Faculty Collaboration Database

Selective mitochondrial KATP channel opening controls human myocardial preconditioning: too much of a good thing? Surgery 2000 Aug;128(2):368-73

Date

08/03/2000

Pubmed ID

10923018

DOI

10.1067/msy.2000.107423

Scopus ID

2-s2.0-0033624359 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

BACKGROUND: Paradoxically, patients with noninsulin-dependent diabetes mellitus experience a higher cardiovascular mortality rate than patients with insulin-dependent diabetes mellitus. We have shown that K(ATP) channel inhibition, with oral sulfonylureas, prevents myocardial preconditioning and may explain the paradox of cardiovascular death in patients with noninsulin-dependent diabetes mellitus. Cardiac preconditioning is an attractive protective strategy against any elective ischemia/reperfusion (I/R) injury. The relationship between the K(ATP) channels and human myocardial preconditioning has not previously been elucidated.

METHODS: Human atrial trabeculae were harvested, placed in organ baths, and paced (1 Hz). Developed force was recorded during simulated 37 degrees C I/R (30/45 or 45/60 minutes). Before I/R, trabeculae were treated transiently with a selective mitochondrial K(ATP) channel opener for 5 minutes, followed by a 10-minute washout, or were exposed to the channel opener throughout ischemia. Recovery of function is expressed as percentage of baseline developed force. Conserved creatine kinase activity (units per gram of wet tissue) was measured at the end of reperfusion as an indicator of cellular protection.

RESULTS: Transient mitochondrial K(ATP) channel opening provided protection from both I/R insults. Surprisingly, there was no protection afforded by continuous mitochondrial K(ATP) channel opening.

CONCLUSIONS: Transient selective mitochondrial K(ATP) channel opening protects both viability and function of human myocardium against I/R injury, although prolonged opening of the mitochondrial K(ATP) channel does not. These results reinforce the concept of preconditioning as a transient event that must be completed before the onset of ischemia.

Author List

Pomerantz BJ, Robinson TN, Heimbach JK, Calkins CM, Miller SA, Banerjee A, Harken AH

Author

Casey Matthew Calkins MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Cardiopulmonary Bypass
Connective Tissue
Coronary Artery Bypass
Creatine Kinase
Diazoxide
Heart Atria
Heart Rate
Humans
In Vitro Techniques
Ion Channel Gating
Ischemic Preconditioning, Myocardial
Mitochondria, Heart
Myocardial Reperfusion
Potassium Channels