Dose-Response Head-to-Head Comparison of Inodilators Dobutamine, Milrinone, and Levosimendan in Chronic Experimental Pulmonary Hypertension

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Tavares Silva, M (Author) FMUP; Alaa, M (Author) Other; Leite, S (Author) FMUP; Oliveira Pinto, J (Author) FMUP; Lopes, L (Author) Other; Leite-Moreira AF (Author) FMUP; Andre P Lourenco (Author) FMUP

Journal

Title: Journal of Cardiovascular Pharmacology and Therapeutics

Vol. 22

Pages: 485-495

ISSN: 1074-2484

Publisher: SAGE

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 17 Citations

Other information

Authenticus ID: P-00M-XB6

DOI: 10.1177/1074248417696818

Abstract (EN): The choice of inodilator drug in the acute management of patients with pulmonary hypertension (PH) having right ventricular (RV) failure remains unsettled and challenging. Comprehensive experimental evaluations may provide further insight and fundamental translational research clues to support inodilator selection and clinical trial design. Our aim was to compare acute dose-response hemodynamic effects of inodilators dobutamine (DOB), milrinone (MIL), and levosimendan (LEV) in chronic experimental PH. Seven-week-old male Wistar rats were randomly injected with 60 mgkg(-1) monocrotaline (MCT) or vehicle (Ctrl, n = 7) and underwent systemic and pulmonary artery (PA) pressure and RV pressure-volume (PV) hemodynamic evaluation under halogenate anesthesia 24 to 30 days after injection. The MCT-injected animals (n = 7 each) randomly received dose-response infusions of DOB (1, 3, 6 and 12 gkg(-1)min(-1)), MIL (MIL: 1, 3, 6 and 12 gkg(-1)min(-1)), or LEV (0.3, 0.6, 1.2 and 2.4 gkg(-1)min(-1)). Load-independent indexes were obtained by inferior vena cava occlusion at baseline and after the last dose. All inodilators increased RV ejection fraction, preload recruitable stroke work, and ventricular-vascular coupling without jeopardizing perfusion pressure. Dobutamine raised heart rate and PA pressure. Only LEV increased cardiac index and decreased PA elastance and pulmonary vascular resistance (PVR). Moreover, only LEV downward-shifted the end-diastolic PV relationship, thereby improving RV compliance. Adding sildenafil to LEV further decreased PVR. Levosimendan had beneficial acute systolic and diastolic functional effects in experimental chronic PH and RV afterload compared to DOB and MIL. It should be further tested in clinical trials enrolling patients with PH in the perioperative and critical care settings.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11