This study demonstrated cerebrovascular effects induced by RIPC consistent with transient vasodilation. Cerebral metabolic effects suggest protection from ischemia and cell membrane preservation lasting up to 2 days following RIPC.

Proton nuclear magnetic resonance (H-NMR) spectroscopic analysis of cerebral spinal fluid provides a quick, non-invasive modality for evaluating the metabolic activity of brain-injured patients. In a prospective study, we compared the CSF of 44 TBI patients and 13 non-injured control subjects. CSF was screened for ten parameters: β-glucose (Glu), lactate (Lac), propylene glycol (PG), glutamine (Gln), alanine (Ala), α-glucose (A-Glu), pyruvate (PYR), creatine (Cr), creatinine (Crt), and acetate (Ace). Using mixed effects measures, we discovered statistically significant differences between control and trauma concentrations (mM). TBI patients had significantly higher concentrations of PG, while statistical trends existed for lactate, glutamine, and creatine. TBI patients had a significantly decreased concentration of total creatinine. There were no significant differences between TBI patients and non-injured controls regarding β- or α-glucose, alanine, pyruvate or acetate. Correlational analysis between metabolites revealed that the strongest significant correlations in non-injured subjects were between β- and α-glucose (r = 0.74), creatinine and pyruvate (r = 0.74), alanine and creatine (r = 0.62), and glutamine and α-glucose (r = 0.60). For TBI patients, the strongest significant correlations were between lactate and α-glucose (r = 0.54), lactate and alanine (r = 0.53), and α-glucose and alanine (r = 0.48). The GLM and multimodel inference indicated that the combined metabolites of PG, glutamine, α-glucose, and creatinine were the strongest predictors for CMRO2, ICP, and GOSe. By analyzing the CSF of patients with TBI, our goal was to create a metabolomic fingerprint for brain injury.

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.

RIPC by limb ischemia appears to prolong the PT and INR in human subjects with SAH after at least 4 sessions, correlating with the number of sessions. However, values remained within normal range and there were no hemorrhagic complications.

Exposure of one tissue to ischemia-reperfusion confers a systemic protective effect, referred to as remote ischemic preconditioning (RIPC). Confirmation that the desired effect of ischemia is occurring in tissues used to induce RIPC requires an objective demonstration before this technique can be used consistently in the clinical practice. Enrolled patients underwent three to four RIPC sessions on non-consecutive days. Sessions consisted of 4 cycles of 5 min of leg cuff inflation to 30 mmHg above the systolic blood pressure followed by reperfusion. Absence of leg pulse was confirmed by Doppler evaluation. To evaluate limb transient ischemia, patients were monitored with muscle microdialysis. Glucose, lactate, lactate/pyruvate ratio, and glycerol levels were measured. Fourteen microdialysis sessions were performed in seven patients undergoing RIPC (42.8 % male; mean age, 51.8; Fisher grade 4 in all seven patients, Hunt and Hess grade 5 in five patients, four in one patient and one in one patient). An average follow-up of 29 days demonstrated no complications associated with the procedure. Muscle microdialysis during RIPC sessions showed a significant increase in lactate/pyruvate ratio (21.2 to 26.8, p = 0.001) and lactate (3.0 to 3.9 mmol/L, p = 0.002), indicating muscle ischemia. There was no significant variation in glycerol (234 to 204 μg/L, p = 0.43), indicating no permanent cell damage. The RIPC protocol used in this study is safe, well tolerated, and induces transient metabolic changes consistent with sublethal ischemia. Muscle microdialysis can be used safely as a confirmatory tool in the induction of RIPC.