Exocrine pancreatic response to secretin and bethanechol in rabbits under hypothermia

The effect of the administration of secretin and bethanechol on exocrine pancreatic secretion was studied in rabbits subjected to temperature changes; these involved a drop from 38 degrees C +/- 1 to 28 degrees C +/- 1 (hypothermia) and a subsequent return to 38 degrees C +/- 1 (normothermia). It was observed that hypothermia does not depress the action of secretin on the secretion of fluid, HCO3- and Cl-. Neither was the action of bethanechol on the enzyme secretion affected by changes in body temperature.     

局部亚低温联合硫酸镁对局灶性脑缺血大鼠的保护作用

目的:探讨联合应用局部亚低温(32-35℃)及硫酸镁对局灶性脑缺血大鼠的保护作用及其可能机制。方法:通过线栓法建立大鼠大脑中动脉阻塞(MCAO)模型,将40只雄性Wistar大鼠随机分为假手术组、常温组、亚低温组、硫酸镁组、亚低温+硫酸镁组,每组8例,采用Longa神经功能评分、TTC染色、TUNEL技术,检测和比较各组脑缺血后大鼠的神经功能、脑梗死体积、凋亡细胞数。结果:与常温组相比,亚低温组与亚低温+硫酸镁组的梗死体积、神经功能评分、凋亡细胞数均明显降低,差异有显著意义(P0.05);而与亚低温组相比,亚低温+硫酸镁组局灶脑缺血大鼠的脑梗死体积、神经功能评分、凋亡细胞数均显著减少,差异有显著意义(P0.05)。结论:与单独应用亚低温相比,局部亚低温与硫酸镁联合应用,对局灶性脑缺血大鼠可发挥更有效的脑保护作用,其机制可能与抑制脑缺血后凋亡有关。     

亚低温联合镁剂对脑缺血再灌注大鼠保护作用的研究

目的:rt-PA溶栓为缺血性卒中最有效的治疗方法,脑血流再通后挽救濒临死亡的神经细胞同时,也可能发生更为严重而持久的脑缺血再灌注损伤。本研究探讨联合应用局部亚低温(32-35℃)及硫酸镁对局灶性脑缺血再灌注大鼠的保护作用及其可能机制。方法:通过线栓法建立大鼠大脑中动脉阻塞(MCAO)及再通模型,将50只雄性Wistar大鼠随机分为假手术组、常温组、亚低温组、硫酸镁组、亚低温+硫酸镁组,每组10例,采用Longa神经功能评分、TTC染色、干湿重法、TUNEL技术,检测和比较各组脑缺血再灌注后大鼠的神经功能、脑梗死体积、脑组织含水量及凋亡细胞数。结果:与常温组相比,亚低温组与亚低温+硫酸镁组的梗死体积、神经功能评分、脑组织含水量、凋亡细胞数均明显降低,差异有显著意义(P0.05);而与亚低温组相比,亚低温+硫酸镁组局灶脑缺血大鼠的脑梗死体积、神经功能评分、脑组织含水量、凋亡细胞数均显著减少,差异有显著意义(P0.05)。结论:与单独应用亚低温相比,局部亚低温与硫酸镁联合应用,对局灶性脑缺血再灌注大鼠可发挥更有效的脑保护作用。其机制可能与抑制脑缺血再灌注后凋亡及减轻脑水肿有关。二者联用可能为缺血性卒中患者提供一种减轻溶栓后再灌注损伤的有效脑保护方法。     

