title: Maintenance of physiological coronary endothelial function after 3.3 h of hypothermic oxygen persufflation preservation and orthotopic transplantation of non-heart-beating donor hearts.
abstract: OBJECTIVE
  The use of non-heart-beating donors (NHBD) might increase the number of grafts available for transplantation. Experiments on heart transplantation from NHBDs demonstrated the necessity for oxygenation during preservation to allow sufficient myocardial recovery. It has been shown that, after 16 min normothermic ischemia followed by 3.3-h hypothermic preservation, excellent myocardial and cardiovascular recovery is attained, if coronary oxygen persufflation (COP) is included in the preservation protocol. Here tests are presented on the recovery of coronary endothelium derived relaxation (EDR) of NHBD hearts after preservation including COP.
  
  
  METHODS
  After 16 min normothermic ischemia, pig hearts were stored for 3.3 h at 0-1 degrees C in modified HTK plus COP (mBHTK+COP, n=6) or in two control groups without COP: (1) with mBHTK (n=6); and (2) with HTK (n=4). Following orthotopic transplantation and 3 h of reperfusion with full blood, coronary EDR was tested in vitro using Substance P (SP) under indomethacin for prostaglandin blockage. Additional tests were performed adding L-NIL to block the NO-production by iNOS or L-NNA to block total NO production.
  
  
  RESULTS
  The EDR in percent of precontraction was 78 +/- 7% after mBHTK+COP and 77 +/- 20% (mBHTK) or 72 +/- 7% (HTK) in the controls without significant differences between the groups. Physiologic values of normal coronaries were 75 +/- 9%. L-NIL for blockage of NO-production by iNOS resulted in unchanged relaxations. After blockage of total NO production by L-NNA, the SP-induced dilation was significantly reduced to 58 +/- 8% (mBHTK+COP) and to 48 +/- 8% (mBHTK) or 55 +/- 13% (HTK) in the controls.
  
  
  CONCLUSIONS
  Even after 16 min of warm ischemia followed by 3.3 h of preservation with gaseous oxygen persufflation, orthotopic transplantation, and reperfusion the endothelium derived coronary dilatation was unchanged from physiologic values and similar to the controls without COP. Blockage of NO production by L-NNA resulted in equal values of EDR with or without COP, while blockage of NO production by iNOS did not influence the EDR reaction. Thus COP preservation, which has been shown to allow excellent recovery of preserved NHBD hearts, caused no damage to the coronary EDR mechanisms.
authors.affiliation: Institute of Experimental Medicine, University of Cologne, Robert-Koch-Str 10, 50931 Cologne, Germany. jh.fischer@uni-koeln.de
authors.forename: Jürgen H
authors.initials: JH
authors.lastname: Fischer
authors.forename: Claudia
authors.initials: C
authors.lastname: Funcke
authors.forename: Goichi
authors.initials: G
authors.lastname: Yotsumoto
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jeschkeit-Schubbert
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Kuhn-Régnier
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000502:physiology*; D015237:Dinoprost / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D015199:Extracorporeal Membrane Oxygenation; D006324:Heart Arrest, Induced; D016027:Heart Transplantation; D006979:Hyperthermia, Induced; D019520:Living Donors; D009200:Myocardial Contraction / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D015237:Dinoprost