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PubMedDate not supplied

On the role of hsp72 in heat-induced intranuclear protein aggregation.

Heat treatment of cells results in an increased protein content of nuclei and nuclear matrices when isolated after the heat treatment. This increase of TX-100 insoluble protein is interpreted as being the result of protein denaturation and subsequent aggregation. After the heat treatment cells can (partly) recover from these aggregates. Recent data suggest that heat shock proteins (hsps) might be involved in the recovery (disaggregation) from these heat-induced insoluble protein complexes. In this report, the role of hsp72 in the process of aggregation and disaggregation was investigated using: non-tolerant rat-1 cells, thermotolerant rat-1 cells (rat-1 TT), and transfected rat-1 cells constitutively expressing the human inducible hsp72 gene (HR-24 cells). After heating the various cells, it was observed that the expression of the human hsp72 confers heat resistance (43-45 degrees C). Heat-induced intranuclear protein aggregation was less in HR and rat-1 TT cells as compared to nontolerant rat-1 cells. After heat treatments leading to the same initial intranuclear protein aggregation, rat-1 TT cells recovered more rapidly from these aggregates, while HR cells recovered at the same rate as nontolerant rat-1 cells. Our data suggest that increased levels of hsp72 can confer heat resistance at the level of initial (nuclear) heat damage. Elevated levels of hsp72 alone, however, do not enable cells to recover more rapidly from heat-induced intranuclear protein aggregates.

Animals↗
PubMedDate not supplied

Development of a new heating needle for interstitial hyperthermia compatible with interstitial radiotherapy.

PURPOSE: We have developed a new heating needle for interstitial hyperthermia compatible with brachytherapy. We studied the heating characteristics of interstitial needles and the usefulness of these needles for interstitial hyperthermia. MATERIALS AND METHODS: As heating needles, we used MicroSelectron HDR interstitial needles. These needles were only heated at the metal tip, and were insulated in the middle and grounded from the top. The hyperthermia system was based on the principles of RF capacitive heating, and we used a Thermotron RF-8. We examined whether the temperature and the heating area could be elevated to a level required for hyperthermia. RESULT: Good heating was obtained around the metal tip of the needle. The heating area of the longitudinal axis of the needle varied with the length of the metal part, while the transverse heating area of the needle was almost unchanged. If heating was performed while maintaining the elevation of temperature in each needle at the same level using variable coils (tuning box), heating was homogeneous over the regions in accordance with the arrangement of the needles. CONCLUSION: With this heating system, the temperature rises easily, and a uniform temperature distribution can be obtained.

Brachytherapy↗
PubMed2000

[Effects of pre-heating on the sensitivity of K562 cell to tumor necrosis factor-alpha].

In order to study the effects of pre-heating on the sensitivity of cells to tumor necrosis factor-alpha (TNF-alpha), the K562 cells were pre-heated at 40 degrees C for different times to induce heat shock protein 70 (HSP70). To observe the effects of TNF-alpha concentration on the sensitivity of pre-heated cells, cells were pre-heated for 60 min and treated with TNF-alpha (50, 100, 200 and 400 U/ml) for 16 hours, and the cells vitalities were detected by MTT. In order to observe the effect of pre-heating time on the sensitivity of cells to TNF-alpha, the pre-heated cells were treated with 100 U/ml TNF-alpha for 24 hours. The levels of HSP70 were tested by reversed transcription-PCR(RT-PCR). The results showed that HSP70 could be induced by pre-heating, and reached its top level after 120 mins, and the sensitivity of non-heated cells to TNF-alpha was lower than that of pre-heated cells. To 100 U/ml TNF-alpha, the sensitivity was lowest after the cells were pre-heated for 120 min. The results suggested that pre-heated could induce the expression of HSP70 and inhibit the sensitivity of cell to TNF-alpha, the mechanism may be involved with the overexpression of HSP70.

