This study utilized microvascular corrosion casting techniques to evaluate changes in the microvascular patency of rat hindpaws cooled to four different subzero temperatures. Left hindpaws of anesthetized rats in group 1 were cooled to -5 degrees C, in group 2 to -15 degrees C, in group 3 to heat of fusion (HOF), and in group 4 to HOF and then to -15 degrees C. Although freezing did not take place in the hindpaws of groups 1 and 2, initiation of freezing in the tissues, as indicated by HOF, did occur in groups 3 and 4. Cooled hindpaws were rapidly rewarmed. Right hindpaws served as controls. Microvascular corrosion casts were made from the left and right hindpaws of all animals. There was no significant difference when the mean cast weights of cooled hindpaws from groups 1, 2, and 3 were compared to the mean cast weights of their respective control hindpaws. In group 4, there was a significant difference (P less than 0.05) when the mean cast weight of the cooled hindpaws (47.69 +/- 9.05, mg +/- SEM) was compared to that of the control hindpaws (80.63 +/- 12.23). Since, in this acute experiment, a loss of vascular integrity occurred when the hindpaws in group 4 were cooled to -15 degrees C after reaching HOF, the initiation of freezing alone was not sufficient to reduce mean cast weight.

Passive rewarming of a cold-water stressed foot was evaluated in 33 recovered trenchfoot (TF) patients and 15 uninjured men. Infrared images were recorded prior to immersion, immediately following, and at 1-min intervals for 20 min. Individual baseline temperature (IBT) recovery was used to separate subjects into three groups designated Good and Poor Rewarming Controls (GRC and PRC) and Injured Subjects (Inj Sub). IBTs were significantly less (p less than 0.01) for Inj Sub compared to both GRC and PRC while no difference existed between GRC and PRC. This relationship changed when slopes of and areas under the mean rewarming curves were compared. Both these criteria were significantly greater (p less than 0.01) for GRC than for PRC and Inj Sub, while no difference was noted between PRC and Inj Sub. It could not be determined if the poor response of Inj Sub was inherent or a result of injury. We conclude that previously injured subjects and nearly 60% of a normal population may be at significant risk for cold injury.

In brief: Everyone, regardless of climate, occasionally feels cold. The hands and feet, with their somewhat remote location from the heart, are particularly prone to cold sensation. But in addition to those who are just cold, there is a group of individuals who have significant problems with peripheral blood flow. These are people who have either primary or secondary Raynaud's disease. The author has developed a simple conditioning treatment that patients can do at home and that can make cold-weather activities possible without pain.

Frostbite was produced in the skin of five Hanford Miniature Swine by exposing local areas to chilled air (-75 degrees C) for 1, 3, 5, 10, or 20 min. A copper-constantan thermocouple was inserted into the dermis to measure the temperature. The mean freezing time (the time required to reach 0 degrees C) was approximately 1.9 min. The mean lowest temperatures were 8.8, -15.7, -20.9, -22.5, and -23.4 degrees C for the 1-, 3-, 5-, 10-, and 20-min freezes, respectively. The mean times to rewarm the skin to 25 degrees C were 3.1, 4.5, 5.5, 7.0, and 8.6 min for the 1-, 3-, 5-, 10-, and 20-min freezes, respectively. Significant linear correlations existed between duration of freeze and rewarming times, duration of freeze and lowest temperature, and lowest temperature and rewarming times.

Frost-bite lesions were produced in five Hanford Miniature Swine exposed to - 75 degrees C air for 1, 3, 5, 10 or 20 min. Biopsies were taken at 0, 3, 6, 12, 24 and 48 h and 1 and 2 weeks. Two hundred slides were evaluated microscopically: pyknosis, vacuolation, individualization of cells, and degeneration were graded from 0-5; 0, no change; 5, severe change. Necrosis, new epithelium, and microabscesses were recorded as present or absent. Early changes of vacuolation of keratinocytes, individualization of cells and pyknosis increased with biopsy time until 1 week, at which time more severe changes predominated. Intermediate changes of advanced degeneration and dermoepidermal microabscesses were seen at 48 h and 1 and 2 weeks. Late changes of necrosis and epithelial regeneration occurred, both separately or together in the same tissue, at 1 and 2 weeks. Regeneration occurred either as complete replacement of epithelium, or as crescents of new epithelium beneath degenerating epithelium. The results show that necrosis is a late development, so prognosis based on early skin biopsies must be guarded to unfavourable. Furthermore, these findings suggest that cold has a direct effect on epithelial cell membranes.

