Potassium channel openers attenuate atrioventricular block by bupivacaine in isolated hearts.
Our purpose was to test if pinacidil and bimakalim (EMD 52692 or SR 44866), which are ATP-sensitive K+ (K+ATP) channel openers, can attenuate bupivacaine-induced atrioventricular (AV) block. Bupivacaine-induced AV block was studied in 24 isolated guinea pig hearts with or without either pinacidil or bimakalim. Hearts were perfused at 55 mm Hg with a modified Krebs' perfusate. Variables monitored were: heart rate, AV conduction time, left ventricular pressure, coronary flow, and myocardial oxygen extraction. Bupivacaine was infused at a constant concentration of 4 microM to induce first degree AV block and 15-25 microM to induce second degree heart block. During a stable AV block (e.g., first degree, 2:1, 3:2, or 4:3), K+ channel openers, pinacidil (up to 30 microM) or bimakalim (up to 2 microM) were added to perfusate containing bupivacaine. The effects of K+ channel openers were also examined in the presence of the selective K+ATP channel blocker, glibenclamide (2.2 microM). On the average, 4 microM bupivacaine prolonged AV conduction by 53%, and decreased heart rate by 13%, left ventricular pressure by 26%, coronary flow by 6%, and percent oxygen extraction by 7%. In the presence of bupivacaine, pinacidil and bimakalim additionally decreased left ventricular pressure and oxygen extraction, markedly increased coronary flow, and attenuated the prolongation of AV conduction by 20% with no further change in heart rate. The beneficial effect of bimakalim on AV block was reversed by glibenclamide. Second degree AV block produced by higher doses of bupivacaine was converted to first degree AV block by either pinacidil or bimakalim in 6 of 8 and 7 of 8 hearts, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
M
M
Boban
D F
DF
Stowe
G J
GJ
Gross
G M
GM
Pieper
J P
JP
Kampine
Z J
ZJ
Bosnjak
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D002045:Bupivacaine / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004095:Dihydropyridines / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D006168:Guinea Pigs; D006327:Heart Block / Q000139:chemically induced* / Q000517:prevention & control; D066298:In Vitro Techniques; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D001578:Benzopyrans; D004095:Dihydropyridines; D006146:Guanidines; D015221:Potassium Channels; D014665:Vasodilator Agents; C061050:bimakalim; D020110:Pinacidil; D005905:Glyburide; D002045:Bupivacaine