Oxygen consumption in adult and aged C57BL/6J mice during acute treadmill exercise of different intensity

Submaximal and maximal oxygen consumption was determined in untrained adult and aged male C57BL/6J mice during treadmill running. Each of 12-month-old (ADULT) and 24-month-old (AGED) male mice was tested on a motor-driven treadmill once at different speeds. VO₂ was measured before, during, and after exercise by means of indirect calorimetry in metabolic treadmill chambers. The resting VO₂ averaged 3064.67 ± 87.71 mL/kg/h for ADULT mice and 2472.95 ± 69.41 mL/kg/h for AGED mice. During exercise, VO₂ increased linearly with work intensity (running speed): ADULT mice-from 5908.06 ± 422.35 mL/kg/h at 3 m/min to 10861.99 ± 174.03 mL/kg/h at 25 m/min; AGED mice-from 5217.25 ± 263.26 mL/kg/h at 3 m/min to 7817.32 ± 290.28 mL/kg/h at 20 m/min. Further increase of the running speed resulted in a decline of VO₂ in ADULT and refusal to run in AGED mice. The results of this study demonstrated that in untrained C57BL/6J mice VO₂max and maximal exercise capacity declined with age. At the same absolute and relative workloads, VO₂ was lower in AGED mice.     

Nonshivering thermogenesis during acute cold exposure in adult and aged C57BL/6J mice

In C57BL/6J adult and aged mice, housed at room temperature (22.5 ± 1°C), we measured O₂ consumption and CO₂ production and calculated metabolic heat production under conditions of anesthesia and myorelaxation during acute cold stimulation when body temperature was lowered 7.5°C below control level. An independent group of mice was subjected to a three hour partial physical restraint at 6°C and concentration of uncoupling protein (thermogenin) was measured in interscapular brown adipose tissue mitochondria at different times after cold exposure. Heat production under anesthesia and myorelaxation was about 57–66% lower than in nonanesthetized conditions, but increased significantly during cold stimulation in both age groups. Under anesthesia and myorelaxation before and during cold stimulation aged mice produced about 20% more heat than adult mice. Because in these experiments all sources of facultative thermogenesis, except nonshivering, were suppressed by anesthesia and myorelaxation, and because brown adipose tissue is the major source of nonshivering thermoproduction, we concluded that aged mice housed at room temperature have an increased thermogenesis in brown adipose tissue. This conclusion was also supported by the finding that the concentration of uncoupling protein measured in the mitochondria of brown adipose tissue after single cold exposure was significantly higher in aged than in adult mice. Therefore, we propose that the lower, cold-induced, heat production typically observed in nonanesthetized aged mice may reflect reduced thermogenic capacity of skeletal muscles. While aged mice have less brown adipose tissue than adult animals, the remaining brown adipose tissue may compensate by increasing the concentration of uncoupling protein.     

The effect of exercise training in a cold environment on thermoregulation in adult and aged C57BL/6J mice

We studied the effect of exercise training in cold environment (six weeks of daily, one-hour runs on a treadmill at ambient temperature of 6 ± I°C at 60±65% of VO_2max) on cold-induced metabolic heat production, heat loss, and cold tolerance in adult and aged C57BL/6J male mice. In adult mice, exercise training in cold environment resulted in greater cold-induced heat production and cold tolerance without changes in heat loss, similar to the effects of daily cold exposure without exercise. In aged mice, daily cold exposures did not affect cold tolerance and cold-induced heat production, but exercise training in the cold resulted in greater cold-induced heat production and cold tolerance. Heat loss in aged mice increased similarly after both repeated cold exposures and exercise training in the cold. Therefore, mechanisms of effect of exercise training on cold tolerance are different in adult and aged animals. Exercise training in cold environment does not affect cold-induced heat production and cold tolerance in adult mice, but improves them in aged animals.     