Frost-bite lesions were produced in five Hanford Miniature Swine exposed to - 75 degrees C air for 1, 3, 5, 10, or 20 min. Biopsies were taken at 0, 3, 6, 12, 24, and 48 h, and 1 and 2 weeks. Two hundred slides were evaluated microscopically: superficial and deep hyperaemia, vascular inflammation, medial degeneration, and thrombosis were graded from 0 to 5; 0, no change; 5, severe change. Haemorrhage was recorded as present or absent. Hyperaemia was the earliest change seen, both grossly and microscopically. Leucocyte emigration and vasculitis were intermediate stages seen most commonly in the 6, 12, and 24 h biopsies. Medial degeneration and thrombosis, the most severe vascular changes, were not seen until 1-2 weeks following frost-bite injury. These findings show that the outcome of frost-bite can not be accurately predicted from early frost-bite lesions, because thrombosis and medial degeneration are not evident in early lesions.

The use of vascular microcorrosion casts (vascular replicas) has made it possible to demonstrate the degree of damage to the microcirculation in experimentally induced frostbite. This approach provides a direct method for demonstrating vascular patency. Four groups of animals were used in this investigation. The left hind limbs of anesthetized rats were cooled to -10 degrees C in groups one and three and to -20 degrees C in groups two and four, as measured by needle thermocouples placed under the gastrocnemius muscles. Thermocouples were also placed in the left hind footpads of groups three and four. The sheathed limbs were cooled in an alcohol bath at approximately 1.1 degree C per minute. All limbs exposed to the cold bath were rewarmed to 37 degrees C in a 40 degree C water bath. The right hind limbs served as uninjured controls. The footpad temperatures recorded in groups three and four were used in conjunction with the temperatures recorded under the gastrocnemius muscles to characterize the footpad temperatures in groups one and two. Vascular microcorrosion casts were made from the left and right hind paws of groups one and two using Batson's modified methyl methacrylate. Scanning electron microscopic examination of the casts demonstrated dramatic differences between the vascular integrity of control paws and that of frozen paws. Exposure to the cold temperatures destroyed most of the microcirculation. In addition, the weights of the casts from the control paws were significantly different from the weights of the casts from the frozen paws. It was concluded that this model for evaluating frostbite injury accurately demonstrates the extent of microvascular damage and has significant potential as a method for evaluating therapeutic drug regimens.

Bromelain is a plant proteinase derived from the stem of the pineapple plant that has been used successfully to debride the eschar from third-degree burn injuries. Its applicability to frostbite eschar removal was extrapolated and investigated. Third-degree frostbite lesions were produced on swine using supercooled air as the freezing media, and the resulting eschars were treated with a bromelain preparation. In the initial trial, no debridement other than that of the superficial layers of the eschar was noted. The experiment then was repeated with the introduction of third-degree burn injuries as a control to validate the efficacy of the enzyme preparation. Although the burn injuries debrided to a graftable bed after two applications of the enzyme, the frostbite injuries remained unaffected. It was concluded that the patent vasculature, resulting tissue edema, and lack of coagulation of proteins found in the freeze injury are sufficient to inactivate the bromelain enzyme before tissue digestion and dissection can be effected.

Ten patients with Raynaud's disease treated themselves at home using induced vasodilation 3 times/day, every other day, for 18 treatment days. The patients, dressed in indoor clothing, immersed both hands in warm tap water (43-45 degrees C) for 8-10 min while exposed to naturally occurring ambient cold. Results of pre- and posttreatment cold exposures showed a significant mean increase in digital temperature of 3.4 degrees C (p less than .001). Conditioning therapy appears to be an effective, feasible alternative to drug or surgical therapy.

