Purpose: To elucidate mechanisms by which remifentanil, an ultra-short-acting µ-opioid receptor agonist, causes hypotension and bradycardia.Methods: Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were measured and recorded after bolus injections of 1, 2 or 5 µg·kg -1 of remifentanil in neuraxis intact (n=6 for each dose) and baro-denervated rabbits (n=6 for each dose). Arterial baroreflex sensitivity was assessed by depressor tests. An additional six baro-denervated animals received remifentanil, 5 µg·kg -1 after pretreatment with naloxone, 40 µg·kg -1 .Results: All values were expressed in % change from baseline. In the neuraxis intact animals, MAP and HR were decreased briefly immediately after remifentanil injection. RSNA was increased dose-dependently: 137 ± 8% (mean ± SE), 170 ± 14% (P < 0.05) and 225 ± 29% (P < 0.05) after 1, 2 and 5 µg·kg -1 remifentanil, respectively. RSNA was increased even after MAP and HR had returned to baseline values. The depressor tests revealed that remifentanil did not attenuate arterial baroreflex sensitivity. In the baro-denervated animals, MAP and HR decreased gradually to 77 ± 3% (P < 0.05) and 94 ± 1% (P < 0.05), respectively 300 sec after 5 µg·kg -1 remifentanil. At that time, increased RSNA (159 ± 9%, P < 0.05) had returned to baseline. Pretreatment with naloxone in the baro-denervated animals abolished these changes. Conclusion:Remifentanil decreases HR and MAP by its central vagotonic effect and by stimulating peripheral µ-opioid receptors. These effects appear to be counteracted and masked by its central sympathotonic effect and by maintaining arterial baroreflex integrity.Objectif : Expliquer les mécanismes par lesquels le rémifentanil, un agoniste à action ultra brève du récepteur de µ-opioïde, provoque de l'hypotension et de la bradycardie.Méthode : La tension artérielle moyenne (TAM), la fréquence cardiaque (FC) et l'activité nerveuse sympathique rénale (ANSR) ont été mesurées et notées après l'injections de bolus de 1, 2 ou 5 µg·kg -1 de rémifentanil dans le névraxe de lapins intacts (n=6 pour chaque dose) et de lapins baroénervés (n=6 pour chaque dose). La sensibilité artérielle baroréflexe a été évaluée par des tests dépresseurs. Six animaux supplémentaires, baroénervés, ont reçu 5µg·kg -1 de rémifentanil après un prétraitement avec 40µg·kg -1 de naloxone.Résultats : Toutes les valeurs sont exprimées en % de changement par rapport aux mesures de base. Chez les animaux intacts, la TAM et la FC ont brièvement baissé immédiatement après l'injection de rémifentanil. L'ANSR s'est accrue d'une manière dépendante de la dose : 137 ± 8 % (moyenne ± écart type), 170 ± 14 % (P < 0,05) et 225 ± 29 % (P < 0,05) après 1, 2 et 5 µg·kg -1 de rémifentanil, respectivement. L'ANSR a augmenté même après que la TAM et la FC ont retrouvé les valeurs de base. Les tests dépresseurs ont révélé que le rémifentanil n'a pas atténué la sensibilité artérielle baroréflexe. Chez les lapins baroénervés, la TAM et la FC ont diminué graduellement jusqu'à...
BackgroundThe student costs of residency interviewing are of increasing concern but limited current information is available. Updated, more detailed information would assist students and residency programs in decisions about residency selection. The study objective was to measure the expenses and time spent in residency interviewing by the 2016 graduating class of the University of Kansas School of Medicine and assess the impact of gender, regional campus location, and primary care application.MethodsAll 195 students who participated in the 2016 National Residency Matching Program (NRMP) received a 33 item questionnaire addressing interviewing activity, expenses incurred, time invested and related factors. Main measures were self-reported estimates of expenses and time spent interviewing. Descriptive analyses were applied to participant characteristics and responses. Multivariate analysis of variance (MANOVA) and chi-square tests compared students by gender, campus (main/regional), and primary care/other specialties. Analyses of variance (ANOVA) on the dependent variables provided follow-up tests on significant MANOVA results.ResultsA total of 163 students (84%) completed the survey. The average student reported 38 (1–124) applications, 16 (1–54) invitations, 11 (1–28) completed interviews, and spent $3,500 ($20–$12,000) and 26 (1–90) days interviewing. No significant differences were found by gender. After MANOVA and ANOVA analyses, non-primary care applicants reported significantly more applications, interviews, and expenditures, but less program financial support. Regional campus students reported significantly fewer invitations, interviews, and days interviewing, but equivalent costs when controlled for primary care application. Cost was a limiting factor in accepting interviews for 63% and time for 53% of study respondents.ConclusionsStudents reported investing significant time and money in interviewing. After controlling for other variables, primary care was associated with significantly lowered expenses. Regional campus location was associated with fewer interviews and less time interviewing. Gender had no significant impact on any aspect studied.
The reason why adenine compounds when used as hypotensive agents are devoid of significant reflex sympathetic activity, such as rebound hypertension and tachycardia, is not clearly understood. This study, performed on alpha-chloralose-anesthetized dogs, examined, first, the effects of adenosine triphosphate (ATP) and adenosine as compared with those of sodium nitroprusside on efferent renal sympathetic nerve activity (RSNA), as an indicator of general reflex sympathetic activity, and second, whether vagal involvement could be demonstrated in the action of ATP and adenosine on RSNA. Renal sympathetic nerve activity increased progressively with increasing doses of sodium nitroprusside (5, 10, and 20 micrograms/kg) and adenosine (0.5, 2.0, and 4.0 mg/kg), whereas ATP suppressed RSNA at 2.0 and 4.0 mg/kg. High doses of ATP and adenosine (4.0 mg/kg) were injected into intact (n = 7) and vagotomized dogs (n = 7). Both ATP and adenosine induced rapid onset of hypotension without rebound hypertension and tachycardia. After vagotomy, the attenuation of RSNA by ATP was completely abolished and rebound hypertension and tachycardia were observed. Vagotomy did not alter the effect of adenosine on RSNA. It is concluded that ATP-induced hypotension is associated with attenuation of sympathetic efferent nerve activity mediated through vagal afferent pathways. Vagal afferent impulses are thought to be one of the mechanisms that inhibit reflex sympathetic activities, such as rebound hypertension after ATP-induced hypotension. The mechanisms by which adenosine inhibits reflex sympathetic activity are not, however, secondary to vagal afferent involvement and must be multifactorial.
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