Temperature effects on thyroid function in the lizard Sceloporus cyanogenys

The effects of chronic and acute cold temperature exposure on thyroid function were investigated in groups of adult lizards, Sceloporus cyanogenys. Some animals were placed in constant temperature chambers at 16°C for 2 wk prior to testing, while those exposed to acute cold were placed in a 4°C environment for 0.5 hr preceded by a 14-day acclimation period at 32°C. Various parameters of thyroid function were measured, including total thyroid ¹³¹I uptake, thyroxine synthesis, and protein-bound iodine. Pituitary-thyroid relationships in both thermal situations were indirectly determined by comparing hypophysectomized and/or TSH injected animals to controls. Chronic cold reduced thyroid activity while acute cold stress apparently stimulated pituitary TSH secretion. Though TSH could not increase oxygen consumption in tissue slices from cold-treated animals, injection of this hormone did cause thyroid hormone uptake by peripheral neurons under similar conditions. Furthermore, serum proteins seem to act as peripheral storage depots for thyroxine during periods of cold-induced inactivity. TSH can apparently free the protein-bound hormone under appropriate conditions. A discussion of the possible role of thyroxine in reptilian thermoregulation is included.     

Effect of age and salicylate on rectal temperature during heat exposure

Fischer 344, male rats (ages 8, 14, 28 months) were exposed for one hour to ambient temperatures of 21°, 32° and 38°C, 50% rh. The animals were treated with either 50 mg·kg⁻¹ of sodium salicylate or saline and rectal temperatures were determined at 0, 30 and 60 minutes of exposure. At 32° and 38°C, 50% relative humidity (rh), a significant rise in rectal temperature was observed in all saline treated animals. During the 38°C, 50% rh exposure, the 28-month old animals exhibited a significantly greater rise in rectal temperatures at 60 minutes of exposure than 8 and 14 month old animals. Salicylate treatment resulted in a significantly greater rise in rectal temperatures for the 28-month old than for the 8 and 14-month old animals at 30 and 60 minutes during a 38°C, 50% rh exposure. Comparing saline and salicylate treatment, the 28-month old salicylate treated animals had a significantly greater rise in rectal temperature at 30 and 60 minutes during the 32°C, 50% rh exposure. The 38°C, 50% rh exposure resulted in a significantly greater rise in rectal temperature for all three ages at 50 minutes of exposure. The 28-month old animals also exhibited significantly greater rectal temperatures at 30 minutes of exposure. It was concluded from these experiments that the thermoregulatory mechanism(s) of 28-month old animals exposed to a high ambient temperature is less effective than that of the younger 8 and 14-month old animals. Salicylate administrations may further stress the thermoregulatory mechanism(s) of the older animals.     

A longitudinal study of tolerance to cold stress among C57BL/6J mice

C57BL/6J male mice of different ages were movement-restricted and exposed to 10 degrees C for 3-hr periods every other week while colonic temperature was measured. A longitudinal trend in cold tolerance related to age and to initial colonic temperature was demonstrated. Adaptative thermoregulatory changes during cold exposure occurred during the first two tests. These were similar for all age groups except 30-month-old mice. There was no adaptation of colonic temperature during cold exposure among aged mice with repeated testing; however, their baseline colonic temperatures prior to testing increased after the first two tests. This finding suggests that old animals adjust to repeated cold stress differently than do younger mice. Specifically, younger animals are capable of adjusting their thermoregulatory response during cold stress with no change in baseline (pre-stress) temperature. Old animals do not modify the responses emitted during the stress; however, they do adapt by raising their baseline temperatures. Repeated cold exposure started later in life increased mortality among old animals but did not affect maximum lifespan.     

The effect of exercise training in cold on shivering and nonshivering thermogenesis in adult and aged C57BL/6J mice

To understand the mechanisms of improvement of cold-induced heat production in aged mice following exercise training, the relative contributions of shivering and nonshivering thermogenesis to cold-induced metabolic responses were assessed in adult and aged C57BL/6J male mice, which inhabited sedentarily at room temperature, or were subjected either to a regimen of moderate intensity exercise training at 6°C, or to sedentary repeated exposures to the same temperature. The main findings were that (1) aged mice had greater cold-induced nonshivering thermogenesis, but lower shivering than adult mice; (2) exercise training in a cold environment enhanced cold-induced nonshivering thermogenesis in adult mice, but suppressed it in aged animals; (3) exercise training in a cold environment increased shivering thermogenesis in both age groups, but this increase was much greater in aged mice; (4) the increase of cold-induced shivering thermogenesis was mainly responsible for increased cold tolerance in aged mice after exercise training in a cold environment.     