Effect of pentoxiphylline on oxygen transport during hypothermia

At least two investigators have demonstrated a reduction in O2 extraction during induced hypothermia (Cain and Bradley, J. Appl. Physiol. 55: 1713-1717, 1983; Schumacker et al., J. Appl. Physiol. 63: 1246-1252, 1987). We hypothesized that administration of pentoxiphylline (PTX), a theobromine that lowers blood viscosity and has vasodilator effects, would increase O2 extraction during hypothermia. To test this hypothesis, we studied O2 transport in anesthetized, paralyzed, mechanically ventilated beagles exposed to hypoxic hypoxia during either 1) normothermia (38 degrees C), 2) hypothermia (30 degrees C), or 3) hypothermia + PTX (30 degrees C and PTX, 20 mg.kg-1.h-1). Measurements included arterial and mixed venous PO2, hemoglobin concentration and saturation, cardiac output, systemic vascular resistance (SVR), blood viscosity, and O2 consumption (VO2). Critical levels of O2 delivery (DO2, the product of arterial O2 content and cardiac output) were determined by a system of linear regression. Hypothermia significantly decreased base line cardiac output (-35%), DO2 (-37%), and VO2 (-45%), while increasing SVR and blood viscosity. Addition of PTX increased cardiac output (35%) and VO2 (14%), and returned SVR and blood viscosity to normothermic levels. Hypothermia alone failed to significantly reduce the critical level of DO2, but addition of PTX did [normothermia, 11.4 +/- 4.2 (SD) ml.kg-1.min-1; hypothermia, 9.3 +/- 3.6; hypothermia + PTX, 6.6 +/- 1.3; P less than 0.05, analysis of variance]. The O2 extraction ratio (VO2/DO2) at the critical level of DO2 was decreased during hypothermia alone (normothermia, 0.60 +/- 0.13; hypothermia, 0.42 +/- 0.16; hypothermia + PTX, 0.62 +/- 0.19; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Post-ischemic hypothermia promotes generation of neural cells and reduces apoptosis by Bcl-2 in the striatum of neonatal rat brain

Hypothermia is a potential therapy for cerebral hypoxic ischemic injury in adults and neonates. However, the mechanism of hypothermia neuroprotection after hypoxic-ischemia (HI) on the developing rat brain remains unclear. In this research, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 2h. They were divided into hypothermia (rectal temperature, 32-33°C for 24h) and normothermia (36-37°C for 24h) groups immediately after hypoxia-ischemia. All rats were given 50mg/kg/day 5-bromodeoxyuridine (BrdU) intraperitoneally at 4-6 days and sacrificed at 1 or 2 weeks after HI. There was a significant decrease in infarct volume in the hypothermia group at 7 days after HI compared with that in the normothermia group. The numbers of nestin-labeled cells did not change greatly, but β-tubulin III (Tuj-1) immuno-positive cells increased significantly in the striatum at 1 and 2 weeks after HI in the hypothermia compared to normothermia group. Neurogenesis was assessed by double immunohistochemical/immunofluorescent labeling of BrdU with nestin, Tuj-1 or microtubule-associated protein 2 (Map-2). Newborn neural progenitors (BrdU(+)-nestin(+)) did not change dramatically, but newborn immature (BrdU(+)-Tuj-1(+)) and mature (BrdU(+)-Map-2(+)) neurons increased significantly in the hypothermia compared with normothermia group. Meanwhile, the apoptosis rate of neural precursors, immature and mature neurons, assessed by double labeling of active Casp-3 with nestin/Tuj-1/Map-2, decreased noticeably in the hypothermia compared with normothermia group. We also found that hypothermia significantly increased expression of Bcl-2, which coexisted with nestin/Tuj-1/Map-2. Inhibition of Bcl-2 expression reversed the decreased apoptosis rate of neural precursors and neurons in hypothermia animal striatum of neonatal rat brain. These results suggest that neuroprotection effects of hypothermia on injured developing rat brain may associate with enhanced generation of neuronal cells and Bcl-2-mediated reduction of apoptosis of these cells. These observations are noteworthy regarding clinical hypothermia therapy following cerebral HI injury during the perinatal period.     

