Pulmonary fat embolism induced by exposure to high ambient temperature in rats with a fatty liver

The aim of this study was to investigate whether a fatty liver contributes to pulmonary embolism under a high ambient temperature. As an experimental model, we exposed fatty liver rats to a high temperature (45°C) and then looked for fat emboli in the alveolar capillaries using the fat-staining method. Fat emboli were detected in the alveolar capillaries of the fatty liver rats, but not in those of the normal liver rats. Moreover, the degree of pulmonary fat embolism tended to become more severe in proportion to the severity of the fatty liver. In addition, fat emboli did not appear at a core body temperature of 40°C, but were detected at a core body temperature of 44°C. From these results, we conclude that a fatty liver may contribute to the formation of pulmonary fat embolism and that high temperatures act as a trigger for the onset of pulmonary embolism. Moreover, it is possible that fatty liver affects the development of heat stroke induced by exposure to a high ambient temperature and that pulmonary fat embolism is a significant finding which helps to enable a diagnosis of heat stroke in autopsy cases.     

No effect of moderate hypohydration or hyperthermia on anaerobic exercise performance

PURPOSE: This study examined the effects of hypohydration and moderate hyperthermia (core temperature elevation) on anaerobic exercise performance in a temperate environment. METHODS: Eight active males completed two passive heat exposure trials (180 min, 45 degrees C, 50% rh) with (EUH) and without (HYP) fluid replacement. A single 15-s Wingate anaerobic test (WAnT) was used to assess anaerobic performance (peak power, mean power, and fatigue index) before (-180 min) and again at three time points after passive heat exposure to include immediately (0 min), 30 min, and 60 min after in a temperate environment (22 degrees C). Rectal temperature (Tc) was measured throughout the experiment. RESULTS: HYP reduced body mass (2.7+/-0.7%) (P<0.05) but had no effect on any WAnT performance measure. Passive heat exposure elicited moderate hyperthermia in both trials (EUH: 0.6 degrees C; HYP: 1.0 degrees C) and returned to baseline within 30-60 min following similar decay curves. HYP Tc remained higher (0.4 degrees C) than EUH throughout testing (P<0.05), but moderate hyperthermia itself produced no independent effect on anaerobic exercise performance in either trial. CONCLUSIONS: This study demonstrates that neither moderate HYP nor the moderate hyperthermia accompanying HYP by passive heat exposure affect anaerobic exercise performance in a temperate environment.     

Experimental study of ferromagnetic induction heating combined with hepatic arterial embolization for treatment of liver tumors

The induction heating to ferromagnetic implants (Ferromagnetic Induction Heating: FIH) has been developed for the purpose of selective hyperthermia on deep-seated tumors. In this investigation, the procedure of FIH combined with hepatic arterial embolization (HAE) was experimentally studied on VX2 liver tumor of rabbit. The induction heating unit is composed of radiofrequency generator (500 KHZ, 6-12 KW) and circular applicator (60 cm in diameter). Ferromagnetic implant used was pure iron particles (100 mu in size), which were suspended in tenacious polysaccharide solution to be injectable through a needle. After HAE with gelatin sponge powder had been made, iron particle suspension was injected into the cavity of tumor with subsequent exertion of induction heating (9KW) for 15 minutes. The measurement of temperature was made on the tumor and the liver parenchyma by fluoroptic thermometer with thin, flexible probe which readily passed through a needle. The temperature measured at peripheral area of tumor elevated at range from 2.5 to 7.1 degrees C, corresponding to the dose of iron particles injected; 2.5 degrees C with 1 g, 4.9 degrees C with 2 g, 7.1 degrees C with 3 g. In contrast, the temperature of liver parenchyma elevated at range of less than 2.5 degrees C, to indicate a successful selective heating of liver tumor. An additional experiment for the effect of heat on normal liver of rabbit were made using a microwave heating system. The histological and serologic examinations after heating of below 40 degrees C did not show any abnormal findings. After heating of 42-43 degrees C, however, serum GOT and GPT transiently elevated more than 3 times to that of before heating. Histologically, there were extensive degeneration and necrosis of liver tissue. From the results we concluded that FIH combined with HAE could provide an intensive therapeutic effect for treatment of well-localized liver tumors with minimal damages to the liver parenchyma, because of selective heating of the tumor.     

