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Biomedical subjects

A M Harper

Publications and source records attributed to A M Harper.

At least 55 records · Page 3Linked to original sources
PubMed1981

Oxidation-reduction properties of the cytochrome b found in the plasma-membrane fraction of human neutrophils. A possible oxidase in the respiratory burst.

The oxidation-reduction midpoint potential of the cytochrome b found in the plasma membrane of human neutrophils has been determined at pH 7.0 (Em,7.0) from measurements of absorption spectra at fixed potentials. In both unstimulated and phorbol myristate acetate-stimulated cells Em,7.0 was -245 mV. Changes in pH affected the Em of the cytochrome b, with a slope of approx. 25 mV/pH unit change. The Em,7.0 of the haem group(s) of the membrane-bound myeloperoxidase of human neutrophils was found to be +34 mV. The plasma membranes contained no detectable ubiquinone, and no iron-sulphur compounds were detected by e.p.r. spectroscopy at 5-20 K. No flavins were detected by e.p.r. spectroscopy. The cytochrome b-245 was not reduced by added NADH or NADPH. Dithionite-reduced cytochrome b-245 formed a complex with CO, supplied as a saturated solution, which was dissociated with 26 microseconds illumination from a xenon flash lamp, and the recombination with CO had a half-time of approx. 6 ms. Partly (80%) reduced cytochrome b-245 was oxidized by added air-saturated buffer with a half-time faster than 1 s at 20 degrees C, a resolution limited by mixing time. These results are compatible with cytochrome b-245 acting as an oxidase.

Cell Membrane↗
PubMed1981

Cerebral circulation and histamine: 2. Responses of pial veins and arterioles to receptor agonists.

H2-receptors predominantly mediate pial arteriolar dilatation in response to histamine, but the reaction of pial veins to histamine has not been clearly identified. In anesthetized cats, we examined responses of pial veins and arterioles to perivascular microapplication of histamine and specific histamine H1 and H2 receptor agonists. Arterioles were very sensitive to the H2-receptor agonist impromidine, with significant dilatation (+16%) occurring at concentrations as low as 10(-10) M. Arteriolar responses to H1 receptor stimulation by 2.2-pyridylethylamine were small, even at high concentrations. The order of potency and maximum dilatations found for the receptor agonists were: H2 (43%) greater than histamine (28%) greater than H1 (17%). By contrast, pial veins did not respond to histamine or the receptor agonists. The results indicate that pial venomotor activity to histamine is negligible, and suggest a sparse distribution of histamine receptors on the outer surfaces of pial veins.

Animals↗
PubMed1981

Effect of the calcium antagonist, nimodipine, on cerebral blood flow and metabolism in the primate.

The effect of the calcium antagonist nimodipine was tested in anaesthetised primates. A rapid intravenous injection of 3 or 10 micrograms kg-1 produced a transient rise in end-tidal PCO2 and a fall in arterial blood pressure, but 10 min after the injection there was no significant change in CBF. A continuous intravenous infusion of 2 micrograms kg-1 min-1 caused a modest fall in mean arterial blood pressure and an increase in cerebral blood flow (CBF), which gradually increased to 27% above control after 50 min infusion. There was no significant change in CMRO2. A continuous intracarotid infusion of 0.67 micrograms kg-1 min-1 caused an increase in CBF of between 46 and 57%. This was further increased to 87% above control after disruption of the blood-brain barrier with hyperosmolar urea. Thirty minutes after the urea, the CBF returned to 43% above control. Twenty minutes after the infusion of nimodipine had been stopped, the CBF had returned to control values. EEG studies in this group showed no obvious increase in electrocortical activity. This evidence suggests that nimodipine has no effect on cerebral metabolism but increases CBF, particularly after disruption of the blood-brain barrier.

Animals↗
PubMed1980

The hepatic arterial blood flow response to portal vein occlusion in the dog: the effect of hepatic denervation.

The acute effect of portal vein occlusion on hepatic arterial blood flow was studied in a group of nine anaesthetised dogs. The influence of hepatic artery denervation and total liver denervation on the hepatic arterial flow response was determined subsequently. Blood flows in the hepatic artery and portal vein were measured with electromagnetic flowmeters, and hepatic tissue perfusion with 85Krypton clearance. A side-to-side mesocaval shunt was constructed to provide a drainage channel for the mesenteric venous blood during the periods of portal vein occlusion. Occlusion of the portal vein produced an immediate and significant increase in hepatic arterial flow which was sustained at approximately 80% above control for the 6 min period of observation. Total liver blood flow and hepatic tissue perfusion were both significantly reduced by about 40%. Denervation either of the hepatic artery alone or the entire liver produced no change in the response, and it is concluded that there is no neurogenic component either initiating or modifying the early changes in hepatic arterial flow.

