Effect of Bupivacaine and Levobupivacaine on Exocytotic Norepinephrine Release from Rat Atria

Background: The cardiotoxic mechanism of local anesthetics may include interruption of cardiac sympathetic reflexes. The authors undertook this investigation to determine if clinically relevant concentrations of bupivacaine and levobupivacaine interfere with exocytotic norepinephrine release from cardiac sympathetic nerve endings.

Methods: Rat atria were prepared for measurements of twitch contractile force and 3[H]-norepinephrine release. After nerve endings were loaded with 3[H]-norepinephrine, the tissue was electrically stimulated in 5-min episodes during 10 10-min sampling periods. After each period, a sample of bath fluid was analyzed for radioactivity and 3[H]-norepinephrine release was expressed as a fraction of tissue counts. Atria were exposed to buffer alone during sampling periods 1 and 2 (S1 and S2). Control atria received saline (100 [mu]l each, n = 6 atria) in S3-S10. Experimental groups (n = 6 per group) received either bupivacaine or levobupivacaine at concentrations (in [mu]M) of 5 (S3-S4), 10 (S5-S6), 30 (S7-S8), and 100 (S9-S10).

Results: Bupivacaine and levobupivacaine decreased stimulation-evoked fractional 3[H]-norepinephrine release with inhibitory concentration 50% values of 5.1 +/- 0.5 and 6.1 +/- 1.3 [mu]m. The inhibitory effect of both local anesthetics (~70%) approached that of tetrodotoxin. Local anesthetics abolished the twitch contractions of atria with inhibitory concentration 50% values of 12.6 +/- 5.0 [mu]m (bupivacaine) and 15.7 +/- 3.9 [mu]m (levobupivacaine). In separate experiments, tetrodotoxin inhibited twitch contractile force by only 30%.     

Immature circulating lymphocytes in severely malnourished Guatemalan children

The percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E-rosettes) was determined in 33 severely malnourished Guatemalan children, and in two groups of clinically well but mildly growth retarded children from the same environment. Mean E-rosettes in the acutely ill patients was lower than the value observed in the mildly malnourished children, although there was considerable overlap between groups. These data differ from previously published studies of severely malnourished children from other parts of the world in that not all patients had decreased values for E-rosettes, in contrast to the uniform depression reported by others. As all patients were clinically similar, the results suggest that there may be specific nutrient defects associated with protein-energy malnutrition that particularly affect immune function. In addition, in vitro incubation of lymphocytes from the acutely malnourished children with the thymic factor, thymosin fraction 5, increased the percentage of E-rosettes in a dose-dependent fashion. These data suggest that immature, thymosin-responsive T cells are present in circulation. It is possible that in vivo thymosin administration may be beneficial for malnourished individuals.     

Double-orifice mitral valve with intact atrioventricular septum: an echocardiographic study with anatomic and functional considerations.

We identified 18 patients with double-orifice mitral valve (DOMV) and intact atrioventricular (AV) septum out of 40,179 echocardiographic studies performed between 1997 and 2002 at Children's Hospital, Denver, CO. In this study we describe (1) the anatomic characteristics of the DOMV in the absence of AV septal defect, (2) the function of the mitral valve by spectral and color Doppler flow mapping, and (3) associated lesions. The topographic location of the orifices in the leaflets suggests possible embryologic mechanisms of DOMV. In this series, DOMV was most commonly associated with left-sided obstructive lesions (in 39% of patients). Spectral and color Doppler interrogation demonstrated a normal flow profile in most cases; only 2 patients had significant mitral regurgitation or stenosis. Therefore, due to the uncertain natural history of this lesion and the potential need for endocarditis prophylaxis, careful imaging of the mitral valve is recommended, particularly in the presence of left-sided obstructive lesions.     

Diabetes mellitus-associated diffuse autonomic dysfunction causing debilitating hypotension manifested after rapid weight loss in a morbidly obese patient: case report and review of the literature.

The association between weight and blood pressure is well established, especially the paradigm of obesity-related hypertension. The relationship between diffuse autonomic dysfunction and orthostatic hypotension in patients with long-term diabetes mellitus is also well known. We report on a 57-year-old morbidly obese male with a long medical history of hypertension, myocardial infarction, type 2 diabetes mellitus, and hypothyroidism. After a loss of 147 pounds (representing a percent excess weight loss of 76%) within 6 months after gastric bypass surgery, the patient developed worsening orthostatic hypotension and near-syncopal episodes requiring medication. The subsequent diagnosis and treatment, as well as a literature review, are presented.     

Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat

The purposes of this study were (1) to document the histopathological consequences of moderate traumatic brain injury (TBI) in anesthetized Sprague-Dawley rats, and (2) to determine whether posttraumatic brain hypothermia (30°C) would protect histopathologically. Twenty-four hours prior to TBI, the fluid percussion interface was positioned over the right cerebral cortex. On the 2nd day, fasted rats were anesthetized with 70% nitrous oxide, 1% halothane, and 30% oxygen. Under controlled physiological conditions and normothermic brain temperature (37.5°C), rats were injured with a fluid percussion pulse ranging from 1.7 to 2.2 atmospheres. In one group, brain temperature was maintained at normothermic levels for 3 h after injury. In a second group, brain temperature was reduced to 30°C at 5 min post-trauma and maintained for 3 h. Three days after TBI, brains were perfusion-fixed for routine histopathological analysis. In the normothermic group, damage at the site of impact was seen in only one of nine rats. In contrast, all normothermic animals displayed necrotic neurons within ipsilateral cortical regions lateral and remote from the impact site. Intracerebral hemorrhagic contusions were present in all rats at the gray-white interface underlying the injured cortical areas. Selective neuronal necrosis was also present within the CA3 and CA4 hippocampal subsectors and thalamus. Post-traumatic brain hypothermia significantly reduced the overall sum of necrotic cortical neurons (519±122 vs 952±130, mean ±SE, P=0.03, Kruskal-Wallis test) as well as contusion volume (0.50±0.14 vs 2.14±0.71 mm³, P=0.004). These data document a consistent pattern of histopathological vulnerability following normothermic TBI and demonstrate hypothermic protection in the post-traumatic setting.Supported by USPHS Grants NS30291 and NS27127     

Union after multiple anterior cervical fusion: 21 cases followed for 1-6 years

With a mean follow-up of 3 (1-6) years, we report on 21 patients who underwent multiple level cervical fusion, using autologous iliac crest grafts. Dis-cectomies were performed in 14 patients and cor-pectomies in another 7. Instrumentation was used in all patients with colectomies and in 2 patients who underwent 2-level and 3-level discectomies. Non-union occurred in 1 patient at 1 level. Graft displacement requiring reoperation was observed in 2 patients with massive corpectomies, in 1 of them as a consequence of trauma. In both patients complete bony fusion was obtained after reoperation and no other complications were observed. We conclude that the success rate with multiple-level fusion is comparable to that of single-level fusion when adequate fixation is achieved.     

Correlation of radiographic and endoscopic evaluation of gastrojejunal anastomosis after Roux-en-Y gastric bypass.

BACKGROUND: Anastomotic stenosis presents as one of the most common late complications in the postoperative period after bariatric surgery. It is often diagnosed by upper gastrointestinal series (UGIS) and/or upper endoscopy (UE). The aim of this study was to determine whether a correlation exists between the Gastrografin UGIS and UE findings in the determination of gastrojejunal anastomotic strictures after Roux-en-Y gastric bypass (RYGB). METHODS: Between July 2001 and October 2003, all medical records of patients who underwent RYGB at our institution were retrospectively reviewed. The medical records of patients who underwent UE because of symptoms suggestive of gastric outlet obstruction and those of patients who were initially evaluated by Gastrografin UGIS before UE were evaluated further. RESULTS: Of 535 morbidly obese patients who underwent RYGB, 52 (9.7%) had UE and were included in this study. The mean number of UEs performed per patient was 2.67. Of these 52 patients, 30 underwent Gastrografin UGIS before UE. The mean diameter of the anastomosis on the first UE was 5.97 mm and on Gastrografin UGIS was 6.83 mm. A good correlation was found between the Gastrografin UGIS and UE findings using Pearson's correlation coefficient (0.44, P = .02) and single linear regression analysis using the endoscopic diameter as the outcome and radiographic findings as the predictor (beta = 0.27, P = .025, 95% confidence interval 0.30-0.49). CONCLUSION: In our study, the Gastrografin UGIS findings correlated positively with the endoscopic gastrojejunal anastomosis findings in patients with anastomotic stricture who had undergone RYGB.