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PubMed2000

Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: A case-control study: the Copenhagen Stroke Study.

BACKGROUND AND PURPOSE: Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients with acute stroke. METHODS: We prospectively included 17 patients (cases) with stroke admitted within 12 hours from stoke onset (mean 3.25 hours). They were given hypothermic treatment for 6 hours by the "forced air" method, a surface cooling method that uses a cooling blanket with a flow of cool air (10 degrees C). Pethidine was given to treat compensatory shivering. Cases were compared with 56 patients (controls) from the Copenhagen Stroke Study matched for age, gender, initial stroke severity, body temperature on admission, and time from stroke onset to admission. Blood cytology, biochemistry, ECGs, and body temperature were monitored during hypothermic treatment. Multiple regression analyses on outcome were performed to examine the safety of hypothermic therapy. RESULTS: Body temperature decreased from t(0)=36.8 degrees C to t(6)=35.5 degrees C (P:<0.001), and hypothermia was present until 4 hours after therapy (t(0)=36.8 degrees C versus t(10)=36.5 degrees C; P:=0.01). Mortality at 6 months after stroke was 12% in cases versus 23% in controls (P:=0. 50). Final neurological impairment (Scandinavian Stroke Scale score at 6 months) was mean 42.4 points in cases versus 47.9 in controls (P:=0.21). Hypothermic therapy was not a predictor of poor outcome in the multivariate analyses. CONCLUSIONS: Modest hypothermia can be achieved in awake patients with acute stroke by surface cooling with the "forced air" method, in combination with pethidine to treat shivering. It was not associated with a poor outcome. We suggest a large, randomized clinical trial to test the possible beneficial effect of induced modest hypothermia in unselected patients with stroke.

Acute Disease↗
PubMed1994

Tepid sponging to reduce temperature in febrile children in a tropical climate.

The effectiveness of tepid sponging, in addition to antipyretic medication, in the reduction of temperature in febrile children living in a tropical environment, was assessed in a prospective, randomized, open trial. Seventy-five children aged between 6 and 53 months who attended the casualty department of the Children's Hospital, Bangkok, Thailand, with fever (rectal temperature > or = 38.5 degrees C) of presumed viral origin were randomized to received either tepid sponging and oral paracetamol (sponged group) or paracetamol alone (control group). Rectal temperature and the occurrence of crying, irritability, and shivering were recorded over the following 2 hours. A greater and more rapid fall in mean rectal temperature occurred in the sponged group than in the control group. Temperature fell below 38.5 degrees C sooner in children in the sponged group than in control children (P < 0.001). At 60 minutes, 38 (95.0%) of the controls still had a temperature of 38.5 degrees C or greater, compared with only 15 children (42.9%) in the sponged group (P < 1 x 10(-5). Crying was associated with sponging, but shivering and irritability occurred in only one child who was being sponged. It is concluded that tepid sponging, in addition to antipyretic medication, is clearly more effective than antipyretic medication alone in reducing temperature in febrile children living in a tropical climate.

Acetaminophen↗
PubMedDate not supplied

Intravenous administration of BCG in advanced melanoma patients.

From June 1975 to August 1977, 19 patients with distant metastases of malignant melanoma of the skin that were no longer responsive to chemotherapy were treated with BCG given intravenously. A single dose of lyophilized Pasteur BCG ranging from 2 X 10(7) to 3 X 10(8) viable units was given in 500 ml of saline infused in 5 to 6 h. Seven of the 16 evaluable patients benefited from treatment; 3 showed an objective regression of more than 50% of the original tumor volume, and 4 an arrest of tumor growth. The objective regressions lasted from 2 to 5 months, and 1 case had an arrest of tumor growth for 29 months. The regression rate was related to the BCG dosage: 2 X 10(8) viable units appears to be the dosage that gives severe but reversible toxicity and is able to induce objective regression. The most responsive lesions were skin and subcutaneous deposits (5 of 7) and lung metastases (1 of 4). Toxic effects seem to be related to the number of bacilli injected. In the group of 10 cases treated with less than 10(8) units, toxicity was modest: 4 patients had fever (up to 38.5 degrees C) that lasted a few days, and in 3 cases it was associated with shivering during the infusion period and weakness. One case only had vomiting and jaundice. Toxicity was severe in the 9 patients that were treated with a dosage higher than 10(8): patients had fever and weakness for at least 4 days and shivering during the infusion. Two had adrenal insufficiency and 7 had liver enlargement and jaundice with return to normality by day 21. In the whole series 8 patients had leucopenia and 5 thrombocytopenia for 2 to 3 days: only 1 patient required blood and platelet transfusion. No significant variations in immunoglobulin levels were observed. No variations of PPD or BCG skin tests were observed after treatment. Three patients expired; the first treated with 6 X 10(7) unit, had an intercurrent disease (autopsy showed a heart infarction); the second, treated with 1.8 X 10(8), showed a rapid growth of lung metastases and died 15 days after treatment; the death of the third patient was probably due to anaphylactic shock. All 3 patients had been previously treated with BCG, given by scarification or intranodular injection.

