prostaglandin-d2 and Arrhythmias--Cardiac

To identify the arrhythmogenic and the antiarrhythmic eicosanoids, cultured, spontaneously beating, neonatal rat cardiac myocytes were used to examine the effects of various eicosanoids added to the medium superfusing the cells at different concentrations on the contraction of the myocytes. Superfusion of the myocytes with the prostaglandins (PGD2, PGE2, PGF2 alpha) or the thromboxane (TXA2)-mimetic, U 46619, induced reversible tacharrhythmias characterized by an increased beating rate, chaotic activity and contractures. These effects are concentration-dependent. PGF2 alpha and U 46619 were much more potent than PGD2 or PGE2 in the production of tachyarrhythmias. Prostacyclin (PGI2) induced a marked reduction in the contraction rate of the cells with a slight increase in the amplitude of the contractions and showed a protective effect against the arrhythmias induced by PGF2 alpha and TXA2 (U 46619). PGE1 exerted a dose-dependent dual effect on the contraction of the myocytes. At low concentrations (< 2 microM), PGE1 reduced the contraction rate of the cells with an increase in the amplitude of the contractions and effectively terminated the tachyarrhythmias induced by arrhythmogenic agents, such as isoproterenol, ouabain and U 46619. At higher concentrations (> 5 microM), PGE1 caused cell contractures and chaotic activity. In contrast, the lipoxygenase products [leukotriene (LT) B4, LTC4, LTD4 & LTE4] of arachidonic acid (AA) had no significant effect on the myocyte contractions. The eicosanoids derived from eicosapentaenoic acid (EPA), including both the cyclooxygenase products (PGD3, PGE3, PGF3 alpha, TXB3) showed lesser effects on the contraction of the myocytes. The lipoxygenase products (LTB5, LTC5, LTD5 & LTE5), as with the AA metabolites showed little effect on the contraction of cardiac myocytes. The arrhythmias induced by the arrhythmogenic prostaglandins and thromboxane A2 could be suppressed by the nonmetabolizable AA analog eicosatetraynoic acid (ETYA) or free AA and EPA, indicating a distinction in the effect on cardiac arrhythmia between the precursor fatty acids (AA & EPA) themselves and their metabolites. In conclusion, the major arrhythmogenic eicosanoids are the cyclooxygenase products of AA, whereas those products of EPA are much less or not effective; PGE1, PGI2, ETYA and EPA have antiarrhythmic effects.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Animals, Newborn; Arachidonic Acid; Arrhythmias, Cardiac; Cells, Cultured; Dinoprost; Dinoprostone; Eicosanoids; Eicosapentaenoic Acid; Epoprostenol; Heart; Heart Rate; Lipoxygenase; Myocardial Contraction; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Thromboxane A2

Tumor necrosis factor-alpha production and products of mast cell, basophil, and eosinophil degranulation (prostaglandin D2, histamine, and eosinophil cationic protein) were prospectively studied in 26 children undergoing cardiac operations. The relationship between inflammatory response to cardiopulmonary bypass and transient postoperative arrhythmias was analyzed. Cardiopulmonary bypass was conducted with circulatory arrest and deep hypothermia in 10 patients and with continuous low-flow and moderate hypothermia in 16 patients. Transient postoperative arrhythmias diagnosed on standard or atrial electrocardiograms (or both) were seen in eight of the 26 examined children: accelerated junctional rhythm (n = 3), junctional ectopic tachycardia (n = 3), second-degree atrioventricular block (n = 1), and third-degree atrioventricular block (n = 1). Children with transient postoperative arrhythmias were younger than those without (p < 0.05). Compared with baseline values, there was in all patients a significant release of histamine and eosinophil cationic protein (p < 0.05) related to cardiopulmonary bypass, reaching peak values 4 hours after the operation. In contrast, tumor necrosis factor-alpha production and prostaglandin D2 release were not significant. This suggests that activated basophils but not mast cells are the major sources of histamine liberated during and after cardiopulmonary bypass. Histamine release but not eosinophil cationic protein release correlated with circulatory arrest and deep hypothermia (p < 0.05), suggesting the participation of physicochemical alterations of circulating basophils leading to histamine liberation. Four hours after the operation, patients with transient postoperative arrhythmias had significantly higher blood concentrations of histamine (p < 0.02) and eosinophil cationic protein (p < 0.05) than did those without transient postoperative arrhythmias. On the first postoperative day, four of the eight patients with transient postoperative arrhythmias had persisting elevated histamine levels, whereas in patients without transient postoperative arrhythmias histamine reached baseline values. The multivariate analysis retained histamine release and eosinophil cationic protein variations related to cardiopulmonary bypass for the emerging model to predict transient postoperative arrhythmias. The results of this study show significant histamine release related to cardiopulmonary bypass. Furthermore, they document a possible relat

Topics: Adolescent; Arrhythmias, Cardiac; Blood Proteins; Cardiopulmonary Bypass; Child; Child, Preschool; Eosinophil Granule Proteins; Female; Histamine; Histamine Release; Humans; Male; Postoperative Complications; Prostaglandin D2; Ribonucleases; Tumor Necrosis Factor-alpha