Chronic in utero mitral inflow obstruction unloads left ventricular volume in a novel late gestation fetal lamb model.

Autor:	Onohara D; Structural Heart Research and Innovation Laboratory, Carlyle Fraser Heart Center at Emory University Hospital Midtown, Atlanta, Ga.; Division of Cardiothoracic Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, Ga., Hagen M; Center for Development Health, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Ore., Louey S; Center for Development Health, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Ore., Giraud G; Center for Development Health, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Ore.; Department of Cardiology, Portland Veterans Affairs Medical Center, Portland, Ore., Jonker S; Center for Development Health, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Ore., Padala M; Structural Heart Research and Innovation Laboratory, Carlyle Fraser Heart Center at Emory University Hospital Midtown, Atlanta, Ga.; Division of Cardiothoracic Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, Ga.
Jazyk:	angličtina
Zdroj:	JTCVS open [JTCVS Open] 2023 Oct 04; Vol. 16, pp. 698-707. Date of Electronic Publication: 2023 Oct 04 (Print Publication: 2023).
DOI:	10.1016/j.xjon.2023.09.036
Abstrakt:	Objective: The in utero no flow/no grow hypothesis postulates that reduced inflow of blood into the left ventricle due to a stenotic mitral valve could lead to ventricular hypoplasia and hypoplastic left heart syndrome. This has been demonstrated in chick embryos, but less so in large animals. We investigated the impact of mitral obstruction on left and right ventricular growth in fetal lambs. Methods: Twelve pregnant ewes, most bearing twins, were instrumented at 119 ± 1 days gestational age. Carotid artery and jugular vein catheters, an ascending aorta flow probe, and a left atrial deflated balloon catheter were implanted into 1 fetus (left atrial balloon group), and the twin remained an uninstrumented control. The balloon was inflated gradually over 8 days until net antegrade aortic flow was eliminated. Fetal transesophageal echocardiography was performed at the time of surgery and just before termination in both groups. Results: Terminal fetal body weights were comparable between groups. Terminal heart/body weight ratio was higher in left atrial balloon group fetuses (6.9 ± 0.8 g/kg) compared with controls (5.9 ± 0.6 g, P  = .0126). The left ventricular/right ventricular weight ratio was 24% ( P  = .0077) lower in left atrial balloon group fetuses than in controls. Left ventricular/heart weight (0.24 ± 0.04 g/g vs 0.30 ± 0.04 g/g, P  = .0009), left ventricular end-diastolic volume (2.3 ± 0.7 mL vs 7.1 ± 0.8 mL; P  = .0012), and left ventricular end-systolic volume (1.01 mL [0.95-1.95 mL] vs 3.38 mL [3.28-3.57 mL], P  = .0042) were lower in left atrial balloon group fetuses compared with controls. Right ventricular weight (g/kg), right ventricular end-diastolic volume, and right ventricular end-systolic volume were similar between groups. Conclusions: In this late-gestation fetal lamb model, in utero obstruction of mitral inflow slowed left ventricular growth and caused right ventricular remodeling. Competing Interests: M.P. reports stock ownership, board directorship, and employment in Nyra Medical Inc; receives personal consulting fees from Heart Repair Technologies and research grants from Heart Reparit Technologies; received Single Ventricle Blue Sky grant from Additional Ventures; and led this work when he was at Emory University. D.O. received personal consulting fees from Nyra Medical Inc. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest. (© 2023 The Author(s).)
Databáze:	MEDLINE
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