Influence of various types of species-specific acoustic signals on the heart rate of mammals

INTRODUCTION: Successful radiofrequency ablation of an accessory pathway has been demonstrated to be associated with an electrode-tissue interface temperature of approximately 60 degrees C or an impedance change of -5 to -10 omega. However, the temperature and impedance changes associated with ablation of AV nodal reentrant tachycardia (AVNRT) using the slow pathway approach have not been reported. Therefore, the purpose of this study was to define the temperature and impedance changes achieved during ablation of AVNRT: METHODS AND RESULTS: The study included 35 consecutive patients with AVNRT undergoing radiofrequency ablation of the slow pathway with a fixed power output of 32 W, and using a catheter with a thermistor bead embedded in the distal 4-mm electrode. The procedure was successful in each patient. The steady-state electrode-tissue interface temperature during successful applications of energy was 48.5 +/- 3.3 degrees C (range 42 degrees to 56 degrees C), and the steady-state temperature during ineffective applications was 46.8 degrees +/- 5.5 degrees C (P = 0.03). The mean impedance change during all applications of energy was -1.4 +/- 2.8 omega, and did not differ significantly during effective and ineffective applications. Coagulum formation resulted during five applications (2.7%) in two patients (5.7%). There were no recurrences during 114 +/- 21 days of follow-up. CONCLUSIONS: Successful ablation of AVNRT using fixed power output is achieved at an electrode-tissue interface temperature of approximately 48 degrees C and is associated with a drop in impedance of 1 to 2 omega. These findings suggest that slow pathway ablation requires less heating at the electrode-tissue interface than does accessory pathway or AV junction ablation.     

Leg heat content continues to decrease during the core temperature plateau in humans anesthetized with isoflurane

BACKGROUND: Sufficient hypothermia during anesthesia provokes thermoregulatory responses, but the clinical significance of these responses remains unknown. Nonshivering thermogenesis does not increase metabolic heat production in anesthetized adults. Vasoconstriction reduces cutaneous heat loss, but the initial decrease appears insufficient to cause a thermal steady state (heat production equaling heat loss). Accordingly, the authors tested the hypotheses that: 1) thermoregulatory vasoconstriction prevents further core hypothermia; and 2) the resulting stable core temperature is not a thermal steady state, but, instead, is accompanied for several hours by a continued reduction in body heat content. METHODS: Six healthy volunteers were anesthetized with isoflurane (0.8%) and paralyzed with vecuronium. Core hypothermia was induced by fan cooling, and continued for 3 h after vasoconstriction in the legs was detected. Leg heat content was calculated from six needle thermocouples and skin temperature, by integrating the resulting parabolic regression over volume. RESULTS: Core temperature decreased 1.0 +/- 0.2 degrees C in the 1 h before vasoconstriction, but only 0.4 +/- 0.3 degrees C in the subsequent 3 h. This temperature decrease, evenly distributed throughout the body, would reduce leg heat content 10 kcal. However, measured leg heat content decreased 49 +/- 18 kcal in the 3 h after vasoconstriction. CONCLUSIONS: These data thus indicate that thermoregulatory vasoconstriction produces a clinically important reduction in the rate of core cooling. This core temperature plateau resulted, at least in part, from sequestration of metabolic heat to the core which allowed core temperature to remain nearly constant, despite a continually decreasing body heat content.     

The LETR-Principle: a novel method to assess electrode-tissue contact in radiofrequency ablation

INTRODUCTION: Stable electrode-tissue contact is crucial for successful radiofrequency ablation of cardiac tachyarrhythmias. In this in vitro study, a custom-made radiofrequency generator was used to evaluate the correlation between tip temperature response to a minimal radiofrequency power delivery (Low Energy Temperature Response: LETR-Principle) and electrode-tissue contact as well as lesion size. METHODS AND RESULTS: A battery-powered radiofrequency generator (LETR-Box, 500 kHz, 0.1 to 0.3 W) could measure the temperature increase at the tip electrode with 0.01 degrees C accuracy. The device was tested in vitro using isolated porcine ventricular tissue. For various electrode-tissue settings (i.e., 0 to 0.89 N contact force), the temperature increase (deltaT) due to 0.1-W power delivery for 10 seconds was recorded. Subsequently, for the same electrode-tissue contact, a temperature-controlled radiofrequency ablation was performed (70 degrees C target temperature, 50-W maximum output, 30 sec). Thereafter, the lesion size was measured histologically. To prove the safety of the applied LETR-Principle, the tissue was inspected microscopically after continuous radiofrequency power delivery of 0.3 W for 1 hour with high contact pressure (1.33 N). The delivery of 0.1-W radiofrequency power resulted in an average deltaT of 0.18 degrees +/- 0.13 degrees C. During temperature-controlled radiofrequency ablation, the tip temperature was 59 degrees +/- 8.5 degrees C, resulting in a lesion depth of 4.8+/-0.6 mm. The correlation coefficient between deltaT and contact force was 0.97 and 0.81, respectively, for lesion depth. No lesion was microscopically visible after power delivery of 0.3 W for 1 hour with 1.33 N contact pressure. CONCLUSION: The LETR-Principle safely indicates electrode-tissue contact and lesion depth under in vitro conditions and can be useful for catheter positioning during radiofrequency ablation procedures.     

