Kirk T. Benson

In rabbits, landiolol, a new ultra-short-acting β-blocker, exerts a more potent negative chronotropic effect and less effect on blood pressure than esmolol

PurposeTo compare the cardiovascular and sympathetic effects of a new ultra-short-acting, highly cardioselective β-blocker, landiolol, with esmolol, using anin vivo rabbit model.MethodsDifferent bolus doses of landiolol (0.3, 1.0, 3.0 and 10.0 mg·kg−1) or esmolol (0.5, 1.5 and 5.0 mg·kg−1) were given intravenously, and the effects on heart rate (HR) mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were compared.ResultsBoth landiolol and esmolol produced a dose-dependent decrease in HR. The maximum percent reductions of HR were similar with landiolol 3 mg·kg−1 and esmolol 5 mg·kg−1 (−14.0 ± 0.9% and −13.9 ± 1.4%, mean ± SE, respectively). HR decreased more rapidly with landiolol than with esmolol. Esmolol produced a dose-dependent decrease in MAP that was not observed with landiolol. The percent maximum reduction of MAP was-38.2 ± 3.2% with esmolol 5 mg·kg−1. RSNA increased in a dose-dependent fashion with esmolol, but no changes were noted with landiolol.ConclusionThese results suggest that, in rabbits, landiolol has slightly more potent negative chronotropic action than esmolol with significantly less effects on blood pressure.RésuméObjectifComparer les effets cardiovasculares et sympathiques d’un nouveau β-bloquant à action très brève et hautement cardiosélectif le landiolol, avec ceux de lésmolol, en utilisant un modèle in vivo chez le lapin.MéthodeOn a administré différents bolus Intraveineux de landiolol (0,3 ; 1,0 ; 3,0 et 10,0 mg·kg−1) ou désmolol (0,5 ; 1,5 et 5,0 mg·kg−1) et comparé les effets sur la fréquence cardiaque (FC), la tension artérielle moyenne (TAM) et l’activité sympathique rénale (ASR).RésultatsLe landiolol et l’esmolol ont produit une baisse de la FC proportionnelle à la dose. Les réductions maximales de FC ont été similaires avec 3 mg·kg−1 de landiolol et 5 mg·kg−1 désmolol (−14,0 ± 0,9 % et −13,9 ± 1,4 %, moyenne ± écart type, respectivement). La FC a baissé plus rapidement avec le landiolol qu’avec l’esmolol. L’esmolol, contrairement au landiolol, a produit une baisse de la TAM proportionnelle à la dose. La réduction maximale de TAM a été de −38,2 ± 3,2 % avec 5 mg·kg−1 désmolol. L’ASR a augmenté selon la dose avec l’esmolol, mais aucun changement n’a été observé avec le landiolol.ConclusionCes résultats suggèrent que, chez les lapins, le landiolol présente une action chronotropique négative plus puissante que l’esmolol et des effets significativement plus faibles sur la tension artérielle.

Pulse oximetry and circulatory kinetics associated with pulse volume amplitude measured by photoelectric plethysmography

Through a catheter placed in a superficial vein on the finger, we observed a pulsatile venous pressure. To delineate the relationship between the pulsatile venous pressure and the pulse volume amplitude (PVA) recorded by photoelectric plethysmography (PEPG), both tracings were simultaneously recorded. When the PVA changed acutely or gradually, the venous pulse pressure and mean venous pressure simultaneously followed the same trend. We also found that mean PvO2 (135 mm Hg) was greater when the PVA and venous pulse pressure increased above the level (50 mm Hg) observed when they decreased. These findings suggested that the finger pulse detected by PEPG, as well as by pulse oximetry, is caused by pulsations in veins rather than by pulsations in arterial beds. In experiments to evaluate the validity of this hypothesis, we found that the average value of hemoglobin saturation (%SaO2) measured by the pulse oximeter of the dependent fingertip and finger base when dependent was 1.5% and 7.8% lower than when the fingertip and finger base were elevated. Also, the PVA detected by the pulse oximeter followed the same trend as %SaO2. This finding was explained by venous congestion in the dependent finger. On the basis of the high venous pressure, the behavioral trends between the PVA and venous pressure, the high Pvo2, and the low %SaO2 and PVA in the dependent finger, we conclude that the PVA of the PEPG is determined mainly by venous pulse volume generated by shunting of arterial pulse via open arteriovenous (AV) anastomoses in the cutaneous circulation.

