Abstract
This study was done using Wistar rats to determine if the actions of propofol (22 ± 1, 40 ± 2, 64 ± 3 and 102 ± 3 mg · kg−1 · hr−1) decreased blood pressure and heart rate through depression of brain stem vasomotor centres. All rats were given atropine to block vagal influences on the heart. Propofol decreased renal nerve activity as well as blood pressure and heart rate in a dose-dependent manner. Infusion of the lowest dose of propofol (22 ± 1 mg · kg−1 · hr−1) had no effect on blood pressure, heart rate and renal nerve activity. Infusion of propofol at 40 ± 2 mg · kg−1 · hr−1 decreased renal activity by 22 ± 4% (mean ± SEM) and at 64 ± 3 mg · kg−1 · hr−1 it decreased renal nerve activity by 36 ± 6%. Finally, infusion of the largest dose of propofol (102 ± 3 mg · kg−1 · hr−1) decreased nerve activity by 50 ± 5%. The haemodynamic changes observed in our experiments during the infusion of propofol paralleled the changes in sympathetic firing, suggesting that hypotension was caused by central actions of propofol to depress sympathetic firing. In experiments with bolus injections of propofol, the renal nerve activity returned to normal before arterial pressure and heart rate recovered. Because decreases in blood pressure and heart rate were longer-lasting than changes in renal nerve activity, a part of the vasodepression and bradycardia caused by propofol likely resulted from direct actions on blood vessels and the heart. Sympathetic and cardiovascular responses to blocking neurons in the ventrolateral medulla with microinjection of glycine were depressed by propofol. However, responses to blockade of this important brainstem structure were elicited at all doses of propofol suggesting that, while it causes depression of CNS neurons responsible for control of resting arterial pressure and heart rate, this depression is not maximal and substantial control remains.
Résumé
Cette étude a été réalisée avec des rats Wistar afin de déterminer si l’action du propofol (22 ± 1, 40 ± 2, 64 ± 3, et 102 ± 3 mg · kg−1 · h−1) diminue la pression artérielle et la fréquence cardiaque par une dépression des centres vasomoteurs du tronc cérébral. Tous les rats ont reçu de l’atropine pour bloquer les effets vagaux sur le coeur. Le propofol diminue l’activité rénale d’origine nerveuse autant que la pression artérielle et la fréquence cardiaque d’une manière dose-dépendante. La perfusion de la plus faible dose de propofol (22 ± 1 mg · kg−1 · h−1) n’a pas d’effet sur la pression artérielle, la fréquence cardiaque et l’activité d’origine nerveuse. Une perfusion de propofol à 40 ± 2 mg · kg−1 · h−1) diminue l’activité rénale d’origine nerveuse 22 ± 4% (moyenne ± erreur type), à 64 ± 3 mg · kg−1 · h−1, elle diminue cette activité de 36 ± 6%. Finalement, l’infusion de la dose la plus élevée de propofol (102 ± mg · kg−1 · h−1) diminue cette activité nerveuse de 50 ± 5%. Les variations hémodynamiques observées dans notre expérience pendant la perfusion de propofol se profilent aux modifications de décharges sympathiques suggérant que l’hypotension est causée par une action centrale de dépression sympathique par le propofol. Lors d’injections de propofol par bolus, l’activité rénale d’origine nerveuse se normalise avant la pression artérielle et la fréquence cardiaque. Puisque les diminutions de pression artérielle et de fréquence cardiaque ont duré plus longtemps que celle de l’activité rénale d’origine nerveuse, une part de la vasodépression et de la bradycardie causée par le propofol résulte vraisemblablement d’une action directe sur les vaisseaux sanguins et le coeur. Les réponses sympathiques et cardiovasculaires au blocage des neurones de la région ventrolatérale par des microinjections de glycine sont déprimées par le propofol. Cependant les réponses au blocage de cette importante structure du tronc cérébral sont obtenues pour toutes les doses de propofol. Ceci suggère que bien que le propofol amène une dépression des neurons du SNC responsables du contrôle de la pression artérielle et de la fréquence cardiaque, cette dépression n’est pas maximale et un contrôle substantiel subsiste.
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References
Aun C, Major E. The catdiorespiratory effects of ICI 35 868 in patients with valvular heart disease. Anaesthesia 1984; 39: 1096–100.
Glen JB, Hunter SC. Pharmacology of an emulsion formulation of ICI 35 868. Br J Anaesth 1984; 56: 617–25.
Goodchild CS, Serrao JM. Cardiovascular effects of propofol in the anaesthetized dog. Br J Anaesth 1989; 63: 87–92.
Mackenzie N, Grant IS. Comparison of propofol with methohexitone in the provision of anaesthesia for surgery under regional blockade. Br J Anaesth 1985; 57: 1167–72.
Sebel PS, Lowden JD. Propofol: a new intravenous anaesthetic. Anesthesiology 1989; 71: 260–77
Blake DW, Jover B, McGrath BE Haemodynamic and heart rate reflex responses to propofol in the rabbit. Br J Anaesth 1988; 61: 194–9.