A comparison of thermal responses of human and rodent cells

A comparison of heat responses of cells from human and rodent tumors indicates the following: (1) human cells appear to be appreciably more heat-resistant than are rodent cells in the range 41-45 degrees C; (2) while rodent cells show a marked increase in sensitivity as the temperature is increased from 42 and 43 degrees C, this change occurs at approximately 44 degrees C or higher for the human lines examined; (3) rodent cells are unable to acquire thermotolerance during exposure to 43 degrees C; the human cells do so readily; (4) decay of tolerance tends to be complete in 72 h in rodent cells; in human cells it may take twice that time. These results may have important implications for the clinical use of hyperthermia.     

Modification of bleomycin-induced chromosome aberrations by hyperthermia and under energy depleting conditions in human peripheral lymphocytes.

Synergistic effects of bleomycin (BLM) and hyperthermia were studied in human peripheral lymphocytes (HPL). The frequencies of breaks produced by BLM were dependent on dose, incubation temperature, and treatment time. Heat alone did not induce chromosome aberrations. Synergistic effects of heat and BLM occurred at 43 degrees C, either when hyperthermia was for 60 min following treatment with BLM or when hyperthermia was for 30 min simultaneously with BLM treatment. At incubation temperatures below 43 degrees C as many dicentric chromosomes as chromosome breaks were found, but about twice as many dicentric chromosomes as chromosome breaks were found when cells were treated with BLM at 43 degrees C for 60 min. In all experiments with BLM chromosomal anomalies were overdispersed. Comparison with unstimulated HPL, heated after X-irradiation, suggested that heat inhibits repair of BLM-induced lesions to a smaller extent than X-ray-induced lesions. Experiments with sodium azide and 2-deoxyglucose led to the conclusion that cellular uptake of BLM is partly energy-dependent. Additionally, an energy-independent uptake of BLM, which could not be blocked by inhibitors, was apparent.     

Hyperthermia combined with ethanol administration induces c-fos expression in the central amygdaloid nucleus of the mouse brain. A possible mechanism of heatstroke under the influence of ethanol intake

Heatstroke is defined as a core body temperature that rises above 40.6°C and is accompanied by mental status abnormalities such as delirium, convulsions, or coma resulting from exposure to environmental heat. There is fairly wide agreement that ethanol intake is a predisposing factor in heatstroke. This study was performed to identify the brain changes induced by heatstroke, using a mouse hyperthermia model with and without preceding ethanol administration. Exposure to heat of 42°C until the core temperature reached to 43°C followed by exposure to 37°C for 15 min decreased the levels of partial pressures of O₂ in blood. Preceding ethanol administration and heat exposure induced hypotension, severe metabolic acidosis and respiratory failure, and, accordingly, produced heatstroke. Immunohistochemistry of the brains showed that preceding ethanol administration increased the number of c-fos-immunoreactive neurons, as a marker of neuronal activation, in the central amygdaloid nucleus, which is involved in thermoregulation. These results indicate that combined effects of ethanol and heat exposure induce heatstroke that is associated with activation of the central amygdaloid nucleus, implicating the pathophysiology and mechanisms of heatstroke under the influence of ethanol intake.     

Death as a result of heat stroke in a vehicle: an adult case in winter confirmed with reconstruction and animal experiments

A 54-year-old man was found dead in the driver's seat of his vehicle on a winter's day. Investigations of the vehicle revealed that the engine was running, and the car heater was left on with the maximum temperature and velocity. The body was found excessively sweating. Rectal temperature of the body was 43 degrees C at 10 h post mortem. In autopsy, several superficial skin burns were observed on the face, the shoulders and the legs. The lungs were heavily congested and hemorrhagic. The liver showed typical alcohol-induced micronodular cirrhosis. The alcohol concentrations were 0.17% in the blood of both the left and the right heart, 0.17% in the femoral-vein blood, 0.21% in the bladder urine and 0.34% in the gastric contents. A reconstruction experiment demonstrated that the temperature inside the vehicle rose rapidly and reached 50-58 degrees C in 3 h. Animal experiments showed that the temperature threshold for rats to succumb to heat was between 40 and 45 degrees C. This case shows that heat stroke in a vehicle can occur in adults with chronic diseases or alcoholism, such as in this particular case, even in the winter.     

