Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice

Abstract

The function of the right heart is to pump blood through the lungs, thus linking right heart physiology and pulmonary vascular physiology. Inflammation is a common modifier of heart and lung function, by elaborating cellular infiltration, production of cytokines and growth factors, and by initiating remodeling processes 1 .Compared to the left ventricle, the right ventricle is a low-pressure pump that operates in a relatively narrow zone of pressure changes. Increased pulmonary artery pressures are associated with increased pressure in the lung vascular bed and pulmonary hypertension 2 . Pulmonary hypertension is often associated with inflammatory lung diseases, for example chronic obstructive pulmonary disease, or autoimmune diseases 3 . Because pulmonary hypertension confers a bad prognosis for quality of life and life expectancy, much research is directed towards understanding the mechanisms that might be targets for pharmaceutical intervention 4 . The main challenge for the development of effective management tools for pulmonary hypertension remains the complexity of the simultaneous understanding of molecular and cellular changes in the right heart, the lungs and the immune system.Here, we present a procedural workflow for the rapid and precise measurement of pressure changes in the right heart of mice and the simultaneous harvest of samples from heart, lungs and immune tissues. The method is based on the direct catheterization of the right ventricle via the jugular vein in close-chested mice, first developed in the late 1990s as surrogate measure of pressures in the pulmonary artery [5][6][7][8][9][10][11][12][13] . The organized team-approach facilitates a very rapid right heart catheterization technique. This makes it possible to perform the measurements in mice that spontaneously breathe room air. The organization of the work-flow in distinct work-areas reduces time delay and opens the possibility to simultaneously perform physiology experiments and harvest immune, heart and lung tissues.The procedural workflow outlined here can be adapted for a wide variety of laboratory settings and study designs, from small, targeted experiments, to large drug screening assays. The simultaneous acquisition of cardiac physiology data that can be expanded to include echocardiography 5,14-17 and harvest of heart, lung and immune tissues reduces the number of animals needed to obtain data that move the scientific knowledge basis forward. The procedural workflow presented here also provides an ideal basis for gaining knowledge of the networks that link immune, lung and heart function. The same principles outlined here can be adapted to study other or additional organs as needed. Video LinkThe video component of this article can be found at

Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension

“…3 mg/kg/day) has been used previously to successfully attenuate liver fibrosis in mice [ 20 ]. Mice were then placed under surgical anesthesia (Avertin) and RVSP measured through a catheter introduced into the right heart through the right jugular vein in a closed-chested procedure, as previously described [ 22 ]. After sacrifice by exsanguination under tribromoethanol or pentobarbital anesthesia, tissues were collected for further analysis.…”

Modification of Hemodynamic and Immune Responses to Exposure with a Weak Antigen by the Expression of a Hypomorphic BMPR2 Gene

“…The analysis was performed without prior knowledge of group designation of the mice [62] using a protocol developed in Dr. West's laboratory [22]. Mice were anaesthetized by intraperitoneal injection of Avertin (tribromoethanol, Sigma-Aldrich, up to 500 mg/kg).…”

“…Bronchoalveolar lavage and tissue harvest was performed as described [3], [27]–[30], [62]. Briefly, a tracheal catheter was inserted and bronchoalveolar lavage (BAL) was performed by gently washing with three 1 ml aliquot of Hanks Balanced Salt solutions.…”

Interleukin 13– and Interleukin 17A–Induced Pulmonary Hypertension Phenotype Due to Inhalation of Antigen and Fine Particles from Air Pollution

“…2B, 2C ) Functional evaluation and tissue collection RVSP was measured after inserting a catheter via the jugular vein in anaesthetized, spontaneously breathing mice. 40,44 Right ventricular hypertrophy was determined as right ventricular weight relative to the weight of the left ventricle and septum. 44 Bronchoalveolar lavage (BAL) and tissue harvest were performed after right heart catheterization and euthanasia of animals.…”