Cold acclimation-induced increase of systolic blood pressure in rats is associated with volume expansion

To investigate the mechanisms of cold-induced hypertension, the systolic blood pressure (SBP) and average daily water consumption were measured weekly in 6-month-old male Wistar rats; they were subsequently acclimated to thermoneutrality (26°C for 7 weeks), to cold temperature (6°C for 9 weeks), and then again reacclimated to 26°C for 5 weeks. Circulating plasma volume and whole blood viscosity were measured in subgroups of rats at the end of acclimation to 26°C after 2 days, after 1, 6, and 8 weeks of cold, and after 2 and 5 weeks of rewarming. The control values obtained at the end of thermoneutral period were: SBP = 130.8 ±18.6 mm Hg, plasma volume = 41.9 ± 4.64 mL/kg, whole body viscosity at shear rate of 22.5 per sec = 6.7 ± 0.48 cps, and daily water consumption = 42.25 ± 16.81 mL. After 48 h of cold exposure there was almost a 50% increase in plasma volume that persisted to a lesser degree throughout the whole period of cold exposure (P < .05). After 2 weeks of cold exposure the daily water consumption increased and SBP began to increase. After 6 weeks of cold exposure the SBP was 30 mm Hg above that of the control level (P < .001) and was accompanied by a 25% increase in whole blood viscosity (P < .05). At the end of 8 weeks of cold exposure the plasma volume was 56.8 ± 9.51 mL/kg and the whole blood viscosity was 8.0 ± 1.79 cps at the 22.5 per sec shear rate. During the 5 weeks of rewarming the elevation of SBP and increased whole blood viscosity persisted, whereas the increased daily water consumption and expanded plasma volume returned to normal. Therefore, the acclimation to cold is accompanied by the development of a volume-associated hypertension, which is sustained after rewarming without volume expansion.     

Metabolic heat production during repeated testing at 24 degrees C and 6 degrees C in adult and aged male C57BL/6J mice: the effect of physical restraint before cold stress

Adult (9-14 month) and aged (29-31 month) male C57BL/6J mice were subjected to 3 baseline tests (BASE), 3 cold tests (COLD), or 3 baseline immediately followed by cold tests (BASE/COLD). All tests consisted of partial restraint, and baseline tests were at 24 degrees C for 1 h while cold tests were at 6 degrees C for 3 h. All tests were started at 0900 and were repeated every 2 weeks. Mice were weighed before each test and colonic temperature, O2 consumption, and CO2 production were measured every 4 min for the duration of the test. Mean metabolic heat production during baseline and/or cold and slopes of colonic temperature over time during cold were calculated for each animal. Metabolic heat production at 24 degrees C in both BASE and BASE/COLD was the same in aged mice as adults, however, at degrees C BASE/COLD adult mice increased metabolic heat production compared to 24 degrees C, while aged mice produced a similar amount of heat at both 6 degrees C and 24 degrees C. When comparing metabolic heat production at 6 degrees C between COLD and BASE/COLD mice, adult COLD mice demonstrate an habituation to repeated cold exposure accompanied by increasing heat production, while BASE/COLD adults produce higher heat in all 3 cold exposures. The authors suggest that this is due to a priming of heat production in adults by restraint before the cold. In aged mice, neither COLD nor BASE/COLD groups demonstrate habituation, but BASE/COLD mice produce more heat than COLD during cold exposure, again indicating baseline priming of heat production. The data imply that aged mice have an impairment in specific cold-induced thermogenesis, while their abilities to produce heat in response to restraint-induced sympathetic activation remains intact.     