Animals↗
PubMed1980

Adenosine response on pial arteries, influence of CO2 and blood pressure.

The television image-splitting technique was used to study the influence of arterial pCO2 and blood pressure on the dilatatory response of pial arterioles to topically applied adenosine in chloralose anaesthetised cats. At normocapnia (pCO2 congruent to 35 mm Hg) 10(-5) adenosine caused pial arteriole dilatation of 29.2 +/- 2.7% (S.E.M.). This was significantly reduced to 14.5 +/- 1.6% (P < 0.001) at pCO2 25 mm Hg and to 8.5 +/- 1.6% (P Ø 0.001) at pCO2 48 mm Hg. Lowering the blood pressure to 65--85 mm Hg had no significant effect on the adenosine response, but raising the blood pressure to 140--160 mm Hg significantly reduced the adenosine response to 22.1 +/- 1.8% (P < 0.005). The response was independent of vessel size except at hypertension where vessels < 150 micrometer were significantly more reactive than the larger vessels (P < 0.01). These results indicate that adenosine induced vasodilatation of pial arterioles shows little change in the face of alterations in vessel tone induced by altering blood pressure, but is markedly decreased by the combination of changing perivascular pH and vascular resistance through moderate changes in arterial pCO2. The importance of these results in assessing the role of adenosine as a cerebral vasodilator is discussed.

Adenosine↗
PubMed1980

Hepatic tissue perfusion studies during distal splenorenal shunt.

Hepatic tissue perfusion was measured by the krypton-85 clearance technique during surgery in four patients with bleeding esophageal varices before and immediately after Warren distal splenorenal shunt. No significant reduction in perfusion was found in any patient, thus confirming the concept that this type of portasystemic shunt maintains portal flow to the liver.

Adult↗
PubMed1979

Effects of increasing arterial pressure on cerebral blood flow in the baboon: influence of the sympathetic nervous system.

The influence of stimulation of the cervical sympathetic chain on the response of cerebral blood flow to hypertension induced by the intravenous infusion of angiotensin was studied in anaesthetised baboons. Cerebral blood flow was measured by the intracarotid 133Xenon injection technique. Possible lesions of the blood-brain barrier were studied by injecting Evans blue towards the end of the experiment and ischaemic brain damage was assessed following perfusion fixation. In a control group of five baboons blood flow increased by 53 +/- 9% (mean +/- S.E.) from the base line values in the arterial pressure range 130-159 mm Hg. In four baboons subjected to unilateral sympathetic stimulation flow increased by 16 +/- 4% in the same pressure range. In three baboons subjected to bilateral sympathetic stimulation there were no significant increases in flow until the arterial pressure had increased above 159 mm Hg. Disruption of the blood-brain barrier in the parietooccipital regions was only seen in the control animals but not in the stimulated baboons. Ischaemic brain damage was not observed with the exception of one small lesion in a single stimulated baboon. These findings provide strong support for the observations of Bill and Linder (1976) that activation of the cervical sympathetic can modify the level at which breakthrough of cerebral blood flow occurs in association with systemic hypertension.

Angiotensin II↗
PubMed1979

Effect of adenosine triphosphate and some derivatives on cerebral blood flow and metabolism.

1. Responses of cerebral blood vessels to peri- and intravascular doses of ATP (adenosine triphosphate) and some derivatives were studied in cat and baboon. 2. Perivascular application of ATP to cat pial arterioles gave a threshold dilatory effect at a concentration of 10(-11) M. This figure is comparable to the amount of ATP calculated to be released from electrically stimulated brain slices. 3. It is concluded that adenine nucleotides have a major role to play in the local control of cerebral blood flow. 4. Intracarotid injection of ATP showed a calculated threshold effect at 4 x 10(8) M in the cat and 4 x 10(-9) M in the baboon. 5. The threshold response of the vasculature to intracarotid adenosine lay between 4 x 10(-7) M and 4 x 10(-6) M in the baboon. Little effect was produced with AMP, pyrophosphate and inorganic phosphate. 6. Intracarotid ATP increased the oxygen consumption of the baboon brain parenchyma. This effect was attributed in part to an elevation of the cellular cyclic AMP levels. 7. Osmotic disruption of the blood-brain barrier in baboon did not affect the vasodilatory or metabolic effect of intracarotid ATP. 8. It is postulated that circulating purine compounds mediate a form of metabolic communication inthe body. Also, release of purine compounds from active local nerves might influence cerebral blood flow.

Adenosine Triphosphate↗
PubMed1979

Factors influencing the response of the cerebral circulation to phenylethylamine.

