Background: Brief cycles of ischemia and reperfusion in tissues remote from the heart, i.e. remote ischemic conditioning (RIC), induce cardioprotection through neuronal and humoral factors. Humoral cardioprotective factors can be transferred with plasma-dialysate from human donors undergoing RIC to isolated recipient hearts where they reduce infarct size. Neuronal responses involve vagal nerve activation which can be traced by heart rate variability parameters. Hypothetically, left-sided RIC may have greater impact through stronger ipsilateral projections of the left-sided vagal innervation. However, whether or not sidedness really impacts on RIC’s efficacy to induce cardioprotection is unknown.

Purpose: To study in healthy volunteers whether the sidedness of the RIC stimulus impacts on the high frequency band of heart rate variability which is considered to reflect vagal innervation of the heart and on the release of humoral cardioprotective factors which were assessed from their transfer by plasma-dialysate taken before/ after left- or right-sided RIC to isolated rat heart preparations subjected to global ischemia/ reperfusion.

Methods: Healthy volunteers (3 females, 7 males, 26 ± 5 years) were randomized to RIC at the right or left arm or to a respective placebo protocol. Protocols were performed with an interval of at least two weeks. RIC was induced by 3 x 5 min blood pressure cuff inflation at 200 mmHg on the upper arm/ 5 min deflation. Heart rate and spectral power in the high frequency (HF) band were assessed non-invasively through analysis from continuously recorded electrocardiograms (Kubios HRV standard 3.4.2, Kubios Oy,Kuopio, Finland). Venous blood samples were taken before and 60 min after RIC or placebo, respectively, and used to prepare plasma-dialysates (1:10 dialysis against buffer for 24 h, cut-off 12-14 kDa). Male Lewis rats were sacrificed and their hearts isolated and perfused at constant pressure with buffer. Plasma-dialysates from samples taken before and 60 min after left- or right-sided RIC or placebo, respectively, were infused for 8 min into rat hearts followed by 2 min washout before global 30 min ischemia/ 120 min reperfusion. Infarct size was demarcated by triphenyl tetrazolium chloride staining and calculated as percent of ventricular mass.

Results: With infusion of plasma-dialysate before left- or right-sided RIC, infarct size was
36 ± 6 % or 34 ± 3 % of ventricular mass. Infusion of plasma-dialysate after left- or right-sided RIC reduced infarct size to 20 ± 4 % and 23 ± 5 %. Infarct sizes were similar with infusion of plasma-dialysates prepared before/after the respective placebo protocol (see Figure, A). Neither HR (Figure, B) nor HF (Figure, C) band were altered by left- or right sided RIC compared to placebo.

Conclusion: RIC, no matter whether left-or right-sided, does not alter heart rate variability parameters or the release of humoral cardioprotective factors in healthy human volunteers.