Hypothermic Rat Research Articles

Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs.

Victims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow. Isolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (PLW), which was based on body weight (BW) according to the formula: PLW = 0.0053 BW - 0.48 and presented as KfcPLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p < 0.05 considered as significant. Perfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, KfcPLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within the Constant flow group and between the groups at cessation of the experiments. In hypothermic rat lungs perfused at constant flow, fluid filtration coefficient per gram PLW and B/P ratio increased more than 10-fold concerted by increased hemoconcentration, but the changes were less in hypothermic lungs perfused at constant PPA.

Dielectric relaxation of normothermic and hypothermic rat corneas

This paper aims at the presentation of the results of in vitro research on the dielectric properties of the cornea specimen collected from the rats subjected to in vivo hypothermia.The average values of the relative permittivity and dielectric loss are about 40% higher for the hypothermic cornea than those for the normothermic tissue at the same water content of 12% for both samples and at 25°C. Whereas, at 50°C this effect of increase in the dielectric properties of the hypothermic cornea when compared to the normothermic one is observed clearly only in the relative permittivity of about 19%. In the temperature range of 25–50°C, the activation energy of conductivity associated with the release of loosely bound water takes the average values of 45kJ/mol and 30kJ/mol for the normothermic and hypothermic corneas, respectively. The study provided information on dielectric polarization and conductance mechanisms in the cornea which may be helpful in interpreting clinical results of human cornea examination, currently obtained by means of such electrodiagnostic methods as conductive keratoplasty, electroretinography or electrooculography.

Short-Term Effects of Hypothermia on Axonal Injury, Preoligodendrocyte Accumulation and Oligodendrocyte Myelination after Hypoxia-Ischemia in the Hippocampus of Immature Rat Brain

Hypothermia is known to improve neurological recovery of animals and humans exposed to hypoxic-ischemic (HI) injury. However, the underlying mechanisms of the neuroprotective effects of hypothermia are only partially understood, including decreased excitotoxicity and apoptosis, and suppressed inflammation. There are few studies about the hypothermic effects on axonal injury and oligodendrocyte (OL) lineage degeneration, which are important components of neonatal brain injuries that cause cognitive disability. We hypothesized that mild hypothermia would reduce axonal injury and increase myelination in the hippocampus after HI. We performed left carotid artery ligation followed by 8% oxygen for 2 h in 7-day-old rats. Animals were divided into a hypothermic group (rectal temperature 32-33°C for 24 h) and a normothermic group (36-37°C for 24 h) immediately after HI. Animals were sacrificed at 1, 3 and 7 days for immunohistochemistry or Western blot analysis. We detected neuron loss by microtubule-associated protein 2 labeling and axonal injury by non-phosphorylated neurofilament (SMI32) with neurofilament 200 (NF200) double staining. We examined early OL progenitors by A2B5 or NG2, preoligodendrocytes (preOLs) by O4, and mature OLs by 2,3-cyclic nucleotide 3-phosphodiesterase (CNPase) and glutathione S-transferase (GST)-pi staining. Apoptosis was studied by active caspase-3. Hypothermia was associated with a significant elevation of neurons and axons in the hippocampal CA1 region after HI. Early OL progenitors (A2B5⁺) were elevated, but preOLs (O4⁺) and active caspase-3 were dramatically reduced in the hypothermic rat brain. Further study showed that the apoptotic rate of preOLs (caspase-3⁺-O4⁺/O4⁺) was markedly attenuated by hypothermic treatment compared to normothermic animals. The immunoreactivity of CNPase and GST-pi and the protein level of the myelin basic protein significantly increased in the hippocampus of hypothermia-treated rat brain. Axonal myelination also increased in hypothermic animals, which were tested by myelin basic protein and NF200 double staining and electron microscopy. These results showed that hypothermia reduced HI damage to axons and OL myelination coincided with increased early OL progenitor proliferation and decreased preOL accumulation and apoptosis. This study suggested new aspects that may contribute to elucidate the mechanism of hypothermic neuroprotection in neonatal rat brain.

