Influence of anesthesia on ocular effects and temperature in rabbit eyes exposed to microwaves

To investigate the effect of systemic anesthesia on ocular effects and temperature in rabbit eyes exposed to microwaves, one eye each of 43 male pigmented rabbits (Dutch, 1.8-2.2 kg) was exposed at 2.45 GHz for 60-20 min (300 mW/cm2; 108 W/kg), either under anesthesia (ketamine hydrochloride (5 mg/kg) + xylazine (0.23 mg/kg)) or without anesthesia. Changes in the anterior segment were evaluated by image analysis utilizing a Scheimpflug camera, specular microscopy, and a laser flare cell meter. Temperatures within the eye were measured during microwave exposure by a Fluoroptic thermometer. The exposed eyes showed miosis, conjunctival congestion, corneal edema, and an increase in the light scattering of the anterior shallow cortex in the pupillary area of the lens. The group under systemic anesthesia showed much stronger symptoms than those treated without anesthesia. All of the anterior ocular changes disappeared within a week. The highest temperature during exposure was in the vitreous, followed by the anterior chamber, and the retrobulbar cavity of the orbit. The ocular temperatures of the rabbits under systemic anesthesia were 2-9 degrees C higher than those without anesthesia. Body temperature showed an increase of 1 degrees C during the exposure. Acute high intensity microwave exposure temporarily induced anterior segments inflammation and lens changes. The more pronounced ocular effects in the anesthetized rabbits were associated with the significantly higher ocular temperatures in the anesthetized animals. The influence of systemic anesthesia on ocular changes should be considered.     

戊巴比妥钠和乌拉坦对超声检测兔肾血流动力学变化的影响探讨

目的比较戊巴比妥钠和乌拉坦两麻醉剂在超声监测兔肾血流动力学变化的影响。方法选用日本大耳白兔24只,随机分组,戊巴比妥钠和乌拉坦麻醉两组,每组12只。采用频谱多普勒检测兔肾各级肾动脉血流参数。结果乌拉坦组各级肾动脉收缩期峰值流速（Vmax）,舒张期最低流速（Vmin）均明显高于戊巴比妥钠组（P〈0.05）,动脉搏动指数（PI）和阻力指数（RI）无明显变化（P〉0.05）。结论为保证超声监测兔肾血流动力学实验数据的准确性,戊巴比妥钠麻醉较乌拉坦麻醉更适合。     

Tissue-specific extravasation of albumin-bound Evans blue in hypothermic and rewarmed rats

The effects of hypothermia and rewarming on endothelial integrity were examined in intestines, kidney, heart, gastrocnemius muscle, liver, spleen, and brain by measuring albumin-bound Evans blue loss from the vasculature. Ten groups of twelve rats, normothermic with no pentobarbital, normothermic sampled at 2, 3, or 4 h after pentobarbital, hypothermic to 20, 25, or 30 degrees C, and rewarmed from 20, 25, or 30 degrees C, were cooled in copper coils through which water circulated. Hypothermic rats were cooled to the desired core temperature and maintained there for 1 h; rewarmed rats were cooled to the same core temperatures, maintained there for 1 h, and then rewarmed. Following Evans blue administration, animals were euthanized with methoxyflurane, tissues removed, and Evans blue extracted. Because hypothermia and rewarming significantly decrease blood flow, organ-specific flow rates for hypothermic and rewarmed tissues were used to predict extravasation. Hypothermia decreased extravasation in tissues with continuous endothelium (brain, muscle) and increased it in tissues with discontinuous endothelium (liver, lung, spleen). All tissues exhibited significant (p < 0.05) differences from normothermic controls. These differences are attributed to a combination of anesthesia, flow, and (or) change in endothelial permeability, suggesting that appropriate choice of organ and temperature would facilitate testing pharmacological means of promoting return to normal perfusion.     

Thermal cataract formation in rabbits

Intraocularly circulating hot water was used to produce cataracts in nine eyes of seven rabbits by maintaining their retrolental temperatures between 43 degrees C and 45 degrees C. A rapid rate of heating (1.3 degrees C/min) plus a sharp temperature gradient across the eye may have been contributing factors in the consistent production of cataracts at these temperatures. Biomicroscopy and light microscopy showed lens changes similar to those associated with acute exposure to microwave radiation. These findings support the assumption that microwave cataractogenesis is due to the local production of elevated temperatures.     

