The Time Profile Of Mast Cells Accumulation And Pulmonary Vascular Remodeling In Pulmonary Hypertension Owing To Left Heart Disease

[Background and purposes]Pulmonary hypertension owing to left heart disease (PH-LHD) belongs to thesecond major type of pulmonary hypertension(PH),which is very common in theclinical practice. Both of its mechanisms and pathophysiology remain unclear,sothere is no specific treatment for its therapy.According to the latest research,not onlymast cell accumulation and pulmonary vascular remodeling were observed throughthe model animal，but also proved that the mast cells played a critical role as a catalystfor pulmonary vascular remodeling,and its accumulation and degranulation behavioris closely linked to the pulmonary hypertension pathogenesis and pathologicalprogress. While the use of mast cell stabilizer(antagonize the mast cells aggregationand degranulation) can alleviate or relieve pulmonary hypertension and pulmonaryvascular remodeling.Therefore,intervention and treatment for mast cells is about tocreate a brand new promising and strategic way for the treatment of pulmonaryhypertension.But for the clinical implementation of the mast cells treatment forpulmonary hypertension,there are still many problems need to be solved,such as theresearch for the reverse timing of pulmonary hypertension,the right timing ofmedication and treatment.The purpose of this research is to find out the time profile ofmast cells accumulation and pulmonary vascular remodeling in pulmonaryhypertension owing to left heart disease,which will be the theoretical basis andfoundation of treatment through the mast cell ways for pulmonary hypertension.[Methods]Juvenile SD rat (body weight90.17±8.81g) model of PH-LHD was induced bysupracoronary aortic banding.On d1、d3、d5、d8、d15、d22、d36、d50、d64aftertreatment,hemodynamics data for heart rate,artery pressure,change rate of right ventricular pressure,blood gas analysis was chronologically collected.At each timepoint, lung tissues were fixed by4%paraformaldehyde through pulmonary artery andleft atrium cannulation and prepared for pathological slides with HE and TB staining.Mast cell accumulation and degranulation were observed by blinded analysis of lungtissues pathological slides under microscopy.Pulmonary vascular remodeling wasanalyzed employing computerized morphometric system (QWin; Leica).The tendencychart of PH,pulmonary vascular remodeling and mast cell activities weredemonstrated to elucidate the correlation among PH, pulmonary vascular remodelingand mast cell activities.Rats without any treatment on d0and rats undergone shamoperation on d64were used as controls.[Result]1.On d64,unchanged artery pressure,increased right ventricular pressure,medialthickening in pulmonary arterioles, and medial muscularize of pulmonary arterioleswith diameter20-50μm,reduced pulmonary arteriole lumen size were observed,indicating rat model of PH-LHD was successfully induced.2.Variation tendency from d1to d64(1) Hemodynamic change: right ventricular pressure increased from d15.(2) Pulmonary vascular remodeling:Medial thickening was mainly observed inpulmonary arterioles with diameter <100μm. Medial thickening was seen inpulmonary arterioles with diameter50-100μm and20-50μm from d15and d50respectively. Medial muscularize of pulmonary arterioles and reduced pulmonaryarteriole lumen size were mainly observed in arterioles with diameter20-50μm.Arterioles Muscularize deteriorated with time,. reduced pulmonary arteriole lumensize was seen since d50.(3) Mast cell activities: Obvious mast cell agregation was observed since d36inperivasular area of pulmonary arterioles with diameter <100μm, and most cells weredegranulated. The increased density of mast cells in whole lung tissue were observed.Mast cell agregation was observed since d50in perivasular area of pulmonaryarterioles with diameter>100μm, and most cells were granulated. [conclusion]1. Supracoronary aortic banding is an ideal treatment to establish PH-LHD rat model.2. During process of PH-LHD rat model establishment, mast cell agregation andpulmonary vascular remodeling are mutually promoted and closely associated.Mastcell agregation and pulmonary vascular remodeling of pulmonary arterioles withdiameter <100μm play major roles in PH-LHD development of rat model whilepulmonary arterioles with diameter>100μm presents small impact.3. D15after supracoronary aortic banding is a key time point of hemodynamic change.Thus the best time to apply intervention treatment of mast cells or Mast cell-derivedmediators on PH-LHD rat model will be earlier than two weeks after treatment.