Adolescent↗
PubMed2005

Synergistic effect of intrathecal fentanyl and bupivacaine in spinal anesthesia for cesarean section.

BACKGROUND: Potentiating the effect of intrathecal local anesthetics by addition of intrathecal opiods for intra-abdominal surgeries is known. In this study by addition of fentanyl we tried to minimize the dose of bupivacaine, thereby reducing the side effects caused by higher doses of intrathecal bupivacaine in cesarean section. METHODS: Study was performed on 120 cesarean section parturients divided into six groups, identified as B8, B10 and B 12.5 8.10 and 12.5 mg of bupivacaine mg and FB8, FB10 and FB 12.5 received a combination of 12.5 mug intrathecal fentanyl respectively. The parameters taken into consideration were visceral pain, hemodynamic stability, intraoperative sedation, intraoperative and postoperative shivering, and postoperative pain. RESULTS: Onset of sensory block to T6 occurred faster with increasing bupivacaine doses in bupivacaine only groups and bupivacaine -fentanyl combination groups. Alone lower concentrations of bupivacaine could not complete removed the visceral pain. Blood pressure declined with the increasing concentration of Bupivacaine and Fentanyl. Incidence of nausea and shivering reduces significantly whereas, the postoperative pain relief and hemodynamics increased by adding fentanyl. Pruritis, maternal respiratory depression and changes in Apgar score of babies do not occur with fentanyl. CONCLUSION: Spinal anesthesia among the neuraxial blocks in obstetric patients needs strict dose calculations because minimal dose changes, complications and side effects arise, providing impetus for this study. Here the synergistic, potentiating effect of fentanyl (an opiod) on bupivacaine (a local anesthetic) in spinal anesthesia for cesarian section is presented, fentanyl is able to reduce the dose of bupivacaine and therefore its harmful effects.

Journal Article↗
PubMed2005

Patient preferences for anesthesia outcomes associated with cesarean delivery.

UNLABELLED: When deciding on neuraxial medication (e.g., spinal opioids) for cesarean delivery (CS) under regional anesthesia, anesthesiologists make treatment decisions that "trade off" relieving pain with the potential for increased risk of side effects. No previous studies have examined obstetric patients' anesthesia preferences. Researchers administered 100 written surveys to pregnant women attending our institutions' expectant parent class. We determined patients' preferences for importance of specific intraoperative and postoperative anesthesia outcomes using priority ranking and relative value scales. We also explored patients' fears, concerns, and tolerance regarding CS and analgesics. Eighty-two of 100 surveys were returned and analyzed. Pain during and after CS was the greatest concern followed by vomiting, nausea, cramping, pruritus, and shivering. Ranking and relative value scores were closely correlated (R2 = 0.7). Patients would tolerate a visual analog pain score (0-100 mm) of 56 +/- 22 before exposing their baby to the potential effects of analgesics they receive. In contrast to previous general surgical population surveys that found nausea and vomiting as primary concerns, we found pain during and after CS as parturients' most important concern. Common side effects such as pruritus and shivering caused only moderate concern. This information should be used to guide anesthetic choices, e.g., inclusion of spinal opioids given in adequate doses. IMPLICATIONS: Medical care can be improved by incorporating patients' preferences into medical decision making. We surveyed obstetric patients to determine their preferences regarding potential cesarean delivery anesthesia outcomes. Unlike general surgical patients who rate nausea and vomiting highest, parturients considered pain during and after cesarean delivery the most important concern.

