Cerebral mechanisms in cardiovascular control : Studies on haemorrhage and effects of sodium

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Physiology and Pharmacology

Sammanfattning: This thesis describes experiments investigating the influence of the brain on cardiovascular adaptations to haemorrhage and excess sodium in conscious chronically prepared sheep. A continuous reduction in blood volume eventually activates a reflex that causes a fall in vascular resistance and heart rate and thereby also in arterial blood pressure. The mechanisms behind this reaction, usually referred to as the decompensatory phase, are not known in detail but it is likely to be neurally mediated. Elevated body fluid NaCl, on the other hand, increases blood pressure. This is mainly achieved by enlarging the plasma volume. However, a putative cerebral action of increased sodium concentration may also contribute to the pressor response. Infusion of hypertonic NaCl solutions is widely acclaimed as an efficient way of restoring haemorrhagic hypotension but investigations concerning the role of the brain in mediating this effect have been largely neglected. Intracerebroventricular infusion of the unspecific opioid antagonist naloxone prior to haemorrhage significantly postponed blood loss induced hypotension, whereas the unspecific opioid agonist morphine had the opposite effect. Further studies revealed that activation of kappa- and delta-opioid receptors, but not mu-opioid receptors adjacent to the ventricular compartment, contributed to initiate haemorrhagic hypotension and bradycardia. However, blockade of these receptors delayed, but could not totally prevent the decompensatory phase. Isoflurane anaesthesia abolished the cerebral effects of hypertonic NaCl on the circulation. As the improvement in cardiovascular function was impaired, it appears that there is a cerebral component crucial for the full effect of hypertonic NaCl resuscitation. This hypothesis was investigated in a separate study of haemorrhage, where it was shown that increased periventricular sodium concentration and cerebral angiotensin II receptors type 1 (AT1)-receptors contribute, together with plasma volume expansion, to improve systemic haemodynamics after intravenous treatment with hypertonic NaCl. Thus, resuscitation with hypertonic NaCl after haemorrhage partly depends on brain mechanisms. Using a newly developed technique for intracerebral injections in conscious chronically prepared sheep it was also demonstrated that reversible inhibition of the neurotransmission within the paraventricular nucleus of the hypothalamus with lidocaine had no apparent effect per se but effectively abolished the increase in arterial blood pressure, central venous pressure and glomerular filtration rate as well as the decrease in plasma angiotensin II levels seen in responses to elevated cerebrospinal fluid sodium concentration. These results indicate an influence of this brain structure on the non-volume dependent cardiovascular adaptations to hypertonicity.

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