J.G. Bajorek

Postmenopausal hot flushes: A disorder of thermoregulation

The changes in cutaneous and body temperature and cutaneous conductance during hot flushes in eight postmenopausal women were studied. The vasomotor changes occurred approx. 45 sec after the patients experienced the initial subjective symptoms of the attacks. The rise in skin conductance appeared to be a more reliable index of the flushing episode than did the change in skin temperature. On the basis of the changes recorded it is suggested that the hot flush syndrome may represent a specific thermoregulatory disorder rather than being due to a non-specific central autonomic discharge. The episodes may be triggered by a neuroendocrine imbalance following the disruption of ovarian function and fall in estrogen production. In assessing the frequency and severity of hot flushes, and the effects of treatment, objective measurements of skin and core temperature and skin conductance should replace subjective criteria.

Ethanol-Induced Hypothermia in the Rat

Ethanol (0.5-3.2g x kg-1 i.p.) caused a dose-dependent fall in body temperature in rats. A dose of 1.5g x kg-1 i.p. led to a fall of 1.6 +/- 0.20 degrees C over 60 min at an environmental temperature of 18 +/- 1 degrees C. There was no evidence of acute tolerance when the hypothermic response was elicited by the same dose of ethanol (0.7--20.0g x kg-1 i.p.) 24 h later; indeed the second response was consistently, although not significantly, greater than the first. Behavioral thermoregulatory studies indicated that the fall in temperature after ethanol is due, at least in part, to a downward setting in the thermoregulatory set point. These results suggest that the rat may be a suitable animal model for a study of accidental hypothermia following ethanol ingestion and exposure to low environmental temperatures.

Thermpregulatory mechanisms and ethanol hypothermia

The mechanisms underlying the hypothermic effect of ethanol have been investigated in rats. At an ambient temperature of 26 degrees C, at which tail skin blood flow will normally be expected to play a role in regulating core temperature, no change in tail cutaneous temperature occurred during the period in which the core temperature was falling after administration of ethanol. As the drug effect waned tail skin temperature fell below the initial temperature as the hypothermia was corrected. This last observation confirms earlier results indicating a shift in the thermoregulatory set point after administration of ethanol. There was no significant change in oxygen consumption related to the ethanol induced fall in core temperature so decreased heat production would not appear to be a factor in the thermal imbalance. Neither was there any change in respiratory rate or minute volume to account for an increase in convective or evaporative heat loss via the lungs. From these results it is not clear by what mechanism the ethanol induced lowering of the set point leads to a fall in core temperature. Other avenues of heat loss, for example from other cutaneous surfaces, and further detailed thermal balance studies will be needed to resolve this problem.

Similar anticonvulsant, but unique, behavioural effects of opioid agonists in the seizure-sensitive mongolian gerbil

Opioid agonists were used to investigate the modulation of seizures mediated by mu, kappa and delta opiate receptors in the seizure-sensitive Mongolian gerbil. Morphine (1.0-25 mg/kg, s.c.) were used as prototypic agonists for mu, kappa and delta opiate receptors. Each opioid decreased the incidence and severity of the seizure as compared to control values. The anticonvulsant effects of morphine (10 mg/kg, s.c.) and ketocyclazocine (0.5 mg/kg, s.c.) were reversed by naloxone (1.0 mg/kg, s.c.), while the anticonvulsant effects of N-allylnormetazocine (2 mg/kg, s.c.) were not significantly changed by naloxone. Additionally, abnormal behavior was observed following administration of the opioids. Morphine (10 mg/kg, s.c.) produced excitation and hyperresponsiveness with intermittent cataleptic-like states. Ketocyclazocine (10 mg/kg, s.c.) predominantly produced a stuporous, immobile state, accompanied by some loss of posture. N-allylnormetazocine (10 mg/kg, s.c.) produced ataxia and stereotypic side-to-side head nodding . Naloxone was able to reverse the behavioral effects produced by morphine and ketocyclazocine but not those produced by N-allylnormetazocine. The data presented are consistent with earlier studies which demonstrated the anticonvulsant effects of beta-endorphin in the gerbil. This study further suggests that opioids have a protective role against seizure activity in the gerbil and the opioid anticonvulsant effect is not specific to one type of opioid agonist.

Monitoring the pathophysiological correlates of postmenopausal hot flushes

Clinical assessment of the severity and frequency of post-menopausal hot flushes can be made objectively by measuring the associated changes in skin conductance and skin and core temperature. Such measurements provide a more reliable index of the response to therapy than does subjective reporting which has been employed in the past. The design and use of a working analyzer is presented that is sufficiently simple, rugged, safe and portable to be used under normal clinical conditions to provide a permanent record of the attacks.

THERMOREGULATORY CHANGES FOLLOWING THE MENOPAUSE

Publisher Summary This chapter presents a study to examine thermoregulatory changes following menopause. Eight patients were studied of whom five had spontaneously entered the climacteric and three had undergone oophorectomy. The age range was 37–66 years. Four normal menstruating subjects in the early follicular phase of the cycle were also studied. Measurements were carried out during a 24 h period on two separate occasions, approximately 7 days apart, with the subjects lightly clothed in bed in a thermally controlled room. During the first period of study, the patient was allowed to sleep during the normal time; in the second period, her sleeping time was reversed. Twenty-five flushing episodes were analyzed in detail in the postmenopausal patients. The mean values of the measured parameters are illustrated in the chapter.