Whole body hyperthermia in the treatment of neoplastic disease

Hyperthermia, the elevation of body or tissue temperature, has been used to treat various ailments including cancer since ancient times. During the past 15 years, laboratory evidence has developed to provide a scientific rationale for its use in the treatment of neoplastic diseases. Generally, temperatures in excess of 41 degrees C in vitro will kill neoplastic cells exponentially as a function of time. The direct cytotoxic effects of heat alone, however, may have limited clinical utility due to poor response rates and response durations. The greatest potential of hyperthermia resides in its use as an adjunct to other forms of therapy. As hyperthermia is nonmyelosuppressive and can potentiate the tumoricidal effects of radiation, chemotherapy, and immunotherapy, its use as part of a multimodality treatment approach is attractive. Three forms of hyperthermia have been developed for clinical application: local, regional, and whole body. As WBH addresses the issue of cancer as a systemic disease, it has perhaps the greatest potential for curative success when used as an adjunct to other therapeutic modalities. Using a variety of WBH methodologies, core temperatures have been maintained at 41 degrees C or 42 degrees C in humans for several hours with variable morbidity and occasional mortality. Most systems for WBH include a requirement for general anesthesia, as well as complex equipment to regulate patient temperature. The system most used to date worldwide is based on extracorporeal heating. A hot water suit system, developed at the National Cancer Institute, has also undergone extensive testing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral changes during exercise in the heat

This review focuses on cerebral changes during combined exercise and heat stress, and their relation to fatigue. Dynamic exercise can elevate the core temperature rapidly and high internal body temperatures seem to be an independent cause of fatigue during exercise in hot environments. Thus, in laboratory settings, trained participants become exhausted when they reach a core temperature of approximately 40 degrees C. The observation that exercise-induced hyperthermia reduces the central activation percentage during maximal isometric muscle contractions supports the idea that central fatigue is involved in the aetiology of hyperthermia-induced fatigue. Thus, hyperthermia does not impair the ability of the muscles to generate force, but sustained force production is lowered as a consequence of a reduced neural drive from the CNS. During ongoing dynamic exercise in hot environments, there is a gradual slowing of the electroencephalogram (EEG) whereas hyperthermia does not affect the electromyogram. The frequency shift of the EEG is highly correlated with the participants' perception of exertion, which furthermore may indicate that alterations in cerebral activity, rather than peripheral fatigue, are associated with the hyperthermia-induced development of fatigue. Cerebral blood flow is reduced by approximately 20% during exercise with hyperthermia due to hyperventilation, which causes a lowering of the arterial CO(2) pressure. However, in spite of the reduced blood flow, cerebral glucose and oxygen uptake does not seem to be impaired. Removal of heat from the brain is also an important function of the cerebral blood flow and the lowered perfusion of the brain during exercise and heat stress appears to reduce heat removal by the venous blood. Heat is consequently stored in the brain. The causal relationship between the circulatory changes, the EEG changes and the hyperthermia-induced central fatigue is at the present not well understood and future studies should focus on this aspect.     

Temperature distribution and geometry of the electrodes in RF interstitial hyperthermia using circular and interstitial electrodes]

To evaluate the feasibility of clinical application of a newly developed interstitial hyperthermia system, which consists of an 8 MHz radiofrequency generator, interstitial needle electrodes, and a superficial circular electrode, we conducted preclinical experiments using an agar phantom and VX-2 carcinoma in the rabbit. In the experiment with an agar phantom, four 4 cm needle electrodes were placed in a square array at intervals of 1.0, 1.5, and 2.0 cm. Thermography demonstrated homogeneous temperature distribution at electrode intervals of 1.0 and 1.5 cm, but hot spots around the electrodes at an interval of 2.0 cm. When electrode deviation was less than 8 degrees from the parallel plane, no temperature deviation was observed. Using two 2 cm electrodes and two 4 cm electrodes in square array, thermography demonstrated a homogeneous temperature distribution in the area surrounded by the electrodes. Even if the electrodes were located at the periphery of the agar phantom, a homogeneous temperature distribution was obtained in the area surrounded by the electrodes. Using four 4 cm electrodes at intervals of 1.5 cm in VX-2 carcinoma in the rabbit, ideal heating was obtained: 42 degrees C at the periphery of the tumor and 43 degrees C at the center. These data suggest that the newly developed interstitial hyperthermia apparatus provides homogeneous heat distribution at electrode intervals of 1.5 cm or less and can be used in a Phase I study for deep-seated or superficial tumors.     

