Cardioprotective and antioxidant effects of apomorphine.
Apomorphine is a potent antioxidant that infiltrates through biological membranes. We studied the effect of apomorphine (2 microM) on myocardial ischemic-reperfusion injury in the isolated rat heart. Since iron and copper ions (mediators in formation of oxygen-derived free radicals) are released during myocardial reperfusion, apomorphine interaction with iron and copper and its ability to prevent copper-induced ascorbate oxidation were studied. Apomorphine perfused before ischemia or at the commencement of reperfusion demonstrated enhanced restoration of hemodynamic function (i.e. recovery of the work index (LVDP x HR) was 69.2 +/- 4.0% with apomorphine pre-ischemic regimen vs. 43.4 +/- 9.01% in control hearts, p < 0.01, and 76.3 +/- 8.0% with apomorphine reperfusion regimen vs. 30.4 +/- 11.1% in controls, p < 0.001). This was accompanied by decreased release of proteins in the effluent and improved coronary flow recovery in hearts treated with apomorphine after the ischemia. Apomorphine forms stable complexes with copper and with iron, and inhibits the copper-induced ascorbate oxidation. It is suggested that these iron and copper chelating properties and the redox-inactive chelates formed by transition metals and apomorphine play an essential role in post-ischemic cardioprotection.
Khaliulin
Igor
I
The Joseph Lunenfeld Cardiac Surgery Research Center, Hadassah University Hospital, Jerusalem, Israel.
Borman
Joseph B
JB
Chevion
Mordechai
M
Schwalb
Herzl
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006321:Heart / Q000187:drug effects; D007477:Ions; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008956:Models, Chemical; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013053:Spectrophotometry; D013997:Time Factors
D000975:Antioxidants; D018491:Dopamine Agonists; D005609:Free Radicals; D007477:Ions; D003300:Copper; D007501:Iron; D001058:Apomorphine; D001205:Ascorbic Acid; D010100:Oxygen