The effect of ischemic preconditioning in patients with cerebral small vessel disease

Rationale: There is no proven effective treatment to attenuate the progression of cerebral small vessel disease (cSVD), leading to long-term disability and mortality in patients who suffer from this disease. A new innovative treatment option could be related to preconditioning. There are several methods to apply preconditioning, including Remote ischemic conditioning (RIC) and exercise conditioning (EC). Although preconditioning represents a low-cost non-invasive treatment strategy to potentially attenuate the progression of cerebral small vessel disease, little work examined the potential distinct physiological responses between single versus repeated preconditioning. Secondly, although both ischemic and exercise conditioning may have clinical benefit, little work explored whether both types of preconditioning elicit a comparable physiological response.

Objective: To explore the effect of single versus repeated preconditioning on circulating blood factors (i.e. metabolomics analysis) as a likely mechanism in patients with cSVD. Secondly, we explore whether the effects of single versus repeated preconditioning differs between ischemic and exercise conditioning on circulating blood factors of patients with cSVD.

We hypothesize that both remote ischemic conditioning and exercise conditioning activate the release of circulating blood factors. We expect that the repeated application shows higher levels op these circulating blood factors

Cross-over 2x one week (with one week of wash-out in between). Every week we have three time points:
- Baseline
- 1 hour after a single bout of ischemic conditioning
- After 4 days of repeated ischemic conditioning

Remote ischemic conditioning: inflation of a small cuff around the upper arm at 200 mmHg or 20 mmHg above systolic blood pressure: 4x5 min with 5 minutes of reperfusion. This procedure will be performed twice a day (morning and afternoon) for 4 days.
Exercise conditioning (EC): 4x5 min of handgrip exercise, followed by 5 minutes rest. Twice daily for four days. This exercise will be performed twice a day (morning and afternoon) for 4 days.