TABLE 1

Effects of XO inhibitors in myocardial ischemia-reperfusion injury


Model

Disease or Trigger

Mode of XO Inhibition

Effects of XO Inhibition

Reference
Rat Myocardial infarction-induced by isoproterenol Allopurinol Reduced myocardial damage Wexler and McMurthy (1981)
Rat Myocardial I/R Allopurinol Decreased reperfusion-induced arrhythmias Manning et al. (1984)
Rat heart Myocardial I/R Oxypurinol Reduction of myocardial damage and decrease of myocardial vascular resistance Badylak et al. (1987)
Rat heart Hypothermic cardioplegia, myocardial I/R Allopurinol Improved cardiac function Bergsland et al. (1987)
Rat Myocardial I/R Allopurinol Reduction of myocardial infarct size Montor et al. (1987)
Rat/rabbit heart Myocardial I Allopurinol Improved postischemic function in rats but not in rabbits Grum et al. (1987)
Rat heart Myocardial I/R Allopurinol Improved function during reperfusion and higher ATP levels Lasley et al. (1988)
Rat heart Myocardial I/R Allopurinol Better ventricular function after I/R Brown et al. (1988)
Rat heart Myocardial I/R Allopurinol Better recovery of ventricular function and decreased incidence and duration of reperfusion-induced arrhythmias without effects on recovery of ATP, creatine and inorganic phosphates, and H+ Headrick et al. (1990)
Rat Myocardial I Allopurinol No effect on the infarct size and failure to improve cardiac function Boucher and de Leiris (1991)*
Rat heart Myocardial I/R Allopurinol Improved postischemic recovery of cardiac function, but this result is attributed to an unrelated effect to XO inhibition Chambers et al. (1992)
Rat heart Myocardial I/R Allopurinol Increased XO activity during I/R in interstitial cells, coronary vessel endothelium, and smooth muscle cells detected by immunocytochemistry, which was reduced by allopurinol Ashraf and Samra (1993)
Rat heart Myocardial I/R Allopurinol Intermittent infusion of allopurinol during global myocardial ischemia resulted in improved myocardial functional recovery and improved preservation of high-energy phosphates Sakakibara (1993)
Rat heart Myocardial I/R Allopurinol Reduced the incidence and severity of reperfusion arrhythmias and increased the tissue ascorbate levels Yang et al. (1995)
Rat heart, right ventricular trabeculae Myocardial I/R Allopurinol, Oxypurinol Ca2+-sensitizing effect of allopurinol and oxypurinol underlying the preservation of contractility in a model of stunned myocardium Perez et al. (1998)
Rat heart Myocardial I/R Allopurinol Reduced accumulation of mRNA for heat shock proteins (HSP70 and HSP90) after repetitive ischemia/reperfusion Nishizawa et al. (1999)
Rat heart Myocardial I/R Allopurinol Allopurinol significantly inhibited myocardial xanthine oxidase activity, improved left ventricular dysfunction after ischemia, and decreased myocardial lipid peroxidation and superoxide formation King et al (1998)*
Guinea pig isolated right ventricular segment Myocardial I/R Allopurinol Reduced the incidence and severity of reperfusion arrhythmias Li and Ferrier (1992)
Rabbit Myocardial I/R Allopurinol Decreased reperfusion-induced arrhythmias and protected against ultrastructural damage Godin et al. (1986)
Rabbit Myocardial I/R Allopurinol Protection of the I/R myocardium to t-butylhydroperoxide induced glutathione depletion and production of thiobarbituric acid reactive substances, which was not associated with any significant alterations in tissue ATP levels or in the activities of the myocardial antioxidant enzymes catalase, Cu,Zn-superoxide dismutase, or glutathione peroxidase, suggesting that allopurinol may exert its effects by direct radical scavenging or by some other mechanism unrelated to xanthine oxidase inhibition. Godin and Garnett (1989)
Rabbit Myocardial I/R Allopurinol Better preservation of cellular ATP levels and mitochondrial ATP generation during ischemia and prevention of the decrease in left ventricular pressure, sodium and calcium accumulation, and decreases in sarcolemmal Na+,K+-stimulated and sarcoplasmic reticulum K+,Ca2+-stimulated ATPase activities Godin and Bhimji (1987)
Rabbit heart Hypothermic cardioplegia, myocardial I/R Allopurinol Improved cardiac function Myers et al. (1986)
Rabbit heart Myocardial I/R Allopurinol No detectable XO activity and reduction of the infarct size Downey et al. (1987)*
Rabbit heart Myocardial I/R Allopurinol Decreased XO activity and improved ventricular developed pressure, peak systolic pressure, and coronary flow Terada et al. (1991)
Dog Myocardial I Allopurinol No reduction of the infarct size Shatney et al. (1976)*
Dog Myocardial I/R Allopurinol Reduction of infarct size Chambers et al. (1985)
Dog Myocardial I Allopurinol Reduction of infarct size Akizuki et al. (1985)
Dog Myocardial I/R Allopurinol No reduction of the infarct size Reimer and Jennings (1985)*
Dog Hypothermic cardioplegia, myocardial I/R Allopurinol Improved left ventricular function Stewart et al. (1985)
