The importance of capillary density–stroke work mismatch for right ventricular adaptation to chronic pressure overload
Authors: Benoit Decante
Julien Guihaire
Jennifer Arthur-Ataam
Pierre-Emmanuel Noly
Peter Dorfmüller
Fanny Loisel
Elie Fadel
François Haddad
Nathaniel Langer
Lilia Lamrani
Olaf Mercier
Journal: Journal of Thoracic and Cardiovascular Surgery (2017)
Discipline: CLINICAL MEDICINE
Keywords: adaptive remodeling; angiogenesis; fibrosis; pulmonary hypertension; right ventricle.
Affiliations: School of Medicine, Paris-Sud University and Paris-Saclay University, Kremlin-Bicêtre, France; Research and Innovation Unit, Marie Lannelongue Hospital, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, DHU Thorax Innovation, Marie Lannelongue Hospital, Le Plessis Robinson, France., Research and Innovation Unit, Marie Lannelongue Hospital, Le Plessis Robinson, France; Division of Cardiovascular Medicine, Stanford University, Palo Alto, Calif., Research and Innovation Unit, Marie Lannelongue Hospital, Le Plessis Robinson, France; INSERM UMR-S 999, LabEx LERMIT, Marie Lannelongue Hospital, Le Plessis Robinson, France., School of Medicine, Paris-Sud University and Paris-Saclay University, Kremlin-Bicêtre, France; Research and Innovation Unit, Marie Lannelongue Hospital, Le Plessis Robinson, France., School of Medicine, Paris-Sud University and Paris-Saclay University, Kremlin-Bicêtre, France; Research and Innovation Unit, Marie Lannelongue Hospital, Le Plessis Robinson, France; INSERM UMR-S 999, LabEx LERMIT, Marie Lannelongue Hospital, Le Plessis Robinson, France; Department of Pathology, Marie Lannelongue Hospital, Le Plessis Robinson, France., Research and Innovation Unit, Marie Lannelongue Hospital, Le Plessis Robinson, France., Research and Innovation Unit, Marie Lannelongue Hospital, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, DHU Thorax Innovation, Marie Lannelongue Hospital, Le Plessis Robinson, France., School of Medicine, Paris-Sud University and Paris-Saclay University, Kremlin-Bicêtre, France; Research and Innovation Unit, Marie Lannelongue Hospital, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, DHU Thorax Innovation, Marie Lannelongue Hospital, Le Plessis Robinson, France; INSERM UMR-S 999, LabEx LERMIT, Marie Lannelongue Hospital, Le Plessis Robinson, France., School of Medicine, Paris-Sud University and Paris-Saclay University, Kremlin-Bicêtre, France; Research and Innovation Unit, Marie Lannelongue Hospital, Le Plessis Robinson, France; Department of Thoracic and Vascular Surgery and Heart-Lung Transplantation, DHU Thorax Innovation, Marie Lannelongue Hospital, Le Plessis Robinson, France; INSERM UMR-S 999, LabEx LERMIT, Marie Lannelongue Hospital, Le Plessis Robinson, France. Electronic address: .

Abstract:  Objective: Mechanisms of right ventricular (RV) adaptation to chronic pressure overload are not well understood. We hypothesized that a lower capillary density (CD) to stroke work ratio would be associated with more fibrosis and RV maladaptive remodeling. Methods: We induced RV chronic pressure overload over a 20-week period in 2 piglet models of pulmonary hypertension; that is, a shunt model (n = 5) and a chronic thromboembolic pulmonary hypertension model (n = 5). We assessed hemodynamic parameters and RV remodeling as well as RV CD, fibrosis, and angiogenic factors expression. Results: Although RV was similarly hypertrophied in both models, maladapted RV remodeling with impaired systolic function was only seen in chronic thromboembolic pulmonary hypertension group members who had lower CD (484 ± 99 vs 1213 ± 74 cap/mm2; P &lt; .01), lower CD to stroke work ratio (0.29 ± 0.07 vs 0.82 ± 0.16; P = .02), higher myocardial fibrosis (15.4% ± 3.8% vs 8.0% ± 2.5%; P &lt; .01), as well as a higher angiogenic and fibrosis factors expression. Conclusions: The RV adaptive response to chronic pressure overload differs between 2 different piglet models of PH. Mismatch between angiogenesis and workload (CD to stroke work ratio) was associated with greater degree of myocardial fibrosis and RV dysfunction and could be a promising index of RV maladaptation. Further studies are needed to understand the underlying mechanisms. 

Retracted: No

PubPeer comments:
 Dear authors, Could you please check Fig. 4: The WesternBlot contains 4 lanes for CTEPH (1 marker lane?), 3 lanes for SHUNT and 3 bands for SHAM = 10 lanes. The GAPDH control however only shows 8 lanes. Could you please explain. ![file] , 
 It has been more than 1 year since pointing out the above issue, could the authors and the journal please take action. ,