Dielectric properties of hypothermic rat artery

The temperature and frequency dependencies of the dielectric parameters for the rat artery are used to analyse effects of hypothermia on this tissue. Measurements were performed over the frequency range 500Hz to 100kHz and at temperatures from 19 to 60°C. The artery samples contained about 12% water by mass at room temperature at a relative humidity of 70%. The frequency dependencies of the loss tangent for the control, mild hypothermic and moderate hypothermic artery exhibit two peaks at 2kHz and 35kHz in the α-dispersion region. The results were discussed in terms of the distribution of relaxation frequencies and the activation energy for the conduction and polarization mechanisms particularly in the elastin–water and collagen–water systems. The knowledge about dielectric behavior of the hypothermic rat artery in vitro is important due to clinical application of local and systemic hypothermia.

Noninvasive and Three-Dimensional Imaging of CMRO2 in Rats at 9.4 T: Reproducibility Test and Normothermia/Hypothermia Comparison Study

Ability to image cerebral metabolic rate of oxygen (CMRO(2)) is essential for studying the fundamental role of oxidative metabolism in brain function and disease. We have demonstrated recently that three-dimensional (3D) CMRO(2) images can be obtained in the rat brain during a 2-min (17)O(2) inhalation using the (17)O MR spectroscopic imaging (MRSI) approach at high field. The feasibility for establishing a completely noninvasive approach for imaging CMRO(2) has also been demonstrated. In this study, we further explored the feasibility of (17)O MRSI approach for performing repeated CMRO(2) measurements within a short period of time and evaluated the reproducibility of the repeated measurements. Subsequently, we applied the (17)O MRSI approach to measure CMRO(2) and cerebral blood flow (CBF) values at two brain temperatures in the alpha-chloralose anesthetized rat brain at 9.4 T. Finally, we tested the validity of simplified model for noninvasively determining CMRO(2) in normothermic and hypothermic rat brain. The results show (i) an excellent reproducibility among repeated measurements of 3D CMRO(2) images under the same physiologic condition; (ii) a 44% decrease of CMRO(2) across the rat brain at mild hypothermic (32 degrees C) condition as compared with normothermic (37 degrees C) condition; and (iii) a close correlation between CMRO(2) and CBF within a relatively wide physiologic range. This study demonstrates the capability of (17)O MRSI approach for noninvasively imaging CMRO(2) and its changes caused by physiologic perturbation. This approach, thus, should provide a promising neuroimaging modality for studying oxidative metabolism and bioenergetics associated with brain functions and diseases.

Hypothermia Affects Translocation of Numerous Cytoplasmic Proteins Following Global Cerebral Ischemia

Using a decapitation ischemia model, we studied translocation of proteins to and from the cytosol in normothermic (NT) and hypothermic (HT) rat brains. 2D gel analysis identified 74 proteins whose cytosolic level changed significantly after 15 min of ischemia. HT preserved the cytosolic levels of several glycolytic enzymes, as well as many plasticity related proteins, otherwise decreased following NT ischemia. The levels of redox-related proteins was lower in HT than in NT. Our results indicate that translocation of proteins to and from the cytosol is an important issue during ischemia.

Evaluation of preservation solutions by ESR-spectroscopy: Superior effects of University of Wisconsin over Histidine–Tryptophan–Ketoglutarate in reducing renal reactive oxygen species

