dinoprost and Arrhythmias--Cardiac

Since prostaglandin (PG) F2 alpha had been shown to act anti-arrhythmically in various animal models and also in preliminary investigations in man, further evaluation of this effect was made in 30 patients with cardiac extrasystoles and in 2 patients with tachycardias. PGF2 alpha was infused intravenously at individually adapted consecutive rates from 5 to 100 micrograms/min each for at least 5 min. In the incidence of extrasystoles a mean maximum decrease of 41% (P less than 0.001) was obtained. One patient showed repeated short interruptions of a ventricular tachycardia. A dose-dependent significant rise in blood pressure and no significant influences on heart rate, PQ interval and QRS interval of the ECG were found. It is concluded that PGF2 alpha has probably no practical importance for the therapy of cardiac arrhythmias.

Topics: Adult; Aged; Arrhythmias, Cardiac; Blood Pressure; Clinical Trials as Topic; Dinoprost; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Prostaglandins F; Tachycardia

Postoperative hypomagnesemia is common in patients who have undergone cardiac operations and is associated with clinically significant morbidity resulting from atrial and ventricular dysrhythmias. Magnesium supplementation may increase the cardiac index in the early postoperative period.. The action of the magnesium cation on coronary vascular reactivity was studied. Segments of canine epicardial coronary artery were suspended in organ chambers to measure isometric force (95% O2/5% CO2, 37 degrees C).. In coronary segments constricted with prostaglandin F2alpha (2 x 10[-6] mol/L), acetylcholine and adenosine diphosphate (10[-9] to 10[-4] mol/L) induced vasodilation in arteries with endothelium (n=10, each group; p < 0.05). Acetylcholine-mediated vasodilation was blocked by NG-monomethyl-L-arginine (10[-4] mol/L) and NG-nitro-L-arginine (10[-4] mol/L), two inhibitors of nitric oxide synthesis from L-arginine (n=10, p < 0.05). The removal of magnesium from the organ chamber solution impaired vasodilation in response to acetylcholine and adenosine diphosphate. However, normal endothelium-dependent vasodilation could be restored by return of magnesium to the bathing solution. Vascular relaxation in response to bradykinin (10[-9] to 10[-6] mol/L), which was found to induce endothelium-dependent vasodilation independent of nitric oxide production, was unaffected by magnesium removal (n=10).. Hypomagnesemia selectively impaired the release of nitric oxide from the coronary endothelium. Because nitric oxide is a potent endogenous nitro-vasodilator and inhibitor of platelet aggregation and adhesion, hypomagnesemia could promote vasoconstriction and coronary thrombosis in the early postoperative period.

Topics: Acetylcholine; Adenosine Diphosphate; Animals; Arrhythmias, Cardiac; Bradykinin; Cardiac Output; Cardiac Surgical Procedures; Coronary Thrombosis; Coronary Vessels; Dinoprost; Dogs; Endothelium, Vascular; Enzyme Inhibitors; Female; Infusions, Intravenous; Magnesium; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; omega-N-Methylarginine; Pericardium; Platelet Aggregation Inhibitors; Postoperative Complications; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

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

In 47 patients with acute myocardial infarction and in 17 healthy volunteers blood concentration and urinary excretion of PGE2, PGF2 alpha, 6-keto-PGF1 alpha--hydrolysis product of prostacyclin--and TXB2 were determined using RIA. Myocardial infarction patients were found to have significantly higher blood level and urinary excretion of 6-keto-PGF1 alpha, higher blood level of PGF2 and higher urinary excretion of TXB2 than controls, PGE2 urinary excretion was significantly lower. Increased excretion of 6-keto-PGF1 alpha was observed in patients with ventricular arrhythmias. Excretion of all determined prostaglandins was increased in patients with myocardial infarction complicated by atrioventricular block as compared to the other patients. The results suggest, that increase of prostacyclin synthesis in the acute phase of myocardial infarction may provide protection mechanism against heart muscle damage and improve coronary blood flow.

