Prolonged deep hypothermic circulatory arrest in rats can be achieved without cognitive deficits

Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) enable surgical repair of cardiovascular defects. However, neurological complications can result after both CPB and DHCA. We sought to investigate if 75 min of CPB or DHCA caused motor, cognitive or histological deficits in rats. Three groups were studied: DHCA, CPB, and sham. Rats in the DHCA group were subjected to 75 min DHCA at 15 degrees C, with a total CPB duration of 75 min. Rats in the CPB group were subjected to 75 min of normothermic CPB. Shams received the same anesthesia, cannulations and infusions. Motor function was assessed using beam testing on days 3-13. Cognitive performance was evaluated using Morris water maze tasks on days 7-13. Overall Performance Category (OPC) and Neurologic Deficit Score (NDS) were assessed daily. Histological Damage Score (HDS) was assessed in survivors on day 14. Sustained deficits on beam testing were seen only in the CPB group. Rats in the CPB and DHCA groups exhibited similar cognitive performance vs. sham. There were no differences in OPC or NDS between groups. Neuronal degeneration was present only in small foci in rats after DHCA (n=4/7). However, HDS was not different in individual brain regions or viscera between DHCA or CPB vs. sham. Surprisingly, CPB, but not DHCA was associated with motor deficits vs. sham, and no cognitive deficits were seen in either group vs. sham. Future studies with longer DHCA duration will be necessary to provide targets to assess novel preservation strategies.     

Albumin synthesis and catabolism following partial hepatectomy in the rat. The effects of amino acids and adrenocortical steroids on albumin synthesis after partial hepatectomy.

Plasma albumin levels were measured in partially hepatectomized, sham operated and control rats. The levels fell in both the partially hepatectomized and sham operated groups; while the latter group returned to normal within a few days, the low plasma albumin in the partially hepatectomized animals was sustained. Albumin synthesis rates in the isolated perfused rat liver were measured in the three groups of animals at varying intervals after partial hepatectomy. There was a significant depression of albumin synthesis rate in terms of both liver and whole animal weights when compared to the sham operated and control animals. This depression was almost completely reversed by the addition of arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine added together to 10 times their normal plasma concentrations. The addition of hydrocortisone had no effect on the albumin synthesis rate after partial hepatectomy. Studies in vivo in the three groups of animals (partially hepatectomized, sham operated and control animals) revealed a fall in the albumin catabolic rate after partial hepatectomy coinciding with the fall in the albumin synthesis rate. An hypothesis whereby the amino acids may have their stimulatory effect is proposed.     

Pre-emptive and continuous inhaled NO counteracts the cardiopulmonary consequences of extracorporeal circulation in a pig model.

Cardiopulmonary bypass (CPB) activates a systemic inflammatory response characterized clinically by alterations in cardiovascular and pulmonary function. The aim of this study was to measure the cardiopulmonary consequences in sham-operated pigs, and in animals subjected to CPB in the presence or absence of lipopolysaccharide (LPS). We also investigated, if the perioperative administration of inhaled NO exerts significant cardiopulmonary effects in an anaesthetized and mechanically ventilated pig model of extracorporeal circulation. Thirty pigs were randomized into six equal groups (sham; sham+INO; CPB; CPB+INO; CPB+LPS; CPB+LPS+INO) and subjected to anaesthesia with mechanical ventilation for up to 24h. We found that CPB+LPS group has the highest degree of lung injury. We also demonstrated that there was a significant difference on the cardiovascular parameters (heart rate, central venous pressure, stroke volume index, and mean systemic arterial blood pressure) between the CPB groups and the sham groups. The deteriorated lung mechanics was associated with a decrease in active subfraction of surfactant (LA) with time during the procedure (P=0.0003), on which inhaled NO had only an initial beneficial effect. In our model, inhaled NO had no long-term beneficial effect on lung mechanics and surfactant homeostasis despite improving lung haemodynamics, inflammation, and oxygenation. We conclude from this study that the use of pre-emptive and continuous inhaled NO therapy has protective and safe effects against lung ischemia/reperfusion associated with CPB.     