Effects of hypothermia and re-warming on the inflammatory response in a murine multiple hit model of trauma

INTRODUCTION: Although, hypothermia is a frequent event after trauma, it is unclear whether its beneficial or detrimental effects are more important. This study aims to quantify the effects of hypothermia and re-warming on the inflammatory response after fracture/hemorrhage and subsequent fracture stabilization with resuscitation. MATERIALS AND METHODS: Eighty-one male C57Bl/6 mice (aged 8-10 weeks, weighing 22.0+/-3.0 g) underwent femoral fracture and hemorrhage followed by resuscitation and splint fixation of the fracture. Animals were sacrificed 3h after induction of hemorrhage and fracture. Besides a sham group (n=6), four experimental groups were created: A: normothermia (n=12), B: hypothermia after trauma (n=21), C: re-warming after resuscitation and before stabilization (n=21), and D: hypothermia before trauma (n=21). Groups B-D were further subdivided into three subgroups according to the degree of hypothermia (subgroup 1: 35-33 degrees C, subgroup 2: 32.9-30.0 degrees C, and subgroup 3: 29.9-27.0 degrees C). Plasma cytokine (TNF-alpha, IL-6, and IL-10) and chemokine (MCP-1) concentrations were determined by ELISA, pulmonary permeability changes were quantified, and histological analysis of lung and liver tissues was performed. RESULTS: Normothermia resulted in a significantly increased early mortality rate. A significantly increased pro-inflammatory and decreased anti-inflammatory responses were also observed in normothermia as compared to hypothermia. The extent of these changes was most pronounced in the severe hypothermic group. Re-warming after mild hypothermia resulted in a pro-inflammatory response comparable to normothermia. CONCLUSION: Hypothermia has a beneficial effect on early survival after trauma, which appears to be independent of the level of hypothermia and re-warming. Re-warming, however, enhanced the pro-inflammatory response. Further studies with a longer posttraumatic observation period are required to investigate the long term effects of the hypothermia and re-warming-induced changes on the pro- and anti-inflammatory responses.     

Effects of regional body temperature variation during asphyxial cardiac arrest on mortality and brain damage in a rat model

To date, hypothermia has focused on improving rates of resuscitation to increase survival in patients sustaining cardiac arrest (CA). Towards this end, the role of body temperature in neuronal damage or death during CA needs to be determined. However, few studies have investigated the effect of regional temperature variation on survival rate and neurological outcomes. In this study, adult male rats (12 week-old) were used under the following four conditions: (i) whole-body normothermia (37 ± 0.5 °C) plus (+) no asphyxial CA, (ii) whole-body normothermia + CA, (iii) whole-body hypothermia (33 ± 0.5 °C)+CA, (iv) body hypothermia/brain normothermia + CA, and (v) brain hypothermia/body normothermia + CA. The survival rate after resuscitation was significantly elevated in groups exposed to whole-body hypothermia plus CA and body hypothermia/brain normothermia plus CA, but not in groups exposed to whole-body normothermia combined with CA and brain hypothermia/body normothermia plus CA. However, the group exposed to hypothermia/brain normothermia combined with CA exhibited higher neuroprotective effects against asphyxial CA injury, i.e. improved neurological deficit and neuronal death in the hippocampus compared with those involving whole-body normothermia combined with CA. In addition, neurological deficit and neuronal death in the group of rat exposed to brain hypothermia/body normothermia and CA were similar to those in the rats subjected to whole-body normothermia and CA. In brief, only brain hypothermia during CA was not associated with effective survival rate, neurological function or neuronal protection compared with those under body (but not brain) hypothermia during CA. Our present study suggests that regional temperature in patients during CA significantly affects the outcomes associated with survival rate and neurological recovery.     

浅低温对失血性休克早期血清乳酸及肝功能的影响

目的研究人工诱导浅低温对创伤性失血性休克兔早期复苏的影响。方法将SPF级健康新西兰大白兔20只,随机分为2组,浅低温组和常温组,每组10只。予乌拉坦麻醉后,采用肾动脉放血法并行小肠夹伤,建立出血未控制失血性休克兔模型。止血前分别将两组实验动物肛温控制在常温(38℃)或浅低温(34℃),顺序予以限制性液体复苏、止血、常压液体复苏并观察8h。期间在基础点(BL),休克起始点(T0),T120(T1),T240(T2),T360(T3),T480(T4)共6个时间点检测血清乳酸(LACT)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)浓度,以及终点时存活数、总输液量,并进行分析比较。结果 (1)实验终点时,浅低温复苏组存活兔(9/10只,生存时间477min)较常温复苏组(8/10只,生存时间461min)稍高,但无统计学意义(P0.05);(2)浅低温组T1~T4各时间点的血清乳酸ALT、AST均低于常温组(P0.05)。结论创伤性失血性休克早期应用浅低温治疗有利于抑制酸中毒进展及保护肝脏功能,其机制可能与低温能减轻休克导致的缺血再灌注损伤所引起的损害有关。     