Despite the causative role of oxidative stress in renal ischemia-reperfusion (I-R) injury effects of preservation solutions on reactive oxygen species (ROS) release have not been sufficiently evaluated. We compared the effects of most common solutions in kidney transplantation, University of Wisconsin (UW) and Histidine-Tryptophan-Ketoglutarate (HTK). ROS formation in isolated perfused rat kidney was detected by electron spin resonance spectroscopy using spin label 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Donor kidneys from Lewis rats were pretreated with saline (controls), in therapeutic groups, kidneys underwent 18 h of cold storage (CS) preserved by HTK or UW solution. Experimental protocol included a stabilization period followed by additional I-R. Kidneys preserved by HTK produced highest ROS values in the control period after CS, whereas levels in UW and control group did not vary significantly. A peak release induced by additional I-R was also significantly highest in HTK kidneys, and UW did not differ from controls. During reperfusion, levels in HTK exceeded control and UW values. Renal vascular resistance, caspase-3-activity, and tissue hydration were enhanced in HTK compared with UW group, whereas ATP concentration was less reduced in UW-preserved tissue. These data show the greater antioxidative potential of UW solution, which also attenuated organ impairment after CS in the early reperfusion period.

Taurine prevents myocardial ischemia/reperfusion-induced oxidative stress and apoptosis in prolonged hypothermic rat heart preservation

Taurine (2-aminoethanesulfonic acid) is a potent antioxidant and inhibits cell apoptosis in ischemic reperfusion injury. In this study we evaluated whether addition of taurine to St. Thomas' cardioplegic solution enhances its myocardial protective effects in prolonged hypothermic heart preservation in rats. Hearts isolated from male Sprague-Dawley rats were mounted on a Langendorff apparatus to estimate baseline cardiac function, then arrested and stored in St. Thomas' cardioplegic solution, with taurine (10 mM; taurine group, n = 8) or without taurine (control group, n = 8), for 6 h at 4 degrees C. After storage, the hearts were reperfused and heart rate (HR), coronary flow (CF), left ventricular developed pressure (LVP), and positive maximum left ventricular developing pressure (max LV dp/dt) were measured. The LV tissue was examined immunohistochemically for determining DNA oxidative stress and cell apoptosis. Compared with control groups, recovery of LVP (P < 0.001), max LV dp/dt (P < 0.001), and coronary flow (P < 0.001) were significantly enhanced, whereas glutamic oxaloacetic transaminase (P < 0.01), lactate dehydrogenase (P < 0.05), creatine phosphate kinase (P < 0.01), 8-hydroxy-2'-deoxyguanosine index (P < 0.01), caspase-3 mRNA expression (P < 0.05), and percentage of TUNEL-positive cardiomyocytes (P < 0.05) were reduced in the taurine group. Addition of taurine to St. Thomas' cardioplegic solution improved cardiac function recovery for prolonged hypothermic rat heart preservation by suppressing DNA oxidative stress and cell apoptosis.

Oxygenation during hypothermic rat liver preservation: An in vitro slice study to demonstrate beneficial or toxic oxygenation effects

Hypothermic machine perfusion (HMP) of abdominal organs is shown to be superior compared to cold storage. However, the question remains if oxygenation is required during preservation as oxygen is essential for energy resynthesis but also generates toxic reactive oxygen species (ROS). To determine if oxygenation should be used during HMP, urea-synthesis rate, adenosine triphosphate (ATP), and generation of ROS were studied in an in vitro model, modeling ischemia-reperfusion injury. Furthermore, expression of uncoupling protein-2 (UCP-2) mRNA was assessed since UCP-2 is a potentially protective protein against ROS. Rat liver slices were preserved for 0, 24, and 48 hr in University of Wisconsin machine perfusion solution (UW-MP) with 0%, 21%, or 95% oxygen at 0-4 degrees C and reperfused for 24 hours. In the 0% and 95% groups, an increase of ROS was found after cold storage in UW-MP. After slice reperfusion, only the 0% oxygen group showed higher levels. The 0% group showed a lower urea-synthesis rate as well as lower ATP levels. mRNA upregulation of UCP-2 was, in contrast to kidney mRNA studies, not observed. In conclusion, oxygenation of UW-MP gave better results. This study also shows that ROS formation occurs during hypothermic preservation and the liver is not protected by UCP-2. We conclude that saturation of UW-MP with 21% oxygen allows optimal preservation results.