Hyperresponsiveness of residual thyroid lobe of hemithyroidectomised rat to thyrotropin

The effects of hemithyroidectomy and thyrotropin administration on rat thyroid gland function were studied in adult male rats. Immediately after surgery or sham operation rats were treated daily with 0.12 IU of bovine thyrotropin (TSH) for 3 or 5 days. In control rats TSH dose applied resulted in an increase in serum T4 level at day 5 of experiment. Serum thyroxine concentration markedly decreased in sham operated and hemithyroidectomised rats, an effect observed at days 3 and 5 of experiment. TSH administration had no effect on serum T4 concentration in sham operated rats while in hemithyroidectomised animals such a treatment resulted in a marked increase in serum T4 level, a phenomenon observed in both time intervals studied. The reasons for hemithyroidectomy-induced hyperresponsiveness of rat thyroid residual lobe to thyrotropin are unknown.     

Long-term effects of pinealectomy on the annual cycle of golden-mantled ground squirrels,Spermophilus lateralis

Summary Pinealectomies and radical sham pinealectomies were performed on adult golden-mantled ground squirrels (Spermophilus lateralis) approximately one month prior to the beginning of the normal winter hibernation season. The cyclic components of the overwintering period and subsequent active season (the rhythms of homeothermy-heterothermy, body mass and testicular function) of the first year were not disrupted in either of the operated groups as compared with the intact animals. In the second year, the initiation of the hibernatory period occurred as usual in all intact, pinealectomized, and sham operated animals, but the pinealectomized group failed to show the progressive increase in the length of heterothermic bouts that was characteristic of the intact and sham-pinealectomized squirrels. The loss of body mass also was accelerated in the pinealectomized squirrels with respect to the intact and sham groups and appeared to be associated with terminal arousal which occurred approximately six weeks earlier in the second year after pinealectomy. Additionally, male squirrels showed a correspondingly early onset of testicular development as compared to the intact and sham operated males.     

Compensatory growth of adipose tissue after partial lipectomy: involvement of serum factors

The regulation of body weight/fat was studied by investigating mechanisms for compensatory adipose tissue growth after removal of bilateral epididymal fat pads from male adult Wistar rats. Food intake during the first 4 weeks and energy expenditure on Days 8-10 postsurgery were not different between lipectomized and sham operated rats. During Days 29-31 post surgery, a small (2.4%) but significant (P < 0.05) increase in heat production per metabolic body size was detected in lipectomized as compared with sham operated rats. The carcass composition of lipectomized and sham operated rats was not significantly different 16 weeks after surgery. The compensatory growth was fat pad-specific: mesenteric, retroperitoneal, and inguinal fat pads, but not perirenal fat pads, were heavier in lipectomized rats than in sham operated rats as early as 4 weeks postsurgery. Examination of fat cell size distribution in the compensating pads indicated a shift toward larger cells in retroperitoneal fat, but not in inguinal fat of lipectomized as compared with sham operated rats. Serum from lipectomized rats, but not media conditioned by exposure to retroperitoneal fat pads from lipectomized rats, stimulated proliferation of preadipocytes in vitro more than that from sham operated rats. Thus, compensatory adipose tissue growth after lipectomy may be mediated, in part, by blood-borne factors that are derived from tissues other than adipose tissue.     

Brain cortical amino acids measured by intracerebral dialysis in portacaval shunted rats

The extracellular amino acid content was measured in the parietal cortex in portacaval and sham operated rats, using the brain dialysis technique. The amino acid content of the perfusate was determined for 10 min before and during stimulation with potassium chloride. Basal levels of aspartate, glutamine, glycine, methionie, valine, phenylalanine and leucine were 2-to 6-fold higher in the PC-shunted as compared to the sham operated rats. For glutamate, taurine, and GABA no differences were observed between the two groups. After KCl stimulation the release of glutamate and GABA increased significantly in both groups. For GABA this rise was approximately twice as high in the PC-shunted rats (+300%,P<0.01) as in the sham operated rats (+150%,P<0.01 as compared to basal). In the sham operated, but not in the PC-shunted rats, methionine and valine levels rose significantly (+200%,P<0.05) and glutamine release decreased (–50%,P<0.05). These findings suggest that the brain metabolism of amino acids is altered after a portacaval shunt. This could in turn alter the neurotransmission and partly explain the low spontaneous motor activity seen in these animals.     

