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