The aim of this study was to compare physiological effects of hindlimb suspension (HLS) in tail- and pelvic-HLS rat models to determine if severe stretch in the tail-HLS rats lumbosacral skeleton may contribute to the changes traditionally attributed to simulated microgravity and musculoskeletal disuse in the tail-HLS model. Adult male Sprague-Dawley rats divided into suspended and control-nonsuspended groups were subjected to two separate methods of suspension and maintained with regular food and water for 2 weeks. Body weights, food and water consumption, soleus muscle weight, tibial bone mineral density, random plasma insulin, and hindlimb pain on pressure threshold (PPT) were measured. X-ray analysis demonstrated severe lordosis in tail- but not pelvic-HLS animals. However, growth retardation, food consumption, and soleus muscle weight and tibial bone density (decreased relative to control) did not differ between two HLS models. Furthermore, HLS rats developed similar levels of insulinopenia and mechanical hyperalgesia (decreased PPT) in both tail- and pelvic-HLS groups. In the rat-to-rat comparisons, the growth retardation and the decreased PPT observed in HLS-rats was most associated with insulinopenia. In conclusion, these data suggest that HLS results in mild prediabetic state with some signs of pressure hyperalgesia, but lumbosacral skeleton stretch plays little role, if any, in these pathological changes.

No abstract

The effects of gramnegative endotoxin-induced myocardial failure in the pentobarbital-anesthetized dog were examined by monitoring its influence on cardiac myofibrillar ATPase activity. Myofibrils were isolated from endo- and epicardial portions of the left ventricular wall. ATPase activities were determined in animals treated with 4 mg/kg endotoxin and monitored 5 h, in animals monitored for 5 h without endotoxin (controls), and in animals implanted with a unilateral femoral shunt and given endotoxin. No differences were seen in the activities between the endo- and epicardial portions of any preparation. Activity was significantly depressed in endotoxemic animals. Increasing venous return by 313 +/- 71 ml/min significantly increased coronary flow by reducing coronary vascular resistance and prevented any observed depression of myofibrillar ATPase activity. In in vitro studies, adding endotoxin directly to a myofibril preparation did not modify normal activity. It appears that the mechanical and myofibrillar dysfunctions are due to the action of endotoxin at sites not associated with the actomyosin ATPase, but may be due to the production of an intermediary agent in concert with a decreased venous return.

Hindlimb suspension or better known as hind-limb unloading (HLU) of rats is a validated model representing weightlessness, simulating microgravity. This is accomplished by removal of weight-bearing loads from hindquarters producing a cephalic fluid shift. The current study examines whether exposure to microgravity by hind-limb unloading will activate oxidant/antioxidant defense system. Tissue levels of malondialdehyde (MDA), total glutathione (GSH+GS-SG) and superoxide dismutase (SOD) were measured in harvested tissues following HLU and reloading. To rule out any variability in normal dietary oxidant intake, all animals received in their diet Purina rat chow containing 9.6% soy meal (4.8% soy protein). Results show that tissues harvested from rats following 2 weeks of unloading had significantly elevated MDA levels ranging from 0.3-0.8 M/mg protein when compared to paired loaded controls (0.2-0.4μM/mg protein, p < 0.5). Tissues from rats reloaded for 2 weeks following unloading decreased MDA levels from their peak values (p<0.05). GSH levels increased up to 350 M depending on tissues as a result of unloading, and two weeks of reloading decreased GSH levels to 250 M from their peak levels. SOD levels increased in all harvested organs in unloaded group ranging from 0.8-4.0 M with continued increase after two weeks of reloading, p < 0.05). Our data indicate that oxidative stress is induced during unloading as evidenced by increased tissue MDA levels. The response involves an increase in GSH and SOD levels, but two weeks of reloading decreased MDA and GSH levels, while further increasing SOD levels, implying the tissue adaptation to induced oxidative stress. Daily Food Consumption 21.56 ± 2.75 gm Water Intake (ml/rat/day) 28.92 ± 0.27 versus Gr. II p < 0.05 versus Gr. III p < 0.05 Water Intake (ml/rat/day) 20.64 ± 1.91 versus Gr. III p < 0.05 Water Intake (ml/rat/day) 25.23 ± 3.60 p < 0.05, significant differences between the initial and final values.

The observed relationship between insulin and PPT levels in the HLS rats was similar to that observed in rats with STZ-induced insulinopenia. These data suggest that moderate insulinopenia may affect the rat's sensitivity to deep pressure directly, without affecting glucose homeostasis. In addition, our data suggest that HLS rats may develop peripheral neuropathy.