Efeitos do propofol na resposta contrátil do miocárdio à dopamina e dobutamina: estudo experimental em corações isolados de ratos

Pontes, José Carlos Dorsa; Medeiros, Carlos Geraldo Sobral; Gomes, Otoni M

doi:10.1590/S0102-76381996000400012

Resumos

OBJETIVO: Estudo experimental das ações farmacodinâmicas do propofol e sua interação com a dopamina e dobutamina em corações isolados de ratos. MÉTODO: Foram estudadas as variações da contratilidade miocárdica (dT/dt), em 30 corações isolados de ratos. Em todos os animais, após anestesia por inalação de éter, os corações foram excisados e perfundidos em sistema de Langendorff com solução de Krebs - Hensleit enriquecida com 95% O2 e 5% CO2, (pressão de 90 cm de H2O, temperatura constante de 37,0ºC ± 0,5ºC). Foram estudados 30 animais divididos em: Grupo I (controle) - 10 corações perfundidos durante 11 minutos com solução de Krebs - Hensleit; Grupo II (dopamina-propofol-dopamina) -10 corações onde foram administrados dopamina (50 mcg/ml) e analisados os resultados nos 1º, 3º e 5º minutos e, posteriormente, propofol, (25 mcg/ml) infundindo-se 1 minuto após, dopamina (50 mcg/ml) e analisando-se os 1º, 3º e 5º minutos. Grupo III (dobutamina-propofol-dobutamina) - diferiu do Grupo II pela substituição da dopamina por dobutamina (50 mcg/ml). RESULTADOS: No Grupo I observou-se que a dT/dt variou de 39,57 ± 3,97 (g.seg-1) a 39,37 ± 3,44 (g.seg-1) (p>0,05) no período estudado. No Grupo II observou-se que, após a administração de propofol e dopamina, a dT/dt em (g.seg-1) apresentou queda de 17,61% (p<0,05) no 1º minuto; 8,37% (p<0,05) no 3º minuto e 10,84% (p<0,05) no 5º minuto, comparado à injeção isolada da dopamina. No Grupo III observou-se que, após a administração de propofol e dobutamina a dT/dt em (g.seg-1) sofreu acréscimo de 6,16% (p>0,05) no 1º minuto; 3,62% (p>0,05) no 3º minuto e 3,08% (p>0,05) no 5º minuto, comparado à injeção isolada da dobutamina. CONCLUSÃO: O propofol (25 mcg/ml) não alterou a resposta contrátil do miocárdio à dobutamina (50 mcg/ml); no entanto, inibiu a resposta esperada pela ação da dopamina (50 mcg/ml) na contratilidade miocárdica.

Contração miocárdica; Propofol; Dopamina; Dobutamina; Ratos

PURPOSE: Experimental investigation of the pharmacodynamic effects of propofol with and without simultaneous injections of dopamine or dobutamine in isolated hearts of rats. METHODS: In all animals under anaesthesia the hearts were removed and irrigated by a Krebs-Hensleit solution containing O2 (95%) and CO2 (5%), under constant pressure of 90 cm H2O and at 37ºC. After stabilization of the heart activity during 15 minutes, the control values were obtained. The following groups were considered: Group I (control) - 10 hearts perfused only with the Krebs-Hensleit solution during 11 minutes after the control values registration. Group II (dopamine-propofol-dopamine) -10 hearts with the following sequency of drug injections and results values registration: dopamine (50 mcg/ml), 1.3 and 5 minutes registration; propofol (25 mcg/ml), 1 minute period registration; dopamine again in the same dosis, 1.3 and 5 minutes values registration. Group III (dobutamine-propofol-dobutamine) -10 hearts with the following sequency of drug injections and results values registration: dobutamine (50 mcg/ml), 1.3 and 5 minutes registration: propofol (25 mcg/ml), 1 minute period registration; dobutamine again in the same dose and 1.3 and 5 minutes of registration. RESULTS: In Group I hearts, the dT/dt mean values changed only from 39.57 ± 3.97 to 39.37 ± 3.44 g.seg-1 (p>0.05). In Group II after propofol and dopamine the dT/dt fell 17.61 % (p<0.05) in the 1 min; 8.37% (p<0.05) in the 3rd min and 10.84% (p<0.05) in 5 th min, when compared with the results from isolated dopamine injections. In Group III the dT/dt increased 6.16% (p>0.050) in the 1 st min; 3.62% (p<0.05) in 3rd min and 3.08% (p>0.05) in the 5th min, over the values from isolated dobutamine injections. CONCLUSIONS: The myocardial contractile response to dopamine (50 mcg-ml-1) was partially inhibited; by propofol (25 mcg/ml-1) action was not altered.

