Potential humoral mediators of remote ischemic preconditioning in patients undergoing surgical coronary revascularization

Abstract

Remote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion may reduce myocardial ischemia/reperfusion injury and improve patients‘ prognosis after elective coronary artery bypass graft (CABG) surgery. The signal transducer and activator of transcription (STAT)5 activation in left ventricular myocardium is associated with RIPC´s cardioprotection. Cytokines and growth hormones typically activate STATs and could therefore act as humoral transfer factors of RIPC´s cardioprotection. We here determined arterial plasma concentrations of 25 different cytokines, growth hormones, and other factors which have previously been associated with cardioprotection, before (baseline)/after RIPC or placebo (n = 23/23), respectively, and before/after ischemic cardioplegic arrest in CABG patients. RIPC-induced protection was reflected by a 35% reduction of serum troponin I release. With the exception of interleukin-1α, none of the humoral factors changed in their concentrations after RIPC or placebo, respectively. Interleukin-1α, when normalized to baseline, increased after RIPC (280 ± 56%) but not with placebo (97 ± 15%). The interleukin-1α concentration remained increased until after ischemic cardioplegic arrest and was also higher than with placebo in absolute concentrations (25 ± 6 versus 16 ± 3 pg/mL). Only interleukin-1α possibly fulfills the criteria which would be expected from a substance to be released in response to RIPC and to protect the myocardium during ischemic cardioplegic arrest.

Remote Ischemic Preconditioning Induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway

“…We found that RIPC induces the expression of IL-6 at the preconditioned hindlimb muscle and increases plasma IL-6 secretion in vivo ( Figure 4A,B), a finding that aligns with our previous in vitro findings [32]. However, Gedik and colleagues did not detect any significant change in IL-6 levels in arterial plasma sample collected after RIPC from patients undergoing elective CABG [74]. Age, presence of co-morbidity, medications, anesthetic regimen, and extent of preconditioning stimuli may all interfere with the cardioprotective modalities of RIPC [13] and may explain the discrepancy with our findings.…”

Remote Ischemic Preconditioning With the Use of Lower Limb Before Coronary Artery Bypass Surgery With Cardiopulmonary Bypass and Anesthesia With Propofol

“…Достаточно подробно, хотя и не до конца, изучен механизм защитного эффекта ишемического прекондиционирования. Короткие эпизоды ишемии приводят к выбросу в системный кровоток таких биологически активных веществ, как аденозин, брадикинин и эндорфины [8,9], увеличивается концентрация оксида азота [10], интерлейкина-1а [11], а также специфической микро-РНК 144 [12]. В результате запускаются процессы антиоксидантной защиты, повышается противовоспалительный потенциал.…”

Extracellular vesicles isolated from patients undergoing remote ischemic preconditioning decrease hypoxia-evoked apoptosis of cardiomyoblasts after isoflurane but not propofol exposure

“…In a randomized subprotocol (amendment: 08-21-2011, also approved by the ethics commission), we used a proof-of principle design to prospectively investigate whether the RIPC maneuver results in a changed EV concentration along with the search for humoral factors transferring a protective RIPC signal [21]. For the present in vitro study, EVs from 10 randomly selected patients (n = 5 RIPC, n = 5 Sham) matched for similar demographics were used.…”