Reversible and irreversible glucose disposal in dogs: Influence of fasting and cold exposure

Rates of total glucose entry rate, irreversible loss, and recycling were measured in unanesthetized dogs with indwelling arterial and venous catheters. Four experimental conditions were selected: 16 or 26 hr of fasting and neutral (+25°C) or cold (?21°C) ambient temperatures. A mixture of U ¹⁴C-glucose and 2-³H-glucose was used as a tracer, according to the primed infusion technique. No matter what the ambient temperature was, increase of fasting time from 16 to 26 hr induced a slight, but nonsignificant, decrease in both the total glucose entry rate and the irreversible loss. At neutral ambient temperature, the amount of glucose promptly recycled was less after 16 hr than after 26 hr of fasting, while an opposite pattern was observed during cold exposure. Thus, that part of hepatic glucose entry promptly recycled was significantly increased from 22% (16 hr of fasting) to 31% (26 hr of fasting) at neutral ambient temperature. It remained almost unchanged (20% and 18%) in cold. It was, therefore, suggested that this increase might be considered as an compensatory mechanism, exerting a sparing effect on glucose utilization. This mechanism does not occur in cold ambient temperature, thus, worsening a possible shortage in glucose supply.     

Febrile temperatures control antineutrophil cytoplasmic autoantibody–induced neutrophil activation via inhibition of phosphatidylinositol 3‐kinase/Akt

Objective

Neutrophil activation by antineutrophil cytoplasmic autoantibodies (ANCAs) is central to the pathogenesis of the ANCA‐associated vasculitides. Febrile infections occur frequently during these diseases, often in the context of immunosuppressive treatment. Heat exposure may affect the underlying pathophysiologic processes of the vasculitis. In this study we tested the hypothesis that short‐term exposure to heat inhibits ANCA‐induced neutrophil activation.

Methods

After exposure to temperatures from 37°C to 42°C, human neutrophils were primed with either tumor necrosis factor α (TNFα) or granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and stimulated with monoclonal antibodies to myeloperoxidase or to proteinase 3. Respiratory burst activity was assayed using rhodamine and a nitroblue tetrazolium reduction assay. Specific inhibition experiments against p38 MAPK, ERK, and phosphatidylinositol 3‐kinase (PI 3‐kinase)/Akt, and Western blotting with phospho‐specific antibodies were used to identify key components in the antibody‐induced respiratory burst.

Results

A temperature‐dependent reduction in ANCA‐induced respiratory burst was observed over a range of heat exposures from 37°C to 42°C. Inhibition of human ANCA–induced neutrophil stimulation was significant at 40°C (after priming with 2 ng/ml TNFα, mean [± SEM] fluorescence intensity [MFI] 114 ± 12 at 37°C versus 53 ± 6 at 40°C; after priming with 20 ng/ml GM‐CSF, MFI 92 ± 16 at 37°C versus 35 ± 6 at 40°C; both P < 0.01). In the priming phase, the transient activation of the p38 MAPK, ERK, and PI 3‐kinase/Akt pathways by TNFα was blocked by prior exposure of the neutrophils to heat, but GM‐CSF–induced activation was unaltered by heat. However, in the second, antibody‐induced wave of kinase activation, exposure to heat inhibited only the PI 3‐kinase/Akt pathway, and these effects were independent of the priming agent used.

Conclusion

Short‐term spikes of modest heat abrogate ANCA‐induced activation of neutrophils via inhibition of PI 3‐kinase/Akt signaling. Febrile responses in ANCA‐mediated diseases may therefore have a physiologic purpose.

     

Effects of local heat and cold treatment on surface and articular temperature of arthritic knees

Objective. To evaluate and compare the effects of locally applied heat and cold treatments on skin and intraarticular temperature in patients with arthritis. Methods. Thirty-nine patients with arthritis of the knee were divided at random into 4 treatment groups (ice chips, nitrogen cold air, ligno-paraffin, and placebo short wave). A temperature probe was inserted into the knee joint cavity and another placed on the overlying skin, and changes in temperature over 3 hours were recorded for each treatment group. Results. The mean temperature of the surface of the skin dropped from 32.2°C to 16.0°C after application of ice chips and from 32.6°C to 9.8°C after application of nitrogen cold air; the mean intraarticular temperature decreased from 35.5°C to 29.1°C and from 35.8°C to 32.5°C, respectively, after these treatments. Treatment with ligno-paraffin increased the surface temperature by 7.5°C and the temperature in the joint cavity by 1.7°C. No significant changes were observed with placebo short wave diathermy. Conclusion. The traditional model, that intraarticular temperature is decreased by superficial heat and increased by superficial cold, must be discarded. In arthritis patients, intraarticular temperature is increased by superficial heat and decreased by superficial cold. This has clear consequences for treatment policy.     

