title: Sildenafil after cardiac arrest and infarction; an experimental rat model.
abstract: OBJECTIVE
  Resuscitation after cardiac arrest may lead to ischemia-reperfusion injury and infarction. We evaluated whether sildenafil, a phosphodiesterase-5 inhibitor, has an impact on recovery after cardiac arrest in a rat cardiac transplantation model.
  
  
  METHODS
  Sixty-one Fischer344 rats underwent syngeneic heterotopic cardiac transplantation after ischemia and ligation of the left anterior coronary artery of the heart to yield myocardial infarction (IRI + MI). Of these, 22 rats received subcutaneously injected sildenafil (1 mg/kg/day) (IRI +MI + S). Twenty-three additional grafted animals with transplantation only served as controls with ischemia reperfusion injury (IRI). After 2 days, immunohistochemistry for eNOS, and RT-PCR for iNOS and Aquaporin-7 were performed after graft harvesting and histology.
  
  
  RESULTS
  Two days after transplantation, remote intramyocardial arteries were more preserved in IRI + MI + S as compared with IRI +MI and IRI (0.74 ± 0.14, 0.56 ± 0.23 and 0.55 ± 0.22, PSU, p < 0.05, respectively). Decreased eNOS staining confirmed the presence of developing infarction in IRI + MI and IRI + MI + S. The expression of iNOS was significantly lower during IRI + MI +S as compared with IRI + MI (0.02 ± 0.01 and 1.02 ± 0.02, FC, p < 0.05).
  
  
  CONCLUSIONS
  Administered at the onset of reperfusion and developing infarction, sildenafil has an impact on myocardial recovery after cardiac arrest and ischemia.
authors.affiliation: Heart Center, Cardiac Research, Tampere University Hospital and Tampere University, Finland. ari.mennander@sydankeskus.fi
authors.forename: Ari A
authors.initials: AA
authors.lastname: Mennander
authors.forename: Vilma
authors.initials: V
authors.lastname: Vuohelainen
authors.forename: Riikka S
authors.initials: RS
authors.lastname: Aanismaa
authors.forename: Susanna
authors.initials: S
authors.lastname: Narkilahti
authors.forename: Timo
authors.initials: T
authors.lastname: Paavonen
authors.forename: Matti
authors.initials: M
authors.lastname: Tarkka
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000235:genetics; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006323:Heart Arrest / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology; D016027:Heart Transplantation; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D009203:Myocardial Infarction / Q000150:complications*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: C491926:Aqp7 protein, rat; D020346:Aquaporins; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat