Xiping Zhou

Role of Adenosine Triphosphate-sensitive Potassium Channels in Coronary Vasodilation by Halothane, Isoflurane, and Enflurane

Background Halothane, isoflurane, and enflurane cause coronary vasodilation and cardiac depression. This study was performed to assess the role of adenosine triphosphate (ATP)‐sensitive potassium channels (K (ATP) channels) in these effects. Methods Twenty‐five thoracotomized dogs were anesthetized with fentanyl and midazolam. The left anterior descending coronary artery was perfused via either of two pressurized (80 mmHg) reservoirs. One reservoir was supplied with arterial blood free of a volatile anesthetic, and the second reservoir was supplied with arterial blood equilibrated in an oxygenator with a 1 minimum alveolar concentration of either halothane (0.9%, n = 10), isoflurane (1.4%, n = 28), or enflurane (2.2%, n = 7). Coronary blood flow (CBF) was measured using a Doppler flow transducer, and segmental shortening (SS) was measured with ultrasonic crystals. Responses to the volatile anesthetics were assessed under control conditions, during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 micro gram/min), and after cessation of glibenclamide (recovery). The effectiveness of glibenclamide was verified from inhibition of coronary vasodilator responses to the KATP channel opener cromakalim without effect on those to the KATP channel‐independent vasodilators, sodium nitroprusside and acetylcholine. Results Under control conditions, the volatile anesthetics caused pronounced increases in CBF (isoflurane > halothane = enflurane), and decreases in SS (enflurane > halothane = isoflurane). Glibenclamide blunted significantly (and reversibly) the increases in CBF, but it had no effect on the decreases in SS. Conclusions The KATP channels play an important role in coronary vasodilation but apparently are not involved in cardiac depression caused by halothane, isoflurane, and enflurane in canine hearts in situ.

Direct coronary vasomotor effects of Sevoflurane and desflurane in in situ canine hearts

Background: An extracorporeal system was used to investigate the direct coronary vasomotor effects of sevoflurane and desflurane in vivo. The role of the adenosine triphosphate–sensitive potassium channels (KATP channels) in these effects was evaluated. Methods: Twenty-one open-chest, anesthetized (fentanyl–midazolam) dogs were studied. The left anterior descending coronary artery was perfused at controlled pressure (80 mmHg) with normal arterial blood or arterial blood equilibrated with either sevoflurane or desflurane. Series 1 (n = 16) was divided into two groups of equal size on the basis of whether sevoflurane (1.2, 2.4, and 4.8%) or desflurane (3.6, 7.2, and 14.4%) was studied. The concentrations for the anesthetics corresponded to 0.5, 1.0, and 2.0 minimum alveolar concentration (MAC), respectively. Coronary blood flow (CBF) was measured with an ultrasonic, transit-time transducer. Local coronary venous samples were obtained and used to evaluate changes in myocardial oxygen extraction (EO2). In series 2 (n = 5), changes in CBF by 1 MAC sevoflurane and desflurane were assessed before and during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 &mgr;g/min). Results: Intracoronary sevoflurane and desflurane caused concentration-dependent increases in CBF (and decreases in EO2) that were comparable. Glibenclamide blunted significantly the anesthetic-induced increases in CBF. Conclusions: Sevoflurane and desflurane have comparable coronary vasodilative effects in in situ canine hearts. The KATP channels play a prominent role in these effects. When compared with data obtained previously in the same model, the coronary vasodilative effects of sevoflurane and desflurane are similar to those of enflurane and halothane but considerably smaller than that of isoflurane.

Isoflurane-induced Dilation of Porcine Coronary Arterioles Is Mediated by ATP-sensitive Potassium Channels

Background Isoflurane causes increases in coronary blood flow in vivo, which are mediated by the adenosine triphosphate (ATP)‐sensitive potassium channels, but the role of the arterioles (resistance vessels) in these responses is controversial. Methods Medium porcine coronary arterioles (internal diameter, 172 +/‐ 51 [SD] [micro sign]m) were placed in a chamber supplied with Krebs buffer, pressurized (40 mmHg), and preconstricted with acetylcholine (10‐8 ‐10 (‐6) M). Vascular diameter (VD) was assessed using an optical density video‐detection system. Isoflurane (in 95% oxygen and 5% carbon dioxide) was added to buffer using a membrane oxygenator supplied by a calibrated vaporizer. In series 1 (n = 14), 2% isoflurane was administered according to an abrupt (ISO‐A) and gradual (ISO‐G) protocol. In series 2 (n = 13) and 3 (n = 6), ISO‐A (1.5%) was assessed before and after glibenclamide (an ATP‐sensitive potassium channel antagonist) or 8‐phenyltheophylline (a nonselective adenosine receptor antagonist), respectively. In series 4 (n = 5), validation studies were performed using sodium nitroprusside and adenosine diphosphate to verify that the vascular smooth muscle and endothelium of the vessels were functionally intact. In series 5 (n = 6), ISO‐A (0.75 and 1.5%) was compared during preconstriction with acetylcholine and the thromboxane analog U46619 (10‐6 M). Results ISO‐G caused essentially concentration‐dependent increases in VD. At 2% isoflurane, the increases in VD were greater during ISO‐A than ISO‐G. Gilbenclamide, but not 8‐phenyltheophylline, attenuated isoflurane‐induced increases in VD. Both sodium nitroprusside and adenosine diphosphate caused dose‐dependent increases in VD. Isoflurane caused equivalent concentration‐dependent increases in VD during acetylcholine and U46619. Conclusions Isoflurane is a concentration‐dependent dilator of porcine coronary arterioles preconstricted with acetylcholine or U46619. This effect is blunted by gradual administration, suggesting that the vessels may adapt to the relaxing effects of isoflurane. Isoflurane‐induced dilation of coronary arterioles is mediated by the ATP‐sensitive potassium channels but not by the adenosine receptors.