Eighty-four hours of sustained operations alter thermoregulation during cold exposure

PURPOSE; This study examined the effects of short-term (3.5 d) sustained military operations (SUSOPS) on thermoregulatory responses to cold stress. METHODS: Ten men (22.8 +/- 1.4 yr) were assessed during a cold-air test (CAT) after a control week (control) and again after an 84-h SUSOPS (sleep = 2 h.d (-1), energy intake = approximately 1650 kcal.d(-1), and energy expenditure = approximately 4500 kcal.d(-1). CAT consisted of a resting subject (seminude) being exposed to an ambient temperature ramp from 25 degrees C to 10 degrees C during the initial 30 min of CAT, with the ambient temperature then remaining at 10 degrees C for an additional 150 min. RESULTS: SUSOPS decreased (P< 0.05) body weight, % body fat, and fat-free mass by 3.9 kg, 1.6%, and 1.8 kg, respectively. During CAT, rectal temperature decreased to a greater extent (P< 0.05) after SUSOPS (0.52 +/- 0.09 degrees C) versus control (0.45 +/- 0.12 degrees C). Metabolic heat production was lower (P< 0.05) after SUSOPS at min 30 (55.4 +/- 3.3 W.m (-2)) versus control (66.9 +/- 4.4 W.m(-2)). Examination of the mean body temperature-metabolic heat production relationship indicated that the threshold for shivering was lower (P< 0.05) after SUSOPS (34.8 +/- 0.2 degrees C) versus control (35.8 +/- 0.2 degrees C). Mean weighted skin temperatures ( degrees C) were lower during the initial 1.5 h of CAT in SUSOPS versus control. Heat debt was similar between trials. CONCLUSION: These results indicate that sustained (84-h) military operations leads to greater declines in core temperature, due to either a lag in the initial shivering response or heat redistribution secondary to an insulative acclimation.     

Adverse effects of dietary and furosemide-induced sodium depletion on thermoregulation

In this study, the diuretic furosemide was used in combination with dietary sodium (Na) restriction to quantify the effects of moderate to severe Na depletion on heat tolerance in a validated model of heat stress in rats. Rats were subjected to an Na depletion regimen as follows: a control group (I, n = 17) had free access to a normal diet and tap water; group II (n = 20) consumed the same normal diet and tap water, but was treated with the diuretic furosemide at a dose of 10 mg.kg-1.d-1, ip; group III (n = 18) had free access to an Na-free diet and deionized drinking water; group IV (n = 21) consumed the same Na-free diet and electrolyte-free water, but was also treated with furosemide. Both the dietary and drug manipulations affected significant (p less than 0.05) negative electrolyte and water balances. Group IV consistently exhibited the greatest decrements. Following the 4-d depletion all four groups were acutely exposed to a 42 degrees C, 25-30% rh environmental heat stress during which time core body temperature increased. The time required for rectal temperature to reach 42.6 degrees C was significantly (p less than 0.05) decreased from a time of 242 +/- 8 min in the control group to 176 +/- 14, 181 +/- 8, and 111 +/- 11 min in groups II, III and IV, respectively. We concluded that Na deprivation and diuretic treatment can elicit a 25-50% reduction in heat tolerance due to electrolyte depletion and dehydration. These data confirm that during environmental heat stress uncompensated negative Na balance may predispose an individual to heat illnesses.     

Exercising in environmental extremes : a greater threat to immune function?

Athletes, military personnel, fire fighters, mountaineers and astronauts may be required to perform in environmental extremes (e.g. heat, cold, high altitude and microgravity). Exercising in hot versus thermoneutral conditions (where core temperature is > or = 1 degrees C higher in hot conditions) augments circulating stress hormones, catecholamines and cytokines with associated increases in circulating leukocytes. Studies that have clamped the rise in core temperature during exercise (by exercising in cool water) demonstrate a large contribution of the rise in core temperature in the leukocytosis and cytokinaemia of exercise. However, with the exception of lowered stimulated lymphocyte responses after exercise in the heat, and in exertional heat illness patients (core temperature > 40 degrees C), recent laboratory studies show a limited effect of exercise in the heat on neutrophil function, monocyte function, natural killer cell activity and mucosal immunity. Therefore, most of the available evidence does not support the contention that exercising in the heat poses a greater threat to immune function (vs thermoneutral conditions). From a critical standpoint, due to ethical committee restrictions, most laboratory studies have evoked modest core temperature responses (< 39 degrees C). Given that core temperature during exercise in the field often exceeds levels associated with fever and hyperthermia (approximately 39.5 degrees C) field studies may provide an opportunity to determine the effects of severe heat stress on immunity. Field studies may also provide insight into the possible involvement of immune modulation in the aetiology of exertional heat stroke (core temperature > 40.6 degrees C) and identify the effects of acclimatisation on neuroendocrine and immune responses to exercise-heat stress. Laboratory studies can provide useful information by, for example, applying the thermal clamp model to examine the involvement of the rise in core temperature in the functional immune modifications associated with prolonged exercise. Studies investigating the effects of cold, high altitude and microgravity on immunity and infection incidence are often hindered by extraneous stressors (e.g. isolation). Nevertheless, the available evidence does not support the popular belief that short- or long-term cold exposure, with or without exercise, suppresses immunity and increases infection incidence. In fact, controlled laboratory studies indicate immuno-stimulatory effects of cold exposure. Although some evidence shows that ascent to high altitude increases infection incidence, clear conclusions are difficult to make because of some overlap with the symptoms of acute mountain sickness. Studies have reported suppressed cell-mediated immunity in mountaineers at high altitude and in astronauts after re-entering the normal gravity environment; however, the impact of this finding on resistance to infection remains unclear.     