Adult↗
PubMed2005

Epidural fentanyl speeds the onset of sensory and motor blocks during epidural ropivacaine anesthesia.

In this study we examined the onset times of sensory and motor block during epidural ropivacaine anesthesia with and without the addition of fentanyl to the epidural solution. Forty-five young male patients undergoing knee arthroscopic surgery were randomly allocated into 3 groups of 15 patients each: epidural fentanyl (EF; epidural administration of 15 mL of 1% ropivacaine plus 100 mug fentanyl followed by IV injection of 2 mL of normal saline); IV fentanyl (IF; epidural administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline followed by IV injection of 100 mug fentanyl); and control (C; epidural administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline followed by IV injection of 2 mL of normal saline). The sensory and motor blocks were assessed by pinprick and modified Bromage scale, respectively. The hemodynamic changes, postepidural shivering, and side effects of epidural fentanyl were also recorded. There was no difference in the distribution of age, weight, and height among the 3 groups. The onset time of sensory block to the T10 dermatome was significantly more rapid in the EF group (13.0 +/- 3.0 min) than in the IF group (16.2 +/- 3.5 min, P < 0.05) or C group (17.7 +/- 3.6 min, P < 0.05). The onset times of motor block up to Bromage scale 1 and 2 were significantly more rapid in the EF group (11.9 +/- 4.6 and 24.4 +/- 5.9 min) than in the IF group (16.9 +/- 4.7 and 30.8 +/- 5.6 min, P < 0.05) or C group (18.3 +/- 4.9 and 32.7 +/- 5.7 min, P < 0.05). There was no difference in the incidence of shivering among the three groups. Pruritus was observed in three patients of the EF group and one patient of the IF group. No nausea, vomiting, respiratory depression, urinary retention, or hypotension was observed in any patient. We conclude that epidural administration of the mixture of 100 mug fentanyl and 1% ropivacaine solution accelerated the onset of sensory and motor blocks during epidural ropivacaine anesthesia without significant fentanyl-related side effects.

Adult↗
PubMed1995

Daily variations in the response of wood mice Apodemus sylvaticus to noradrenaline

Non-shivering thermogenesis (NST) is an important mechanism for heat production in many small rodent species. Daily rhythms of body (rectal) temperature (Tb) reflect the relationship between heat production and heat dissipation. The roles of photoperiod and the time of day at which NST is measured were studied in wood mice Apodemus sylvaticus. Mice of both sexes (N=18) were acclimated to two different photoperiod regimes (16 h:8 h L:D and 8 h:16 h L:D) at a constant ambient temperature (Ta) of 24 &deg;C. Non-shivering thermogenesis was measured as the maximal response of oxygen consumption (V(dot)O2NA) and body temperature (TbNA) to a noradrenaline (NA) injection (1.5 mg kg-1 subcutaneously) in unanaesthetized mice at three different times in the daily rhythm of Tb (N=6 in each group). Mice acclimated to 8 h:16 h L:D had a greater response to noradrenaline at the three different times of the day compared with those acclimated to 16 h:8 h L:D. The extent of the response to noradrenaline within each group varied with time of day; the smallest response was recorded at 18:00&plusmn;1.5 h, and the greatest was at 01:00 h. These results suggest that photoperiod is an important cue for seasonal acclimatization in this species and that the response to noradrenaline follows a daily rhythm.

Journal Article↗
PubMed1995

Hindleg muscle energy and substrate balances in cold-exposed rats.

