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Biomedical subjects

L J McLeod

Publications and source records attributed to L J McLeod.

18 recordsLinked to original sources
PubMed1993

Propofol attenuates the myogenic response of vascular smooth muscle.

The myogenic response is the tendency of certain vessels, most notably small arteries and arterioles, to constrict in response to an increase in intravascular pressure. The effects of propofol on the myogenic response of the isolated pressurized rabbit ear artery were studied in segments preconstricted either with norepinephrine or 5-hydroxytryptamine and subjected to pressure increases from 60 to 100 mm Hg applied either rapidly (jumps over 500 ms) or slowly (ramps over 120 s). In the control experiments the preconstricted vessels initially dilated, then rapidly returned toward their initial diameter. In response to pressure ramps, vessels slowly dilated, but closely retained their resting diameter. Administration of propofol (1.6 x 10(-4) to 1.6 x 10(-3) M) resulted in dilation of the constricted vessels. With pressure jumps vessels had a reduced capacity to recover their initial diameters, and with pressure ramps vessels dilated to greater diameters. When the concentration of vasoconstrictor was increased to antagonize the propofol-induced dilation the myogenicity was not restored. This attenuation of myogenicity, distinct from the drug's vasodilator effect may represent a further mechanism by which anesthetic agents can affect cardiovascular function.

Animals↗
PubMed1992

Intraarterial propofol is not directly toxic to vascular endothelium.

To determine if accidental intraarterial injection of propofol results in vascular damage, the effect of bolus administration of propofol on vascular smooth muscle and the endothelium was investigated using the isolated rabbit ear artery. Ear artery segments, removed from urethane anesthetized rabbits, were perfused with Krebs solution (1 ml.min-1) and pressurized to 60 mmHg before being constricted with extraluminal norepinephrine (1.8-4.2 x 10(-6) M). The external diameter of the vessel was measured by an array of light-dependent diodes. Functional responsiveness was determined by the degree of constriction to norepinephrine and the subsequent dilatation of the artery to intraluminal acetylcholine (2 x 10(-6) M) and glyceryl trinitrate (2 x 10(-6) M), and by the myogenic reactivity to a pressure increase from 60 to 100 mmHg. These responses were measured before and after perfusion with 1% propofol for 120 s. Administration of propofol did not result in any vasoactivity nor did it increase the sensitivity to norepinephrine. Vessels maintained their capacity to dilate to both agents, while the myogenic activity was unaffected. Histologic examination of the propofol exposed vessels showed no changes to smooth muscle structure, and the endothelial layer remained intact.

Animals↗
PubMed1991

Intra-arterial thiopentone is directly toxic to vascular endothelium.

Ear artery segments removed from urethane-anaesthetized rabbits were mounted, perfused with Krebs solution, and pressurized before constriction with extraluminal noradrenaline. Vessel diameter was measured using a diode array mounted above the artery. After the degree of dilatation in response to intraluminal acetylcholine and glyceryl trinitrate was measured, vessels were perfused for 120 s with solutions of either 2.5-10% thiopentone or isotonic sodium carbonate in saline of matched pH. Administration of thiopentone solutions in all concentrations resulted in destruction of endothelial cells. The dilatation of vessels to glyceryl trinitrate and their myogenic reactivity was unaltered. Isotonic solutions of sodium carbonate (pH 10.6) had no effect on either endothelial cell function or direct vasodilatation. These data show that administration of thiopentone removes arterial endothelial cells, while vascular smooth muscle function is essentially unaltered.

Acetylcholine↗
PubMed1991

Measurement of gastric secretion as a student teaching exercise.

Teaching gastrointestinal physiology to preclinical medical students presents problems in finding suitable practical exercises to demonstrate the physiology of gastric acid secretion. In our course, students measure their own gastric secretory activity by the use of nasogastric tubes. Gastric secretion can be stimulated by insulin-induced hypoglycemia or by pentagastrin, a synthetic gastrin analogue. The time course of the secretory responses, i.e., volume, acid output, and pH, are followed by collecting control and poststimulatory secretions into 15-min samples. The effect of antiulcer drugs, such as cimetidine, can be easily studied in such experiments. The results of these experiments are very reproducible, allowing year-to-year comparisons of treatments. Examples of results of various experimental protocols are shown. We believe this to be a useful class exercise not only because of the excellent results it yields but because of the experience and insights it produces.

