Biomedical subjects

A Galland

Publications and source records attributed to A Galland.

10 recordsLinked to original sources

PubMed1998

Differential inhibition of human platelet aggregation and thromboxane A2 formation by L-arginine in vivo and in vitro.

We compared the effects of L-arginine (L-ARG), the precursor of endogenous NO, on platelet aggregation and thromboxane A2 formation in vivo and in vitro. Human platelet-rich plasma (PRP) was anticoagulated with citrate (which decreases extracellular Ca2+) or with recombinant hirudin (which does not affect extracellular Ca2+). Two groups of 10 healthy male volunteers received intravenous infusions of L-ARG (30 g or 6 g, 30 min) or placebo. Blood was collected immediately before and at the end of the infusions for aggregation by ADP or collagen. Infusion of L-ARG inhibited ADP-induced aggregation in PRP anticoagulated with citrate by 37.5+/-6.3% (P < 0.05). In PRP anticoagulated with hirudin, aggregation was inhibited by 33.6+/-16.0% (P < 0.05). L-ARG infusion also inhibited platelet TXB2 formation and slightly, but not significantly decreased the urinary excretion rate of 2,3-dinor-TXB2; cGMP concentrations in PRP were significantly elevated during L-arginine infusion. In vitro preincubation with L-ARG (10 microM-2.5 mM) inhibited platelet aggregation in PRP anticoagulated with rhirudin, but not citrate. This effect was stereospecific for L-arginine, as D-arginine had no effect. It was dependent upon NO synthase activity, as indicated by increased cGMP levels in PRP. Moreover, both the NOS inhibitor L-NMMA and the inhibitor of soluble guanylyl cyclase ODQ antagonized the effects of L-ARG. Haemoglobin, an extracellular scavenger of NO, partly antagonized the antiplatelet effects of L-ARG. 8-Br-cyclic GMP and the exogenous NO donor linsidomine inhibited aggregation in PRP anticoagulated with citrate or r-hirudin. The inhibitory effects of L-ARG on platelet aggregation in vitro were paralleled by increased cyclic GMP levels; L-ARG also inhibited platelet TXB2 formation in PRP anticoagulated with r-hirudin, but not citrate. We conclude that the L-arginine/NO pathway is present in human platelets as a Ca2+-dependent anti-aggregatory pathway. In vivo the formation of NO from L-ARG by endothelial cells may contribute to the platelet-inhibitory effects of L-ARG. NO-releasing compounds like linsidomine inhibit platelet aggregation in vitro independent of extracellular Ca2+.

Adult↗

PubMed1998

Assessment of coronary blood flow in humans using phase difference MR imaging. Comparison with intracoronary Doppler flow measurement.

Coronary blood flow quantification provides essential information on the hemodynamic significance of coronary artery stenoses. Recently, magnetic resonance (MR) flow mapping has emerged as a new promising method to noninvasively determine flow velocity and flow volume within the coronary arteries. The aim of this study was to compare phase difference (PD) MR flow quantification with intracoronary Doppler flow measurements in 15 patients with suspected or known coronary artery disease. Flow quantification was attempted before and after systemic application of 5mg Isosorbiddinitrate (ISDN) in order to determine possible alterations in coronary flow volume. PD MR flow mapping was performed successfully in 13 of the 15 patients. For flow velocities and flow volume values, a close correlation between PD MR and Doppler flow measurements was found (r = 0.79 and r = 0.90, respectively). However, average flow measured by PD MR was significantly lower than the invasively obtained values (9.0 +/- 4.4 cm/sec vs. 11.7 +/- 4.9 cm/sec; p < 0.001 and 46.3 +/- 28.7 ml/min vs. 53.4 +/- 32.8 ml/min; p < 0.05). Although the mean flow volume remained constant in the entire patient group after ISDN application, individual changes (increase in 6, decrease in 4 cases) could be documented with PD MR imaging and showed a good correlation to the Doppler method (r = 0.82). In conclusion, PD MR flow mapping is a promising method for the noninvasive quantification of coronary blood flow and therefore offers the potential of assessing coronary artery stenoses. However, technical improvements are mandatory in order to increase accuracy of the method.

Blood Flow Velocity↗

PubMed1998

L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship.

