Allopurinol improves myocardial reperfusion injury in a xanthine oxidase-free model.
The ability of allopurinol to protect against reperfusion injury in the heart has usually been attributed to its xanthine oxidase (XO)-inhibiting properties. Human myocardium however, has exhibited low levels of XO activity. To investigate the effects of allopurinol in an XO-free model and determine whether pretreatment is necessary, 12 domestic pigs (15 kg to 20 kg) underwent occlusion of the left circumflex for 8 minutes followed by reperfusion for 4 hours. One group received allopurinol infusion (5 mg/kg IV) at occlusion over 45 minutes and a control group (n = 6) received a saline infusion (same volume). Left ventricular and aortic pressure, electrocardiograms, and regional wall motion (sonomicrometry) were monitored throughout the process. Regional blood flow (microspheres) were obtained before, during, and 5, 10, and 30 minutes after ischemia. Occlusion decreased transmural flow at the midpapillary level by 75% (0.28 versus 1.10 mL/minute/g). The allopurinol-treated group exhibited a mild, generalized hyperemia at 5 minutes (ischemic zone: 1.44 versus 1.10 mL/min/g, which returned to control levels at 10 and 30 minutes. In contrast, the control group was associated with only 80% restoration of resting blood flow at 5 minutes (0.84 versus 1.10 mL/min/g), which stabilized at 63% of control levels at 10 and 30 minutes. When evaluated for the propensity of arrhythmias using an arbitrary arrhythmia score, the allopurinol group demonstrated no myocardial ectopy when compared with the focal ectopy routinely encountered in the control group at all time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
Hopson
S B
SB
Department of Surgery, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, USA.
Lust
R M
RM
Sun
Y S
YS
Zeri
R S
RS
Morrison
R F
RF
Otaki
M
M
Chitwood
W R
WR
D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D006940:Hyperemia / Q000139:chemically induced; D007275:Injections, Intravenous; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000201:enzymology / Q000628:therapy; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D000493:Allopurinol; D014969:Xanthine Oxidase