Pulmonary edema following phenylephrine intranasal spray administration during the induction of general anesthesia in a child

Topical phenylephrine, an agent used to facilitate nasotracheal intubation and prevent nasal mucosal bleeding, can cause severe hypertension in some patients, secondary to its stimulation of alpha-adrenergic receptors. Moreover, a high incidence of pulmonary edema is found in patients whose phenylephrine administration is followed by treatment with beta-blocking agents. We report a case of acute pulmonary edema in a pediatric patient who developed severe hypertension after the inadvertent administration of a large dose of topical nasal phenylephrine, followed by beta-adrenergic antagonists (esmolol).     

Effects of vasoactive agents on intracellular calcium and force in myometrial and subcutaneous resistance arteries isolated from preeclamptic, pregnant, and nonpregnant woman

OBJECTIVE: Preeclampsia is a common and serious complication of pregnancy, characterized by maternal hypertension and proteinuria, placental insufficiency, and fetal growth restriction. The purpose of this study was to investigate whether intracellular Ca 2+ ([Ca 2+ ] i ) and contractile responses of vascular smooth muscle to vasoactive agents are altered in preeclampsia compared with normal pregnancy and the nonpregnant state. STUDY DESIGN: Subcutaneous and myometrial resistance arteries from women who had preeclampsia, normal pregnancy, and nonpregnant women were obtained at the time of cesarean section or hysterectomy. Arteries were mounted on an isometric myograph and loaded with the Ca 2+ indicator, fura-2AM, to permit simultaneous measurement of force and [Ca 2+ ] i . Reponses to endothelium-dependent relaxants (acetylcholine and substance P) and vasoconstrictors (depolarizing potassium solution, phenylephrine, and angiotensin II) were examined. RESULTS: The fall in [Ca 2+ ] i and relaxation in response to acetylcholine was significantly inhibited in both myometrial and subcutaneous arteries from preeclamptic women compared with arteries from nonpregnant or normal pregnant women. However, responses to substance P did not differ between the 3 groups. There were no significant differences in [Ca 2+ ] i or force responses to high potassium, phenylephrine, or angiotensin II in myometrial and subcutaneous resistance vessels in women with preeclampsia compared with normal pregnant women. However, force, but not [Ca 2+ ] i responses to angiotensin II, in subcutaneous vessels from normal pregnant and preeclamptic women were reduced compared with subcutaneous arteries from nonpregnant women, indicating that pregnancy is associated with a reduction in Ca 2+ sensitization in this tissue. A similar effect was not seen in myometrial arteries. CONCLUSION: Endothelial function is altered in preeclampsia, with loss of effect of acetylcholine, but not substance P. Vasoconstrictor reactivity is not increased in preeclampsia compared with uncomplicated normal pregnancy, and this is unlikely to be an explanation for the increased peripheral vascular resistance seen in preeclampsia.     

α-adrenoceptors mediating the positive inotropic effect of phenylephrine in the right ventricular muscle of the monkey (Macaca fuscata)

Summary The property of adrenoceptors mediating the positive inotropic effect (PIE) in the ventricular muscle of the Japanese monkey (Macaca fuscata) was investigated by the use of phenylephrine (PE) and adrenoceptor antagonists. The intrinsic activity (0.6) and the pD₂-value (5.41) for PE were comparable to those in other mammalian species. The -adrenoceptor antagonist, pindolol (3×10^–8 mol/l) shifted only the upper part of the concentration-response curve (CRC) for PE to the right; the pD₂-value for PE was not significantly affected by pindolol. On the other hand, phentolamine (10^–6 mol/l) shifted the lower part of the CRC for PE more than the upper part. In the presence of both pindolol and phentolamine the curve was shifted to the right in a parallel manner. The time required for twitch relaxation was negatively correlated to the degree of PIE of PE in the presence of phentolamine but not pindolol. These results indicate that both - and -adrenoceptors mediate the positive inotropic action in the ventricular muscle of the Japanese monkey and that in contrast to the action via -adrenoceptors the action via -adrenoceptors is not accompanied by the relaxant effect.     

Negligible role of catecholaminergic receptors in the anteroventral third ventricular region in mediating vasopressin-releasing and cardiovascular actions of prostaglandin E2

