Related Experiment Videos
Cardioprotective and antioxidant effects of apomorphine
Igor Khaliulin1, Joseph B Borman, Mordechai Chevion
1The Joseph Lunenfeld Cardiac Surgery Research Center, Hadassah University Hospital, Jerusalem, Israel.
Abstract:
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.
Insights
Apomorphine, a potent antioxidant, protects rat hearts from ischemic-reperfusion injury by chelating iron and copper ions. This antioxidant action improves cardiac function and recovery after ischemia.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Biochemistry
Background:
- Myocardial ischemic-reperfusion injury is exacerbated by oxygen-derived free radicals.
- Iron and copper ions are released during reperfusion and mediate free radical formation.
- Apomorphine is a known antioxidant capable of crossing biological membranes.
Purpose of the Study:
- To investigate the cardioprotective effects of apomorphine against myocardial ischemic-reperfusion injury in isolated rat hearts.
- To determine if apomorphine's interaction with iron and copper ions contributes to its protective effects.
- To assess apomorphine's ability to prevent copper-induced oxidative damage.
Main Methods:
- Isolated rat heart model subjected to ischemia-reperfusion.
- Administration of apomorphine before ischemia or at the onset of reperfusion.
- Measurement of hemodynamic function (work index, heart rate, developed pressure).
- Quantification of protein release and coronary flow recovery.
- In vitro studies on apomorphine's interaction with iron and copper, and its effect on ascorbate oxidation.
Main Results:
- Apomorphine administration significantly improved the recovery of hemodynamic function compared to controls.
- Pre-ischemic apomorphine perfusion resulted in 69.2% work index recovery (vs. 43.4% in controls).
- Reperfusion with apomorphine led to 76.3% work index recovery (vs. 30.4% in controls).
- Apomorphine treatment decreased protein release and improved coronary flow recovery post-ischemia.
- Apomorphine formed stable complexes with iron and copper and inhibited copper-induced ascorbate oxidation.
Conclusions:
- Apomorphine exhibits significant cardioprotective effects against myocardial ischemic-reperfusion injury.
- The cardioprotection is attributed to apomorphine's ability to chelate iron and copper ions.
- Formation of redox-inactive chelates with transition metals likely plays a key role in apomorphine's post-ischemic benefits.