Differential Effects of Etomidate, Propofol, and Midazolam on Calcium and Potassium Channel Currents in Canine Myocardial Cells

Buljubasic, Nediljka; Marijic, Jure; Bérczi, Viktor; Supan, Darko F.; Kampine, John P.; Bošnjak, Željko J.

doi:10.1097/00000542-199611000-00018

Cited by 116 publications

(68 citation statements)

References 44 publications

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“…32,33 These observations suggest that at high concentrations, midazolam possesses the calcium-channel antagonist property of acting directly on voltage-operated calcium channels. 12,17,[34][35][36][37] The calcium-antagonist property of midazolam supports the endothelium-independent mechanism of midazolam-induced vasodilation that we observed in this study. In fact, endothelium-deprived rings were not different from endothelium-intact rings with respect to the vasodilation induced by the high dose of midazolam, and only the high dose of midazolam reduced CaCl 2 -induced vasoconstriction (Figures 3a and 4).…”

Section: Discussionsupporting

confidence: 87%

“…Neither the GABA A receptor nor TSPO appear to be involved in the vasodilatory effect of midazolam. Although our study provides evidence for a functional interaction between midazolam and voltage-operated calcium channels and previous studies have supported the view of a direct interaction, [34][35][36][37] it would be worthwhile to test this interaction in drug-protein binding studies. From this perspective, midazolam could be considered for clinical trials for the treatment of hypertensive crises.…”

Section: Discussionmentioning

confidence: 49%

“…Furthermore, many studies using the patch clamp technique have documented that midazolam can inhibit inward calcium current in different animal species and tissues. 13,34,36,37 In this study, we have investigated the vasodilatory effect of midazolam; however, vasodilation has also been reported with other BDZs. In pilot experiments in which aortic rings were exposed to increasing doses of diazepam, we found a vasodilatory response that was comparable to that of midazolam (data not shown).…”

Section: Discussionmentioning

confidence: 99%

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Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation

et al. 2011

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Benzodiazepine (BDZ) infusion has been shown to reduce blood pressure in both humans and animals. Although the inhibitory effects of BDZ on the central nervous system have been well documented, less is known about the direct effects of BDZ on the vascular bed. The aims of this study were to assess the effects of the BDZ midazolam on the vascular system in C57/BL6 mouse aortic rings and to investigate the mechanisms of its direct vascular action. We found that midazolam induced reversible, dose-dependent vasodilation in potassium-and phenylephrine-precontracted rings. In rings that were precontracted with potassium or phenylephrine, treatment with 10 lmol l À1 midazolam increased vasodilation by 15 and 60%, respectively, compared with baseline. Vasodilation increased by 80 and 87%, respectively, after treatment with 50 lmol l À1 midazolam. Only the low concentration of midazolam (10 lmol l À1 ) induced endothelium-dependent vasodilation in phenylephrine-precontracted rings. Vasodilation increased by 60% in rings with endothelium and by 20% in rings without endothelium. Conversely, only the high concentration of midazolam (50 lmol l À1 ) reduced the CaCl 2 -induced vasoconstriction of aortic rings with EC 50 (the concentration giving 50% of the maximal effect) values of 1 and 6 mmol l À1 for vehicle-and midazolam-treated rings, respectively. Furthermore, the incubation of phenylephrine-precontracted rings with an inhibitor of the nitric oxide synthase (NOS) NG-nitro-L-arginine methyl ester or the inhibitors of central or peripheral type BDZ receptors (flumazenil or PK 11195, respectively) produced no change in midazolam-induced vasodilation. Thus, low concentrations of midazolam induce vasodilation via an endothelium-dependent mechanism that does not involve NO production. In contrast, high concentrations of midazolam induce vasodilation via an endothelium-independent mechanism that implies reduced sensitivity of aortic rings to calcium ions. Additionally, neither the central c-amino-butyric acid receptor type A nor the peripheral type BDZ receptors seem to be involved in the mechanism of midazolam-induced vasodilation.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

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Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation

et al. 2011

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“…The effects of sedation on hemodynamics are always a concern as both isoflurane (14) and propofol (10) have been shown to negatively affect the myocardium. As this was a closed chest model, we were able to minimize the use of anesthetic to produce shallow anesthesia once instrumentation was completed.…”

Section: Discussionmentioning

confidence: 99%

Postnatal neonatal myocardial adaptation is associated with loss of tolerance to tachycardia: a simultaneous invasive and noninvasive assessment