Altered expression of angiotensin AT1a and vasopressin V1a receptors and nitric oxide synthase mRNA in the brain of rats with renovascular hypertension.

Previous studies revealed that the brain angiotensinergic, vasopressinergic and nitrergic systems are involved in regulation of blood pressure and that their function is altered in various forms of hypertension. The purpose of our investigation was to determine whether expression of AT1a angiotensin receptors (AT1aR) mRNA, V1a vasopressin receptors (V1aR) mRNA and neuronal nitric oxide synthase (NOS1) mRNA is altered in the brain of rats with the renovascular hypertension. Eight male Sprague Dawley (SD 2K,1C) rats were subjected to constriction of the left renal artery in order to produce the renovascular hypertension whereas nine SD rats underwent the sham surgery. In both groups blood pressure was determined before and after the surgery. Four weeks after the surgery the brain fragments were harvested for determination of mRNA expression. Competitive PCR method was applied for relative quantitative analysis of V1aR mRNA, AT1aR mRNA and NOS1 mRNA in the preoptic, diencephalic, mesencephalopontine, medullary and cerebellar fragments of the brain. Blood pressure was significantly higher in the 2K,1C than in the sham operated rats. In the preoptic, mesencephalopontine and medullary regions AT1aR mRNA expression was significantly lower in the 2K,1C rats than in the sham operated rats. The 2K,1C rats manifested also significantly higher expression of V1aR mRNA and NOS1 mRNA in the preoptic brain region in comparison to the sham operated rats. The study provides evidence for significant changes of expression of AT1aR mRNA, V1aR mRNA and NOS1 mRNA in the specific brain regions of rats with the renovascular hypertension.     

Contribution of renal innervation to hypertension in rat autosomal dominant polycystic kidney disease

The kidney has both afferent (sensory) and efferent (sympathetic) nerves that can influence renal function. Renal innervation has been shown to play a role in the pathogenesis of many forms of hypertension. Hypertension and flank pain are common clinical manifestations of autosomal dominant (AD) polycystic kidney disease (PKD). We hypothesize that renal innervation contributes to the hypertension and progression of cystic change in rodent PKD. In the present study, the contribution of renal innervation to hypertension and progression of renal histopathology and dysfunction was assessed in male Han:SPRD-Cy/+ rats with ADPKD. At 4 weeks of age, male offspring from crosses of heterozygotes (Cy/+) were randomized into either 1) bilateral surgical renal denervation, 2) surgical sham denervation control, or 3) nonoperated control groups. A midline laparotomy was performed to allow the renal denervation (i.e., physical stripping of the nerves and painting the artery with phenol/alcohol). Blood pressure (tail cuff method), renal function (BUN) and histology were assessed at 8 weeks of age. Bilateral renal denervation reduced the cystic kidney size, cyst volume density, systolic blood pressure, and improved renal function (BUN) as compared with nonoperated controls. Operated control cystic rats had kidney weights, cyst volume densities, systolic blood pressures, and plasma BUN levels that were intermediate between those in the denervated animals and the nonoperated controls. The denervated group had a reduced systolic blood pressure compared with the operated control animals, indicating that the renal innervations was a major contributor to the hypertension in this model of ADPKD. Renal denervation was efficacious in reducing some pathology, including hypertension, renal enlargement, and cystic pathology. However, sham operation also affected the cystic disease but to a lesser extent. We hypothesize that the amelioration of hypertension in Cy/+ rats was due to the effects of renal denervation on the renin angiotensin system.     