HSP70 Heat-Shock Proteins↗
PubMed2005

[Effects of heating on the epithelia of benign prostate hyperplasia in vitro].

OBJECTIVE: To investigate the biological changes of the epithelia of benign prostate hyperplasia under heating at different temperatures and at different points of time after heating. METHODS: Cell morphology, MTT, flow cytometer, and the immunocytochemical method for detecting heat shock protein 70 and prostate specific antigen were used to observe the effect of heating on the primarily cultured epithelia of benign prostate hyperplasia at 45 degrees C and 60 degrees C and at 1 hour and 12 hours after heating. RESULTS: Heating at 45 degrees C for 15 min resulted in apoptosis, and at 60 degrees C, necrosis in most of the cells. The inhibiting effect of heating on the growth of cells was observed, more significant in the 60 degrees C group than in the 45 degrees C group. The cell phase arrest induced by heat, mainly G0/G1 arrest, was more significant in the 12 h group than in the 1 h group. Heating up-regulated the expressions of heat shock protein 70 and prostate specific antigen in cells. CONCLUSION: Heating can induce apoptosis, necrosis and growth suppression of the epithelia of benign prostate hyperplasia. Its process and mechanism are correlated with the cell phase arrest and the up-regulation of the expressions of heat shock protein 70 and prostate specific antigen.

Apoptosis↗
PubMed1990

Affinity isolation of heat-shock and other calmodulin-binding proteins following hyperthermia.

The interaction of calmodulin (CaM) with heat-shock and other binding proteins was studied in rat adenocarcinoma cells. Cells were equilibrium-labeled for 48 h prior to heating for 1 h at 43 degrees C, or pulse-labeled for 2 h at 37 degrees C after heating, to monitor the effect of heat on the affinity of CaM-binding proteins synthesized under these conditions. A CaM antagonist shown to sensitize to heat killing, W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], was used in competition assays to help monitor any changes in affinity. We found that heating tended to reduce the CaM-binding of proteins synthesized before heating relative to their 37 degrees C controls and proteins synthesized after heating tended to have increased binding relative to their respective controls. Members of the heat-shock protein (hsp) 90-, 70-, and 26-kDa families were among the proteins that bound to CaM and were eluted by W-7. The peak elution fractions for the hsp's and other cellular proteins varied, but hsp-70 eluted in the early fractions. The hsp-70 family was also found to be among a number of W-7-binding proteins. We conclude that the assumption that CaM antagonists potentiate killing of heated cells solely by competing nonspecifically for CaM-binding protein sites on CaM does not explain the process completely. These antagonists could also act by competing for CaM-binding sites with specific proteins whose interaction with CaM is important for survival following heating, or by directly binding to other proteins whose function is important for survival and inhibiting their activity. We do not have sufficient data to discern the predominant mechanism among these possibilities, but we believe all are likely to occur in heated cells and speculate that inhibition of the functions of the hsp-70 family is important in several of these antagonist actions.

Adenocarcinoma↗
PubMed1990

Time course of recovery and heat acclimation ability of prior exertional heatstroke patients.

Our understanding of the time course of recovery from exertional heatstroke (EH) and the heat acclimation ability of prior EH patients is limited. This manuscript reviews previous findings regarding recovery from EH and presents original research involving the heat acclimation ability of 10 prior EH patients (PH) and 5 control subjects. Heat acclimation, by definition, distinguishes heat-intolerant from heat-tolerant prior heatstroke patients. Nine PH exhibited normal heat acclimation adaptations (40.1 degrees C, 7 d, 90 min.d-1), thermoregulation, sweat gland function, whole-body sodium and potassium balance, and blood values at 61 +/- 7 d after EH. One PH (subject A) did not adapt to exercise in the heat, was defined heat intolerant, but subsequently was declared heat tolerant (11.5 months post-EH). Three PH exhibited large, unexpected increases in serum CPK levels, which resolved upon subsequent testing, and were probably related to their detrained state and the exercise which they performed. It was concluded that: 1) sleep loss and generalized fatigue were the most common predisposing factors for PH; 2) recovery from EH was idiosyncratic and may require up to 1 year in severe cases; 3) PH were not hereditarily heat intolerant, prior to EH; 4) no measured variable predicted recovery from EH, or heat acclimation responses; 5) heat intolerance occurs in a small percentage of prior heatstroke patients, and may be transient or persistent.

