Mathematical modeling of thermal and circulatory effects during hemodialysis.

Intradialytic hypotension (IDH) is one of the most common complications of hemodialysis (HD) treatment. The initiating factor of IDH is a decrease in blood volume, which is related to an imbalance between ultrafiltration (UF) and refilling rate. Impaired reactivity of resistance and capacitance vessels in reaction to hypovolemia plays possibly a major role in the occurrence of IDH. These vessels also fulfill an important function in body temperature regulation. UF-induced cutaneous vasoconstriction would result in a reduced surface heat loss and an increase in core temperature. To release body heat, skin blood flow is increased at a later stage of the HD treatment, whereby possibly IDH can occur. The aim of the study is to develop a mathematical model that can provide insight into the impact of thermoregulatory processes on the cardiovascular (CV) system during HD treatment. The mathematical procedure has been created by coupling a thermo-physiological model with a CV model to study regulation mechanisms in the human body during HD + UF. Model simulations for isothermal versus thermoneutral HD + UF were compared with measurement data of patients on chronic intermittent HD (n = 13). Core temperature during simulated HD + UF sessions increased within the range of measurement data (0.23°C vs. 0.32 ± 0.41°C). The model showed a decline in mean arterial pressure of -7% for thermoneutral HD + UF versus -4% for isothermal HD + UF after 200 min during which relative blood volume changed by -13%. In conclusion, simulation results of the combined model show possibilities for predicting circulatory and thermal responses during HD + UF.

Effects of temperature and doxorubicin exposure on keratinocyte damage in vitro.

Cancer chemotherapy treatment often leads to hair loss, which may be prevented by cooling the scalp during drug administration. The current hypothesis for the hair preservative effect of scalp cooling is that cooling of the scalp skin reduces blood flow (perfusion) and chemical reaction rates. Reduced perfusion leads to less drugs available for uptake, whereas the reduced temperature decreases uptake of and damage by chemotherapy. Altogether, less damage is exerted to the hair cells, and the hair is preserved. However, the two mechanisms in the hypothesis have not been quantified yet. To quantify the effect of reduced drug damage caused by falling temperatures, we investigated the effect of local drug concentration and local tissue temperature on hair cell damage using in vitro experiments on keratinocytes. Cells were exposed for 4 h to a wide range of doxorubicin concentrations. During exposure, cells were kept at different temperatures. Cell viability was determined after 3 d using a viability test. Control samples were used to establish a concentration-viability curve. Results show that cell survival is significantly higher in cooled cells (T < 22 degrees C) than in non-cooled cells (T = 37 degrees C), but no significant differences are visible between T = 10 degrees C and T = 22 degrees C. Based on this result and previous work, we can conclude that there is an optimal temperature in scalp cooling. Further cooling will only result in unnecessary discomfort for the patient and should therefore be avoided.

Discrete vessel heat transfer in perfused tissue--model comparison.

The aim of this paper is to compare two methods of calculating heat transfer in perfused biological tissue using a discrete vessel description. The methods differ in two important aspects: the representation of the vascular system and the algorithm for calculating the heat flux between tissue and blood vessels. The first method was developed at the University of Utrecht between 1994 and 1998 and has been used in several clinical applications. The second method has been proposed by the first author. The methods are briefly described, their assumptions and limitations are discussed. Finally, the test simulation is introduced and the results produced by both methods are compared. The test indicates that the simpler, and less computationally intensive method proposed by the present author for calculating 2D problems containing countercurrent blood vessel systems can reproduce quite well some features of the solution obtained by the more complex 3D method. The observed discrepancies could be explained on physical grounds.

Effect of forced-air heaters on perfusion and temperature distribution during and after open-heart surgery.