Nitric oxide does not modulate the increases in blood flow, O2 consumption, or contractility during CaCl2 administration in canine hearts

OBJECTIVE Endothelium-derived nitric oxide (EDNO) has been shown to have vascular, metabolic, and contractile effects in the heart. We evaluated these effects during intracoronary (i.c.) administration of CaCl2 in dogs. METHODS The left anterior descending coronary artery of nine anesthetized, open-chest dogs was perfused at controlled pressure (80 mm Hg) with arterial blood. Coronary blood flow (CBF) was measured with a Doppler transducer and segmental shortening (SS) with ultrasonic crystals. Myocardial oxygen consumption (MVO2) and oxygen extraction (EO2) were calculated. Responses were assessed during i.c. infusions of CaCl2 (5, 10, 15 mg min-1) before and after administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 300 micrograms min-1 for 15 min, i.c.). RESULTS Before L-NAME, CaCl2 caused dose-dependent, proportional increases in SS and MVO2. Although CBF also increased, these responses were less than proportional to those in MVO2, and thus EO2 increased. L-NAME did not alter the cardiac effects of CaCl2. CONCLUSIONS (1) CaCl2 had direct inotropic and coronary vasoconstricting effects. (2) The vasoconstricting effect impaired coupling of CBF to the augmented metabolic demands by local vasodilating mechanisms. (3) EDNO did not modulate the increases in CBF, MVO2, or SS during administration of CaCl2.

Influence of nitric oxide on vascular, metabolic, and contractile responses to dobutamine in in situ canine hearts

The left anterior descending coronary arteries of 30 anesthetized, open-chest dogs were perfused via an extracorporeal circuit. Coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and segmental shortening (SS) were measured. Studies were performed with coronary perfusion pressure (CPP) or CBF constant. With CPP constant, effects of intracoronary (IC) infusions of dobutamine (2.5, 5.0, or 10.0 [micro sign]g/min) were evaluated alone (control) and after inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine methyl ester (L-NAME). With CBF constant, a NO donor (sodium nitroprusside [SNP] 80 [micro sign]g/min IC) or nitroglycerin [NTG] 40 [micro sign]g/min IC) or a releaser of endogenous NO (acetylcholine [ACh]; 20 [micro sign]g/min IC) was infused along with dobutamine. Increases in CBF during dobutamine and isoproterenol were compared before and after blockade of beta1-adrenergic receptors with atenolol. Dobutamine caused proportional, dose-dependent increases in CBF, MVO2, and SS, which were not altered by L-NAME. Administration of the NO donors or ACh during dobutamine markedly decreased CPP, but only ACh also reduced SS and MVO2. These latter effects persisted after L-NAME. Atenolol blunted increases in CBF by dobutamine more than those by isoproterenol. We conclude that endogenous NO did not modulate the coronary vasodilation or the increases in myocardial contractility and MVO2 during dobutamine. In addition, neither SNP nor NTG altered myocardial contractility or MVO2 in dobutamine-stimulated myocardium, whereas ACh had a negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO. Implications: Endogenous nitric oxide (NO) did not modulate increases in coronary blood flow, myocardial contractility, or myocardial oxygen consumption during intracoronary infusions of dobutamine. The NO donors sodium nitroprusside and nitroglycerin had no effect on contractility or oxygen consumption in dobutamine-stimulated myocardium. Acetylcholine had negative inotropic effect in dobutamine-stimulated myocardium that was independent of NO. (Anesth Analg 1998;87:994-1001)

Hemodilution does not alter the coronary vasodilating effects of endogenous or exogenous nitric oxide.