Acclimatization↗
PubMed1985

Effect of heat shock on the intracellular distribution of proteins.

Exposure of cells to heat induces thermotolerance, a transient resistance to subsequent heat challenges. It has been shown that thermotolerance is correlated in time with the enhanced synthesis of heat shock proteins. In this study, the association of induced heat shock proteins with various cellular fractions was investigated and the heat-induced changes in skeletal protein composition in thermotolerant and control cells was compared. All three major heat shock proteins induced in Chinese hamster fibroblasts after a 46 degrees C, 4-min heat treatment (70, 87, and 110 kDa) were purified with the cytoplasmic fraction, whereas only the 70-kDa protein was also found in other cell fractions, including that containing the cellular skeleton. Immediately after a second heat treatment at 45 degrees C for 45 min, the 110-kDa protein from thermotolerant cells also purified extensively with the cellular skeletal fraction. In this regard, the 110-kDa protein behaved similarly to many other cellular proteins, since we observed an overall temperature-dependent increase in the total labeled protein content of the high-salt-resistant cellular skeletal fraction after heat shock. Pulse-chase studies demonstrated that this increased protein content gradually returned to normal levels after a 3-hr incubation at 37 degrees C. The alteration or recovery kinetics of the total labeled protein content of the cellular skeletal fraction after heat shock did not correlate with the dramatic increase in survival observed in thermotolerant cells. The relationship between heat shock proteins and thermotolerance, therefore, does not correlate directly with changes in the heat-induced cellular alterations leading to differences in protein fractionation.

Acclimatization↗
PubMed1997

Heat-induced thermal tolerance and radiation resistance to apoptosis in human lymphocytes.

We have investigated heat- and radiation-induced apoptosis in human lymphocytes in vitro. We have previously shown that apoptosis was induced by radiation at doses as low as 0.05 Gy. Here we report that heat induced apoptosis in human lymphocytes in a temperature- and time-dependent manner. Temperatures at or below 42 degrees C, for up to 90 min, did not cause lymphocytes to undergo apoptosis, whereas temperatures at or above 43 degrees C, for 30 min and longer, did induce apoptosis. Lymphocytes were protected against apoptosis induced by 44 degrees C heat by a prior heat shock of 42 degrees C for 30 min. Heat-induced thermal tolerance developed immediately following the inducing heat shock, was greater after 4 h, and persisted for at least 24 h. While heat also induced radiation resistance, this change was minor and not apparent until about 24 h after the heat shock. Prior to the development of radiation resistance, heat shock sensitized lymphocytes to radiation-induced apoptosis. We have previously shown that radiation-induced apoptosis in lymphocytes varies between donors and therefore may be useful in assessing individual radiosensitivity. We report here that heat also induced variable levels of apoptosis in lymphocytes from different donors, although the range of responses was not as large as those observed with radiation-induced apoptosis. In summary, heat shock induces tolerance to heat-induced apoptosis and results first in sensitization and then protection of lymphocytes against radiation-induced apoptosis.

Apoptosis↗
PubMed2006

Effects of sequential exposure to lipopolysaccharide and heat stress on dental pulp cells.