Mild hypothermia protects against postischemic hepatic endothelial injury and decreases the formation of reactive oxygen species

The ability of mild hypothermia (MH; 34 degrees C) to protect against postischemic endothelial injury and decrease reactive oxygen species' (ROS) formation was studied using lucigenin and luminol enhanced chemiluminescence (CL). Lucigenin CL is largely specific for superoxide, while luminol reacts with many ROS. Isolated rat livers perfused under constant flow in a non-recirculating system were exposed to 2.5 h of ischemia after 0.5 h perfusion with Krebs-Henseleit buffer at either normothermia (38 degrees C) or mild hypothermia (34 degrees C) (n = 5, all groups). CL (cps), vascular resistance (Woods units), O2 consumption, and potassium efflux were measured at the end of perfusion, and at 0 min reperfusion, and every 30 min during reperfusion. For both the lucigenin and luminol groups, CL and vascular resistance increased significantly (repeat measures ANOVA, P <0.05) for normothermia (NT, 38 degrees C) but not mild hypothermia. Potassium efflux did not change significantly for the mild hypothermia groups. In the luminol enhanced group, oxygen consumption was greater in the mildly hypothermic group at 1 h and 1.5 h of reperfusion. Mild hypothermia decreased postischemic ROS production. Increased vascular resistance in the normothermia group may indicate an endothelial injury. Mild hypothermia appears to protect against this injury.     

Influence of glucocorticoids on the secretion of pancreatic juice in the rat

The influence of adrenalectomy and hydrocortisone treatment on the exocrine pancreatic secretion has been studied in anaesthetized rats. In the adrenalectomized animals Na+ administered in the saline solution provided for drinking was able to maintain standard sodium levels in serum. In these animals an increase of Na+ secretion in pancreatic juice was observed. Furthermore, the osmotic effect created by the increase in Na+ would account for the increase in pancreatic flow. In these adrenalectomized rats, an increase in K+ output is observed, which can be explained by the high K+ concentrations in serum. Likewise adrenalectomy decreased pancreatic enzyme secretion and produced a loss in weight of the organ that is accounted for by a lack of glucocorticoids. Hydrocortisone administration did not affect neither the secretion nor the weight of the pancreas of the control rats but the hormone proved to be effective in adrenalectomized rats producing a pancreatic secretion close to normal, balancing the secretory rate of water, Na+ and K+, completely restoring total protein secretion and the weight of the pancreas but amylase secretion in part only. It is therefore concluded that the weight of the pancreas and its exocrine secretion are clearly influenced by adrenalectomy and by substitution therapy with hydrocortisone. The administration of this hormone (25 mg.kg-1.day-1 along 6 days) did not affect intact animals.     

Investigations on isolated islets of Langerhans in vitro. XIII. Experiments concerning the preparation conditions with collagenase.

During the digestion of pancreatic pieces with collagenase for prepartion of isolated islets the enzymes in incubation medium (collangenolytic and/or proteolytic) can alter the secretion behavior of A- and B-cells. Insulin release after such an enzymatic attack is characterized by an enhanced basal secretion and a diminished and delayed glucose response. Overdigestion results in a decreased glucagon secretion in response to arginine, a diminished insulin content, and a decreased thiol-protein-disulfide-oxidoreductase activity of the islets. Increased albumin concentrations did not prevent the collagenase effect.     

