Pre-oxygenation with facemask oxygen vs high-flow nasal oxygen vs high-flow nasal oxygen plus mouthpiece: a randomised controlled trial.

High-flow nasal oxygen used before and during apnoea prolongs time to desaturation at induction of anaesthesia. It is unclear how much oxygenation before apnoea prolongs this time. We randomly allocated 84 participants to 3 minutes of pre-oxygenation by one of three methods: 15 l.min-1 by facemask; 50 l.min-1 by high-flow nasal cannulae only; or 50 l.min-1 by high-flow nasal cannulae plus 15 l.min-1 by mouthpiece. We then anaesthetised and intubated the trachea of 79 participants and waited for oxygen saturation to fall to 92%. Median (IQR [range]) times to desaturate to 92% after pre-oxygenation with facemask oxygen, high-flow nasal oxygen only and high-flow nasal oxygen with mouthpiece, were: 309 (208-417 [107-544]) s; 344 (250-393 [194-585]) s; and 386 (328-498 [182-852]) s, respectively, p = 0.014. Time to desaturation after facemask pre-oxygenation was shorter than after combined nasal and mouthpiece pre-oxygenation, p = 0.006. We could not statistically distinguish high-flow nasal oxygen without mouthpiece from the other two groups for this outcome. Median (IQR [range]) arterial oxygen partial pressure after 3 minutes of pre-oxygenation by facemask, nasal cannulae and nasal cannulae plus mouthpiece, was: 49 (36-61 [24-66]) kPa; 57 (48-62 [30-69]) kPa; and 61 (55-64 [36-72]) kPa, respectively, p = 0.003. Oxygen partial pressure after 3 minutes of pre-oxygenation with nasal and mouthpiece combination was greater than after facemask pre-oxygenation, p = 0.002, and after high-flow nasal oxygen alone, p = 0.016. We did not reject the null hypothesis for the pairwise comparison of facemask pre-oxygenation and high-flow nasal pre-oxygenation, p = 0.14.

Differential sensitivity of proximal and distal coronary arteries to a nitric oxide donor following reperfusion injury or inhibition of nitric oxide synthesis.

OBJECTIVE: The effect of the nitric oxide donor, SIN-1, in proximal and distal coronary arteries with normal endothelium was characterised before and after inhibition of NO synthesis with L-nitroarginine methyl ester (L-NAME). The effect of reperfusion injury in vivo in similar vessels on the response to SIN-1 was also assessed. METHODS: In vitro reactivity of preconstricted coronary arterial rings was studied in control dogs (group 1), and dogs in which the left circumflex coronary artery was subjected in vivo to four acute occlusions of 5 min duration, with three intervening reperfusion periods of 5 min and a final reperfusion period of 60 min (group 2). The effects of acetylcholine and SIN-1 on the tone of left circumflex and left anterior descending coronary vascular rings were examined before and after treatment with L-NAME. RESULTS: Proximal [1851 (SEM 82) microns] and distal [477(19) microns] vessels were studied. In control dogs (group 1) acetylcholine caused relaxation in proximal and distal coronary arteries (p > 0.05). No difference in responsiveness of left circumflex or left anterior descending coronary arteries was observed in the control group. In group 2 the response to acetylcholine was significantly (p < 0.05) attenuated in left circumflex coronary arteries exposed to ischaemia and reperfusion compared with left anterior descending control rings from the same heart. Proximal vessels in group 1 and group 2 showed greater sensitivity to the vasodilator effects of SIN-1 than distal vessels. Proximal left circumflex vessels exposed to ischaemia and reperfusion showed enhanced sensitivity to the relaxant effects of SIN-1 compared to control proximal vessels obtained from the same hearts. Reperfusion was not associated with any alteration in sensitivity of distal vessels to SIN-1. Similarly, inhibition of the synthesis of endothelium derived relaxing factor (EDRF) by L-NAME resulted in an enhanced response to SIN-1 in proximal vessels only. CONCLUSIONS: Endothelium dependent vasodilatation is attenuated by ischaemia and reperfusion in both proximal and distal coronary arteries of the size studied. The response to direct nitric oxide donation (bypassing vascular endothelial synthesis of EDRF) is inhibited by a basal endothelial process present in proximal coronary arteries only. This inhibition is abolished following reperfusion injury or inhibition of NO synthesis.

