Preconditioning Shields Against Vascular Events in Surgery

The demand for major vascular surgery is increasing [1]. Patients requiring procedures such as aortic aneurysm repair, carotid endarterectomy, lower limb surgical re-vascularisation and major lower limb amputation for end-stage vascular disease constitute a high-risk surgical cohort. Peri-operative complications such as myocardial infarction, cerebrovascular accident, renal failure and death are common [2,3]. Multiple potential mechanisms may result in these complications. For example, myocardial injury may result from systemic hypotension leading to reduced flow across a tight coronary artery stenosis or, alternatively, it may arise due to acute occlusion when an unstable plaque ruptures. Most strategies aimed at peri-operative risk reduction target a single potential mechanism. For example, beta-blockade may prevent myocardial injury due to overwork, but cannot prevent acute coronary occlusion. There is a requirement for a simple, effective intervention that protects tissues against injury via multiple different mechanisms. Remote ischemic preconditioning (RIPC) may be suitable.

Ischemic preconditioning is a phenomenon whereby a brief period of non-lethal ischemia in a tissue renders it resistant to the effects of a subsequent much longer ischaemic insult. It was first described in the canine heart [4]. Subsequent clinical trials showed that ischemic preconditioning reduced heart muscle damage following coronary artery bypass grafting [5] and liver dysfunction following hepatic resection [6]. Following cardiac surgery, it is associated with a reduction in critical care stay, arrhythmias and inotrope use [7]. However, ischemic preconditioning requires direct interference with the target tissues' blood supply, limiting its clinical utility. Further experimental work suggested that brief ischemia in one tissue, such as the kidneys, could confer protection on distant organs such as the heart [8]. A similar effect was observed after transient skeletal muscle ischemia [9-11]. This effect is referred to as 'preconditioning at a distance' or 'remote ischemic preconditioning' (RIPC).

Inclusion criteria

• Age greater than 18 years
• patient willing to give full informed consent for participation
• Patients undergoing elective carotid endarterectomy or
• Patients undergoing open abdominal aortic aneurysm repair or
• Patients undergoing endovascular abdominal aneurysm repair or
• Patients undergoing surgical lower limb revascularisation (suprainguinal or infrainguinal)

Exclusion criteria

• Patients less than 18 years of age
• Patients who are unable or unwilling to give full informed consent
• Pregnancy
• Significant upper limb peripheral arterial disease
• Patients on glibenclamide or nicorandil (these medications may interfere with remote ischaemic preconditioning)
• Patients with an estimated pre-operative glomerular filtration rate < 30mls/min/1.73m2
• Patients with a history of myocarditis, pericarditis or amyloidosis
• Patients undergoing Fenestrated or branched EVAR.