Rats chronically cannulated in the carotid artery and the muscular branch of the femoral vein were subjected to a cold (4 degrees C) environment for up to 2 h. The changes in blood flow (measured with 46Sc microspheres) and arterio-venous differences in the concentrations of glucose, lactate, triacylglycerols and amino acids allowed the estimation of substrate (and energy) balances across the hindleg. Mean glucose uptake was 0.28 mumol min-1, mean lactate release was 0.33 mumol min-1 and the free fatty acid basal release of 0.31 mumol min-1 was practically zero upon exposure to the cold; the initial uptake of triacylglycerols gave place to a massive release following exposure. The measurement of PO2, PCO2 and pH also allowed the estimation of oxygen, CO2 and bicarbonate balances and respiratory quotient changes across the hindleg. The contribution of amino acids to the energy balance of the hindleg was assumed to be low. These data were used to determine the sources of energy used to maintain muscle shivering with time. Three distinct phases were observed in hindleg substrate utilization. (1) The onset of shivering, with the use of glucose/glycogen and an increase in lactate efflux. Lipid oxidation was practically zero (respiratory quotient near 1), but the uptake of triacylglycerols from the blood remained unchanged. (2) A substrate-energy shift, with drastically decreased use of glucose/glycogen, and of lactate efflux; utilization of triacylglycerol as practically the sole source of energy (respiratory quotient approximately 0.7); decreasing uptake of triacylglycerol and increased tissue lipid mobilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed2006

Skin-derived precursors generate myelinating Schwann cells for the injured and dysmyelinated nervous system.

Although neural stem cells hold considerable promise for treatment of the injured or degenerating nervous system, their current human sources are embryonic stem cells and fetally derived neural tissue. Here, we asked whether rodent and human skin-derived precursors (SKPs), neural crest-related precursors found in neonatal dermis, represent a source of functional, myelinating Schwann cells. Specifically, cultured SKPs responded to neural crest cues such as neuregulins to generate Schwann cells, and these Schwann cells proliferated and induced myelin proteins when in contact with sensory neuron axons in culture. Similar results were obtained in vivo; 6 weeks after transplantation of naive SKPs or SKP-derived Schwann cells into the injured peripheral nerve of wild-type or shiverer mutant mice (which are genetically deficient in myelin basic protein), the majority of SKP-derived cells had associated with and myelinated axons. Naive rodent or human SKPs also generated Schwann cells that myelinated CNS axons when transplanted into the dysmyelinated brain of neonatal shiverer mice. Thus, neonatal SKPs generate functional neural progeny in response to appropriate neural crest cues and, in so doing, provide a highly accessible source of myelinating cells for treatment of nervous system injury, congenital leukodystrophies, and dysmyelinating disorders.

Animals↗
PubMed2006

Thermal insulation and body temperature wearing a thermal swimsuit during water immersion.

This study evaluated the effects of a thermal swimsuit on body temperatures, thermoregulatory responses and thermal insulation during 60 min water immersion at rest. Ten healthy male subjects wearing either thermal swimsuits or normal swimsuits were immersed in water (26 degrees C or 29 degrees C). Esophageal temperature, skin temperatures and oxygen consumption were measured during the experiments. Metabolic heat production was calculated from oxygen consumption. Heat loss from skin to the water was calculated from the metabolic heat production and the change in mean body temperature during water immersion. Total insulation and tissue insulation were estimated by dividing the temperature difference between the esophagus and the water or the esophagus and the skin with heat loss from the skin. Esophageal temperature with a thermal swimsuit was higher than that with a normal swimsuit at the end of immersion in both water temperature conditions (p<0.05). Oxygen consumption, metabolic heat production and heat loss from the skin were less with the thermal swimsuit than with a normal swimsuit in both water temperatures (p<0.05). Total insulation with the thermal swimsuit was higher than that with a normal swimsuit due to insulation of the suit at both water temperatures (p<0.05). Tissue insulation was similar in all four conditions, but significantly higher with the thermal swimsuit in both water temperature conditions (p<0.05), perhaps due to of the attenuation of shivering during immersion with a thermal swimsuit. A thermal swimsuit can increase total insulation and reduce heat loss from the skin. Therefore, subjects with thermal swimsuits can maintain higher body temperatures than with a normal swimsuit and reduce shivering thermo-genesis.

Adult↗
PubMed1982

Baroreflex suppression of nonshivering thermogenesis in rats.

