John Ludbrook APPS Symposium Neural Mechanisms In The Cardiovascular Responses To Acute Central Hypovolaemia

Abstract

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 vasoconstriction and cardio-acceleration. Phase II commences once CO has fallen to a critical level of 50-60% of its resting value, equivalent to loss of approximately 30% of blood volume. 2. During phase II, sympathetic vasoconstrictor and cardiac drive fall abruptly and cardiac vagal drive increases. In humans, this response is invariably associated with fainting and has been termed vasovagal syncope. 3. In both experimental animals and in humans, the responses to acute central hypovolaemia are greatly affected by anaesthetic agents, in that the compensatory 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 response to hypovolaemia depends chiefly on the results of experiments in conscious animals. Use of techniques for simulating haemorrhage has greatly enhanced 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 to hypovolaemia is triggered, at least in part, by a signal from cardiac vagal afferents. There is also strong evidence that phase II depends on brainstem delta-opioid receptor and nitrergic mechanisms and can potentially be modulated by circulating or neuronally released adrenocorticotropic hormone, 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 interact and their precise neuroanatomical arrangements.

Involvement of arginine vasopressin in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats

“…AVP gene transcription increases rapidly after hypotensive haemorrhage [37] and the sympathoinhibitory phase of haemorrhagic shock is characterised by increased plasma AVP concentration [11]. Indeed, the present results demonstrate 14.1-and 17.5-fold higher plasma AVP levels in the post-bleeding period in comparison to the baseline values.…”

“…There are two integrated phases of haemodynamic and neurohumoral response to blood loss [11]. An initial phase is characterised by good maintenance of MAP due to a reflexinduced increase in the sympathetic system activity.…”

“…An initial phase is characterised by good maintenance of MAP due to a reflexinduced increase in the sympathetic system activity. In contrast, there is a rapid decrease in MAP with bradycardia in the second phase of regulation as a result of withdrawal of the sympathetic tone (sympathoinhibitory phase), despite activation of humoral compensatory mechanisms, such as secretion of adrenal catecholamines and arginine vasopressin (AVP), and activation of the renin-angiotensin system [11]. Previous studies by the author clearly show the role of the sympathetic nervous system [12] and the renin-angiotensin system [13] in the central histamine-induced reversal of the sympathoinhibitory phase.…”

Cardiac and regional haemodynamic effects of histamine N-methyltransferase inhibitor metoprine in haemorrhage-shocked rats

“…Indeed, critical hypotension is associated with pronounced bradycardia [3 -4], which, as postulated, results from the stimulation of left ventricular unmyelinated nerve fibres and a reflexinduced increase in parasympathetic and a decrease in sympathetic activity [22]. The study confirms that hypotension of 20 -25 mmHg is associated with an extreme decrease in CI and an increase in TPRI.…”

“…The study confirms that hypotension of 20 -25 mmHg is associated with an extreme decrease in CI and an increase in TPRI. Rises in regional vascular resistance can be explained by the activation of humoral compensatory mechanisms in the post-bleeding period [22].…”