thromboxane-a2 and anisodamine

Thromboxane (TXA2) and prostacyclin (PGI2) levels, circulatory platelet aggregate ratios (CPAR), CPK, LDH, GOT, platelet counts, blood viscosity, cortisol and urine epinephrine contents were determined in 42 burned patients who were divided into two groups: Group I control (n = 34) and Group II (n = 8) treated with TXA2 synthesis inhibitor, anisodamine. It was found that in controls, both TXA2 and the TXA2/PGI2 ratio increased significantly. There was no marked difference in PGI2 levels between the two groups. Platelet counts and CPAR decreased, while blood viscosity, CPK, LDH, GOT, cortisol and epinephrine in the controls were all significantly higher than those found in Group II patients. All these findings suggested that the changes of TXA2 and the TXA2/PGI2 ratios played an important role in the haemodynamics and haemorrheology in burn shock. The TXA2 synthesis inhibitor, anisodamine, showed beneficial effects by restoring the haemodynamic and rheological disturbances towards normal by virtue of their ability to induce vascular constriction, platelet aggregation, cellular destruction, destabilization of membranes and release of chemical mediators (including enzymes). Furthermore, at 1-3 days postburn, the levels of CPK, LDH and GOT in controls were higher than those measured at 12 h postburn, but this phenomenon was not marked in the treated group, suggesting that after resuscitation, reperfusion damage had occurred and TXA2 might be responsible for the damage. It is assumed that anisodamine could protect tissues from reperfusion damage. The findings also suggested that anisodamine could quicken the restoration of neuroendocrine disturbance initiated by shock (stress).

Topics: Adolescent; Adult; Aspartate Aminotransferases; Burns; Creatine Kinase; Epinephrine; Female; Humans; Hydrocortisone; Infusions, Intravenous; L-Lactate Dehydrogenase; Male; Middle Aged; Shock; Solanaceous Alkaloids; Thromboxane A2; Thromboxane B2; Vasodilator Agents

Anisodamine, an anticholinergic drug, is widely used in China for treatment of infants with septic shock and has been reported to inhibit thromboxane synthesis in cultured cells. Thromboxane A2 plays an important role in the early pulmonary hypertension in sepsis; however, the role of thromboxane A2 later in sepsis is unclear. We tested the hypothesis that thromboxane A2 synthesis inhibition with dazmegrel, and cholinergic blockade with anisodamine, would attenuate the later phase of pulmonary hypertension induced by 4 h of group B streptococcus (GBS) infusion. 1 mg/kg of dazmegrel reversed the pulmonary hypertension and slightly increased cardiac output; these hemodynamic improvements persisted for 30-60 min. Plasma thromboxane B2 levels returned toward pre-GBS baseline values after dazmegrel treatment. Thus, thromboxane A2 is still a major mediator of pulmonary hypertension in piglets after 4 h of continuous GBS infusion. 0.5 mg/kg of anisodamine had no significant hemodynamic effect. 2 and 4 mg/kg of anisodamine each caused transient, dose-related decreases in systemic artery pressure; cardiac output also fell after the highest anisodamine dose. Pulmonary hypertension was not alleviated by anisodamine. All hemodynamic changes induced by anisodamine were short-lived and returned to preanisodamine values within 10 min. Anisodamine did not ameliorate thromboxane-mediated pulmonary hypertension in this animal model, and therefore may not inhibit thromboxane synthesis in vivo. The results of this study do not support the use of anticholinergic therapy to improve hemodynamics in GBS sepsis, but do suggest that thromboxane synthesis inhibition may be a clinically useful therapy in advanced GBS sepsis.

Topics: Animals; Blood Gas Analysis; Dose-Response Relationship, Drug; Female; Hemodynamics; Hypertension, Pulmonary; Imidazoles; Parasympatholytics; Pulmonary Circulation; Solanaceous Alkaloids; Streptococcal Infections; Streptococcus agalactiae; Swine; Thromboxane A2; Thromboxane-A Synthase; Thromboxanes; Vasodilator Agents