The effects of an elevation of arterial blood pressure (BP) on heat production (M) and interscapular brown adipose tissue temperature (Tbat) were studied at 15 degrees C in unanesthetized 5 degrees C-acclimated rats. The elevation in blood pressure (BP), caused by phenylephrine (PHE: 5-30 micrograms/(kg x min)) infusion for 10 min, decreased M and Tbat accompanied by a marked bradycardia. The decrease in M was not due to the suppression of shivering, because shivering did not appear under the present experimental conditions. After sinoaortic baroreceptor denervation, PHE infusion failed to produce these changes. After premedication with atropine, PHE infusion suppressed M and Tbat without the bradycardia. These results indicate that nonshivering thermogenesis (NST) in the brown adipose tissue (BAT) is suppressed by a sinoaortic baroreceptor reflex in response to an elevation of BP. Since metabolism of BAT is controlled by the sympathetic nervous system, the baroreflex inhibition of NST in the BAT may be largely attributed to the decrease of sympathetic nervous outflow to the BAT.

Adipose Tissue, Brown↗
PubMed1998

Nonshivering thermoregulatory responses in trained athletes: effects of physical fitness and body fat.

We studied the difference of thermoregulatory responses between trained male athletes (TR, n = 9) and untrained men (UT, n = 7) during 60 min of cold exposure (15 degrees C) without shivering, and examined the effects of physical fitness and body fat on these responses. Mean skin temperature (Tsk), esophageal temperature (Tes), and skin conductance (Kb) were similar between TR and UT, and heat production (M) for TR increased significantly during exposure at 15 degrees C. The M at 15 degrees C correlated positively with maximal oxygen uptake and negatively with body fat (%BF), but not with Tes. The Kb correlated negatively with Tes and positively with Tsk. The %BF also correlated negatively with Kb and Tsk during exposure at 15 degrees C, and the slope of %BF vs. Tsk relationship was significantly steeper in TR than in UT. These results suggest that (1) body temperature is maintained by the reduction of skin conductance, and (2) heat insulation independent of body fat is enhanced in trained athletes during cold exposure without shivering.

Adipose Tissue↗
PubMed1988

Abnormal thermoregulation in diabetic autonomic neuropathy.

Hypothermia has been reported to be more common in diabetic people than in nondiabetic people, and we have investigated the possibility that autonomic neuropathy may be associated with disordered thermoregulation. After an overnight fast and maintenance of normoglycemia, 12 insulin-treated diabetic patients with and 11 without neuropathy and 12 nondiabetic control subjects, all less than 55 yr, were subjected to external cooling by perfusing water at 16 degrees C through a liquid-conditioned coverall for less than or equal to 45 min. Patients with autonomic neuropathy had impaired vasoconstriction to cooling, particularly in the foot, calf, and forearm. Core temperature rose by 0.2 degrees C in control subjects and by 0.15 degrees C in patients with diabetes but no neuropathy. In contrast, group mean core temperature was unchanged in those with autonomic neuropathy and fell in 3 subjects (P less than .001). Cooling caused shivering in 6 patients with diabetic autonomic neuropathy, but not in those with neuropathy or control subjects (P less than .05). Baseline metabolic rates were similar in all three groups, but the increase after cooling was significantly greater among those who shivered (P less than .05-.02). Thus, young diabetic patients with autonomic neuropathy have impaired thermoregulation to a relatively short period of external cooling, even during metabolic stability, which may predispose to hypothermia.

Adult↗
PubMed1998

Subarachnoid fentanyl with diluted small-dose bupivacaine for cesarean section delivery.

BACKGROUND: The use of neuraxial opioid was very popular in recent years, and they may augment the analgesia produced by local anesthetic through direct binding with the spinal opioid receptors. Hemodynamic stability is very important during Cesarean section. Theoretically, the reduction of local anesthetic by addition of fentanyl would provide better hemodynamic stability and good anesthetic status. METHODS: Thirty healthy parturients undergoing Cesarean section were assessed in a randomized fashion. They were divided into two groups. Each subject received 5 mg hyperbaric bupivacaine plus 25 micrograms fentanyl (0.5 ml) and cerebrospinal fluid (CSF) 0.6 ml (Group M + F) or 8 mg hyperbaric bupivacaine plus 0.5 ml of CSF (Group M). The effects of hemodynamic stability, side effects, and complete analgesic duration were observed. RESULTS: It was disclosed that the hemodynamic status was more stable in group M + F. The incidence of nausea and vomiting appeared to be not statistically significant between groups. The incidence of pruritus was apparently higher in group M + F (93.5% vs. 0) but the incidence of shivering was much lower in group M + F (0 vs. 33.3%). The complete analgesic duration was longer in group M + F (146 +/- 47 min vs. 104 +/- 44 min). There were no significant differences in the anesthetic and surgical status, 1-min and 5-min Apgar scores, and the time of regression of sensory level to T10. CONCLUSIONS: The combination of small-dose bupivacaine with fentanyl could provide more stable hemodynamic status, longer postoperative analgesia, and lower incidence of shivering. The incidence of pruritus in group M + F was high, but it was usually mild.