Effects of moderate hypothermia on in situ cardiac sympathetic nerve endings

Although hypothermia is known to alter neuronal control of circulation, it has been uncertain whether clinically used hypothermia (moderate hypothermia) affects in situ cardiac sympathetic nerve endings. We examined the effects of moderate hypothermia on cardiac sympathetic nerve ending function in anesthetized cats. By use of a cardiac dialysis technique, we implanted dialysis probes in the midwall of the left ventricle and monitored dialysate norepinephrine (NE) levels as an index of NE output from cardiac sympathetic nerve endings. Hypothermia (27.0+/-0.5 degrees C) induced decreases in dialysate NE levels. Dialysate NE levels did not return to the control level at normothermia after rewarming. Dialysate NE response to inferior vena cava occlusion was attenuated at hypothermia but restored at normothermia after rewarming. Dialysate NE response to high K(+) (100 mM) was attenuated at hypothermia and was not restored at normothermia after rewarming. Hypothermia induced increases in dialysate dihydroxyphenylglycol (DHPG) levels. There were no differences in desipramine (neuronal NE uptake blocker, 10 microM) induced increment in dialysate NE level among control, hypothermia, and normothermia after rewarming. However, hypothermia induced an increase in DHPG/NE ratio. These data suggest that hypothermia impairs vesicle NE mobilization rather than membrane NE uptake. We conclude that moderate hypothermia suppresses exocytotic NE release via central mediated reflex and regional depolarization.     

Effects of hypothermia on rat brain pHi and phosphate metabolite regulation by 31P-NMR

The effects of arterial alphastat regulation on brain intracellular pH (pHi) and several phosphate metabolites were assessed in anesthetized rats during hypothermia (28.6 +/- 0.2 degrees C) and normothermia (36.2 +/- 0.2 degrees C) by using 31P high-field (8.5 T) nuclear magnetic resonance (NMR). There were significant differences in pHi and metabolite ratios at the two temperatures under conditions of equal minute ventilation. During hypothermia, the brain pHi was 0.09 U higher, the phosphocreatine-to-inorganic phosphate (PCR/Pi) ratio 49% larger, and Pi-to-ATP 20% lower than at normothermia. These changes were fully reversible on warming the animal. The change in brain pHi/temperature was -0.011U/degrees C (95% confidence interval -0.007 to -0.016). The brain's ability to regulate its pHi and phosphate metabolism during hypercapnic acid-base stress was studied by using 10% CO2 ventilation. Hypothermic rats showed a larger fall in brain pHi (0.145 +/- 0.01 U, 7.15-7.01) with 10% CO2 than normothermic rats (0.10 +/- 0.02 U, 7.06-6.96). Similarly ventilated rats had a larger fall in arterial pH with 10% CO2 at hypothermia (0.36 +/- 0.04 U) than normothermia (0.24 +/- 0.01 U), so the delta brain pH/delta arterial pH was the same at both temperatures. The brain PCr-to-Pi ratio decreased approximately 20% during 10% CO2 breathing in both hypothermic and normothermic animals. Brain pHi and metabolite ratios returned to base line 30-50 min after CO2 washout in both groups. In summary, lowering body temperature while maintaining constant ventilation leads to changes in brain pHi and metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischemia hypothermia improved contractility under normothermia reperfusion in the model of cultured cardiomyocyte

Though mild hypothermia displays an optimistic alleviation of contractive failure in the ischemia/reperfusion myocardium, we still lacked answers to many questions about its potential mechanisms. Our hypothesis is that hypothermia (32°C) induced in ischemia can ease mitochondrial injury resulting in improvement of myocardial contractility even under the condition of a normothermic reperfusion. Fifty newly born 1-2 d Sprague-Dawley rats were executed and the primary cardiomyocytes were obtained and cultivated in vitro. Myocytes were randomized into three groups and then subjected to ischemia either at 32°C or 37°C, both prior to undergoing reperfusion at 37°C. Contractility was presented as frequency and velocity. Ultrastructural alterations of cardiomyocytes and mitochondrion underwent semi-quantitative analysis with transmission electron microscopy and respiratory function of mitochondria was further assessed simultaneously. During cooling ischemia and following reperfusion, cardiomyocytes acquired a more immediate restoration to baseline level and had a significant difference as compared with those in normothermia (P < 0.05). Furthermore, hypothermia preserved the ultrastructure of myocytes and mitochondrion after ischemia. However, measurement on Heart Injury Score and form factor revealed no differences after 2-h reperfusion either in hypothermia or normothermia. On the contrary, the surface area and respiratory function of mitochondrion in reperfusion differed significantly in both groups (P < 0.05) which had an accordance with the variation on contractile performance. Hypothermia only induced in ischemia can bring contractility benefit even under a normothermia reperfusion in cultured cardiomyocytes.     