Topics: Adult; Aged; Arrhythmias, Cardiac; Dinoprost; Dinoprostone; Epoprostenol; Fatty Acids, Unsaturated; Female; Humans; Male; Middle Aged; Myocardial Infarction; Reference Values; Thromboxanes

Topics: Arrhythmias, Cardiac; Blood Viscosity; Coronary Disease; Dinoprost; Heart Conduction System; Humans; Nucleotides, Cyclic; Platelet Aggregation; Prognosis; Thrombosis; Thromboxane B2

The possible role of prostaglandins (PG) in arrhythmias associated with ischemia and reperfusion was studied in isolated, superfused canine Purkinje tissues. Ischemic conditions caused partial depolarization and decrease of excitability. Neither inhibition of PG synthesis (ibuprofen, 30 micrograms/mL) nor addition of exogenous PGF2 alpha (1 ng/mL) modified responses to "ischemia." Reperfusion with normal Tyrode's solution stimulated PG production (measured as 6-keto-PGF1 alpha) and induced a series of electrophysiological events. Under control conditions, Purkinje fibres rapidly repolarized. Subsequently, these tissues began to depolarize and oscillatory afterpotentials appeared. Purkinje tissues depolarized further and became temporarily inexcitable. Return of activity was associated with depolarization-induced automaticity. Ibuprofen prevented reperfusion-stimulated PG release. Ibuprofen also increased the magnitude of early repolarization and greatly attenuated subsequent depolarization. Depolarization-induced automaticity was not observed under these conditions; however, oscillatory afterpotentials were not abolished by ibuprofen. Addition of PGF2 alpha to "ischemic" and reperfusion solutions in the presence of ibuprofen restored the arrhythmogenic responses. We conclude that release of endogenous prostaglandins contributes to electrophysiological changes elicited by reperfusion in canine Purkinje fibres.

Topics: Animals; Arrhythmias, Cardiac; Aspirin; Dinoprost; Dogs; Heart Conduction System; Ibuprofen; In Vitro Techniques; Male; Membrane Potentials; Myocardial Reperfusion Injury; Purkinje Fibers

We developed a new method for introducing drugs into the basal cistern of rabbits. With minimal surgical invasion, we used either the opening of the craniopharyngeal duct to access the chiasmatic cistern or the suture between the basisphenoid and basioccipital bones to access the interpeduncular cistern. With our method, 0.5 ml contrast medium injected into three rabbits was determined roentgenographically to remain in the basal cistern; histologically, all the brain tissue remained intact. Intracisternal injection of 0.5 ml physiological saline into five rabbits had no effect on the cardiovascular system. In 23 rabbits, injection of 0.5 ml 0.1% prostaglandin F2 alpha led to a variety of electrocardiographic changes, including sinus bradycardia (in 43.5%), premature atrial contractions (in 17.4%), and premature ventricular contractions (in 39.1%). In 15 rabbits with severe changes, arrhythmia was followed by ST depression (in 30.4%), ST elevation (in 8.7%), T wave inversion (in 4.3%), ventricular tachycardia (in 17.4%), or ventricular fibrillation (in 4.3%). Intracisternal injection of 0.5 ml 1.0% lidocaine into the 23 rabbits was very effective in overcoming bradycardia and arrhythmias. We conclude that the clinical features of electrocardiographic changes seen in patients with subarachnoid hemorrhage are reproducible in this rabbit model.

Topics: Animals; Arrhythmias, Cardiac; Dinoprost; Disease Models, Animal; Electrocardiography; Injections; Lidocaine; Models, Cardiovascular; Rabbits; Radiography; Skull; Subarachnoid Hemorrhage; Subarachnoid Space

A modified method of producing ouabain-induced cardiac arrhythmias in chloralose-anesthetized cats has been developed, whereby prolonged arrhythmias with low incidence of mortality (12%) are observed. Furthermore, the employment of a modified arrhythmia scale in the present model allowed a quantitative estimation of antiarrhythmic efficacy of test drugs and also made it possible to unravel the arrhythmogenic nature of these substances. This improved method could be conveniently used for the quantitative screening of both the antiarrhythmic or the arrhythmogenic nature of test drugs.