The aim of this study was to pursue the roles of the catecholamine receptors in the anteroventral third ventricular region (AV3V), a cerebral site engaged in various stress responses, in prostaglandin (PG) E₂-evoked vasopressin (AVP) release and cardiovascular action. Experiments were conducted in conscious rats in which cerebral and vascular cannulae had been implanted chronically. Local infusion (0.5 μl, 1 min) of dopamine (150 nmol), a D₁-dopaminergic agonist SKF 38393 (17 nmol) and an α-adrenergic agonist phenylephrine (150 nmol), as well as PGE₂ (7 nmol), into the AV3V enhanced plasma AVP 5 min later, without affecting plasma osmolality and electrolytes. In contrast to the increases in both arterial pressure and heart rate observed when PGE₂ was applied, dopamine and SKF 38393 did not affect these variables, and phenylephrine elevated only arterial pressure. The AV3V infusion of a β-agonist isoproterenol (100 nmol) did not change plasma AVP, although it decreased arterial pressure and increased heart rate. The increase in plasma AVP by dopamine was not blocked by the preinfusion of the D₂-antagonist sulpiride (13 nmol) into the AV3V 10 min before, but was abolished by that of the D₁-antagonist SCH-23390 (8 nmol). The effects of phenylephrine on both plasma AVP and the blood pressure were prevented by the preadministration of the α-antagonist phenoxybenzamine (13 nmol). However, the pretreatments with phenoxybenzamine, sulpiride or SCH 23390 did not inhibit the responses of AVP, arterial pressure and heart rate caused by PGE₂. These antagonists were without significant effect on AVP and other variables when given alone. The infusion sites of PGE₂ and the other drugs identified histologically included the AV3V structures such as the organum vasculosum laminae terminalis or its vicinity, median preoptic nucleus, medial preoptic nucleus and periventricular hypothalamic nucleus. Dopamine or phenylephrine administered into the cerebral ventricle at the same dose as used in the AV3V application did not exert a significant effect on plasma AVP, arterial pressure and heart rate. These results suggest that catecholamine receptors in the AV3V may not be involved in the AVP-secreting, tachycardiac and pressor responses evoked by topical action of PGE₂ on this area, despite their ability to influence hormone release and cardiovascular function. Received: 3 November 1998 / Accepted: 7 July 1999     

Chronic hypoxia alters vasoconstrictive responses of femoral artery in the fetal sheep

The purpose of this study was to determine if mild hypoxia alters the responsiveness to vasoactive agents in the renal and the femoral arteries in the fetal sheep. Ten pregnant sheep were operated under halothane anesthesia at 116 to 124 days' gestation. A maternal tracheal catheter was placed for infusing compressed air (control group, n=5) or nitrogen (hypoxia group, n=5) starting on post operative day 6 and maintained for 5 days. Femoral and renal arteries were harvested from the fetus to study the constriction response to phenylephrine (PE 10(-9) to 10(-5)mol/L). To determine the involvement of nitric oxide as a modulator of vessel constriction, N-nitro-L-arginine methyl ester (L-NAME) was used at a concentration of 10 -4 mol/L in parallel chambers. In the hypoxia group, maternal PaO2 significantly decreased from a base-line of 110.4+/-1.4 to 80.5+/-1.6 (mmHg, p<0.01), fetal PaO2 significantly decreased from a baseline of 20.9+/-0.3 to 15.5+/-0.1 (mmHg, p<0.01). Hypoxia was associated with a significant increase in PE maximal response in the absence (184.5+/-6.6 vs. 146.2+/-4.3) and presence (166.9+/-6.3 vs. 145.0+/-4.5) of L-NAME, and a decrease in EC50 in the absence (6.0+/-1.1 vs. 27.0+/-4.1) of L-NAME of femoral arteries. However, there were no significant differences in PE maximal response and EC50 in the absence and presence of L-NAME of renal arteries. We concluded that mild chronic hypoxia seems to increase the fetal femoral artery response to PE, but not in the fetal renal artery. This observation is consistent with a redistribution of cardiac output away from the carcass.     

Impedance cardiography-derived hemodynamic responses during baroreceptor testing with amyl nitrite and phenylephrine: a validity and reliability study

Baroreflex (BR) testing with phenylephrine (PE) and amyl nitrite (AN) provided an opportunity to evaluate the ability of impedance cardiography (IC) to track the rapid hemodynamic (HD) changes elicited by these drugs. The AN response was measured after inhalation and the PE response was measured after a bolus injection in 19 subjects on two occasions. High reliability was observed for all of the HD measures. Blood pressure (BP), peripheral resistance (PR), and preejection period (PEP) decreased significantly after administration of AN, whereas heart rate (HR) and cardiac output (Q) increased. BP and total PR increased significantly after administration of PE; HR and Q decreased and PEP did not change significantly. Stroke volume did not change significantly with either drug. The BR slope was reliably elicited with AN and PE. The IC and Finapres BP consistently detected short-term changes in HD responses to AN and PE. The pharmacological interventions demonstrated that IC measures followed the course predicted by the actions of the drugs. Change in PEP and dZ/dt reflected increased contractility. The BR sensitivity was also reproducible.     