Myocardial contraction; Propofol; Dopamine; Dobutamine; Rats

ARTIGOS ORIGINAIS

Efeitos do propofol na resposta contrátil do miocárdio à dopamina e dobutamina: estudo experimental em corações isolados de ratos

Effects of the propofol in the myocardial contractile response to dopamine and dobutamine in isolated rat's heart

José Carlos Dorsa Pontes^I; Carlos Geraldo Sobral Medeiros^II; Otoni M. Gomes^II

^IDo departamento de Clínica Cirúrgica da Universidade de Mato Grosso do Sul

^IIDo Serviço do Coração H.S.F.A. - Belo Horizonte

^{Endereço para correspondência} Endereço para correspondência: José Carlos Dorsa V. Pontes Rua Sergipe 73, Vila Célia Campo Grande - MS, Brasil. CEP: 79020-161

RESUMO

OBJETIVO: Estudo experimental das ações farmacodinâmicas do propofol e sua interação com a dopamina e dobutamina em corações isolados de ratos.

MÉTODO: Foram estudadas as variações da contratilidade miocárdica (dT/dt), em 30 corações isolados de ratos. Em todos os animais, após anestesia por inalação de éter, os corações foram excisados e perfundidos em sistema de Langendorff com solução de Krebs - Hensleit enriquecida com 95% O₂ e 5% CO₂, (pressão de 90 cm de H₂O, temperatura constante de 37,0ºC ± 0,5ºC). Foram estudados 30 animais divididos em: Grupo I (controle) - 10 corações perfundidos durante 11 minutos com solução de Krebs - Hensleit; Grupo II (dopamina-propofol-dopamina) -10 corações onde foram administrados dopamina (50 mcg/ml) e analisados os resultados nos 1º, 3º e 5º minutos e, posteriormente, propofol, (25 mcg/ml) infundindo-se 1 minuto após, dopamina (50 mcg/ml) e analisando-se os 1º, 3º e 5º minutos. Grupo III (dobutamina-propofol-dobutamina) - diferiu do Grupo II pela substituição da dopamina por dobutamina (50 mcg/ml).

RESULTADOS: No Grupo I observou-se que a dT/dt variou de 39,57 ± 3,97 (g.seg^-1) a 39,37 ± 3,44 (g.seg^-1) (p>0,05) no período estudado. No Grupo II observou-se que, após a administração de propofol e dopamina, a dT/dt em (g.seg^-1) apresentou queda de 17,61% (p<0,05) no 1º minuto; 8,37% (p<0,05) no 3º minuto e 10,84% (p<0,05) no 5º minuto, comparado à injeção isolada da dopamina. No Grupo III observou-se que, após a administração de propofol e dobutamina a dT/dt em (g.seg^-1) sofreu acréscimo de 6,16% (p>0,05) no 1º minuto; 3,62% (p>0,05) no 3º minuto e 3,08% (p>0,05) no 5º minuto, comparado à injeção isolada da dobutamina.

CONCLUSÃO: O propofol (25 mcg/ml) não alterou a resposta contrátil do miocárdio à dobutamina (50 mcg/ml); no entanto, inibiu a resposta esperada pela ação da dopamina (50 mcg/ml) na contratilidade miocárdica.

Descritores: Contração miocárdica, efeitos de drogas. Propofol, farmacologia. Dopamina, farmacologia. Dobutamina, farmacologia. Ratos, estudos experimentais.

ABSTRACT

PURPOSE: Experimental investigation of the pharmacodynamic effects of propofol with and without simultaneous injections of dopamine or dobutamine in isolated hearts of rats.

METHODS: In all animals under anaesthesia the hearts were removed and irrigated by a Krebs-Hensleit solution containing O₂ (95%) and CO₂ (5%), under constant pressure of 90 cm H₂O and at 37ºC. After stabilization of the heart activity during 15 minutes, the control values were obtained. The following groups were considered: Group I (control) - 10 hearts perfused only with the Krebs-Hensleit solution during 11 minutes after the control values registration. Group II (dopamine-propofol-dopamine) -10 hearts with the following sequency of drug injections and results values registration: dopamine (50 mcg/ml), 1.3 and 5 minutes registration; propofol (25 mcg/ml), 1 minute period registration; dopamine again in the same dosis, 1.3 and 5 minutes values registration. Group III (dobutamine-propofol-dobutamine) -10 hearts with the following sequency of drug injections and results values registration: dobutamine (50 mcg/ml), 1.3 and 5 minutes registration: propofol (25 mcg/ml), 1 minute period registration; dobutamine again in the same dose and 1.3 and 5 minutes of registration.

RESULTS: In Group I hearts, the dT/dt mean values changed only from 39.57 ± 3.97 to 39.37 ± 3.44 g.seg^-1 (p>0.05). In Group II after propofol and dopamine the dT/dt fell 17.61 % (p<0.05) in the 1 min; 8.37% (p<0.05) in the 3^rd min and 10.84% (p<0.05) in 5 ^th min, when compared with the results from isolated dopamine injections. In Group III the dT/dt increased 6.16% (p>0.050) in the 1 ^st min; 3.62% (p<0.05) in 3^rd min and 3.08% (p>0.05) in the 5^th min, over the values from isolated dobutamine injections.

CONCLUSIONS: The myocardial contractile response to dopamine (50 mcg-ml^-1) was partially inhibited; by propofol (25 mcg/ml^-1) action was not altered.

Descriptors: Myocardial contraction, drug effects. Propofol, pharmacology. Dopamine, pharmacology. Dobutamine, pharmacology. Rats, experimental studies.

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Full text available only in PDF format.

Trabalho realizado no Centro de Pesquisas Experimentais do Serviço do Coração H.S.F.A. Belo Horizonte, MG, Brasil e no Laboratório de Cirurgia Cardiovascular Experimental da Disciplina de Cirurgia Cardiovascular do Departamento de Clínica Cirúrgica da Universidade Federal de Mato Grosso do Sul, MS, Brasil.

Apresentado ao 23º Congresso Nacional de Cirurgia Cardíaca. Recife, PE, 20 a 23 de março, 1996.