Malignant melanoma in Europe: changes in mortality rates (1970-90) in European Community countries

We measured metabolic rates (mL O2 h-1, converted to kcal d-1), deep body temperatures (degree C), and skin temperatures (degree C) and calculated whole-animal thermal conductances (mL O2 g-1 h-1 degree C-1) of five 3-yr-old harbor seals (Phoca vitulina concolor) at air temperatures between -20 degrees and 35 degrees C. The mean thermal neutral zone of these seals extended from a lower critical temperature of -12.9 degrees +/- 1.6 degrees C (SD) to an upper critical temperature of 28.6 degrees +/- 1.7 degrees C. Hyperthermia was observed at an ambient air temperature of 35 degrees C. Mean standard metabolic rate was 1,553.6 +/- 168.2 kcal d-1, about 1.2 times the value expected for adult animals of similar body mass (mean mass = 49.2 +/- 7.5 kg). Mean deep body temperature increased from 37.5 degrees +/- 0.30 degrees C at an ambient temperature of 30 degrees C and reached 39.3 degrees +/- 0.33 degrees C at an ambient temperature of 35 degrees C. Skin temperature decreased with decreasing ambient temperature but remained well above ambient temperature. Mean whole-animal thermal conductance decreased from an ambient temperature of 35 degrees C until it reached a minimum value of 0.007 mL O2 g-1 h-1 degree C-1 at -4.0 degrees C; it then increased with a further decrease in ambient temperature. In comparison to the thermal limits of the same seals during their first year of life, the results indicate a broadening of the thermal neutral zone with age: an 11 degrees C decrease in the lower critical temperature and a 3.5 degrees C increase in the upper critical temperature. These findings suggest that warm ambient air temperatures should not pose any particular thermoregulatory problems for larger and older harbor seals, even beyond the limits of their current annual distribution.     

A system for inducing hyperthermia in sheep

A system that produces hyperthermia in pregnant sheep in a consistent and reproducible manner was designed. The experimental approach was through control of ambient temperature and relative humidity in a closed chamber; the sheep was unable to lose its metabolic heat in an environment of 42 degrees C and 75% relative humidity. This system resulted in a steady and progressive temperature rise of 2.5 degrees C in the maternal abdominal aorta in 120 +/- 17 min.     

Exercise and extracorporeal blood cooling during hemodialysis

Intradialytic exercise may improve hemodialysis efficiency. Because exercise interferes with thermal energy and fluid balance, relative blood volume changes (deltaBV%), arterial blood temperatures (T(art)), mean arterial blood pressures, and heart rates (HR) were measured using different dialysate temperatures (Tdia). Four stable patients (age, 49.9 +/- 7.7 years) were studied during 22 treatments that either maintained Tdia at 35.9 degrees C +/- 0.1 degrees C (standard) or provided maximum extracorporeal cooling (cool, Tdia = 34.8 degrees C +/- 0.8 degrees C) in attempts to maintain a constant T(art). Patients exercised for 1 hr at a resistance of 21 +/- 5 W on a stationary bicycle ergometer. Energy expenditure monitored by indirect calorimetry increased from 117 +/- 38 W (baseline) to 338 +/- 116 W (exercise). Mean arterial blood pressures increased by 7 +/- 7 mmHg with cool Tdia, but remained unchanged (-1 +/- 4 mmHg) with standard Tdia (p < 0.05). However, the increase in T(art) was smaller with cool (0.1 degrees C +/- 0.3 degrees C) than with standard (0.3 degrees C +/- 0.2 degrees C) Tdia (p < 0.05). The larger increase in O2 uptake per change in HR (68 +/- 56 vs 38 +/- 17 ml/beat) indicated an increase in stroke volume when cool dialysate was used (p = NS). Exercise produced a small (0.95% +/- 0.95%), but significant, decrease in deltaBV% that reversed at the end of exercise. Intradialytic exercise was well tolerated, especially when Tdia was lowered such that hemodynamic stress to dissipate excess heat through the cutaneous circulation was reduced and blood pressure stability was improved.     

