title: Atrial natriuretic peptide protects against ischemia-reperfusion injury in the isolated rat heart.
abstract: BACKGROUND
  Atrial natriuretic peptide (ANP), a stimulator of particulate guanylate cyclase, has been found to protect against reoxygenation-induced hypercontracture in isolated cardiomyocytes by increasing cyclic guanosine monophosphate synthesis. The purpose of this study was to investigate the cardioprotective effects of ANP against ischemia-reperfusion injury in isolated rat hearts.
  
  
  METHODS
  Twenty-four hearts were perfused with ANP at 0.01, 0.1, and 1 micromol/L or without ANP (n = 6 each) in normoxic conditions. Because 0.1 micromol/L ANP induced a threefold increase in cyclic guanosine monophosphate release into the coronary effluent without any effect on cardiac function, we used the 0.1 micromol/L ANP dose for ischemia-reperfusion studies. Eighteen hearts were subjected to 15 minutes of normothermic global ischemia followed by 15 minutes of reperfusion. The hearts were divided into three groups (n = 6 each).
  
  
  RESULTS
  In group 1, ANP was added before ischemia. In group 2, ANP was added to the reperfusate. Hearts were untreated in the control group. In group 1, the postischemic recovery of cardiac output, coronary flow, and cyclic guanosine monophosphate release was similar to the control group. In group 2, the recovery of cardiac output was significantly better than the control group (82.1% +/- 9.8% vs 61.8% +/- 6.8%, respectively, p < 0.01) with a similar trend to recovery of coronary flow (90.7% +/- 8.5% vs 79.3% +/- 11.8%, respectively). The improved cardiac function was closely related to a significant increase in postischemic cyclic guanosine monophosphate release.
  
  
  CONCLUSIONS
  Administration of ANP at the time of reperfusion protects the myocardium from ischemia-reperfusion injury. The concentrations of administration must not only increase the release of cyclic guanosine monophosphate release, but also lack negative inotropic effects.
authors.affiliation: Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sangawa
authors.forename: Koji
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Kozo
authors.initials: K
authors.lastname: Ishino
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawada
authors.forename: Shunji
authors.initials: S
authors.lastname: Sano
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D009320:Atrial Natriuretic Factor