Análise comparativa dos efeitos do diazepam, midazolam, propofol e etomidato na contratilidade miocárdica e no fluxo coronariano: estudo em corações isolados de ratos

Abstract

Objective: The effects on myocardial contractility (dT/dt max ) and coronary blood flow of common drugs used in clinical practice (diazepam, midazolam, propofol and etomidate) were studied.Method: Fifty Wistar rat hearts were divided into five groups of ten and perfused using the Langendorff method with Krebs-Henseleit solution (K-H), with the perfusion pressure stable at 90 cm H 2 O and the temperature at 37.0 ± 0.5 °C. With the exception of Group I (control), they were submitted to single one-minute infusions of diazepam (50 micrograms) -Group II; midazolam (25 micrograms) -Group III; propofol (25 and 50 micrograms) -Group IV and etomidate (25 micrograms) -Group V. The drugs were diluted in 0.1 mL of K-H solution and the coronary blood flow rate and perfusion pressure controlled during infusion. The heart rate (beats per minute), myocardial tension (grams) and coronary blood flow (millimeters per minute) were measured at 1, 3, 5, 10, 15, 20, 25 and 30 minutes. The myocardial contractility was obtained by calculating the first derived tension/time (dT/dt max ), at each time interval.Results: The heart rate showed variations in Groups I, III and IV. A variation in the myocardial tension was seen in all groups except Group I and alterations in the coronary blood flow were seen in all groups except Group IV during the experiment. The myocardial contractility decreased in all groups, except for Group I.Conclusion: The assayed drugs diminished the myocardial contractility (p<0.05); the variations of the coronary blood flow were not directly correlated to those that occurred with the myocardial contractility.Descriptors: Myocardial contraction. Diazepam. Midazolam. Propofol. Etomidate. Resumo: Objetivo: Avaliar o efeito, na contratilidade miocárdica e no fluxo coronariano, de drogas comumente utilizadas na prática clínica (diazepam, midazolam, propofol e etomidato).Método: Foram estudados 50 corações isolados de ratos Wistar divididos em cinco grupos de dez, em preparação de Langendorff com líquido de perfusão de Krebs-Henseleit (K-H), mantendo-se constantes a pressão de perfusão (90 centímetros de água) e a temperatura (37° + 0,5 graus Celsius). Com exceção do Grupo I (Controle), foram feitas infusões Análise comparativa dos efeitos do diazepam, midazolam, propofol e etomidato na contratilidade miocárdica e no fluxo coronariano: estudo em corações isolados de ratosEffects of diazepam, midazolam, propofol and etomidate in myocardial contractility and coronary blood flow: comparative analysis in isolated rat's hearts 158 MEDEIROS, CGS ET AL -Effects of diazepam, midazolam, propofol and etomidate in myocardial contractility and coronary blood flow: comparative analysis in isolated rat's hearts Bras Cir Cardiovasc 2004; 19(2): 157-164 Rev

<![CDATA[<b>Effects of diazepam, midazolam, propofol and etomidate in myocardial contractility and coronary blood flow</b>: <b>comparative analysis in isolated rat's hearts</b>]]>

“…Taking into account the mean coronary blood flow of 7.2 mL/min at the moment of injection of the drug, the employed dose corresponds to 3.74 mcg/mL of midazolam, thus less than the plasma concentration determined by the dose of 0.3 mg/kg which is currently used in anesthesia (0.4 to 2.0 mg/kg) [19]. The data reported here confirm the results obtained by REVES et al [20] in 1984, MEDEIROS et al [8] in 1995 and PONTES [9] in 1994, who described myocardial depressant effects caused by the use of midazolam. These results did not agree, on the other hand with those published by MARTY & NITENBERG [6] in 1990, who did not evidence a depressant action in the myocardium that justified the hypertensive effect observed after the use of midazolam.…”

“…Thus the concentration is within the range currently used in clinical practice which is between 5 and 32 mcg/mL [19]. The results we obtained with the use of diazepam confirmed the conclusions of CHAI & WANG [1] in 1966, DANIELL [4] in 1975, GONZALES et al [5] in 1990, MEDEIROS et al [8] in 1995 and PONTES [9] in 1994. However our results differ from those of PRINDLE et al [2] and ABEL et al [3] in 1970, who demonstrated an innocuous action or even a positive inotropic action after the use of the drug.…”

“…HERNÀNDEZ [7], in 1991, MEDEIROS et al [8], in 1995 and PONTES [9], in 1994, demonstrated using isolated rat hearts, inhibition of the myocardial contractility after the infusion of diazepam, midazolam and propofol, reaffirming previously reported concepts.…”

Preconditioning abolishion by midazolam in isolated hearts of rats

“…Ozturk et al 8 observed that midazolam, in doses ranging from 10mcg and 100mcg, have caused myocardium depression in rabbits. Medeiros et al 6 , studying the effects of diazepam, midazolam and propofol in isolated hearts of rats, reported that benzodiazepines have caused depression in myocardial contractility. The present investigation confirms the data initially reported 19 , showing that the statistical comparison of dP/dt values in the groups ischemia (GII) and IPC (GIII) confirm the protective effects of the IPC in the ischemic myocardium.…”

“…Hernández 4 , Pontes 5 , and Medeiros et al 6 demonstrated, in isolated hearts of rats, inhibition of the myocardial contractility after diazepam, midazolam and propofol infusion, and the depressive myocardial effect of midazolam was confirmed by Hekerdemian et al 7 and Ozturk et al 8 . The present study has the purpose to analyze the influence of midazolam in the ischemic preconditioning induced in isolated hearts of rats.…”