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J T Stitt

Publications and source records attributed to J T Stitt.

At least 37 records · Page 2Linked to original sources
PubMed1985

Comparison of febrile responsiveness of rats and rabbits to endogenous pyrogen.

The fever responses of rats and rabbits were compared in detail using a single common source of semipurified endogenous pyrogen prepared from human monocytes. The characteristics and dynamics of the fever-response curves for each species were examined and their dose-response curves were determined and compared. The fevers displayed by rats were qualitatively similar to those of rabbits, but, typically, they developed and terminated more rapidly than those of rabbits. Rabbits were much more sensitive to the endogenous pyrogen than rats. The threshold dose of pyrogen required to elicit a fever was 5 times lower in the rabbit, and the slope of the rabbit's dose-response curve was 1.5 times steeper than that of the rat. The maximum fevers attainable in rabbits were approximately twice those attainable in rats. It was also shown that the more rapid febrile responses of the rat were not due to the 10-fold smaller mass of the rat; instead, we proposed that this difference was more likely due to a closer diffusional proximity of the pyrogen receptor sites to the circulation in rats. The lower sensitivity of the rat to endogenous pyrogen was attributed to a relative insensitivity of the pyrogen receptor sites in rats in the translation of the endogenous pyrogen stimulus into fever.

Animals↗
PubMed1984

An analysis of the purinergic component of active muscle vasodilatation obtained by electrical stimulation of the hypothalamus in rabbits.

In anaesthetized rabbits, electrical stimulation of the hypothalamus in areas analogous to the defence area in cats produces the 'defence reaction.' This response includes signs of arousal and a large increase in blood flow to skeletal muscle in the hind limb caused by a vasodilatation in the skeletal muscle vasculature. The vasodilatation is a sympathetic response, and it is not dependent upon muscle activity in the hind limb. The muscle vasodilatation is insensitive to alpha-adrenoceptor, beta-adrenoceptor, cholinoceptor and histamine receptor antagonists. Intra-arterial injections of the purinoceptor agonists, adenosine triphosphate (ATP) and adenosine, mimic the vasodilatation produced by electrical stimulation. The P1-purinoceptor blocker, aminophylline, attenuates adenosine-induced vasodilatation, but it does not affect the vasodilatation produced by ATP or hypothalamic stimulation. The P2-purinoceptor blocker, antazoline, attenuates the vasodilatation produced by both ATP and hypothalamic stimulation. Our results suggest that the muscle vasodilatation produced by hypothalamic stimulation is mediated by purinergic nerves which release ATP and act on P2-purinoceptors.

Animals↗
PubMed1983

Inhibition of shivering during restraint hypothermia.

Restraint hypothermia has often been described, but its cause has never been clarified. We hypothesized that it might be due to a suppression of shivering thermogenesis. Thus, we restrained conscious rats in an ambient temperature of 2 degrees C while measuring rectal (Tre) and tail skin temperatures, metabolic rate (MR), and shivering activity. When rats were cold exposed but not restrained, Tre fell 1.4 +/- 0.2 degrees C (SE) during the 1st h. When these same rats were restrained, Tre fell at a rate of 6.5 +/- 0.2 degrees C/h. MR averaged 15.7 +/- 1.4 W/kg for the unrestrained rats, but it averaged only 9.0 +/- 1.1 W/kg for the restrained rats. The restrained rats showed no signs of shivering. The animals were then subjected to a restraint adaptation regimen and then reexposed to cold. Restraint now produced a fall in Tre of only 2.6 +/- 0.7 degrees C/h. The animals shivered and generated an MR of 15.8 +/- 0.9 W/kg. Naive rats became hypothermic because restraint suppressed shivering activity. However, adapted rats continued to shiver and remained normothermic. We suggest that a stressful or threatening situation, such as restraint for a naive rat, inhibits shivering and leads to hypothermia in a cold environment. This would not occur in adapted rats because restraint is no longer stressful.

Adaptation, Psychological↗
PubMed1981

Neurophysiology of fever.