Dog Myocardial I/R Allopurinol Reduction of infarct size Werns et al. (1986)
Dog Myocardial I/R Allopurinol Better recovery of systolic contractile function following reperfusion Charlat et al. (1987)
Dog Myocardial I/R Allopurinol No decrease in I/R-induced arrhythmias Parratt and Wainwright, (1987)*
Dog Myocardial I Allopurinol Reduction of infarct size Kingma et al. (1987, 1989)
Dog Myocardial I/R Oxypurinol Improved regional ventricular function after reperfusion, but failed to reduce infarct size Puett et al. (1987)
Dog Myocardial I Allopurinol Delayed but did not prevent infarction in the permanent occlusion model Miura et al. (1988)
Dog Myocardial I/R Oxypurinol No reduction of the infarct size Kinsman et al. (1988)*
Dog Myocardial I Allopurinol No reduction of the infarct size if allopurinol was given 1 min postocclusion Kingma et al. (1988)*
Dog Myocardial I/R Allopurinol, Oxypurinol Oxypurinol but not allopurinol given before reperfusion reduced the infarct size but not ventricular arrhythmias Matsuki et al. (1990)
Dog Myocardial I/R Oxypurinol, Amflutizole Xanthine oxidase inhibition was demonstrated in each of the drug treatment groups, but only oxypurinol limited the extent of myocardial injury Werns et al. (1991)
Dog Myocardial I/R Allopurinol Reduction of infarct size Motoe and Yoshida (1991)
Dog Myocardial I/R Allopurinol Improved endothelium-dependent coronary vascular relaxation in vitro Sobey et al. (1992)
Dog Myocardial I/R Allopurinol Improved contractility, decreased lipid peroxidation Konya et al. (1993)
Dog Myocardial I/R Allopurinol Improved endothelium-dependent coronary vascular relaxation in vivo Sobey et al. (1993)
Dog Myocardial I/R Allopurinol Inhibition of XO activity by allopurinol resulted in a dose-dependent increase in cardiac interstitial fluid hypoxanthine and xanthine levels and a decrease in uric acid Kuzmin et al. (1995)
Newborn lamb Low O2 ventilation and blood volume reduction-induced hypoxic injury Allopurinol Allopurinol exerted a beneficial effect on the pump function by afterload reduction but not by changes in contractility and also inhibited uric acid formation with a consequent decrease in antioxidative capacity Shahid et al. (1999)
Pig heart Myocardial I/R Allopurinol, Oxypurinol Decreased reperfusion injury, free radical scavenging effect Das et al. (1987)
Pig heart and lung I/R associated with heart-lung transplantation Allopurinol Better recovery of cardiac and pulmonary function and generalized alterations in tissue antioxidant status Qayumi et al. (1993)
Pig Myocardial I/R Allopurinol Better recovery of cardiac function and decreased propensity of reperfusion arrhythmias Hopson et al. (1995)
Human (169 patients) Coronary bypass surgery Allopurinol Decreased hospital mortality rate, increased cardiac index Johnson et al. (1991)
Human (90 patients) Coronary bypass surgery Allopurinol Reduced arrhythmias, need for inotropes and perioperative myocardial infarction in patients Rashid and William-Olsson (1991)
Human (140 patients) Myocardial I Allopurinol Increased incidence of infarct extensions in the treatment group Parmley et al. (1992)*
Human (80 patients) Ischemic heart disease Allopurinol + erinit Decreases in serum and daily urinary levels of uric acid and lipid peroxidation antioxidative system and an improvement of central hemodynamics Kaliakin and Mit'kin (1993)
Human (50 patients) Coronary bypass surgery Allopurinol Improves postoperative recovery and reduces lipid peroxidation in patients undergoing coronary artery bypass grafting Coghlan et al. (1994)
Human (20 patients) Coronary bypass surgery Allopurinol Failed to demonstrate a cardioprotective effect of allopurinol in patients with good left ventricular function undergoing elective coronary artery surgery Taggart et al. (1994)*
Human (20 patients) Coronary bypass surgery Allopurinol Allopurinol suppressed the reaction rate of xanthine oxidase; therefore, the levels of intermediates, hypoxanthine and xanthine, were high, and the level of the final product, uric acid, was low—however, allopurinol had no efficacy for the level of lactate, pyruvate, CK, and CK-MB Yamazaki et al. (1995)*
Human (33 patients) Coronary bypass surgery Allopurinol Better recovery of cardiac output and left ventricular stroke work after bypass surgery and reduction of plasma XO activity and concentrations of uric acid Castelli et al. (1995)
Human (52 patients) Coronary bypass surgery Allopurinol Allopurinol failed to improve left ventricular stroke work after cardiopulmonary bypass surgery Coetzee et al. (1996)*
Human (38 patients)
Percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction
Allopurinol
Allopurinol pretreatment was effective in inhibiting generation of oxygen-derived radicals during reperfusion and in the recovery of left ventricular function
Guan et al. (2003)
  • I/R, ischemia-reperfusion; I, ischemia; CK, creatine kinase.

  • * Studies concluded with negative results