Abstract
We examined the effects of midazolam and flumazenil on cardiac function and metabolism in the isolated rat heart-lung preparation. Wistar rats were divided into five groups (each group:n=8) as follows: (1) control (saline); (2) flumazenil (1.3×10−5M); (3) flumazenil (10−4M); (4) midazolam (60μg·ml−1); and (5) midazolam (60μg·ml−1) and flumazenil (1.3×10−5M). Systolic blood pressure and calculated left ventricular dP/dt maximum in the midazolam or midazolam conbined with flumazenil groups increased significantly in comparison with those in the control group. Heart rate in the midazolam group was lower than that in the control group. However, in the flumazenil group, there were no effects on the hemodynamics. There were no significant differences in the myocardial tissue concentration of ATP, lactate, and glycogen in all groups. In this study, midazolam decreased heart rate; however, flumazenil had no effect on the heart, nor did it antagonize the cardiac effects of midazolam. These results suggest that flumazenil has no effect on the peripheraltype benzodiazepine receptor of the myocardium.
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Fragen RJ, Gahl F, Caldwell N (1978) A water-soluble benzodiazepine, Ro 21-3981, for induction of anesthesia. Anesthesiology 49: 41–43
Reves JG, Corssen G, Holcomb C (1978) Comparison of two benzodiazepines for anesthesia induction: midazolam and diazepam. Can Aaesth Soc J 25: 211–214
Westphal LM, Gheng EY, White PF, Sladen RN, Rosenthal MH, Sung ML (1987) Use of midazolam infusion for sedation following cardiac surgery. Anesthesiology 67: 257–262
Reves JG, Mardis M, Strong S (1978) Cardiopulmonary effects of midazolam. Ala J Med Sci 15: 347–351
Jones DJ, Stehling LC, Zauder HL (1979) Cardiovascular responses to diazepam and midazolam maleate in the dog. Anesthesiology 51: 430–434
Reves JG, Samuelson PN, Lewis S (1978) Midazolam induction in patients with ischemic heart disease: haemodynamic observations. Can Anaesth Soc J 26: 402–409
Samuelson PN, Reves JG, Kouchoukos NT, Smith LR, Dole KM (1981) Hemodynamic responses to anesthetic induction with midazolam or diazepam in patients with ischemic heart disease. Anesth Analg 60: 802–809
Reves JG, Kissin I, Fournier S (1984) Negative inotropic effects of midazolam. Anesthesiology 60: 517–518
Darragh A, Lambe R, Kenny M, Brick I (1983) Tolerance of healthy volunteers to intravenous administration of the benzodiazepine antagonist Ro 15-1788. Eur J Clin Pharmacol 24: 569–570
Schuöpf J, Laurian S, Le PK, Gaillard JM (1984) Intrinsic activity of the benzodiazepine antagonist Ro 15-1788 in man: an electrophysiological investigation. Pharmacopsychiatry 17: 79–83
Kashimoto S, Kume M, Kumazawa T (1990) Functional and metabolic effects of bupivacaine and lignocaine in the rat heart-lung preparation. Br J Anaesth 65: 521–526
Nonaka A, Kashimoto S, Nakamura T, Kumazawa T (1994) Effects of intravenous anaesthetics on function and metabolism in the isolated rat heart-lung preparation. Eur J Anaesth 11: 213–219
Wynants J, Van Belle H (1985) Single-run high-performance liquid chromatography of nucleotides, and major purine bases and its application to different tissue extracts. Anal Biochem 144: 258–266
Bergmeyer HU (1975) Neue Werte für die molaren Extinktions-Koeffizienten von NADH und NADPH zum Gebrauch im Routine-Laboratorium. Z Klin Chem Klin Biochem 13: 507–508
Werner W, Rey HG, Wielinger H (1970) Über die Eigenschaften eines neuen Chromogens für die Blutzuckerbestimmung nach der GOD/POD-Methode. Z Anal Chem 252: 224–228
Stowe DF, Bosnjak Z, Kampine JP (1992) Comparison of etomidate, ketamine, midazolam, propofol, and thiopental on function and metabolism of isolated hearts. Anesth Analg 74: 547–558
Lepage YJ, Blanloeil Y, Pinaud M, Helias J, Auneau C, Cozian A, Souron R (1986) Hemodynamic effects of diazepam, flumazenil, and midazolam in patients with ischemic heart disease: Assessment with a radionuclide approach. Anesthesiology 65: 678–683
Lauven PM, Stoeckel H, Schwilden H (1982) Ein pharmakokinetisch begründetes Infusionsmodell für Midazolam. Anaesthesist 31: 15–20
Marty J, Joyon D (1988) Haemodynamic responses following reversal of benzodiazepine-induced anaesthesia or sedation with flumazenil. Eur J Anaesth 2 [Suppl]: 167–171
Sonne NM, Wegmann F, Crawford ME, Boysen K, Krintel JJ, Valentin N (1991) Recovery after total intravenous anaesthesia using combined midazolam/alfentanil infusion and reversal with flumazenil. Acta Anaesthesiol Scand 35: 750–754
Geller E, Chernilas J, Halpern P, Niv D, Miller HI (1986) Hemodynamics following reversal of benzodiazepine sedation with Ro 15-1788 in cardiac patients. Anesthesiology 65: A49
Ozawa Y, Fujihara A, Sato S (1990) General pharmacology of flumazenil. Clin Rep 24: 3811–3826
Hunkeler W, Mohler M, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290: 514–516
Mohler H, Richards JG (1981) Agonist and antagonist benzodiazepine receptor interaction in vitro. Nature 294: 763–765
Mestre M, Carriot C, Belin C, Uzan A, Renault C, Dubroeucq MC, Guérémy C, Le Fur G (1984) Electrophysiological and pharmacological characterization of peripheral benzodiazepne receptors in guinea pig heart preparation. Life Sci 35: 953–962
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Nakamura, T., Kashimoto, S., Nonaka, A. et al. Flumazenil does not antagonize the cardiac effects of midazolam in the isolated rat heart-lung preparation. J Anesth 10, 190–193 (1996). https://doi.org/10.1007/BF02471389
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DOI: https://doi.org/10.1007/BF02471389