Fever is a primary disorder of thermoregulation and a common clinical sign in many diseases. It is characterized by an upward displacement in the level at which body temperature is regulated. Early attempts to study hypothalamic neuronal activity in relation to fever described the behavior of isolated single units after intravenous injections of endotoxin pyrogen. It was concluded that the thermosensitivity of many warm-sensitive units was depressed after pyrogen injections, but due to the indirect technique employed, it is not possible to distinguish whether this observation is the cause or result of fever. A decrease in hypothalamic thermosensitivity is contrary to observations made during fever in conscious animals. More specific applications of pyrogenic stimuli such as prostaglandin E1 onto individual hypothalamic neurons using the technique of microelectrophoresis have not borne out these earlier observations. A major obstacle to studying the neurophysiology of thermoregulation and fever is the absence of any obvious correlation between neuroanatomy and function in the hypothalamus. Present methods of identifying and classifying hypothalamic cells as participants in thermoregulation are patently inadequate. Until a more specific correlation between anatomy and function is established, the neurophysiological mechanisms of fever will remain obscure.

Animals↗
PubMed1980

Prostaglandin E levels in third ventricular cerebrospinal fluid of rabbits during fever and changes in body temperature.

1. A method was devised to sample cerebrospinal fluid (c.s.f.) from the third ventricle of conscious rabbits.2. Levels of PGE were measured in c.s.f. withdrawn from the third ventricle of rabbits exposed to a variety of manipulations of both brain and body core temperatures which mimicked various facets of fever in these animals. These results were compared to the levels of PGE in the c.s.f. of the same rabbits made febrile by I.V. injections of endogenous pyrogen.3. Levels of PGE in ventricular c.s.f. remained unaltered at 2-3 ng/ml. during exposure to cold, hyperthermia due to heat exposure, hypothalamic cooling or hypothalamic heating, whereas during fever produced by endogenous pyrogen, they rose to an average of 11-12 ng/ml. Furthermore, a significant positive correlation was established between the level of PGE measured in the c.s.f. and the subsequent height of the fever produced by the pyrogen.4. Since production of PGE within the brain is not caused by changes in the brain or body temperatures which are comparable to those observed during fever, and yet greater than fivefold increases in the PGE levels in c.s.f. are produced by I.V. injections of endogenous pyrogen, it is concluded that PGE production in the brain is involved in the pathogenesis of fever.

Animals↗
PubMed1980

Variable open-loop gain in the control of thermogenesis in cold-exposed rabbits.

We have previously demonstrated a multiplicative interaction between mean skin temperature (Tsk) and hypothalamic temperature (Thy) in the control of thermogenesis in cold exposed rabbits. Such a model predicts that open-loop gain will not be constant, but will vary according to the direction and degree of Thy displacements and to the prevailing level of Tsk when Thy is altered. Open-loop gain was calculated from steady-state displacements in body temperature induced by sustained step displacements in Thy. Hypothalamic temperature of rabbits was clamped at various levels ranging from 2 degrees C above to 3 degrees C below normal Thy and the resulting changes in rectal temperature attained at steady state were recorded. Experiments were conducted at ambient temperatures (Ta) of 2 degrees and 15 degrees C. Open-loop gain in response to hypothalamic heating was always greater than that obtained in response to equivalent levels of hypothalamic cooling. Furthermore, at lower levels of Tsk (Ta = 2 degrees C) open-loop gain was greater for all levels of Thy displacement when compared to that measured at higher levels of Tsk (Ta = 15 degrees C).

Animals↗
PubMed1979

Fever versus hyperthermia.

A variety of conditions that result in the elevation of body temperature are described and discussed. These hyperthermias are divided into four categories; fever, exercise hyperthermia, hyperthermias due to inadequate means of heat dissipation, and hyperthermias resulting from pathological or pharmacological impairments of thermoregulatory mechanisms. A comparison of the physical and physiological characteristics of these hyperthermias is presented and distinctions are drawn on the basis of these characteristics. Fever is shown to differ markedly from all other forms of hyperthermias. Specifically, the elevation in body temperature encountered during fever is a regulated rise that is defended by fully functional thermoregulatory mechanisms; the thermopreferendum is also elevated in fever, particularly at the onset or "chill phase"; and aspirin-like drugs can intervene in febrile hyperthermia and will return body temperature to its normal level. No other forms of hyperthermia possess these characteristics and thus only fever can be attributed to an upward displacement of the "set point" for body temperature regulation. Furthermore, in attempting to control rises in body temperature, it is apparent that aspirin is effective only in fever, while whole-body cooling is all but ineffective. In all other forms of hyperthermia, whole-body cooling is the only effective treatment.

Animals↗
PubMed1976

The regulation of respiratory evaporative heat loss in the rabbit.