Adult↗
PubMed2000

[Anesthesia with remifentanil combined with desflurane or sevoflurane in lumbar intervertebral disk operations].

Recovery characteristics, haemodynamic profile, analgesic requirement and costs were evaluated and compared in patients undergoing elective lumbar discectomy with remifentanil-based anaesthesia using either desflurane or sevoflurane as the volatile anaesthetic agent. Sixty-two patients (ASA I/II status) were randomly assigned to receive either desflurane and remifentanil or sevoflurane and remifentanil (in oxygen/air) for anaesthesia. After induction with 0.5 microgram/kg/min remifentanil, 4 to 5 mg/kg thiopentone and 0.5 mg/kg atracurium, the patients received 0.25 microgram/kg/min remifentanil and 0.5 +/- 0.05 MAC of one of the volatile anaesthetic agents for further maintenance of anaesthesia. At the end of surgery, early emergence from anaesthesia was recorded by assessing the time to sufficient spontaneous respiration, eye opening and tracheal extubation. The total demand of piritramide in the postoperative period was determined using patient-controlled analgesia (PCA device). Quality of pain therapy was assessed via a verbal ranking scale (VRS). Side-effects such as postoperative nausea, vomiting or shivering were recorded in the postanaesthetic care unit. In both groups, the haemodynamic profile was nearly identical. Mean arterial pressure (-18%) and heart rate (-23%) were significantly reduced throughout anaesthesia in both groups. All recovery parameters were significantly shorter in the desflurane group in comparison with the sevoflurane group (e.g. time to tracheal extubation: 8.5 +/- 3.0 min vs. 11.9 +/- 4.6 min). No significant differences between the groups were observed concerning the amount of piritramide required, side-effects such as nausea and vomiting or the total cost of anaesthesia. In conclusion, both anaesthetic techniques provide adequate haemodynamic stability and postoperative pain control in a surgical procedure with minimal trauma. Incidence and severity of side-effects such as nausea, vomiting or shivering did not differ between the groups and were acceptable under clinical conditions. Costs for desflurane were significantly higher than those for sevoflurane, but total costs were not different between the groups. Concerning recovery profile, desflurane/remifentanil seems to have small advantages over sevoflurane/remifentanil in patients undergoing lumbar vertebral disc resection.

Adult↗
PubMed2001

Ten-day cold exposures develop adaptation-compensatory mechanisms of regulation of heat exchange and breathing.

The purpose of the study was to determine types of general cold adaptation and to reveal adaptation-compensatory regulation mechanisms of heat exchange and breathing. 24 healthy subjects were tested. Thermoregulation and gas exchange was measured before, during and after a 10-day cold exposure (13 degrees C, 2 h). Before and after cold exposures the ventilatory CO2 and O2 sensitivity was measured by the rebreathing method. The gas-analyser Eos Sprint ("Erich Jaeger", Germany) was used. The whole group exhibited the hypothermic isoinsulative adaptation type: during cold exposure Tre decreased (P < 0.01), Tsk did not change, the delay for the onset of shivering increased (P < 0.001), Tre of the onset of shivering decreased (P < 0.01). According to Tre measured at 120 min of the 10th day the group was divided in two. In the first group the adaptive response was based on thermoregulation changes only. In the second group adaptive response was based on both thermoregulation changes and breathing regulation changes: ventilatory CO2 and O2 sensitivity increased (P < 0.01), the oxyhaemoglobin dissociation curve moved to the right (P < 0.01). Thus we can propose that subjects of the first group will be more successful in cold adaptation, whereas the second group will be unsuccessful in cold adaptation and at risk for respiratory diseases.