Hypothermia eliminates isoflurane requirements at 20 degrees C

BACKGROUND: Hypothermia decreases anesthetic requirements, but the temperature that completely eliminates anesthetic needs has not been previously determined. METHODS: Eight female goats were anesthetized with isoflurane and catheters were placed in the femoral artery and cranial vena cava, after which the right carotid artery and external jugular vein were dissected free. Peripheral temperature was monitored in the rectum and core temperature in the vena cava. A thermistor was placed in the epidural space via a small burr hole to monitor brain temperature. Minimum alveolar concentration (MAC) for isoflurane was determined by eliciting gross, purposeful movement with a tail clamp. Cardiopulmonary bypass (CPB) was established using bubble oxygenators with venous blood drained from a jugular vein and arterial blood infused with a roller pump into the carotid artery. The animals were cooled to approximately 29 degrees C, and MAC redetermined, after which further cooling to 20 degrees C was accomplished. Isoflurane was eliminated, core and brain temperature adjusted in 2-3 degrees C increments, and the tail clamp applied until two temperatures were found that just permitted and just prevented movement. The animals were rewarmed, isoflurane added, and post-CPB MAC determined. RESULTS: At 38.5 degrees C, pre-CPB MAC was 1.3 +/- 0.1% (mean +/- SEM). At 29.0 degrees C, MAC was 0.7 +/- 0.1%, and the anesthetizing temperature was 20.1 +/- 0.6 degrees C. At 37.3 degrees C, post-CPB MAC was 1.0 +/- 0.1% (P < 0.05 vs. pre-CPB). CONCLUSIONS: These results confirm the rectilinear decrease in MAC seen in previous studies and establishes the anesthetizing temperature at 20 degrees C.     

Ambient temperature effects on thermoregulation and endurance in anticholinesterase-treated rats

In sedentary animals, physostigmine (PH) administration resulted in a decreased core temperature that is ambient temperature (Ta) dependent. PH administration in rats exercising on a treadmill (26 degrees C, 50% rh, 11m/min, 6 degrees incline) decremented endurance and increased rate of rise of core temperature (heating rate, HR). This study was undertaken to examine the effects of Ta on the endurance and thermoregulatory decrements of PH-treated running rats. Adult male rats (510-530g) were given either 0.2ml saline (C) or 100 ug/kg physostigmine salicylate in 0.2 ml saline via tail vein 15 min prior to the start of running to exhaustion at 10, 15, 26, or 30 degrees C. In both C- and PH-treated groups, endurance decreased and HR increased with increasing Ta from 15 to 30 degrees C. At 15 and 26 degrees C the C rats ran significantly (p < .05) longer and had significantly lower HR than the PH rats: C15 = 90 +/- 8 min, 0.022 +/- 0.006 degrees C/min; C26 = 67 +/- 6, 0.051 +/- 0.007; PH15 = 57 +/- 5, 0.052 +/- 0.008; and PH26 = 43 +/- 6, 0.092 +/- 0.007. At 10 and 30 degrees C there were no significant differences between C and PH-treated rats. A Ta of 30 degrees C was too high for effective cooling in either group, and at 10 degrees C both groups were able to dissipate heat despite the increased metabolic rate of the PH-treated rats. The PH-treated rat model of cholinergic drug effect is useful at a Ta of 15 and 26 degrees C.     

Beta-adrenoceptor stimulation-mediated preconditioning-like cardioprotection in perfused rat hearts

The metabolic rates of six female grey seal (Halichoerus grypus) pups were measured during their postweaning fast at air temperatures between -15 degrees and 30 degrees C. The composite of their individual thermal neutral zones extended from a mean lower critical temperature of -7.1 degrees +/- 0.7 degree C to a mean upper critical temperature of 23.0 degrees +/- 0.4 degree C. Within the thermal neutral zone, mean standard metabolic rate of the fasting animals was 1,265 +/- 82 kcal d-1, or about 1.1 times the value predicted for an adult animal of similar body mass (mean mass = 40.9 +/- 1.2 kg). For those grey seal populations that reproduce during winter months in the eastern and western Atlantic and in the Baltic Sea, the lower critical temperature of fasting pups corresponds closely with the coldest mean monthly air temperature at the northern end of their breeding ranges. This observation supports the hypothesis that cold ambient air temperatures limit the northern breeding distribution of grey seals, primarily through their thermoregulatory effects on small, fasting pups before they enter the water.     

