A comparative study of diazepam and midazoiam induced actions in isolated rat hearts

González, Rosendo Bugarín; Zeegers, A.; Eigenhuis, J.J.; Leevwin, R.S.; Wilgenburg, H. van

doi:10.1016/0014-2999(90)93593-f

Cited by 5 publications

(8 citation statements)

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“…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.…”

Section: Commentssupporting

confidence: 86%

“…GONZALES et al [5], in 1990, using isolated rat hearts, observed different responses of the myocardial contractility (increase or reduction), near to concentrations of administered diazepam or midazolam. MARTY & NITENBERG [6], in the same year, contested that myocardial depression determined by midazolam could cause the hypotensor effect observed after its use, rekindling an old controversy about the action of the benzodiazepinic agents on the myocardial contractility.…”

Section: Introductionmentioning

confidence: 99%

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

Medeiros¹,

Pontes²,

Gomes³

et al. 2004

Rev Bras Cir Cardiovasc

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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

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Section: Commentssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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

Medeiros¹,

Pontes²,

Gomes³

et al. 2004

Rev Bras Cir Cardiovasc

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“…The effect of diazepam on cardiac contractility remains unclear. There have been various reports of negative (Daniell 1975;Herna Ândez 1991), positive (Castillo-Ferrando et al 1985) and biphasic inotropic effects (Gonza Âlez et al 1990).…”

mentioning

confidence: 99%

“…Activation of these receptors increase chloride conductance, leading to hyperpolarization. So-called peripheral type benzodiazepine binding sites, not associated with GABA-A receptors (Benavides et al 1984), have been iden-ti®ed in several non-neural tissues, including the heart (Taniguchi et al 1982;Gonza Âlez et al 1990) kidneys (Schoemaker et al 1983) and intestines (Bonnafous et al 1994).…”

mentioning

confidence: 99%

“…The mechanism underlying the inotropic effect of benzodiazepines is not fully understood. Flumaze-nil, a selective antagonist of the CNS benzodiazepine receptor, has been reported to inhibit the effect of benzodiazepines on the heart (Herna Ândez 1991) and to exert a dose-dependent antagonist or synergistic effect (Gonza Âlez et al 1990). PK-11195, a selective antagonist of peripheral benzodiazepine receptors, can block the positive, but not the negative, inotropic effect of diazepam (Leewin et al 1996).…”

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confidence: 99%

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Positive Inotropic Effect of Diazepam in Rat Myocardium Mediated by β-Adrenergic and Peripheral Benzodiazepine Receptor Stimulation

Vásquez¹,

Romero-Vecchione²,

Davoli³

et al. 1999

Pharmacy and Pharmacology Communications

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The positive inotropic effect of diazepam on rat isolated right ventricular myocardium was studied. Diazepam (3–30 μmol L−1) produced a concentration‐dependent increase in ventricular contractile tension. PK‐11195 (8 μmol L−1), a selective peripheral benzodiazepine receptor antagonist, effectively antagonized the ventricular response to 3 and 10 μmol L−1 diazepam by 60 and 50%, respectively. Flumazenil (10 μmol L−1), a neuronal benzodiazepine receptor antagonist, had no effect on the diazepam‐induced increase in ventricle tension, indicating that the benzodiazepine receptors located on myocardial tissue are of the peripheral type. Isoproterenol (0.01 pmol L−1), a non‐selective β‐adrenergic agonist, significantly (P < 0.01) potentiated the diazepam‐induced increase in ventricle tension. Atenolol (0.1 μmol L−1), a selective β1‐adrenegic receptor antagonist, significantly (P < 0.05) antagonized the positive inotropic effect of diazepam by 40%. Nitrendipine (0.1 μmol L−1), an L‐type Ca2+ channel blocker, significantly (P < 0.05) antagonized the increase of contractile force induced by diazepam by 55%. The results indicate that the positive inotropic effect of diazepam is mediated by a β1‐adrenergic stimulating effect and peripheral benzodiazepine receptor stimulation.

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Diazepam potentiates the positive inotropic effect of isoprenaline in rat ventricle strips: role of cyclic AMP

Martinez

Peñafiel

Collado

et al. 1995

European Journal of Pharmacology

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A comparative study of diazepam and midazoiam induced actions in isolated rat hearts

Cited by 5 publications

References 2 publications

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

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

Positive Inotropic Effect of Diazepam in Rat Myocardium Mediated by β-Adrenergic and Peripheral Benzodiazepine Receptor Stimulation

Diazepam potentiates the positive inotropic effect of isoprenaline in rat ventricle strips: role of cyclic AMP

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