title: Hemodynamic effects of the new antiarrhythmic agent restacorin in patients with normal and decreased left ventricular function.
abstract: The hemodynamic and pharmacokinetic effects of the novel class 1c antiarrhythmic drug restacorin were investigated in two groups of patients. Group I consisted of 5 patients with normal left ventricular (LV) function, and group II consisted of 10 patients with mild heart failure [New York Heart Association (NYHA) II; mean LV ejection fraction 33 +/- 6%]. The study had an open label, baseline-controlled, single-dose design. Restacorin was infused in a total dosage of 1.2 mg/kg. In group I, the only significant change as compared with baseline findings was a 25% increase in right atrial pressure. In group II; cardiac output (CO), dP/dt, and stroke work index (SWI) decreased significantly (-18, -11, and -24%, respectively). In addition, a significant 32% increase was noted in pulmonary artery wedge pressure (PAWP), and a 27% increase occurred in systemic vascular resistance (SVR). No changes were observed in heart rate (HR) or mean arterial blood pressure (MAP). CO and SVR at baseline correlated with the average plasma concentrations (r = -0.65 and p = 0.009 and r = 0.56 and p = 0.028 respectively). Creatinine clearance was inversely correlated to the restacorin plasma concentration (r = -0.51, p = 0.05). The half-life (t1/2) elimination time of restacorin was 2.60 h for group I, and 4.06 h for group II. Clearance was 51.4 and 32.2 L.h-1, respectively. Restacorin appears to be well tolerated in patients with normal LV function. The drug is not recommended for use in patients with reduced LV function because of its moderate negative inotropic effect.
authors.affiliation: Department of Cardiology, University Hospital, Groningen, The Netherlands.
authors.forename: Y S
authors.initials: YS
authors.lastname: Tuininga
authors.forename: H J
authors.initials: HJ
authors.lastname: Crijns
authors.forename: B
authors.initials: B
authors.lastname: Oosterhuis
authors.forename: A C
authors.initials: AC
authors.lastname: Wiesfeld
authors.forename: L M
authors.initials: LM
authors.lastname: van Wijk
authors.forename: F
authors.initials: F
authors.lastname: Albronda
authors.forename: H
authors.initials: H
authors.lastname: de Bruin
authors.forename: J H
authors.initials: JH
authors.lastname: Jonkman
authors.forename: C
authors.initials: C
authors.lastname: Kozma
authors.forename: K I
authors.initials: KI
authors.lastname: Lie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D006146:Guanidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006333:Heart Failure / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D006146:Guanidines; C059816:restacorin