Agonistic and antagonistic activities of bacterially derived Rhodobacter sphaeroides lipid A: comparison with activities of synthetic material of the proposed structure and analogs.

Lipid A from the photosynthetic bacterium Rhodobacter sphaeroides (RSLA) has been previously shown to antagonize many of the effects of endotoxins from more pathogenic gram-negative bacteria. We have reported on the synthesis of the proposed structure of RSLA and determined that bacterially derived RSLA is not identical to its proposed structure (W.J. Christ, P. D. McGuinness, O. Asano, Y. Wang, M. A. Mullarkey, M. Perez, L. D. Hawkins, T. A. Blythe, G. R. Dubuc, and A. L. Robidoux, J. Am. Chem. Soc. 116:3637-3638, 1994). Here we report results of analyzing the antagonistic and agonistic activities of bacterially derived RSLA in comparison with the activities of chemically synthesized material of the proposed structure of RSLA and analogs. Results indicated that all compounds were approximately equally potent at inhibiting endotoxin-induced release of tumor necrosis factor alpha from human monocytes and human whole blood as well as endotoxin-induced generation of nitric oxide in murine macrophages. In addition, all compounds were of equivalent potencies at inhibiting the binding of 125I-labelled lipopolysaccharide derivatized with 2-(p-azido-salicylamido) ethyl-1-3'-dithiopropionate to murine macrophages. Higher concentrations of bacterially derived RSLA (10 to 100 microM) were agonistic in human and murine assays. In gamma interferon-treated murine macrophages, agonism was exhibited at concentrations as low as 100 nM. In contrast, all synthetic materials were either dramatically less agonistic or devoid of agonistic activity when tested at concentrations as high as 100 microM. It is possible either that bacterially derived RSLA contains a small amount of a highly agonistic impurity or that the agonistic activity of RSLA is intrinsic to its molecular structure. In either case, these biological results support our previous report concluding that biologically derived RSLA is not identical to synthetic material of its proposed structure.     

Prevention of venous thromboembolism following cardiac, vascular or thoracic surgery

In the absence of thromboprophylaxis, coronary artery bypass graft surgery (CABG), intrathoracic surgery (thoracotomy or video-assisted thoracoscopy), abdominal aortic surgery and infrainguinal vascular surgery are high-risk surgeries for the development of venous thromboembolic events (VTE). The incidence of VTE following surgery of the intrathoracic aorta, carotid endarterectomy or mediastinoscopy is unknown. Data from the litterature are lacking to draw evidence-based recommandations for venous thromboprophylaxis after these three types of surgeries, and the following guidelines are but experts'opinions (Grade D recommendations). Thromboprophylaxis is recommended after CABG (Grade D), with either subcutaneous (SC) low molecular weight heparin (LMWH) or SC or intravenous (i.v.) unfractioned heparin (UH) (PTT target = 1.1-1.5 time control value) (both grade D). This may be combined with the use of intermittent pneumatic compression device (Grade B). After valve surgery. The anticoagulation recommended to prevent valve thrombosis is sufficient in order to prevent VTE. We recommend thromboprophylaxis with either LMWH or low dose UH to prevent VTE after aortic or lower limbs infrainguinal vascular surgery (both grade B and D). Vitamine K antagonists (VKA) are not recommended in this indication (Grade D). We recommend thromprophylaxis following intrathoracic surgery via thoracotomy or videoassisted thoracoscopy (grade C). Either subcutaneous LMWH or subcutaneous or i.v. low dose UH may be used (Grade C). Efficacy of intermittent pneumatic compression device has been demonstrated in a study (grade C). VKA are not recommended (grade D). No further recommendation regarding the duration of thromboprophylaxis after these three types of surgeries can be made.     

Mid-lumbar segments are needed for the expression of locomotion in chronic spinal cats

In acute experiments performed in decerebrated and spinalized (T13) cats, an intraspinal injection of clonidine, a noradrenergic agonist, restricted to mid-lumbar segments L3-L4, can induce hindlimb locomotion, whereas yohimbine, a noradrenergic antagonist, can block spinal locomotion, and a second spinal lesion at L4 can abolish all locomotor activity. In the present study, we investigated whether the abolition of locomotion after this second spinal lesion was due to an acute spinal shock or to the functional disconnection of the rostral and caudal lumbar segments. In seven cats, first spinalized at T13 and having recovered treadmill locomotion, a second transection was performed at lower lumbar levels. Video and electromyographic recordings were used to evaluate locomotor performance. Results show that after a second transection at L2 or rostral L3 levels, spinal locomotion was maintained; when the second lesion was performed at caudal L3 or L4, all locomotor activity was abolished even after several weeks of attempted locomotor training; vigorous fast paw shakes (FPS) were observed in all cases; and after an intraperitoneal injection of clonidine in cats with a second transection below L4, perineal stimulation induced hyperextension of the hindlimbs but no locomotion. Considering that the main motoneuron pools of the hindlimbs are caudal to L4 and are still functional after the second spinal transection, as evidenced by the presence of FPS, we conclude that the mid-lumbar spinal segments are essential for the specific expression of spinal locomotion but not necessarily for other rhythmic motor patterns.     