The cerebrovascular actions of phenylethylamine, an amine that has been implicated in the pathogenesis of migraine, were investigated in 16 anesthetized baboons. The influence of monoaminergic blocking agents and of a specific inhibitor of monoamine oxidase upon the cerebral circulatory and metabolic actions of phenylethylamine were examined. The reductions in cerebral blood flow (28 percent) and cerebral oxygen consumption (31 percent) that accompany the intracarotid administration of phenylethylamine (2 X 10(-6) moles per kilogram per minute) were unaffected by the prior administration of either phenoxybenzamine (1.5 mg per kilogram, IV) or pimozide (0.5 mg per kilogram, IV). The administration of phenoxybenzamine and pimozide per se did not significantly disturb cerebral blood flow or oxygen consumption. The ability of migraine patients to oxidatively deaminate phenylethylamine is reduced at the time of their attacks. In the present experiments, the administration of the monoamine oxidase type B inhibitor, deprenyl (1 mg per kilogram, IV), did not effect significant changes in cerebral blood flow or cerebral oxygen consumption. However, following deprenyl, the administration of phenylethylamine (4 X 10(-8) moles per kilogram per minute), a concentration which was without effect in normal animals, significantly reduced cerebral blood flow. Some of the possible mechanisms influencing the sensitivity of the cerebral circulation to phenylethylamine, and their relationship to migraine, are considered.

Animals↗
PubMed1979

A simple technique of measuring liver blood flow--intrasplenic injection of 133Xenon.

Intrasplenic injection of 133Xe was studied as an inert gas clearance technique for measuring liver blood flow in 13 dogs. This was done by comparing technique with intraportal injection of 133Xe (n = 41), and with electromagnetic flowmeter measurements of total liver blood flow. Very good correlation was obtained against the two latter techniques, the correlation coefficients being 0.99 and 0.90 respectively. The comparisons were made over a range of liver blood flow rates from 37 to 297 ml 100 g-1 min-1. The technique is potentially suitable for preoperative measurements, and may be particularly convenient when performed in conjunction with splenoportovenography.

Animals↗
PubMed1979

Rupture strength of skin wounds in jaundiced rats.

The rupture strength of 7-day-old wounds in normal rats, in rats in which there had been a previous skin incision, and in sham bile-duct-ligated and bile-duct-ligated jaundiced groups of rats was studied. It was found that wounds in jaundiced rats were significantly weaker than the wounds in the normal group of rats. Skin wounds in normal animals were significantly stronger than wounds in animals with sham bile-duct ligation. No difference was seen between sham bile-duct-ligated and bile-duct-ligated jaundiced rats.

Animals↗
PubMed1978

Indirect sympathomimetic agents and cerebral blood flow and metabolism.

The effects upon cerebral blood flow (CBF) and oxygen consumption (CMRO2) of the infusion into the internal carotid artery of tyramine and amphetamine were investigated in 24 anaesthetized baboons. The infusion of tyramine was without effect upon CBF and CMRO2 at normocapnia, even at concentrations which significantly raised arterial blood pressure. However, marked reductions in cerebral blood flow were noted at hypercapnia during the infusion of tyramine (2.5 X 10(-7) moles/kg/min). The infusion of amphetamine (7.5 X 10(-10) moles/kg/min) resulted in significant increases in CBF (32%) and CMRO2 (37%). However, an increased concentration of amphetamine (2.5 X 10(-7) moles/kg/min) significantly reduced CBF (22%) and CMRO2 (20%). It is suggested that amphetamine, by virtue of being able to cross the blood--brain barrier and interact with the cerebral monoamine systems, is able to influence cerebral blood flow by inducing changes in cerebral metabolism, and that the minimal reactivity of the cerebral circulation to the infusion of tyramine is the result of the inability of tyramine to cross the blood--brain barrier.

Animals↗
PubMed1978

An isotope clearance method for measurement of liver blood flow during portasystemic shunt in man.

The clearance from the surface of the liver of krypton 85 following its injection into the portal vein was measured in 10 patients. Six control patients (i.e. those not suffering from portal hypertension) averaged flow values of 142 ml per 100 g liver weight per min. A repeat flow estimation in these patients was not significantly different. Four patients with portal hypertension were studied. In 2 with congenital hepatic fibrosis the portal vein was temporarily occluded to allow prediction of the degree of hepatic perfusion likely to be achieved by the hepatic artery alone after portal deviation. The flow after portal venous clamping was unaffected in one of these cases but reduced by 45 per cent in the other. In a patient undergoing a Warren distal splenorenal shunt there was no change in flow after the procedure. If measurements are performed before and during temporary portal vein occlusion, an assessment of the flow reduction to be expected after a shunt procedure can be made. We suggest that a knowledge of liver tissue perfusion might influence the choice of operative procedure.

Blood Flow Velocity↗