Hydration effects on physiological strain of horses during exercise-heat stress

This study examined the effects of hyperhydration, exercise-induced dehydration, and oral fluid replacement on physiological strain of horses during exercise-heat stress. On three occasions, six horses completed a 90-min exercise protocol (50% maximal O2 uptake, 34.5 degrees C, 48% relative humidity) divided into two 45-min periods (exercise I and exercise II) with a 15-min recovery between exercise bouts. In random order, horses received no fluid (NF), 10 liters of water (W), or a carbohydrate-electrolyte solution (CE) 2 h before exercise and between exercise bouts. Compared with NF, preexercise hyperhydration (W and CE) did not alter heart rate, cardiac output (Q), stroke volume (SV), core body temperature, sweating rate (SR), or sweating sensitivity during exercise I. In contrast, after exercise II, exercise-induced dehydration in NF (decrease in body mass: NF, 5.6 +/- 0.8%; W, 1.1 +/- 0.4%; CE, 1.0 +/- 0.2%) resulted in greater heat storage, with core body temperature approximately 1. 0 degrees C higher compared with W and CE. In exercise II, the greater thermal strain in NF was associated with significant (P < 0. 05) decreases in Q (10 +/- 2%), SV (9 +/- 3%), SR, and sweating sensitivity. We concluded that 1) preexercise hyperhydration provided no thermoregulatory advantage; 2) maintenance of euhydration by oral fluid replacement ( approximately 85% of sweat fluid loss) during exercise in the heat was reflected in higher Q, SV, and SR with decreased heat storage; and 3) W or an isotonic CE solution was equally effective in reducing physiological strain associated with exercise-induced dehydration and heat stress.     

Inhibition of shivering increases core temperature afterdrop and attenuates rewarming in hypothermic humans

During severe hypothermia, shivering is absent. To simulate severe hypothermia, shivering in eight mildly hypothermic subjects was inhibited with meperidine (1.5 mg/kg). Subjects were cooled twice (meperidine and control trials) in 8 degrees C water to a core temperature of 35.9 +/- 0.5 (SD) degrees C, dried, and then placed in sleeping bags. Meperidine caused a 3.2-fold increase in core temperature afterdrop (1.1 +/- 0.6 vs. 0.4 +/- 0.2 degree C), a 4.3-fold increase in afterdrop duration (89.4 +/- 31.4 vs. 20.9 +/- 5.7 min), and a 37% decrease in rewarming rate (1.2 +/- 0.5 vs. 1.9 +/- 0.9 degrees C/h). Meperidine inhibited overt shivering. Oxygen consumption, minute ventilation, and heart rate decreased after meperidine injection but subsequently returned toward preinjection values after 45 min postimmersion. This was likely due to the increased thermoregulatory drive with the greater afterdrop and the short half-life of meperidine. These results demonstrate the effectiveness of shivering heat production in attenuating the postcooling afterdrop of core temperature and potentiating core rewarming. The meperidine protocol may be valuable for comparing the efficacy of various hypothermia rewarming methods in the absence of shivering.     

Global analysis of the thermal and chemical denaturation of the N-terminal domain of the ribosomal protein L9 in H2O and D2O. Determination of the thermodynamic parameters, deltaH(o), deltaS(o), and deltaC(o)p and evaluation of solvent isotope effects

The stability of the N-terminal domain of the ribosomal protein L9, NTL9, from Bacillus stearothermophilus has been monitored by circular dichroism at various temperatures and chemical denaturant concentrations in H2O and D2O. The basic thermodynamic parameters for the unfolding reaction, deltaH(o), deltaS(o), and deltaC(o)p, were determined by global analysis of temperature and denaturant effects on stability. The data were well fit by a model that assumes stability varies linearly with denaturant concentration and that uses the Gibbs-Helmholtz equation to model changes in stability with temperature. The results obtained from the global analysis are consistent with information obtained from individual thermal and chemical denaturations. NTL9 has a maximum stability of 3.78 +/- 0.25 kcal mol(-1) at 14 degrees C. DeltaH(o)(25 degrees C) for protein unfolding equals 9.9 +/- 0.7 kcal mol(-1) and TdeltaS(o)++(25 degrees C) equals 6.2 +/- 0.6 kcal mol(-1). DeltaC(o)p equals 0.53 +/- 0.06 kcal mol(-1) deg(-1). There is a small increase in stability when D2O is substituted for H2O. Based on the results from global analysis, NTL9 is 1.06 +/- 0.60 kcal mol(-1) more stable in D2O at 25 degrees C and Tm is increased by 5.8 +/- 3.6 degrees C in D2O. Based on the results from individual denaturation experiments, NTL9 is 0.68 +/- 0.68 kcal mol(-1) more stable in D2O at 25 degrees C and Tm is increased by 3.5 +/- 2.1 degrees C in D2O. Within experimental error there are no changes in deltaH(o) (25 degrees C) when D2O is substituted for H2O.     

