Cerebral blood flow autoregulation to acutely increasing blood pressure during sympathetic stimulation.
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Biomedical subjects
Publications and source records attributed to A M Harper.
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A method for the measurement of liver blood flow (LBF) in rats has been developed by recording the clearance of 85Kr from the liver after injection of a solution of the gas into the portal vein. This technique provides a measure of tissue perfusion at a cellular level. The animal preparation was maintained in a stable haemodynamic and respiratory state for up to 4-3 h by careful fluid and anaesthetic control. Stability of the model was reflected by relative constancy of the LBF measured throughout the experiment in all of the animals studied. The mean LBF determined in six rats was 2-41+/-(s.d.) 0-50 ml/g/min.
The changes in liver haemodynamics following partial hepatectomy (PH) were studied using an 85Kr clearance technique to measure perfusion in the livers of rats before and after both PH and sham operations. Post-operative measurements were made for 8 h following operation and also at 21 and 35 h, when uptake of tritiated thymidine into DNA is maximal in regenerating rat liver. Sham operation did not influence hepatic perfusion, arterial pressure or portal pressure. PH induced an early increase in perfusion of 293% in spite of a decrease in arterial blood pressure during the initial 4 h. The increase in perfusion lasted at least 8 h, had returned to normal values by 35 h, and was not explained solely by an observed elevation of portal pressure of 50% which returned to normal 5 h postoperatively. The total volume flow to the liver remnant after PH, however, was essentially the same as the flow to the liver before operation.
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The accuracy of liver blood flow measurement using the 85Krypton clearance technique depends on the use of an appropriate value for the solubility of 85Kr in liver relative to blood (the partition coefficient, lambda). This factor was studied in the regenerating liver remnant of the rat after a 67% partial hepatectomy, in order to find the influence of the ensuing postoperative fatty infiltration of the liver. There was found to be a rapid increase in lambda from 0-95 in the normal liver to 1-52 in the remnant 7-5 h after operation, followed by a more gradual return to normal levels by 35 h. The results indicate an early increase in the fat content of the liver after 67% hepatectomy and demonstrate that liver blood flow calculated from 85Kr clearance measurements in the early stages of regeneration must take into account the changes in lambda during that time.
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Cerebral blood flow (CBF) was measured by a 133Xe inhalation technique in 8 patients with chronic high spinal cord injuries. Six patients had a physiologically complete cervical cord transection and 1 subject had an incomplete C4-5 lesion but with evidence of interruption of sympathetic pathways. CBF and arterial blood pressure (BP) were measured in the supine position and then in the sitting, or feet up, position to produce a change of BP. In 4 patients CBF was measured during a suction manoeuvre applied to the lower half of the body to produce a fall of BP. There was no significant change of CBF in the patients during hypo- and hypertension. The response of CBF to hyperventilation for 5 min was measured in the supine position and did not differ significantly from that of 13 normal "control" subjects and 1 patient with a lesion at T2-3. It is concluded that the responses of the cerebral circulation to change of blood pressure and to hypocapnia are normal in patients with high spinal cord transection. The mechanisms involved in these responses are therefore independent of control via cervical sympathetic pathways.
The effect of graded, progressive hypotension on the autoregulation of cerebral blood flow was studied in anaesthetised baboons. Progressive hypotension was produced over a period of four to five hours, either by graded haemorrhage or by the administration of increasing concentrations of hypotensive drugs. During haemorrhagic hypotension autoregulation was maintained until the mean arterial pressure had decreased to 65% of its baseline value, below which cerebral blood flow was pressure passive. In those animals subjected to drug-induced hypotension, autoregulation persisted to lower levels of mean arterial pressure (35-40% of baseline). It is postulated that under conditions of haemorrhagic hypotension, constriction of the extraparenchymal cerebral vessels in response to sympathetic stimulation decreases the possible range of autoregulation in the anaesthetised baboon.
The systemic administration of norepinephrine has minimal effects on the cerebral circulation, perhaps due to blood-brain barrier mechanisms. To test hypothesis, the cerebrovascular effects of norepinephrine beyond the blood-brain barrier were studied in anesthetized baboons, Intraventricular norepinephrine (40 mug/kg) resulted in significant increases in cerebral blood flow (40%), cerebral oxygen consumption (21%), and cerebral glucose uptake (153%). Intracarotid hypertonic urea opens the blood-brain barrier by osmotic disruption; Consequent to hypertonic urea, the intracarotid infusion of norepinephrine, 50 ng/kg-min, significantly increase cerebral blood flow (49%), cerebral oxygen consumption (21%), and cerebral glucose uptake (76%), It appears probable that the cerebrovascular responses to norepinephrine are dependent on the integrity of the blood-brain barrier; It is likely that the increase in cerebral blood flow, associated with norepinephrine when it bypasses the barrier, is secondary to an increase in cerebral metabolism.
The influence of brain norepinephrine on cerebral metabolism and blood flow was examined because exogenous norepinephrine, administered in a way that the blood-brain barrier is bypassed, has been shown to effect pronounced changes in the cerebral circulation. Reserpine (40 mug/kg, by intracarotid infusion) was administered in order to release brain norepinephrine in five anesthetized baboons. Reserpine significantly increased cerebral oxygen consumption (23%) and cerebral blood flow (50%). This response lasted for approximately 60 min. In a further five animals, effects of central beta-adrenoreceptor blockade were studied. Pro pranolol (12 mug/kg-min) produced an immediate, significant reduction in both cerebral oxygen consumption (40%) and cerebral glucose uptake (39%). Cerebral blood flow was reduced minimally. However, the responsiveness of the cerebral circulation to induced hypercapnia was severely attenuated from a gradient of 3.22 before, to 1,11 after, administration. These experiments suggest that central norepinephrine can influence the cerebral circulation primarily through noradrenergic effects on brain metabolism.