Effects of fentanyl, diazepam, and the combination of both on arterial baroreflex and sympathetic nerve activity in intact and baro-denervated dogs.

The combination of fentanyl and diazepam significantly decreases systemic vascular resistance and blood pressure. We attempted to elucidate the reason the combination of these drugs can reduce blood pressure. In α-chloralose-anesthetized dogs, we investigated the effects of fentanyl and diazepam on mean arterial pressure (MAP) and arterial baroreflex control of renal sympathetic nerve activity (RSNA) in both intact (Study 1) and baroreflex-denervated dogs (Study 2). Study 1 included five dogs that received fentanyl 10 μg/kg followed by diazepam 0.4 mg/kg after a 10-min interval. Five more received both drugs in reversed sequence. The arterial baroreflex depressor test was performed with sodium nitroprusside before and after administration of each drug. Sensitivity of arterial baroreflex was examined by using the ratio of maximum increase of RSNA to maximum decrease of MAP (δRSNA/δMAP). RSNA and MAP significantly decreased only after both drugs had been administered (P < 0.05). Fentanyl alone did not attenuate arterial baroreflex sensitivity. Diazepam after fentanyl and diazepam alone attenuated baroreflex sensitivity to the same extent (P < 0.05). Study 2 comprised 14 dogs that underwent further surgical preparation of bilateral carotid sinus, aortic, and vagal nerve denervations. Seven received fentanyl, 5 and 10 μ g/kg, and the other seven received diazepam, a total of 0.4 mg/kg. Fentanyl decreased both RSNA and MAP. Diazepam decreased only MAP significantly. The results indicate that fentanyl decreases mainly sympathetic outflow, whereas diazepam attenuates arterial baroreflex. We conclude that these combined effects of fentanyl and diazepam significantly decrease arterial blood pressure.

The Jehovah's witness patient: considerations for the anesthesiologist

Physicians are frequently faced with ethical decisions in the delivery of health care to patients. With regard to certain ethical issues, it is at times difficult to make appropriate decisions because of the absence of any formal education on the subject and a lack of moral and medical consensus. One such issue is the question of blood transfusion and the Jehovah’s Witness patient (1,2). Jehovah’s Witnesses refuse blood or blood products because of religious beliefs. This refusal creates an ethical conflict for the physician wherein a possible lifesaving, medical course of action is unacceptable to the patient. The issue is further compounded by the lack of consistent legal norms and the changing expectations within the physician-patient relationship. Anesthesiologists are in a particularly difficult position because they are responsible for the administration of blood and blood products perioperatively. Their position may be complicated by an agreement between the surgeon and patient that is morally and medically unacceptable to them. It is the purpose of this article to discuss the religious background of the Jehovah’s Witnesses, to consider the ethical conflicts in caring for these patients, to survey the significant past legal decisions rendered concerning medical management of Jehovah’s Witnesses, and to describe options on how to proceed with anesthesia care.

Attenuation of Arterial Baroreceptor Reflex Response to Acute Hypovolemia During Induced Hypotension

Preservation of the arterial baroreflex response is important to restore cardiac output and blood pressure by reflex sympathetic nerve activation in the event of sudden hypotension caused by acute blood loss during surgery. However, the arterial baroreflex may be significantly attenuated by both anesthetics and hypotensive agents. In isoflurane-anesthetized dogs, the authors investigated the arterial baroreflex response 1) to bolus injections of sodium nitroprusside (SNP), prostaglandin E1 (PGE1) and trimethaphan (TM); and 2) to rapid blood loss (5 ml/kg) before and during induced hypotension with SNP, PGE1, and TM by measuring mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Hypotension produced by both SNP and PGE1 was accompanied by an increase in RSNA and HR. The increase in RSNA and HR following the SNP bolus injection was significantly greater than that following injection of PGE1 (P less than 0.05). Trimethaphan was associated with a decrease in RSNA and HR. Rapid blood loss resulted in the same degree of MAP reduction (20 +/- 2 mmHg) before and during induced hypotension. Sensitivities of baroreflex, as evaluated by ratios of maximum changes in RSNA or HR to MAP (delta RSNA/delta MAP, delta HR/delta MAP), in response to rapid blood loss, were significantly suppressed during continuously induced hypotension, as compared with responses before induced hypotension. Despite the same degree of induced hypotension (70 +/- 5 mmHg of MAP), delta RSNA/delta MAP and delta HR/delta MAP in response to rapid blood loss were significantly greater with PGE1 than those with SNP (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial baroreflex attenuation during and after continuous propofol infusion