1 Cockshotti I D, Briggs L P, Douglas E J, White M - Pharmacokinetics of propofol in female patients. Br J Anaesth 1987; 59: 1103-10.
2 Rosengarten H, Schweitzer J W, Friedhoff A J - Induction of oral dyskinesias in native rats by D1 stimulation. Life Sci 1983; 33: 479.
3 Simmons P J, Cockshott I D, Douglas E J, Gordon E A, Hopkins K, Rowland M - Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C - propofol. Xenabiotica 1988; 18: 429-40.
4 Twersky R S - The pharmacology of anesthetics used for ambulatory surgery. ASA Annual Refresher Courses Lectures 1993; 21: 159-75.
5 Brusel T, Theissen J L, Vigfusson G, Lukenheimer P P, Van Aken H, Lawin P - Hemodynamic and cardiodynamic effects of propofol etomidate negative inotropic properties of propofol. Anesth Analg 1989; 69: 35-40.
6 Pagel D S & Waltier D C - Negative inotropic of propofol as evaluated by the regional preload recruitable stroke work relationship in chronically instrumented dogs. Anesthesiology 1993; 78: 100-8.
7 Puttick R M & Tenar D A - Effects of propofol and anflurane on action potencials membrane currents and contraction of guinea-pig isolated ventricular myocytes. Br J Pharmacol 1992; 107: 559-65.
8 Shyr M H, Yang C A, Kuo T B, Pan W H, Tan P P, Chan S H - Power spectral analysis of the electroencephalografic and hemodynamic correlates of propofol anesthesia in the intravenous bolus administration. Neuroscir Lett 1993; 153: 161-7.
9 Coates D P, Prys-Roberts C, Speline K R, Monk C R, Norley I - Propofol (Diprivan) by intravenous infusion with nitrous oxide: dose requirements and haemodynamic effects. Postgrag Med J 1985; 61:(Suppl.): 76-9.
10 Claeys M A, Gept E, Camu T - Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anesth 1988; 60: 3-9.
11 Gauss A, Heinrich H, Wilder-Smith H G - Echocardiographic assessment of the haemodynamic effects of propofol: a comparison with etomidate and propofol. Anaesthesia 1991; 46: 99-105.
12 Wouters P F, Marcus M, Ruyter H A, Flameng W, Van Aken H - Cardiovascular effects of propofol in chronically instrumented dogs. Anesth Analg 1993; 76: (Suppl.): S470.
13 Puttick R M, Diedericks J, Sear J W, Glen J B, Fox P, Ryder W A - Effect of graded infusion rates of propofol on regional and global left ventricular function in the dog. Br J Anaesth 1992; 69: 375-81.
14 Goodchild C S & Serrao J M - Cardiovascular effects of propofol in the anasthetized dog. Br J Anaesth 1989; 63: 87-92.
15 Nascimento C, Braz J R C, Curi P R, Vane L V, Castiglia Y M M - Effects of continuous infusion of propofol on renal function in the dog: comparative study with pentobarbital sodium. Rev Bras Anestesiol 1994; 44: 163-70.
16 Medeiros CGS - Análise comparativa dos efeitos do diazepan, midazolan e propofol na contratilidade miocárdica; estudo em corações isolados de ratos [Tese. Mestrado] Belo Horizonte: Curso de Pós-Graduação em Cardiologia e Cirurgia Cardiovascular. Serviço do Coração do Hospital São Francisco de Assis - CMC - SSVP, 1994.
17 Coetzee A, Fourie P, Coetzee J - Effect of various propofol plasma concentration on regional myocardial contractility and left ventricular afterload. Anaesth Analg 1989; 69: 473-83.
18 Riou B, Besse S, Lecarpentier Y, Viars P - In vitro effects of propofol on rat myocardium. Anesthesiology 1992; 76: 609-16.
19 Di Florio T - Department of Anaesthesia, Sir Charles Gaidner Hospital. Verdun Street, Nedlands WA 6009, Australia.
20 Dingwall A E - Oculogyric crisis after day case anaesthesia. Anaesthesia, 1987; 42: 565.
21 Kebabian J W & Calne D B - Multiple receptors for dopamine. Nature, 1979; 277: 93-6.
22 Langendorff O - Untersuchungen am Uberlebenden saugethierherzen. Arch Ges Physiol 1985; 61: 291.
23 Krebs H A & Hensleit K - Untersuchungem uber die Hanstoffbildung im tierkoeper. Hope Seylers Z Physiol Chem 1932; 210: 33.
24 Hopkins C S - Recurrent opisthotonus associated with anaesthesia. Anaesthesia 1988; 43: 904.
25 Pitchon M - Proteção miocárdica. "Paradoxo do cálcio": estudo em corações isolados de ratos [Tese Mestrado] Belo Horizonte: Curso de Pós-Graduação em Cardiologia e Cirurgia Cardiovascular. Serviço do Coração do Hospital São Francisco de Assis - CMC - SSVP, 1992.
26 Snedecor W G & Cochran W C - The comparison of two samples. In: Statistical methods. 7. ed. AMES: The State University Press, 1980: 83.
27 Coates D P, Monk C R, Prys-Roberts C, Turtle M - Hemodynamic effects of infusions of the emulsion formulation of propofol during nitrous oxide anesthesia in humans. Anesth Analg 1987; 66: 64-70.
28 Monk C R, Coates D P, Prys-Roberts C, Turtle M J, Spelina K - Haemodynamic effects of a prolonged infusion of propofol as a supplemnt to nitrous oxide anaesthesia. Br J Anaesth 1987; 59: 954-60.
29 Patrick M R, Blair I J, Feneck R O, Sebel P S - A comparison of the haemodynamic effects of propofol (Diprivan) and thiopentone in patients with coronary artery disease. Postgrad Med J 1985; 61 (Suppl.) 23-7.
30 Stephan H, Sonntag H, Schenk H D, Kettler D, Khambatta H J - Effects of propofol on cardiovascular dynamics, myocardial blood flow and myocardial metabolism in patients with coronary artery disease. Br J Anaesth 1986; 58: 969-75.
31 Vermeyen K M, Erpels F A, Janssen L A, Beeckman C P, Hanegreefs G H - Propofol-fentanyl anaesthesia for coronary bypass surgery in patients with good left ventricular function. Br J Anaesth 1987; 59: 1115-20.
32 Larsen R, Rathgeber j, Bagdahn A, Lange H, Rieke H - Effects of propofol on cardiovascular dynamics and coronary blood flow in geriatric patients: a comparasion with etomidate. Anaesthesia 1988; 43(Suppl.): 25-31.