Supplementation of Nucleoside-Nucleotide Mixture Enhances Functional Recovery and Energy Metabolism Following Long-Time Hypothermic Heart Preservation

OG-VI, a well-balanced mixture of nucleoside and nucleotides, has been demonstrated to have a favorable effect on energy metabolism. In this study, we tested the hypothesis that addition of OG-VI to the University of Wisconsin solution can improve the cardiac functional recovery following long-time hypothermic preservation. Forty-two male Wistar rats were randomized into four groups. After 30-min of isolated working heart perfusion, the rat hearts were arrested with St. Thomas cardioplegic solution and preserved at 4 degrees C in saline, OG-VI, UW, and UW+OG-VI, respectively. After 12-h of preservation, the hearts were reperfused for 60-min during which the recovery of cardiac functions were monitored continuously. Myocardial adenine nucleotides were analyzed using high-performance liquid chromomatograph. In the UW+OG-VI group, the recovery of cardiac output, coronary flow, aortic flow, rate-pressure product, left ventricle stroke volume, and stroke work were significantly higher than other groups (P < 0.05). Furthermore, all phosphate high-energy compounds were significantly higher in the UW+OG-VI group than in the other groups (P < 0.05). Coronary vascular resistance and myocardial wet/dry weight ratio were obviously lower in the UW+OG-VI group, compared to the other groups (P < 0.05). Heart function was better recovered when nucleoside-nucleotide mixture was added to UW solution during long-time hypothermic rat heart preservation. The mechanism is not totally clear, but enhancement of high-energy phosphate production is possible.

Electrical bioimpedance measurement during hypothermic rat kidney preservation for assessing ischemic injury

Non-heart-beating donors sustain an ischemic insult of unknown severity and duration, which can compromise the viability of the graft. This preliminary study aimed to assess whether electrical bioimpedance monitoring of cold preserved organs could be useful to identify kidneys that have suffered previous warm ischemia (WI). Two rat groups were studied during 24 h of preservation in University of Wisconsin solution (UW): a control cold ischemia group and another group subjected previously to 45 min of WI. Multi-frequency bioimpedance was monitored during preservation by means of a miniaturized silicon probe and the results were modeled according to the Cole equation. Tissular ATP content, lactate dehydrogenase in UW solution and histological injury were assessed. Renal function and cell injury, evaluated during 3 h of ex vivo reperfusion using the isolated perfused rat kidney model, demonstrated differences between groups. Bioimpedance results showed that the time constant and the high frequency resistivity parameters derived from the Cole equation were able to discriminate between groups at the beginning of the preservation (Δ τ ∼ 78%, Δ R ∞ ∼ 36%), but these differences tended to converge as preservation time advanced. Nevertheless, another of the Cole parameters, α, showed increasing significant differences until 24 h of preservation (Δ α ∼ 15%).

Comparison of University of Wisconsin, Euro-Collins, low-potassium dextran, And Krebs-Henseleit solutions for hypothermic lung preservation

Objective: We sought to test the effectiveness of 4 different solutions for hypothermic rat lung preservation. Methods: One hundred ninety-two rats were used. The rats were divided into 4 groups, and University of Wisconsin, Euro-Collins, low-potassium dextran, or Krebs-Henseleit solution was used in each group. They were further divided into 6 subgroups of 8 rats each. The lungs were preserved at 4°C for 0, 4, 6, 8, 12, or 24 hours, respectively, and lung function was studied by using a living rat perfusion model. Results: Pulmonary arterial flow decreased in each group after 4 to 6 hours of preservation; the low-potassium dextran group decreased the least and the Krebs-Henseleit group decreased the most. Pulmonary vascular resistance increased in each group after 6 hours of preservation; the Krebs-Henseleit group increased the most. Although airway pressure increased, static lung compliance and gas exchange capacity decreased after 8 hours of preservation; the Krebs-Henseleit group exhibited the worst values. Lung tissue wet/dry weight ratio increased gradually during preservation; the University of Wisconsin group exhibited the least increase. An ultrastructural study indicated the least morphologic changes in the low-potassium dextran group at 24 hours. Conclusions: At 4°C, all solutions preserved rat lungs for 4 hours with acceptable function. However, 6 hours of preservation resulted in damaged pulmonary function in some lungs, and this damage increased when preservation time was extended. The lungs preserved in low-potassium dextran solution had the best overall function, but the lungs preserved in University of Wisconsin solution had less edema. (J Thorac Cardiovasc Surg 2000;119:921-30)

