The roles of adenosine and KATP channels in coronary autoregulation were investigated in closed-chest anesthetized dogs during graded reductions in coronary artery pressure before and after the combined adenosine and KATP channel blocker glibenclamide (1 mg/kg, iv) was given. The coronary circulation displayed autoregulation between 100 mmHg and 70 mmHg without any changes in interstitial adenosine concentration, estimated from coronary venous adenosine measurements using a mathematical model. At a critical pressure below 60 mmHg, left ventricular dp/dtmax, cardiac lactate extraction, and coronary venous PO2 fell while interstitial adenosine increased modestly. After glibenclamide autoregulation was well maintained, but basal coronary blood flow decreased by 15% without a change in myocardial oxygen consumption, and coronary venous PO2 was reduced from 19 to 15 mmHg. Despite the drop in PO2 due to glibenclamide, interstitial adenosine concentration did not change in the autoregulatory range of 100 to 70 mmHg. In conclusion, KATP channel blockade decreased basal coronary blood flow and venous PO2 without a change in interstitial adenosine. Coronary autoregulation was uncompromised after glibenclamide, suggesting that adenosine and KATP channels are not required for autoregulation.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology