Animals ; Humans ; Hydrogen Sulfide ; Hypertension, Pulmonary ; etiology ; pathology ; physiopathology ; Pulmonary Artery ; physiopathology ; Pulmonary Circulation

OBJECTIVETo explore the alterations in pulmonary arterial reactivity during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats.

METHODSSixty-six male Sprague-Dawley rats were randomly divided into 2 groups: bleomycin (BLM) group and sham group. The rats in BLM group were received single intratracheal instillation of BLM (5 mg/kg), and the rats in sham group received equal volume of 0.9% normal saline (NS). The alterations in pulmonary arterial reactivity were measured by vascular tension detected technique, the pathomorphological changes in the wall of pulmonary arteries were displayed with Hematoxylin-Eosin (HE) staining, the degree of fibrosis in lung was revealed with Masson staining, and the mean pulmonary arterial pressure was detected via a catheter in the pulmonary artery.

RESULTS(1) The contractile response to a- adrenoceptor agonist phenylephrine (PE), of pulmonary arteries both with remaining endothelium and with removing endothelium, from BLM-treated rats , was reduced significantly, compared with sham rats (P both < 0.05). (2) The relaxant response to the endothelially dependent vasodilator acetylcholine (Ach), of pulmonary arteries with remaining endothelium, from BLM-treated rats, was also reduced, compared with sham rats (P < 0.01). (3) In sham rats, the contractile response to (omega) -nitro-L-arginine methyl ester (L-NAME) plus PE, of pulmonary arteries with remaining endothelium, was enhanced, compared with that to PE alone (P < 0.01), while in BLM group, the contractile responses to L-NAME plus PE, of pulmonary arteries with remaining endothelium, was not different from that to PE alone (P > 0.05). (4) In BLM group, vascular endothelial cells lost. (5) In BLM group, the initial stage of fibrogenesis was observed in lungs, and the mean pulmonary arterial pressure increased, compared with that in sham group (P < 0.05).

CONCLUSIONThe abnormal responsibility of pulmonary arteries occurred during pulmonary arterial hypertension at the early-stage of pulmonary fibrosis in rats.

Animals ; Familial Primary Pulmonary Hypertension ; Hypertension, Pulmonary ; complications ; physiopathology ; Male ; Pulmonary Artery ; physiopathology ; Pulmonary Fibrosis ; complications ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Vasomotor System ; physiology

Child, Preschool ; Coronary Vessel Anomalies ; physiopathology ; Coronary Vessels ; physiopathology ; Female ; Humans ; Pulmonary Artery ; abnormalities

OBJECTIVETo investigate the imaging and hemodynamical features of pulmonary artery branches in chronic obstructive pulmonary disease (COPD) with pulmonary artery hypertension (PAH).

METHODSCT pulmonary angiography (CTPA) with ECG-gating was performed in 13 patients with clinical diagnosed COPD and 25 normal subjects. The thin-slice multiple plane reconstruction in systole and diastole phase was conducted, which in turn was used to generate the InSpace reconstructed images with reference frame of the main pulmonary artery and the first two grades branches, the contour of the branches was depicted. On the base of coordinates, the GAMBIT was used to generate nodes and furthermore meshes, then the software Fluent was used for numerical calculation and flow simulation. The velocity and pressure changes in the main pulmonary artery and the first two grades branches during different periods of cardiac cycle were observed in both groups.

RESULTCTPA showed that the diameter of the main pulmonary before bifurcate and proximal of the first two branches was larger in systole period than that in diastole period. The diameter of the second segmental artery of right upper lobe was larger during diastole period. The length of the main pulmonary and the first two branches showed no significant difference in both diastole and systole periods. There was no significant difference in length of pulmonary arteries between COPD and normal groups. The main pulmonary to distal right pulmonary artery appeared larger in diastole period. Compared with normal, in COPD group several arteries increased in diameter including proximal and distal of the proximal right pulmonary artery and the proximal right pulmonary artery during systole and diastole periods. In systole period only the diameter of the main pulmonary before bifurcate got larger and the back basic segmental artery of both lower lobe show smaller than normal. The flow condition analysis in COPD and normal groups suggested higher pressure in pulmonary arteries during systole period than that in diastole period, both groups showed high pressure area below the branching point. In COPD patients the right lower lobe artery endured the most significant pressure fall during the two periods and high pressure distributed larger area than normal. Flow velocity in main branch was faster than lower grade branches and that in systole period was faster than that in diastole period. The trend of diffusion of high pressure area was more prominent in diastole period than normal and the influence more prominent.

CONCLUSIONThe distal part of right pulmonary artery to lower lobe artery may be affected earlier when the pulmonary pressure increased. It is feasible to study the changes of flow condition in pulmonary artery branches though the combination of CTPA image and relevant software.

Adult ; Angiography ; methods ; Case-Control Studies ; Humans ; Hypertension, Pulmonary ; etiology ; physiopathology ; Middle Aged ; Pulmonary Artery ; diagnostic imaging ; physiopathology ; Pulmonary Disease, Chronic Obstructive ; complications ; physiopathology ; Tomography, Spiral Computed

OBJECTIVEPulmonary hypertension (PH) is a common complication of congenital heart defects with a left-to-right shunt characterized by high pulmonary blood flow. Pulmonary vascular structural remodeling (PVSR) is the pathological basis of PH. However, the pathophysiologic features and mechanisms responsible for PH and PVSR induced by increased pulmonary blood flow have not been fully understood. The present study was designed to explore the possible effect and mechanism of hydrogen sulfide (H(2)S) on the regulation of PVSR induced by high pulmonary flow in rats.

METHODSThirty-two male SD rats, weighing 120 - 140 g, were randomly divided into shunt group (n = 8), shunt + NaHS group (n = 8), control group (n = 8) and control + NaHS group (n = 8). Rats in shunt group and shunt + NaHS group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. Rats in the control and control + NaHS groups underwent the same experimental protocol as mentioned above except for the shunt procedure. Rats in the shunt + NaHS and control + NaHS groups were intraperitoneally injected with NaHS at 56 micromol/(kgxd), and rats in the shunt and control groups were injected with the same volume of physiological saline. After 11 weeks of experiment, rats were sacrificed and lung tissues were obtained. The percentage of muscularized artery (MA) was calculated. The changes in relative medial thickness (RMT) in small pulmonary arteries and median pulmonary arteries were examined. Proliferative cell nuclear antigen (PCNA), extracellular signal-regulated kinase (ERK1) and phosphorylation extracellular signal-regulated kinase (P-ERK1) protein expression were examined by Western blot, and at the same time, PCNA protein expression by pulmonary artery smooth muscle cells was observed by immunohistochemistry.

RESULTSAfter 11 weeks of shunt, compared with control group, the percentage of MA increased significantly (25.12 +/- 2.26 vs 14.42 +/- 3.41, P < 0.05), and RMT in small pulmonary arteries and median pulmonary arteries increased significantly in rats of shunt group (23.6 +/- 3.5 vs 12.6 +/- 2.1, 24.8 +/- 1.9 vs 13.5 +/- 2.2, P < 0.05 for all). PCNA protein expression in small and median pulmonary arteries increased significantly (0.49 +/- 0.04 vs 0.39 +/- 0.07, 0.46 +/- 0.08 vs 0.36 +/- 0.05, P < 0.01 for all), and the ratio of PERK/ERK1 protein expression of pulmonary arteries increased significantly (P < 0.01) in rats of shunt group compared with those of control group. After the administration of exogenous H(2)S donor, NaHS, for 11 weeks, in contrast to rats in shunt group, the percentage of MA decreased significantly (21.5 +/- 2.0 vs 25.1 +/- 2.3, P < 0.05), and RMT in small and median pulmonary arteries decreased significantly (20.2 +/- 2.8 vs 23.6 +/- 3.5, 20.8 +/- 3.1 vs 20.8 +/- 3.1, P < 0.05 for all) in rats of shunt + NaHS group. PCNA protein expression in small and median pulmonary artery smooth muscle cells decreased significantly (0.32 +/- 0.06 vs 0.49 +/- 0.04, 0.29 +/- 0.07 vs 0.46 +/- 0.08, P < 0.01 for all), and the ratio of PERK/ERK1 protein expression of pulmonary arteries decreased significantly (P < 0.01) in rats of shunt + NaHS group compared with that of shunt group.

CONCLUSIONH(2)S may play a regulatory role in pulmonary vascular structural remodeling induced by high pulmonary blood flow via mitogen-activated protein kinase (MAPK)/ERK signal transduction pathway.

Animals ; Hydrogen Sulfide ; pharmacology ; Hypertension, Pulmonary ; pathology ; physiopathology ; Lung ; pathology ; Male ; Pulmonary Artery ; drug effects ; physiopathology ; Rats ; Rats, Sprague-Dawley

Animals ; Hemorheology ; Isoflavones ; administration & dosage ; pharmacology ; Male ; Pulmonary Artery ; physiopathology ; Pulmonary Heart Disease ; blood ; physiopathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVEThe assessment of pulmonary vascular reactivity plays an important role in the management of idiopathic pulmonary arterial hypertension (IPAH). The aim of this study was to explore the indications and methodology of pulmonary vasodilator testing in children with IPAH.

METHODSFrom October 2009 to June 2011, a cohort of pediatric patients with IPAH in WHO functional classes II to III were enrolled in the study. Right heart catheterization was performed in all patients. After baseline hemodynamics were obtained, adenosine infusions were started at a dose of 50 µg/(kg·min), increased by 25 µg/(kg·min) at 2 min intervals to a maximum of 250 µg/(kg·min) or until a positive acute response.

RESULTSA total of 15 patients with IPAH were enrolled in the study. The mean age of the patients was 6.3 yrs. Mean pulmonary artery pressure (mPAP) was (67.1 ± 15.9) mm Hg. Pulmonary capillary wedge pressure (PCWP) was (9.7 ± 2.9) mm Hg. Pulmonary vascular resistance index (PVRI) was (17.9 ± 7.5) Wood U·m(2). Three patients were responders, defined as a fall in mPAP of at least 10 mm Hg to a pressure level of 40 mm Hg or lower. Twelve patients were nonresponders according to the same criteria. Five out of the 15 patients experienced adverse effects, including chest discomfort (n = 1), systemic hypotension (n = 3) and bradycardia (n = 1). All side effects abated within 30-60 s of the discontinuation of the adenosine infusion.

CONCLUSIONAdenosine is an effective vasodilator in children with IPAH and can be used for safe and rapid assessment of vasodilator reserve in these patients.

Adenosine ; Adolescent ; Child ; Child, Preschool ; Familial Primary Pulmonary Hypertension ; Female ; Humans ; Hypertension, Pulmonary ; physiopathology ; Infant ; Male ; Pulmonary Artery ; physiopathology ; Pulmonary Wedge Pressure ; Vascular Resistance ; Vasodilator Agents

OBJECTIVETo study the selective dilatation effects of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener, on pulmonary arterioles in hypoxic pulmonary hypertensive rat.

METHODSSD male rats were divided into 3 groups, control group, the rest were fed in hypoxic and normobaric environment (O2 10% +/- 0.5%, 8 h/d and 6 d/week) and divided into hypoxia group and hypoxia plus acetazolamide (Acz) group (hypoxic rats were treated with ig acetazolamide (Acz) 80 mg x kg(-1) d(-1)) . After 12 weeks, pulmonary arteriole rings about (197 +/- 4) microm were isolated and the tension of hypoxic pulmonary arterioles pre-contracted by 6 nmol/L endothelin-1 (FT-1) was observed with wire myograph system model (DMT 610 m). The relaxing response of hypoxic pulmonary arterioles induced by different concentration of Ipt were detected and endothelial activity was also tested by acetylcholine.

RESULTS10(-5) mol/L acetylcholine (ACh)-mediated vasodilatation was greatly reduced in the hypoxic group than those in control group (P < 0.01) and there was no significant difference between Acz treatment group and control group (P > 0.05). Ipt at the concentration ranging from 10(-11) mol/L to 10(-4) mol/L, caused dose dependent vasodilation on both hypoxic pulmonary arterioles and Acz treatment group (P > 0.05), but not on normal group.

CONCLUSIONThe endothelial function of pulmonary arterioles was damaged under hypoxic pulmonary hypertensive state, and Ipt showed selective dilatation effects on hypoxic pulmonary arterioles. Acz could improve the dysfunction of endothelial cells induced by hypoxic pulmonary hypertensive state, which didn't affect the selective dilatation effects of Ipt on hypoxic pulmonary arterioles.