Differential relaxant effect of high concentrations of intravenous anesthetics on endothelin-constricted proximal and distal canine coronary arteries.

This study determined the direct effect of three intravenous anesthetics on isolated canine coronary arteries constricted with the potent endogenous vasoconstrictor endothelin. Arteries were divided into groups of large (1.3-2.5 mm) and small (250-500 microns) vessels, and arterial rings were suspended in tissue baths. The rings were stretched to an optimal resting tension and then preconstricted with an EC50 concentration of endothelin that was equivalent for both groups. Incremental concentrations (5 x 10(-6) M to 1.6 x 10(-2) M) of thiopental, ketamine, and propofol were added to the baths, and the relaxant responses were recorded. Small arteries demonstrated greater vasodilation at equivalent drug concentrations than did large arteries. These results demonstrate antagonism of the vasoconstrictor endothelin by intravenous anesthetics. Distal vessels are more sensitive than proximal vessels to the relaxant effects of the intravenous anesthetics studied. Direct effects on coronary vascular tone, however, are only apparent at concentrations above those seen clinically. Despite the potential for a differential effect on proximal and distal coronary arteries, we conclude that thiopental, ketamine, and propofol do not possess a direct effect on the tone of large or small canine coronary arteries at concentrations seen in routine clinical practice.

Effect of K+ channel blockade with tetraethylammonium on anesthetic-induced relaxation in canine cerebral and coronary arteries.

The mechanism by which volatile anesthetics produce their direct effects on vascular smooth muscle remains unknown. The authors previously reported that volatile anesthetics decrease both Ca2+ and K+ currents, however the role of Ca(2+)-activated K+ channels during the vasorelaxation by anesthetics has not been investigated. The purpose of this study was to determine whether blockade of the K+ channel alters the response to volatile anesthetics. Responses were studied in canine middle cerebral arteries and proximal and distal canine coronary arteries. Vascular rings (2-mm length) were suspended in tissue baths, and isometric tension was recorded. Rings were constricted with 40 mM KCl and prostaglandin F2 alpha (middle cerebral arteries only) and subsequently exposed to enflurane (3.25%), halothane (1.35%), and isoflurane (2.1%). Volatile anesthetics produced vasorelaxation with relative potency in order: enflurane > halothane > isoflurane. The procedure was repeated in the presence of the K+ channel blocker tetraethylammonium chloride (TEA, 20 mM). In all groups of vessels TEA alone elicited either no increase or only a transient increase in tension, however constrictions to both agonists were augmented in the presence of TEA. The presence of TEA significantly augmented anesthetic-induced vasorelaxation in small and large coronary vessels and in middle cerebral arteries. However, this effect was more pronounced in the cerebral as compared to coronary arteries. Constrictions produced in cerebral vessels by 15 microM prostaglandin F2 alpha were comparable with constrictions produced by 5 microM prostaglandin F2 alpha in the presence of TEA. The subsequent relaxant response of these vessels to enflurane was also comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Transforming growth factor beta 1 preserves endothelial function after multiple brief coronary artery occlusions and reperfusion.