The reduction of arterial blood pressure produced by propofol maybe, in part, attributable to impaired baroreflex integrity. The purpose of this study was to investigate arterial baroreflex sensitivity during and after continuous propofol infusion. In urethane anaesthetized rabbits, left renal sympathetic nerves were exposed and placed on a bipolar silver electrode to record renal sympathetic nerve activity (RSNA). Mean arterial pressure (MAP) via a femoral artery and heart rate (HR) by electrocardiogram were continuously recorded. The rabbits were divided into two groups of eight each: Group 1, propofol 5 mg · kg−1 bolus followed by infusion 0.5 mg · kg−1 · min−1; Group 2, propofol 2 mg · kg−1 bolus followed by 0.2 mg · kg−1 · min−1. Phenylephrine pressor and sodium nitroprusside (SNP) depressor tests were carried out before propofol was started (control), at 15 and 30 min during 30 min infusion, and at 15, 30 and 60 min after its discontinuation. The change of RSNA was plotted with respect to every 5 mmHg increment and decrement of MAP to construct sympathetic baroreflex sigmoid curves, and to evaluate baroreflex sensitivity. The baroreflex sensitivity was also evaluated by calculating the ratio of maximum increase of RSNA or HR to SNP-induced maximum decrease of MAP (ΔRSNA/ΔMAP, ΔHR/ΔMAP). Despite the same decreases or increases in MAP, RSNA was attenuated after 15 and 30 min of propofol infusion in both groups compared with control (P < 0.05). Decreased ΔRSNA/ΔMAP gradually returned to the control level 60 min after discontinuation of propofol in Group 1. The baroreflex sensitivity for control of HR was attenuated only at 30 min in the higher propofol infusion group (P < 0.05). It is concluded that propofol attenuates baroreflex sensitivity for control of RSNA in a dose-dependent manner during infusion. Although recovery from anaesthesia is rapid, our data indicate that the attenuated arterial baroreflex may persist after discontinuing propofol infusion.RésuméOn attribue en partie la baisse de la pression arterielle sous propofol, à une défalliance dans le fonctionnement des barorécepteurs. L’étude de la sensibilité baroréflexe artérielle pendant et après une perfusion de propofol constitue l’objectif du présent travail. Chez des lapins sous anesthésie à l’uréthane, nous avons disséqué les nerfs sympathiques rénaux gauches sur lesquels on a inséré une électrode dargent bipolaire dans le but d’étudier l’activité nerveuse sympathique rénale (ANSR). Nous avons enregistré en continu la pression artérielle moyenne (PAM) fémorale directe et la fréquence cardiaque (Fc) par électrocardiographie. Les lapins ont été repartis en deux groupes: le groupe 1 reçoit une injection de propofol 5 mg · kg−1 suivie d’une perfusion de 0,5 mg · kg−1 · min−1; le groupe 2, une injection de propofol 2 mg · kg−1 suivie par 0,2 mg · kg−1 · min−1. Des epreuves de vasosensibilité sont réalisés avec la phényléphrine pour la résponse vasopressive et avec le nitroprussiate de soude (SNP) pour la réponse dépressive. Ces tests sont effectués avant l’administration du propofol (contrôle), à 15 et 30 minutes pendant une perfusion de 30 minutes, et à 15, 30, et 60 minutes aprés l’arrêt de la perfusion. On enregistre les changements de l’ANSR en relation avec toute augmentation ou diminution par pallier de 5 mmHg de la PAM pour construire des courbes d’activité baroréflexe sympathique et en évaluer la sensibilite. La sensibilité baroréflexe est aussi évaluée par le calcul du rapport de l’accroissement maximal de l’ANSR ou de la fréquence cardiaque avec la baisse maximale de la PAM induite par le SNP. (ΔANSR/ΔPAM, ΔFc/Δ/PAM). Malgré les mêmes augmentations ou diminutions de PAM, l’ANSR montre une baisse aprés 15 et 30 minutes de perfusion de propofol dans les deux groupes comparés au contrôle (P < 0,05). La diminution du ΔANSR/ΔPAM revient rapidement aux niveaux du contrôle 60 minutes apres l’arrêt du propofol dans le groupe 1. La sensibilité baroréflexe pour le contrôle de la fréquence cardiaque est atténuée seulement à la trentième minute dans le groupe où la perfusion de propofol est la plus élevée (P < 0,05). Nous concluons que le propofol diminue la sensibilité des barorécepteurs et que cette dépression est reliée à la dose pendant la perfusion. Bien que la récupération postanesthésique soit rapide, nos données montrent que cette hyposensibilité peut durer même aprés l’arrêt de la perfusion.

