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Abstract

This research was designed to test the hypothesis that ischemic preconditioning can be transferred between animals via whole blood transfusion. Preconditioning at a distance refers to the reduction in myocardial infarct size seen when coronary artery occlusion is preceded by brief ischemic episodes of noncardiac tissue. Isolation of the trigger signal responsible for this effect may be useful in the diagnosis and treatment of acute coronary occlusive syndromes. Rabbits were paired by crossmatching blood samples prior to experimentation. Crossmatched pairs were placed into either preconditioned (P) or control sets. Rabbits in the preconditioned sets were further divided into donor (PD) and acceptor (PA) animals. PD animals underwent five episodes of circumflex and renal artery occlusion followed by reperfusion. Before and after each preconditioning episode, a whole blood exchange was performed between PD and PA animals. Alternatively, control rabbits underwent the same surgical procedures and time-sequenced transfusion without preconditioning. All animals then underwent prolonged circumflex occlusion (60 minutes) followed by reperfusion (30 minutes). The area of myocardium at risk (R) was determined by isotope-labeled microsphere injection. Infarct size (I) was determined by NBT staining. The percent infarct within the risk area (I/R) was then compared. The I/R was significantly lower in the PA (14.0% +/- 12.2) and PD (14.3% +/- 11.2) groups as compared with controls (61% +/- 20. 6). There was no significant difference between the tPA and TPD groups. In conclusion, the ischemic preconditioning effect can be transferred to nonpreconditioned animals via whole blood transfusion, suggesting a humoral mechanism for preconditioning at a distance.

Remote Limb Ischemic Conditioning at Two Cuff Inflation Pressures Yields Learning Enhancements in Healthy Adults

“…There is mounting evidence that RLIC-facilitated protection is mediated by humoral factors (Dickson et al, 1999; Hess et al, 2015; Sebastian Koch, 2010; S. Koch et al, 2014; Konstantinov et al, 2005).…”

“…This study included exploration of a panel of blood-borne biomarkers of RLIC because there is evidence that the underlying factors responsible for the protective effects of ischemic conditioning are present in the blood (Dickson et al, 1999; Hess et al, 2015; Meller & Simon, 2015). Moreover, a recent study found that a global proteomic response was stimulated in the serum of healthy volunteers who had undergone RLIC (Hepponstall et al, 2012).…”

Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic conditioning

“…Clinical trials have demonstrated the efficacy of RIc in reducing infarct size in patients with an acute myocardial infarction (AMI), 4 , 5 in reducing myocardial damage during cardiac surgery 6 and improving long term prognosis in both patient cohorts 6 , 7 . Although the exact mechanisms underlying RIc cardioprotection are not fully understood, a number of studies suggested the involvement of both humoral 8–11 and neural signalling pathways 1 , 12–14 . Several candidate humoral factors of RIc have been proposed, including stromal cell-derived factor-1α, 15 nitrite/nitric oxide, 16 interleukin-10, 17 microRNA-144, 18 apolipoprotein A-I 19 and alpha-ketoglutarate-dependent dioxygenase Egln1 20 .…”

Remote ischaemic conditioning: cardiac protection from afar

“…Dickson et al. 16, 17 discovered that the ischaemic preconditioning effect could be transferred from one rabbit to another non‐preconditioned rabbit, first via whole blood transfusion, and second via transfer of coronary effluent (IPC effluent) from a preconditioned, to a naïve isolated heart. Hence, the presence and necessity of a blood‐borne cardioprotective factor is clear.…”