In the present study, we examined the effects of sequential exposure to bacterial lipopolysaccharide (LPS) and heat stress on dental pulp cells. LPS induced the proliferation of pulp cells through the activation of p38 MAPK. HSP27 was expressed in cells with or without LPS during the entire period of heat stress, while transiently phosphorylated by short-term heat stress. In LPS-treated cells, short-term heat stress also induced the phosphorylation of HSF1. The immediate phosphorylation of HSF1 and HSP27 in LPS-treated cells by short-term heat stress occurred dependent on the activation of p38 MAPK. However, with long-term heat stress, the activation of HSF1 and induction of HSP27 occurred independent of p38 MAPK. Further, full activation of Akt in LPS-treated cells was immediately induced by short-term heat stress and lasted during the entire period of heat stress. IkappaB alpha was induced and phosphorylated throughout sequential exposure to LPS and heat stress. These results suggest that LPS has the unique effects on the cytoprotection and the cell death of pulp cells during heat stress through the modification and the activation of heat stress responsive molecules, HSF1 and HSP27, and cell survival molecules, Akt and NF-kappaB/IkappaB alpha.

Animals↗
PubMed1996

HSF recruitment and loss at most Drosophila heat shock loci is coordinated and depends on proximal promoter sequences.

The heat shock response in Drosophila is primarily dependent on the binding of the heat shock transcription factor, HSF, to conserved sequences in heat shock gene promoters, the heat shock elements (HSEs). Here we examine the kinetic relationship of HSF binding to chromosomal loci and heat shock gene transcription in vivo. The features of heat shock promoters that determine the kinetics of HSF binding are also examined. Analyses of HSF association by indirect immunofluorescence with an anti-HSF antibody reveal that fluorescent signals at many loci on polytene chromosomes rapidly increase and then gradually decrease as heat shock time progresses. While overall amounts of fluorescent signal vary from locus to locus, the patterns of acquisition and loss of HSF at most loci are coordinated with only one identified exception. Immunostaining with an anti-RNA polymerase II antibody indicates that the kinetics of RNA polymerase II accumulation on the heat shock loci are similar to those of HSF. Furthermore, nuclear run-on assays confirm that the major heat shock genes are coordinately transcribed during the attenuation period. In contrast, the kinetics of HSF association with HSE "polymers" in a transgenic fly strain are not coordinated with those of endogenous loci. The addition of core promoter sequences to one of the HSEs found in the polymer restores coordinate HSF binding, suggesting that the kinetic patterns of HSF binding depend on a core promoter located near the HSEs. Finally, the distribution of the heat shock protein HSP70 is examined for its role in regulating the attenuated response of HSF to heat shock.

Animals↗
PubMed2003

Changes in the number of HSF1 positive granules in the nucleus reflects heat shock semiquantitatively.

PURPOSE: The purpose of this study is to examine the changes in the number of HSF1 granules in the nucleus caused by different degree of heat stress. MATERIALS AND METHODS: A human esophageal cancer cell line, TE-2, was used. HSF1 granules were examined in an immunofluorescence study, and the changes in the average number of HSF1 granules after heat alone or heat in combination with KNK437, Hsp inhibitor, were evaluated. A band shift of HSF1 was also determined by western blot. RESULTS: HSF1 granules appeared soon after the start of heating at 43 degrees C and reached a peak at 60 min and gradually disappeared after discontinuation of heat. In the fractionated heat treatment, preheating (43 degrees C, 30 min) suppressed the increase in the number of the granules during the second heating, but suppression of Hsp72 by KNK437 resulted in increase in the number of granules. Continued heating at 43 degrees C with or without KNK437 maintained the number of the granules at the peak level during heat treatment. The band shift of HSF1 examined by western blot correlated with the changes in the number of granules. The number of granules also reflected the degree of stress according to different temperature. CONCLUSION: The number of HSF1 granules in the nucleus well reflected heat stress, and was almost consistent with phosphorylation of HSF1. The number of HSF1 granules would be a useful tool for evaluating different degrees of heat stress semiquantitatively.

Benzhydryl Compounds↗
PubMed2003

Stimulation of glycogen synthesis by heat shock in L6 skeletal-muscle cells: regulatory role of site-specific phosphorylation of glycogen-associated protein phosphatase 1.

