Impact Of Remote Ischemic Preconditioning On Contractile Function Of Human Atrial Trabeculae Subjected To Hypoxia/Reoxygenation

Remote ischemic preconditioning (RIPC), i.e., repeated cycles of brief ischemia/reperfusion in a tissue or organ remote from the heart, attenuates troponin release in patients undergoing surgical coronary revascularization and improves outcome in some, but not all studies. The signal transduction of such cardioprotection is largely unknown. Without knowledge of the area at risk, troponin release does not reflect protection or lack of it in an individual patient, making it impossible to analyze signal transduction in an individual patient. Therefore, we developed a bioassay to reflect RIPC-induced protection and to identify the underlying protective signal(s) in an individual patient. Patients undergoing elective CABG surgery underwent RIPC by 3 cycles of 5 min upper arm ischemia/5 min reperfusion (n=35) or a sham (n=39) procedure. Demographics and intraoperative variables were comparable between the groups. Myocardial protection by RIPC was reflected by 14 % decreased area under the curve of serum troponin I/T concentrations over 72 h after surgery vs. sham. Trabeculae (≥ 3 mm length, ≤ 1 mm diameter) were isolated in cardioplegic buffer and transferred to Tyrode buffer. Electrically initiated (1 Hz) developed force of contraction (mN/mm 2 ) was measured under baseline conditions (95% O 2 – 5% CO 2 , glucose) for 10 min. Hypoxia/reoxygenation (60 min/30 min) was induced by changing the buffer gas supply and composition and by increasing stimulation rate (95% N 2 – 5% CO 2 , choline chloride, 3 Hz) and returning back to baseline. Baseline contractile function and the recovery of contractile function during reoxygenation were improved in trabeculae from patients with RIPC vs. sham (see Figure). RIPC by repetitive upper arm ischemia/reperfusion improves ex vivo contractile function of human atrial trabeculae before and after hypoxia/reoxygenation. This bioassay will now permit an identification of signaling molecules in the same individual tissue.