The effect of daily repeated sedation using ketamine or ketamine combined with medetomidine on physiology and anesthetic characteristics in rhesus macaques.

BACKGROUND: Non-human primates are frequently sedated to permit handling that can alter physiological values. The purpose of this study was to identify the effects of daily serial sedation using ketamine (K) or ketamine combined with medetomidine (KM). We hypothesized KM would reduce observed effects of repeated sedation. METHODS: Eight rhesus macaques were anesthetized for three consecutive days. Physiological data were recorded daily at 5-minute intervals. Time intervals from injection to ataxia, recumbency, first movement and recovery were recorded. Depth of anesthesia was evaluated. RESULTS: Data showed an 11.7% increased heart rate at 5 minutes between the first and third day of injection with K and 17.9% with KM. Time from injection to ataxia increased 13.7% with K and 14.3% with KM. Time to recumbency increased 34.7% with K and 37.1% with KM. CONCLUSION: These findings demonstrate repeated anesthesia with ketamine can initiate changes suggesting a tolerance effect.

Effects of serial anesthesia using ketamine or ketamine/medetomidine on hematology and serum biochemistry values in rhesus macaques (Macaca mulatta).

BACKGROUND: This study aimed at determining the cumulative effect of daily anesthesia, using two drug regimens, over hematological and biochemical parameters. METHODS: Blood samples were obtained from rhesus monkeys 20 minutes after intramuscular administration of ketamine or ketamine/medetomidine combination for three consecutive days and results were evaluated to determine their effect on hematological and serum biochemistry values. Statistical significance of drug, day, and interaction of these two variables were evaluated. RESULTS: Drug effect resulted in a dramatic increase of aspartate aminotransferase and creatine kinase values. Day effect resulted in decreases of RBC, HCT, Hgb, and alkaline phosphatase but an increase of other biochemical parameters evaluated. The drug/day interaction effect was found to be -significant for RBC, platelets, aspartate aminotransferase, alanine aminotransferase, and creatine kinase values. CONCLUSION: The results of our study suggest a cumulative effect of serial anesthesia and should be an important consideration when interpreting hematology and serum biochemistry in rhesus macaques.

Transforming growth factor-alpha, epidermal growth factor receptor, and PCNA immunoexpression in uterine leiomyosarcomas and leiomyomas in B6C3F1 mice.

The role of growth factors in the development of murine uterine mesenchymal tumors is unknown. In this study, immunohistochemical expression of transforming growth factor alpha (TGF-alpha) and its receptor epidermal growth factor (EGF-R) was assessed in spontaneous uterine leiomyomas and leiomyosarcomas in B6C3F1 mice. Cell proliferation, which has been induced by some growth factors, was evaluated by immunohistochemical detection of an endogenous marker of cell proliferation, proliferating cell nuclear antigen (PCNA). PCNA labeling indices were determined and compared to the intensity and distribution of TGF-alpha staining in sequential sections of control myometrium or tumor tissue. Results showed uterine leiomyosarcomas had positive cytoplasmic staining for TGF-alpha; however, all uterine leiomyomas evaluated were negative. Positive EGF-R staining was also observed in the uterine leiomyosarcomas, but not in the leiomyomas. EGF-R immunoexpression was detected primarily within the cytoplasm of the leiomyosarcoma cells, with occasional nuclear immunoreactivity. Immunohistochemical staining for PCNA was more intense and there were increased numbers of positively staining nuclei in the leiomyosarcomas compared to samples of control myometrium or leiomyomas. The mean labeling index for the uterine leiomyosarcomas (7.40%) was significantly (p < 0.01) higher than that of leiomyomas (0.29%) and control uterine myometrium (0.13%). We conclude, that TGF-alpha and its receptor, EGF-R, are expressed more intensely in uterine leiomyosarcomas, compared to leiomyomas in B6C3F1 mice. Immunoexpression of TGF-alpha may be an important biomarker of malignancy in uterine smooth muscle tumors in mice. Futhermore, TGF-alpha may play a critical role in increased proliferation of uterine smooth muscle tumor cells as suggested by increased immunolocalization of PCNA in rodent leiomyosarcomas expressing TGF-alpha, although other factors regulating cell replication can not be ruled out.

Median effective dose determination and histologic characterization of porcine (Sus scrofa domestica) dermal lesions induced by 1540-nm laser radiation pulses.

BACKGROUND AND PURPOSE: Light amplification by stimulated emission of radiation (laser) systems operating in the so-called "eye safe" region are gaining widespread use in industry, medicine, and military applications. This research effort was geared to study the effects of laser tissue interaction on human skin by using in vivo porcine skin as an animal model. The goals of the study were to determine the median effective dose (ED50) for 1540-nm laser exposures, to evaluate the Yorkshire pig and the Yucatan mini-pig as animal models for laser exposure, and to characterize laser-induced skin lesions histologically. METHODS: A 1540-nm wavelength laser was used to expose multiple sites on the flanks of 10 pigs, using 0.8-ms pulses, ranging from 7 to 96 joules (J)/cm2. Single pulses were delivered to the flank of Yorkshire and Yucatan pigs in a grid pattern. Exposure sites were evaluated immediately after exposure and at 1 hour and 24 hours for presence of gross lesions. Representative biopsy specimens were collected from lesion sites for histologic evaluation at the 24-hour endpoint. RESULTS: The ED50 for the two breeds differed in the amount of energy required to induce dermal lesions. Grossly, lesions in each breed were well demarcated and pale gray to brightly erythematous. Microscopically, lesions had epidermal layer damage as cellular swelling and nuclear pyknosis, loss of cellular detail, and coagulation necrosis at the dermal layer. CONCLUSIONS: Findings suggest the presence of a different mechanism of laser-tissue damage in these two breeds. Photo-thermal mechanism appears to induce the skin lesions in the Yorkshire pig, whereas photo-thermal and photochemical mechanisms appear to be involved in lesion formation in the Yucatan mini-pig. All data obtained in this study will become part of database used by the American National Standards Institute (ANSI) to recommend laser safety standards for the occupational health and safety programs (OHSP), which will be used by industry and the military to base and update their current OHSP.