Acetazolamide ; Animals ; Arterioles ; drug effects ; physiopathology ; Hypertension, Pulmonary ; physiopathology ; Hypoxia ; physiopathology ; Male ; Propylamines ; pharmacology ; Pulmonary Artery ; drug effects ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Vasodilator Agents ; pharmacology

UNLABELLEDTo explore the changes of time-dependent pulmonary artery structural remodeling in pulmonary hypertension induced by high pulmonary flow in rats.

METHODSEighty male SD rats were randomly divided into control group (n =40) and shunt group (n = 40). Rats in shunt group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. In the control group, rats experienced the same experimental processes except the shunting procedure. After 1 day, 3 days, 1 week, 4 weeks, and 8 weeks of experiment, systolic pulmonary artery pressure (SPAP) and mean pulmonary artery pressure (MPAP) of each rat were evaluated by using a right cardiac catheterization procedure. Heart tissues were separated as right ventricle (RV) and left ventricle plus septum (LV+SP), and the ratio of RV to LV+SP [RV/ (LV+ SP)] was calculated. The morphologic changes including micro- and ultra-structural changes of pulmonary arteries of rats were observed under optical microscope and electro-microscope, respectively. The percentages of muscularized artery (MA), partial muscularized artery (PMA) and non-muscularized artery (NMA) in small pulmonary arteries and median pulmonary arteries were calculated. The changes of relative medial thickness (RMT) and relative medial area (RMA) of pulmonary arteries were examined.

RESULTSCompared with control group, SPAP and MPAP did not change on day 1, day 3, and week 4. However, in week 1 and week 8 of experiment, SPAP and MPAP increased significantly (P < 0.01). Meanwhile, in week 8 of experiment, RV/ (LV+SP) increased significantly (P < 0.05). In contrast to control group, the percentages of MA, PMA, and NMA did not change in day 1, day 3 and week 1. But in week 4 and week 8, the percentages of MA and PMA increased significantly (P < 0.01) but that of NMA decreased significantly (P < 0.01). RMT and RMA did not change in day 1, day 3, week 1 and even week 4 in shunt group as compared with those of control group, but they increased significantly in week 8 (P < 0.05). The changes of ultra-structure of pulmonary arteries included that endothelial cells became swollen and large in size on day 3, smooth muscular cells increased in size besides the change of endothelial cells in week 1, and they changed from contractile phenotype to synthetic phenotype in week 4. Collagen deposited in pulmonary arteries markedly in week 8.

CONCLUSIONPulmonary artery structural remodeling develops in a time-dependent manner. Endothelial cells of pulmonary arteries become swollen firstly, followed by the proliferation of smooth muscular cells and finally by remodeling of extra cellular matrix.

Animals ; Blood Pressure ; Hypertension, Pulmonary ; pathology ; physiopathology ; Male ; Pulmonary Artery ; pathology ; ultrastructure ; Pulmonary Circulation ; Random Allocation ; Rats ; Rats, Sprague-Dawley

AIMTo study human urotensin II (hUII) expression in intrapulmonary arteries of rats with pulmonary hypertension induced by high pulmonary blood flow and explore the role of hU II in the development of pulmonary hypertension induced by left to right shunt.

METHODSAortocaval shunting was produced for 11 weeks in rats. Pulmonary artery mean pressure (PAMP) of each rat was evaluated using right cardiac catheterization. The pulmonary vascular structural changes, including the percentage of muscularized arteries of small pulmonary vessels and relative medial thickness of intra-acinar pulmonary arteries were examined. Meanwhile, the expression of hU II by pulmonary arteries was detected by immunohistochemistry.

RESULTSAfter 11-week aortocaval shunting, PAMP was significantly increased. The percentage of muscularized arteries of small pulmonary vessels and relative medial thickness of pulmonary arteries were obviously increased in shunting rats compared with controls (P < 0.01, respectively). Meanwhile, hU II expression by pulmonary artery endothelial cells and smooth muscle cells was significantly augmented in rats of shunt group, which was positively correlated with PAMP and the structural changes in pulmonary arteries.

CONCLUSIONThe up-regulation of hU II in pulmonary arteries might be involved in the development of pulmonary vascular structural remodeling and pulmonary hypertension induced by high pulmonary blood flow.

Animals ; Humans ; Hypertension, Pulmonary ; metabolism ; Male ; Pulmonary Artery ; metabolism ; physiopathology ; Pulmonary Circulation ; Rats ; Rats, Sprague-Dawley ; Urotensins ; metabolism