Topics: Anesthesia; Animals; Arrhythmias, Cardiac; Cats; Dinoprost; Electrocardiography; Epoprostenol; Female; Heart Rate; Hemodynamics; Infusions, Intravenous; Lidocaine; Male; Ouabain; Time Factors

The effect of antiarrhythmic drugs, ritmilen and allapinin, on endogenic prostanoid and cyclic nucleotide levels was examined in patients with heart rhythm disorders. Intravenous administration of antiarrhythmic agents is shown to be accompanied with increased release of prostacyclin that has antiarrhythmic properties into myocardial outflow. Both ritmilen and allapinin promoted the predominance of prostacyclin over thromboxane, with its intrinsic arrhythmogenic properties. Ritmilen- or allapinin-induced changes in prostaglandins E and F2 alpha consisted in that PGE prevailed, as compared to PGF2 alpha. There were no significant changes in cyclic nucleotide ratios (cAMP/cGMP) in response to treatment.

Topics: Aconitine; Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cyclic AMP; Cyclic GMP; Dinoprost; Disopyramide; Female; Humans; Male; Middle Aged; Nucleotides, Cyclic; Prostaglandins; Prostaglandins E; Prostaglandins F; Stimulation, Chemical

We examined the hypothesis that endogenous prostaglandins participate in the arrhythmogenic influence of ouabain in guinea pig hearts. Addition of ouabain (10 ng/ml) resulted in a 5-fold increase in the release of 6-keto-prostaglandin F1 alpha in the coronary effluent. Ten of 13 hearts studied (77%) demonstrated arrhythmic activity with a mean time to the onset of arrhythmias of approximately 35 min. The nonsteroidal antiinflammatory drugs indomethacin and acetylsalicylic acid which significantly inhibited the efflux of 6-keto-prostaglandin F1 alpha also reduced the incidence of arrhythmias to 10 of 30 hearts studied. In those hearts in which arrhythmias occurred, the time to onset was significantly increased to approximately 50 and 55 min for acetylsalicylic acid and indomethacin, respectively. In contrast, exogenous prostaglandin F2 alpha (0.1 and 1 ng/ml) and prostacyclin (0.1 and 10 ng/ml) increased the incidence of arrhythmias to 100% (10 of 10 hearts studied) and decreased the time to onset to approximately 10 min. These prostaglandin pretreatments were also able to reverse the protective actions of both acetylsalicylic acid and indomethacin. Other concentrations (10 ng/ml prostaglandin F2 alpha and 1 ng/ml prostacyclin) had no influence either on the incidence of arrhythmias or their time to onset. Prostaglandin E2 (0.1 ng/ml) produced a modest but not significant decrease in the time to onset of arrhythmias although this concentration was significantly effective in reversing the nonsteroidal antiinflammatory drug effects. The inotropic, chronotropic and coronary constricting actions of ouabain were unaffected either by nonsteroidal antiinflammatory drug or prostaglandin pretreatment. These studies suggest that prostaglandins are involved, at least in part, in the arrhythmogenic actions of ouabain in the isolated guinea pig heart.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arrhythmias, Cardiac; Coronary Circulation; Dinoprost; Epoprostenol; Guinea Pigs; Heart; Heart Rate; In Vitro Techniques; Male; Myocardial Contraction; Ouabain; Prostaglandins; Prostaglandins F; Radioimmunoassay

Topics: Adult; Aged; Alprostadil; Arrhythmias, Cardiac; Dinoprost; Humans; Male; Middle Aged; Myocardial Infarction; Prostaglandins F; Shock, Cardiogenic

The effects of prostaglandin F2 alpha (PGF2 alpha) on ouabain-induced cardiac arrhythmias were investigated in chloralose-anaesthetized cats. Bilateral vagotomy and atropine intervention were employed to elucidate the involvement of vagal neural influences. PGF2 alpha (2-16 micrograms/kg i.v. bolus) predominantly suppressed the ouabain-induced ventricular and supraventricular arrhythmias and less commonly aggravated them in vagi-intact cats. The antiarrhythmic effect of PGF2 alpha was considerably, but not statistically significantly, decreased while its arrhythmogenic effect was significantly (p less than 0.05) increased in atropine-pretreated group. In vagotomised group PGF2 alpha failed to abolish the arrhythmias but it aggravated them to a degree comparable to that observed in vagi-intact group. It is concluded that the PGF2 alpha exhibits both antiarrhythmic and arrhythmogenic properties and these are largely due to elicitation of two opposing neural reflexes - one being protective and another being deleterious to ouabain-induced arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Atropine; Cats; Dinoprost; Female; Heart; Male; Ouabain; Prostaglandins F; Vagotomy

