Ischemic Preconditioning and Clinical Scenarios

Srinivasan V. Narayanan; Kunjan R. Dave; Miguel A. Perez-Pinzon

Disclosures

Curr Opin Neurol. 2013;26(1):1-7. 

In This Article

Clinical Scenarios for Ischemic Preconditioning

There exist many clinical scenarios for when IPC treatment could be beneficial, most of which involve patients undergoing invasive or long surgeries and being subjected to procedures that could result in a relative state of ischemia. Therefore, patient outcome following surgery might be improved through IPC treatment. Additionally, chronic IPC treatments may afford ischemic and anti-inflammatory protection in patients who suffer from metabolic syndrome, cardiovascular and cerebrovascular disease, or in patients at risk for recurrent ischemic attacks.

Models of Ischemic Preconditioning in Clinic

Most in-vivo models of IPC performed in rodent animals are usually invasive and thus impractical to translate into a clinical setting. However, a modified form of IPC known as remote ischemic preconditioning (RIPC) could prove to have high translational value. RIPC involves cycles of temporary occlusion and restoration of blood flow in a forelimb far removed from the desired sight of cytoprotection. Repeated cycles of temporary ischemia in this area can trigger the release of soluble protective factors into the blood, which can be delivered to the target organ and confer protection.[63] For example, clinical trials have already utilized blood pressure cuffs to induce temporary occlusion and restoration of blood flow in an arm or thigh of patients, thus constituting one model of RIPC.[64] A previous study reported that RIPC-treated patients showed improved ejection fraction, graft patency, and electrocardiogram parameters following coronary artery bypass surgery.[65] In stable angina pectoris patients, three 2-min coronary artery balloon inflation and deflation cycles demonstrated improved cardiac contractility and decreased chest pain.[66] In patients undergoing coronary angioplasty or coronary artery bypass procedures, the induction of carotid artery balloon inflations and deflations just prior to the main surgical procedure could mimic 'early-window' IPC-induced cytoprotection. Lastly, RIPC has been shown to be safe and well tolerated in critically ill patients with subarachnoid hemorrhage,[67] suggesting that RIPC may represent a feasible, prophylactic therapy.

Pharmacologic Therapies

Perhaps more clinically applicable is the use of a pharmacologic agent that can activate pathways critical for IPC-induced neuroprotection. Our laboratory has previously shown the contribution of Sirtuin 1 (SIRT1, a class III NAD+-dependent histone deacetylase) to mediate delayed IPC-induced neuroprotection.[68] Therefore, a potent activator of SIRT1 such as the polyphenol resveratrol could represent a potential therapy for cerebral ischemia. Although the safety of resveratrol in humans has already been profiled,[69] further understanding of its mechanisms is imperative before utilizing this compound for clinical IPC treatment. Isoflurane, commonly used for the fast induction of anesthesia, has been shown to mimic IPC through the activation of mitoK+ATP channels.[70] Thus, brief patient exposures to isoflurane hours to days prior to invasive surgery could represent another clinical use of IPC.

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