Sialic acid and neuraminidase activity in rat kidneys 6 months after uninephrectomy

Sialic acid and neuraminidase activity were determined in the cortex of the remnant kidneys of six uninephrectomized rats. As controls served either the kidneys removed at operation or age-matched kidneys from eight sham operated rats. Six months after uninephrectomy the kidneys became hypertrophied and their mean weight was about 40% higher than age-matched kidneys. Blood urea and creatinine and protein levels in 24-hr urine collections were significantly higher in the experimental animals as compared to those of the same animals before nephrectomy and to sham operated rats, indicating a marked impairment of kidney function. The mean concentration of sialic acid in the cortex of hypertrophied kidneys was not statistically different from either that of the removed or that of the age-matched kidneys. Neuraminidase activity expressed as either per gram fresh tissue or per milligram protein, was not different in the removed and in the hypertrophied kidney. The activity, however, in the latter was significantly lower than in the age-matched kidneys. Whether this finding can be associated with the impairment of kidney function in rats 6 months after uninephrectomy remains to be studied.     

Influence of pinealectomy and long-term melatonin administration on bone metabolism in orchidectomized rats

INTRODUCTION: The aim of the study was to demonstrate whether pinealectomy and long-term MEL administration can affect bone metabolism (as evaluated on the basis of serum concentrations of PICP and ICTP) in orchidectomized rats. MATERIAL AND METHODS: The study included 248 adult male Wistar rats; 6 remained intact, 120 were orchidectomized (Orch), and the remaining ones underwent a sham operation (SOrch). Two weeks after surgery, the rats were divided into 8 groups: 1) SOrch + SPx; 2) SOrch + SPx + MEL; 3) Orch + SPx; 4) Orch + SPx + MEL; 5) SOrch + Px; 6) SOrch + Px + MEL; 7) Orch + Px; 8) Orch + Px + MEL. Animals from 5(th), 6(th), 7(th) and 8(th) groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery rats in the 2(nd), 4(th), 6(th) and 8(th) groups were administered MEL (50 microg/100 g of bm) intraperitoneally while the remaining animals were administered solvent only (daily between 5 and 6 pm during a month). The animals were decapitated before the experiment (intact rats), after 2 weeks from Orch and SOrch, Px and SPx, after 4 weeks from MEL or solvent administration and after 4 and 8 weeks from discontinuing administration of MEL, and blood was collected for PICP and ICTP concentrations assays with the use of RIA method. DISCUSSION: In Orch rats, a distinct tendency to increase the studied bone markers, especially ICTP was shown. Pinealectomy had inducing, while MEL suppressing effect upon the level of PICP and ICTP; these changes were more pronounced in Orch + Px and SOrch + Px + MEL groups, respectively. After discontinuing administration of MEL distinct tendency to increase of PICP and ICTP level was shown. CONCLUSIONS: Our findings indicate that MEL is an important modulator of bone tissue metabolism in male rats and that deficiency of MEL concentration may be a co-factor in osteoporosis development.     

The prenatal development of the organ of Zuckerkandl in rats

The effect of maternal glucocorticoid depletion upon the fetal development of the organ of Zuckerkandl (OZ) in rats was determined. Maternal hypophysectomy at 13d8h gestation resulted in a fifty percent decrease in plasma corticosterone levels at 18d8h when compared to both sham operated and unoperated controls. No differences in the volume of the OZ among the three groups of animals were found. The chromaffinity of the OZ was decreased in the hypophysectomized and sham operated groups suggesting a stress-induced depletion of catecholamine stores. The data suggests that the OZ participates in fetal sympathoadrenal activity and that its development is independent of maternal corticosterone titers.     

