| Autor: |
Barry, William H., Zhang, Xiu Q., Halkos, Michael E., Vinten-Johansen, Jakob, Saegusa, Noriko, Spitzer, Kenneth W., Matsuoka, Nobuhiro, Sheets, Michael, Rao, Narayanam V., Kennedy, Thomas P. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Jan2010, Vol. 298 Issue 1, pH102-H111, 10p, 4 Charts, 8 Graphs |
| Abstrakt: |
Heparin desulfated at the 2-0 and 3-0 positions (ODSH) decreases canine myocardial reperfusion injury. We hypothesized that this occurs from effects on ion channels rather than solely from anti-inflammatory activities, as previously proposed. We studied closed-chest pigs with balloon left anterior descending coronary artery occlusion (75-mm) and reperfusion (3-h). ODSH effects on [Na+]i (Na Green) and [Ca2+]i (FIuo-3) were measured by flow cytometry in rabbit ventricular myocytes after 45-mm of simulated ischemia [metabolic inhibition with 2 mM cyanide, 0 glucose, 37°C, pacing at 0.5 Hz; i.e., pacing-metabolic inhibition (PMI)I. Na+/Ca2+ exchange (NCX) activity and Na+ channel function were assessed by voltage clamping. ODSH (15 mg/kg) 5 mm before reperfusion significantly decreased myocardial necrosis, but neutrophil influx into reperfused myocardium was not consistently reduced. ODSH (100 p.g/ml) reduced [Na+] and [Ca2+]i during PMI. The NCX inhibitor KB-R7943 (10 μM) or the late Na+ current (INa-L) inhibitor ranolazine (10μM) reduced [Ca2+]i during PM! and prevented effects of ODSH on Ca2+ loading. ODSH also reduced the increase in Na+ loading in paced myocytes caused by 10 nM sea anemone toxin II, a selective activator of INa-L. ODSH directly stimulated NCX and reduced INa-L. These results suggest that in the intact heart ODSH reduces Na+ influx during early reperfusion, when INa-L is activated by a burst of reactive oxygen production. This reduces Na+ overload and thus Ca2+ influx via NCX. Stimulation of Ca2+ extrusion via NCX later after reperfusion may also reduce myocyte Ca2+ loading and decrease infarct size. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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