title: Ranolazine injection into coronary or femoral arteries exerts marked, transient regional vasodilation without systemic hypotension in an intact porcine model.
abstract: BACKGROUND
  We examined whether intracoronary or intrafemoral administration of ranolazine produces local vasodilation.
  
  
  RESULTS
  Effects of intra-arterial ranolazine on coronary and femoral artery vasodilation and systemic hemodynamic function were studied in anesthetized pigs (n=27). Ranolazine, nitroglycerin, or saline (control) was injected into the left anterior descending (LAD) coronary artery or femoral artery (2-mL bolus in 10 seconds). Pretreatment with prazosin (300 μg/kg IV) allowed determination of α(1)-adrenergic receptor involvement (n=8). Rapid intracoronary administration of ranolazine (0.048 mg/kg) to achieve high local concentrations resulted in 91±11% increase in LAD coronary artery flow and 39±7% reduction in coronary vascular resistance (both, P<0.0001). This effect lasted 2-3 minutes without change in heart rate or rate-pressure product. Mean arterial pressure decreased marginally (by 2±1 mm Hg, P=0.01). Maximum systemic plasma concentration (0.93±0.29 μmol/L) remained in subtherapeutic range. Pretreatment with prazosin abolished these effects. Intracoronary nitroglycerin (100 μg) increased LAD coronary artery flow by 112±25% (P=0.02), but the effect lasted <2 minutes; mean arterial pressure decreased by 4±1 mm Hg (P=0.01). Intrafemoral injection of ranolazine (0.24 mg/kg, ie, one-tenth of the systemic bolus) resulted in a 70±19% increase in femoral artery flow (P=0.05) and 26±5% reduction in femoral artery resistance (P=0.004). At 2 minutes after the injection, the femoral flow remained 16±9% above the baseline and dilatory effects occurred without tolerance to repeated injections.
  
  
  CONCLUSIONS
  Intracoronary or intrafemoral ranolazine bolus exerts a marked, 2- to 3-minute dilatory effect that is comparable to nitroglycerin in magnitude but more persistent, attributable primarily to α(1)-adrenergic blockade.
authors.affiliation: Harvard Medical School, Beth Israel Deaconess Medical Center, Harvard-Thorndike Electrophysiology Institute, 99 Brookline Ave, Boston, MA 2215, USA.
authors.forename: Tuomo
authors.initials: T
authors.lastname: Nieminen
authors.forename: Caio A M
authors.initials: CA
authors.lastname: Tavares
authors.forename: José R M
authors.initials: JR
authors.lastname: Pegler
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.forename: Richard L
authors.initials: RL
authors.lastname: Verrier
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage* / Q000009:adverse effects; D058646:Adrenergic alpha-1 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects; D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005263:Femoral Artery / Q000378:metabolism; D006801:Humans; D023421:Models, Animal; D005996:Nitroglycerin / Q000008:administration & dosage / Q000009:adverse effects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011224:Prazosin / Q000008:administration & dosage / Q000009:adverse effects; D000069458:Ranolazine; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000083:Acetanilides; D058646:Adrenergic alpha-1 Receptor Agonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D000069458:Ranolazine; D005996:Nitroglycerin; D011224:Prazosin