Adaptation, Physiological↗
PubMedDate not supplied

Mammalian hibernation: lessons for organ preparation?

The adaptations to low environmental temperatures exhibited in mammalian hibernation are many and varied, and involve molecular and cellular mechanisms as well as the systematic physiology of the whole organism. Natural torpidity is characterised by a profound reduction in body temperature and other functions lasting from a few hours to several weeks. Controlled reduction of heart rate, respiration and oxygen consumption is followed by the fall in body temperature. However, thermoregulation persists such that a decrease in ambient temperature below dangerous levels typically triggers arousal, and shivering and non-shivering thermogenesis from brown fat provide the heat to restore body temperature to normal levels. Many of the cellular mechanisms for survival are similar to those brought into play during medium-term storage of organs destined for transplantation. For example maintenance of ionic regulation and membrane fluxes is fundamental to cell survival and function at low body temperatures. Differences between hibernating and non-hibernating species are marked by differences in Na+/K+ transport and Ca++pumps. These in turn are probably associated with alterations in the lipoproteins of the plasma membrane and inner mitochondrial membrane. We have accordingly conducted a series of pilot studies in captured Richardson's ground squirrels kept in laboratory conditions as a model for hypothermic organ preservation. Tissue function was compared during the summer (non-hibernating season) with that in the winter when the animals could be: (i) in deep hibernation in a cold chamber at 4 degree C; (ii) maintained in an ambient temperature of 4 degree C but active and awake; or (iii) active at an ambient temperature of 22 degree C. The studies involved: whole animal monitoring of standard physiological parameters; whole organ (kidney) storage and transplantation for viability assessment; storage and functional assessment on an ex vivo test circuit with capacity for perfusion at normothermic and hypothermic temperatures; measurement of thyroid function; measurements of total nucleotides (ATP, ADP and AMP)and ratios by standard techniques after freeze-clamping of organs; similar nucleotide and pH measurements using31P-NMR as a non-invasive whole animal technique; and measurement of O2 uptake and gluconeogenesis using isolated renal tubules and isolated hepatocytes. Marked differences in cold tolerance were demonstrated between organs taken from hibernating versus non-hibernating individuals. In particular kidneys transplanted from animals in deep hibernation were capable of withstanding up to 72 hours of cold storage as compared with up to 24 hours in non-hibernating squirrels or in comparable sized rats. Adaptations which might provide valuable clues in our attempts to better preserve human organs for transplantation are explored in some depth in this report.

Journal Article↗
PubMed1991

Pathophysiology of thermoregulation in patients with poikilothermia.

To investigate the thermoregulatory mechanisms underlying poikilothermia in man, we have studied 4 female patients (age 28-37 yr) with poikilothermia, most probably of hypothalamic origin, as well as 4 female volunteers of similar age. In a climatic chamber the participants were subjected to cold stress (16.5 degrees C) and subsequent heat exposure (40 degrees C). In the volunteers cold stress did not influence the rectal temperature; cooling induced a marked shivering response and an immediate peripheral vasoconstriction. Subsequent heat challenge induced a slight rise in the rectal temperature (from 36.3 +/- 0.2 to 37.0 +/- 0.3 degrees C) and a marked sweat secretion in all control subjects. All patients were hypothermic at the start of the experiment. Cooling induced a decrease in the rectal temperature of 0.3-0.9 degrees C. Three patients showed neither peripheral vasoconstriction nor a shivering response to cold stress. In contradistinction to the control subjects, in all patients an afterdrop of the rectal temperature of 0.3-0.5 degrees C was observed once heating of the environment had started; thereafter a progressive rise in core temperature occurred up to 38.5 (38.0) degrees C. In none of the patients sweat secretion was clinically visible. These results reveal that in these patients with poikilothermia the disorder of thermoregulation is accompanied by inadequate cutaneous vasomotor adjustment and disturbed sweat response and likely reduced metabolic response to cold stress.

Adult↗