title: Postischemic left ventricular dysfunction is abolished by alpha-adrenergic blocking agents.
abstract: OBJECTIVE
  We sought to evaluate the efficacy of alpha-adrenergic blocking agents in counteracting left ventricular (LV) dysfunction occurring after transient ischemia in humans.
  
  
  BACKGROUND
  The mechanisms underlying postischemic LV dysfunction are largely unknown.
  
  
  METHODS
  Percutaneous transluminal coronary angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. In 50 patients undergoing coronary stenting for 77+/-5% stenosis, LV function was monitored by transesophageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 microg/kg body weight of the alpha-blocker phentolamine intracoronarily, 15 patients received 600 microg/kg of the alpha1-blocker urapidil intravenously, 10 patients received the combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10 patients received saline.
  
  
  RESULTS
  Fifteen minutes after successful coronary dilation, significant contractile dysfunction occurred in previously ischemic and nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coronary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34+/-9% to 45+/-8% and to 49+/-8%, respectively (p < 0.05). After the administration of propranolol combined with phentolamine, LV dysfunction remained unchanged (34+/-6%), as in control subjects.
  
  
  CONCLUSIONS
  LV dysfunction occurs after PTCA, as described in animal models after ischemia. Alpha-blockers abolished LV, macrocirculatory and microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by combining alpha- and beta-blockers. The evidence of diffuse rather than regional dysfunction, together with the opposite effects of alpha- and beta-blockade, supports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction.
authors.affiliation: Clinica Medica Generale, Ospedale Maggiore-IRCCS, University of Milano, Italy. gregorm@imiucca.csi.unimi.it
authors.forename: L
authors.initials: L
authors.lastname: Gregorini
authors.forename: J
authors.initials: J
authors.lastname: Marco
authors.forename: C
authors.initials: C
authors.lastname: Palombo
authors.forename: M
authors.initials: M
authors.lastname: Kozàkovà
authors.forename: G B
authors.initials: GB
authors.lastname: Anguissola
authors.forename: B
authors.initials: B
authors.lastname: Cassagneau
authors.forename: M
authors.initials: M
authors.lastname: Bernies
authors.forename: A
authors.initials: A
authors.lastname: Distante
authors.forename: I
authors.initials: I
authors.lastname: Marco
authors.forename: J
authors.initials: J
authors.lastname: Fajadet
authors.forename: A
authors.initials: A
authors.lastname: Zanchetti
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D017548:Echocardiography, Transesophageal; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology / Q000628:therapy; D015607:Stents; D014655:Vascular Resistance / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000317:Adrenergic alpha-Antagonists