OBJECTIVES: After cardiopulmonary bypass, patients often show redistribution hypothermia, also called afterdrop. Forced-air blankets help to reduce afterdrop. This study explores the effect of forced-air blankets on temperature distribution and peripheral perfusion. The blood perfusion data is used to explain the observed temperature effects and the reduction of the afterdrop. METHODS: Fifteen patients were enrolled in a randomised study. In the test group (n=8), forced-air warmers were used. In the control group (n=7), only passive insulation was used. Core and skin temperatures and thigh temperatures at 0, 8, 18 and 38 mm depth were measured. Laser Doppler flowmetry (LDF) was used to record skin perfusion from the big toe. Blood flow through the femoral artery was determined with ultrasound. RESULTS: Afterdrop in the test group was smaller than in the control group (1.2+/-0.2 degrees C vs 1.8+/-0.7 degrees C: P=0.04) whilst no significant difference in mean tissue thigh temperature was found between the groups. Local skin temperature was 2.5-3.0 degrees C higher when using forced-air heaters. However, skin perfusion was unaffected. Ultrasound measurements revealed that leg blood flow during the first hours after surgery was reduced to approximately 70% of pre- and peri-operative values. CONCLUSIONS: Forced-air blankets reduce afterdrop. However, they do not lead to clinical relevant changes in deep thigh temperature. LDF measurements show that forced-air heating does not improve toe perfusion. The extra heat especially favours core temperature. This is underlined by the decrease in postoperative leg blood flow, suggesting that the majority of the warmed blood leaving the heart flows to core organs and not to the periphery.

The relationship between local scalp skin temperature and cutaneous perfusion during scalp cooling.

Cooling the scalp during administration of chemotherapy can prevent hair loss. It reduces both skin blood flow and hair follicle temperature, thus affecting drug supply and drug effect in the hair follicle. The extent to which these mechanisms contribute to the hair preservative effect of scalp cooling remains unknown. The purpose of this study was to establish a relationship between local scalp skin temperature and cutaneous blood flow during scalp cooling. We measured skin temperature and cutaneous perfusion during a cooling and re-warming experiment. Experiments on a single subject showed that the measurements were reproducible and that the response was identical for the two positions that were measured. Inter-subject variability was investigated on nine subjects. We found that for the first 10 degrees C of cooling, perfusion of the scalp skin decreases to below 40%. Perfusion can be further reduced to below 30% by a few degrees more cooling, but a plateau is reached after that. We found that a generally accepted relation in thermal physiology between temperature and perfusion (i.e. Q(10) relation) does not describe the data well, but we found an alternative relation that describes the average behavior significantly better.

Molecular simulation of water vapor outgassing from silica nanopores.

The outgassing problem is solved numerically by molecular dynamics. A slit-shaped nanopore consisting of cavity and channel is built with an implicit tabulated wall potential that describes the water-silicon/silica interaction. A flexible three-point water model is used for the simulation. The effects of varying the system temperature, outlet pressure, geometry, and materials of the nanopore on the outgassing rate are investigated. The results show that the temperature plays an important role in the outgassing rate, while the effect of the outlet pressure is negligible as long as it is in the high to medium vacuum range. The geometry of the channel also has an influence on the outgassing rate, but not as much as the surface material. Three different types of silica materials are tested: silicon, silica-cristobalite (hydrophilic material), and silica-quartz (super hydrophilic material). The fastest outgassing rate is found for a silicon nanopore. It is also found that a thin water film is formed on the surface of the silica-quartz nanopore. This material shows hardly any outgassing of water.

Measurement of model coefficients of skin sympathetic vasoconstriction.

Many researchers have already attempted to model vasoconstriction responses, commonly using the mathematical representation proposed by Stolwijk (1971 NASA Contractor Report CR-1855 (Washington, DC: NASA)). Model makers based the parameter values in this formulation either on estimations or by attributing the difference between their passive models and measurement data fully to thermoregulation. These methods are very sensitive to errors. This study aims to present a reliable method for determining physiological values in the vasoconstriction formulation. An experimental protocol was developed that enabled us to derive the local proportional amplification coefficients of the toe, leg and arm and the transient vasoconstrictor tone. Ten subjects participated in a cooling experiment. During the experiment, core temperature, skin temperature, skin perfusion, forearm blood flow and heart rate variability were measured. The contributions to the normalized amplification coefficient for vasoconstriction of the toe, leg and arm were 84%, 11% and 5%, respectively. Comparison with relative values in the literature showed that the estimated values of Stolwijk and the values mentioned by Tanabe et al (2002 Energy Build. 34 637-46) were comparable with our measured values, but the values of Gordon (1974 The response of a human temperature regulatory system model in the cold PhD Thesis University of California, Santa Barbara) and Fiala et al (2001 Int. J. Biometeorol. 45 143159) differed significantly. With the help of regression analysis a relation was formulated between the error signal of the standardized core temperature and the vasoconstrictor tone. This relation was formulated in a general applicable way, which means that it can be used for situations where vasoconstriction thresholds are shifted, like under anesthesia or during motion sickness.

