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High-dose midazolam and the attenuation of the contractile response to vasoconstrictors in coronary artery segments

Published online by Cambridge University Press:  02 June 2005

A. P. Klockgether-Radke ,
A. Thudium ,
A. Frerichs ,
D. Kettler  and
G. Hellige
A. P. Klockgether-Radke
Affiliation:
Georg-August University of Göttingen, Department of Anaesthesiological Research, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Göttingen, Germany
A. Thudium
Affiliation:
Georg-August University of Göttingen, Department of Anaesthesiological Research, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Göttingen, Germany
A. Frerichs
Affiliation:
Georg-August University of Göttingen, Department of Anaesthesiological Research, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Göttingen, Germany
D. Kettler
Affiliation:
Georg-August University of Göttingen, Department of Anaesthesiological Research, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Göttingen, Germany
G. Hellige
Affiliation:
Georg-August University of Göttingen, Department of Anaesthesiological Research, Centre of Anaesthesiology, Emergency and Intensive Care Medicine, Göttingen, Germany
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Extract

Summary

Background and objective: Benzodiazepines may cause hypotension and are reported to interfere with smooth vascular muscle activity. The aim was to elucidate the influence of three different benzodiazepines on the vascular reactivity of coronary arteries.

Methods: Using the model of isolated vessels, we studied the impact of midazolam (0.15, 1.5, 15 μg mL−1), diazepam (0.1, 1.0, 10 μg mL−1) and flunitrazepam (0.01, 0.1, 1.0 μg mL−1) on the contractile responses to histamine (2 × 10−5 mol L−1) and serotonin (3 × 10−5mol L−1) in isolated intact and denuded coronary arteries.

Results: Midazolam significantly attenuated the contractile response when administered in high concentrations (15 μg mL−1). This effect was more pronounced in intact than in denuded preparations (histamine: −22.7 versus −7.3%, P = 0.0079; serotonin: −47.1 versus −15.9%, P < 0.0001). Diazepam and flunitrazepam exerted no significant effects on the vascular tone of coronary arteries.

Conclusions: Midazolam, but not diazepam or flunitrazepam, attenuates the contractile responses to vasoconstrictors in concentrations beyond those used in clinical practice. This effect is in part mediated by endothelial factors.

Keywords

ARTERIES, coronary vesselsBENZODIAZEPINES, midazolamENDOTHELIUM, VASCULAR
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 4 , April 2003 , pp. 289 - 293
Copyright
© 2003 European Society of Anaesthesiology

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References

Jones DJ, Stehling LC, Zauder HL. Cardiovascular responses to diazepam and midazolam maleate in the dog. Anesthesiology 1979; 51: 430–434.Google Scholar
Reves JG, Kissin I, Fournier S. Negative inotropic effects of midazolam. Anesthesiology 1984; 60: 517–518.Google Scholar
Reves JG, Samuelson PN, Lewis S. Midazolam maleate induction in patients with ischaemic heart disease: haemodynamic observations. Can Anaesth Soc J 1979; 26: 402–409.Google Scholar
Samuelson PN, Reves JG, Kouchoukos NT. Hemodynamic responses to anesthetic induction with midazolam or diazepam in patients with ischemic heart disease. Anesth Analg 1981; 60: 802–809.Google Scholar
Chai CY, Wang SC. Cardiovascular actions of diazepam in the cat. J Pharmacol Exp Ther 1966; 154: 271–280.Google Scholar
Marty J, Gauzit R, Lefevre P. Effects of diazepam and midazolam on baroreflex control of heart rate and on sympathetic activity in humans. Anesth Analg 1986; 65: 113–119.Google Scholar
Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288: 373–376.Google Scholar
Chen G, Suzuki H, Weston AH. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol 1988; 95: 1165–1174.Google Scholar
Moncada S, Vane JR. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin. Pharmacol Rev 1978; 30: 293–320.Google Scholar
Mangano DT, Browner WS, Hollenberg M, et al. Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. The Study of the Perioperative Ischemia Research Group. N Engl J Med 1990; 323: 1781–1788.Google Scholar
Chang KSK, Feng MD, Davis RG. Midazolam produces vasodilation by mixed endothelium-dependent and -independent mechanisms. Anesth Analg 1994; 78: 710–717.Google Scholar
Shiraishi Y, Ohashi M, Kanmura Y, et al. Possible mechanisms underlying the midazolam-induced relaxation of the noradrenaline-contraction in rabbit mesenteric resistance artery. Br J Pharmacol 1997; 121: 1155–1163.Google Scholar
Yamaguchi S, Kanmura Y, Yoshimura N. Effects of midazolam on contractions in smooth muscle of the rabbit mesenteric artery. Anesth Analg 1997; 84: 199–205.Google Scholar
Ishii K, Kano T, Ando J. Pharmacological effects of flurazepam and diazepam on isolated canine arteries. Jpn J Pharmacol 1983; 33: 65–71.Google Scholar
Hong SJ, Damron DS, Murray PA. Benzodiazepines differentially inhibit phenylephrine-induced calcium oscillations in pulmonary artery smooth muscle cells. Anesthesiology 1998; 88: 792–799.Google Scholar
Grupp IL, French JF, Matlib MA. Benzodiazepine Ro 5-4864 increases coronary flow. Eur J Pharmacol 1987; 143: 143–147.Google Scholar
Nilsson A, Tamsen A, Persson P. Midazolam–fentanyl anesthesia for major surgery. Plasma levels of midazolam during prolonged total intravenous anaesthesia. Acta Anaesthesiol Scand 1986; 30: 66–69.Google Scholar
Lauven PM, Stoeckel H, Schwilden H. Ein pharmakokinetisch begründetes Infusionsmodell für Midazolam. Anaesthesist 1982; 31: 15–20.Google Scholar
Moschitto LJ, Greenblatt DJ. Concentration-dependent plasma protein binding of benzodiazepines. J Pharm Pharmacol 1983; 35: 179–180.Google Scholar
Gamble JAS, Dundee JW, Gray RC. Plasma diazepam concentrations following prolonged administration. Br J Anaesth 1976; 48: 1087–1090.Google Scholar
Grahnen A, Wennerlund P, Dahlstrom B, Eckernas SA. Inter- and intraindividual variability in the concentration– effect (sedation) relationship of flunitrazepam. Br J Clin Pharmacol 1991; 31: 89–92.Google Scholar