Inhibitory effects of procainamide on rabbit platelet aggregation and thromboxane B2 production in vitro.

AIM: To study the influences of procainamide (PA) on thrombin-induced rabbit platelet aggregation and thromboxane B2 (TXB2) production in vitro. METHODS: Turbidimetry and radioimmunoassay were used. RESULTS: PA 8.5, 34, 136, and 544 mumol.L-1 inhibited thrombin-induced platelet aggregation and TXB2 production, and the inhibitory rates were 45% +/- 37%, 48% +/- 32%, 88% +/- 23%, 92% +/- 15% and 53% +/- 24%, 65% +/- 26%, 90% +/- 6%, 95% +/- 6%, respectively. There was positive correlation between PA concentration and efficiency of inhibition of platelet aggregation and TXB2 production, and also between the inhibition % of platelet aggregation and that of production of TXB2. The three linear equations and main parameters were Y = 0.2075X-4.9157, r = 0.9985; Y = 0.9546X-34.6724, r = 0.9921; Y = 0.8202X + 19.7062, r = 0.9921. CONCLUSION: PA inhibited thrombin-induced platelet aggregation and TXB2 production in rabbits.

Effect of procainamide on ultrastructure of blood platelet in rabbits.

AIM: To study the effect of procainamide (PA) on the ultrastructure of blood platelets. METHODS: Arachidonic acid was added to PA-treated platelet-rich plasma to induce platelet aggregation. The 50-nm sections were examined with a transmission electron microscope. RESULTS: PA 8.5-136 mumol.L-1 markedly inhibited changes of pseudopods, alpha-granules, dense granules, glycogens, open canalicular system, and dense tubular system. CONCLUSION: PA markedly inhibited the changes of ultrastructure of blood platelet and releasing response.

Effect of procainamide on pulmonary thromboembolism and platelet malondialdehyde in mice.

AIM: To study the effect of procainamide (PA) on pulmonary thromboembolism, platelet malondialdehyde (MDA) level and platelet aggregation induced by collagen and adrenaline. METHODS: Pulmonary thromboembolism, 2-thiobarbituric acid fluorescence micro-determination, conventional microscopic counting, and platelet aggregation test were used. RESULTS: PA (10-20 mg.kg-1) and mannitol (200 mg.kg-1) reduced thrombosis by 30%-75% and 75%, respectively. Thrombocytopenia followed thrombosis increased after the pretreatment of PA and mannitol. MDA decreased by both of them in vivo. In vitro, PA inhibited platelet aggregation and MDA production induced concentration-dependently by collagen and adrenaline. CONCLUSION: Inhibition of PA on pulmonary thromboembolism is involved in the decrease of platelet aggregation and MDA production.

[Effect of thrombin on cytosolic calcium and membrane potential in single human platelets].

Fluo-3 and di-BA-C4 (3) -loaded human platelets were immobilized on a fibrinogen-coated surface and the cytosolic free [Ca2+]i and the membrane potentials were measured in single thrombin-activated platelets by ACAS-570 (Adherent Cell Analysis and Sorting Cytometer). Fluorescence of fluo-3 and di-BA-C4 (3) was low in rest immobilized platelets without obviously repetitive spiking. When the platelets were activated by thrombin, a rapid rise of cytosolic [Ca2+]i and membrane potential was observed. Subsequently, oscillations in [Ca2+]i to an extent of about 500 fluorescent units were observable, whereas the membrane potential remained at the peak level, i.e., the change of [Ca2+]i in no way of accord with that membrane potential. The above results indicate that the thrombin induced membrane depolarization is not due to influx of Ca2+.

Effect of procainamide on platelet adhesion in rats.

Effect of procainamide on platelet adhesion in rats was studied with the improved rotating glass sphere method. Procainamide of 136.0, 34.0, 8.5 mumol.L-1 in vitro and 10 mg.kg-1 in vivo inhibited significantly the platelet adhesion with the inhibitory rates of 56%, 28%, 8%, and 24%, respectively. It showed that procainamide given in vitro or in vivo produced an inhibition on platelet adhesion.

Pharmacokinetics and tissue distribution of human recombinant interleukin-2 in mice.

125I-labeled human recombinant interleukin-2 (125I-rIL-2) was prepared by iodogen method with rIL-2 and Na125I. Product was purified by Sephacryl S-200 gel filtration. Eluate fractions were identified by SDS-PAGE and compared with standard rIL-2. Radioactive 95% purified 125I-rIL-2 fractions were selected for pharmacokinetic study, with a specific activity of 56 PBq.mol-1. Concentration-time curves after iv 75, 530, 603, and 6767 ng of 125I-rIL-2/mouse were fitted to a 3-compartment model: with a fast distribution phase T1/2 of 2 min, a slow distribution phase T1/2 of 30-120 min, and a terminal elimination T1/2 of 6-15 h. AUC was linearly related to the dosage (r = 0.9998). Systematic clearances were independent of the dosages. SDS-PAGE of plasma and urine samples showed that radioactivities due to 125I-rIL-2 were 81 +/- 13% (n = 16) and 91 +/- 8% (n = 3, at 4 h), respectively. Levels of 125I-rIL-2 after im were lower than those after i.v., with bioavailability of 0.57. Time to peak concentration was about 1.1 h. The highest levels were seen at 15 min after i.v. in liver, bile and kidneys, the concentration gradients were blood > adrenals > plasma > lungs > thyroid > spleen > jejunum > mesenteric lymph nodes > jejunum contents > ovaries > heart > bladder > thymus > feces in colon > thigh skeletal muscle > testes > brain > fat. Peak concentration time in most tissues were found at 15 min, but at 4 h in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)

Blockage of clonidine-induced platelet aggregation in rabbits by procainamide.

Procainamide was capable of blocking the alpha 2-adrenergic receptor agonist clonidine-induced platelet aggregation, giving an antagonistic index, pA2, of 5.0 +/- 0.6 and half antagonistic concentration, A2, of 10.4 mumol.L-1. Clonidine showed half efficacy concentrations (EC50) of 44, 82, 182, 485, and 662 nmol.L-1, and affinity parameter (pD2) of 7.4, 7.1, 6.7, 6.3, and 6.2 respectively when different concentrations of procainamide were used as blocking reagent. The results indicated that the mechanism of inhibitory effect of procainamide on clonidine-induced platelet aggregation was to competitively antagonize activating alpha 2-receptors and others of clonidine on platelet membrane.

[Influences of 3,4,5-trihydroxystibene-3-beta-mono-D-glucoside on rabbits' platelet aggregation and thromboxane B2 production in vitro].

Platelet aggregation and thromboxane B2 (TXB2) production induced by arachidonic acid (AA) or Adenosine diphosphate (ADP) were studied by turbidimetry and radioimmunoassay in rabbits. 3,4,5-tri-hydroxystibene-3-beta-mono-D-glucoside (PD) 6.7-107.2 mumol/L inhibited platelet aggregation and the production of TXB2 as well. The inhibitions by PD were dose-dependent: 48-90% (AA-induced) and 43-69% (ADP-induced) for platelet aggregation; 50-87% (AA-induced) and 43-68% (ADP-induced) for TXB2. There were positive correlations between the inhibition of platelet aggregation and production of TXB2.