Endereço para correspondência:

José Carlos Dorsa V. Pontes

Rua Sergipe 73, Vila Célia

Campo Grande - MS, Brasil. CEP: 79020-161

Datas de Publicação

Publicação nesta coleção
16 Dez 2010
Data do Fascículo
Dez 1996

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1 Cockshotti I D, Briggs L P, Douglas E J, White M - Pharmacokinetics of propofol in female patients. Br J Anaesth 1987; 59: 1103-10.

[2] 2 Rosengarten H, Schweitzer J W, Friedhoff A J - Induction of oral dyskinesias in native rats by D1 stimulation. Life Sci 1983; 33: 479.

[3] 3 Simmons P J, Cockshott I D, Douglas E J, Gordon E A, Hopkins K, Rowland M - Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C - propofol. Xenabiotica 1988; 18: 429-40.

[4] 4 Twersky R S - The pharmacology of anesthetics used for ambulatory surgery. ASA Annual Refresher Courses Lectures 1993; 21: 159-75.

[5] 5 Brusel T, Theissen J L, Vigfusson G, Lukenheimer P P, Van Aken H, Lawin P - Hemodynamic and cardiodynamic effects of propofol etomidate negative inotropic properties of propofol. Anesth Analg 1989; 69: 35-40.

[6] 6 Pagel D S & Waltier D C - Negative inotropic of propofol as evaluated by the regional preload recruitable stroke work relationship in chronically instrumented dogs. Anesthesiology 1993; 78: 100-8.

[7] 7 Puttick R M & Tenar D A - Effects of propofol and anflurane on action potencials membrane currents and contraction of guinea-pig isolated ventricular myocytes. Br J Pharmacol 1992; 107: 559-65.

[8] 8 Shyr M H, Yang C A, Kuo T B, Pan W H, Tan P P, Chan S H - Power spectral analysis of the electroencephalografic and hemodynamic correlates of propofol anesthesia in the intravenous bolus administration. Neuroscir Lett 1993; 153: 161-7.

[9] 9 Coates D P, Prys-Roberts C, Speline K R, Monk C R, Norley I - Propofol (Diprivan) by intravenous infusion with nitrous oxide: dose requirements and haemodynamic effects. Postgrag Med J 1985; 61:(Suppl.): 76-9.

[10] 10 Claeys M A, Gept E, Camu T - Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anesth 1988; 60: 3-9.

[11] 11 Gauss A, Heinrich H, Wilder-Smith H G - Echocardiographic assessment of the haemodynamic effects of propofol: a comparison with etomidate and propofol. Anaesthesia 1991; 46: 99-105.

[12] 12 Wouters P F, Marcus M, Ruyter H A, Flameng W, Van Aken H - Cardiovascular effects of propofol in chronically instrumented dogs. Anesth Analg 1993; 76: (Suppl.): S470.

[13] 13 Puttick R M, Diedericks J, Sear J W, Glen J B, Fox P, Ryder W A - Effect of graded infusion rates of propofol on regional and global left ventricular function in the dog. Br J Anaesth 1992; 69: 375-81.