Introduction: It is well known that hemoglobin is a scavenger of nitric oxide (NO). The present study used a canine model to test the hypothesis that acute normovolemic hemodilution (ANH) affects NO-mediated coronary vasodilation.Methods: Studies were performed in 18 open-chest, anesthetized dogs. In Series 1, the contribution of endogenous NO to coronary vasodilatation during ANH with 5% dextran-40 (reduction in hematocrit by 50%) was assessed. This was accomplished by comparing myocardial blood flow (MBF; radioactive microspheres) in the left anterior descending (LAD) region, which was treated with the NO synthase inhibitor, NG-nitro-Larginine methyl ester (L-NAME), to that in the circumflex (control) region. In Series 2, the LAD was perfused via a controlledpressure extracorporeal system with coronary blood flow (CBF) measured with an ultrasonic, transit-time flow transducer. The dose-dependent increases in CBF caused by acetylcholine (ACh), which releases endogenous NO from the vascular endothelium, and sodium nitroprusside (SNP), which provides exogenous NO, were compared before and during ANH.Results: Acute normovolemic hemodilution caused similar (approximately twofold) increases in MBF (P<0.01) in the absence and presence of L-NAME, and it did not affect the dose-related increases in CBF caused by ACh and SNP.Conclusions: Series 1: under baseline conditions, hemoglobin in red blood cells does not limit the coronary vasodilatation resulting from tonic release of NO; NO does not mediate coronary vasodilation during ANH. Series 2: ANH does not influence the coronary vasodilating effects of increased levels of NO, whether due to endogenous release (ACh) or infusion of an NO donor (SNP).RésuméIntroduction: Le fait que l’hémoglobine puisse désactiver l’oxyde nitrique (NO) est bien connu. Cette étude s’est servi d’un modèle canin pour tester l’hypothèse que l’hémodilution normovolémique aiguë (ANH) affecte la vasodilatation coronarienne produite par l’oxyde nitrique.Méthode: Les études ont été réalisées sur 18 chiens anesthésiés, à thorax ouvert. Dans la série 1, nous avons évalué la contribution d’oxyde nitrique endogène à la vasodilatation coronarienne pendant une ANH avec du dextran-40 5 % (réduction de 50 % de l’hématocrite). Pour ce faire, nous avons comparé le débit sanguin myocardique (MBF ; microsphères radioactives) dans la région de l’artère interventriculaire antérieure (LAD — left anterior descending), qui a été traitée avec l’inhibiteur de synthase d’oxyde nitrique, le NG-nitro-L-arginine methyl ester (L-NAME), à celle de l’artère auriculoventriculaire (témoin). Dans la série 2, la LAD a été perfusée via un système extracorporel à pression contrôlée avec un débit coronarien (CBF) mesuré à l’aide d’un capteur ultrasonique de débit mesurant le temps de transit. Les augmentations de CBF liées à la dose provoquées par l’acétylcholine (ACh), qui libère de l’oxyde nitrique endogène de l’endothélium vasculaire, et par le nitroprussiate de sodium (SNP), qui fournit de l’oxyde nitrique exogène, ont été comparées avant et pendant l’ANH.Résultats: L’hémodilution normovolémique aiguë a provoqué des augmentations similaires (environ deux fois) de MBF (P<0,01) en l’absence et en présence de L-NAME, et cela n’a pas affecté les augmentations liées à la dose du CBF provoquées par l’ACh et le SNP.Conclusion: Série 1 : dans des conditions de base, l’hémoglobine dans les érythrocytes ne limite pas la vasodilatation coronarienne résultant de la libération tonique d’oxyde nitrique ; l’oxyde nitrique ne joue pas de rôle vasodilatateur durant une ANH. Série 2 : L’ANH n’influence pas les effets vasodilatateurs coronariens de niveaux élevés d’oxyde nitrique, que ce soit en raison d’une libération endogène (ACh) ou d’une perfusion d’un donneur d’oxyde nitrique (SNP).

Is calcium a coronary vasoconstrictor in vivo

Background Calcium produces constriction in isolated coronary vessels and in the coronary circulation of isolated hearts, but the importance of this mechanism in vivo remains controversial. Methods The left anterior descending coronary arteries of 20 anesthetized dogs whose chests had been opened were perfused at 80 mmHg. Myocardial segmental shortening was measured with ultrasonic crystals and coronary blood flow with a Doppler flow transducer. The coronary arteriovenous oxygen difference was determined and used to calculate myocardial oxygen consumption and the myocardial oxygen extraction ratio. The myocardial oxygen extraction ratio served as an index of effectiveness of metabolic vasodilation. Data were obtained during intracoronary infusions of CaCl2 (5, 10, and 15 mg/min) and compared with those during intracoronary infusions of dobutamine (2.5, 5.0, and 10.0 micro gram/min). Results CaCl2 caused dose‐dependent increases in segmental shortening, accompanied by proportional increases in myocardial oxygen consumption. Although CaCl2 also increased coronary blood flow, these increases were less than proportional to those in myocardial oxygen consumption, and therefore the myocardial oxygen extraction ratio increased. Dobutamine caused dose‐dependent increases in segmental shortening and myocardial oxygen consumption that were similar in magnitude to those caused by CaCl2 In contrast to CaCl2, however, the accompanying increases in coronary blood flow were proportional to the increases in myocardial oxygen consumption, with the result that the myocardial oxygen extraction ratio remained constant. Conclusions Calcium has a coronary vasoconstricting effect and a positive inotropic effect in vivo. This vasoconstricting effect impairs coupling of coronary blood flow to the augmented myocardial oxygen demand by metabolic vascular control mechanisms. Dobutamine is an inotropic agent with no apparent direct action on coronary resistance vessels in vivo.