Bucillamine prevents myocardial reperfusion injury

Injury during reperfusion can partially offset the benefit of relief of isc hemia in myocardial infarctions rapidly treated with thrombolytic drugs or angioplasty. We assessed whether bucillamine (N-[2-mercapto-2-methylpropion yl]-L-cysteine) is potentially useful to treat myocardial reperfusion injur y. Bucillamine is a potent sulfhydryl donor not previously tested as a trea tment of reperfusion injury. Cardiac myocytes were exposed to hydrogen pero xide or a xanthine/xanthine oxidase system resulting in injury-induced rele ase of lactate dehydrogenase. Bucillamine (125-500 muM) prevented lactate d ehydrogenase release in a concentration-dependent manner. Bucillamine, whic h has two donatable thiol groups, was twice as protective as N-2-mercaptopr opionyl glycine, which contains a single donatable thiol group. Dogs were t hen exposed to 90 min of coronary artery occlusion and 48 h of reperfusion before sacrifice. Beginning at the onset of reperfusion, bucillamine, 11 or 22 mg/kg per hour, or vehicle (saline) was administered intravenously for 3 h. There was a dose-related response to bucillamine for infarct size. nor malized for size of the region at risk and adjusted for collateral blood fl ow to the ischemic region. Infarct size was reduced by 41% in the group tre ated with bucillamine 22 mg/kg per hour, compared with the vehicle group. B ucillamine, probably through an antioxidant mechanism, reduced infarct size when administered during reperfusion.