Theoretical analysis of evaporative cooling of classic heat stroke patients.

Heat stroke is a serious health concern globally, which is associated with high mortality. Newer treatments must be designed to improve outcomes. The aim of this study is to evaluate the effect of variations in ambient temperature and wind speed on the rate of cooling in a simulated heat stroke subject using the dynamic model of Wissler.

50 years of computer simulation of the human thermoregulatory system.

This paper presents an updated and augmented version of the Wissler human thermoregulation model that has been developed continuously over the past 50 years. The existing Fortran code is translated into C with extensive embedded commentary. A graphical user interface (GUI) has been developed in Python to facilitate convenient user designation of input and output variables and formatting of data presentation.

An investigation into the structure-activity relationships associated with the systematic modification of the β(2)-adrenoceptor agonist indacaterol.

The synthesis of a series of indacaterol analogues in which each of the three structural regions of indacaterol are modified in a systematic manner is described. Evaluation of the affinity of these analogues for the β(2)-adrenoceptor identified the 3,4-dihydroquinolinone and 5-n-butylindanyl analogues to demonstrate the most similar profiles to indacaterol. An α-methyl aminoindane analogue was discovered to be 25-fold more potent than indacaterol, and functional studies revealed an atypical β(2)-adrenoceptor activation profile for this compound consistent with that of a slowly dissociating 'super agonist'.

Identifying a long standing error in single-bolus determination of the hepatic extraction ratio for indocyanine green.

For approximately 50 years, hepatic clearance of indocyanine green (ICG) has been used to assess liver function. Steady-state infusion of ICG with simultaneous measurement of arterial and hepatic venous ICG concentrations provides unambiguous measures of the extraction ratio for ICG and the hepatic blood flow rate, but also requires cannulation of a hepatic vein. Transient clearance following injection of a single bolus of ICG, which typically involves only measurement of arterial ICG concentration, is a more commonly used procedure.

The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist.

Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of beta(2)-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human beta(2)-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference beta(2)-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds.

A simple theoretical model of heat and moisture transport in multi-layer garments in cool ambient air.

Overall resistances for heat and vapor transport in a multilayer garment depend on the properties of individual layers and the thickness of any air space between layers. Under uncomplicated, steady-state conditions, thermal and mass fluxes are uniform within the garment, and the rate of transport is simply computed as the overall temperature or water concentration difference divided by the appropriate resistance. However, that simple computation is not valid under cool ambient conditions when the vapor permeability of the garment is low, and condensation occurs within the garment.

A quantitative assessment of skin blood flow in humans.

Various aspects of skin blood flow (SkBF) in human beings have been studied experimentally for more than seven decades. While reasonably complete phenomenological descriptions of individual factors have emerged from those investigations, little effort has been devoted to assembling the component parts into a coherent description of the entire system. This paper describes an effort to do that.

Thermoregulatory models of space shuttle and space station activities.

Background: Thermoregulation is critical for survival in space, especially during contingencies demanding of human cognitive and physical performance. A review of the negative feedback human thermoregulatory system is provided. The Advanced Crew Escape Suit is worn by astronauts during ascent and descent on the Space Shuttle to provide active cooling for nominal and contingency operations and protection from loss of cabin pressure mishaps.

Long-chain formoterol analogues: an investigation into the effect of increasing amino-substituent chain length on the beta2-adrenoceptor activity.

The synthesis of a series of long-chain formoterol analogues in which the terminal ether residue of the beta-phenethyl-amino-substituent has been extended beyond the methyl ether residue present in the parent compound are described. Evaluation of these analogues as beta(2)-adrenoceptor agonists was used to provide an insight into the factors controlling the magnitude and duration of receptor activation.

Probability of survival during accidental immersion in cold water.

Background: Estimating the probability of survival during accidental immersion in cold water presents formidable challenges for both theoreticians and empirics. A number of theoretical models have been developed assuming that death occurs when the central body temperature, computed using a mathematical model, falls to a certain level. This paper describes a different theoretical approach to estimating the probability of survival.

Model of human/liquid cooling garment interaction for space suit automatic thermal control.

The Wissler human thermoregulation model was augmented to incorporate simulation of a space suit thermal control system that includes interaction with a liquid cooled garment (LCG) and ventilation gas flow through the suit. The model was utilized in the design process of an automatic controller intended to maintain thermal neutrality of an exercising subject wearing a liquid cooling garment. An experimental apparatus was designed and built to test the efficacy of specific physiological state measurements to provide feedback data for input to the automatic control algorithm.

Automatic control of thermal neutrality for space suit applications using a liquid cooling garment.

Background: Thermal control in the EVA spacesuit requires attention from the astronaut which is not always desirable or feasible. Improvements in thermal control involve implementation of an automatic thermal control system operating independently of the knowledge of the working astronaut.

Methods: A control system was designed, developed, and tested to automatically maintain a subject's thermal neutrality while wearing a liquid cooling garment (LCG).

Pennes' 1948 paper revisited.

A paper published by Harry H. Pennes in Volume 1 of the Journal of Applied Physiology defined the theoretical basis for a considerable body of analysis performed by many investigators during the ensuing half century. However, during the past decade, the Pennes' model of heat transfer in perfused tissue has been criticized for various reasons, one of which is that his own experimental data seemed to be at variance with the model.

An analytical solution countercurrent heat transfer between parallel vessels with a linear axial temperature gradient.

Presented in this paper is a solution for countercurrent heat exchange between two parallel vessels embedded in an infinite medium with a linear temperature gradient along the axes of the vessels. The velocity profile within the vessel is assumed to be parabolic. This solution describes the temperature field within the vessels, as well as in the tissue, and establishes that the intravessel temperature is not uniform, as is generally assumed to be the case.

Immersion cooling: effect of clothing and skinfold thickness.

Accidental immersion often involves the threat of death due to hypothermia. Clothing to control heat loss in water is generally selected to minimize bulk while providing the necessary protection. While water temperature (Tw) and possible immersion time are often considered, another relevant variable is the insulation provided by subcutaneous fat.

Influence of hypothermia and circulatory arrest on cerebral temperature distributions.

A finite element model of the bioheat transfer equation has been developed to simulate the temperature distribution in the head of a subhuman primate. Simulations were made of the induction of deep hypothermia and of subsequent hypothermic circulatory arrest (HCA). Simulations of the circulatory arrest phase were performed with different values of surface heat transfer coefficient and tissue metabolic heat generation.

Errors involved in using thermal flux transducers under various conditions.

Commercially available sensors are being used by several investigators to measure thermal flux through the skin and skin temperature at a given site. Since these transducers place an additional thermal resistance into the system, they perturb the quantities that are being measured. This problem has been analyzed theoretically to obtain the following relatively simple equations: (Q0 - Q)/Q0 = EQ = QRt/(Ta - Te) and (Ts - Ts,0)/(Ta - Te) = [EQ/(1 - EQ)] [1 - EQ2 - (Ts - Te)/(Ta - Te)] in which Q = measured thermal flux; Rt = thermal resistance of the transducer; Ta, Ts, and Te = deep tissue, skin, and environmental temperatures, respectively; and the subscript 0 denotes unperturbed values.

A model for deposition of stable and unstable aerosols in the human respiratory tract.

A model has been developed for deposition of stable and unstable aerosols in the human respiratory tract. This model has the advantages of employing a realistic asymmetric lung model and utilizing actual breath curves. Results from the model are presented for normal and abnormal breath patterns for both stable and unstable particles.