High-frequency jet ventilation for resection of congenital lobar emphysema.

Chez un nourrisson de 3 mois. Une acidose respiratoire legere est probablement attribuable au faible volume courant secondaire a la faible ventilation de la jet ventilation. Le malade reste stable sur le plan hemodynamique

Hemodynamic and sympathetic effects of fenoldopam and sodium nitroprusside

Background: Fenoldopam is a novel dopamine‐1 receptor selective agonist that can be used as a vasodilator perioperatively to treat hypertension and to produce induced hypotension. We were interested to find out whether there were any differences between fenoldopam (FM) and sodium nitroprusside (SNP), one of the most popular vasodilators, in their effects on hemodynamics and sympathetic outflow using not only neuraxis intact but also baro‐denervated animal models.

Renal Sympathetic Nerve Activity After Dexmedetomidine in Nerve-Intact and Baroreceptor-Denervated Rabbits

To determine the effects of intravenous dexmedetomidine (DMED) on the sympathetic nervous system and to elucidate the mechanism of hypotension, we administered 3 micro gram/kg of DMED to nerve-intact and baroreceptor-denervated rabbits and compared the changes in renal sympathetic nerve activity (RSNA) and hemodynamic variables. In nerve-intact animals, mean arterial pressure (MAP) was increased briefly and then decreased significantly. Changes in RSNA were reciprocal to those of MAP. Heart rate decreased throughout the period of observation. In baroreceptor-denervated rabbits, both MAP and RSNA decreased significantly (-39.4% +/- 3.8% and -21.3% +/- 4.7%, respectively) after the initial increase of MAP. Twenty minutes after administration, hypotension had still continued (-21.1% +/- 3.2%) although RSNA returned to the baseline value. These results indicate that suppression of sympathetic nerve discharge is indeed one of the mechanisms of DMED-induced hypotension, although it may not be the principal one. (Anesth Analg 1996;83:477-81)

Alteration of red cell deformability during extracorporeal bypass: membrane ν bubble oxygenator

Red cell deformability is essential for normal microcirculation, since the red cell is greater in diameter than the caliber of small capillaries. Red cell filtration rate (RFR) was measured using a 5 microns nucleopore polycarbonate filter as an index of red cell deformability before, during, and after two hours of extracorporeal circulation for coronary artery bypass surgery, with a bubble oxygenator (eight patients) or a hollow fiber membrane oxygenator (14 patients). RFR decreased steadily and significantly during bypass in the bubble oxygenator group. After the start of bypass, RFR was significantly higher at all measurement intervals in the membrane oxygenator group as compared with the bubble oxygenator group. It can be postulated that significantly impaired red cell deformability caused by the bubble oxygenator is attributed to mechanical damage secondary to a huge blood-gas interface, and possibly to neutrophil-mediated oxygen free radical formation due to complement activation. Results indicate that the hollow fiber membrane oxygenator is superior to the bubble oxygenator in maintaining red cell deformability.