Since pathological changes in the liver are among the consistent findings in humans subsequent to heatstroke, specimens were taken from the liver in rats during a study to assess the rat as a model for human heatstroke. Tissues from four groups of rats were processed for light and electron microscopy. The groups consisted of control rats, rats run to exhaustion at 5 C, rats exhausted at 26 C, and rats restrained at 41.5 C until their rectal temperatures reached 42.3 C. Exhaustive exercise at 5 C produced neither fatalities nor pathological changes in the livers. Exhaustive exercise at 26 C and restraint at 41.5 C were fatal for most rats. Histological and/or ultrastructural changes, which included centrilobular necrosis, vacuolization and diminution of hepatocellular microvilli, and loss of sinusoidal endothelium, were observed in livers from rats that were run to exhaustion at 26 C and from those rats restrained at 41.5 C. This work supports the validity of the rat model, since human heatstroke results in similar hepatic changes.

Frostbite is thought to result from initial vasoconstriction, ischemia, intracellular ice crystal formation, and inflammation caused by reperfusion injury. Corticosteroids have demonstrated beneficial anti-inflammatory effects in the treatment of other ischemia/reperfusion clinical conditions. The objective of this study was to determine the effect of dexamethasone (dex) on wound healing, inflammatory response, and vasculogenesis in a mouse skin frostbite model.Treatment and control groups of C57/BL6 mice were subjected to frostbite using a previously described model. Treatment with intraperitoneal dex (1 mg·kg-1·d-1) began on the day of frostbite induction and lasted for 7 d. Over 4 wk, we compared wound diameter; morphology by visual inspection, hematoxylin–eosin staining, and Masson’s trichrome staining; density of inflammatory cytokines IL-1β and TNFα using Western blot analysis; and formation of microvasculature using immunofluorescence staining. Data were analyzed using 1-way or 1-way repeated-measures analysis of variance.After frostbite injury, morphological images demonstrated epidermal necrosis and loss in the frostbitten skin as well as infiltration of inflammation-related leukocytes. Increased production of inflammatory cytokines and disappearance of the microvasculature also occurred in the frostbitten skin. In comparison to the control group, treatment with dex promoted wound healing as demonstrated by decreased wound diameter; decreased levels of inflammatory cytokines, and accelerated formation of mature microvasculature.In this animal model, dex improved wound healing in frostbitten skin and demonstrated both anti-inflammatory effects and stimulation of vasculogenesis. This study suggests that the use of potent anti-inflammatory agents may be an effective strategy for mitigating frostbite injury.

Two groups of eight dogs were subjected to an experimentally induced hypothermia of 25 °C. One group was rewarmed externally using a circulating water blanket while the other group was rewarmed by peritoneal dialysis. Glomerular filtration rate, renal blood flow, and urine flow were reduced while filtration fraction and the extraction of PAH (Epah) were increased during hypothermia. Immediately upon rewarming, RBF and GFR remained significantly depressed in both groups when compared to control values. By 12 hr post-rewarming, however, the group rewarmed by peritoneal dialysis showed a complete return of GFR and RBF to prehypothermic levels while in the externally rewarmed group these variables remained depressed. The data suggest that peritoneal dialysis is an effective means of core rewarming producing an earlier return of renal function to control levels that the more conventional means of external rewarming.

ArticlePeritoneal clearance of urea and potassium following experimental hypothermia.J F Patton, W H Doolittle, and M P HamletJ F Patton, W H Doolittle, and M P HamletPublished Online:01 Apr 1974https://doi.org/10.1152/jappl.1974.36.4.403MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByA Model to Study the Transport Function of the Intestinal Viscera During Peritoneal DialysisAmerican Journal of Kidney Diseases, Vol. 23, No. 5Pharmacological Alteration of UltrafiltrationComments on Dialysis Solution, Antibiotic Transport, Poisonings, and Novel Uses of Peritoneal DialysisThe Importance of the Abdominal Viscera to Peritoneal Transport During Peritoneal Dialysis in the DogThe American Journal of the Medical Sciences, Vol. 292, No. 4Comments on dialysis solution, antibiotic transport, poisoning, and novel uses of peritoneal dialysisComments on Dialysis Solution Composition, Antibiotic Transport, Poisoning, and Novel Uses of Peritoneal Dialysis More from this issue > Volume 36Issue 4April 1974Pages 403-6 https://doi.org/10.1152/jappl.1974.36.4.403PubMed4820320History Published online 1 April 1974 Published in print 1 April 1974 Metrics