Melanin-concentrating hormone receptor 1 deficiency increases insulin sensitivity in obese leptin-deficient mice without affecting body weight

The hypothalamic peptide melanin-concentrating hormone (MCH) plays important roles in energy homeostasis. Animals overexpressing MCH develop hyperphagia, obesity, and insulin resistance. In this study, mice lacking both the MCH receptor-1 (MCHr1 knockout) and leptin (ob/ob) double-null mice (MCHr1 knockout ob/ob) were generated to investigate whether the obesity and/or the insulin resistance linked to the obese phenotype of ob/ob mice was attenuated by ablation of the MCHr1 gene. In MCHr1 knockout ob/ob mice an oral glucose load resulted in a lower blood glucose response and markedly lower insulin levels compared with the ob/ob mice despite no differences in body weight, food intake, or energy expenditure. In addition, MCHr1 knockout ob/ob mice had higher locomotor activity and lean body mass, lower body fat mass, and altered body temperature regulation compared with ob/ob mice. In conclusion, MCHr1 is important for insulin sensitivity and/or secretion via a mechanism not dependent on decreased body weight.     

Psychophysiological characteristics of women suffering from stress‐related fatigue

Stress‐related fatigue has been attributed to excessive sympathetic nervous system and hypothalamic–pituitary–adrenal (HPA) axis activation, but findings have been equivocal as to whether the HPA axis or the autonomic nervous system (ANS) are affected in this condition and how. Whether task performance deficits are associated with this condition is also uncertain. The present study investigated possible differences between women with stress‐related fatigue and healthy women in heart rate variability (HRV) and other autonomic and respiratory measures, task performance and in salivary cortisol response to awakening. Thirty‐six women with stress‐related fatigue were compared with 19 female healthy controls matched in age. Four indices of HRV and other autonomic and respiratory measures were recorded during baseline, task performance and relaxation phases of a laboratory session. Saliva cortisol was measured four times during the hour after awakening. The fatigued group showed less HRV in three measures, higher temperature, lower O₂ saturation at the surface of the finger, lower end‐tidal pCO₂, and greater cortisol response. This group responded faster on the task but with more errors. Women with stress‐related fatigue show signs of hyperarousal on ANS, respiratory and HPA axis measures. The lower HRV may indicate greater cardiovascular risk. Results for task performance confirm subjectively reported deficits. Copyright © 2009 John Wiley & Sons, Ltd.     

Prevention of atelectasis formation during the induction of general anesthesia in morbidly obese patients

Atelectasis caused by general anesthesia is increased in morbidly obese patients. We have shown that application of positive end-expiratory pressure (PEEP) during the induction of anesthesia prevents atelectasis formation in nonobese patients. We therefore studied the efficacy of PEEP in morbidly obese patients to prevent atelectasis. Twenty-three adult morbidly obese patients (body mass index >35 kg/m(2)) were randomly assigned to one of two groups. In the PEEP group, patients breathed 100% oxygen (5 min) with a continuous positive airway pressure of 10 cm H(2)O and, after the induction, mechanical ventilation via a face mask with a PEEP of 10 cm H(2)O. In the control group, the same induction was applied but without continuous positive airway pressure or PEEP. Atelectasis, determined by computed tomography, and blood gas analysis were measured twice: before the induction and directly after intubation. After endotracheal intubation, patients of the control group showed an increase in the amount of atelectasis, which was much larger than in the PEEP group (10.4% +/- 4.8% in control group versus 1.7% +/- 1.3% in PEEP group; P < 0.001). After intubation with a fraction of inspired oxygen of 1.0, PaO(2) was significantly higher in the PEEP group compared with the control group (457 +/- 130 mm Hg versus 315 +/- 100 mm Hg, respectively; P = 0.035) We conclude that in morbidly obese patients, atelectasis formation is largely prevented by PEEP applied during the anesthetic induction and is associated with a better oxygenation. IMPLICATIONS: Application of positive end-expiratory pressure during induction of general anesthesia in morbidly obese patients prevents atelectasis formation and improves oxygenation. Therefore, this technique should be considered for anesthesia induction in morbidly obese patients.     

Reduced bleeding through temporary balloon occlusion in hip and knee revision surgery

We used temporary balloon occlusion of the iliac or femoral artery to reduce blood loss in major hip or knee operations in 15 cases in 13 patients. The balloon was introduced by an interventional radiologist in the afternoon of the day before surgery or in the morning before. A latex occlusion balloon was inserted via the transfemoral ipsi- or contralateral route. The patients received two 40 mg doses of low molecular weight heparin. At the beginning of the operation, saline was injected into the predetermined volume to inflate the balloon. The balloons were inflated during 1-6 hours. In each case, the balloon occlusion clearly reduced bleeding in the surgical field and facilitated surgery. The perioperative bleeding was reduced by half, as compared to a retrospective control group. We measured the intraarterial blood pressures distally to the balloon in 2 patients. They decreased from 120 to 40 mm Hg and 155 to 50 mm Hg, respectively, after inflation. Two complications occurred, one bleeding due to catheter dislocation the night before surgery and one postoperative necrosis of the tip of a toe in a patient in whom the deflated balloon was not extruded until the day after surgery and the dose of heparin was too low.     