Energy turnover and heat exchange in mature lean and obese Zucker rats acutely exposed to three environmental temperatures for 24 hours

Differences between lean (FA/?, n = 6) and obese (fa/fa, n = 6) mature male Zucker rats' energy turnover and heat storage were compared during a 24-h period when the animals were exposed to ambient temperatures of 30, 15 or 5 degrees C. Energy turnover was examined through measurements of heat production rates via indirect calorimetry and heat loss rates via direct calorimetry. Heat storage rates were calculated as the difference between heat production and heat loss rates. Predicted heat storage rates were also calculated as the product of the change in core temperature and the calculated specific heat of the animal based on body composition (carcass) analysis. A minimal heat loss rate was determined for each animal representing a period of least activity. Various comparisons were made: between groups (lean/obese), temperature (30, 15, 5 degrees C), calorimetry method (indirect/direct), period (light/dark), heat storage (experimental/predicted), and minimal heat loss. Immediately before a test, pretest weight and colonic temperature were obtained. Then, the animal was placed into the calorimeter chamber and remained there unrestrained for 24 h. Normal light/dark periods were maintained. On removal from the calorimeter, core temperature and body weight measurements were again obtained. Upon completion of all tests, body composition was analyzed and surface area determined. Energy turnover, i.e. both heat production and heat loss in the lean and obese animals differed among the 30, 15 and 5 degrees C exposures. The obese animals had relatively greater heat production rate and heat loss rate (kcal/day or kcal/kg (FFM)/day than the lean animals at 30, 15 and 5 degrees C. But, on a relative basis, the increments in heat production in the cold environments were greater for the lean animals. Both the lean and obese animals tended to be more active during the dark period when at 30 degrees C, but the difference was less at 15 degrees C and even less at 5 degrees C. Experimental heat storage rates did not differ significantly from predicted values at any of the temperatures with the possible exception of the animals at 5 degrees C. It was concluded that the mature obese Zucker rats had no major discernible defect in thermoregulation as revealed by rates of heat production and loss, although three of the obese rats did elicit a drop in colonic temperature during exposure to 5 degrees C, i.e. their excessive subcutaneous adiposity and thermal insulation did not prevent a fall in colonic temperature.(ABSTRACT TRUNCATED AT 400 WORDS)     

Simple adjuncts which maintain septal temperature below 20° C during ischemic arrest for coronary artery bypass grafting

One of the key elements of intraoperative myocardial protection is maintaining myocardial temperature below 20° C during ischemic arrest; however, many diverse techniques have been advocated to achieve this goal. One hundred and thirteen patients undergoing myocardial revascularization with one period of ischemic arrest were randomized: group A (n = 52) received continuous (150 to 200 cc/min) profound (4° C) topical hypothermia and group B (n = 61) received identical topical hypothermia plus one initial 500 cc aortic root bolus of cold (4° C) hyperkalemic cardioplegic solution. Perfusion technique was identical for both groups. The two groups were statistically indistinguishable when 30 preoperative and intraoperative characteristics were compared, including the distribution and number of vessels diseased, degree of left ventricle dysfunction, average number of coronary artery bypass grafts, aortic crossclamp times, and cardiopulmonary bypass times. Myocardial septal temperature (° C ± SD) was measured following each distal anastomosis. For group A the values were 29.6 ± 2.7° C for the first anastomosis, 24.4 ± 2.7° C for the second anastomosis, 20.8 ± 2.57° C for the third anastomosis, and 21.5 ± 3.3° C for the fourth anastomosis (p < 0.001). For group B the values were 18.7 ± 4.2° C for the first anastomosis, 17.5 ± 2.9° C for the second anastomosis, 16.7 ± 3.1° C for the third anastomosis, and 16.7 ± 3.1° C for the fourth anastomosis (p < 0.001). These data show that midseptal myocardial temperature can be reliably maintained below 20° C for up to 1 hour of ischemic arrest in patients undergoing coronary artery bypass grafting after one bolus of cold cardioplegia if: (1) perfusion flow and pressure are lowered, (2) venous drainage is maximized, and (3) supplemental topical hypothermia is assiduously carried out. Furthermore, myocardial temperature in group B was reduced more rapidly and remained significantly lower than that in group A. This simplified technique provides effective myocardial cooling without the complexities of multidose cardioplegia or profound systemic hypothermia.     

Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice

Aims/hypothesis

Adiponectin is an adipocyte-derived hormone that plays an important role in energy homeostasis. The main objective of this study was to investigate whether or not adiponectin regulates brown adipose tissue (BAT) activation and thermogenesis.

Methods

Core body temperatures (CBTs) of genetic mouse models were monitored at room temperature and during cold exposure. Cultured brown adipocytes and viral vector-mediated gene transduction were used to study the regulatory effects of adiponectin on Ucp1 gene expression and the underlying mechanisms.

Results

The CBTs of adiponectin knockout mice (Adipoq ^?/?) were significantly higher than those of wild type (WT) mice both at room temperature and during the cold (4°C) challenge. Conversely, reconstitution of adiponectin in Adipoq ^?/? mice significantly blunted β adrenergic receptor agonist-induced thermogenesis of interscapular BAT. After 10 days of intermittent cold exposure, Adipoq ^?/? mice exhibited higher UCP1 expression and more brown-like structure in inguinal fat than WT mice. Paradoxically, we found that the anti-thermogenic effect of adiponectin requires neither AdipoR1 nor AdipoR2, two well-known adiponectin receptors. In sharp contrast to the anti-thermogenic effects of adiponectin, AdipoR1 and especially AdipoR2 promote BAT activation. Mechanistically, adiponectin was found to inhibit Ucp1 gene expression by suppressing β₃-adrenergic receptor expression in brown adipocytes.

Conclusions/interpretation

This study demonstrates that adiponectin suppresses thermogenesis, which is likely to be a mechanism whereby adiponectin reduces energy expenditure.     

Ethanol Withdrawal: Altered Ambient Temperature Selection in Rats

Ethanol withdrawal in rats previously on an ethanol-containing diet for 6 wk resulted in prolonged (4–6 days) alteration in ambient temperature selection. When placed in a T-maze with a cold (2° C), a neutral (19° C), and a warm (30° C) alley, control and ethanol-imbibing animals chose to remain in the neutral alley. In contrast, during and up to 6 days after ethanol withdrawal, animals consistently preferred the warm alley of the T-maze. The withdrawal animals showed less locomotor activity, but lack of mobility, differences in body temperature, and direct disturbances in central monoamines probably were not responsible for the warm-alley preference. Impaired ambient temperature selection was less if animals were on the ethanol-containing diet for only 2 wk. It is suggested that longer lasting hormonal and/or metabolic derangements were possibly responsible for the impaired ambient temperature selection by animals undergoing withdrawal from ethanol.     

Delayed Thermoregulatory Changes in the Immature Rat Following a Single Injection of Ethanol

Adult rats exhibit rebound hyperthermia within 24 hr following a single injection of ethanol (EtOH). Tests were conducted to determine whether similar changes in thermoregulatory ability occur in the immature rat. Animals were administered saline or EtOH (4 g/kg BW; intraperitoneally) at 2 to 3, 8 to 9, or 14 to 15 days of age. Littermates were handled or left undisturbed with the dams to serve as controls. All rats were tested at 24 or 48 hr post-treatment to measure steady-state colonic temperature (Tco), tail skin temperature and metabolic rate (MR) at both thermoneutral and cold ambient temperatures (Tas). The youngest group exhibited no delayed change in body temperature or MR at 24 or 48 hr post-treatment with EtOH. Likewise, thermoregulatory ability of rats pretreated with EtOH at 8 or 9 or 14 to 15 days of age was not significantly different from controls when tested 24 hr post-treatment at thermoneutral Ta. In contrast, Tco of EtOH-treated rats in the two older age groups was 1 degree C above control level when tested 24 hr post-treatment at cold Ta. This Tco response can be explained by differences in heat transfer to the tail and MR. No altered response to cold Ta was found at 48 hr postinjection, indicating recovery from the EtOH effect. A single injection with EtOH at 2 to 15 days of age results in a change in Tco, which is dependent on postinjection time, age, and Ta.     

