title: Effects of sildenafil on myocardial blood flow in humans with ischemic heart disease.
abstract: BACKGROUND
  We tested the hypothesis that sildenafil increases myocardial dilator reserve in humans with ischemic heart disease.
  
  
  METHODS
  Positron emission tomography measured myocardial blood flow in 14 patients with ischemic heart disease. Patients were studied twice, in double-blind, placebo-control, cross-over design with sildenafil (or placebo) given approximately 2-3 h before measurements of hemodynamics and myocardial blood flow: at rest, with cold pressor stress and with adenosine. All myocardial segments of each patient with myocardial blood flow <1.65 ml/min per g with adenosine under placebo conditions were combined into one abnormal zone for that patient. Segments with myocardial blood flow >1.65 ml/min per g were averaged and combined into a normal zone for that patient.
  
  
  RESULTS
  At rest, rate pressure product (heart rate x systolic arterial pressure, mmHg/min) was comparable, as was abnormal zone myocardial blood flow (ml/min per g; 0.76+/-0.48 placebo versus 0.64+/-0.20 sildenafil, both P=NS; mean+/-SD). Both rate pressure product and myocardial blood flow increased (P<0.01) with cold pressor stress (11+/-3 K and 1.14+/-0.59 placebo versus 10+/-3 K and 1.21+/-0.62 sildenafil). However, sildenafil failed to improve the myocardial blood flow response to cold pressor stress in abnormal or normal zones. In contrast, abnormal zone myocardial blood flow reserve with adenosine and sildenafil (2.6+/-0.7) exceeded that with adenosine and placebo (2.0+/-1.3, P<0.04, paired sign test).
  
  
  CONCLUSIONS
  Sildenafil improves myocardial blood flow dilator response to adenosine in abnormal zones, possibly by augmenting nitric oxide-mediated increases in cGMP because adenosine response in part is nitric oxide dependent. Failure to improve myocardial blood flow response to cold pressor stress suggests that alpha-adrenergic constriction may offset enhanced nitric oxide effects. Clinically, the data suggest sildenafil may exert an anti-ischemic effect in patients with coronary artery disease.
authors.affiliation: Department of Medicine (Cardiac Unit), Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.forename: Kusai
authors.initials: K
authors.lastname: Aziz
authors.forename: Raymond
authors.initials: R
authors.lastname: Migrino
authors.forename: Justyna
authors.initials: J
authors.lastname: Watkowska
authors.forename: Randall
authors.initials: R
authors.lastname: Zusman
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Alpert
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: Henry
authors.initials: H
authors.lastname: Gewirtz
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001794:Blood Pressure; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D004311:Double-Blind Method; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*; D010879:Piperazines / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate