Correlation of (-)N6-phenylisopropyladenosine blood levels with cardiac responses in the anesthetized guinea pig.
This study was designed to develop a high-performance liquid chromatography-based analytical method to measure the blood concentration of (-)N6-phenylisopropyladenosine (R-PIA) in order to correlate such levels with cardiac responses, and to determine the pharmacokinetics of R-PIA. Experiments were carried out in anesthetized adult guinea pigs instrumented for measurement of the surface ECG. After i.v. (50 micrograms/kg; n = 9) or i.p. (3.5 mg/kg; n = 5) administration of R-PIA, the atrial rate and P-R interval were determined, and arterial blood samples (0.5 ml) were collected. The R-PIA content of plasma ultrafiltrates was determined by reversed-phase high-performance liquid chromatography. The ratio of R-PIA concentrations in whole blood and in ultrafiltrated plasma (free or unbound) at 35-37 degrees C was 2.51 +/- 0.10 (n = 7) and was relatively independent of R-PIA concentration. The concentration of unbound R-PIA in whole blood correlated well with cardiac responses. Two distinct patterns of cardiac response to varying R-PIA levels were observed. In 4 of 14 animals, R-PIA caused a prolongation of the P-R interval at a relatively constant atrial rate, whereas in 10 animals, R-PIA caused both a slowing of atrial rate and a prolongation of the P-R interval. An increase in the unbound concentration of R-PIA caused a decrease in atrial rate and an increase in P-R interval. Unbound R-PIA was rapidly cleared from blood (CL = 40 +/- 7 ml/kg/min) and had a large volume of distribution (VSS = 1.45 +/- 0.21 L/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Dennis
D M
DM
Department of Medicine, University of Florida, Gainesville.
Shryock
J
J
Belardinelli
L
L
D000758:Anesthesia; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008297:Male; D010660:Phenylisopropyladenosine / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*
D010660:Phenylisopropyladenosine