Apomorphine-induced myocardial protection is due to antioxidant and not adrenergic/dopaminergic effects.
Apomorphine (Apo), a dopaminergic agonist used for treatment of Parkinson disease, is a potent antioxidant. In addition to its antioxidative effects, the dopaminergic and adrenergic effects of Apo were studied. Isolated perfused rat hearts were exposed to 25 min of no-flow global ischemia (37 degrees C) and 60 min of reperfusion (I/R, control). Drugs were introduced for the first 20 min of reperfusion. The LVDP of the control group recovered to 54.6 +/- 3.3%. Apo-treated hearts had significantly improved recovery (61.6 +/- 5%, p < 0.05). The recovery of the work index LVDP x HR was even bigger: 67.8 +/- 3.7% (Apo treatment) vs 41.7 +/- 4.6% (control, p < 0.001). Haloperidol, a dopaminergic antagonist, did not affect the recovery with Apo. Propranolol, a beta-adrenergic blocker, initially inhibited the effect of Apo. However, the recovery of the combined group (Apo + propranolol) increased and reached significance (LVDP, p < 0.05 vs control group) after cessation of propranolol perfusion. At 60 min of reperfusion this group was superior to Apo-treated hearts (LVDP, p < 0.05). Propranolol (without Apo) did not improve the hemodynamic recovery. The same pattern of recovery applies also to the recovery of the +dP/dt during the reperfusion. L-DOPA was less effective than Apo. I/R caused significant increase in carbonylation of proteins. Apomorphine inhibited the increase in carbonylation. Haloperidol did not affect this beneficial effect of Apo. L-DOPA significantly decreased the carbonylation of proteins. We conclude that the antioxidative effect of Apo is its main mechanism of cardioprotection.
Khaliulin
Igor
I
The Joseph Lunenfeld Cardiac Surgery Research Center, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91120, Israel.
Schneider
Aviva
A
Houminer
Esther
E
Borman
Joseph B
JB
Schwalb
Herzl
H