Fructose-1,6-diphosphate and a glucose-free solution enhances functional recovery in hypothermic heart preservation

Background Fructose-1,6-diphosphate (FDP) has been shown to protect tissue during hypoxia under various ischemic conditions, including isolated heart perfusion. We tested the hypothesis that adding FDP to St. Thomas solution can extend hypothermic heart preservation time. Methods Sixteen adult Sprague-Dawley rats were used. Under general anesthesia, the hearts were removed and preserved at 4°C in St. Thomas solution (30 ml/kg) for 12 hours. FDP (5 mM) was added to the St. Thomas solution in the study group ( n = 8), whereas no FDP was used in the control group ( n = 10). The hearts were reperfused after 12 hours of preservation using a working heart model. Results In the study group, cardiac output ranged from 13.00 ± 2.34 to 17.66 ± 1.71 ml/min, maximum aortic flow was 3.40 ± 1.99 to 9.26 ± 1.72 ml/min, left ventricular stroke volume ranged from 0.074 ± 0.014 to 0.092 ± 0.009 ml, left ventricular stroke work ranged from 6.22 ± 0.39 to 7.95 ± 0.44 ml/mmHg, and maximum left ventricular generated power was 14.38 ± 2.94 to 20.16 ± 2.49 Joules/min. All of these parameters were higher than those in the control group ( p < 0.001). Coronary vascular resistance and myocardial tissue wet/dry weight ratio were lower in the study group than in the control group ( p < 0.05). Conclusions Heart function was better preserved when FDP was added to St. Thomas solution during hypothermic rat heart preservation. The mechanism is not totally clear, but enhancement of high-energy phosphate production during ischemia is possible. Key words: heart, procurement, hypothermia, fructose-1,6-diphosphate.

Enhancement of Hypothermic Heart Preservation with Fructose 1,6-Diphosphate

Background. We hypothesized that the addition of fructose 1,6-diphosphate (FDP) to a hypothermic heart preservation solution could improve metabolic recovery because it has several beneficial effects.Materials and Methods. Twenty adult Sprague-Dawley rats were used to study hypothermic heart preservation. The hearts were removed under general anesthesia and preserved at 4°C in Euro-Collins solution (30 ml/kg) for 8 h. In the study group (N = 10), FDP (5 mM) was added to the Euro-Collins solution. In the control group (N = 10), no FDP was added. Heart function was studied after preservation using a working heart model. The ability of various concentrations of fructose 1,6-phosphate to passively diffuse through an egg phosphatidylcholine multilamellar vesicle (MLV) membrane bilayer was examined.Results. Cardiac output ranged from 17.0 ± 1.9 to 24.9 ± 1.6 ml/min in the study group vs 2.0 ± 1.0–12.3 ± 1.7 ml/min for controls, average aortic flow was 10.8 ± 1.4 ml/min in the study group vs −1.3 ± 1.6 ml/min for controls, and maximum LV generated power was 22.8 ± 1.7 J/min vs 10.1 ± 1.6 J/min for controls. Coronary flow, left ventricular stroke volume and stroke work, and myocardial oxygen consumption were much higher in the study group than in the control group. Coronary vascular resistance was lower in the study group than in the control group. Electron microscopic study indicated that many myocytes displayed patches of swollen mitochondria in the control group, but was rarely observed in the study group. The addition of 50 mM FDP caused substantial changes in MLV permeability. No dose of sucrose buffers outside the vesicles resulted in a significant changes of MLV permeability.Conclusions. Our results indicate that the addition of FDP to Euro-Collins solution significantly improves hypothermic rat heart preservation, and FDP appeared to cross the membrane bilayer.

