Combined intravenous treatment with ascorbic acid and desferrioxamine to reduce myocardial reperfusion injury in an experimental model resembling the clinical setting of primary PCI.
BACKGROUND
During reperfusion of ischemic myocardium, oxygen-derived free radicals are produced and can cause deleterious effects, known as reperfusion injury. We aimed to determine if a combination of the antioxidant ascorbic acid and an iron-chelating agent desferrioxamine, which reduces the production of the hydroxyl radical via ferrum-catalyzed reactions, can exert a protective action against reperfusion injury.


METHODS
Twenty-two young male farm pigs were anesthetized and subjected to 45 mins of ischemia and 3 and a half hours of reperfusion, in the left circumflex coronary artery territory, via the inflation and deflation of an angioplasty balloon. Animals were randomly assigned to receive either an intravenous infusion of 100 mg/ kg ascorbic acid and 60 mg/kg desferrioxamine (treatment group, TG) or an equal amount of normal saline (control group, CG). The I/R ratio, the ratio of the infarcted (necrotic) zone (I) to the myocardial area at risk (R) after 3 and a half hours of reperfusion, was calculated using the tetrazolium staining method. Left ventricular end diastolic pressure (LVEDP), number of episodes of ventricular arrhythmias, TIMI flow in the reperfused vessel, and left ventricular ejection fraction (LVEF) were evaluated within the first hour post reperfusion in order to assess further injury severity.


RESULTS
There was no significant difference in the I/R between the TG (27.9 ± 2.2%) and the CG (32.9 ± 2.4%) (p=0.15). In both groups there was a significant reduction in LVEF (-11.6 ± 2.28% for TG and -12.0 ± 2.27% for CG, p<0.01 for both groups) and a significant increase in LVEDP (+3.2 ± 0.9 mmHg for TG and +4.6 ± 0.9 mmHg for CG, p<0.01 for both groups) compared to the baseline values. No significant difference was noted between groups (p=0.61 for LVEF and p=0.60 for LVEDP values, at one hour post reperfusion). In all other parameters measured, no significant difference was observed between the study groups.


CONCLUSIONS
Intravenous treatment with a combination of the antioxidant ascorbic acid and the iron-chelating agent desferrioxamine does not provide significant protection against myocardial reperfusion injury.
Michaelideion Cardiac Center, Ioannina Medical School, Ioannina, Greece.
Georgios N
GN
Chatziathanasiou
Dimitrios N
DN
Nikas
Christos S
CS
Katsouras
Nikolaos D
ND
Kazakos
Vasiliki
V
Bouba
Theodoros
T
Vougiouklakis
Katerina K
KK
Naka
Lampros K
LK
Michalis
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac; D001205:Ascorbic Acid / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000503:physiopathology*; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D011897:Random Allocation; D013318:Stroke Volume; D034421:Sus scrofa
D000975:Antioxidants; D003676:Deferoxamine; D001205:Ascorbic Acid