The objective of this investigation was to determine the effect of transforming growth factor beta 1 (TGF-beta 1) on endothelium-dependent relaxation in isolated epicardial coronary artery rings obtained from anesthetized dogs after multiple brief episodes of coronary artery occlusion and reperfusion in vivo. Dogs were subjected to four 5-minute periods of left anterior descending coronary artery occlusion interspersed with 5 minutes of reperfusion and followed by a final 1-hour period of reperfusion. Normal left circumflex coronary arteries were used as control samples. Repetitive ischemia and reperfusion significantly (p < 0.01) inhibited the relaxation response to acetylcholine in rings preconstricted with potassium. In an additional group of dogs subjected to the same protocol, 10 micrograms of human recombinant TGF-beta 1 was infused into the left anterior descending coronary artery distal to the site of occlusion via a diagonal branch at 0.3 ml/min immediately before and during the repetitive occlusions and reperfusions. TGF-beta 1 prevented impaired endothelium-dependent relaxation after multiple brief occlusions and reperfusions. These results demonstrate a protective role for TGF-beta 1 in the endothelial injury that occurs during repeated episodes of coronary artery occlusion and reperfusion.

Cultured endothelial cells restore vasodilator responses to coronary arteries with impaired endothelial function and alter the response to a nitric oxide donor.

The objective of this investigation was to determine the effect of cultured human umbilical vein endothelial cells (HUVEC) on the vascular response to canine coronary arteries in which the endothelium had been either mechanically removed or injured by multiple brief episodes of occlusion and reperfusion in vivo. The endothelium-dependent vasodilator, A23187 (10(-6) mol/l) did not cause any significant relaxation in vessels from which the endothelium had been removed. However, following addition of cultured HUVEC to the tissue bath (75 x 10(3) cells/ml), A23187 produced a significant (p < 0.05) relaxation. This effect was abolished by inhibition of nitric oxide synthase with Nw-nitro-l-arginine methyl ester (L-NAME). Vascular relaxation caused by the nitric oxide donor SIN-1 was significantly (p < 0.05) enhanced when cultured HUVEC were added to vessels mechanically denuded of endothelium. Repetitive ischemia and reperfusion significantly inhibited the relaxant response to A23187. Addition of cultured HUVEC to the tissue bath partially restored the response to A23187. In contrast to the mechanically damaged vessels the relaxant response to SIN-1 was unaffected by cultured HUVEC in reperfusion-injured vessels. These results demonstrate that cultured endothelial cells partially restore endothelium-dependent vasodilation of vessels in which the endothelium is not functional following mechanical- or reperfusion-induced damage. The differential effect of endothelial cells on the response to SIN-1 suggests that mechanical and reperfusion injury alter the coronary vascular response to SIN-1 by different mechanisms.

Direct coronary and cerebral vascular responses to dexmedetomidine. Significance of endogenous nitric oxide synthesis.

Dexmedetomidine activates alpha 2-adrenergic receptors in the central nervous system and in the peripheral vasculature. In vivo dexmedetomidine has been found to cause alterations in coronary and cerebral blood flows and arterial pressure by stimulation of vascular smooth muscle alpha 2 receptors. The direct vasoconstrictor effects of alpha 2-adrenergic agonists may be opposed by release of endothelium-derived relaxing factor believed to be nitric oxide. A functional endothelium was demonstrated recently in canine coronary collateral vessels. The objective of the current study was to assess the direct effect of dexmedetomidine on isolated canine proximal and distal coronary arteries, coronary collateral vessels, and middle cerebral arteries. Responses were measured in tissue baths in the presence of indomethacin 10(-5) M and in the absence and presence of NG nitro-l-arginine methyl ester (L-NAME), an inhibitor of vascular nitric oxide synthesis. Dexmedetomidine (3 x 10(-8) to 3 x 10(-3.9) M) caused constriction (3.9, 5.5, 72.8, and 2.3% for proximal and distal coronary arteries, middle cerebral arteries, and coronary collateral vessels, respectively, expressed as a percentage of KCl-induced contraction) in all vessels. This constriction was enhanced by the presence of L-NAME in all vessels except cerebral arteries. The selective alpha 2-adrenergic antagonist atipamezole (10(-4) M) abolished the response to low but not high concentrations of dexmedetomidine in middle cerebral arteries, proximal coronary arteries, and coronary collateral vessels.(ABSTRACT TRUNCATED AT 250 WORDS)