SUMMARY1. The defence areas of the rat brain stem have been extensively explored using electrical and chemical stimulation in an attempt to locate the regions containing the perikarya of neurones which may initiate or integrate the visceral and behavioural components of the defence reaction.2. In rats anaesthetized with alphaxalone-alphadolone, a cannula electrode was used to compare the responses to electrical stimuli with those evoked by microinjection of the excitatory amino acid D,L-homocysteic acid (DLH), at the same site. A total of 128 sites throughout the brain stem was studied in 75 rats.3. The pattern of visceral and somatic changes characteristic of the defence reaction, viz. increases in arterial blood pressure and heart rate, vasodilatation in hind-limb muscles and vasoconstriction in the kidney, hyperpnoea and tachypnoea, exophthalmos, mydriasis, twitching of the vibrissae and retroflexion of the tail, was evoked by electrical stimulation within well-defined regions of the brain stem, from the anterior hypothalamus to the pons.4. Microinjection of DLH into the same regions could evoke the full defence reaction, as defined above, but only from the dorsomedial periaqueductal grey matter. Three other regions were defined from which almost all the autonomic components of the defence reaction were evoked, except that blood pressure fell. These were located: (a) immediately dorsal to the optic chiasma, (b) in the medial tuberal region of the hypothalamus and (c) in the lateral pontine tegmentum.5. In conscious rats with implanted guide cannulae, darting and flight responses were evoked by microinjections of DLH into the periaqueductal grey matter but not from the hypothalamus or tegmentum. Brisk locomotion followed injections of DLH into the region overlying the optic chiasma.6. It is concluded that the brain stem neurones involved in integrating the somatic and visceral components of the defence reaction are concentrated within the four regions defined above. Whereas neurones in the periaqueductal grey matter can initiate the fully integrated defence reaction, those concentrated in the three other areas cannot be shown to do so. Of these three cell groups, the suprachiasmatic neurones seem to be closer in function to the periaqueductal group than are the neurones in the tuberal hypothalamus and pontine tegmentum.

SUMMARYThe effects of bilateral hind-limb ischaemia on blood pressure and on the blood pressure-heart rate reflex have been studied in the rat. Limb ischaemia increased blood pressure and decreased the elevation and slope of the regression line describing the relationship between heart period (H.P.) and mean arterial pressure (M.A.P.). Nociceptive afferents from muscle receptors using long fibre tracts in the anterolateral part of the spinal cord seem to be responsible for the changes seen. The changes in the blood pressure-heart rate reflex were mediated by a combination of vagal inhibition and sympathetic activation. The efferent pathway for the pressor effect was in the sympathetic outflow. Central catecholaminergic neurones were involved in the pressor effect of limb ischaemia but not in the changes in the blood pressure-heart rate reflex. Electrolytic lesions in the posterior hypothalamus attenuated the inhibition of the reflex and it is suggested that neurones in the defence area may be activated by limb ischaemia. The interaction between limb ischaemia and the H.P.-M.A.P. relationship was not affected by opioid antagonists. After the period of ischaemia there was an increase in the elevation of the regression line describing the relationship between H.P. and M.A.P. which was secondary to the fall in body temperature characteristic of this phase of the response to injury.

SUMMARYThe effects of two components of tissue injury, namely fluid loss from the circulation and tissue ischaemia, on cardiovascular reflex activity have been studied. Moderate blood loss (10-20% blood volume) in the unanaesthetized rat increased the slope of the regression line relating heart period to mean arterial blood pressure and usually displaced it to the left (i.e. towards a relative bradycardia). A blood donation of 500 ml (approximately 10% blood volume) increased the Valsalva ratio in conscious man without a change in resting pulse rate. However, a 15 min period of unilateral limb ischaemia in man reduced the Valsalva ratio. The pattern of change in the pulse rat response to the Valsalva manoeuvre produced by limb ischaemia closely resembles that found previously after limb injury in man. There was no evidence that the endogenous opioids were involved in the interaction between limb ischaemia and cardiovascular reflex activity in man.

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