Cimetidine↗
PubMed1991

Myogenic response of isolated pressurized rabbit ear artery is independent of endothelium.

Central ear artery segments, removed from urethan-anesthetized rabbits, were used to assess whether distention activation was dependent on intact and functional endothelium (ENDO). Changes in external arterial diameter were measured with light-dependent diode array mounted above the vessel. After constriction with norepinephrine, slow increases in pressure from 60 to 80 or 100 mmHg performed over 120 s (pressure ramps) failed to initiate distention, but initial diameter was maintained. Rapidly applied (500 ms) pressure increases (pressure jumps) across same pressure ranges gave rise to initial distention and a myogenic response resulting in a return to almost initial diameter while new pressure was maintained for 120 s. Myogenic activity was measured from extent of recovery of vessel to its initial diameter during maintenance of pressure jumps or ramps. Rapid jumps and slow ramps were performed in presence of an intact ENDO and again after ENDO was removed by passage of intraluminal gas. With pressure jumps 60 to 80 mmHg, degree of recovery in ENDO-denuded vessels was 91.9% compared with 89.5% in ENDO intact vessels. For pressure jumps 60 to 100 mmHg, extent of recovery was 87.4 and 89.6%. During application of pressure ramps of 20 or 40 mmHg, vessel diameter did not increase by greater than 5%. There are no significant differences in these data, and we conclude that myogenic response in rabbit ear artery is mediated independently of endothelial-derived factors, irrespective of whether myogenic activation is induced by pressure jumps or ramps.

Animals↗
PubMed1990

Selective inhibition of platelet cyclooxygenase with controlled release, low-dose aspirin.

The hypothesis that slow administration of low doses of aspirin may selectively inhibit platelet cyclooxygenase and thromboxane A2 formation was evaluated using controlled release aspirin formulations. In the first study, doses of either 50, 100, 325 and 1,300 mg of these formulations and 300 mg soluble aspirin were ingested daily by healthy volunteers for one week. In the second study, doses of 5, 10, 25 and 50 mg controlled release aspirin, 50 mg soluble aspirin and 100 mg aspirin and glycine formulation were ingested daily for ten days. Platelet function and urinary prostaglandin production were assessed immediately before and on the seventh day of dosing in both studies and in the second study, repeated on the tenth day of dosing. Platelet function and serum thromboxane B2 production were fully inhibited by all formulations of 50 mg aspirin and above, but not by doses of controlled release aspirin below 50 mg doses. The excretion of urinary 6-keto-PGF1 alpha (a major metabolite of prostacyclin) was significantly reduced at controlled release aspirin doses above 100 mg and at all doses of rapidly absorbed aspirin tested. As no significant reduction in the urinary 6-keto-PGF1 alpha production was observed at doses of controlled release aspirin of 50 and 100 mg and below, it appeared that these doses did not inhibit the systemic vascular cyclooxygenase. These data are consistent with a selective inhibition of platelet function by daily doses of 50 and 100 mg of the controlled release formulation of aspirin.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Trapping sheep blowflies using bait-bins.

A bait-bin designed to attract and kill sheep blowflies is described. It is composed of a garbage bin plus lid, attractant and insecticide-treated offal. Fly entry holes are covered with differentiator wire to increase selectivity of kill. Placing bait-bins in preferred habitats of blowflies to optimise kill is outlined and temporal insecticide strategies to increase effectiveness of kill and reduce blowfly resistance are suggested. Preliminary data supporting the effectiveness of bait-bins in reducing blowfly numbers and flystrike in combination with good management practices to reduce sheep susceptibility to flystrike in the arid zone of New South Wales are presented and cost-effectiveness of bait-bins is analysed.

Animals↗
PubMed1986

The effects of different doses of some acetylsalicylic acid formulations on platelet function and bleeding times in healthy subjects.