Recent evidence suggests that glycogen-associated protein phosphatase 1 (PP-1(G)) is essential for basal and exercise-induced glycogen synthesis, which is mediated in part by dephosphorylation and activation of glycogen synthase (GS). In the present study, we examined the potential role of site-specific phosphorylation of PP-1(G) in heat-shock-induced glycogen synthesis. L6 rat skeletal-muscle cells were stably transfected with wild-type PP-1(G) or with PP-1(G) mutants in which site-1 (S1) Ser(48) and site-2 (S2) Ser(67) residues were substituted with Ala. Cells expressing wild-type and PP-1(G) mutants, S1, S2 and S1/S2, were examined for potential alterations in glycogen synthesis after a 60 min heat shock at 45 degrees C, followed by analysis of [(14)C]glucose incorporation into glycogen at 37 degrees C. PP-1(G) S1 mutation caused a 90% increase in glycogen synthesis on heat-shock treatment, whereas the PP-1(G) S2 mutant was not sensitive to heat stress. The S1/S2 double mutant was comparable with wild-type, which showed a 30% increase over basal. Heat-shock-induced glycogen synthesis was accompanied by increased PP-1 and GS activities. The highest activation was observed in S1 mutant. Heat shock also resulted in a rapid and sustained Akt/ glycogen synthase kinase 3 beta (GSK-3 beta) phosphorylation. Wortmannin blocked heat-shock-induced Akt/GSK-3 beta phosphorylation, prevented 2-deoxyglucose uptake and abolished the heat-shock-induced glycogen synthesis. Muscle glycogen levels regulate GS activity and glycogen synthesis and were found to be markedly depleted in S1 mutant on heat-shock treatment, suggesting that PP-1(G) S1 Ser phosphorylation may inhibit glycogen degradation during thermal stimulation, as S1 mutation resulted in excessive glycogen synthesis on heat-shock treatment. In contrast, PP-1(G) S2 Ser phosphorylation may promote glycogen breakdown under stressful conditions. Heat-shock-induced glycogenesis appears to be mediated via phosphoinositide 3-kinase/Akt-dependent GSK-3 beta inactivation as well as phosphoinositide 3-kinase-independent PP-1 activation.

Androstadienes↗
PubMed1999

Heat shock response decreases endotoxin-induced acute lung injury in rats.

OBJECTIVE: Transient whole-body hyperthermia was reported to reduce lung damage in a rat with intra-abdominal sepsis produced by caecal perforation. METHODOLOGY: In order to determine the effect of heat shock response on acute lung injury induced by endotoxin, which plays a central role in the pathogenesis of sepsis, we instilled either saline or lipopolysaccharide (LPS) intravenously with and without heat pretreatment in rats. The heated rats had their rectal temperature raised to more than 40 degrees C for 13 min 18 h before intravenous administration of saline or LPS. RESULTS: We found that the lung leak was significantly increased among the rats given LPS intravenously with (median, 0.17; range, 0.15-0.22; n = 10) and without heat pretreatment (0.23; 0.17-0.30; n = 10) compared with those of saline-treated rats (0.13; 0.10-0.14; n = 10) (P < 0.05 in each). However, rats given LPS after heat pretreatment had significantly decreased lung leak index compared with those of LPS-treated rats without heat pretreatment (P < 0.05). Rats administered LPS intravenously showed increased myeloperoxidase activity without heat pretreatment (19.01; 9.34-28.00 U/g; n = 10) compared with that of saline-treated rats (7.09; 4.49-10.56 U/g; n = 5) (P < 0.05) (Fig. 2). Myeloperoxidase activity of the rats treated with LPS with heat pretreatment (5.57; 2.87-8.96 U/g; n = 10) was significantly decreased to the level of normal control compared with that of LPS-treated rats without heat pretreatment (P < 0.05). The levels of heat shock proteins (HSP72) in lung tissue, which were examined by western blot analysis, were increased over baseline levels at 23 h after hyperthermic stress. CONCLUSIONS: These observations show that brief heat shock response is associated with the induction of HSP72 protein synthesis and attenuated neutrophil recruitment and acute lung leak is induced by endotoxin in rats.

