title: Right ventricular end-diastolic stiffness heralds right ventricular failure in monocrotaline-induced pulmonary hypertension.
abstract: Recent studies suggest right ventricular (RV) stiffness is important in pulmonary hypertension (PH) prognosis. Smaller stroke volume (SV) variation after a certain RV end-diastolic pressure (EDP) respiratory variation as assessed by spectral transfer function (STF) may identify RV stiffness. Our aim was to evaluate RV stiffness in monocrotaline (MCT)-induced PH progression and to validate STF gain between EDP and SV as marker of stiffness. Seven-week-old male Wistar rats randomly injected with 60 mg/kg MCT or vehicle were divided into three groups (n = 12 each) according to cardiac index (CI): controls (Ctrl), preserved CI (MCT pCI), and reduced CI (MCT rCI). All underwent RV pressure-volume (PV) evaluation 24-34 days after MCT, under halogenate anesthesia and constant positive-pressure ventilation. End-diastolic stiffness (βi), end-systolic elastance (Eesi), arterial elastance for indexed volumes (Eai), and preload recruitable stroke work (PRSW) were obtained and beat-to-beat fluctuations during ventilation assessed by STF. Eaiwas the strongest determinant of CI, alongside βibut not PRSW. MCT rCI showed impaired ventricular-vascular coupling (VVC) and higher βi, along with low end-diastolic pressure (EDP) and stroke volume index (SVi) STF gain, denoting impaired preload reserve. On multivariate analysis βiand not Eesicorrelated with EDP-SViSTF gain (P < 0.001). Receiver-operating characteristics (ROC) curve analysis of EDP-SViSTF gain showed an area under curve of 0.84 for βiprediction (P = 0.002). Afterload, impaired VVC and RV stiffness are major players in RV failure. RV stiffness can be assessed by STF gain analysis of respiratory fluctuations between EDP and SVi, which may constitute a prognostic tool in PH.
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Cardiothoracic Surgery, Suez Canal University, Ismailia, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Alaa
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; Division of Cardiology, Medical University of Graz, Graz, Austria.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abdellatif
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Cardiology, Hospital São João, Porto, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Tavares-Silva
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Vascular Surgery, Hospital São João, Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Oliveira-Pinto
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Lucas
authors.initials: L
authors.lastname: Lopes
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Leite
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Cardiothoracic Surgery, Hospital São João, Porto, Portugal; and.
authors.forename: Adelino F
authors.initials: AF
authors.lastname: Leite-Moreira
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Anesthesiology, Hospital São João, Porto, Portugal aplourenco@yahoo.com.
authors.forename: André P
authors.identifier: 0000-0002-5756-9535
authors.initials: AP
authors.lastname: Lourenço
mesh_terms: D000818:Animals; D003971:Diastole; D004548:Elasticity; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D015999:Multivariate Analysis; D012372:ROC Curve; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume; D059289:Vascular Stiffness; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology*; D017725:Ventricular Pressure
chemical_list: D016686:Monocrotaline
keywords: diastolic dysfunction; pulmonary hypertension; right ventricular failure; spectral transfer function analysis