Morbid obesity treated by gastroplasty: radionuclide gastric emptying studies

Mechanisms by which gastroplasty for morbid obesity causes weight loss are poorly understood. We studied the role of altered gastric emptying in 50 patients before surgery, 1-4 weeks after surgery, and 2-24 months after surgery using technetium-99m pentetate in water for liquid meals and a Tc-99m styrene divinylbenzene copolymer resin in oatmeal for semisolid meals. We determined the emptying half-times of the stomach before and after surgery in the proximal and distal compartments. The proximal compartment emptied promptly in the early and late postoperative periods. The distal compartment emptied liquids at rates similar to those before surgery, while the late postoperative emptying of semisolids was significantly faster. The stoma connecting the two compartments thus permits rapid transit of liquids and semisolids without delay of distal compartment emptying. No correlation was seen between the emptying half-times or changes thereof and eventual weight loss. Delayed gastric emptying is therefore not the mechanism for satiety and weight loss after gastroplasty has been performed.     

High incidence of myocardial ischemia during postpartum hemorrhage

BACKGROUND: Postpartum hemorrhage remains a major cause of global maternal morbidity and mortality, even in developed countries, despite the use of intensive care units. This study sought to (1) assess whether myocardial ischemia could be associated with and even aggravate hemorrhagic shock in young parturients admitted for postpartum hemorrhage, and (2) identify the independent risk factors for myocardial ischemia. METHODS: On their referral to the intensive care unit, a multidisciplinary team managed parturients with severe postpartum hemorrhage. Ventilation, transfusion, catecholamines, surgery, or angiography with uterine embolization were provided as clinically indicated. Plasma cardiac troponin I levels were used as a surrogate marker of acute myocardial injury and electrocardiograms of myocardial ischemia. RESULTS: A total of 55 parturients were referred with severe postpartum hemorrhage, all in hemorrhagic shock. Twenty-eight parturients (51%) had elevated serum levels of cardiac troponin I (9.4 microg/l [3.7-26.6 microg/l]), which were associated with electrocardiographic signs of ischemia and deteriorated myocardial contractility and correlated with the severity of hemorrhagic shock. Indeed, multivariate analysis identified low systolic and diastolic arterial blood pressure (< 88 and < 50 mmHg, respectively) and increased heart rate (> 115 beats/min) as independent predictors of myocardial injury. In addition, all patients who were given catecholamines also had elevated cardiac troponin I levels. CONCLUSIONS: These results suggest that treatment of postpartum hemorrhage-induced hemorrhagic shock should be coupled with concomitant prevention of myocardial ischemia, even in young parturients.     

Is muscle relaxant necessary for cardiac surgery?

The need for continuous and complete paralysis during the entire cardiac surgery has not yet been investigated and is still controversial. In a series of 87 patients undergoing cardiac surgery with normothermic cardiopulmonary bypass, we studied the delay of recovery, incidence of residual paralysis, unwanted patient movement, and difficult surgical conditions after a single dose of atracurium (0.5 mg/kg) or cisatracurium (0.15 mg/kg). Anesthesia was induced with etomidate and remifentanil followed by tracheal intubation. The delay to obtain a train-of-four ratio of >0.9 was longer with cisatracurium than with atracurium (86 +/- 18 versus 97 +/- 19 min). However, at the end of surgery, this ratio was >0.9 for all patients. The presence of unwanted patient movement, diaphragmatic contractions, and difficult surgical conditions were observed. Delay of extubation of the trachea was similar in both groups. We conclude that there is no need for continuous neuromuscular blockade during cardiac surgery. A single dose of either atracurium or cisatracurium is sufficient to provide efficient paralysis from the start of induction leading to quicker recovery from paralysis in fast-track cardiac surgery.     

.VO2 is attenuated above the lactate threshold in endurance-trained runners

PURPOSE: To determine whether a deviation from linearity occurs in the .VO2-speed relationship, above the lactate threshold (LT) in running; and whether the length of the submaximal exercise bouts alters the magnitude of any deviation. METHODS: Ten endurance-trained runners (N = 3 state level, N = 4 club level, and N = 3 recreational) (mean +/- SE; age 24.4 +/- 2.8 yr, mass 76.1 +/- 2.2 kg, .VO2 59.3 +/- 10.6 mL.kg-1.min-1) completed a .VO2, LT test and 10 x 4-min submaximal constant load exercise bouts. Data were evenly spread above and below LT, which was fitted by a dual linear regression model. RESULTS: There was a significant decrease (51.4%) in slope of the .VO2-speed relationship above LT. The use of 3-min, in comparison with 4-min, submaximal data did not alter the slope of the .VO2-speed regression above LT. There was no significant difference in the .VO2max estimated from the .VO2-speed regression above LT (58.1 +/- 3.3 mL.kg-1.min-1) but a significant difference below LT (63.6 +/- 3.9 mL.kg-1.min-1) to that obtained during the .VO2max test. CONCLUSION: Data from the current study suggest that the use of the linear regression of .VO2-speed data below the LT may potentially overestimate the prediction of .VO2 values above LT.