1. Respiratory evaporative heat loss in the rabbit has a minimum value of 0-2-0-3 W/kg and a maximum value of about 1-1 W/kg in non-evaporatively limited environments. 2. Both skin temperature and hypothalamic temperature influence respiratory evaporative heat loss, and they do so in a multiplicative fashion. Thus, at low skin temperature the hypothalamic temperature threshold for the onset of panting is above normal hypothalamic temperature and hypothalamic thermosensitivity is high. On the other hand, at high skin temperatures, the hypothalamic temperature threshold for the onset of panting is well below normal hypothalamic temperature, but hypothalamic thermosensitivity is greatly reduced. 3. The influence of mean skin temperature (Tsk) and hypothalamic temperature on respiratory evaporative heat loss (Eres) in the rabbit can be described by the equation: Eres=1-1-0-08 (Tsk-39-7) (Thy-42-9) greater than or equal to 0-3 W/kg. 4. Thus, the ability of a lowered mean skin temperature to increase the thermosensitivity of the hypothalamus in response to local temperature changes applies to heat loss mechanisms as well as heat production mechanisms. It is suggested that the characteristics of this peripheral input into the C.N.S. are fulfilled by tonic cold fibre input originating from the peripheral cold receptors on the body surface.

Animals↗
PubMed1975

Behavioural and autonomic induction of prostaglandin E-1 fever in squirrel monkeys.

1. Prostaglandins E1 (PGE1) was injected into the preoptic/anterior hypothalamic (PO/AH) area of the squirrel monkey. 2. Increases in rectal temperature (Tre) produced by PGE1 injections of 20 ng to 500 ng were dose-dependent. 3. When ambient temperature (Ta) was below the thermoneutral zone, increases in Tre were produced entirely by increases in metabolic rate. With Ta at the upper end of the thermoneutral zone, increases in Tre were produced by vasoconstriction in addition to lesser increases in metabolic rate. 4. During sessions of behavioural temperature regulation, PGE1 injections were followed by the selection of a higher Ta, increased skin temperature and subsequent increases in Tre. 5. PGE1 injections produce dose-dependent increases in Tre which are similar regardless of ambient temperature or whether behavioural or autonomic means are utilized to raise the heat content of the body.

Animals↗
PubMed1975

Microelectrophoresis of PGE1 onto single units in the rabbit hypothalamus.

Prostaglandin E1 (PGE1) when micro-injected into the preoptic anterior hypothalamus (PO/AH) of conscious rabbits is a potent pyrogenic agent. We have investigated the action of PGE1 on the activity of single units of the PO/AH area using the microelectrophoretic technique. One hundred and thirty-eight PO/AH units were tested both for their response to changes in local PO/AH temperature and for their response to PGE1 application. Less than 9.0% of the total population of units tested showed any response to PGE1 application. When present, the response was invariably one of mild facilitation. No specific unit type (thermally sensitive or insensitive) appeared to be selectively affected by PGE1. Thus, the proportion of units affected by PGE1 was constant at 8-10% for warm-sensitive, cold-sensitive, or thermally insensitive units. There was no evidence to support an antagonistic role for PGE1 on the effects on norepinephrine on PO/AH units. On the basis of these results, we cannot predicate any simple neuronal basis for the action of PGE1 in producing fever in conscious rabbits. However, it is suggested that the action of PGE1 might be the modulation of presynaptic release of neurotransmitter onto the units of the PO/AH area.

Animals↗
PubMed1973

Prosaglandin E1 fever induced in rabbits.

1. Micro-injections of prostaglandin E(1) (PGE(1)) into the anterior hypothalamus of the rabbit produced fever which was nearly immediate in onset. The prostaglandin sensitive region appears to be identical to that described as being fever sensitive to leucocytic pyrogen.2. Micro-injections of PGE(1) into the posterior hypothalamus and midbrain reticular formation of the rabbit did not produce fever.3. The febrile response to PGE(1) injected into the anterior hypothalamus was dose dependent over a range of 20-1000 ng.4. Ambient temperature influenced the thermoregulatory mechanism by which PGE(1) fever evolved. In the cold, PGE(1) fever was due to increased heat production while during heat exposure both evaporative and dry heat losses were reduced without significant changes in heat production. Vasoconstriction, confined mainly to the ears, was effective in producing fever in standard room environments (24-25 degrees C) along with a small increase in heat production.5. The preoptic anterior hypothalamic area retained its thermosensitivity during PGE(1) fever; heating this area attenuated, while cooling augmented the fever.6. The results support the view that PGE(1) is a mediator of pyrogen induced fever.

Animals↗