Original article
Influence of allopurinol on cardiac complications in open heart operations

https://doi.org/10.1016/0003-4975(91)91433-VGet rights and content

Abstract

During cardiac operations, the heart is subjected to total ischemia and reperfusion, causing serious operative and postoperative complications such as arrhythmias, heart failure, and infarctions that may be partly due to free radical generation. Thus, allopurinol was tested to see if it could reduce cardiac complications during open heart operations. Ninety patients undergoing elective coronary artery bypass grafting were studied prospectively. Fortyfive patients were treated with allopurinol and 45 patients acted as controls. Treatment requiring arrhythmias in the allopurinol group was 6.6% compared with 33.3% in the control group (p < 0.01). The percentage of patients requiring inotropes was significantly lower in the allopurinol group than in the control group (4.4% versus 26.6%; p < 0.01). Perioperative myocardial infarction did not occur in the allopurinol group but was seen in 8 patients (17.7%) in the control group. Intraaortic balloon pumping was used in 5 control patients (11.1%) but not in the allopurinol group. This study shows that allopurinol decreases significantly the incidence of cardiac complications in open heart operations.

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Cited by (59)

  • Allopurinol attenuates oxidative injury in rat hearts suffered ischemia/reperfusion via suppressing the xanthine oxidase/vascular peroxidase 1 pathway

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    Actually, several small-scale clinical trials for patients with acute myocardial infarction, who were undergoing coronary bypass surgery or angioplasty, have been performed to evaluate the effects of allopurinol on myocardial I/R injury. Most clinical studies reported that allopurinol showed cardioprotective effects, including improvement of cardiac performance (scored by cardiac index and the need for inotropic or mechanical support), decrease of the incidence of cardiac complications (such as arrhythmias, heart failure, and myocardial infarction) and inhibition of oxidative stress (Coghlan et al., 1994; Guan et al., 2003; Johnson et al., 1991; Rashid and William-Olsson, 1991; Castelli et al., 1995). However, another clinical study showed that allopurinol failed to improve cardiac function after cardiopulmonary bypass surgery (Coetzee et al., 1996).

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    In a RCT enrolling 169 patients, pre-treatment of allopurinol (400–800 mg/day for 2 days) reduced in-hospital mortality (4 vs 18%; p = 0.014) and the need for post-operative inotropic or mechanical support (12 vs 26%; p = 0.021) [135]. Peri-operative allopurinol treatment (300–600 mg/day for 5 days) also reduced the risk of cardiac complications, including arrhythmias (p < 0.01), MI (p < 0.01) and requirement for intra-aortic balloon pump support (p = 0.05) [136]. On the contrary, other studies failed to show benefit with allopurinol treatment.

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    These ‘leaked’ electrons combine with molecular oxygen to form superoxide anions (Burgoyne et al., 2013). Recognition of the importance of XO-derived ROS generation has prompted the evaluation of allopurinol in clinical models of IRI (Table 1 (Bochenek et al., 1990; Castelli et al., 1995; Coetzee, Roussouw, & Macgregor, 1996; Coghlan et al., 1994; Gimpel, Lahpor, van der Molen, Damen, & Hitchcock, 1995; Guan et al., 2003; Johnson, Kayser, Brenowitz, & Saedi, 1991; Movahed, Nair, Ashavaid, & Kumar, 1996; Parmley, Mufti, & Downey, 1992; Rashid & William-Olsson, 1991; Rentoukas et al., 2010; Sisto et al., 1995; Tabayashi et al., 1991; Taggart et al., 1994; Talwar et al., 2010)). In a randomised, placebo-controlled trial of 169 patients undergoing elective coronary artery bypass grafting (CABG) (Johnson et al., 1991), which has previously been shown to result in oxidative stress upon reperfusion (Chambers, 2007; Zakkar, Guida, Suleiman, & Angelini, 2015), the use of oral allopurinol reduced in-hospital mortality (4 vs. 18%, p = 0.014) and the need for post-operative inotropic or mechanical support (12 vs. 26%, p = 0.021).

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