Reproductive changes during the early stages of chronic renal insufficiency in the male rat

To examine the reproductive abnormalities during the early stages of chronic renal insufficiency, male rats were studied 1, 2, or 4 weeks after a 2-stage 5/6 nephrectomy or sham surgery. Serum creatinine and urea nitrogen were elevated 3 to 4-fold in nephrectomized rats at all times. Absolute testicular weight was not different between groups but relative testicular weight was higher in nephrectomized animals because of their lower body weight. Absolute prostate and seminal vesicle weights were depressed nephrectomized rats at 4 weeks. Serum luteinizing hormone (LH) was depressed by nephrectomy at all times whereas follicle-stimulating hormone (FSH) was elevated at 4 weeks. Testosterone and androstenedione in serum and testicular interstitial fluid were depressed by nephrectomy at all times. Pituitary LH and FSH were depressed in nephrectomized rats by 2 weeks. These data indicate that some, but not all, of the reproductive defects that accompany chronic renal insufficiency are already present 1 week after a large reduction in renal mass and that defects in both pituitary and testicular function probably occur.     

Gonadectomy impairs T-maze acquisition in adult male rats

Recent studies have shown that chronic gonadectomy increases the density of dopaminergic axons in prefrontal but not sensorimotor cortices in adult male rats. Since supranormal prefrontal cortical dopamine stimulation is known to impair rats' performance in T-maze delayed alternation paradigms, we tested whether long-term gonadectomy might also impair T-maze performance. For comparison, sensorimotor functions were also assessed. Adult male rats were gonadectomized and placebo-, estradiol-, or testosterone propionate-treated or were sham operated and placebo-treated. Four weeks after surgery, the subjects were tested using a rotorod apparatus and in the acquisition of a T-maze delayed alternation paradigm. Gonadectomized placebo-treated and estradiol-treated rats took significantly longer to acquire the T-maze rule than controls, and gonadectomized, testosterone-treated rats acquired the task within the same time frame as controls. No group differences were detected in rotorod performance. Thus, chronic gonadectomy induced testosterone-sensitive, estradiol-insensitive acquisition deficits in a spatial learning task but had no demonstrable effects on the sensorimotor functions tested.     

Cognitive impairment in rats after long-term exposure to GSM-900 mobile phone radiation

Considering the frequent use of mobile phones, we have directed attention to possible implications on cognitive functions. In this study we investigated in a rat model the long-term effects of protracted exposure to Global System for Mobile Communication-900 MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed for 2 h each week for 55 weeks to radio-frequency electromagnetic radiation at different SAR levels (0.6 and 60 mW/kg at the initiation of the experimental period) emitted by a (GSM-900) test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After this protracted exposure, GSM-900 exposed rats were compared to sham exposed controls. Effects on exploratory behaviour were evaluated in the open-field test, in which no difference was seen. Effects on cognitive functions were evaluated in the episodic-like memory test. In our study, GSM exposed rats had impaired memory for objects and their temporal order of presentation, compared to sham exposed controls (P = 0.02). Detecting the place in which an object was presented was not affected by GSM exposure. Our results suggest significantly reduced memory functions in rats after GSM microwave exposure (P = 0.02).     

Adrenalectomy does not prevent the hyperprolactinemic, induced sexual behavior deficits in CDF male rats

Inbred male CDF rats were bilaterally adrenalectomized and received either two pituitaries under each kidney capsule or were sham operated. They were tested at approximately four, seven and eight weeks after surgery. Between the first and second behavioral test, the animals received corticosterone replacement therapy. In each of the three tests, grafted animals exhibited deficits in male sexual behavior as compared to sham-grafted controls. These results suggest that, at least in CDF inbred rats, the adrenal gland is not necessary for the reduction in male sex behavior resulting from chronic hyperprolactinemia.     

