Acute Effects of “Delayed Postconditioning” With Periodic Acceleration After Asphyxia Induced Shock in Pigs

0031-3998/08/6405-0533 PEDIATRIC RESEARCH Copyright © 2008 International Pediatric Research Foundation, Inc. Vol. 64, No. 5, 2008 Printed in U.S.A. Acute Effects of “Delayed Postconditioning” With Periodic Acceleration After Asphyxia Induced Shock in Pigs JOSE A. ADAMS, JORGE A. BASSUK, JAQUELINE ARIAS, HENG WU, VINOD JORAPUR, GERVASIO A. LAMAS, AND PAUL KURLANSKY Divisions of Neonatology [J.A.A., J.A.B., J.A., H.W.], and Cardiology [V.J., G.A.L.], Mt Sinai Medical Center, Miami Beach, Florida 33140; Florida Heart Research Institute [P.K.], Miami, Florida 33137 to its initiation immediately upon reperfusion. Clearly, it would be desirable if a method were available which did not have such rigorous time constraints Whole body periodic acceleration (pGz) might serve such a purpose. The application of pGz, sinusoidal head to foot motion produces pulsatile shear stress to the vascular endothelium. This causes release of endothelial derived vasoactive and cardioprotective substances, such as endothelial derived nitric oxide (eNO), prostaglandins, tissue plasminogen activator (t-PA), and adrenomedullin into the circulation (3,16 –19). These substances have been found to be cardioprotective in several ischemia reperfusion models (20 –33). The purpose of this study was to demonstrate the acute benefits of pGz as a means of delayed post C in CPR after asphyxia induced shock, e.g. institution of pGz 15 min after ROSC. These benefits include improved acute post resuscitation myocardial stunning and regional blood flows as well as decreased post resuscitation inflammatory cytokine surge and neutrophil infiltration. ABSTRACT: Asphyxia cardiac arrest and shock are models for whole body ischemia reperfusion injury. Periodic acceleration (pGz) achieved by moving the body on a platform is a novel method for inducing pulsatile vascular shear stress and endogenous production of endothelial nitric oxide, prostaglandin E2, tissue plasminogen activator, and adrenomedullin. The aforementioned are cardioprotective during and after ischemia reperfusion injury. We investigated whether pGz, applied 15 min after return of spontaneous circulation (ROSC) would serve as an effective “delayed” post conditioning tactic to lessen acute reperfusion injury markers in a pediatric swine model of asphyxia induced shock. Asphyxia shock was induced in 20 swine weight 3.9 ⫾ 0.6 kg. Fifteen minutes after ROSC, the animals were randomized to receive conventional mechanical ventilation (CMV, [Control]) or CMV with pGz. All animals had ROSC and no significant differences in blood gases or hemodynamics after ROSC. pGz treated had significantly less myocardial dysfunction post resuscitation, (i.e. better % ejection fraction (EF), % fractional shortening (FS), and wall motion score index) and lower biochemical indices of reperfusion injury (lower TNF-␣, IL-6, and Troponin I, and myeloperoxidase activity). Delayed postconditioning with pGz ameliorates acute post resuscitation reperfusion injury and improves myocardial dysfunction after asphyxia-induced shock. (Pediatr Res 64: 533–537, 2008) METHODS ardiac arrest is a model of whole body ischemia reperfusion injury (1–3). In the pediatric population, asphyxial cardiac arrest is one of the commonest causes of cardiac arrest, and is becoming a more frequently recognized cause in adults (4 – 6). Acute post arrest reperfusion injury is characterized by similar functional and biochemical changes, which occur after reperfusion injury. Post resuscitation myocardial dysfunction, inflammatory cascade activation, tissue injury, and reactive oxygen species activation are hallmarks of reperfusion injury (7–12). Postconditioning (Post C) performed immediately upon reperfusion, by pharmacological or mechanical methods ameliorates reperfusion injury (13–15). Postconditioning is accomplished by brief interruptions in reperfusion of the target organ, (ischemia Post C) or by ischemia of remote organs (remote Post C). Ischemia or remote postconditioning can only be performed under controlled circumstances owing Animal preparation. The Institutional Animal Care and Use Committee of Mount Sinai Medical Center of Greater Miami approved all animal studies in compliance with the Animal Welfare Act. Twenty male Yorkshire juvenile pigs weighing 4 ⫾ 0.7 kg (age 2–3 mos) were used in this study. The animals were initially anesthetized with ketamine (10 mg/kg, intramuscularly) and maintained in a surgical plane of anesthesia with intravenous propofol. An airway was established by direct laryngoscopy and intubation carried out with a 5.0 mm cuffed endotracheal tube. The animals were paralyzed with pancuronium bromide (0.1 mg/kg) and ventilated with a volume ventilator (Puritan Bennett, Pleasanton, CA) at 10 mL/kg tidal volume to achieve normal arterial carbon dioxide tension. FiO2 was maintained at 0.21. Intravascular catheters were placed into the femoral artery to measure systemic blood pressure by connecting the fluid filled catheter to a pressure transducer (Transpac, Abbott Critical Care Systems, North Chicago, IL). A right atrial catheter was placed via the left external jugular vein for administration of fluids and drugs and the measurement of right atrial pressure. Arterial blood gases and electrolytes were measured using a blood gas analyzer (Rapid Lab TM348, Bayer Diagnostics, Tarrytown, NY). A left ventricular catheter was placed via the right carotid artery, and location confirmed by typical left ventricular waveforms, echocardiography and post mortem, for microsphere injections. An 5.5 F balloon-tipped flow-directed thermodilution pulmonary arterial catheter (OpticomTM, Abbot Laboratories, Chicago, IL) was inserted via the right Received March 6, 2008; accepted May 29, 2008. Correspondence: Jose A. Adams, M.D., Mt. Sinai Medical Center, Division of Neonatology, 3-BLUM, 4300 Alton Road, Miami Beach, FL 33140; e-mail: Supported by a Grant in Aid from the American Heart Association No. 0555133, and the Florida Heart Research Institute. Abbreviations: CPR, cardiopulmonary resuscitation; CMV, conventional mechanical ventilation; EF, ejection fraction; eNO, endothelial nitric oxide; FS, fractional shortening; MPO, myeloperoxidase; pGz, periodic acceleration; Post C, postconditioning; ROSC, return of spontaneous circulation; WMSI, wall motion score index C 533 534 ADAMS ET AL. jugular vein and floated into the pulmonary artery under direct pressure monitoring for measurements of pulmonary arterial pressure, right atrial pressure, core body temperature and cardiac output. Placement was confirmed by the typical wave form of the pulmonary artery, and further confirmed at necropsy. The cardiac output was determined by thermodilution in triplicate using ice-cold saline. Body temperature was maintained between 37 and 39°C by means of heating pad. A standard 3-lead electrocardiogram (ECG) configuration was continuously monitored. Platform design. The motion platform, which imparts w (...truncated)