O efeito de epinefrina,norepinefrina e fenilefrina no tratamento da hipotensão pós‐raquianestesia: estudo clínico comparativo

Background and objectivesLimited data are present on safety and efficiency of epinephrine for the prophylaxis and treatment of spinal‐hypotension. This study was conducted to compare the effect of epinephrine with norepinephrine and phenylephrine on the treatment of spinal‐hypotension and ephedrine requirement during cesarean delivery.MethodsOne hundred and sixty parturients with uncomplicated pregnancies undergoing elective cesarean delivery under spinal anesthesia were recruited. They were allocated randomly to receive norepinephrine 5 μg.mL^‐1 (n = 40), epinephrine 5 μg.mL^‐1 (n = 40), phenylephrine 100 μg.mL^‐1 (n = 40) or 0.9% saline infusions (n = 40) immediately after induction of spinal anesthesia. Whenever systolic blood pressure drops to less than 80% of baseline, 5 mg of iv ephedrine was administered as rescue vasopressor. The incidence of hypotension, total number of hypotension episodes, the number of patients requiring ephedrine, the mean amount of ephedrine consumption and side effects were recorded.ResultsThere was no statistically significant difference in incidence of maternal hypotension between groups. The number of patients requiring ephedrine was significantly greater in group saline than in group phenylephrine (p < 0.001). However, it was similar between phenylephrine, norepinephrine, and epinephrine groups. The mean ephedrine consumption was significantly higher in group saline than in norepinephrine, epinephrine, phenylephrine groups (p = 0.001).ConclusionThere is no statistically significant difference in incidence of hypotension and ephedrine consumption during spinal anesthesia for cesarean delivery with the use of epinephrine when compared to norepinephrine or phenylephrine. Epinephrine can be considered as an alternative agent for management of spinal hypotension.     

Alpha-1-adrenoceptor subtype selective regulation of connexin 43 expression in rat cardiomyocytes

Connexin43 (Cx43) is the predominant intercellular gap junction protein in the heart providing intercellular communication for the cell-to-cell transfer of electrical activation. In a previous study, we could show that α-adrenoceptor stimulation can affect Cx43 expression and function. We now wanted to elucidate which α1-adrenoceptor subtype might be involved. Cultured neonatal rat cardiomyocytes were exposed to various concentrations of phenylephrine (0.1–1,000 nM) for 24 h (n = 6). Thereafter, cells were harvested, and after lysis, Cx43 content was determined using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot. Results were normalised to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Finally, we determined the effect of this treatment on intercellular gap junction conductivity using dual whole-cell voltage clamp. Similarly, we tested the effect of an additional treatment with either 10 nM prazosin or, to assess the subtypes, 10 nM of the α_1A-antagonist RS17053 (n = 6), 500 nM of the α_1B-antagonist AH1111OA (n = 6), or 50 nM of the α_1D-antagonist BMY7378 (n = 6). Moreover, we incubated the cells for 24 h with the α_1A-adrenoceptor agonist A61603 (10 nM). Phenylephrine led to enhanced Cx43 expression with a pEC50 8.00 ± 0.06. The other cardiac connexins, Cx40 and Cx45, as well as GAPDH were not affected. This increase in Cx43 expression resulted in enhanced gap-junction conductance (44 ± 4 nS vs 26 ± 4 nS). As expected, the increased Cx43 expression could be antagonized by prazosin. Moreover, it was nearly completely inhibited by BMY7378 but was not significantly affected by RS17053. AH1111OA led to a moderate but incomplete inhibition. In contrast, β-actin expression was also up-regulated by phenylephrine but was inhibited by prazosin or RS17053, while it was not affected by BMY7378 or AH1111OA. About 24 h exposure to the α_1A-adrenoceptor agonist A61603 led to a twofold increase in β-actin but did not affect Cx43. The low pEC50 value of about 1 nM for noradrenaline reported in our earlier study fits well to the hypothesis of an effect mediated predominantly via α_1D-adrenoceptors, which is further supported by the finding of a nearly complete antagonisation of the phenylephrine effect by BMY7378. Thus, we conclude that cardiac Cx43 expression seems to be regulated via α₁-adrenoceptors predominantly by subtype α_1D-adrenoceptors, while other proteins like β-actin seem to be regulated via α_1A-adrenoceptors.     

应用去氧肾上腺素后脉搏压变异度和每搏量变异度相关性研究

目的：探讨应用去氧肾上腺素后脉搏压变异度（PPV）和每搏量变异度（SVV）的相关性。方法选择肝胆外科择期肝脏切除手术患者20例,全麻诱导后循环稳定时,记录心率（HR）、动脉收缩压（SAP）、心输出量（CO）、心输出量指数（CI）、每搏量（SV）、每搏量指数（SVI）、PPV和SVV ,改变去氧肾上腺素泵入速度使SAP分别提高10%<ΔSAP≤20%、20%<ΔSAP≤30%和30%<ΔSAP≤40%并记录上述参数,对各个压力阶段的PPV和SVV进行相关性分析。结果去氧肾上腺素降低PPV和SVV值,各压力水平的PPV和SVV的数值具有高度相关性：T1,r=0.935,P<0.01;T2,r=0.947,P<0.01;T3,r=0.971,P<0.01;T4,r=0.973,P<0.01。结论虽然去氧肾上腺素高估了容量状态,但是脉搏压变异度（PPV）和每搏量变异度（SVV）在应用去氧肾上腺素后依然具有高度相关性。