[14] 14 Goodchild C S & Serrao J M - Cardiovascular effects of propofol in the anasthetized dog. Br J Anaesth 1989; 63: 87-92.

[15] 15 Nascimento C, Braz J R C, Curi P R, Vane L V, Castiglia Y M M - Effects of continuous infusion of propofol on renal function in the dog: comparative study with pentobarbital sodium. Rev Bras Anestesiol 1994; 44: 163-70.

[16] 16 Medeiros CGS - Análise comparativa dos efeitos do diazepan, midazolan e propofol na contratilidade miocárdica; estudo em corações isolados de ratos [Tese. Mestrado] Belo Horizonte: Curso de Pós-Graduação em Cardiologia e Cirurgia Cardiovascular. Serviço do Coração do Hospital São Francisco de Assis - CMC - SSVP, 1994.

[17] 17 Coetzee A, Fourie P, Coetzee J - Effect of various propofol plasma concentration on regional myocardial contractility and left ventricular afterload. Anaesth Analg 1989; 69: 473-83.

[18] 18 Riou B, Besse S, Lecarpentier Y, Viars P - In vitro effects of propofol on rat myocardium. Anesthesiology 1992; 76: 609-16.

[19] 19 Di Florio T - Department of Anaesthesia, Sir Charles Gaidner Hospital. Verdun Street, Nedlands WA 6009, Australia.

[20] 20 Dingwall A E - Oculogyric crisis after day case anaesthesia. Anaesthesia, 1987; 42: 565.

[21] 21 Kebabian J W & Calne D B - Multiple receptors for dopamine. Nature, 1979; 277: 93-6.

[22] 22 Langendorff O - Untersuchungen am Uberlebenden saugethierherzen. Arch Ges Physiol 1985; 61: 291.

[23] 23 Krebs H A & Hensleit K - Untersuchungem uber die Hanstoffbildung im tierkoeper. Hope Seylers Z Physiol Chem 1932; 210: 33.

[24] 24 Hopkins C S - Recurrent opisthotonus associated with anaesthesia. Anaesthesia 1988; 43: 904.

[25] 25 Pitchon M - Proteção miocárdica. "Paradoxo do cálcio": estudo em corações isolados de ratos [Tese Mestrado] Belo Horizonte: Curso de Pós-Graduação em Cardiologia e Cirurgia Cardiovascular. Serviço do Coração do Hospital São Francisco de Assis - CMC - SSVP, 1992.

[26] 26 Snedecor W G & Cochran W C - The comparison of two samples. In: Statistical methods. 7. ed. AMES: The State University Press, 1980: 83.

[27] 27 Coates D P, Monk C R, Prys-Roberts C, Turtle M - Hemodynamic effects of infusions of the emulsion formulation of propofol during nitrous oxide anesthesia in humans. Anesth Analg 1987; 66: 64-70.

[28] 28 Monk C R, Coates D P, Prys-Roberts C, Turtle M J, Spelina K - Haemodynamic effects of a prolonged infusion of propofol as a supplemnt to nitrous oxide anaesthesia. Br J Anaesth 1987; 59: 954-60.

[29] 29 Patrick M R, Blair I J, Feneck R O, Sebel P S - A comparison of the haemodynamic effects of propofol (Diprivan) and thiopentone in patients with coronary artery disease. Postgrad Med J 1985; 61 (Suppl.) 23-7.

[30] 30 Stephan H, Sonntag H, Schenk H D, Kettler D, Khambatta H J - Effects of propofol on cardiovascular dynamics, myocardial blood flow and myocardial metabolism in patients with coronary artery disease. Br J Anaesth 1986; 58: 969-75.

[31] 31 Vermeyen K M, Erpels F A, Janssen L A, Beeckman C P, Hanegreefs G H - Propofol-fentanyl anaesthesia for coronary bypass surgery in patients with good left ventricular function. Br J Anaesth 1987; 59: 1115-20.

[32] 32 Larsen R, Rathgeber j, Bagdahn A, Lange H, Rieke H - Effects of propofol on cardiovascular dynamics and coronary blood flow in geriatric patients: a comparasion with etomidate. Anaesthesia 1988; 43(Suppl.): 25-31.