Propofol-induced Depression of Cultured Rat Ventricular Myocytes Is Related to the M2-acetylcholine Receptor–NO–cGMP Signaling Pathway

Yamamoto, Saburo; Kawana, Shin; Miyamoto, Atsushi; Ohshika, Hideyo; Namiki, Akiyoshi

doi:10.1097/00000542-199912000-00024

Cited by 26 publications

(14 citation statements)

References 38 publications

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“…The decrease in blood pressure without any change in the heart rate at T2 and T5 indicate that propofol attenuated the baroreflex activity [28], despite the increase of the cardiac sympathetic activity. In an animal study, propofol was shown to exert a negative chronotropic effect in a dose-dependent manner [29]. The discrepancy between the change in heart rate and cardiac autonomic activity in our study showed that propofol had direct effects on the heart.…”

Section: Discussioncontrasting

confidence: 57%

Haemodynamic changes and heart rate variability during midazolam‐propofol co‐induction*

Win¹,

Kohase

Yoshikawa

et al. 2007

Anaesthesia

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SummaryIn a prospective, blind, randomised study, we examined the effects of midazolam-propofol co-induction on haemodynamic (blood pressure, heart rate and stroke volume) and heart rate variability. The latter was measured by spectral analysis using the maximum-entropy method to calculate the following: the low frequency component (LF), which reflects both the cardiac sympathetic and parasympathetic activity, the high frequency component (HF) and entropy, which reflects the cardiac parasympathetic activity, the total power (TP), calculated by the addition of LF and HF, and the LF ⁄ HF ratio, which reflects the balance between the cardiac sympathetic and parasympathetic nervous activity. Forty patients were randomly allocated to the propofol group and the midazolam-propofol group, and the parameters described above were calculated at baseline (T1), post induction (T2), after tracheal intubation (T3), and 3 min (T4) and 5 min after intubation (T5). Propofol was administered at 2.5 mg.kg )1 in the propofol group and midazolam at 0.1 mg.kg )1 followed by propofol at 1.5 mg.kg )1 in the midazolam-propofol group for anaesthesia induction. Then, propofol was administered at 4-6 mg.kg )1 propofol for maintenance in both groups. The midazolam-propofol group showed compensated haemodynamic changes, which were related to significant increases in the LF ⁄ HF ratio at T2, T4 and T5 (p = 0.011, 0.038 and 0.034). These results suggest that the midazolam-propofol combination yielded compensated modulatory effects on the cardiovascular system, including preserved baroreflex activity. Combined induction (co-induction) refers to the administration of a small dose of a sedative or anaesthetic agent prior to the induction of anaesthesia, with the aim of achieving more specific 'target' responses, while minimising side-effects. Co-induction with midazolam and propofol has been mainly studied in relation to the drugs' synergistic hypnotic actions of the drugs and haemodynamic changes [1-4] during induction of anaesthesia, but there are no reports to date of the haemodynamic changes occurring during tracheal intubation. Propofol decreases the arterial blood pressure, associated with a decrease of the cardiac output ⁄ index, stroke volume index, and systemic vascular resistance [5]; on the other hand, the cardiac output ⁄ index and ventricular filling pressures are maintained after the administration of midazolam [5,6]. The autonomic nervous system exerts important neural control on the heart for maintaining cardiovascular stability. Previous studies have evaluated the effects of propofol [7][8][9][10] and midazolam [11][12][13] on the cardiac autonomic nervous system by means of heart rate variability (HRV) analysis, a non-invasive technique [14][15][16]. There are, however, no reports on simultaneous analysis of the changes of the stroke volume and HRV during midazolam-propofol co-induction. The aim of this study was to investigate the haemodynamic changes and heart rate variability during midazolam co-induction with propofol as comp...

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Section: Discussioncontrasting

confidence: 57%

Haemodynamic changes and heart rate variability during midazolam‐propofol co‐induction*

Win¹,

Kohase

Yoshikawa

et al. 2007

Anaesthesia

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“…Propofol administration should also be considered another potential source of bradycardia. Propofol can cause bradycardia through β-2 adrenergic receptors block [23] or through M-2 acetylcholine receptor activation [24]. However, in the clinical setting, the occurrence of bradycardia with propofol (in the absence of concomitant opioid administration) has been reported only when associated with preexisting myocardial depression [25] or as part of the propofol infusion syndrome (PRIS) [26].…”

Section: Discussionmentioning

confidence: 99%

Bradycardia leading to asystole during dexmedetomidine infusion in an 18 year-old double-lung transplant recipient

Zhang

Schmidt

Wain

et al. 2010

Journal of Clinical Anesthesia

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“…In cultured porcine aortic endothelial cells and rat ventricular myocytes, PPF has been shown to enhance NO production and cause the vasodilatation or negative chronotropy (Petros et al 1993;Yamamoto et al 1999). A study on canine pulmonary arterial rings revealed that PPF selectively attenuated acetylcholine-induced relaxation by inhibiting NO synthesis (Beutler and Poltorak 2001).…”

Section: Introductionmentioning

confidence: 99%

Propofol reduces nitric oxide biosynthesis in lipopolysaccharide-activated macrophages by downregulating the expression of inducible nitric oxide synthase

Chen

Wu²,

Tai

et al. 2003

Archives of Toxicology

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Nitric oxide is an active oxidant that contributes to the physiology and pathophysiology of macrophages. Propofol has been widely used in intravenous anesthesia. It possess antioxidant and immunomodulating effects. This study aimed to evaluate the effects of propofol on nitric oxide production in lipopolysaccharide-activated macrophages. Exposure of macrophages to propofol (25, 50 and 75 micro M), to lipopolysaccharide (0.5, 1, 1.5 and 2 ng/ml) or to a combination of propofol and lipopolysaccharide did not affect cell viability. However, propofol at 100 micro M led to significant cell death ( P<0.05). The levels of nitrite, an oxidative product of nitric oxide, were increased in lipopolysaccharide-treated macrophages in a concentration-dependent manner ( P<0.01), while propofol could concentration-dependently decrease the lipopolysaccharide-enhanced nitrite levels ( P<0.01). Immunoblotting analysis revealed that lipopolysaccharide increased the protein level of inducible nitric oxide synthase (iNOS). The co-treatment of propofol and lipopolysaccharide significantly reduced this lipopolysaccharide-induced iNOS protein (357+/-49 x 10(3) versus 92+/-6 x 10(3) arbitrary units, P<0.01). Analysis by reverse transcriptase-polymerase chain reaction showed that lipopolysaccharide induced mRNA of iNOS, but that the inductive effect was inhibited by propofol (95+/-7 x 10(2) versus 30+/-4 x 10(2) arbitrary units, P<0.01). This study has demonstrated that propofol, at therapeutic concentrations, could suppress nitric oxide biosynthesis by inhibiting iNOS expression in lipopolysaccharide-activated macrophages. The mechanism of suppression was at a pretranslational level.

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Propofol-induced Depression of Cultured Rat Ventricular Myocytes Is Related to the M2-acetylcholine Receptor–NO–cGMP Signaling Pathway

Abstract: These results suggest that the negative chronotropy induced by propofol is mediated in part by M2-acetylcholine receptor activation, which involves the enhancement of NO production in cultured rat ventricular myocytes.

Cited by 26 publications

References 38 publications

Haemodynamic changes and heart rate variability during midazolam‐propofol co‐induction*

Haemodynamic changes and heart rate variability during midazolam‐propofol co‐induction*

Bradycardia leading to asystole during dexmedetomidine infusion in an 18 year-old double-lung transplant recipient

Propofol reduces nitric oxide biosynthesis in lipopolysaccharide-activated macrophages by downregulating the expression of inducible nitric oxide synthase

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