Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet

The overall goal of this procedure is to create a reliable and reproducible piglet model of chronic thromboembolic pulmonary hypertension to study the mechanisms of chronic right ventricular dysfunction. This is accomplished by first performing a ligation of the left main pulmonary artery in a three week old piglet. In the second step, the mean pulmonary vascular resistance is increased by a progressive obstruction of the pulmonary vascular bed.

Next, the right ventricular function is assessed by echocardiography, and the tight ventricular pulmonary arterial coupling is measured by right ventricular pressure volume loop assessment In the final step, fresh right ventricular tissue is harvested through endo myocardial biopsies. Ultimately, the resting pulmonary and right ventricular remodeling can be assessed by histological analysis. This model can answer key questions regarding the underlying mechanisms of red ventrical dysfunctions, such as what factors play a role in the metabolic or mi choal disorders of cardiomyocytes.

Before beginning the procedure, place a continuous monitoring device on a three week old anesthetized piglet. Insert a catheter in the piglet's ear vein and inject anesthetics. And then under e iconography guidance, insert an arterial fluid field catheter through the carotid artery to monitor the systemic arterial pressure.

Next, with the piglet in the left side lying position, shave the operative area and disinfect the skin with an alcohol solution. Then to ligate the left pulmonary artery, open the chest through a five to 10 centimeter left lateral thoracotomy in the fourth intercostal space, taking care not to go behind the tip of the scapula and carefully retract the lung towards the diaphragm. When the ideal surgical window has been located, retract the left ous vein, then dissect the main left pulmonary artery, followed by ligation with a non-absorbable 2.0 silk.

Taking care not to open the pericardium cardium under fluoroscopic guidance. Insert a five French angiographic catheter through the eight French sheath until the right pulmonary artery, until the tip of the catheter is in a segmental lower lobe pulmonary artery. When the catheters are in place, inject 0.2 to 0.4 milliliters of freshly prepared pulmonary artery embolization material into the pulmonary artery.

Then assess the tolerance of the embolization by measuring the mean pulmonary artery pressure to mean systemic blood pressure ratio. Do not repeat the embolization. If the oxygen saturation is less than 90%the mean systemic blood pressure drops under 60 millimeters of mercury and or the cardiac output is under two liters per minute.

The mean pulmonary pressure must increase by 10 millimeters of mercury. To perform a hemodynamic assessment, install the piglet in a supine position, place continuous monitoring as previously shown, and catheterize the piglet under general anesthesia. Insert a 10 French catheter percutaneously in the superior vena cava and place a seven French swan gans catheter into the pulmonary artery trunk.

Then inject 10 milliliters of four degrees Celsius saline solution through the Swan gans catheter to assess the cardiac output. To assess the right ventricle by echocardiography. Install the piglet in the supine position.

Then perform a transthoracic echocardiography according to the human guidelines for right ventricle screening. Recording the video loops during an end expiratory pause for pressure volume loop assessment under general anesthesia with continuous monitoring. Insert an arterial eight French catheter into the right or left carotid artery and an angiographic catheter into the left ventricle.

Then insert a 12 French sheath into the inferior vena cava and eight French into the right or left femoral artery and an arterial pico catheter into the right or left femoral artery. Next, perform the pressure and volume calibration of the conductance probe according to the manufacturer's recommendations. To measure the blood resistivity, harvest five milliliters of arterial blood, de air the syringe and fill the probe.

Then insert the conductance catheter into the right ventricle through the nine French sheath in the superior vena cava. Using fluoroscopic guidance, introduce the tip of the catheter into the apex of the right ventricle and insert as much of the catheter as possible into the rest of the ventricle. After confirming that the volume segments of the probe are in diastole and systole phase by the good shape of the loop, insert an expendable balloon into the inferior vena CVA through the femoral vein, placing the extremity just below the right atrium.

Then record the pressure volume loops of the right ventricle under basal conditions and during inferior vena CVA occlusion for endo myocardial biopsy of the right ventricle percutaneously. Insert a 10 French sheath into the superior vena CVA and a seven French swan gans probe and a long 7.5 French catheter sheath into the right atrium. When the tip of the Swan gans probe is in place within the right ventricle, inflate the balloon of the probe and push the long sheath catheter within the right ventricle against the balloon.

Then deflate the balloon and remove the probe leaving the long sheath catheter in place. Finally, insert a biot into the long sheath and perform endo myocardial biopsies under echo graphic fluoroscopic and EKG control as demonstrated in this intraoperative view, an increase of the systemic vasculature of the lung and bronchial circulation hypertrophy was noted in the obstructed left lung right lower lobe and mediastinal pleura territories large and numerous submucosal. Bronchial small arteries were also observed in the obstructive left lung and right lower lobe as well.

Reflecting an increase in angiogenesis in these areas post obstructive pulmonary vasculopathy with media hypertrophy was also found in the obstructed areas of the left lung and right lower lobe with overflow vasculopathy observed in the non-obstructive areas of the right upper lobe. As these images illustrate a chronic obstruction of the right lower pulmonary artery lobe by an unresolved thrombus of end butyl two cyanoacrylate and fibrin was also evident six weeks later. The right ventricle and atrial areas, right ventricle diameters and right ventricle wall thicknesses were increased after repeated embolizations.

A significant enlargement of the right ventricle associated with right ventricular hypertrophy was noted intraoperatively. This increase in right ventricular hypertrophy correlated with an increase in the mean pulmonary arterial pressure. Further pressure volume analysis revealed an impaired function of the right ventricle with an accompanying decrease in the ventricular arterial coupling a after its development.

This model part the way for researcher in the field of T neurological dysfunction to explore metabolic and mitochondrial disorders, and also to allow many clinical therapeutic studies.