Journal of Invasive Cardiology

Ischemic preconditioning has been shown to provide myocardial protection, especially in patients undergoing cardiac surgery;¹⁰ however, this method remains invasive and impractical as it causes ischemia to the vital organs. Oxman et al¹¹ used the non-invasive technique of applying a hind-limb tourniquet for 10 minutes to reduce reperfusion arrhythmias in a rat heart following a sustained ischemic insult. Since then, different investigators have successfully demonstrated the beneficial effects of remote ischemic preconditioning (RIPC) on the heart by applying remote ischemia to the intestine,^12-21 kidneys,^22-28 aorta,^29,30 extremities,^31-34 carotid35 and femoral^36,37 vessels in rats,^{11,12,14-22,26-30,32,34,36,38} pigs,³³ mice,^35,37 and rabbits.^13,23-25,31 These benefits have ranged from reduction in myocardial infarct size by 40-50% and reduction in reperfusion arrhythmias to improvement in left ventricular ejection fraction. MacAllister and co-workers^39-41 pioneered this technique of transient ischemia and reperfusion in humans by 3 repetitive cycles of alternating inflation and deflation of a blood pressure cuff placed on the upper arm to 200 mm Hg for 5 minutes each. This evolved to be the most common protocol used as of now, though minor variations by different investigators have included up to 6 cycles in place of the commonly used 3 cycles (Table 1). Potential mechanistic pathways underlying remote ischemic preconditioning involve neural (adenosine,²² bradykinin,¹⁴ or calcitonin gene-related peptide¹³), humoral (adenosine,²⁴ bradykinin,¹⁷ opioids,^18,29 endocannabinoids,²⁰ or angiotensin I²⁶) or systemic pathways (inflammation/apoptosis^37,38). Activation of mitogen-activated protein kinases, p38, Erk1/2, and JNK²¹ within the remote organ also have been implicated in RIPC-induced cardioprotection.

Human randomized clinical trials evaluating the role of RIPC as a protective strategy have been conducted in patients undergoing CABG, PCI (both elective and emergent), AAA repair, and carotid endarterectomy. Although initial trials evaluating the role of RIPC in patients undergoing CABG yielded positive results, recent trials show no benefits.^42,43 Mixed results have also been obtained when RIPC was used in patients undergoing PCI.^44-46 Besides that, the trials published thus far have been only powered to detect differences in biomarkers of myocardial and renal injury and not clinical endpoints, such as death, myocardial infarction, or arrhythmias. We conducted a meta-analysis with an aim to assess the effect of RIPC on myocardial and renal injury in patients undergoing cardiovascular interventions as measured by biomarkers. We also pooled the available clinical data to evaluate the effects of RIPC on clinical outcomes.