thromboxane-a2 and Heart-Arrest

Hypoxia and ischemia cause endothelial cell damage with consequent platelet activation. The hypothesis that human cardiac arrest accelerates platelet activation and the formation of prostanoids was tested.. Prospective, observational cohort study.. Emergency Department and general Intensive Care Unit in a city hospital.. Basic and advanced life support.. Forty-seven out-of-hospital cardiac arrest patients. The patients were classified into two groups, those who were resuscitated (n = 18) and those who died (n = 29).. Serial levels of platelet aggregation, thromboxane B2 (TXB2), 11-dehydro-TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured. The results of measurements and demographic data were compared between the groups. Platelet counts decreased at the end of cardiopulmonary resuscitation (CPR), the decrease of the platelet counts showed statistical significance especially in the patients who died (p < 0.001). Platelet aggregation induced by adenosine diphosphate, epinephrine and collagen decreased to the lower limits of normal during and after CPR. Although high values of TXB2 and 11-dehydro-TXB2 continued throughout the study period in the resuscitated patients, 6-keto-PGF1 alpha decreased to the normal range (22.7 +/- 3.6 pg.ml-1. p < 0.05 at -24 h after arrival at the Emergency Department.. Platelet activation with the massive formation of thromboxane A2 (TXA2) occurs in patients with out-of-hospital cardiac arrest. Successful resuscitation is not associated with the balanced production of PGI2 against the TXA2 formation.

Topics: Aged; Analysis of Variance; Cardiopulmonary Resuscitation; Chi-Square Distribution; Cohort Studies; Dinoprost; Female; Heart Arrest; Humans; Male; Middle Aged; Platelet Activation; Prospective Studies; Prostaglandins F; Reperfusion Injury; Thromboxane A2

The effect of KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl) ethylidene]-6,11-dihydrodibenz[b,e] oxepine-2-carboxylate monohydrate, CAS 127166-41-0), a novel thromboxane A2 (TxA2) receptor antagonist, on collagen-induced coronary ischemia was studied in guinea-pigs. Under pentobarbital anaesthesia, intravenous injection (i.v.) of collagen (1 mg/kg) induced abnormal ECG changes such as ST-T changes, elevation of T-wave arrhythmia and cardiac arrest in severe cases. The changes of ECG (leads I, II and III) were recorded for 10 min following collagen injection. KW-3635 (25-50 mg/kg p.o.) remarkably improved the collagen-induced ischemic ECG changes. The effect of KW-3635 was more potent than those of daltroban, isbogrel and ticlopidine. Neither nifedipine nor propranolol had any effect. The plasma thromboxane B2 level in the KW-3635-treated animals was lower in comparison with those in both the control and daltroban-treated animals. These results suggest that TxA2 may play a role in this model of coronary ischemia and that KW-3635 is effective in the treatment of ischemic heart disease.

Topics: Animals; Arrhythmias, Cardiac; Benzimidazoles; Benzoxepins; Collagen; Coronary Disease; Cyclooxygenase Inhibitors; Electrocardiography; Guinea Pigs; Heart Arrest; Male; Nifedipine; Phenylacetates; Propranolol; Sulfonamides; Thromboxane A2; Thromboxane B2; Thromboxanes; Ticlopidine