Validation of an individualised model of human thermoregulation for predicting responses to cold air.

Most computer models of human thermoregulation are population based. Here, we individualised the Fiala model [Fiala et al. (2001) Int J Biometeorol 45:143-159] with respect to anthropometrics, body fat, and metabolic rate. The predictions of the adapted multisegmental thermoregulatory model were compared with measured skin temperatures of individuals. Data from two experiments, in which reclining subjects were suddenly exposed to mild to moderate cold environmental conditions, were used to study the effect on dynamic skin temperature responses. Body fat was measured by the three-compartment method combining underwater weighing and deuterium dilution. Metabolic rate was determined by indirect calorimetry. In experiment 1, the bias (mean difference) between predicted and measured mean skin temperature decreased from 1.8 degrees C to -0.15 degrees C during cold exposure. The standard deviation of the mean difference remained of the same magnitude (from 0.7 degrees C to 0.9 degrees C). In experiment 2 the bias of the skin temperature changed from 2.0+/-1.09 degrees C using the standard model to 1.3+/-0.93 degrees C using individual characteristics in the model. The inclusion of individual characteristics thus improved the predictions for an individual and led to a significantly smaller systematic error. However, a large part of the discrepancies in individual response to cold remained unexplained. Possible further improvements to the model accomplished by inclusion of more subject characteristics (i.e. body fat distribution, body shape) and model refinements on the level of (skin) blood perfusion, and control functions, are discussed.

Heat production and body temperature during cooling and rewarming in overweight and lean men.

OBJECTIVE: To compare overweight and lean subjects with respect to thermogenesis and physiological insulation in response to mild cold and rewarming. RESEARCH METHODS AND PROCEDURES: Ten overweight men (mean BMI, 29.2 +/- 2.8 kg/m(2)) and 10 lean men (mean BMI, 21.1 +/- 2.0 kg/m(2)) were exposed to cold air for 1 hour, followed by 1 hour of rewarming. Body composition was determined by hydrodensitometry and deuterium dilution. Heat production and body temperatures were measured continuously by indirect calorimetry and thermistors, respectively. Muscle activity was recorded using electromyography. RESULTS: In both groups, heat production increased significantly during cooling (lean, p = 0.004; overweight, p = 0.006). The increase was larger in the lean group compared with the overweight group (p = 0.04). During rewarming, heat production returned to baseline in the overweight group and stayed higher compared with baseline in the lean group (p = 0.003). The difference in heat production between rewarming and baseline was larger in the lean (p = 0.01) than in the overweight subjects. Weighted body temperature of both groups decreased during cold exposure (lean, p = 0.002; overweight, p < 0.001) and did not return to baseline during rewarming. DISCUSSION: Overweight subjects showed a blunted mild cold-induced thermogenesis. The insulative cold response was not different among the groups. The energy-efficient response of the overweight subjects can have consequences for energy balance in the long term. The results support the concept of a dynamic heat regulation model instead of temperature regulation around a fixed set point.

Cold-induced heat production preceding shivering.

Individual changes in heat production and body temperature were studied in response to cold exposure, prior to shivering. The subjects ten women (seven men) were of normal weight, had a mean age of 23 (SD 3) years and average BMI 22.2 (SD 1.6) Kg/m2. They were lying supine under thermoneutral conditions for 30 min and were subsequently exposed to air of 15 degrees C until shivering occurred. Heat production was measured with a ventilated hood. Body composition was measured with underwater weighing and 2H dilution. Body temperatures were measured with thermistors. Heat production during cold exposure prior to shivering increased and reached a plateau. Skin temperature decreased and did not reach a plateau during the test period. The non-shivering interval (NSI) ranged from 20 to 148 min, was not related to body composition and was not significantly different between women (81 (sd 15) min) and men (84 (sd 34) min). NSI was negatively related to skin temperature (r2 0.44, P=0.004), and skin temperature was related to heat production (r2 0.39, P=0.007). In conclusion, subjects with a relatively large heat production during cold exposure maintained a relatively high skin temperature but showed a short NSI, independent of differences in body composition.