Hypoplastic left heart syndrome and ventricular remodelling after surgical norwood procedures: Role of stem cells in cardiac hypertrophy

Objective: The Norwood procedure is a surgical technique which separates the two circulations and transforms the right ventricle in a systemic ventricle with ventricular and parietal remodelling in Hypoplastic Left Heart Syndrome hearts. Recently it has been demonstrated that cardiac hypertrophy is the result of ventricular remodelling which involves cardiac stem cells and myocyte regeneration. The purpose was to analyze the right ventricular remodelling, in a group of patients (pts) affected by Hypoplastic Left Heart Syndrome who died after Norwood surgical procedure carried out with two different procedures: the Blalock-Taussig shunt (BT) and the Sano procedures. Myocytes, extra-cellular matrix and stem cells were considered to define ventricular remodelling. Material and methods. Two groups of pts were studied: 5 pts with BT procedures (age 10\u2013210 days 9; 6 pts with Sano procedures (age 9 \u2013365 days). Six pts with normal hearts were considered as control group (age 2\u2013390 days). Inflow and outflow right ventricle samples were evaluated with histology, immunohistochemistry and morphometry to assess myocyte diameters, fibrosis, type I and III collagen, and presence and stem cells phenotype. Results. Myocyte diameters were 10,74\ub11,99; 10,23\ub12,1; 5,77\ub10,23 micron in BT, Sano and Controls respectively ( p = 0,008 BT vs Controls). Fibrosis was in percentage 16,15\ub15,22; 29,4\ub16,84; 13,05\ub18,36 in BT, Sano and Controls respectively; inflow and outflow: p = 0,006 BT vs Sano; p = 0,004 Sano vs Controls. Collagen I was higher in BT compared with Sano (60,1\ub127,23; 44,98\ub126,71 respectively, p = 0,035) and Controls, while collagen III was higher in Sano than in the BT and Controls. As regards stem cells, only c-Kit, CD105 positive cells were found in Norwood. Conclusions. Stem cells localized both in the interstitial space and in the vessels endothelium and were mainly endothelial precursors cells. Fibrous tissue was higher in Sano pts and in the last type III collagen was increased with an increased number of stem cells. These preliminary data suggest that stem cells contribute in particular to extra-cellular matrix and that Sano procedure produces a worse right ventricular remodelling with a possible earlier and more severe haemodynamic and electrical instability