Fettleber und Fettembolie

We report the case of a 77-year-old woman who was admitted to hospital with a relapsed vertebral compression syndrome due to herniation of the intervetrebral disk. Death occurred 2 days after admittance to hospital and the autopsy and histology revealed sepsis originating from purulent bronchopneumonia. In addition, pulmonary fat embolism grade II-III was present and was also detectable in other organs. The pathogenesis of fat embolism is discussed in the light of the literature. In the present case, postmortem findings in conjunction with the preceding clinical course favour the concept of a hepatic origin of fat embolism due to a pre-existing, partly cystic, fatty degeneration of the liver with spread of fat emboli from congestive liver parenchyma necrosis in the course of increasing right heart insufficiency. Pulmonary fat embolism was clinically relevant and contributed to the fatal outcome.     

Effect of adriamycin combined with 40 and 43 degrees C hyperthermia on cultured V79 cells and S-180 tumor and their uptake of the drug

The combined effects of hyperthermia and chemotherapy with adriamycin (ADR) on both cultured mammalian cells and growing tumors were analyzed according to different temperatures and durations of heating, timing of drug administration, and fractionation of treatments. Furthermore, ADR uptake in tumor was measured to evaluate the effect of ADR in combination with hyperthermia. Hyperthermic cell killing with ADR in vitro was much more potent at 40 degrees C than at 43 degrees C. Results of sequential combinations heating followed by ADR and ADR followed by heating under hyperthermia of 40 and 43 degrees C were not significantly different from those of simultaneous treatment. However, the anti-tumor effect of the combination was much more pronounced at 43 degrees C than at 40 degrees C for up to 60 min of treatment. ADR uptake showed a substantial increase under high temperatures of 40 and 43 degrees C in both cultured cells and tumors. Fractionated treatments combined with chemotherapy and hyperthermia showed no enhanced effects on tumor under temperatures of 40 and 43 degrees C, since three fractionated experiments with ADR and 43 degrees C hyperthermia had an effect almost identical to that of three fractionated experiments with hyperthermia alone, suggesting the possible induction of thermotolerance by ADR. The results of the present study indicate that potentiation of the combined effect of hyperthermia and chemotherapy with ADR may depend only upon the dose in one of these two modalities.     

Clinical experience with thermotron RF-8 capacitive heating for bulky tumors: University of Minnesota experience

We conducted a phase I clinical trial of the feasibility of using the Thermotron RF-8, a capacitative heating device utilizing 8-MHz RF, for the treatment of deep-seated and bulky human tumors. Preclinical studies with agar phantoms demonstrated that deep heating can be achieved with this device when the electrode diameters are sufficiently large relative to the thickness of the heated object. In the clinical application of capacitive heating with radiofrequency, excessive heating of subcutaneous tissue has often been a problem. However, this could be minimized by continuous cooling of the subcutaneous fat with a 10 degrees C saline bolus, beginning more than 20 minutes prior to the start of heating. It was often possible to raise the temperature of deep-seated tumors even in obese patients by applying this pre-cooling method. The mean achieved temperature during 30 to 40 minutes of heating was higher than 42 degrees C and 40 degrees C to 42 degrees C in 26% and 50% of 58 tumors treated, respectively. A combination of hyperthermia (four to ten sessions, twice a week) with full-course or a limited dose of radiotherapy resulted in complete tumor remission in 7% of patients, and partial tumor remission in 50% of patients. In the full-course radiotherapy group, 69% of the tumors were judged to show complete or partial regression, and in the low-dose group, 43% of the tumors regressed completely or partially. Histologic examination of many of the tumors that did not regress showed massive necrosis, indicating that tumor size after hyperthermia is not an accurate criterion of the treatment result. Side effects were minimal, and vital sign changes during heating were insignificant. Our data, together with those reported by Japanese investigators, clearly demonstrated that hyperthermia with the Thermotron RF-8 in combination with radiotherapy is useful in treating deep-seated and bulky tumors that fail to respond to conventional treatment modalities.     

