ABSTRACT
A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitation-contraction (E-C) coupling. We investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than 3 micrometer, diclofenac inhibited reversibly the Na+ current and did irreversibly the L-type Ca2+ channels-mediated inward current (IC50=12.89+/-0.43 micrometer) in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type Ca2+ currents but not the Na+ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type Ca2+ channel, leading to the impairment of E-C coupling in cardiac myocytes.
Subject(s)
Animals , Rats , Anti-Inflammatory Agents, Non-Steroidal , Calcium Channels, L-Type , Diclofenac , Heart , Heart Failure , Ibuprofen , Muscle Cells , Myocytes, Cardiac , Naproxen , Nifedipine , Patch-Clamp TechniquesABSTRACT
No abstract available.
Subject(s)
Humans , Apoptosis , DNA, Complementary , Oligonucleotide Array Sequence Analysis , Periodontal LigamentABSTRACT
Rotation-plasty provides useful knee function and permits use of what is essentially an end-weight-bearing below-the knee prosthesis. This principle of rotating the foot was first used by Borggreve in 1930(3), in a patient with a short femur secondary to infection. Since then, this procedure has been used in congenital short femurs(4,6,7,), malignant bone tumors of the distal femur(1,5)and compound fracture with wide bone defect around the knee(2) We have performed this procedure in a case of focal femoral deficiency with 14cm shorter than the opposite femur due to long standing persistant chronic osteomyelitis in the mid-shaft femur of a nine-year old Korean boy and gave the good result with a conventional but slightly modified below- the-knee brace. The inverted foot was good to control the brace as a below-knee stump and heel functioned as a patella to support the body weight.