Fortin-Pellerin

Khoo

Mills

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Fortin-Pellerin E, Khoo NS, Mills L, Coe JY, Serrano-Lomelin J, Cheung PY, Hornberger LK. Postnatal neonatal myocardial adaptation is associated with loss of tolerance to tachycardia: a simultaneous invasive and noninvasive assessment. Am J Physiol Heart Circ Physiol 310: H598 -H607, 2016. First published December 30, 2015; doi:10.1152/ajpheart.00595.2015-Doppler studies at rest suggest left ventricular (LV) diastolic function rapidly improves from the neonate to infant. Whether this translates to its response to hemodynamic challenges is uncertain. We sought to explore the impact of early LV maturation on its ability to tolerate atrial tachycardia. As tachycardia reduces filling time, we hypothesized that the neonatal LV would be less tolerant of atrial tachycardia. Landrace cross piglets of two age groups (1-3 days; NPs; 14 -17 days, YPs; n ϭ 7/group) were instrumented for an atrial pacing protocol (from 200 to 300 beats/min) and assessed by invasive monitoring and echocardiography. NPs maintained their LV output and blood pressure, whereas YPs did not. Although negative dP/dt in NPs at baseline was lower than that of YPs (Ϫ1,599 Ϯ 83 vs. Ϫ2,470 Ϯ 226 mmHg/s, respectively, P ϭ 0.007), with increasing tachycardia negative dP/dt converged between groups and was not different. Both groups had similar preload reduction during tachycardia; however, NPs maintained shortening fraction while YPs decreased (NPs: 35.4 Ϯ 1.4 vs. 31.8 Ϯ 2.2%, P ϭ 0.35; YPs: 31.4 Ϯ 0.8 vs. 22.9 Ϯ 0.8%, P Ͻ 0.001). Contractility measures did not differ between groups. Peak LV twist and untwisting rate also did not differ; however, NPs tended to augment LV twist through increased apical rotation and YPs through increasing basal rotation (P ϭ 0.009). The NPs appear more tolerant of atrial tachycardia than the YPs. They have at least similar diastolic performance, enhanced systolic performance, and different LV twist mechanics, which may contribute to improved tachycardia tolerance of NPs. HEMODYNAMIC MANAGEMENT OF the critically ill term newborn is complex. Understanding the functional nature of the neonatal myocardium and how it evolves through the first few weeks and months after birth is key to optimizing care. Although many authors have provided their opinions regarding clinical management strategies (1, 12, 32), more translational and clinical studies are needed to provide insight into the functional capacity of the early postnatal heart. In particular, changes in diastolic reserve during the first few weeks and months of life in relation to the known disproportionate left ventricular (LV) growth (3, 27) have been poorly explored.In human infants, most of our understanding of the evolution of diastolic function has been derived from noninvasive Doppler-based studies (16,26,31). These investigations have suggested that the neonatal LV myocardium has less robust diastolic relaxation (16) with greater dependency on atrial contraction for filling, much like that of the diseased adult heart with diastolic dysfunction (15). In the first few mo...

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“…The benzodiazepines have hardly been investigated for myocardial protection. Whether these intravenous anesthetics interfere with neutrophil-endothelium interaction, Ca 2+ infl ux and free radical production still needs to be elucidated [14][15][16][17][18] . It is known, that peripheral benzodiazepine receptors are present in peripheral tissues such as adrenals, kidney and heart, as well as in the brain 19,20 .…”

Section: Discussionmentioning

confidence: 99%

Changes in Biomechanical Parameters During Heart Perfusion and After Midazolam Pre-Medication - Experimental Pilot Study

Bartošíková¹,

Nečas²,

Bartošík³

et al. 2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background:Midazolam is a frequently used benzodiazepine in anaesthesiology and intensive care. Aim: The aim of pilot study was to monitor its eff ect during heart perfusion in the laboratory rat. Methods: The same groups of animals (n = 10). The 1 st group was treated with midazolam in a dose of 0.5mg/kg i.p. The 2 nd group was a placebo. After i.p. administration of heparine injection of 500 IU dose, the hearts were excised and perfused (modifi ed Langendorf's method). Working schedule: stabilization/ischaemia/reperfusion proceed at intervals of 20/30/60 min. Monitored parameters in isolated heart: left ventricle pressure (LVP), end-diastolic pressure (LVEDP), contractility (+dP/dt max ).Results: The treated hearts showed improved postischemic recovery, reaching LVP values of 92 ± 6 % at the end of the reperfusion, placebo only 61 ± 7 %. In placebo hearts LVEDP rose from 10.0 ± 0.5 mmHg to 43 ± 4 mmHg after, in treated animals only about 25 mmHg. The treated hearts improved +dP/dt max recovery during reperfusion to 91 ± 8 %. These values were signifi cantly greater than those obtained from the placebo hearts.Conclusions: Positive changes in monitored parameters were found in this experimental pilot study. We conclude that the administration of midazolam in laboratory rats has a cardioprotective potential against ischemia-reperfusion induced injury.

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Differential Effects of Etomidate, Propofol, and Midazolam on Calcium and Potassium Channel Currents in Canine Myocardial Cells

Cited by 116 publications

References 44 publications

Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation

Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation

Postnatal neonatal myocardial adaptation is associated with loss of tolerance to tachycardia: a simultaneous invasive and noninvasive assessment

Changes in Biomechanical Parameters During Heart Perfusion and After Midazolam Pre-Medication - Experimental Pilot Study

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