Role of blood flow on RF exposure induced skin temperature elevations in rabbit ears

In this in vivo study, we measured local temperature changes in rabbit pinnae, which were evoked by radiofrequency (RF) exposure for 20 min at localized SAR levels of 0 (sham exposure), 2.3, 10.0, and 34.3 W/kg over 1.0 g rabbit ear tissue. The effects of RF exposures on skin temperature were measured under normal blood flow and without blood flow in the ear. The results showed: (1) physiological blood flow clearly modified RF induced thermal elevation in the pinna as blood flow significantly suppressed temperature increases even at 34.3 W/kg; (2) under normal blood flow conditions, exposures at 2.3 and 10.0 W/kg, approximating existing safety limits for the general public (2 W/kg) and occupational exposure (10 W/kg), did not induce significant temperature rises in the rabbit ear. However, 2.3 W/kg induced local skin temperature elevation under no blood flow conditions. Our results demonstrate that the physiological effects of blood flow should be considered when extrapolating modeling data to living animals, and particular caution is needed when interpreting the results of modeling studies that do not include blood flow.     

Microwave method of determining cerebral blood flow

A noninvasive method of quantitative assessment of cerebral blood flow based on heat clearance from brain tissues is described. The rate of heat clearance depends essentially on the blood flow. The employment of microwave techniques permits to warm the investigated brain zone and to record the temperature decrease extracranially. As a thermometer, a microwave radiometer was used. The experiments were carried out on cats. The method was tested by current vasoactive drugs.     

The effects of temperature on the filtration of diluted blood through 3 μm and 5 μm filters

The effect of temperature on the flow of diluted blood [Hct = 0.21], through 5 μm Nuclepore filters, is described by the Arrhenius equation with an energy of activation of 27.7 kJ/mol. Plasma, diluted with PBS, is almost three times less sensitive to temperature, with an energy of activation of 9.8 kJ/mol, while red cells are of intermediate sensitivity, with an energy of activation of 14.7 kJ/mol. The most sensitive elements to changes in temperature are leukocytes, with energies of activation of 31 kJ/mol and 35 kJ/mol for fast-flowing leukocytes (granulocytes and lymphocytes) and slow-flowing leukocytes (monocytes) respectively. Hence, the major determinants of the decline in filterability of blood through micropore filters are the leukocytes. This effect is compounded when blood is kept for 10 minutes or more at 10° C due to activation of granulocytes, which leads to permanent pore blocking when the affected blood is filtered at room temperature. The combination of increased passage time of leukocytes through peripheral areas at abnormally low temperatures and subsequent activation might influence the flow of blood in non-affected tissues. The effect of temperature on the filterability of red blood cells through 3 μm filters is not described by the Arrhenius equation and the deviations are seen as a gradual change of slope rather than a sharp break between two straight lines. The data are consistent with a gradual shift in rate limiting step away from the entry event into pores, which dominates at low temperature but becomes progressively less important at elevated temperatures. The changing parameter is probably the volume of the red cell, which is less important when flow is measured through 5 μm pores.     

Temperature regulation of marine mammals

A mathematical model of heat loss from an aquatic animal to the surrounding water is presented. Heat is generated in metabolically active tissues and distributed by circulating blood and by conduction. The time dependent radial temperature profile of the animal is numerically solved from heat transfer equations by a computer. The model is applied to large whales, porpoises, and seals. For the whales, blood circulation to the dermal layer below appendage and body skin surfaces proved to be essential for sufficient heat dissipation. When decreasing the blood flow below a certain value (dependent on sea temperature and whale activity) the large whales would overheat. Blubber thickness was found to be of minor importance in whale thermoregulation, because the blubber coat can be bypassed by blood circulation. On the other hand, it is in general not possible for small porpoises and seals to stay warm in the coldest waters using normal mammalian resting metabolic rates, even if the peripheral circulation is shut off (or artery-vein heat exchangers used). Heat loss can be reduced if the outermost tissue layers are allowed to cool. This is achieved by minimizing convective radial heat flow via the circulation. (For large whales even minute radial blood flow raises the muscle temperatures to the core temperature level.) Seasonal acclimatization of harbour seals is explained by changes in their effective insulation thickness. Differences in whale activity induce changes in the temperature profile mainly within the first few centimeters from the skin surface. These superficial temperatures, if known, could be used to estimate whale metabolic rates. Since they drop close to the sea water temperature within minutes after whale death, the measurements should be done of live whales.     

A compartment model to calculate time-dependent concentration profiles of topically applied chemical compounds in the anterior compartments of the rabbit eye

Hitherto, none of the existing in vitro methods has been convincingly demonstrated to be suitable as a replacement for the Draize rabbit eye irritation test. We examine the hypothesis that one reason for this is that insufficient consideration has been given to the differences in the effective concentrations at which chemicals operate in vitro and in vivo. When a chemical is applied topically to the eye, the strength of the observed irritation that it elicits depends both on its toxic potential toward cells or tissues, and its effective concentration in the tissues of the eye. Most of the existing in vitro methods are based on isolated cells or tissues, and thus may be useful in assessing the cytotoxic potentials of chemicals. However, a reliable approach to assessing the effective concentrations of chemicals within the various tissues of the eye is lacking. A simplified compartment model is presented for calculating the time-dependent, intra-ocular concentration profiles of topically applied chemicals. The model encompasses the outer surface of the eye, three distinct segments of the cornea (subdivided into the epithelium, stroma and endothelium) and the conjunctiva. Transport through the membranes of these compartments is described as passive diffusion. For the transport coefficients, rate equations are established that contain, as free parameters, the molecular size and the partition coefficient of the chemical, as well as some intrinsic membrane parameters, such as thickness, viscosity and pore density. Numerical values for the unknown membrane parameters were estimated by fitting the theoretical rate equations to measured permeability coefficients. The compartment model was applied to an independent set of 52 test chemicals compiled from the European Commission/UK Home Office validation study. The calculated passage times (required to let 95% of the chemical reach the posterior eye tissues) varied between 0.33 minutes and 50.6 minutes, and are generally much shorter than the typical duration of observed impairments in the cornea or conjunctiva. This finding suggests that short-term contacts of the eye tissues with a chemical are sufficient to elicit long-term eye irritation. An example is given, showing how the conventional approach of using in vitro endpoints as predictors of eye irritation can be improved significantly by incorporating into the prediction the calculated intra-ocular concentration of a chemical.     

Transport of Tryptophan into Brain from the Circulating, Albumin-Bound Pool in Rats and in Rabbits

Tryptophan is the only amino acid in the circulation that is bound by albumin, and previous studies have suggested that the brain tryptophan supply is a function of either the free or the albumin-bound pool of tryptophan in blood. Since the albumin molecule per se does not cross the brain capillary wall, i.e., the blood-brain barrier (BBB), the transport of tryptophan from the circulating albumin-bound pool may involve enhanced dissociation of tryptophan from the albumin binding sites within the cerebral microcirculation. This hypothesis was confirmed in the present studies wherein the dissociation constant (KaD) of albumin binding of tryptophan in the rat or rabbit brain microcirculation was measured in vivo. Brain extraction data for [14C]tryptophan determined with the carotid artery injection technique were fit to the Kety-Renkin-Crone equation modified for protein-bound solute. The KaD of albumin binding in the rat or rabbit brain microcirculation under pentobarbital anesthesia was 1.7 +/- 0.1 and 3.9 +/- 1.0 mM, respectively, as compared to the KD value measured in vitro with equilibrium dialysis, 0.13 +/- 0.03 mM. In contrast, the KaD value of albumin binding of tryptophan in vivo in the rabbit brain microcirculation was reduced by ether anesthesia to a value of 2.1 +/- 0.4 mM. This reduction in the KaD under ether anesthesia was associated with a 2.5-fold increase in cerebral blood flow. In addition, dialyzed rabbit serum caused a statistically significant inhibition in [14C]tryptophan influx during ether, but not pentobarbital, anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thermoregulatory control of finger blood flow.

Three men exercised on a bicycle ergometer at 30, 50, asd 70 per cent of maximal aerobic power in ambient temperatures of 15, 25, and 35 degrees C with water vapor pressure less than 18 Torr. Exercies was used to vary internal temperature during as experiment, and different ambient temperatures were used to vary skin temperatures independently of internal temperature. Finger temperature was fixed at about 35.7 degrees C. Espohageal temperature (Tes) was measured with a thermocouple at the level of the left atrium, and mean skin temperature (Tsk) was calcualted from a weighted mean of thermocouple temperatures at eight skin sites. Finger blood flow (BF) was measured by electrocapacitance plethysmography. Although some subjects showed small and equivocal vasomotor effects of exercise, our data are well accounted for by an equation of the form BF equal to alTes + a2Tsk + b, independent of exercise intensity. For these subjects, the ratios a1/a2 (5.9, 8.6, 9.4) were similar to the ratios of the corresponding coefficients recently reported for thermaoregulatory sweating (8.6, 10.4) and for forearm blood flow (9.6).     

Effect of hyperthermia on tumor blood flow

Differences in blood perfusion rates between tumors and normal tissue can be utilized to selectively heat many solid tumors. Blood flow in normal tissues is considerably increased at temperatures commonly applied during localized hyperthermia. In contrast, tumor blood flow may respond to localized heat typically in two different blood flow patterns: Flow may either decrease continuously with increasing exposure time and/or temperature or flow may exhibit a transient increase followed by a decline. A decrease in blood flow at high thermal doses can be observed in most of the tumors, whereas an increase in flow at low thermal doses seems to occur less frequently. The inhibition of blood flow at high thermal doses may lead to physiological changes in the microenvironment of the cancer cells that increase the cell killing effect of hyperthermia. Flow increases at low thermal doses can enhance the efficiency of other treatment modalities, such as irradiation or the administration of antiproliferate drugs.     

Heat balance of the human body: influence of variations of locally distributed parameters

Human body temperature control is characterized by a local dependence of system variables and parameters. Essential properties regarding inhomogeneity of the passive system have been investigated using mathematical methods. The general diffusion-equation has been solved using implicit finite difference methods with nonlinear boundary conditions. In order to allow comparison with experimental results, a simple ideal controller has been defined. On the basis of an inhomogeneous cylinder model with four concentric layers, influences of variations due to differences between tissues and individuals or measurements of parameters such as basal metabolism and conductivity have been studied. Stationary temperature profiles calculated for homogeneous and inhomogeneous conditions have been compared. Finally, the influence of blood flow has been discussed, as well as the stationary behaviour of profiles due to blood flow and blood flow control. The change of sign of curvature of temperature profile is possible only if blood flow mechanisms and the local distribution of metabolism are taken into account.     

Fluorescence depolarization studies of red cell membrane fluidity. The effect of exposure to 1.0-GHz microwave radiation

The internal viscosity of human red blood cell membranes was investigated during exposure to continuous wave 1.0-GHz microwave radiation using fluorescence measurements of a lipid seeking molecular probe, diphenylhexatriene. Samples were exposed in a Crawford cell arranged so that fluorescence was measured during microwave exposure; specific absorption rates calculated from electrical measurements were approximately 0.6, 2 and 15 W/kg. Measurements were obtained at selected temperatures between 15 °C and 40 °C and as a function of the duration of exposure at 23 °C. Arrhenius-type plots of the temperature profile data were linear and showed no difference between exposed and control samples. The exposure duration data also showed no difference between exposed and control samples except for a small effect of elevated temperature at the highest exposure. The activation energy for motion of the fluorescent probe in its environment within the membrane lipid was not affected by the application of the microwave energy and no evidence for a lipid phase transition was found. These results indicate that the increased cation efflux from red cells, observed by others at certain transition temperatures during microwave exposure, was more likely to have been caused by alteration of the membrane bound protein than by changes in the lipid constituents of the red cell membrane.     

On the solution of the non-linear bio-heat equation

With reference to microwave localized hyperthermia, a non-linear model of the thermal behavior of living tissues, where local thermoregulating convective and conducting effects due to blood flow are taken into account, has been assumed. The non-linear operator equation for the space and time temperature distribution, which describes local energy balance (bio-heat equation), has been linearized and solved by using a variant of the Newton iterative method. Numerical calculations for plane stratified structures simulating living bodies, irradiated by plane electromagnetic waves, have been carried out.     

Investigation of the influence of blood flow rate on large vessel cooling in hepatic radiofrequency ablation.

