-S, Evans blue, and tetrazolium staining, respectively. No-reflow zone size was expressed as a percentage of infarct size (%NR/IS). Hypercholesterolemia was induced by two weeks of cholesterol-enriched diet.

RESULTS:

A K(ATP) channel blocker, glibenclamide (0.3 mg/kg), increased %NR/IS after 30-min ischemia/90-min reperfusion from 33.6 +/- 1.9% to 45.9 +/- 1.6% and %NR/IS after 60-min ischemia/90-min reperfusion from 32.8 +/- 3.4% to 46.1 +/- 1.7%. However, N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide (NO) synthase inhibitor, and nicorandil, a hybrid of K(ATP) channel opener and nitrate, failed to significantly modify %NR/IS. Hypercholesterolemia increased %NR/IS to 61.6 +/- 0.6%, which was not further enlarged by glibenclamide, and delayed infarct healing during the subsequent five days of reperfusion. These effects of hypercholesterolemia were significantly suppressed by nicorandil. Neither glibenclamide, L-NMMA, nicorandil, nor hypercholesterolemia modified infarct size.

CONCLUSIONS:

The K(ATP) channel activation, but not NO, is a major mechanism of protection against microvascular injury, causing the no-reflow phenomenon in the heart. Suppression of K(ATP) channel opening may underlie the hypercholesterolemia-induced extension of no-reflow, which delays infarct healing.

• Authors: Satoshi Genda, Tetsuji Miura, Takayuki Miki, Yoshihiko Ichikawa, Kazuaki Shimamoto
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 40 Issue 7 Pg. 1339-46 (Oct 02 2002) ISSN: 0735-1097 [Print] United States
• PMID: 12383584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channel Blockers
• Potassium Channels
• Vasodilator Agents
• Nicorandil
• omega-N-Methylarginine
• Adenosine Triphosphate
• Nitric Oxide Synthase
• Glyburide

Topics

• Adenosine Triphosphate (antagonists & inhibitors, physiology)
• Analysis of Variance
• Animals
• Chronic Disease
• Coronary Circulation
• Disease Models, Animal
• Glyburide (pharmacology)
• Hemodynamics
• Hypercholesterolemia (complications)
• Male
• Myocardial Infarction (etiology, mortality, physiopathology, prevention & control)
• Nicorandil (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Potassium Channel Blockers
• Potassium Channels (physiology)
• Rabbits
• Vasodilator Agents (pharmacology)
• omega-N-Methylarginine (pharmacology)