Acute Disease↗
PubMed1994

Heat stress induces hsc70/nuclear topoisomerase I complex formation in vivo: evidence for hsc70-mediated, ATP-independent reactivation in vitro.

We previously demonstrated that in murine T cells thermotolerance correlated with heat shock protein 70 (hsp70) synthesis and protection of nuclear type I topoisomerase (topo I). Topo I activity returned to normal levels following heat stress even in cells not rendered thermotolerant by a prior heat shock. Recovery of topo I activity was not dependent on de novo protein synthesis, suggesting that the cell possesses a pathway(s) for refolding this nuclear protein. In this report we demonstrate that topo I and hsc70, the constitutively produced member of the hsp70 family, associated in vivo during heat stress. That this association may play a physiologically important role in protecting topo I activity from heat stress was suggested by the observation that hsc70 protected topo I from heat inactivation in vitro. hsc70 but not actin also reactivated previously heat-denatured topo I in a dose-dependent fashion. However, refolding of heat-denatured topo I by purified hsc70 was inefficient relative to a hsc70-containing cell lysate. Protection from heat inactivation as well as reactivation by hsc70 did not require exogenous ATP. Similarly, reactivation by the cell lysate was not inhibited by ADP or a nonhydrolyzable analogue of ATP. Thus, our studies suggest that nuclear topo I complexes with hsc70 during heat stress, which may explain, at least in part, why hsp70 proteins accumulate in the nucleus, particularly the nucleolus. This interaction may limit heat-induced protein damage and/or accelerate restoration of protein function in an ATP-independent reaction.

Adenosine Triphosphate↗
PubMed2003

Translational thermotolerance provided by small heat shock proteins is limited to cap-dependent initiation and inhibited by 2-aminopurine.

Heat shock results in inhibition of general protein synthesis. In thermotolerant cells, protein synthesis is still rapidly inhibited by heat stress, but protein synthesis recovers faster than in naive heat-shocked cells, a phenomenon known as translational thermotolerance. Here we investigate the effect of overexpressing a single heat shock protein on cap-dependent and cap-independent initiation of translation during recovery from a heat shock. When overexpressing alphaB-crystallin or Hsp27, cap-dependent initiation of translation was protected but no effect was seen on cap-independent initiation of translation. When Hsp70 was overexpressed however, both cap-dependent and -independent translation were protected. This finding indicates a difference in the mechanism of protection mediated by small or large heat shock proteins. Phosphorylation of alphaB-crystallin and Hsp27 is known to significantly decrease their chaperone activity; therefore, we tested phosphorylation mutants of these proteins in this system. AlphaB-crystallin needs to be in its non-phosphorylated state to give protection, whereas phosphorylated Hsp27 is more potent in protection than the unphosphorylatable form. This indicates that chaperone activity is not a prerequisite for protection of translation by small heat shock proteins after heat shock. Furthermore, we show that in the presence of 2-aminopurine, an inhibitor of kinases, among which is double-stranded RNA-activated kinase, the protective effect of overexpressing alphaB-crystallin is abolished. The synthesis of the endogenous Hsps induced by the heat shock to test for thermotolerance is also blocked by 2-aminopurine. Most likely the protective effect of alphaB-crystallin requires synthesis of the endogenous heat shock proteins. Translational thermotolerance would then be a co-operative effect of different heat shock proteins.

2-Aminopurine↗
PubMed2000

Expression of antisense hsp70 is a major determining factor in heat-induced cell death of P-19 carcinoma cells.

