Indocyanine green (ICG) and (+)-propranolol kinetics were determined in the rat following moderate (50%) blood exchange with either Fluosol-DA or 0.9% NaCl (saline). Rats received an intravenous ICG dose (5 mg kg-1) before an intravenous dose of (+)-propranolol (2.5 mg kg-1) 0.5, 24, 48 or 72 h after haemodilution and were compared with non-exchanged controls. Haemodilution with Fluosol-DA reduced the ICG elimination rate constant during the first 24 h while a significant reduction was seen 48 h after normal saline exchange. ICG clearances tended to be less than the control value, and were significantly reduced only at 24 h after Fluosol-DA exchange due to a reduced Varea. (+)-Propranolol half-life was significantly increased 48 and 72 h after saline exchange; (+)-propranolol clearance was also significantly reduced 72 h after Fluosol-DA exchange. ICG clearance may be reflecting a hypovolaemic change which occurs after haemodilution, which would reduce the hepatic blood flow. However, (+)-propranolol clearance was not altered, suggesting that the hepatic blood flow is not changed. It is possible that ICG clearance is changed due to alterations in its extraction ratio instead of hepatic blood flow changes.

Phenytoin kinetics were determined in the rat following moderate (50%) blood exchange with either Fluosol-DA or normal saline. Rats received an intravenous phenytoin dose (10 mg kg-1) 0.5, 24, 48, or 72 h after exchange and were compared with non-exchanged controls. Phenytoin t 1/2 was not altered by exchange with either fluid. Its Cl and Vd were decreased and AUC increased 24, 48, and 72 h after saline exchange and 24 h after Fluosol-DA exchange. (+/-)-5-(4-Hydroxyphenyl)-5-phenylhydantoin (HPPH), a major metabolite of phenytoin, showed a decreased t1/2 and VHPPH 24, 48, and 72 h after exchange with either fluid; t1/2 was also reduced 0.5 h after Fluosol-DA exchange. The decreased Vd and VHPPH may result from changes in cardiac output secondary to haemodilution, or may represent a redistribution in the microcirculation. Fluosol-DA appears to enhance phenytoin and HPPH metabolism 48 and 72 h after exchange.

Phenytoin kinetics were determined in rats in which the blood was moderately haemodiluted with 20 or 40 mL kg-1 of Fluosol-DA or normal saline. Rats received one of three intravenous phenytoin doses (10, 40, 50 mg kg-1) 0.5, 24, 48, or 72 h after haemodilution and were compared with non-exchanged controls. Haemodilution with either 20 or 40 mL kg-1 of Fluosol or saline had no influence on the dose-dependent kinetics of phenytoin. Haemodilution with 40 mL kg-1 of Fluosol decreased the half-life of phenytoin's major metabolite, HPPH, after a 50 mg kg-1 dose. Neither Fluosol nor saline haemodilution affected the normal delay in biliary cycling of HPPH.

Antipyrine disposition and metabolism in conscious, unrestrained rats after 25 or 50% haemodilution with Fluosol or normal (0.9% NaCl) saline is reported. Rats received an intravenous antipyrine dose (20 mg kg-1) 0.5, 24, 48, or 72 h after haemodilution and its pharmacokinetic parameters have been compared with non-exchanged control animals. Haemodilution 25% with Fluosol initially depressed antipyrine metabolism for 24 h by decreasing the antipyrine urinary excretion rate constant and the formation rate constants of 4-hydroxyantipyrine (4-OH) and 3-hydroxymethylantipyrine (3-OHME). Metabolism was then increased for 48 and 72 h with a slight increase in all rate constants. Haemodilution 50% with Fluosol produced a similar pattern but with significant increases in the 3-OHME formation rate constant found at 48 and 72 h. Haemodilution 25% with saline reduced 4-OH formation for 48 h. Haemodilution 50% with saline significantly reduced antipyrine urinary excretion at all times. After a significant increase in the 4-OH and 3-OHME formation rate constants at 24 h following 50% haemodilution with saline, the rate constants were significantly decreased at 48 and 72 h. Haemodilution 25% with Flusol significantly reduced the antipyrine Vd at 0.5 and 72 h. After haemodilution 50% with Fluosol, the Vd alternated between values greater and less than control throughout the 72 h. Haemodilution 25 or 50% with saline had little influence on Vd.

Five patients with respiratory dependent rate responsive pacemakers (Biorate RDP3, Biotec) were studied using ambulatory telemetry to evaluate the sensitivity of this pacing system to nonrespiratory signals. In each case the pacemaker was implanted in the left infraclavicular position with an impedance sensing electrode inserted into the subcutaneous tissues of the anterior chest wall. The pacing rate was 73 +/- 2 beats per minute at rest and rose by 42 +/- 5 beats per minute when the patients were walking with both arms swinging (mean +/- SEM). Three of the five patients had sensing electrodes that extended across the midline. In this subgroup, pacing rate rose by 26 +/- 4 beats per minute when walking with arms held immobile and by 36 +/- 2 beats per minute during sustained voluntary hyperventilation. These same activities did not elicit any appreciable changes in pacing rate in the remaining two patients whose sensing electrodes were confined to the left hemithorax. Recordings taken from all five patients while they were standing upright and regularly swinging one upper limb showed an increase in pacing rate of 15 + 6 beats per minute with movement of the right arm and 46 + 8 with movement of the left. These observations establish that the Biorate RDP3 pacemaker is capable of responding both to changes in respiratory rate and to movement of the upper limbs. The sensitivity to limb movement is greatest when the chest wall impedance sensor does not extend across the midline and is most evident when the arm ipsilateral to the pacemaker is swung.(ABSTRACT TRUNCATED AT 250 WORDS)