In an attempt to find the most appropriate dose and formulation(s) of acetylsalicylic acid (ASA) for thrombosis prophylaxis, healthy volunteers were given doses of ASA for 1 wk daily ranging from 50 to 3900 mg as either Aspro-Clear (soluble), Astrix (enteric coated pellets) or Ecotrin (enteric coated tablets). Platelet function and bleeding times were monitored. All doses of ASA significantly inhibited platelet function (p less than 0.05) and increased bleeding times (p less than 0.05) relative to control values. Irrespective of the formulation, maximum increases in bleeding time and platelet dysfunction were obtained with daily doses of about 100 mg, and no further changes were observed with higher doses.

Adult↗
PubMed1985

The actions of leukotrienes C4 and D4 in the porcine renal vascular bed.

The kidney of anaesthetised pigs was perfused in situ with carotid arterial blood. Renal blood flow and perfusion pressure were recorded. Close intra-arterial injection of leukotriene (LT) C4, D4 or noradrenaline (NA) caused a dose-related increase in vascular resistance. Both LTs were more active than NA by one to two orders of magnitude. Systemically-administered indomethacin potentiated the effect of all three agonists. Incubation of renal artery tissue with calcium ionophore A23187 in the presence of indomethacin resulted in the generation of LT-like material which, when assayed on guinea-pig ileum, was indistinguishable from LTD4. The results show that pig renal vessels produce LT-like material and suggest that the potent vasoconstriction induced by exogenous NA and LTs is modulated in vivo by a vasodilator cyclo-oxygenase product.

Animals↗
PubMed1984

Inhibition of platelet function by a controlled release acetylsalicylic acid formulation--single and chronic dosing studies.

The extent to which a controlled release acetylsalicylic acid (ASA) formulation inhibited platelet function has been evaluated in single and chronic dosing studies. In the single dose study, the platelet inhibitory effect of the controlled release formulation was compared with that of an equivalent dose of soluble ASA and an equimolar dose of sodium salicylate (SA). In the chronic dosing study, ASA dose-response curves for platelet function, including cyclooxygenase activity, were determined for various doses (20-1300 mg) of the controlled release (enteric coated pellets) ASA formulation taken by volunteers daily for one week. Platelet function was assessed by the degree of inhibition of aggregation for several aggregating agents, and the degree of inhibition of activity of platelet cyclooxygenase quantified by the estimation of malondialdehyde (MDA) production. Plasma ASA and SA concentrations were also determined in each study. The controlled release product inhibited platelet function to the same extent as an equimolar dose of soluble ASA, but did so with much lower and sometimes undetectable peak systemic plasma ASA concentrations. SA, the direct metabolite of aspirin, did not have any effect on platelet function. The ASA dose-platelet function response curves obtained from chronic dosing with the controlled release formulation appeared to be similar to those reported previously for the soluble product. The inhibition of platelet function appeared to be unrelated to plasma ASA concentrations.

Adult↗
PubMed1969

Some studies on cytisine and its methylated derivatives.

1. In mice cytisine hydrochloride is less toxic intravenously than nicotine hydrogen tartrate, but more toxic by intraperitoneal or oral administration. Compared with cytisine, caulophylline hydrogen iodide is one-fifth to one-tenth as toxic and caulophylline methiodide is less than one-thirtieth as toxic.2. The surprising low oral toxicity of cytisine and nicotine may be ascribed to the method of administration; if the drug is placed directly in the stomach there is no possibility of absorption through buccal mucous membranes.3. The peripheral effects of nicotine, cytisine and caulophylline are similar, though on some preparations those of nicotine last longer. In most tests cytisine is active in doses from a quarter to three-quarters of those of nicotine, caulophylline in doses from 10 to 20 times those of cytisine. Caulophylline methiodide is virtually inactive.4. Cytisine and caulophylline may differ from nicotine in their central effects.5. Cytisine and caulophylline are active as the cations. The pKa of cytisine is 7.92 and that of caulophylline is 7.04; the difference accounts, in part, for the weaker activity of caulophylline. The caulophylline ion is generally one-sixth to one-third as active as the cytisine ion.6. The introduction of the second methyl group to form the quaternary salt does not appear to cause a dramatic change in the conformation of the molecule. Caulophylline methiodide appears to be feebly active because it has feeble affinity.

Alkaloids↗