Nitroglycerin does not Interfere with Protection by Remote Ischemic Preconditioning in Patients with Surgical Coronary R
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LETTER TO THE EDITOR
Nitroglycerin does not Interfere with Protection by Remote Ischemic Preconditioning in Patients with Surgical Coronary Revascularization under Isoflurane Anesthesia Petra Kleinbongard & Matthias Thielmann & Heinz Jakob & Jürgen Peters & Gerd Heusch & Eva Kottenberg
Published online: 26 February 2013 # Springer Science+Business Media New York 2013
Remote ischemic preconditioning (RIPC) of the myocardium by repeated brief limb ischemia/reperfusion reduces damage from myocardial ischemia/reperfusion. Such protection strategy has been successfully translated from the experiment to clinical use [1–3]. However, the transfer of the protective signal from the ischemic/reperfused limb to the heart remains unknown. Endogenous nitric oxide (NO) is a potential trigger and mediator of pre- and postconditioning [4]. Exogenous NO prior to ischemia attenuates the consequences of myocardial ischemia/reperfusion [5, 6]. Nitroglycerin is a NO releasing drug and used to reduce
P. Kleinbongard : G. Heusch Institute for Pathophysiology, University of Duisburg-Essen, Essen, Germany M. Thielmann : H. Jakob Department of Thoracic and Cardiovascular Surgery, University of Duisburg-Essen, Essen, Germany J. Peters : E. Kottenberg Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany P. Kleinbongard (*) Institut für Pathophysiologie, Universitätsklinikum Essen, Hufelandstr. 55, 45122 Essen, Germany e-mail: [email protected]
preload and consequently cardiac output and blood pressure in various clinical settings, including coronary artery bypass graft (CABG) surgery. We now hypothesized that, if NO is the transfer signal from limb to heart, nitroglycerin via release of NO might induce protection per se and possibly attenuate further protection by RIPC. We have therefore analyzed the effects of concurrent intravenous infusion with nitroglycerin, administered after anesthetic induction but before aortic crossclamping at the discretion of the anesthesiologist to non-diabetic patients undergoing CABG surgery during isoflurane anesthesia with and without RIPC. With approval of the local ethics committee and patients’ written informed consent we retrospectively analyzed in a randomized, single-blind, placebo-controlled study (ClinicalTrials.gov NCT01406678) 176 non-diabetic patients undergoing CABG surgery between July 2008 and August 2012. General anesthesia was induced with sufentanil (1 μg/kg), etomidate (0.3 mg/kg) and rocuronium (0.6 mg/kg) and maintained with isoflurane (0.6 – 1.0 % end-tidal). Troponin I (cTnI) serum concentrations (baseline, and 1, 6, 12, 24, 48, and 72 h postoperatively) were measured to reflect myocardial damage. The RIPC protocol consisted of 3 cycles of 5 min left upper arm ischemia/5 min reperfusion and was compared to Control (cuff left uninflated) [7–9]. Patients were categorized as with or without nitroglycerin after induction of anesthesia until cardiopulmonary bypass.
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Cardiovasc Drugs Ther (2013) 27:359–361
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