Summary
In an ischaemic, exercising limb the metabolic changes found in the femoral venous blood of healthy volunteers are similar to those found in patients with intermittent claudication. This model of ischaemia was therefore used to demonstrate the pharmacodynamic effects of an intra-arterial or intravenous infusion of PGE1 in comparison with a placebo in six healthy male volunteers.
The ischaemia was induced with a pneumatic tourniquet around the thigh. This tourniquet was also used to determine the resting blood flow under venous occlusion with the strain-gauge plethysmography. Blood pressure and pulse rate were measured continuously in the femoral artery. Blood was sampled from the femoral vein before and after the exercise test, to determine lactate, pyruvate, pH, blood gases, base excess, erythrocyte aggregation, fibrinogen, whole-blood viscosity at various degrees of shear rate and plasma viscosity. On each occasion the volunteers were exercised at the same work load on an ergometer under conditions of ischaemia. The exercise test was stopped at the point of maximum ischaemic pain. The total achieved period of exercising was stated in seconds. The volunteers were given, in random sequence, one ampoule of Prostavasin (20µgPGE1) intra-arterially, or 3 ampoules of Prostavasin (60 µgPGE1) intravenously or a placebo (physiological saline solution), in each case over a 60 min period. The wash-out phase was at least 1 week.
With intra-arterial infusion of PGE1 the resting blood flow rose significantly to more than 2.5 times the baseline value. Forty-five minutes after the end of the infusion, resting blood flow was still double the baseline value. With intravenous administration of PGE1 the profile resembled that obtained with the placebo infusion.
The steep rise in the lactate-pyruvate ratio after exercise was significantly reduced by intra-arterial administration of PGE1, and moderately reduced by the intravenous infusion.
Both routes of administration of PGE1 produced a rise in pH as compared with the placebo. In the postischaemic phase the rise in erythrocyte aggregation was reduced by intra-arterial infusion of PGE1 and it was completely abolished by intravenous infusion of PGE1. The achieved exercise period declined under the placebo, whereas under PGE1 there was a significant prolongation of the exercise period (P < 0.05) both after intravenous and particularly after intra-arterial administration.
There were no adverse reactions to any of the infusions.
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References
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© 1986 Springer-Verlag Berlin Heidelberg
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Rudofsky, G. (1986). The Effect of Intra-Arterial and Intravenous Prostaglandin E1 in a Model of Ischaemia in Healthy Volunteers. In: Sinzinger, H., Rogatti, W. (eds) Prostaglandin E1 in Atherosclerosis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71679-9_7
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DOI: https://doi.org/10.1007/978-3-642-71679-9_7
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