AIMS: Administration of L-arginine by intravenous infusion or via oral absorption has been shown to induce peripheral vasodilation in humans, and to improve endothelium-dependent vasodilation. We investigated the pharmacokinetics and pharmacokinetic-pharmacodynamic relationship of L-arginine after a single intravenous infusion of 30 g or 6 g, or after a single oral application of 6 g, as compared with the respective placebo, in eight healthy male human subjects. METHODS: L-arginine levels were determined by h.p.l.c. The vasodilator effects of L-arginine were assessed non-invasively by blood pressure monitoring and impedance cardiography. Urinary nitrate and cyclic GMP excretion rates were measured as non-invasive indicators of endogenous NO production. RESULTS: Plasma L-arginine levels increased to (mean +/- s.e.mean) 6223+/-407 (range, 5100-7680) and 822+/-59 (527-955) micromol l(-1) after intravenous infusion of 30 g and 6 g L-arginine, respectively, and to 310+/-152 (118-1219) micromol l(-1) after oral ingestion of 6 g L-arginine. Oral bioavailability of L-arginine was 68+/-9 (51-87)%. Clearance was 544+/-24 (440-620), 894+/-164 (470-1190), and 1018+/-230 (710-2130) ml min(-1), and elimination half-life was calculated as 41.6+/-2.3 (34-55), 59.6+/-9.1 (24-98), and 79.5+/-9.3 (50-121) min, respectively, for 30 g i.v., 6 g i.v., and 6 g p.o. of L-arginine. Blood pressure and total peripheral resistance were significantly decreased after intravenous infusion of 30 g L-arginine by 4.4+/-1.4% and 10.4+/-3.6%, respectively, but were not significantly changed after oral or intravenous administration of 6 g L-arginine. L-arginine (30 g) also significantly increased urinary nitrate and cyclic GMP excretion rates by 97+/-28 and 66+/-20%, respectively. After infusion of 6 g L-arginine, urinary nitrate excretion also significantly increased, (nitrate by 47+/-12% [P<0.05], cyclic GMP by 67+/-47% [P= ns]), although to a lesser and more variable extent than after 30 g of L-arginine. The onset and the duration of the vasodilator effect of L-arginine and its effects on endogenous NO production closely corresponded to the plasma concentration half-life of L-arginine, as indicated by an equilibration half-life of 6+/-2 (3.7-8.4) min between plasma concentration and effect in pharmacokinetic-pharmacodynamic analysis, and the lack of hysteresis in the plasma concentration-versus-effect plot. CONCLUSIONS: The vascular effects of L-arginine are closely correlated with its plasma concentrations. These data may provide a basis for the utilization of L-arginine in cardiovascular diseases.

Administration, Oral↗

PubMed1997

Dose-related effect of intravenous L-arginine on muscular blood flow of the calf in patients with peripheral vascular disease: a H215O positron emission tomography study.

1. Endothelium-derived nitric oxide (NO) contributes to the regulation of vascular tone and blood pressure. Infusion of L-arginine produces systemic vasodilatation via stimulation of endogenous NO formation. Vasodilatation is accompanied by an increase in peripheral arterial blood flow. However, it is not known whether capillary nutritive blood flow increases as well. The time course and dose-response pattern of this effect remain to be elucidated. 2. Two groups of ten patients with peripheral vascular disease (PVD) received an intravenous infusion of 8 g or 30 g of L-arginine over a period of 40 min. Blood pressure and heart rate were monitored non-invasively. Muscular blood flow (MBF) of the calf was determined at 0, 20, 40, 60, 80 min by positron emission tomography with H215O as flow tracer. Plasma L-arginine and cyclic GMP (cGMP) levels were determined at the same time points. 3. L-arginine induced a dose-related decrease in blood pressure during the infusion period. MBF and plasma cGMP levels during and after the infusion of 8 g of L-arginine did not change significantly. In the patients receiving 30 g of L-arginine, MBF was enhanced significantly from 1.56 +/- 0.14 to 2.09 +/- 0.21 ml min-1 100 ml-1 at 40 min and 2.23 +/- 0.15 ml min-1 100 ml-1 after 80 min (+43.0%). The increase in MBF was paralleled by an increase in plasma cGMP from 4789.8 +/- 392.2 nmol/l at baseline to 9223.2 +/- 1233.6 nmol/l at 40 min. 4. We conclude that intravenous L-arginine enhances nutritive capillary MBF in patients with PVD via the NO-cGMP pathway in a dose-related manner. This effect might be therapeutically beneficial in patients with PVD.

Aged↗

PubMed1981