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Biomedical subjects

A M Harper

Publications and source records attributed to A M Harper.

At least 73 records · Page 4Linked to original sources

Effects of hypotension induced by halothane, on the cerebral circulation in baboons with experimental renovascular hypertension.

The effect of graded, progressive hypotension on the autoregulation of cerebral blood flow was studied in anaesthetized baboons with experimental renovascular hypertension. Graded hypotension was induced over a period of 5-6 h by the administration of increasing concentrations of halothane. In these chronically hypertensive animals cerebral blood flow remained constant until the mean arterial pressure had decreased to approximately 90 mm Hg. At mean arterial pressures of less than this value cerebral blood flow was pressure passive. At the completion of the investigation the brains were fixed by perfusion and submitted to neuropathological examination. Evidence of chronic hypertension and of ischaemic brain damage was found in every animal.

Animals↗

Effect of atypical antibiotic resistance on microorganism identification by pattern recognition.

We classified microorganisms from the clinical laboratory by using information provided by the Gram stain and antibiotic sensitivity profiles obtained with the Bauer-Kirby technique. Approximately 4,000 microorganisms, routinely identified and tested for antibiotic sensitivities in a large hospital microbiology laboratory, were used as a data set for several pattern recognition classification methods: K--nearest-neighbor analysis, statistical isolinear multicomponent analysis, Bayesian inference, and linear discriminant analysis. K--nearest-neighbor analysis yielded the highest prospective classification accuracy for gram-negative organisms, 90%. When those organisms displaying an atypical antibiotic resistance pattern were excluded from the data, the gram-negative classification accuracy improved to 95%. These results are inferior to currently accepted biochemical identification methods. Microorganisms with atypical antibiotic resistance patterns are likely to be misidentified and are common enough (17% of our isolates) to limit the feasibility of routine identification of microorganisms from their antibiotic sensitivities.

Anti-Bacterial Agents↗

A comparative study of liver blood flow using 133Xenon clearance and electromagnetic flowmeter measurements.

Recent work has shown that the slow components of the multiexponential clearance of 133Xenon from the liver are generated by radioactive gas in the stomach and intestines, and that the true intraphepatic clearance is monoexponential (Mackenzie et al., 1976). In the present study, liver blood flow calculated from the fast component of the 133Xenon clearance curve was compared with the total hepatic flow recorded with electromagnetic flow probes on the portal vein and hepatic artery in 8 dogs. Injections of isotope were made intoe the portal vein, and the clearance curves treated simply as biexponentials. A total of 50 pairs of blood flow measurements with the two techniques was obtained over a range of values from 80 to 1400 ml/min, and a close correlation found between them (r = 0.91). This result shows that when the clearance rate of the fast component is used for the flow calculation, the 133Xenon clearance technique provides an accurate measure of liver blood flow.

Animals↗

Hepatic blood flow studies in the rat before and after portacaval transposition.

Portacaval transposition diverts portal blood from the liver and allows systemic venous blood from the caudal inferior vena cava to perfuse the portal bed. Measurement of hepatic tissue blood flow before and after portacaval transposition and its relationship to the liver atrophy seen after portacaval transposition is important. Sequential measurements of hepatic tissue blood flow carried out before and after portacaval transposition have been made using the clearance of the inert radioactive gas 85Krypton after injection into the portal bed. These measurements reveal that hepatic tissue blood flow is not diminished following the operation. The relative liver atrophy seen after portacaval transposition is therefore consequent on portal venous diversion but not on diminished hepatic perfusion.

Animals↗

Liver blood flow measurements in the portacavally transposed rat before and after partial hepatectomy.