Analysis of heat generation during rotational atherectomy using different operational techniques

Rotational atherectomy can generate heat from the friction of the burr as it ablates atherosclerotic plaque. The objective of this study is to correlate Rotablator^® technique and heat generation using two experimental models. First, 2.0 mm burrs were advanced through a lesion model derived from bovine bone implanted with thermal probes. Intermittent ablation with minimal decelerations resulted in a smaller temperature increase than continuous ablation with maximal decelerations (2.6 ± 1.3 vs. 13.9 ± 1.0 °C, respectively, P< 0.01). The second model used porcine femoral arteries cradled in constricting polyethylene grafts with thermal probes in contact with the adventitia. As the burr advanced through the segment, RPM decreases of 5–7 k resulted in a temperature rise of 4.1 ± 1.2 °C, whereas decelerations of 10–20 k resulted in a 11.3 ± 6.2 °C temperature increase. We conclude that excessive drops in speed and aggressive advancement of the burr are related to significant increases in temperature and potential thermal injury. Cathet. Cardiovasc. Diagn. 44:453–455, 1998. © 1998 Wiley-Liss, Inc.     

Therapeutische Hypothermie nach Herz-Kreislaufstillstand

Clinical and experimental investigations have demonstrated, that induction of mild hypothermia following successful cardiopulmonal resuscitation (CPR) improves neurological outcome. Time course and duration to achieve target temperature are important factors that influence patient's outcome. In these patients important time for induction of therapeutic hypothermia will be lost by additional diagnostics, e.g. in heart catheter laboratory. Here we test a combined method to achieve target temperature for induction of therapeutic hypothermia after cardiac arrest. A total of 50 patients were examined after successful CPR. Twenty-nine patients received 4 °C cold infusions after arrival in the heart catheter laboratory. Retrospective data of twenty-one patients who received a volume substitute by means of drips at ambient temperature served as a control group. After admission to the ICU, both groups were immediately connected to an cooling device and were cooled to a target temperature of 33 °C (bladder temperature). The average temperature at admission did not differ in the two groups (35.5 ± 0.9 °C vs 35.89 ± 0.8 °C). In the group with initial cooling following 4 °C cold infusions, a significant temperature decrease could be reached during the invasive coronary diagnostics prior to admission to the ICU. Average chill duration to achieve the target temperature after admission was significantly shorter with the combined method. The period needed to achieve the target temperature after the beginning of the external cooling device with the group of the combined method was significantly shorter. The combined method with initial cooling with 4 °C cold solutions shows a very effective prestationary cooling procedure to introduce and realize mild hypothermia and offers the possibility to reach desired temperature significantly faster. Preclinical introduction of mild hypothermia by means of 4 °C cold solutions could be a beneficial step in the future treatment and probably affects the outcome of these patients     

Role of central angiotensin II receptors in cold-induced hypertension

BackgroundEarlier studies from this laboratory showed that central angiotensin II (AngII) receptors are upregulated by chronic cold exposure. The purpose of this study was to determine whether central AngII receptors may play a role in the development of cold-induced hypertension.MethodsFour groups of rats (six rats each) were used. Two groups were exposed to cold (5°C) and the other two groups were kept at 25°C. One cold-exposed and one warm-adapted group were treated chronically, via osmotic minipumps, with AngII type 1 (AT₁) receptor blocker (losartan, 6.0 μg/2.5 μL/h, intracerebroventricularly) at the beginning of cold exposure.ResultsSystolic blood pressure (BP) of the cold-exposed untreated group increased during week 1 of cold exposure and rose to 160 ± 4 mm Hg by week 4, whereas BP of the losartan-treated group in cold did not increase and remained at 121 ± 3 mm Hg. Cold-induced increases in drinking response to AngII, plasma renin activity, and urine norepinephrine output disappeared in the treated rats, indicating blockade of central AngII receptors. Withdrawal of losartan at 4 weeks resulted in an increase in BP of this group to the cold-exposed untreated level, which was accompanied by an increase in the above parameters. Significant increases in AngII-induced drinking response and hypothalamic AT₁ receptor mRNA content of the cold-exposed rats indicate upregulation of AngII receptors during chronic cold exposure. Hypothalamic AngII level was not affected by cold exposure.ConclusionUpregulation of brain AT₁ receptors plays a role in the development of cold-induced hypertension.