The role of the central nervous system (CNS) in the antiarrhythmic effects of prostaglandins (PGs) E2, F2 alpha, and I2 was studied by administering each agent into the left lateral cerebral ventricle (i.c.v. administration) of chloralose-anaesthetized cats. The cardiac arrhythmias were produced by intravenous (i.v.) infusion of ouabain (1 microgram/kg/min). The PGs E2, F2 alpha and I2 on i.c.v. administration in the dose range of 1 ng to 10 micrograms failed to inhibit ouabain-induced cardiac arrhythmias. However, when infused i.v., PGE2 (1 microgram/kg/min), PGF2 alpha (5 micrograms/kg/min), and PGI2 (2 micrograms/kg/min) effectively suppressed these arrhythmias. The standard antiarrhythmic drug propranolol (0.5-8.0 mg) on i.c.v. administration also significantly reduced the ouabain-induced cardiac arrhythmias. It is suggested that the CNS is not the site of action of PGs E2, F2 alpha, and I2 in antagonising the ouabain-induced cardiotoxicity in cats.

Topics: Animals; Arrhythmias, Cardiac; Cats; Central Nervous System; Dinoprost; Dinoprostone; Epoprostenol; Heart Rate; Heart Ventricles; Injections, Intraventricular; Ouabain; Propranolol; Prostaglandins E; Prostaglandins F

Arrhythmias were produced by ouabain (2.7 X 10(-7) M) in isolated perfused guinea pig hearts. In control hearts the average time to onset of arrhythmias following exposure to ouabain was approximately 35 min. Ligation of the left anterior descending coronary artery significantly shortened the time to arrhythmias to about 15 min. This effect of ligation was attenuated significantly by pretreating the hearts with acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs. In contrast, the protective influence of ASA was reversed by either prostaglandin (PG) E2, PGF2 alpha, or PGI2 (2.8 X 10(-9) M). When PGE2 or PGI2 were present in the absence of ASA, the time to arrhythmias following ouabain administration was significantly shortened. PGF2 alpha had no effect in these experiments. The sensitivity was enhanced significantly by treatment with arachidonic acid. This effect was reduced by treatment with ASA or indomethacin. Prostaglandin production during the experiments was estimated by monitoring release of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin. Abbreviation of time to arrhythmias by ligation was greatest in hearts that released large amounts of 6-keto-PGF1 alpha and least in those that released low amounts. These results suggest that coronary ligation potentiates the arrhythmogenic effects of ouabain by a mechanism probably mediated by prostaglandin(s).

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Arrhythmias, Cardiac; Aspirin; Coronary Circulation; Coronary Disease; Coronary Vessels; Dinoprost; Dinoprostone; Epoprostenol; Guinea Pigs; Ibuprofen; Indomethacin; Ligation; Male; Ouabain; Perfusion; Prostaglandins; Prostaglandins E; Prostaglandins F; Time Factors

The 15-keto-metabolites of PGE2 and PGF2 alpha produced an antiarrhythmic effect on aconitine induced arrhythmias in rats. The ED50 values of these metabolites were approximately 2.0 micrograms/kg. The 13,14-dihydro-15-keto-metabolites of PGE2 and PGF2 alpha had no statistically significant antiarrhythmic effect. PGI2 (0.25-1.00 micrograms/kg) produced an antiarrhythmic effect between 15-54% (ED50 0.75 micrograms/kg), whereas 6-keto-PGF1 alpha, a metabolite of PGI2, showed no significant antiarrhythmic effect. The results suggest a participation of 15-keto-metabolites in the antiarrhythmic effects of PGE2 and PGF2 alpha.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Dinoprost; Dinoprostone; Epoprostenol; Female; Male; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains

This study was designed to clarify the mechanism of reperfusion arrhythmia. In the mongrel dogs, the left anterior descending coronary artery was occluded for 15 min and then the ligation was released. The dogs were divided into two groups: one was the control group, and the other the indomethacin group in which indomethacin, an inhibitor of prostaglandin (PG) biosynthesis, was premedicated at 30 min before ligation. The ventricular multiple response threshold (VMRT), and plasma levels of K+, PG E and PG F2 alpha were measured in the great cardiac vein before and during occlusion, and after reperfusion. In the control group, during occlusion, VMRT decreased and did not return to normal soon after reperfusion. The levels of PG E and PG F2 alpha in the great cardiac vein did not change significantly during occlusion; however, PG E became significantly elevated after reperfusion. In the indomethacin group, the time course of VMRT was essentially similar to that of the control group during occlusion; however, lowering of VMRT after reperfusion was prevented significantly. The PG F2 alpha level in the great cardiac vein did not elevate after reperfusion or during occlusion. In both groups, the level of K+ in the great cardiac vein was elevated during occlusion, but rapidly decreased to normal after reperfusion. These results suggest that PG E, as a washout metabolite, is a key factor in evoking reperfusion arrhythmia.

Topics: Animals; Arrhythmias, Cardiac; Coronary Circulation; Coronary Disease; Dinoprost; Dogs; Female; Indomethacin; Male; Potassium; Prostaglandins E; Prostaglandins F

In anaesthetized open-chest dogs, cardiac arrhythmias (CA) were induced by cumulative intravenous doses of aconitine or ouabain. Aconitine in a dose which did not induce CA had no influence on the PGE and PGF2 alpha effluxes into coronary sinus blood (CSB), whereas the PGE efflux into CSB increased after a subtoxic dose of ouabain. However, both PGE and PGF2 alpha effluxes were increased, when CA had developed. During aconitine induced CA, the PGE efflux was 6.5-fold and that of PGF2 alpha had increased by 80%. During ouabain induced CA, the effluxes of both PGs were about 3-fold. Propranolol and lidocaine decreased the PGF2 alpha efflux into CSB by about 50% and the PGE efflux was doubled after lidocaine and decreased after propranolol by about a third. The increased PGE efflux into CSB during CA was normalized after propranolol and quinidine if the CA was abolished or the cardiac rhythm improved. Lidocaine did not modify the increase in PGE efflux, despite the abolishment of CA. The increase in PGF2 alpha efflux was not influenced by antiarrhythmic drugs. The cyclic AMP and cyclic GMP in CSB remained unchanged during ouabain induced arrhythmias or after propranolol. The increased efflux of PGE into CSB during aconitine and ouabain induced CA and its abolishment by propranolol support the hypothesis that PGE participates in the modulation of increased sympathetic tone during CA.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Vessels; Cyclic AMP; Cyclic GMP; Dinoprost; Dogs; Female; Male; Ouabain; Prostaglandins; Prostaglandins E; Prostaglandins F

1 Various prostaglandins and inhibitors of prostaglandin synthesis were administered prior to acute coronary artery ligation in anaesthetized rats and their effects were assessed on the number and severity of the resulting early arrhythmias (ventricular ectopic activity; incidence and duration of ventricular tachycardia and of ventricular fibrillation). 2 Prostaglandin E2 (PGE2), PGF2 alpha and prostacyclin all showed antiarrhythmic activity; in contrast flurbiprofen increased the incidence of ventricular fibrillation and mortality. 3 Both the number of ventricular ectopic beats and the incidence of ventricular fibrillation were reduced by aspirin. 4 The results suggest that the release of endogenous PGE2, PGF2 alpha and prostacyclin could reduce early post-infarction ventricular arrhythmias whilst the protective effect of aspirin in this model adds further support for the hypothesis that thromboxane release is involved in the genesis of these arrhythmias.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Aspirin; Coronary Vessels; Dinoprost; Electrocardiography; Epoprostenol; Flurbiprofen; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains