title: Chronic overcirculation-induced pulmonary arterial hypertension in aorto-caval shunt.
abstract: Pulmonary arterial hypertension is a common complication of congenital heart defects with left-to-right shunts. Current preclinical models do not reproduce clinical characteristics of shunt-related pulmonary hypertension. Aorto-caval shunt was firstly described as a model of right ventricle volume overload. The pathophysiology and the possible determination of pulmonary arterial hypertension of different periods of shunt exposure are still undefined. A method to create standardized, reproducible aorto-caval shunt was developed in growing rats (260±40 g). Three groups of animals were considered: shunt exposure for 10 weeks, shunt exposure for 20 weeks and control (sham laparotomy). Echocardiography and magnetic resonance revealed increased right ventricular end diastolic area in shunt at 10 weeks compared to control. Hemodynamic analysis demonstrated increased right ventricular afterload and increased effective pulmonary arterial elastance (Ea) in shunt at 20 weeks compared to control (1.29±0.20 vs. 0.14±0.06 mmHg/μl, p=0.004). At the same time point, the maximal slope of end-systolic pressure-volume relationship (Ees) decreased (0.5±0.2 mmHg/ml vs. 1.2±0.3, p<0.001). Consequently, right ventricular-arterial coupling was markedly deteriorated with a ≈50% decrease in the ratio of end-systolic to pulmonary artery elastance (Ees/Ea). Finally, left ventricular preload diminished (≈30% decrease in left ventricular end-diastolic volume). Histology demonstrated medial hypertrophy and small artery luminal narrowing. Chronic exposure to aorto-caval shunt is a reliable model to produce right ventricular volume overload and secondary pulmonary arterial hypertension. This model could be an alternative with low mortality and high reproducibility for investigators on the underlying mechanisms of shunt-related pulmonary hypertension.
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, University of Verona Verona, Italy. Electronic address: alessio.rungatscher@univr.it.
authors.forename: Alessio
authors.initials: A
authors.lastname: Rungatscher
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, University of Verona Verona, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Linardi
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, University of Verona Verona, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Milani
authors.affiliation: Division of Cardiology, University of Novara Novara, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Ucci
authors.affiliation: Department of Neurological and Movement Sciences, University of Verona Verona, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Nicolato
authors.affiliation: Department of Neurological and Movement Sciences, University of Verona Verona, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Merigo
authors.affiliation: Department of Neurological and Movement Sciences, University of Verona Verona, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Salvetti
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, University of Verona Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mazzucco
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, University of Verona Verona, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Luciani
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, University of Verona Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Faggian
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001794:Blood Pressure; D004195:Disease Models, Animal; D004452:Echocardiography; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply; D008279:Magnetic Resonance Imaging; D008297:Male; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013318:Stroke Volume; D018608:Ultrasonography, Doppler; D066253:Vascular Remodeling
keywords: Aorto-caval shunt; Experimental model; Pressure-volume loops; Pulmonary arterial hypertension; Rats; Right ventricle overload; Vascular remodeling; Ventricular interdependence; Ventricular vascular coupling; Volume overload