Peripheral vascular disease as remote ischemic preconditioning, for acute stroke

Abstract

Obectives Remote ischemic preconditioning (RIPC) is a powerful endogenous mechanism whereby a brief period of ischemia is capable of protecting remote tissues from subsequent ischemic insult. While this phenomenon has been extensively studied in the heart and brain in animal models, little work has been done to explore the effects of RIPC in human patients with acute cerebral ischemia. This study investigates whether chronic peripheral hypoperfusion, in the form of pre-existing arterial peripheral vascular disease (PVD) that has not been surgically treated, is capable of inducing neuroprotective effects for acute ischemic stroke. Methods Individuals with PVD who had not undergone prior surgical treatment were identified from a registry of stroke patients. A control group within the same database was identified by matching patient’s demographics and risk factors. The two groups were compared in terms of outcome by NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), mortality, and volume of infarcted tissue at presentation and at discharge. Results The matching algorithm identified 26 pairs of PVD-control patients (9 pairs were female and 17 pairs were male). Age range was 20 to 93 years (mean 73). The PVD group was found to have significantly lower NIHSS scores at admission (NIHSS ≤ 4: PVD 47.1%, Control 4.35%, p < 0.003), significantly more favorable outcomes at discharge (mRS ≤ 2: PVD 30.8%, Control 3.84%, p < 0.012), and a significantly lower mortality rate (PVD 26.9%, Control 57.7% p=0.024). Mean acute stroke volume at admission and at discharge were significantly lower for the PVD group (Admission: PVD 39.6mL, Control 148.3mL, p < 0.005 and Discharge: PVD 111.7mL, Control 275mL, p < 0.001). Conclusion Chronic limb hypoperfusion induced by PVD can potentially produce a neuroprotective effect in acute ischemic stroke. This effect resembles the neuroprotection induced by RIPC in preclinical models.

Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke

“…This was supported with measurement and analysis of creatine kinase, infarct size on imaging, development of malignant arrhythmia, mortality and neurologic disability (Abete et al, 1997; Castillo et al, 2003; Lorgis et al, 2012; Moncayo et al, 2000; Wegener et al, 2004). Also, patients with peripheral vascular disease (PVD) and sleep apnea (through repetitive hypoxic crises) may have experienced naturally occurring ischemic preconditioning (Connolly et al, 2013; Koch et al, 2007). PVD patients had better functional outcomes and smaller stroke volumes according to an observational study.…”

“…PVD patients had better functional outcomes and smaller stroke volumes according to an observational study. Cerebroprotection was felt to be the result of chronic limb ischemia (Connolly et al, 2013). The mechanisms involved in ischemic conditioning have been derived primarily from IPrC research.…”

Neuroprotective and nephroprotective effects of remote postconditioning: Prospects for clinical use

“…В 2013 г. M. Connolly и соавт. опубликовали результаты своих наблюдений у пациентов с ишемическим инсультом (ИИ) [17]. Больных разделили на 2 группы: 1) пациенты с заболеванием периферических сосудов (ЗПС); 2) больные без поражения периферических сосудов.…”

“…Выяснилось, что инсульт протекает легче у пациентов с ЗПС, а частота летальных исходов у них в 2 раза ниже, чем у больных без поражения перифериче-ских артерий. Авторы публикации полагают [17], что ЗПС явля-ется аналогом ДИП у человека и рассматривают полученные дан-ные как доказательство существования нейропротекторного дей-ствия ДП у человека. В 2014 г. опубликованы результаты много-центрового исследования, включавшего 335 больных с острым нарушением мозгового кровообращения (преходящее нарушение мозгового кровообращения -58, ИИ -240, ГИ -37) [18].…”

Full Steam Ahead with Remote Ischemic Conditioning for Stroke

“…Examples of such potential preconditioning include the effects of surgical incisions 25 and underlying vascular disease. Recently, Connolly et al 29 found that patients with pre-existing arterial peripheral vascular disease may be protected from acute ischemic stroke. This might be a result of limb hypoperfusion having similar effects to RIPC.…”