Glen JB. Animal studies of the anaesthetic activity of ICI 35 868. Br J Anaesth 1980; 52: 731–41.
Grounds RM, Twigley AJ, Carli F, Whitwam JG, Morgan M. The haemodynamic effects of intravenous induction. Comparison of the effects of thiopentone and propofol. Anaesthesia 1985; 40: 735–40.
Prys- Roberts C, Davies JR, Calverley RK, Goodman NW. Haemodynamic effects of infusions of diisopropyl phenol (ICI 35 868) during nitrous oxide anaesthesia in man. Br J Anaesth 1983; 55: 105–11.
Calaresu FR, Yardley CP. Medullary basal sympathetic tone. Annu Rev Physiol 1988; 50: 511–24.
Feldberg W. The ventral surface of the brain stem: a scarcely explored region of pharmacological sensitivity. Neuroscience 1976; 1: 427–41.
Beiuli DJ, Weaver LC. Differential control of renal and splenic nerves without medullary topography. Am J Physiol 1991; 260: H1072–9.
Hayes K, Weaver LC. Selective control of sympathetic pathways to the kidney, spleen and intestine by the ventrolateral medulla in rats. J Physiol (Lond) 1990; 428: 371–85.
Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 2nd ed. Orlando: Academic Press, 1986.
Snedecor G, Cochran WG. Statistical Methods. 8th ed. Ames 1A: The Iowa State University Press, 1989.
Claeys MA, Gepts E, Camu F. Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anaesth 1988; 60: 3–9.
Monk CR, Coates DP, Prys-Roberts C, Turtle MJ, Spelina K. Haemodynamic effects of a prolonged infusion of propofol as a supplement to nitrous oxide anaesthesia. Br J Anaesth 1987; 59: 954–60.
Stowe DF, Bosnjak ZJ, Kampine JP. Comparison of etomidate, ketamine, midazolam, propofol and thiopental on function and metabolism of isolated hearts. Anesth Analg 1992; 74: 547–58.
Baron JF, Soughir S, Arthaud M, Mouren S, Viars P. Effects of propofol on coronary circulation and myocardial performance of an isolated rabbit heart. Anaethesiology 1990; 73: A561.
Lin Y, Lee C, Lee T, Virtusio L, Wu SJ. Negative inotropic effects of propofol vs thiopental: assessment in an isolated ventricular septum model. Anesthesiology 1990; 72: A564.
Bentley GN, Gent JP, Goodchild CS. Vascular effects of propofol: smooth muscle relaxation in isolated veins and arteries. J Pharm Pharmacol 1989; 41: 797–8.
Muzi M, Berens RA, Kampine JP, Ebert TJ. Venodilation contributes to propofol-mediated hypotension in humans. Anesth Analg 1992; 74: 877–83.
Gelb AW, Zhang C, Hamilton JT. The in vitro cerebrovascular effects of propofol are due to calcium channel blockade. Anesthesiology 1992; 77: A774.
Concas A, Santoro G, Mascia MP, Serra M, Sanna E, Biggio G. The general anesthetic propofol enhances the function of 7-aminobutyric acid-coupled chloride channel in the rat cerebral cortex. J Neurochem 1990; 55: 2135–8.
Robertson B. Action of anaesthetics and avermectin on GABAA chloride channels in mammalian dorsal root ganglion neurones. Br J Pharmacol 1989; 98: 167–76.
Urbanski RW, Sapru HN. Putative neurotransmitters involved in medullary cardiovascular regulation. J Auton Nerv Syst 1988; 25: 181–93.
Willette RN, Barcas PP, Krieger AJ, Sapru HN. Vasopressor and depressor areas in the rat medulla. Neuropharmacology 1983; 22: 1071–9.
Sellgren J, Pontén J, Wallin BG. Percutaneous recording of muscle nerve sympathetic activity during propofol, nitrous oxide, and isoflurane anesthesia in humans. Anesthesiology 1990; 73: 20–7.
Adam HK, Glen JB, Hoyle PA. Pharmacokinetics in laboratory animals of ICI 35 868, a new i.v. anaesthetic agent. Br J Anaesth 1980; 52: 743–6.
Rhodes G, Longshaw S. Autoradiographic distribution study of a short acting anaesthetic ICI 35 868. Acta Pharmacologica et Toxicologica 1977; 41: 132–3.
Dam M, Ori C, Pizzolato G, et al. The effects of propofol anesthesia on local cerebral glucose utilization in the rat. Anesthesiology. 1990; 73: 499–505.
Van Hemelrijck J, Fitch W, Mattheussen M, Van Aken H, Plets C, Lauwers T. Effect of propofol on cerebral circulation and autoregulation in the baboon. Anesth Analg 1990; 71: 49–54.
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Supported by the Heart and Stroke Foundation of Ontario and the Medical Research Council of Canada/Canadian Hypertension Society.
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Krassioukov, A.V., Gelb, A.W. & Weaver, L.C. Action of propofol on central sympathetic mechanisms controlling blood pressure. Can J Anaesth 40, 761–769 (1993). https://doi.org/10.1007/BF03009773
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DOI: https://doi.org/10.1007/BF03009773