Boban M, Stowe D F, Gross G J, Pieper G M, Kampine J P, Bosnjak Z J
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Anesth Analg. 1993 Jun;76(6):1259-65. doi: 10.1213/00000539-199376060-00013.
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)
我们的目的是测试匹那地尔和比马卡林（EMD 52692或SR 44866）这两种ATP敏感性钾离子（K⁺ATP）通道开放剂是否能减轻布比卡因诱导的房室（AV）传导阻滞。在24个离体豚鼠心脏中研究了布比卡因诱导的AV传导阻滞，这些心脏分别加或不加匹那地尔或比马卡林。心脏在55 mmHg压力下用改良的克雷布斯灌注液进行灌注。监测的变量包括：心率、AV传导时间、左心室压力、冠状动脉血流量和心肌氧摄取。以4 μM的恒定浓度输注布比卡因以诱导一度AV传导阻滞，以15 - 25 μM的浓度输注以诱导二度心脏传导阻滞。在稳定的AV传导阻滞（如一度、2:1、3:2或4:3）期间，将K⁺通道开放剂匹那地尔（高达30 μM）或比马卡林（高达2 μM）添加到含有布比卡因的灌注液中。还在存在选择性K⁺ATP通道阻滞剂格列本脲（2.2 μM）的情况下检查了K⁺通道开放剂的作用。平均而言，4 μM布比卡因使AV传导延长53%，并使心率降低13%，左心室压力降低26%，冠状动脉血流量降低6%，氧摄取百分比降低7%。在存在布比卡因的情况下，匹那地尔和比马卡林还能额外降低左心室压力和氧摄取，显著增加冠状动脉血流量，并使AV传导的延长减轻20%，而心率无进一步变化。格列本脲可逆转比马卡林对AV传导阻滞的有益作用。较高剂量布比卡因产生的二度AV传导阻滞在8个心脏中的6个和8个心脏中的7个中分别被匹那地尔或比马卡林转为一度AV传导阻滞。（摘要截短于250字）
