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. 1993 Jun;109(2):592–599. doi: 10.1111/j.1476-5381.1993.tb13612.x

The antiarrhythmic effects of the nucleoside transporter inhibitor, R75231, in anaesthetized pigs.

C L Wainwright 1, J R Parratt 1, H Van Belle 1
PMCID: PMC2175672  PMID: 8358559

Abstract

1. The effect of R75231, an inhibitor of purine nucleoside transport, were examined on ischaemic arrhythmias in anaesthetized pigs. 2. In closed chest pigs (n = 4), R75231 exerted a moderate dose-dependent decrease in mean arterial blood pressure (from 97 +/- 4 mmHg to 95 +/- 4, 90 +/- 1 and 83 +/- 2 mmHg at 25, 50 and 100 micrograms kg-1 respectively) and produced a dose-related shift to the left of the blood pressure dose-response curve to intravenous bolus doses of adenosine. The degree of inhibition of adenosine uptake by R75231, assessed ex vivo in erythrocyte suspensions, was 43 +/- 5%, 64 +/- 13 and 114 +/- 15% at doses of 25, 50 and 100 micrograms kg-1 respectively. 3. In open chest pigs, intravenous injection of R75231 (50 micrograms kg-1; n = 6 and 100 micrograms kg-1; n = 10) induced a dose-related decrease in both systolic and diastolic arterial blood pressure which was more marked than in closed-chest pigs (mean pressure 86 +/- 4 to 70 +/- 2 mmHg and 88 +/- 6 to 60 +/- 6 mmHg with 50 and 100 micrograms kg-1 respectively), without affecting heart rate or myocardial contractility. Coronary artery occlusion in these pigs caused a secondary decrease in blood pressure. This was not observed in controls (n = 10). The lower dose of R75231 did not exert any antifibrillatory effects, whereas the higher dose significantly reduced the incidence of ventricular fibrillation, from 80% in control pigs to 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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