Normalization of aortic function during arousal episodes in the hibernating ground squirrel

Hypothermia is commonly used to restrict organ damage during preservation of tissue, but does not offer complete protection. Organ damage after reperfusion/rewarming is amongst others caused by an impairment of vascular properties, particularly endothelium-dependent vasodilatation. We hypothesized that hibernating small animals, which frequently cycle through periods of deep cooling (torpor) and full rewarming (arousal), employ specific mechanisms to preserve vascular function after cooling and reperfusion. Therefore we measured contraction of aortic tissue of hibernating European ground squirrels after 24 h and 7 days of torpor, arousal (1.5 h) and in non-hibernating animals. To assess the role of nitric oxide (NO), experiments were performed in the absence and presence of the NO-synthesis inhibitor, L-NMMA (10(-4) M). Maximum contraction to phenylephrine and angiotensin 11 was doubled in 7-days torpid animals without a shift in EC50, compared to the other 3 groups. Maximum contraction to KCl was doubled in 7-days torpid animals compared to the arousal group and non-hibernating animals. Relaxation to acetylcholine (ACh) and sodium nitrite in phenylephrine precontracted rings did not differ between groups. In the presence of L-NMMA, the maximum of concentration-response curves for all three vasoconstrictors was increased by about 30% in the arousal group, but unaffected in other groups. L-NNMA completely inhibited ACh-induced relaxation in 24-h torpid animals and non-hibernating animals, but only partially in 7-days torpid animals and in the arousal group. From this we conclude that vascular adaptation proceeds during torpor. Further, increased contractility of aortic tissue during long torpor returns to normal within 1.5 hours of arousal, which is associated with an increased basal NO synthesis. In addition, involvement of NO in agonist-mediated relaxation differs between the various stages of hibernation. Thus, hibernating animals have effectively developed mechanisms to preserve vascular function after cooling and rewarming. (C) 2002 Elsevier Science Inc. All rights reserved

Development and organization of polarity-specific segregation of primary vestibular afferent fibers in mice

A striking feature of vestibular hair cells is the polarized arrangement of their stereocilia as the basis for their directional sensitivity. In mammals, each of the vestibular end organs is characterized by a distinct distribution of these polarized cells. We utilized the technique of post-fixation transganglionic neuronal tracing with fluorescent lipid soluble dyes in embryonic and postnatal mice to investigate whether these polarity characteristics correlate with the pattern of connections between the endorgans and their central targets; the vestibular nuclei and cerebellum. We found that the cerebellar and brainstem projections develop independently from each other and have a non-overlapping distribution of neurons and afferents from E11.5 on. In addition, we show that the vestibular fibers projecting to the cerebellum originate preferentially from the lateral half of the utricular macula and the medial half of the saccular macula. In contrast, the brainstem vestibular afferents originate primarily from the medial half of the utricular macula and the lateral half of the saccular macula. This indicates that the line of hair cell polarity reversal within the striola region segregates almost mutually exclusive central projections. A possible interpretation of this feature is that this macular organization provides an inhibitory side-loop through the cerebellum to produce synergistic tuning effects in the vestibular nuclei. The canal cristae project to the brainstem vestibular nuclei and cerebellum, but the projection to the vestibulocerebellum originates preferentially from the superior half of each of the cristae. The reason for this pattern is not clear, but it may compensate for unequal activation of crista hair cells or may be an evolutionary atavism reflecting a different polarity organization in ancestral vertebrate ears

Validation of an ultrasound scanner for determing urinary volumes in surgical patients and volunteers

Objective. As bladder distension related to anaesthesia puts patients at risk for permanent dysfunction, perioperative determination of bladder volume is of great importance. The aim of this study is to validate an ultrasonic imaging device for determing bladder urine volume. Method.To evaluate a broad volume range, ultrasonically scanned volumes were compared to true urinary volumes both in surgical patients and in volunteers. After institutional approval and informed consent 60 healthy volunteers were asked not to void for as long as possible. After ultrasound measurements (BladderScan BVI 2500, Diagnostic Ultrasound, Redmond WA, U.S.A.) they voided and true urinary volumes were measured. Fifty surgical patients scheduled for procedures requiring urinary catheterisation were studied. Pre- and post-induction of anaesthesia ultrasound measurements were recorded, followed by urinary catheterisation and measurement of true urinary volume. Urine volumes were compared using Student t-tests and Wilcoxon Rank Tests (p <0.05). For validation linear regression was used together with Bland-Altman analyses. Results. Ultrasonic scanning underestimated the true urine volume by about 7% over the whole volume range (17 ml to 970 ml). Underestimation was larger in females than in males (p <0.02). R-2 values for correlation of measured and scanned urinary volumes ranged between 0.92 and 0.95. Bland and Altman analyses showed a bias of 31 ml in volunteers and of 19 ml in patients and a precision of 110 ml and 80 ml, respectively. Conclusions. The ultrasonic imaging device can be used peri-operatively to establish bladder volume, taking into account the 7% underestimation of the bladder volume

Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolate human atrial muscle

Background: Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effects. The direct inotropic influence of etomidate, ketamine, midazolam, propofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with those reported clinically. Methods: Atrial tissue was obtained from 16 patients undergoing coronary bypass surgery. Each fragment was divided into three strips, and one anesthetic was tested per strip in increasing concentrations (10(-6) to 10(-2) M). Strips were stimulated at 0.5 Hz, and maximum isometric force was measured. Induction agents were studied in two groups, group 1 (n = 7) containing thiopental midazolam, and propofol, and group 2 (n = 9) consisting of etomidate, ketamine, and propofol. Results: The tested anesthetics caused a concentration-dependent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC(50)s (mean +/- SEMI mu M) for inhibition of the contractility were: thiopental 43 +/- 7.6, propofol 235 +/- 48 (group 1), and 246 +/- 42 (group 2), midazolam 145 +/- 54, etomidate 133 +/- 13, and ketamine 303 +/- 54. Conclusions: This is the first study demonstrating a concentration-dependent negative inotropic effect of intravenous anesthetics in isolated human atrial muscle. No inhibition of myocardial contractility was found in the clinical concentration ranges of propofol, midazolam, and etomidate. In contrast, thiopental showed strong and ketamine showed slight negative inotropic properties. Thus, negative inotropic effects may explain in part the cardiovascular depression on induction of anesthesia with thiopental but not with propofol midazolam, and etomidate. Improvement of hemodynamics after induction of anesthesia with ketamine cannot be explained by intrinsic cardiac stimulation