Remote ischaemic preconditioning (RIPC) using transient limb ischaemia failed to improve clinical outcomes following cardiac surgery and the reasons for this remain unclear. In the ERIC-GTN study, we evaluated whether concomitant nitrate therapy abrogated RIPC cardioprotection. We also undertook a post-hoc analysis of the ERICCA study, to investigate a potential negative interaction between RIPC and nitrates on clinical outcomes following cardiac surgery. In ERIC-GTN, 185 patients undergoing cardiac surgery were randomized to: (1) Control (no RIPC or nitrates); (2) RIPC alone; (3); Nitrates alone; and (4) RIPC + Nitrates. An intravenous infusion of nitrates (glyceryl trinitrate 1 mg/mL solution) was commenced on arrival at the operating theatre at a rate of 2–5 mL/h to maintain a mean arterial pressure between 60 and 70 mmHg and was stopped when the patient was taken off cardiopulmonary bypass. The primary endpoint was peri-operative myocardial injury (PMI) quantified by a 48-h area-under-the-curve high-sensitivity Troponin-T (48 h-AUC-hs-cTnT). In ERICCA, we analysed data for 1502 patients undergoing cardiac surgery to investigate for a potential negative interaction between RIPC and nitrates on clinical outcomes at 12-months. In ERIC-GTN, RIPC alone reduced 48 h-AUC-hs-cTnT by 37.1%, when compared to control (ratio of AUC 0.629 [95% CI 0.413–0.957], p = 0.031), and this cardioprotective effect was abrogated in the presence of nitrates. Treatment with nitrates alone did not reduce 48 h-AUC-hs-cTnT, when compared to control. In ERICCA there was a negative interaction between nitrate use and RIPC for all-cause and cardiovascular mortality at 12-months, and for risk of peri-operative myocardial infarction. RIPC alone reduced the risk of peri-operative myocardial infarction, compared to control, but no significant effect of RIPC was demonstrated for the other outcomes. When RIPC and nitrates were used together they had an adverse impact in patients undergoing cardiac surgery with the presence of nitrates abrogating RIPC-induced cardioprotection and increasing the risk of mortality at 12-months post-cardiac surgery in patients receiving RIPC.

使用短暂性肢体缺血的远程缺血预处理 (RIPC) 未能改善心脏手术后的临床结果，其原因尚不清楚。在 ERIC-GTN 研究中，我们评估了同时使用硝酸盐治疗是否会消除 RIPC 心脏保护作用。我们还对 ERICCA 研究进行了事后分析，以调查 RIPC 和硝酸盐之间对心脏手术后临床结果的潜在负面相互作用。在 ERIC-GTN 中，185 名接受心脏手术的患者被随机分配到：(1) 对照组（无 RIPC 或硝酸盐）；(2) 单独的 RIPC；(3); 单独硝酸盐；(4) RIPC + 硝酸盐。到达手术室后开始以 2–5 mL/h 的速度静脉输注硝酸盐（三硝酸甘油酯 1 mg/mL 溶液）以维持平均动脉压在 60 至 70 mmHg 之间，并在患者恢复正常时停止取消了体外循环。主要终点是围手术期心肌损伤（PMI），通过 48 小时曲线下面积高灵敏度肌钙蛋白-T（48 小时 AUC-hs-cTnT）量化。在 ERICCA 中，我们分析了 1502 名接受心脏手术的患者的数据，以调查 RIPC 和硝酸盐之间对 12 个月临床结果的潜在负面相互作用。在 ERIC-GTN 中，与对照组相比，单独使用 RIPC 可将 48 h-AUC-hs-cTnT 降低 37.1%（AUC 比率为 0.629 [95% CI 0.413–0.957]，主要终点是围手术期心肌损伤（PMI），通过 48 小时曲线下面积高灵敏度肌钙蛋白-T（48 小时 AUC-hs-cTnT）量化。在 ERICCA 中，我们分析了 1502 名接受心脏手术的患者的数据，以调查 RIPC 和硝酸盐之间对 12 个月临床结果的潜在负面相互作用。在 ERIC-GTN 中，与对照组相比，单独使用 RIPC 可将 48 h-AUC-hs-cTnT 降低 37.1%（AUC 比率为 0.629 [95% CI 0.413–0.957]，主要终点是围手术期心肌损伤（PMI），通过 48 小时曲线下面积高灵敏度肌钙蛋白-T（48 小时 AUC-hs-cTnT）量化。在 ERICCA 中，我们分析了 1502 名接受心脏手术的患者的数据，以调查 RIPC 和硝酸盐之间对 12 个月临床结果的潜在负面相互作用。在 ERIC-GTN 中，与对照组相比，单独使用 RIPC 可将 48 h-AUC-hs-cTnT 降低 37.1%（AUC 比率为 0.629 [95% CI 0.413–0.957]，p  = 0.031)，并且这种心脏保护作用在硝酸盐存在下被消除。与对照相比，单独用硝酸盐治疗不会降低 48 h-AUC-hs-cTnT。在 ERICCA 中，硝酸盐使用和 RIPC 在 12 个月时的全因死亡率和心血管死亡率以及围手术期心肌梗死风险之间存在负相互作用。与对照组相比，RIPC 单独降低了围手术期心肌梗死的风险，但 RIPC 对其他结果没有显着影响。当 RIPC 和硝酸盐一起使用时，它们会对接受心脏手术的患者产生不利影响，因为硝酸盐的存在会破坏 RIPC 诱导的心脏保护作用，并增加接受 RIPC 的患者在心脏手术后 12 个月的死亡率。