Neural mechanisms in the cardiovascular responses to acute central hypovolaemia

1. The haemodynamic response to acute central hypovolaemia consists of two phases. During phase I, arterial pressure is well maintained in the face of falling cardiac output (CO) by baroreceptor-mediated reflex vasoconstricti on and cardio-acceleration. Phase II commences once CO has fallen to a crit ical level of 50-60% of its resting value, equivalent to loss of approximat ely 30% of blood volume. 2. During phase II, sympathetic vasoconstrictor and cardiac drive fall abru ptly and cardiac vagal drive increases. In humans, this response is invaria bly associated with fainting and has been termed vasovagal syncope. 3. In both experimental animals and in humans, the responses to acute centr al hypovolaemia are greatly affected by anaesthetic agents, in that the com pensatory responses during phase I (e.g. halothane) or their failure during phase II (e.g. alfentanil) are blunted or abolished. 4. Therefore, our present knowledge of the neurochemical basis of the respo nse to hypovolaemia depends chiefly on the results of experiments in consci ous animals. Use of techniques for simulating haemorrhage has greatly enhan ced this research effort, by allowing the effects of multiple treatments on the response to acute central hypovolaemia to be tested in the same animal . 5. The results of such experiments indicate that phase II of the response t o hypovolaemia is triggered, at least in part, by a signal from cardiac vag al afferents. There is also strong evidence that phase II depends on brains tem delta (1)-opioid receptor and nitrergic mechanisms and can potentially be modulated by circulating or neuronally released adrenocorticotropic horm one, brainstem serotonergic pathways operating through 5-HT1A receptors and opioids acting through mu- and kappa -opioid receptors in the brainstem. 6. Phase II also appears to require input from supramedullary brain centres . Future studies should determine how these neurotransmitter systems intera ct and their precise neuroanatomical arrangements.