The haemodynamic changes following partial hepatectomy (PH) in the portacavally transposed rat have been studied using an 85Kr clearance technique. Liver blood flow measurements (LBF) were made before and after portacaval transposition (PCT) and PH was performed either immediately or at 3 weeks after transposition and further blood flow measurements made. No change in LBF was noted after PCT compared with preoperative values. Following PH in the portacavally transposed animals there was no marked increase in LBF. It is suggested that the liver atrophy consequent on portal diversion is due to deviation factors in portal blood and not to a decrease in absolute LBF. Regenerative hyperplasia occurs in the absence of the post-hepatectomy rise in LBF seen in normal animals.

Animals↗

Prostaglandin-induced effects in the primate cerebral circulation.

The effects of intracarotid infusions of prostaglandins E2 and F2alpha on cerebral blood flow (CBF) and oxygen consumption (CMRO2), and on extracranial blood flow, have been studied in anaesthetisex baboons. The 133Xe clearance method was used for measuring CBF, whilst extracranial blood flow was assessed by both the local tissue injection of 133Xe and external carotid artery flowmetry. Both PGF2alpha and PGE2 (10(-7) and 10(-6) g/kg/min) reduced both CBF and CMRO2. Spasm of the internal carotid artery with PGE2 was noted at the higher dose. Following osmotic opening of the blood-brain barrier by the hypertonic urea technique, the effects of small doses of PGE2 and CBF and CMRO2 were greatly potentiated. PGE2 greatly increased extracranial blood flow. Hence, both PGE2 and PGF2alpha reduce CBF and CMRO2, whilst PGE2 greatly increases extracranial blood flow.

Animals↗

Migraine and the blood-brain barrier.

The prodromal (cerebral) symptoms of migraine are associated with a fall in cerebral blood-flow (C.B.F.). The suggestion that various circulating vasoactive agents might be the cause of this fall in C.B.F. ignores the contradictory findings that the cerebral vascular bed is normally unresponsive to such agents; but if the blood-barrier is disrupted, systemically administered monoamines and prostaglandins elicit pronounced changes in cerebral-tissue perfusion and metabolism. A defect in the blood-brain barrier of migraine patients (particularly those in whom an item of diet may trigger an attack) would make the cerebral circulation vulnerable to variations in circulating levels of vasoactive substances. Alternatively, the barrier could be intact in non-dietary patients, but release of monoamines or prostaglandins from the brain itself could account for the observed changes in the cerebral circulation.

Blood-Brain Barrier↗

Effects of 5-hydroxytryptamine on pial arteriolar calibre in anaesthetized cats.

1. The responses of individual pial arterioles and small arteries to perivascular injections of 5-hydroxytryptamine were studied in anaesthetized cats.2. Pial arteriolar calibre was measured by a television image-splitting technique.3. At normotension, the average response of pial vessels was dilatatory at injected 5-hydroxytryptamine concentrations between 10(-10) and 10(-4)M.4. These pial vascular changes were, however, dependent upon the resting vessel calibre: those arterioles < 70 mum dilated universally, whereas small arteries >/= 200 mum in resting diameter tended to constrict in response to 5-hydroxytryptamine.5. The 5-hydroxytryptamine-induced dilatation of pial arterioles < 70 mum in resting calibre was directly dependent on mean arterial pressure, although no such relationship was observed with the larger cerebral vessels.6. It is concluded that the specific cerebrovascular actions of 5-hydroxytryptamine are largely tone-dependent. The greater the resting tone of a pial arteriole, then the greater will be the tendency of that vessel to dilate in response to 5-hydroxytryptamine, and vice versa.7. The direct vascular actions of 5-hydroxytryptamine are in contradistinction to the observed changes in cerebral tissue perfusion and it would therefore appear that the effects of this amine on cerebral metabolism and neuronal activity outweigh its cerebrovascular actions under physiological conditions.

Animals↗

Cerebral circulation: effect of stimulation and blockade of dopamine receptors.