Radiofrequency (RF) ablation using high-frequency current has become an important treatment method for patients with non-resectable liver tumors. Tumor recurrence is associated with tissue cooling in the proximity of large blood vessels. This study investigated the influence of blood flow rate on tissue temperature and lesion size during monopolar RF ablation at a distance of 10 mm from single 4- and 6-mm vessels using two different approaches: 1) an ex vivo blood perfusion circuit including an artificial vessel inserted into porcine liver tissue was developed; and 2) a finite element method (FEM) model was created using a novel simplified modeling technique for large blood vessels. Blood temperatures at the inflow/outflow of the vessel and tissue temperatures at 10 and 20 mm from the electrode tip were measured in the ex vivo set-up. Tissue temperature, blood temperature and lesion size were analyzed under physiological, increased and reduced blood-flow conditions. The results show that changes in blood flow rate in large vessels do not significantly affect tissue temperature and lesion size far away from the vessel. Monopolar ablation could not produce lesions surrounding the vessel due to the strong heat-sink effect. Simulated tissue temperatures correlated well with ex vivo measurements, supporting the FEM model.     

Effect of dermal tumours on temperature distribution in skin with variable blood flow

Several investigations have been made for the heat flow problems in skin and subdermal tissues under normal physiological and atmospheric conditions. This paper considers the existence of a malignant tumour in the underlying tissues of epidermis of a human body. The surrounding tissues are assumed to have normal physiological functions, namely self-controlled metabolic activity, variable blood flow and perspiration. For the malignant portion the metabolic activity is taken to be continuous and uncontrolled. The effect of this factor is studied on the temperature profiles of the skin.     

The effects of some physical factors on the production of hyperthermia by ultrasound in neoplastic tissues

Summary A one-dimensional and a three-dimensional computer model have been built in order to study the importance of blood flow and ultrasonic absorption in tissues during local hyperthermia. The decreased blood flow in the interior of certain tumours and possibly the increased ultrasonic absorption of the malignant tissue in some cases may cause selectively higher temperatures inside the tumours though the heat input is the same as in the surrounding tissues. Also, the vasodilation of blood vessels in normal tissues as a response to heat causes a therapeutically useful temperature difference. These blood flow differences can lead to enhanced effects during sonication to produce hyperthermia in the tumour. The inhomogenity of blood flow in the tumour causes a non-uniform temperature distribution leaving the well-perfused cells in the advancing front at a much lower temperature than the cells in the necrotic centre. Thus, the combination of local hyperthermia with radio-and chemotherapy seems to offer the most attractive means of destroying malignant tissue.     

Effects of substance P on intestinal circulation and oxygen consumption

The effects of intra-arterial administration of substance P upon intestinal blood flow, oxygen consumption, intestinal motor activity, and distribution of blood flow to the compartments of the gut wall were measured in anesthetized dogs. Blood flow to the segment of distal ileum was measured with an electromagnetic blood flow meter and A-VO2 was measured spectrophotometrically. Oxygen uptake was calculated as the product of A-VO2 and total blood flow. The clearance of 86Rb was measured to estimate the density of the perfused intestinal capillaries. Changes in blood flow distribution were estimated from the distribution of radiolabeled microspheres. Motor activity was monitored from changes in intraluminal pressure. Substance P induced a dose-related increase in intestinal blood flow, oxygen consumption, and intestinal motor activity. A significant increase in 86Rb clearance and increase in blood flow to the muscles was also observed. The results of these studies indicate that substance P relaxes intestinal arterioles and precapillary sphincters thereby inducing intestinal hyperemia and increased oxygen consumption. These changes, at least in part, might be due to the increased intestinal motility with enhanced metabolic demands of the muscularis for oxygen.     

Acute toxicity of carminomycin administered perorally to laboratory animals

Rather high species sensitivity to carminomycin was found in the experiment with albino mice, rats, guinea pigs, rabbits and dogs. The highest difference in the antibiotic toxicity for various species of the laboratory animals was shown on oral administration of the drug which was due to the differences in the antibiotic absorption from the gastro-intestinal tract. On single oral administration to the dogs in toxic or lethal doses the antibiotic suppressed the blood formation up to aplasia of the bone marrow. The equitoxic doses of carminomycin on its single oral and intravenous administration differed approximately by 3 times. Carminomycin had no effect on the smooth muscles of the isolated rabbit ear vessels and cat intestine in situ. The antibiotic had an irritating effect on the rabbit eye mucosa. Carminomycin had no skin-irritating effect.