Overexpressed heat shock protein 70 (Hsp70) is known to be associated with thermoprotection in a number of cell lines and transgenic animals. We hypothesized that because overexpression of Hsp70 protects cells from lethal heat stress, inhibition of expression should make cells susceptible to heat stress. The model used for this study was a stably transfected P-19 carcinoma cell line expressing antisense hsp70 under the control of the hsp70b promoter. The results showed marked inhibition of Hsp70 expression after heat shock correlated with heat-induced cell death. Hsp90 and Hsc70 protein expression were not affected by the antisense construct. Unexpectedly, heme oxygenase (HO-1), another highly inducible heat shock protein, was not induced after heat shock in the antisense hsp70 cell line. Heat shock transcription factor-1 (HSF-1) was in a highly phosphorylated state in the antisense cell line before and after heat shock. This was in contrast to the untransfected control P-19 cells where HSF-1 was primarily highly phosphorylated after heat shock. A control cell line expressing only the vector, pMAMneo, without the antisense construct also showed partial loss of Hsp70 induction but not increased cell death after heat shock. The findings support the role of Hsp70 in thermoresistance.

Animals↗
PubMed1996

A method to perfuse liver metastases with heated blood (45 degrees C, 45 min).

To heat the livers in ten pigs (20-30 kg) a system of two pumps, both connected to the cannulated A.femoralis and to two radio-wave heating devices, was used. With pump I the arterial vascular system of the liver was perfused for 45 min via the A.gastroduodenalis with a constant volume of 150-200 ml blood/min, heated to 44-45 degrees C. With pump II 50-700 ml/min heated blood was pumped into the portal vein to raise the temperature and oxygen content of the portal flow. During the heating period the A.hepatica was clamped. A temperature of 45 degrees C is a highly toxic for the differentiated liver tissue, but the more simply structured wall of the arteries tolerates this temperature. This difference in heat resistance allows the perfusion of the arterial vascular system of the liver with blood heated to a temperature that is fatal to liver tissues. On the way from the A.gastroduodenalis to the liver periphery the heated blood becomes cooled by the surrounding cooler liver tissues. Finally the supply to the lobules is a mixture of arterial and venous blood, i.e. the highly toxic agent, heat, becomes "detoxified" by cooling before reaching the heat-sensitive liver lobules. Changing flow and temperature in the portal vein allows the temperature of the liver lobules to be kept within a safe range, i.e. below 43 degrees C. The raised oxygen content in the portal flow allows the arterial perfusion to be stopped for 10 min (to subject a heated metastasis to a period of hypoxia). Liver enzymes reached their maximal level 2 days after heating and returned to normal within 1 week. It is supposed that this method allows the temperature in a liver metastasis to be raised to a tumoricidal level.

Animals↗
PubMed1999

Thermoregulatory responses to acute heat loads in the FOK rat.

FOK is an inbred rat strain with a genotypic adaptation to hot environments. The present study investigated the mechanism of the high heat tolerance of the FOK rat. Male FOK and WKAH rats were used. They were loosely restrained and placed individually in a direct calorimeter with an ambient temperature of 24 degrees C. Their hypothalamic temperature, evaporative and non-evaporative heat loss and heat production were measured. After thermal equilibrium had been attained, the rats were warmed for 30 min with a chronically implanted intraperitoneal electric heater (internal heating). At least 90 min after the heating, the jacket water temperature surrounding the calorimeter chamber was gradually raised from 24 degrees C to 36 degrees C in 80 min (external warming). During the internal heating, changes in the thermoregulatory parameters did not differ between the groups. During the external warming, the evaporative heat loss of the FOK rat was significantly greater than that of the WKAH rat, while changes in nonevaporative heat loss and heat production did not differ between the groups. The results suggest that in the FOK rat, the improved heat tolerance is attributable to an enhanced evaporative heat loss response, but not to a facilitation of nonevaporative heat loss or of metabolic depression.

Acclimatization↗