The effects of stimulation and blockade of dopaminergic receptors on cerebral blood flow and metabolism were investigated in 15 anesthetized baboons. The intravenous administration of apomorphine resulted in immediate, dose-dependent increases in cerebral blood flow (increased by 58% following 0.1 mg/kg apomorphine) which were always accompanied by increases in cerebral oxygen consumption (increased by 36% with 0.1 mg/kg) and glucose uptake (increased by 72% with 0.1 mg/kg). It is suggested that the primary action of apomorphine is on cerebral metabolism and secondarily on cerebral blood flow rather than directly on cerebral vascular smooth muscle. Pimozide, at doses that totally blocked apomorphine-induced increases, was without effect on cerebral blood flow and metabolism. The dilatatory response of the cerebral circulation to hypercapnia was preserved during dopamine-receptor blockade. The basal level of overall cerebral metabolism and hemispheric cerebral blood flow does not appear to be dependent to any large extent on the activity of the dopaminergic pathways in the central nervous system.

Animals↗

Response of the cerebral circulation in baboons to changing perfusion pressure after indomethacin.

An earlier study has demonstrated that indomethacin, a prostaglandin synthesis inhibitor, blocks the cerebrovascular response to hypercapnia. This response is believed to be mediated by a lowering of pH in the cerebral interstitial fluid. Should autoregulation of cerebral blood flow (CBF) to changing perfusion pressure also be mediated by a changing interstitial pH (the "metabolic" theory), then indomethacin should impair autoregulation. This hypothesis was tested in anesthetized baboons. CBF was measured by the intracarotid 133Xe clearance technique; the preparation and the indomethacin protocol were identical to those of our previous investigation. Arterial pressure was increased by the intravenous infusion of angiotensin and decreased by controlled hemorrhage. Indomethacin was given by continuous infusion into the internal carotid artery. Although it reduced resting CBF, the cerebrovascular response to changing perfusion pressure was unchanged. Because indomethacin affects the response to changing CO2 but not that to changing perfusion pressure, the mechanisms for these two reactions presumably are different and it is improbable that changing interstitial pH is responsible for autoregulation in the cerebral circulation.

Animals↗

Responses of the cerebral circulation to hypercapnia and hypoxia after 7th cranial nerve transection in baboons.

It has been proposed that the responses of the cerebral circulation to hypoxia, hypercapnia and hypotension may be partially mediated by an autonomic reflex with receptors in the carotid body or sinus serving as sensors and the efferent limbs being the 7th cranial nerves. Transection of the 7th cranial nerve has been reported to impair the cerebral circulatory response to isolated chemoreceptor stimulation by hypoxia and hypercapnia. To test this hypothesis we measured cerebral blood flow (CBF) by an intra-arterial 133Xe technique in 10 baboons during periods of induced hypoxia and hypercapnia, both before and after transection of the 7th cranial nerve, We found that the responses of CBF were unaltered by either unilateral or bilateral section of the nerve. Our results showing the preservation of normal CBF responses, following transection, suggest that neurogenic control of the cerebral circulation by an autonomic reflex involving the 7th nerve is unlikely.

Animals↗

Phenylethylamine and cerebral blood flow. Possible involvement of phenylethylamine in migraine.

Phenylethylamine can initiate migraine-type headaches in susceptible individuals. Migraine sufferers have a reduced ability to deaminate all monoamines, but particularly phenylethylamine. Phenylethylamine readily crosses the blood-brain barrier and thus could be a mediator of the cerebrovascular disturbances seen in migraine attacks. Cerebral blood flow was measured in 15 anesthetized baboons by the intracarotid 133Xe clearance technique. Phenylethylamine (4 x 10(-7) moles.kg-1min-1) produced significant increases in cerebral blood flow (36 percent) and cerebral oxygen consumption (45 percent) during the first 40 minutes of infusion. In contrast, an increased phenylethylamine concentration (2 X 10(-6) moles.kg-1min-1) constricted the cerebral bed (cerebral blood flow reduced by 28 percent). The response of the cerebral circulation to hypercapnia was preserved during the infusion. Phenylethylamine thus is capable of producing in an experimental animal a pattern of cerebrovascular events similar to those seen in migraine.

Animals↗