Physiological responses in nonheat acclimated horses performing treadmill exercise in cool (20 degrees C/40% RH), hot dry (30 degrees C/40% RH) and hot humid (30 degrees C/80% RH) conditions

The aim of the present study was to determine the effect of different environmental conditions on physiological response to exercise. Four winter acclimatised, nonheat acclimated horses of different breeds were exercised at 20 degrees C/40% RH (CD), 30 degrees C/40% RH (HD) and 30 degrees C/80% RH (HH). The exercise test was designed to represent the structure and intensity of a One star Speed and Endurance test (competition exercise test [CET]). All 4 horses were able to complete the full CET (60 min + 30 min active recovery) in CD and HD, but only one horse completed the CET in HH. Two horses were stopped because of pronounced general fatigue and one because of a right atrial temperature (TRA) of 43 degrees C. Oxygen uptake on each phase was not different between CD and HD, but was higher during Phases B, C and D in HH. Mean peak TRA at the end of Phase D was 40.3 +/- 0.2, 41.6 +/- 0.4 and 42 +/- 0.3 degrees C for CD, HD and HH, respectively. Corresponding, mean peak rectal temperatures (TREC) following Phase D were 39.5 +/- 0.1, 40.6 +/- 0.1 and 41.5 +/- 0.1 degree C for CD, HD and HH, respectively. Mean time to peak TREC was 9.3 +/- 1.1 (CD), 7.3 +/- 1.8 (HD) and 10.8 +/- 2.3 (HH) min and was not significantly different between conditions (P > 0.05). Heat dissipation amounted to 83 +/- 1, 73 +/- 2 and 70 +/- 1% of heat production in CD, HD and HH, respectively. Weight loss was significantly correlated with both body surface area (CD r = 0.85; HD r = 0.87; HH r = 0.81) and bodyweight (CD r = 0.97; HD r = 0.93; HH r = 0.94). The greatest weight loss recorded was 4.6% bodyweight in one horse in HD. The mean increase in exercise intensity over the whole CET (in terms of VO2) of HD and HH and HH compared with CD was 5 +/- 3 and 14 +/- 3% higher, respectively. The exercise induced hyperthermia and the reduced capacity for heat dissipation produced partial compensatory responses in minute ventilation (VE), particularly during Phase C, when the horses were trotting. In HD, the increase in VE was achieved mainly through an increase in frequency, whilst in HH it was achieved through an increase in tidal volume (VT). The horses demonstrated a high degree of tolerance to environmental heat load, suggesting a high thermoregulatory capacity. However, for unacclimatised animals exercising in severely hot and humid conditions, performance may be limited.     

Thermoregulatory vasoconstriction impairs active core cooling

BACKGROUND: Many clinicians now consider hypothermia indicated during neurosurgery. Active cooling often will be required to reach target temperatures < 34 degrees C sufficiently rapidly and nearly always will be required if the target temperature is 32 degrees C. However, the efficacy even of active cooling might be impaired by thermoregulatory vasoconstriction, which reduces cutaneous heat loss and constrains metabolic heat to the core thermal compartment. The authors therefore tested the hypothesis that the efficacy of active cooling is reduced by thermoregulatory vasoconstriction. METHODS: Patients undergoing neurosurgical procedures with hypothermia were anesthetized with either isoflurane/nitrous oxide (n = 13) or propofol/fentanyl (n = 13) anesthesia. All were cooled using a prototype forced-air cooling device until core temperature reached 32 degrees C. Core temperature was measured in the distal esophagus. Vasoconstriction was evaluated using forearm minus fingertip skin-temperature gradients. The core temperature triggering a gradient of 0 degree C identified the vasoconstriction threshold. RESULTS: In 6 of the 13 patients given isoflurane, vasoconstriction (skin-temperature gradient = 0 degrees C) occurred at a core temperature of 34.4 +/- 0.9 degree C, 1.7 +/- 0.58 h after induction of anesthesia. Similarly, in 7 of the 13 patients given propofol, vasoconstriction occurred at a core temperature of 34.5 +/- 0.9 degree C, 1.6 +/- 0.6 h after induction of anesthesia. In the remaining patients, vasodilation continued even at core temperatures of 32 degrees C. Core cooling rates were comparable in each anesthetic group. However, patients in whom vasodilation was maintained cooled fastest. Patients in whom vasoconstriction occurred required nearly an hour longer to reach core temperatures of 33 degrees C and 32 degrees C than did those in whom vasodilation was maintained (P < 0.01). CONCLUSIONS: Vasoconstriction did not produce a full core temperature "plateau," because of the extreme microenvironment provided by forced-air cooling. However, it markedly decreased the rate at which hypothermia developed. The approximately 1-h delay in reaching core temperatures of 33 degrees C and 32 degrees C could be clinically important, depending on the target temperature and the time required to reach critical portions of the operation.     

Postanesthetic vasoconstriction slows peripheral-to-core transfer of cutaneous heat, thereby isolating the core thermal compartment

Forced-air warming during anesthesia increases core temperature comparably with and without thermoregulatory vasoconstriction. In contrast, postoperative forced-air warming may be no more effective than passive insulation. Nonthermoregulatory anesthesia-induced vasodilation may thus influence heat transfer. We compared postanesthetic core rewarming rates in volunteers given cotton blankets or forced air. Additionally, we compared increases in peripheral and core heat contents in the postanesthetic period with data previously acquired during anesthesia to determine how much vasomotion alters intercompartmental heat transfer. Six men were anesthetized and cooled passively until their core temperatures reached 34 degrees C. Anesthesia was then discontinued, and shivering was prevented by giving meperidine. On one day, the volunteers were covered with warmed blankets for 2 h; on the other, volunteers were warmed with forced air. Peripheral tissue heat contents were determined from intramuscular and skin thermocouples. Predicted changes in core temperature were calculated assuming that increases in body heat content were evenly distributed. Predicted changes were thus those that would be expected if vasomotor activity did not impair peripheral-to-core transfer of applied heat. These results were compared with those obtained previously in a similar study of anesthetized volunteers. Body heat content increased 159 +/- 35 kcal (mean +/- SD) more during forced-air than during blanket warming (P < 0.001). Both peripheral and core temperatures increased significantly faster during active warming: 3.3 +/- 0.7 degrees C and 1.1 +/- 0.4 degrees C, respectively. Nonetheless, predicted core temperature increase during forced-air warming exceeded the actual temperature increase by 0.8 +/- 0.3 degree C (P < 0.001). Vasoconstriction thus isolated core tissues from heat applied to the periphery, with the result that core heat content increased 32 +/- 12 kcal less than expected after 2 h of forced-air warming (P < 0.001). In contrast, predicted and actual core temperatures differed only slightly in the anesthetized volunteers previously studied. In contrast to four previous studies, our results indicate that forced-air warming increases core temperature faster than warm blankets. Postanesthetic vasoconstriction nonetheless impeded peripheral-to-core heat transfer, with the result that core temperatures in the two groups differed less than might be expected based on systemic heat balance estimates. Implications: Comparing intercompartmental heat flow in our previous and current studies suggests that anesthetic-induced vasodilation influences intercompartmental heat transfer and distribution of body heat more than thermoregulatory shunt vasomotion.     

High-performance liquid chromatographic method for resolving the enantiomers of mexiletine and two major metabolites isolated from microbial fermentation media

