thromboxane-b2 and Cardiomyopathies

Pravastatin is useful in restoring endothelium-dependent relaxation in hypercholesterolemic animals. A single intravenous bolus injection of N(omega)-nitro-L-arginine methyl ester (L-NAME), a non-specific inhibitor of NO synthase, causes myocardial necrosis and reduces coronary flow in rats. Since rats do not develop hypercholesterolemia and atherosclerosis, we have tested the hypothesis that pravastatin protects the heart from myocardial lesions induced by L-NAME in the absence of alterations in cholesterol levels and plaque formation. Male Wistar rats fed standard chow were divided into four groups: CONTROL (n=14) - rats that received tap water alone for 18 days; L-NAME (n=14) -- rats that received L-NAME (15 mg/kg, i.v.) on the 14th day of the study; PRAVASTATIN (n=11) -- rats that received pravastatin (6 mg/kg/day) in their drinking water for 18 days; PRAVASTATIN+L-NAME (n=12) -- rats that received pravastatin (6 mg/kg/day) and L-NAME (15 mg/kg, i.v.) as indicated in the preceding groups. At the end of 18 days, the rats were sacrificed and the hearts removed for stereological analysis by light microscopy. Plasma nitrate/nitrite and thromboxane B(2) concentrations were determined immediately before and after L-NAME administration. Pravastatin prevented the ischemic lesions induced by the acute inhibition of NO biosynthesis (the area of myocardial lesions in the L-NAME group was greater than in the Pravastatin+L-NAME group: 101.6 microm(2) vs. 1.2 microm(2), respectively; P<0.0001) and markedly increased the plasma nitrate/nitrate concentrations, even before L-NAME administration. There were no significant changes in the plasma thromboxane B(2) concentrations.

Topics: Analysis of Variance; Animals; Anticholesteremic Agents; Cardiomyopathies; Disease Models, Animal; Endothelium, Vascular; Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Necrosis; NG-Nitroarginine Methyl Ester; Nitrates; Nitric Oxide Synthase; Nitrites; Pravastatin; Rats; Rats, Wistar; Thromboxane B2

The clinical use of doxorubicin, an anthracycline chemotherapeutic agent, is limited by cardiotoxicity, particularly when combined with herceptin, an antibody that blocks the HER2 receptor. Doxorubicin induces cyclooxygenase-2 (COX-2) activity in rat neonatal cardiomyocytes. This expression of COX-2 limits doxorubicin-induced cardiac cell injury, raising the possibility that the administration of a prostaglandin may protect the heart during the in vivo administration of doxorubicin. Doxorubicin (15 mg/kg) administered to adult male Sprague Dawley rats induced COX-2 expression and activity in cardiac tissue. Prostacyclin generation measured as the excretion of 2,3-dinor-6-keto-PGF(1alpha) also increased, and this was blocked by a COX-2 inhibitor, SC236. In contrast, administration of a COX-1 inhibitor SC560 at a dose that reduced serum thromboxane B2 by more than 80% did not prevent the doxorubicin-induced increase in prostacyclin generation. Doxorubicin increased cardiac injury, detected as a rise in plasma cardiac troponin T, serum lactate dehydrogenase, and cardiomyocyte apoptosis; this was aggravated by coadministration of SC236 but not SC560. The degree of injury in animals treated with a combination of doxorubicin and SC236 was attenuated by prior administration of the prostacyclin analogue iloprost. These data raise the possibility of protecting the heart during the administration of doxorubicin by prior administration of prostacyclin.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Apoptosis; Arachidonic Acid; Aspirin; Biomarkers; Cardiomyopathies; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Doxorubicin; Enzyme Induction; Epoprostenol; Heart; Iloprost; Isoenzymes; L-Lactate Dehydrogenase; Male; Membrane Proteins; Myocardium; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Cytoplasmic and Nuclear; Sulfonamides; Thromboxane B2; Transcription Factors; Troponin T

The changes in endothelium-derived vascular regulatory factors during dobutamine (DOB)-induced myocardial ischemia (MI) were investigated in 21 patients with Kawasaki disease aged from 11 months to 18 years. They were classified into an ischemia group (8 patients) and a non-ischemia group (13 patients) based on the results of 99mTc myocardial scintigraphy and DOB stress 99mTc myocardial scintigraphy. In the ischemia group, MI was relatively mild, because there were ischemic changes on the electrocardiogram and no significant symptoms during DOB stress. Catheters were positioned near the orifice of the coronary artery (Ao) and at the coronary sinus (CS). Hemodynamics and the blood concentrations of lactic acid and endothelin-1, as well as NO3-, 6-keto-prostaglandin F1alpha, and thromboxane B2, (which are inactive metabolites of nitric oxide, prostaglandin I2 and thromboxane A2, respectively), were measured at rest and after DOB stress (maximum dose: 30 microg x kg(-1) x min(-1)). The CS/Ao ratio was determined for all parameters. The rate-pressure product, an index of work load, and the cardiac index were significantly increased by DOB stress in both groups. Coronary angiography showed no vasospasm of the epicardial coronary arteries before or after DOB stress in either group. The plasma concentrations of endothelin-1 and 6-keto-prostaglandin F1alpha were significantly increased after DOB stress in the ischemia group, but the serum concentration of NO did not increase. The lack of an increase in NO production during DOB stress may have contributed to the worsening of MI in patients with Kawasaki disease.

Topics: Adolescent; Calcinosis; Cardiomyopathies; Child; Child, Preschool; Coronary Angiography; Dobutamine; Endothelin-1; Endothelins; Female; Hemodynamics; Humans; Infant; Lactic Acid; Male; Mucocutaneous Lymph Node Syndrome; Myocardial Ischemia; Nitrates; Nitric Oxide; Prostaglandins F; Rest; Stress, Physiological; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Burns; Cardiomyopathies; Creatine Kinase; Female; Hemodynamics; Humans; Male; Middle Aged; Thromboxane B2; Ventricular Function

By comparison with ventricular tissues, collagenase-dispersed cell suspensions obtained from atrial tissues of sensitized guinea-pigs showed a higher histamine content, a higher proportion of mast cells, and a higher release with antigen or antisera to IgG, IgG1 and IgG2 of the following mediators: histamine, thromboxane B2 and leukotriene C4.

Topics: Animals; Cardiomyopathies; Guinea Pigs; Heart Atria; Heart Ventricles; Histamine Release; Hypersensitivity; Mast Cells; Myocardium; SRS-A; Thromboxane B2