Measurements of mitochondrial K+ fluxes in whole rat hearts using 87Rb-NMR.

The rubidium efflux from hypothermic rat hearts perfused by the Langendorff method at 20 degreesC was studied. At this temperature 87Rb-NMR efflux experiments showed the existence of two 87Rb pools: cytoplasmic and mitochondrial. Rat heart mitochondria showed a very slow exchange of mitochondrial Rb+ for cytoplasmic K+. After washout of cytosolic Rb+, mitochondria kept a stable Rb+ level for >30 min. Rb+ efflux from mitochondria was stimulated with 0.1 mM 2, 4-dinitrophenol (DNP), by sarcolemmal permeabilization and concomitant cellular energy depletion by saponin (0.01 mg/ml for 4 min) in the presence of a perfusate mimicking intracellular conditions, or by ATP-sensitive K (KATP) channel openers. DNP, a mitochondrial uncoupler, caused the onset of mitochondrial Rb+ exchange; however, the washout was not complete (80 vs. 56% in control). Energy deprivation by saponin, which permeabilizes the sarcolemma, resulted in a rapid and complete Rb+ efflux. The mitochondrial Rb+ efflux rate constant (k) decreased in the presence of glibenclamide, a KATP channel inhibitor (5 microM; k = 0.204 +/- 0.065 min-1; n = 8), or in the presence of ATP plus phosphocreatine (1.0 and 5.0 mM, respectively; k = 0.134 +/- 0.021 min-1; n = 4) in the saponin experiments (saponin only; k = 0.321 +/- 0.079 min-1; n = 3), indicating the inhibition of mitochondrial KATP channels. Thus hypothermia in combination with 87Rb-NMR allowed the probing of the mitochondrial K+ pool in whole hearts without mitochondrial isolation.

Observation of Two Inorganic Phosphate NMR Resonances in the Perfused Hypothermic Rat Heart

The effect of hypothermia on isolated perfused rat hearts was studied with31P NMR. Hearts were continuously perfused with phosphate-free Krebs–Henseleit buffer while the perfusate temperature was adjusted. Perfusate pH was kept at 7.40 ± 0.02 throughout the experiments. Using the chemical shift difference between PCr and Pithe intracellular pH was estimated. At 36, 20, and 10°C a cytosolic alkalinization at a pH of 7.05 ± 0.04, 7.21 ± 0.05, and 7.40 ± 0.03 was observed, respectively. At 10°C two Piresonances were observed with a separation of 0.25 ppm. This resonance corresponded to a Piresonance of a cellular compartment with a local pH of 7.78 ± 0.06, likely mitochondrial. This additional resonance disappeared upon warming of the hearts back to 36°C.

Effect of low temperature on the cytosolic free Ca 2+ in rat ventricular myocytes

The effect of low temperature on the cytosolic free Ca 2+ ([Ca 2+] i) has been inventigated in isolated ventricular myocytes from adult rats using the fluorescent probe Indo-1. The distribution of Indo-1 between the mitochondrial and cytoplasmic compartments was first determined in the isolated myocytes using the digitonin and Triton X-100 treatments. By subtracting the mitochondrial [Ca 2+] i from the total [Ca 2+] i measured with Indo-1, the average cytosolic [Ca 2+] i was found to increase significantly ( P < 0.05) from 189 nM to 255 and 297 nM when the temperature was decreased from 37°C to 15° and 5°C, respectively. A marked increase in cytosolic [Ca 2+] i to a new steady state level was observed when the membrane of myocytes was depolarized by 60 mM KCl; the average magnitude of increase being 110, 243 and 186 nM, at 37°, 15° and 5°C respectively. Our results support the hypothesis that the cardiac arrhythmia typically observed in the hypothermic rat is due to an increased cytosolic [Ca 2+] i with decreasing body temperature.