Mild hypothermia protects against postischemic hepatic endothelial injury and decreases the formation of reactive oxygen species

Abstract

The ability of mild hypothermia (MH; 34°C) to protect against postischemic endothelial injury and decrease reactive oxygen species' (ROS) formation was studied using lucigenin and luminol enhanced chemiluminescence (CL). Lucigenin CL is largely specific for superoxide, while luminol reacts with many ROS.

Isolated rat livers perfused under constant flow in a non-recirculating system were exposed to 2.5 h of ischemia after 0.5 h perfusion with Krebs-Henseleit buffer at either normothermia (38°C) or mild hypothermia (34°C) (n = 5, all groups). CL (cps), vascular resistance (Woods units), O₂ consumption, and potassium efflux were measured at the end of perfusion, and at 0 min reperfusion, and every 30 min during reperfusion.

For both the lucigenin and luminol groups, CL and vascular resistance increased significantly (repeat measures ANOVA, P <0.05) for normothermia (NT, 38°C) but not mild hypothermia. Potassium efflux did not change significantly for the mild hypothermia groups. In the luminol enhanced group, oxygen consumption was greater in the mildly hypothermic group at 1 h and 1.5 h of reperfusion.

Mild hypothermia decreased postischemic ROS production. Increased vascular resistance in the normothermia group may indicate an endothelial injury. Mild hypothermia appears to protect against this injury.     

Metabolic level and the function of the peripheral catecholaminergic systems in immobilization hypothermia in rats

Metabolic peculiarities were studied on the model of prolonged immobilization hypothermia in rats (body temperature +20 degrees C for 24 h). Stress reactions and the state of peripheral catecholaminergic systems were compared in hypo- and normothermia. A direct correlation was established between the intensity of metabolism and the mediator activity in adrenergic nerve structures.     

Changes in cardiovascular beta-adrenoceptor responses during hypothermia

The purpose of this study was to determine cardiovascular β-adrenergic responses during hypothermia. In the present study, we used isoproterenol (Iso), a nonselective, potent β-adrenoceptor agonist, well known for its positive chronotropic and inotropic pharmacologic actions at normothermia. Rats were instrumented to measure mean arterial pressure (MAP) and left ventricular (LV) pressure–volume changes using a Millar pressure–volume conductance catheter. Core temperature was manipulated from 37 (normothermia) to 24 °C (hypothermia) and back to 37 °C (rewarming) using both internal and external heat exchangers. During cooling at each temperature (33, 30, 27, and 24 °C), central hemodynamic variables and MAP were measured while intravenously infusing Iso (doses of 1.7, 5, 10, and 20 ng/min). Seven animals underwent all phases of the protocol. At normothermia Iso infusion resulted in a significant, dose-dependent increase in heart rate (HR), stroke volume (SV), cardiac output (CO), LV dP/dt_max (left ventricular maximum derivative of systolic pressure over time) but no change in MAP. During cooling Iso infusion caused no dose-dependent change in any of the hemodynamic variables. After rewarming, baseline HR and LV dP/dt_max were increased, whereas SV was significantly reduced when compared with their pre-hypothermic baseline values. This study shows that physiological cardiovascular responses mediated by the β-adrenoceptor are significantly diminished during core hypothermia.     

Neuroprotective effects of MK 801 and hypothermia used alone and in combination in hypoxic-ischemic brain injury in neonatal rats.

Although accumulating evidence suggests that increased extracellular glutamate concentrations may play an important role in hypoxic-ischemic brain injury, dopamine and other catecholamines also seem to be involved. The N-methyl-D-aspartate receptor antagonist MK 801 and moderate hypothermia (32-34 degrees C) are each known to be neuroprotective, but their combined effect on the release and metabolism of neurotransmitters is unknown. Seven-day-old pups (n: 150) underwent right common carotid artery ligation to induce hemispheric ischemia, and were later subjected to 120 minutes of hypoxia with 8% O2 and 92% N2O. Half the rats (Group I, n: 74) were subjected to normothermic conditions throughout the hypoxic period. Moderate hypothermia (30-32 degrees C) was induced in the other pups (Group II, n: 76) immediately after artery occlusion, and was maintained throughout the hypoxic period. Prior to inducing hypoxia, half of the rats in each group (Groups IA and IIA) received vehicle solution (0.9% NaCI) and the other rats (Groups IB and IIB) received MK 801 (0.5 mg/kg) subcutaneously at 45 and 120 minutes after occlusion. Intracerebral temperature was recorded every 15 minutes after occlusion. Infarct area (n: 40) was calculated after staining with 2% 2,3,5 triphenyltetrazolium chloride. Neuronal damage (n: 42) was assessed by quantifying CA1-CA3 neuronal loss at five hippocampal levels. The amount of damage to the monoamine system of the corpus striatum was determined based on the dopamine and 3,4 dihydroxyphenylacetic acid levels in the corpus striatum in both hemispheres (n: 46), as measured by high-pressure liquid chromatography and compared with normal control pups' values (n: 10). The normothermia/saline-treated pups had significantly larger infarct areas than the MK 801 only, hypothermia only, or MK 801/hypothermia combination groups. Neuropathological examination and striatal tissue monoamine data also confirmed marked neuronal damage in this group. Although MK 801 treatment alone resulted in significantly smaller infarct area and less tissue damage than was observed in the normothermia/saline-treated group, the moderate hypothermia and the MK 801/hypothermia combination treatment groups both exhibited better neuronal protection, especially in the corpus striatum. The rats that received combined treatment also had a significantly lower mortality rate.     

Extracorporeal circulation in the isolated in situ lamb placenta: hemodynamic characteristics.

Decreased placental perfusion and respiratory gas exchange have been observed after experimental fetal cardiopulmonary bypass (CPB). To better characterize placental hemodynamics during CPB, seven isolated in situ lamb placentas were placed on a CPB circuit by use of umbilical arterial and venous cannulation. Measures were taken to simulate normal placental hemodynamics. Perfusion flow rates were varied from 15 to 300 ml.min-1.kg fetal wt-1 during normothermia and hypothermia. Placental vascular resistance (PVR) remained constant when perfusion pressure and flow were varied above 40 mmHg and 150 ml.min-1.kg-1, respectively. Below these values, PVR varied inversely. This increase in PVR was more marked when CPB was performed with hypothermia than with normothermia. The clinical implication is that decreased placental flow and pressure on CPB may lead to a vicious cycle, resulting in further impairment of placental perfusion and respiratory gas exchange. Hypothermia promotes this impairment.     

"Paradoxical" effect of carbon dioxide on common carotid artery blood flow in rabbits during hypothermia and hyperthermia

The relative effects of temperature and CO2 on the blood flow in the common carotid artery (CCBF) were investigated in vagotomized, paralyzed rabbits under urethane-chloralose general anaesthesia with artificial ventilation. During hypothermia a 52% fall of CCBF was observed in rabbits ventilated by the classic method. Administration of a hyperkapnic mixture for breathing caused a further 16% CCBF fall, with a simultaneous rise in PaCO2 by 23%. During ventilation with a respirator triggered by phrenic nerve activity hypothermia caused a 30% CCBF fall without changes in PaCO2 value. Administration of the hyperkapnic mixture for breathing caused, in these circumstances, a 9% CCBF fall with a 7% PaCO2 increase. Hyperthermia caused during ventilation by the classic method a 42% rise in CCBF and a 22% PaCO2 rise. The hyperkapnic mixture given for breathing decreased the CCBF by 9% and increased the PaCO2 by 15%. On the other hand, during ventilation with the respirator triggered by phrenic nerve activity no changes were observed in these parameters. This suggests that the thermic stimulus exerts a direct effect on the regulation of the blood flow to the brain, and during hypothermia it prevails over the stimulus produced by CO2.