PURPOSE: This Phase I trial tests the ability of a new hyperthermia device, the transrectal ultrasound probe, to heat the prostate gland, and evaluates the toxicity of transrectal ultrasound hyperthermia (TRUSH) given with concurrent standard external beam irradiation in the treatment of locally-advanced adenocarcinoma of the prostate. METHODS AND MATERIALS: Between June, 1990 and August, 1991, 14 patients with American Urological Society Stage C2 or D1 adenocarcinoma of the prostate were treated with TRUSH concurrently with standard external beam radiotherapy to the prostate. Twenty-two heat treatments were delivered in 14 patients; 8 patients received two TRUSH procedures, each separated by 1 week. Patient age ranged between 53-86 (mean: 72) years. Three patients had well-, 6 patients had moderately-, and 5 patients had poorly-differentiated adenocarcinoma of the prostate. Karnofsky status ranged from 70-90. Standard radiotherapy to the prostate and periprostatic tissues was delivered using a four-field approach with 1.8-2 Gy daily fractions delivered 5 x/week to a total dose of 67-70 Gy calculated to the minimum tumor volume. TRUSH was delivered after transperineal placement of multipoint thermometry probes by a urologist, under transrectal ultrasound guidance. Two to three thermocouple probes containing seven sensors each were placed in the prostate in an attempt to sample temperatures throughout the gland. The sensor depth from the rectal wall ranged from 5-25 mm. RESULTS: Thirty-six percent of all sensors were heated above 42.5 degrees C averaged over 30 min; and all patients had at least some sensors within the prostate heated to temperatures > or = 42.5 degrees C. The average temperature of all sensors of all sensors (T(ave) +/- s.d.) over all treatments, however, was only 41.9 degrees C +/- 0.9 degrees C over 30 min. The maximum temperature for normal tissues outside the gland was 41.1 degrees C +/- 1.3 degrees C. Treatments have been well-tolerated with few complications. Tolerance has been "good" in 17/22, "fair" in 3/22, and "treatment limiting" in 2/22 treatments secondary to position intolerance and/or pain. There has been one episode of hypotension related to narcotic administration and three episodes of rapidly resolving pain during hyperthermia treatment. Mild hematuria has occurred in 5/22, and moderate hematuria has occurred in 2/22 transperineal thermometer catheter placements. CONCLUSION: In conclusion, TRUSH is well-tolerated and has great potential for consistently heating the prostate gland. We anticipate that further equipment modifications will improve our ability to heat the entire prostate to temperatures > 42.5 degrees C.     

Characterisation of the glass transition of an amorphous drug using modulated DSC

PURPOSE: The use of modulated differential scanning calorimetry (MDSC) as a novel means of characterising the glass transition of amorphous drugs has been investigated, using the protease inhibitor saquinavir as a model compound. In particular, the effects of measuring variables (temperature cycling, scanning period, heating mode) have been examined. METHODS: Saquinavir samples of known moisture content were examined using a TA Instruments 2920 MDSC at a heating rate of 2 degrees C/min and an amplitude of +/-0.159 degrees C with a period of 30 seconds. These conditions were used to examine the effects of cycling between - 50 degrees C and 150 degrees C. A range of periods between 20 and 50 seconds were then studied. Isothermal measurements were carried out between 85 degrees C and 120 degrees C using an amplitude of +/-0.159 degrees C with a period of 30 seconds. RESULTS: MDSC showed the glass transition of saquinavir (0.98 +/- 0.05%w/w moisture content) in isolation from the relaxation endotherm to give an apparent glass transition temperature of 107.0 degrees C +/- 0.4 degrees C. Subsequent temperature cycling gave reproducible glass transition temperatures of approximately 105 degrees C for both cooling and heating cycles. The enthalpic relaxation peak observed in the initial heating cycle had an additional contribution from a Tg "shift" effect brought about by the difference in response to the glass transition of the total and reversing heat flow signals. Isothermal studies yield a glass transition at 105.9 degrees C +/- 0.1 degrees C. CONCLUSIONS: MDSC has been shown to be capable of separating the glass transition of saquinavir from the relaxation endotherm, thereby facilitating measurement of this parameter without the need for temperature cycling. However, the Tg "shift" effect and the number of modulations through the transition should be taken into account to avoid drawing erroneous conclusions from the experimental data. MDSC has been shown to be an effective method of characterising the glass transition of an amorphous drug, allowing the separate characterisation of the Tg and endothermic relaxation in the first heating cycle.     