Effects of hypothalamus destruction on the level of plasma corticosterone after blast injury and its relation to interleukin-6 in rats

Hypothalamus-pituitary-adrenal (HPA) axis is involved in the modulation of the innate immune response. The purpose of this study was to evaluate the dynamic relationship between plasma corticosterone and interleukin-6 in the hypothalamus-destroyed rats after blast injury. A total of 105 Sprague-Dawley rats were divided randomly into normal control (normal), sham operated (sham), blast injury plus sham operated (blast injury) and blast injury plus hypothalamus destruction groups. Symmetric electrolytic bilateral destruction of the hypothalamus was performed for the deeply anesthetic rats under sterile conditions. Seven days after the destruction of the hypothalamus, the animals were succumbed to moderate blast injury using a BST-I bioimpact machine. Plasma corticosterone and IL-6 levels were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. After blast injury, the corticosterone level in the hypothalamus-destroyed rats was significantly lower than that in the rats without destruction of hypothalamus at 3h (P<0.01) or from 5 to 8h (P<0.05). Reduction of corticosterone may be intrinsically correlated with the severe tissue injury and increased mortality (4/15 vs. 0/15, P<0.05). Circulating IL-6 level was markedly elevated in response to blast injury and hypothalamus destruction further increased IL-6 secretion (P<0.05). We concluded that elevation of pro-inflammatory IL-6 secretion might compensate the impaired HPA axis function after the trauma occurred in the hypothalamus-destroyed rats. These results also suggested that release of hypothalamus hormones is necessary to maintain certain magnitude of innate immunity after trauma.     

Evaluation of the role of calcitonin deficiency in ovariectomy-induced osteopenia

Studies were carried out in rats to examine the role of calcitonin deficiency in the pathogenesis of ovariectomy-induced osteopenia. The parathyroid glands of 80 female Wistar rats were autotransplanted to their thigh muscle and the animals divided into 4 groups. Group 1 rats were sham ovariectomized, and thyroidectomized to make them calcitonin deficient; Group 2 rats were thyroidectomized, and ovariectomized to make them deficient in ovarian hormones as well; Group 3 rats were sham thyroidectomized and sham ovariectomized, and Group 4 rats were sham thyroidectomized and ovariectomized. A fifth group of rats were unoperated upon and served as controls. Thyroidectomized animals were maintained on thyroxine replacement and 11 months after ovariectomy all the animals were bled, killed and their femurs dissected out. In both the thyroid intact and thyroidectomized animals, ovariectomy decreased femur density significantly (P less than 0.01). Similarly, ovariectomy resulted in a decrease in femur calcium (P less than 0.01) in both groups of animals, and in a significant decrease in serum calcitonin (P less than 0.05) in the thyroid intact animals. We conclude from these findings that ovarian hormone deficiency can cause bone loss independently of lowering circulating calcitonin levels.     

Testosterone secretion is severely impaired after hepatectomy in rat, dog and man

In 90%-hepatectomized rats, the plasma testosterone level (0.34 +/- 0.07 ng.ml, mean +/- SEM) is significantly lower (P less than 0.001) than in sham operated male rats (1.7 +/- 0.26 ng.ml, mean +/- SEM). In dogs, after 90% hepatectomy, the mean plasma testosterone concentration fell to 1/10 of the plasma testosterone level measured in sham operated animals either 24 or 72 h after surgery. In hepatectomized men, plasma testosterone is markedly decreased in contrast to what is observed after duodeno-pancreatectomy performed under the same conditions of anesthesia. These results suggest that 90% hepatectomy severely alters the Leydig cell function.     

肾性高血压大鼠延髓尾端神经元型一氧化氮合酶表达的改变

实验采用免疫组织化学方法观察两肾一夹肾性高血压大鼠延髓尾端两个区域（延髓腹面降压区和尾端加压区）内神经元型一氧化氮合酶（neuronal oxide synthase,nNOS）表达的变化。肾性高血压大鼠延髓尾端这两个区域的nNOS的表达均增加,说明高血压对L-Arg-NO通路活性增强。NO的前体L-Arg能增强nNOS的表达,nNOS抑制剂L-NAME则降低nNOS的表达。以上两个区域nNOS表达变化的特点在肾性高血压4周和7周的动物相同,肾性高血压7周的nNOS表达和4周比较,未见明显差异。