Hyperthermia: biological studies at the cellular level.

Tissue culture techniques were used to study the effect of hyperthermia on several cell types, including normal liver and hepatoma cells, as well as cell lines that have been established in culture for many years. Short exposures (less than 30 min.) at 45 degrees C readily kill a large proportion of cells. The response to heat was strikingly similar in all cells tested, and no preferential killing of neoplastic cells could be demonstrated. By contrast, hypoxic cells were found to be dramatically more susceptible to killing by heat than aerated cells. This is the reverse of the situation for x irradiation. The effectiveness of x irradiation was potentiated by treating the irradiated cells for 20 min. at 43 degrees C, which did not kill a detectable number of cells.     

Pulmonary fat embolization as a diagnostic finding for heat exposure

The aim of this study was to examine whether the detection of pulmonary fat embolization is valid as a significant indicator of heat exposure in forensic autopsies. In 54 cases where there was no evidence of fracture, burn or pancreatitis, 25 cases (46.3%) showed pulmonary fat embolization, the degree of which was pathohistologically classified as slight in all cases. Among the 25 cases where the pulmonary fat embolization was detected, the individual had died under a high ambient temperature in 14 cases (56%). Based on logistic regression analysis, pulmonary fat embolization was found to be associated with a high ambient temperature, but not associated with coronary arteriosclerosis, fatty infiltration in the liver, severe infectious diseases, intracranial hemorrhage or the detection of methamphetamine in the blood. Further investigations are necessary before these findings can be applied in forensic autopsy cases; however, it is likely that the detection of pulmonary fat embolization is valuable as one of the diagnostic findings indicating antemortem heat exposure.     

Focal gene induction in the liver of rats by a heat-inducible promoter using focused ultrasound hyperthermia: preliminary results

OBJECTIVE: We sought to examine high-intensity focused ultrasound (HIFU)-induced hyperthermia in the liver of a rat model to focally induce green-fluorescent protein (GFP). MATERIALS AND METHODS: A total of 25 Copenhagen rats were included in this study. Rats were divided into groups treated with an adenovirus coding for green fluorescent protein (GFP) under the control of a hsp70B promoter and a CMV promoter. Ad-CMV-GFP-treated rats served as positive control. Untreated controls only subjected to MRI +/- HIFU-treatment served to find out optimal power of HIFU in the target area of the liver. Temperature was noninvasively monitored by temperature sensitive magnetic resonance imaging (MRI). RESULTS: Rats treated with Ad-hsp70B-GFP demonstrated localized gene induction within the liver parenchyma, in good correlation with MRI and histology. Applying an acoustic power of 1.92 W a relatively uniform focal temperature up to 42 +/- 5 degrees C within the liver parenchyma could be documented. 3 x 10(9) plaque-forming units proved to account for a very homogeneous liver infection. Number of fluorescent cells in the region of hyperthermia was similar to the control group treated with Ad-CMV-GFP. CONCLUSION: Using the introduced parameters spatially controlled gene induction within a parenchymal organ such as the liver in rats using HIFU under control of MRI is feasible.     

Induction of thermal tolerance of rat sciatic nerve by mild hyperthermia.

A 5 mm segment of the rat sciatic nerve was treated at 38 or 43 degrees C for 30 min using a brass thermode. This pretreatment was followed by a test heat treatment at 45 degrees C. Different intervals between the pretreatment and test treatment were studied. The effect of fractionated hyperthermia on the motor function of rat sciatic nerve was evaluated using a functional assay, the toe-spreading test. Both pretreatments led to thermal resistance of the nerve, which was maximal 24 h after the pretreatment. Thermal resistance, induced at 38 degrees C, did not show any decay over a period of 6 weeks. Thermal resistance, induced at 43 degrees C, decayed slowly, but after a 6-week interval between priming and test heat treatment thermal resistance was still observed. As the resistance induced by a mild heat pretreatment is transient, we considered this to be thermotolerance. We accounted for the thermal resistance induced by the 38 degrees C pretreatment in the calculation of the thermal tolerance ratio (TTR) after mild heat treatment at 43 degrees C. Maximal thermal tolerance was observed 24 h after mild heat with a TTR of 3.4 +/- 0.6. The TTR after a 6-week interval had declined to 1.4 +/- 0.3.