title: Increased diastolic time fraction as beneficial adjunct of alpha1-adrenergic receptor blockade after percutaneous coronary intervention.
abstract: The effect of alpha1-receptor blockade with urapidil on coronary blood flow and left ventricular function has been attributed to relief of diffuse coronary vasoconstriction following percutaneous coronary intervention (PCI). We hypothesized that an increase in diastolic time fraction (DTF) contributes to the beneficial action of urapidil. In eleven patients with a 63% (SD 13) diameter stenosis, ECG, aortic pressure (Pa) and distal intracoronary pressure (Pd), and blood flow velocity were recorded at baseline and throughout adenosine-induced hyperemia. Measurements were obtained before and after PCI and after subsequent alpha1-receptor blockade with urapidil (10 mg ic). DTF was determined from the ECG and the Pa waveform. Functional parameters such as coronary flow velocity reserve, fractional flow reserve, and an index of hyperemic microvascular resistance (HMR) were assessed. Urapidil administration after PCI induced an upward shift in the DTF-heart rate relationship, resulting in a 3.1% (SD 2.7) increase in hyperemic DTF at a constant heart rate (P < 0.005) due to a shorter duration of systole. Hyperemic Pa and Pd decreased, respectively, by 6.1% (SD 6.6; P < 0.05) and 5.7% (SD 5.8; P < 0.01) after alpha1-blockade. Although epicardially measured functional parameters were on average not altered by alpha1-blockade due to concurrent changes in pressure and heart rate, HMR decreased by urapidil in those patients where coronary pressure remained constant. In conclusion, alpha1-receptor blockade after PCI produced a modest but significant prolongation of DTF at a given heart rate, thereby providing an adjunctive beneficial mechanism for improving subendocardial perfusion, which critically depends on DTF.
authors.affiliation: Department of Biomedical Engineering & Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Christina
authors.initials: C
authors.lastname: Kolyva
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Verhoeff
authors.forename: Jos A E
authors.initials: JA
authors.lastname: Spaan
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.forename: Maria
authors.initials: M
authors.lastname: Siebes
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001794:Blood Pressure / Q000187:drug effects; D003131:Combined Modality Therapy; D003326:Coronary Circulation / Q000187:drug effects*; D023921:Coronary Stenosis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D003971:Diastole / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C015568:urapidil