ラット胃粘膜に対するＧＡＢＡ誘導体（Ｂａｃｌｏｆｅｎ）の潰よう惹起作用

The ulcerogenic action of baclofen, a lipophilic derivative of GABA, was studied in the urethane anesthetized rat in relation to body temperature. Baclofen at the doses of 2, 4 and 8 mg/kg, s.c. induced gastric ulceration in a dose-dependent manner in the hypothermic (body temperature: 28-30 degrees C) rat. Duodenal ulcers were also observed in about 80% of the hypothermic animals treated with the highest dose of baclofen. Baclofen, even at 8 mg/kg, s.c., however, failed to induce gastric ulceration in the normothermic (body temperature: 37-38 degrees C) rat. Histamine, at the secretagogue dose causing acid secretion as potently as 8 mg/kg of baclofen, induced gastric ulcers in both the hypothermic and the normothermic rats. These results indicate that the ulcerogenic effect of baclofen is closely related to the thermoregulation mechanism and may provide important clues for clarifying the pathophysiology of gastroduodenal ulcers induced by hypothermic treatments such as water-immersion stress ulcers or cold exposure ulcers.

Coronary autoregulation and metabolism in hypothermic rat and ground squirrel hearts.

An isovolumic Langendorff preparation was used to perfuse rat and ground squirrel (Spermophilus tridecemlineatus) hearts at 37, 27, 17, and 7 degrees C. Perfusion pressure (PP) was randomly increased or decreased (40, 60, 70, 110, 120, or 140 mmHg) from a control PP of 90 mmHg. Coronary flow (CF) was measured immediately after each PP change (initial CF) and after stable flow was observed (final CF). Compared with initial flow, final CF was decreased at high PPs or increased at low PPs (autoregulation) in hearts from both species, but rat hearts did not autoregulate CF or develop left ventricular systolic pressure (LVSP) at 7 degrees C. Squirrel hearts generated LVSP at all temperatures and perfusion pressures. LVSP and initial CF were proportional to PP in both species, but squirrel heart LVSP was independent of PP at 7 degrees C. Myocardial O2 consumption (MVO2) was highly correlated with CF in all hearts at 37 degrees C but not at lower temperatures. Squirrel hearts were more efficient (MVO2 vs. HR X LVSP) than rat hearts at low temperatures but less efficient at 37 degrees C. The intrinsic temperature adaptations displayed by squirrel hearts would support continued myocardial function when body temperature and blood pressure fluctuate throughout the stages of hibernation.

Acute thermoregulatory responses of the immature rat to warming by low-level 2,450-MHz microwave radiation.

Rats were tested at 6-7 days of age to determine thermoregulatory responses to microwave exposure (2,450-MHz; continuous wave). Each animal was partially restrained in a cylindrical holder and irradiated at a power density of either 5 or 20 mW/cm2 [specific absorption rate = 0.60 (W/kg)/(mW/cm2)] at a cold ambient temperature (Ta). Following a 1-hour thermal equilibration period, each rat was monitored at 1-min intervals during 1-hour microwave exposure and 1-hour recovery periods. Colonic temperature (Tco), determined with a Vitek probe, and metabolic heat production (M), derived from measures of oxygen consumption, were sampled and recorded during these periods. Tco increased significantly above initial level at both power densities and reached a plateau after 45 min of microwave exposure. Tco doubled with a four-fold increase in microwave intensity. Prior to exposure, M was elevated in response to cold Ta and remained unchanged during exposure at 5 mW/cm2, but decreased 7.2 W/kg during exposure at 20 mW/cm2. The results indicate that the hypothermic rat pup can be effectively warmed by low-level microwave irradiation and is capable of altering metabolism in response to such heating.