Paul A. Leonard

A Comparison of the Vasodilating Effects of Halothane and Isoflurane on the Isolated Rabbit Basilar Artery With and Without Intact Endothelium

Although volatile anesthetics result in cerebral arterial dilation, the precise mechanisms underlying this effect are not known. In vitro tension recordings were used to study the vasodilating potencies of halothane and isoflurane in isolated cerebral vessels and to examine the possible role of the endothelium in modulating any effects observed. Cylindrical segments of the rabbit basilar artery and midline ear artery from the same animal were placed in a flow-through bath of 37 degrees C oxygenated (95% O2/5% CO2) physiologic salt solution and stretched to a resting tension of approximately 2,000 dynes. They were then constricted with 3.0 x 10(-2) M K+, 1.0 x 10(-3) M norepinephrine, or 5.0 x 10(-6) M serotonin and exposed to either halothane or isoflurane at concentrations of approximately 0.5, 1.0, 1.5, and 2.0 MAC in varied order for 15 min at each concentration. A 30-min period of perfusion with anesthetic-free, vasoconstrictor-containing perfusate separated successive exposures to an anesthetic. Vessels prepared in this fashion retained their responsiveness to both vasoconstrictors and volatile anesthetics for as long as 4 h. They also relaxed appropriately to acetylcholine, indicating that the endothelium was intact. Concentrations of volatile anesthetic in the tissue perfusate were directly measured using gas chromatography, and the relationship between bath concentrations (expressed as MAC fractions) and the degree of relaxation were determined. The data were analyzed by parallel line regression. Halothane was found to be a significantly more potent vasodilator of the isolated basilar artery than was isoflurane. For example, in K(+)-constricted vessels, the concentration of halothane needed to produce a 50% reduction in tension was 1.32 MAC, compared with 1.66 MAC for isoflurane. Comparable differences were found in the basilar artery in the presence of other constrictors. However, there was no significant difference between the two agents in their effects upon the ear artery. In a separate series of experiments, the endothelium of basilar artery segments was removed by drying. Removal was confirmed by observing a diminished dilator response to acetylcholine. These vessels were subsequently constricted with K+, and relaxation dose-response curves were obtained for both halothane and isoflurane. There were no differences in the dose-response curves for deendothelialized versus intact vessels, with halothane still the more potent relaxant after endothelial removal. These data demonstrate that halothane and isoflurane cause a dose-dependent relaxation of rabbit cerebral vessels, regardless of the vasoconstrictor used. Halothane was a more potent relaxant of the basilar artery when expressed on a MAC-fraction basis.(ABSTRACT TRUNCATED AT 400 WORDS)

Tricyclic antidepressants: Potent blockade of histamine H1 receptors of guinea pig ileum

Six tricyclic antidepressants were tested for their ability to antagonize histamine actions at histamine H1 receptors in a bioassay for these receptors (histamine-induced contractions of guinea pig ileum). All compounds were competitive antagonists with equilibrium dissociation constants in the range of 5.6 x 10(-11) M to 1.5 x 10(-7) M. Doxepin hydrochloride and amitriptyline hydrochloride were the most potent compounds of the series and may be the most potent antihistamines known. Antagonism at histamine H1 receptors by these compounds may explain their sedative effects.

Bradykinin antagonists have no analgesic effect on incisional pain.

Bradykinin, an endogenous nonapeptide and an important mediator of inflammation, is also implicated in the initiation and maintenance of pain. Both des-Arg8, Leu8-bradykinin (dALBK) and HOE-140, the prototypic bradykinin B1 and B2 receptor antagonists, respectively, have been shown to reduce pain behaviors and inflammation in animal models of persistent nociception. We studied them for activity against incision-induced pain behaviors in a rat model for postoperative pain. A 1-cm plantar incision was made in the hind paw of halothane-anesthetized rats and closed with 5–0 nylon. Withdrawal responses to punctate and nonpunctate mechanical stimuli were tested with von Frey filaments and a plastic disk attached to a von Frey filament, respectively. Withdrawal latency to radiant heat was also tested. Rats were tested 1 day before the incision, 1 h after the incision, and 0.5, 1, 1.5, and 2.5 h after the injection of the drug. They were then retested at the same times before and after the injection of the drug on each of the first 2 postoperative days. The rats received the saline vehicle dALBK (0.1, 0.3, 1.0, or 3.0 mg/kg) or HOE-140 (0.1, 0.3, 1.0, or 3.0 mg/kg) IV. Another group of rats had the drug injected 1 h before incision and tested as above. Statistical significance (P < 0.05) was determined with Kruskal-Wallis test and a two-way analysis of variance. None of the doses of either dALBK or HOE-140 affected the responses to punctate or blunt mechanical stimulation or heat, either as a pretreatment or as a posttreatment. These data support the unique mechanisms for incision-induced pain relative to inflammation-related pain. Although inflammation may represent a component of incisional pain, the etiology of inflammation and its role seem different than in other models.

Thyroid Storm Precipitated by Stress in an Undiagnosed Hyperthyroid Patient: A Simulated Medical Crisis

CURRICULAR INFORMATION Educational Rationale Target LearnersVAnesthesia Trainees Thyroid storm is a rare, life-threatening complication of poorly controlled or uncontrolled hyperthyroidism. The mortality rate ranges between 10% and 30% with treatment and may increase to 75% if left untreated. This condition classically occurred during the early postoperative period in hyperthyroid patients who were prepared for thyroidectomy with potassium iodide alone. Such patients were often not euthyroid and would not be considered by contemporary standards to have been adequately prepared for surgery. Improved patient management practices in the period preceding thyroidectomy have greatly decreased the number of cases attributed to surgical resection of the thyroid gland. Thyroid storm may also be precipitated by a number of physiologic stressors, including infection, physical and emotional stress, surgery, trauma, diabetic ketoacidosis, and childbirth. Anesthesia providers routinely care for patients who may be predisposed to developing thyroid storm due to each of these stressors and should be familiar with measures for early treatment and stabilization.

Invited commentary: Simulation training at a large community hospital

We recommend that those who train tomorrow’s providers increase their modeling of many of the attitudes displayed by the authors of The Initiation of Simulation Training at a Large Community Hospital (Article #9 of this issue of Proc Obstet Gynecol). Challenging low-volume, high-risk clinical situations are identified, experienced senior providers are coached using scientifically-informed educational methods with support and resources from leaders in the organization, and an attempt is made to measure progress.