Paradoxical effect of fentanyl on body temperature, hemogram, and circulation in rats under hyperthermia

Introduction. We previously observed that general hyperthermia potentiates the lethal effect of fentanyl in rats. However, the relationship of this phenomenon to indices of vital functions of the organism remains unclear.

Objective. To identify the specific effects of fentanyl on body temperature, blood cell composition, and circulation in rats under heat stress conditions.

Materials and methods. The study was conducted on outbred male albino rats (191–210 g). Two series of experiments were performed on two separate animal samples, each of which was divided into the following groups: “22 °C” (intact), “Fentanyl + 22 °C” (kept at room temperature after fentanyl administration), “40 °C” (placed in a thermal chamber at 40 °C air temperature for 40 min), and “Fentanyl + 40 °C” (placed in the thermal chamber after fentanyl administration). In the first series of experiments, the effect of fentanyl (200 μg/kg) and/or exposure of rats to 40 °C air temperature on mortality over 40 min, body temperature, hemogram parameters, electrocardiogram (ECG), and blood pressure (BP) was studied. In the second series, the effect of fentanyl and/or heat stress on kidney weight, water content, and histological parameters of renal blood filling was studied. Heat stress was modeled by placing perforated restrainers with animals in a thermal chamber for 40 min. Fentanyl solution was administered at a volume of 4 mL/kg and a substance dose of 200 μg/kg into the v. caudalis lateralis. Statistical analysis was performed using OriginPro software.

Results. Isolated exposures were non-lethal, whereas their combination resulted in a mortality rate of 50% in the first series and 38% in the second series of experiments. After fentanyl administration, the following significant (p < 0.05) differences compared to the control groups were observed. Rectal temperature decreased by 5.6 °C at 22 °C but increased by 5.7 °C at 40 °C. At 22 °C, fentanyl decreased the heart rate of rats by 48%, whereas at 40 °C it increased heart rate by 25%. At 22 °C, fentanyl prolonged the RR interval by 90%, while at 40 °C it shortened the RR interval by 23%. In rats that died in the thermal chamber, the relative wet weight of the kidney was increased by 27% and the relative dry weight by 20%. At 40 °C, but not at 22 °C, fentanyl reduced blood leukocyte count by 47% and platelet count by 33%, increased renal cortical blood filling, activated the juxtamedullary shunt, and induced intravascular hemolysis.

Conclusions. For the first time, it has been established that under heat stress, the effects of fentanyl on body temperature, autonomic balance, and cardiac automaticity are opposite to those observed under thermal comfort. The fentanyl-induced changes in hemogram parameters, BP, and renal blood filling at 22 °C and 40 °C differ in magnitude. These fentanyl effects under hyperthermia represent early manifestations of exotoxic shock.

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