Hemodilution elevates cerebral blood flow and oxygen metabolism during cardiopulmonary bypass in piglets

BACKGROUND: Hemodilution continues to be widely used during cardiopulmonary bypass (CPB) for both adults and children. Previous studies with nonbypass models have suggested that an increase in cerebral blood flow (CBF) compensates for the reduced oxygen-carrying capacity; however, this increased CBF is achieved by an increase in cardiac output. We hypothesized that even with the fixed-flow perfusion of CPB, CBF would be increased during hemodilution. METHODS: Two experiments were conducted and analyzed separately. In each experiment, 10 piglets were randomized to two different groups, one with a total blood prime yielding a high hematocrit (25% or 30%), and the other with a crystalloid prime resulting in a low hematocrit (10% or 15%). Animals were cooled with pH-stat strategy at full flow (100 or 150 mL.kg(-1).min(-1)) to a nasopharyngeal temperature of 15 degrees C, a period of low flow (50 mL.kg(-1).min(-1)) preceding deep hypothermic circulatory arrest (45 or 60 minutes), and a period of rewarming at full flow. Cerebral blood flow was measured at the beginning of CPB, at the end of cooling, at the end of low flow, 5 minutes after the start of rewarming, and at the end of rewarming by injection of radioactive microspheres. RESULTS: Mean arterial pressure was significantly greater with higher hematocrit at each time point (p< 0.05). Cerebral blood flow and the cerebral metabolic rate of oxygen decreased during cooling and further during low flow bypass but were significantly greater with lower hematocrit during mild hypothermia and at the end of rewarming (p< 0.05). CONCLUSIONS: Hemodilution is associated with decreased perfusion pressure, increased CBF and increased the cerebral metabolic rate of oxygen during hypothermic CPB.     

Controlled induction of a pseudarthrosis: a study using a rodent model

OBJECTIVES: This study aimed to test the hypothesis that under standardized mechanical and biologic conditions, the process of indirect bone repair in a rodent species could be manipulated to form a reproducible, atrophic, fibrous pseudarthrosis. DESIGN: The model used comprised a mid-diaphyseal, transverse osteotomy in the rat femur, stabilized via a precision miniature external fixator, a constant axial fixation stiffness being defined by a specific frame geometry. MAIN OUTCOME MEASUREMENTS: The repair process for both 0.5-mm and 3.0-mm gap osteotomies was characterized using radiography, dual-energy x-ray absorptiometry, histologic assessment of standardized longitudinal sections, and postmortem mechanical testing. RESULTS: Healing of the defect was highly reproducible, bone union being attained at around 5 weeks postoperatively with a 0.5-mm gap. Increasing the gap width to 3.0 mm resulted consistently in a pseudarthrosis. CONCLUSION: These two reproducible patterns of repair can now be used to elucidate the underlying molecular mechanisms controlling the extent and progression of connective tissue differentiation in indirect bone repair without the additional variable of a nonstandardized mechanical environment.     

Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion: an intravital fluorescence microscopy study in pigs

BACKGROUND: Retrograde cerebral perfusion (RCP) is used in some centers during aortic arch surgery for brain protection during hypothermic circulatory arrest. It is still unclear however whether RCP provides adequate microcirculatory blood flow at a capillary level. We used intravital microscopy to directly visualize the cerebral capillary blood flow in a piglet model of RCP. METHODS: Twelve pigs (weight 9.7 +/- 0.9 kg) were divided into two groups (n = 6 each): deep hypothermic circulatory arrest (DHCA) and RCP. After the creation of a window over the parietal cerebral cortex, pigs underwent 10 minutes of normothermic bypass and 40 minutes of cooling to 15 degrees C on cardiopulmonary bypass ([CPB] pH-stat, hemocrit 30%, pump flow 100 mL x kg(-1) x min(-1)). This was followed by 45 minutes of DHCA and rewarming on CPB to 37 degrees C. In the RCP group the brain was retrogradely perfused (pump flow 30 mL x kg(-1) x min(-1)) during DHCA through the superior vena cava after inferior vena cava occlusion. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD), defined as total length of erythrocyte-perfused capillaries per observation area. Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia. RESULTS: During normothermic and hypothermic antegrade cerebral perfusion the FCD did not significantly change from base line (97% +/- 14% and 96% +/- 12%, respectively). During retrograde cerebral perfusion the FCD decreased highly significantly to 2% +/- 2% of base line values (p < 0.001). Thus there was no evidence of significant capillary blood flow during retrograde cerebral perfusion. The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP. NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue oxygenation. At the end of retrograde cerebral perfusion there was macroscopic evidence of significant brain edema. CONCLUSIONS: RCP does not provide adequate cerebral capillary blood flow and does not prevent cerebral ischemia. Prolonged RCP induces brain edema. However, there might be a role for a short period of RCP to remove air and debris from the cerebral circulation after DHCA because retrograde flow could be detected in cerebral arterioles.     

On the comparative approach to defining health: A reply to Brülde

Medicine, Health Care and Philosophy -