ABSTRACT
We report a case of a 76-year-old-man who developed spontaneous hemarthrosis of his right knee following clopidogrel-aspirin treatment. Clopidogrel is an ADP receptor antagonist and in combination with aspirin widely used in patients with atherosclerotic vascular disease to reduce the incidence of ischemic events. To date, no case of spontaneous hemarthrosis following clopidogrel-aspirin therapy has been reported. Prompt aspiration after discontinuing the ADP receptor antagonist-aspirin combination therapy can assist early diagnosis and may prevent further damage to the joint. In conclusion, spontaneous hemarthrosis is a possible complication following clopidogrel-aspirin therapy and is recommended to be evaluated when appropriate clinical symptoms (e.g., intraarticular effusion) present.
Subject(s)
Angina, Unstable/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/adverse effects , Hemarthrosis/chemically induced , Myocardial Infarction/drug therapy , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2 Receptor Antagonists , Ticlopidine/adverse effects , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Aspirin/administration & dosage , Blood Coagulation Tests , Clopidogrel , Drug Interactions , Drug Therapy, Combination , Hemarthrosis/diagnosis , Humans , Male , Osteoarthritis, Knee/diagnosis , Platelet Aggregation Inhibitors/therapeutic use , Risk Factors , Ticlopidine/administration & dosage , Ticlopidine/analogs & derivativesABSTRACT
S100A1, a Ca(2+) binding protein of the EF-hand type, is preferentially expressed in myocardial tissue and has been found to colocalize with the sarcoplasmic reticulum (SR) and the contractile filaments in cardiac tissue. Because S100A1 is known to modulate SR Ca(2+) handling in skeletal muscle, we sought to investigate the specific role of S100A1 in the regulation of myocardial contractility. To address this issue, we investigated contractile properties of adult cardiomyocytes as well as of engineered heart tissue after S100A1 adenoviral gene transfer. S100A1 gene transfer resulted in a significant increase of unloaded shortening and isometric contraction in isolated cardiomyocytes and engineered heart tissues, respectively. Analysis of intracellular Ca(2+) cycling in S100A1-overexpressing cardiomyocytes revealed a significant increase in cytosolic Ca(2+) transients, whereas in functional studies on saponin-permeabilized adult cardiomyocytes, the addition of S100A1 protein significantly enhanced SR Ca(2+) uptake. Moreover, in Triton-skinned ventricular trabeculae, S100A1 protein significantly decreased myofibrillar Ca(2+) sensitivity ([EC(50%)]) and Ca(2+) cooperativity, whereas maximal isometric force remained unchanged. Our data suggest that S100A1 effects are cAMP independent because cellular cAMP levels and protein kinase A-dependent phosphorylation of phospholamban were not altered, and carbachol failed to suppress S100A1 actions. These results show that S100A1 overexpression enhances cardiac contractile performance and establish the concept of S100A1 as a regulator of myocardial contractility. S100A1 thus improves cardiac contractile performance both by regulating SR Ca(2+) handling and myofibrillar Ca(2+) responsiveness.
Subject(s)
Calcium-Binding Proteins/metabolism , Heart Ventricles/metabolism , Myocardial Contraction/physiology , Myocardium/metabolism , Actin Cytoskeleton/physiology , Animals , Calcium/metabolism , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/pharmacology , Calcium-Transporting ATPases/metabolism , Cells, Cultured , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Gene Expression , Gene Transfer Techniques , Heart Ventricles/cytology , Humans , Intracellular Fluid/metabolism , Isometric Contraction/drug effects , Isometric Contraction/physiology , Myocardial Contraction/drug effects , Myocardium/cytology , Rabbits , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Recombinant Fusion Proteins/pharmacology , S100 Proteins , Sarcoplasmic Reticulum/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases , SwineABSTRACT
S100A1 is a new regulatory protein of myocardial contractility that is differentially expressed in early and late stages of myocardial hypertrophy. In order to further investigate the multiple functions of S100A1 in various assay systems we developed a new strategy for isolating biologically active S100A1 protein. After EDTA extraction of myocardium or recombinant bacteria, S100A1 was purified by Octyl-Sepharose hydrophobic interaction chromatography and HiTrapQ anion-exchange chromatography yielding 1.4-2.0 mg/100 g wet tissue and 0.7-1.0 mg/100 ml bacterial culture. Native porcine as well as human recombinant S100A1 revealed biological activity in physiological and biochemical assays.