Thermogenesis during rest and exercise in cold air

Nine non-cold-acclimated subjects (5 female, 4 male, mean age 22.5 years) were studied to determine whether nonshivering thermogenesis contributes to cold-induced metabolic heat production during rest (50 min standing) and exercise (40 min treadmill walking) in 5 degrees C. Propranolol was administered orally (females, 60 mg, 1.12 mg.kg-1; males, 80 mg, 0.96 mg.kg-1) to block nonshivering thermogenesis. Measurements were taken at both 25 degrees C, 13.1 Torr (water vapor pressure; 1 Torr = 133.3 Pa) and 5 degrees C, 3.6 Torr, with sessions randomly assigned to be drug-neutral (DN), drug-cold (DC), placebo-neutral (PN), and placebo-cold (PC). Body core temperature was not different between any of the experimental conditions. Mean body temperature (5 degrees C, 32.2 +/- 0.20 degrees C (+/- SEM); 25 degrees C, 35.3 +/- 0.20 degrees C) and mean skin temperature (5 degrees C, 22.4 +/- 0.70 degrees C; 25 degrees C, 31.4 +/- 0.60 degrees C) were lower (p < 0.05) in the 5 degrees C than 25 degrees C environment (rest, exercise, drug (D), placebo (P), combined); while shivering (EMG) was higher (16.5 +/- 3.9% above baseline) at 5 degrees C than 25 degrees C (15 +/- 2.1% below baseline) (p < 0.05). The greater VO2 in 5 degrees C compared with 25 degrees C for the same condition is the thermoregulatory VO2 (TVO2). TVO2 (mL.min-1) was lower (p < 0.05) on the D (mean = 189.5 +/- 17.7) than on the P (mean = 238.1 +/- 20.2) during rest and during exercise (D, 206.1 +/- 63.7; P, 338.4 +/- 46.7). The EMG was 21% above baseline in the DC, and 12% above baseline for PC (p > 0.05). These results suggest a nonshivering component to heat production during acute cold exposure, which can be blocked with propranolol.     

The ocular blood flow tonograph: a new instrument for the measurement of intraocular pressure in rabbits

OBJECTIVES: To determine the intraprostatic pathologic changes following accurately measured doses of transurethral microwave thermal energy in patients with benign prostatic hyperplasia. METHODS: Eight patients scheduled for prostate surgery were treated for approximately 1 hour without anesthesia using a newly designed microwave treatment catheter that allows a close impedance match to prostate tissue and concentrates thermal energy preferentially in the anterior and lateral prostate gland. Interstitial, urethral, and rectal temperatures were continuously measured using a novel stereotactic thermal mapping technique. Serial sections of prostate tissue harvested during subsequent surgery were evaluated pathologically with prostate mapping. RESULTS: Microwave treatment resulted in marked and continuous intraprostate temperature elevation, while urethral and rectal temperatures remained low. Peak intraprostate temperatures in individual patients reached as high as 80 degrees C. Mean temperature reached a maximum of 54 degrees C at a radial distance of approximately 0.5 cm from the urethra and remained 45 degrees C or higher up to a distance of 1.6 cm. The predominant pathologic findings were uniform hemorrhagic necrosis and tissue devitalization without significant inflammation. The mean distance from the urethra to the viable-necrotic tissue border was 1.6 +/- 0.2 cm (range, 0.5 to 2.5). At this border, no more than 1 mm in thickness, temperature averaged 45.7 +/- 0.6 degrees C, and there was a suggestion that pure stromal nodules were more resistant to thermal injury. CONCLUSIONS: Microwave treatment can destroy obstructive prostate tissue while maintaining innocuous urethral and rectal temperatures. Temperatures of 45 degrees C or higher for approximately 1 hour cause uniform thermoablation of prostate tissue.     

Measurement of serosal temperatures and depth of thermal injury generated by thermal balloon endometrial ablation in ex vivo and in vivo models

OBJECTIVE: To evaluate the safety profile of endometrial ablation performed with a thermal balloon as defined by serosal temperature elevation and depth of injury. DESIGN: Observational study with histopathologic correlation conducted in ex vivo and in vivo phases. SETTING: Academic medical center. PATIENT(S): Twenty patients undergoing total abdominal hysterectomy. INTERVENTION(S): Endometrial ablation with a thermal balloon. MAIN OUTCOME MEASURE(S): Serosal temperature elevation and histologic depth of injury. RESULT(S): Ex vivo phase results revealed serosal temperatures remained within a safe physiologic range (<45 degrees C). Greatest depth of myometrial injury in the premenopausal uteri was 5.8 mm over the anterior lower uterine segment. In postmenopausal uterus. the greatest depth of myometrial injury was 3.8 mm in the anterior midline. In vivo phase results revealed mean (+/- SD) peak serosal temperatures of 36.1 +/- 1.6 degrees C. As with the ex vivo phase. histologic examination revealed deep endometrial and superficial myometrial damage to all areas. The greatest depth of myometrial injury occurred in the midfundus at 3.4 mm. CONCLUSION(S): No patients experienced complications or adverse events secondary to treatment. Results showed that transuterine thermal injury is a highly unlikely scenario. In both phases of this study, histologic examination revealed that temperatures exposed to the endometrial layer were sufficient to cause tissue damage.