oxalates and Heart-Failure

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Anura; Aortic Valve Stenosis; Autoradiography; Biological Transport; Calcium; Calcium Isotopes; Cell Membrane; Electrophysiology; Guinea Pigs; Heart; Heart Failure; Hypertension; In Vitro Techniques; Methods; Muscle Contraction; Muscle Proteins; Muscle, Smooth; Muscles; Myocardium; Myofibrils; Oxalates; Phosphates; Physical Exertion; Rabbits; Sarcolemma; Sodium

Proton pump inhibitors are used extensively for acid-related gastrointestinal diseases. Their effect on cardiac contractility has not been assessed directly.. Under physiological conditions (37 degrees C, pH 7.35, 1.25 mmol/L Ca2+), there was a dose-dependent decrease in contractile force in ventricular trabeculae isolated from end-stage failing human hearts superfused with pantoprazole. The concentration leading to 50% maximal response was 17.3+/-1.3 microg/mL. Similar observations were made in trabeculae from human atria, normal rabbit ventricles, and isolated rabbit ventricular myocytes. Real-time polymerase chain reaction demonstrated the expression of gastric H+/K+-adenosine triphosphatase in human and rabbit myocardium. However, measurements with BCECF-loaded rabbit trabeculae did not reveal any significant pantoprazole-dependent changes of pH(i). Ca2+ transients recorded from field-stimulated fluo 3-loaded myocytes (F/F0) were significantly depressed by 10.4+/-2.1% at 40 microg/mL. Intracellular Ca2+ fluxes were assessed in fura 2-loaded, voltage-clamped rabbit ventricular myocytes. Pantoprazole (40 microg/mL) caused an increase in diastolic [Ca2+]i by 33+/-12%, but peak systolic [Ca2+]i was unchanged, resulting in a decreased Ca2+ transient amplitude by 25+/-8%. The amplitude of the L-type Ca2+ current (I(Ca,L)) was reduced by 35+/-5%, and sarcoplasmic reticulum Ca2+ content was reduced by 18+/-6%. Measurements of oxalate-supported sarcoplasmic reticulum Ca2+ uptake in permeabilized cardiomyocytes indicated that pantoprazole decreased Ca2+ sensitivity (Kd) of sarcoplasmic reticulum Ca2+ adenosine triphosphatase: control, Kd=358+/-15 nmol/L; 40 microg/mL pantoprazole, Kd=395+/-12 nmol/L (P<0.05). Pantoprazole also acted on cardiac myofilaments to reduced Ca2+-activated force.. Pantoprazole depresses cardiac contractility in vitro by depression of Ca2+ signaling and myofilament activity. In view of the extensive use of this agent, the effects should be evaluated in vivo.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Actin Cytoskeleton; Aniline Compounds; Animals; Anti-Ulcer Agents; Calcium; Calcium Channels, L-Type; Calcium Signaling; Depression, Chemical; Diastole; Female; Fluoresceins; Fluorescent Dyes; Heart Atria; Heart Failure; Heart Ventricles; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Ion Transport; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Oxalates; Pantoprazole; Patch-Clamp Techniques; Polymerase Chain Reaction; Proton Pump Inhibitors; Proton Pumps; Rabbits; Sarcoplasmic Reticulum; Systole; Xanthenes

Topics: Acidosis; Acute Kidney Injury; Adult; Aldehydes; Blood Urea Nitrogen; Brain; Brain Diseases; Ethylenes; Glycols; Glyoxylates; Heart Failure; Humans; Lung Diseases; Male; Oxalates; Poisoning

Topics: Adolescent; Adult; Aged; Cardiomyopathies; Child; Female; Heart Block; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardium; Oxalates

Topics: Adult; Blood Urea Nitrogen; Bone and Bones; Cardiomyopathies; Female; Heart Block; Heart Conduction System; Heart Failure; Humans; Kidney; Kidney Calculi; Kidney Failure, Chronic; Metabolism, Inborn Errors; Myocardium; Nephrectomy; Oxalates; Pancreas; Renal Dialysis; Thyroid Gland

Topics: Animals; Biological Transport; Calcium; Cricetinae; Dose-Response Relationship, Drug; Heart Failure; Hydrogen-Ion Concentration; Kinetics; Male; Microsomes; Mitochondria, Muscle; Muscular Diseases; Myocardium; Oxalates; Potassium Chloride; Sarcoplasmic Reticulum; Sodium Chloride

Topics: Aging; Animals; Biological Transport, Active; Calcium; Cricetinae; Disease Models, Animal; Female; Heart; Heart Failure; Male; Myocardium; Organ Size; Oxalates; Sarcoplasmic Reticulum

Topics: Adenosine Triphosphatases; Animals; Biological Transport, Active; Calcium; Depression, Chemical; Endoplasmic Reticulum; Heart Failure; In Vitro Techniques; Male; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Oligomycins; Oxalates; Perfusion; Rats

Topics: Adenosine Triphosphate; Aging; Animals; Calcium; Cricetinae; Dilatation; Endoplasmic Reticulum; Heart Diseases; Heart Failure; Hypertrophy; Muscles; Myocardium; Oxalates; Time Factors

Topics: Antigens; Blood Preservation; Blood Volume; Chemical Precipitation; Citrates; Factor IX; Factor VIII; Freezing; Glycine; Heart Failure; Hemophilia A; Humans; Hydrogen-Ion Concentration; Oxalates; Transfusion Reaction

Topics: Angina Pectoris; Antimony; Emergencies; Heart; Heart Diseases; Heart Failure; Homeopathy; Humans; Oxalates