Effect of Sevoflurane on Hypoxic Pulmonary Vasoconstriction in the Perfused Rabbit Lung

Ishibe, Yuichi; Gui, Xiaoping; Uno, Hiroshi; Shiokawa, Yasuhiro; Umeda, Takashi; Suekane, Keita

doi:10.1097/00000542-199312000-00026

Cited by 74 publications

(29 citation statements)

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“…The involvement of a Cx40-mediated conducted response in HPV may provide a mechanistic explanation for the characteristic failure of HPV in the clinical settings of systemic inflammatory disorders (54,55) or during administration of volatile anesthetics (56,57). Indeed, inflammatory stimuli rapidly impair interendothelial coupling via Cx40 (58) and decrease its expression in lungs (13), while volatile anesthetics have long been known to inhibit gap junctional communication (59,60).…”

Section: Figurementioning

confidence: 99%

Hypoxic pulmonary vasoconstriction requires connexin 40–mediated endothelial signal conduction

Wang¹,

Yin²,

Nickles³

et al. 2012

J. Clin. Invest.

133

120

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Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism by which pulmonary arteries constrict in hypoxic lung areas in order to redirect blood flow to areas with greater oxygen supply. Both oxygen sensing and the contractile response are thought to be intrinsic to pulmonary arterial smooth muscle cells. Here we speculated that the ideal site for oxygen sensing might instead be at the alveolocapillary level, with subsequent retrograde propagation to upstream arterioles via connexin 40 (Cx40) endothelial gap junctions. HPV was largely attenuated by Cx40-specific and nonspecific gap junction uncouplers in the lungs of wildtype mice and in lungs from mice lacking Cx40 (Cx40 -/-). In vivo, hypoxemia was more severe in Cx40 -/-mice than in wild-type mice. Real-time fluorescence imaging revealed that hypoxia caused endothelial membrane depolarization in alveolar capillaries that propagated to upstream arterioles in wild-type, but not Cx40 -/-, mice. Transformation of endothelial depolarization into vasoconstriction involved endothelial voltage-dependent α 1G subtype Ca 2+ channels, cytosolic phospholipase A 2 , and epoxyeicosatrienoic acids. Based on these data, we propose that HPV originates at the alveolocapillary level, from which the hypoxic signal is propagated as endothelial membrane depolarization to upstream arterioles in a Cx40-dependent manner. IntroductionHypoxic pulmonary vasoconstriction (HPV) is a fundamental physiological mechanism by which the lung optimizes ventilation/ perfusion (V/Q) matching, redirecting blood flow from poorly to better ventilated areas (1). Yet in cases of global hypoxia, HPV may unfavorably increase total pulmonary vascular resistance and right ventricular afterload, thus contributing to the clinical pathology of pulmonary hypertension and cor pulmonale in chronic hypoxic lung diseases or to pulmonary edema at high altitude (1, 2). While the relevance of HPV has been recognized for over 60 years, the underlying oxygen sensing and signal transduction processes remain a topic of intense research and controversy. Current concepts of HPV are largely based on the notion that pulmonary arterial smooth muscle cells (PASMCs) constitute both the sensor and the transducer of the hypoxic signal as well as its contractile effector (1), while the role of the vascular endothelium is at best considered that of a modulating bystander.From a conceptual standpoint, the ideal site for an oxygen sensor in HPV is within the actual area of pulmonary gas exchange,

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Section: Figurementioning

confidence: 99%

Hypoxic pulmonary vasoconstriction requires connexin 40–mediated endothelial signal conduction

Wang¹,

Yin²,

Nickles³

et al. 2012

J. Clin. Invest.

133

120

View full text Add to dashboard Cite

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“…Halothane in humans [3] and isoflurane in dogs [11] have been demonstrated to cause inhibition of HPV. Ishibe et al [12] reported that sevoflurane also inhibited HPV in a doserelated manner, and its potency was similar to that of isoflurane in the perfused rabbit lung. However, some [3] and that the effect of 1%-1.5% isoflurane on HPV was almost unmeasurable in humans [13].…”

Section: Discussionmentioning

confidence: 93%

Effects of sevoflurane compared with those of isoflurane on arterial oxygenation and hemodynamics during one-lung ventilation

Saito

Cho

Morooka

et al. 2000

Journal of Anesthesia

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“…Studies on isolated perfused lungs showed an inhibition of HPV by inhaled agents. 3,4,8 Conversely, experiments with intact mammals showed either an inhibition 23 or no significant effect. 6,9,24 Associated iv anesthetics This experiment required general anesthesia and mechanical ventilation.…”

Section: Desflurane In Hypoxiamentioning

confidence: 96%

“…2 In vitro studies have demonstrated that halothane, enflurane, isoflurane and sevoflurane inhibit hypoxic pulmonary vasoconstriction (HPV). 3,4 However halogenated agents seem to be less effective pulmonary vasodilators in in vivo lung lobes. [5][6][7] Desflurane is a recently introduced inhalational anesthetic.…”

Section: [La Vasoconstriction Pulmonaire Hypoxique N'est Pas Inhibée mentioning

confidence: 99%

Sub-MAC concentrations of desflurane do not inhibit hypoxic pulmonary vasoconstriction in anesthetized piglets

et al. 2001

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P Pu ur rp po os se e: : In vitro, halogenated agents reduce the pulmonary vasoconstrictor response to alveolar hypoxia in isolated perfused lungs. However, studies in intact animals have been less convincing. The aim of the present study was to assess the effect of sub-MAC concentrations of desflurane on hypoxic pulmonary vasoconstriction (HPV) in anesthetized piglets using the pressure/cardiac output relationship (P/Q).M Me et th ho od ds s: : Eleven large white piglets were anesthetized and ventilated mechanically, alternatively in hyperoxia (FIO 2 =0.4) and in hypoxia (FIO 2 =0.12). Multipoint plots of pulmonary arterial pressure (PAP), or differences between PAP and left atrial pressure (LAP) against Q were generated by gradual inflation of a balloon advanced into the inferior vena cava. P/Q relationships were established in hyperoxia and in hypoxia at baseline, and then with gradual concentrations of desflurane.R Re es su ul lt ts s: : In hypoxia, pressure gradients (PAP-LAP) increased significantly at every level of Q, demonstrating active pulmonary vasoconstriction. Desflurane did not affect these P/Q relationships either in hyperoxia, or in hypoxia, when compared with baseline.C Co on nc cl lu us si io on n: : Desflurane at a clinically relevant dose has no significant effect on HPV in anesthetized piglets.Objectif: La plupart des agents halogénés dont le desflurane inhibent la vasoconstriction pulmonaire hypoxique (VPH) sur le poumon isolé de mammifère. Le but de cette étude est d évaluer les effets de cet halogéné sur la VPH du porc entier anesthésié, au moyen de la relation pression vasculaire trans-pulmonaire (PAP-POG)/débit cardiaque (Q). Résultats: En hypoxie, la pente des relations pression/débit a augmenté de façon significative, et ce pour chaque variation de Q mettant ainsi en évidence un phénomène de VPH active. Le desflurane n a pas eu d effet significatif sur les relations (PAP-POG)/Q en hyperoxie, ni en hypoxie. Matériel et méthodes: Conclusion:Contrairement aux études in vitro, le desflurane n inhibe pas, de façon significative la VPH du porc entier anesthésié.

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Effect of Sevoflurane on Hypoxic Pulmonary Vasoconstriction in the Perfused Rabbit Lung

Cited by 74 publications

References 0 publications

Hypoxic pulmonary vasoconstriction requires connexin 40–mediated endothelial signal conduction

Hypoxic pulmonary vasoconstriction requires connexin 40–mediated endothelial signal conduction

Effects of sevoflurane compared with those of isoflurane on arterial oxygenation and hemodynamics during one-lung ventilation

Sub-MAC concentrations of desflurane do not inhibit hypoxic pulmonary vasoconstriction in anesthetized piglets

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