Small Animal Hemodynamic Core

The Small Animal Hemodynamic core, led by Dr. Iain Scott, specializes in acquisition and analysis of hemodynamic data obtained during survival and terminal studies of rat and murine models. Our team consists of surgeons, bioengineers, and technicians who have extensive experience with the design, implementation, analysis, and reporting of such studies.

Our core has streamlined the small animal hemodynamic study process, from protocol conception to final printout, to ensure generation of traceable and reproducible analysis of complex data.

Common survival procedures performed by our surgeons include pulmonary artery banding and transverse aorta constriction.  Terminal procedures include open- and closed-chest hemodynamic assessment of the right ventricle, left ventricle, pulmonary artery, and aorta. Pressure -volume loop measurements acquired via our EMKA system and high-fidelity admittance catheters, along with Doppler velocities acquired via Indus Industries system, can produce in-depth and customized characterization of a rodent’s hemodynamic phenotype.

For further consultation, please contact Dr. Iain Scott.

For procedure scheduling, please contact Jeffrey Baust or Andrea Sebastiani.

Facilities

The Hemodynamic Sub-Core is located within the Vascular Medicine Institute, Department of Medicine at the University of Pittsburgh on the 12th floor of the Biomedical Science Tower East. The Core Facility has the technology and infrastructure in place necessary to acquire direct pressure-volume measurements using Transonic catheters and Doppler flow analyses. The core has two full-equipped stations dedicated exclusively to hemodynamic studies in rodents. The Core has binocular Stereo Zoom Microscopes with Single Arm Boom Stand with halogen dissection lights, rodent ventilators (Harvard Instruments), Advantage Pressure Volume Measurement Systems (Science) with dedicated computers, and Doppler Signal Processing Workstation (Indus Instruments).

Rodent Models of PH, PAH, and Heart Remodeling

The Core has been instrumental for the establishment of multiple models of PAH in mice and rats including PA banding, Hypoxia exposure, Monocrotaline, Sugen/Hypoxia that closely recapitulate the pathogenesis and clinical outcome of human disease, and more importantly, have proven value in evaluating novel therapies.

Publications/Abstracts that involved the Core

Sharifi-Sanjani M, Shoushtari AH, Quiroz M, Baust J, Sestito SF, Mosher M, Ross M, McTiernan CF, St Croix CM, Bilonick RA, Champion HC, Isenberg JS. (2014). Cardiac CD47 drives left ventricular heart failure through Ca2+-CaMKII-regulated induction of HDAC3. J Am Heart Assoc. 3(3):e000670. PMID 24922625. PMC4309049.

Frazziano G, Al Ghouleh I, Baust J, Shiva S, Champion HC, Pagano PJ. (2014).  Nox-derived ROS are acutely activated in pressure overload pulmonary hypertension: indications for a seminal role for mitochondrial Nox4. Am J Physiol Heart Circ Physiol. 306(2):H197-205. PMID 24213612. PMC3920131. DOI:10.1152/ajpheart.00977.2012 

Kelley EE, Baust J, Bonacci G, Golin-Bisello F, Devlin JE, St Croix CM, Watkins SC, Gor S, Cantu-Medellin N, Weidert ER, Frisbee JC, Gladwin MT, Champion HC, Freeman BA, Khoo NK. (2014). Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity. Cardiovasc Res. 101(3):352-63. PMID 24385344. PMC3928004. DOI:10.1093/cvr/cvt341

Ratt NJ, Taabima DM, Specht PA, Tejero J, Champion HC, Kim-Shapiro DB, Baust J, Mik EG, Hildesheim M, Stasch JP, Becker EM, Truebel H, Gladwin MT. (2013). Direct sGC activation bypasses NO scavenging reactions of intravascular free oxy-hemoglobin and limits vasoconstriction. Antioxid Redox Signal. PMID 23697678. PMIC3869448. DOI:10.1089/ars.2013.5181 

Weidert ER, Cantu-Medellin N, Schoenborn, SO, Khoo NK, CHampion HC, Baust J, Devlin J, Tarpey MM, St Croix CM, Kelley EE. (2013). P4: Nitrite-mediated, xanthine oxidase-dependent diminution of obesity-related hyperglycemia and cardiopulmonary dysfunction. Nitric Oxide. 31:S14–S15. DOI:10.1016/j.niox.2013.02.006 

Lai YC, Tabima DM, Baust J, Dube JJ, Chacon A, Alvarez-Perez JC, Goodpaster BH, Garcia-Ocaña A, Tofovic S, Mora AL, Gladwin MT. (2013). P47: AMPK activation by nitrite and metformin increases glut-4 mediated glucose uptake and normalizes pulmonary venous hypertension in a rat model of severe metabolic syndrome. Nitric Oxide. 31:S33–S34. DOI:10.1016/j.niox.2013.02.049 

Gor S, Kelley EE, Baust J, Bonnaci GR, Golin-Bisello F, Cantu-Medellin N, Devlin J, St Croix SM, Watkins SC, Champion HC, Freeman BA, Khoo NK. (2012). Inhibition of Obesity-Induced Pulmonary Arterial Hypertension by Electrophilic Fatty Acids. Free Radical Biology and Medicine. 53:S96. DOI:10.1016/j.freeradbiomed.2012.10.174

Cantu-Medellin N, Khoo NK, Shoenborn CJ, Weidert ER, Baust J, Champion HC, Tarpey MM, Kelley EE. (2012). Manipulation of Xanthine Oxidase-Derived Reactive Species Reduces Obesity-Induced Inflammation and Impairment of Glucose Tolerance. Free Radical Biology and Medicine. 53:S95-S96. DOI:10.1016/j.freeradbiomed.2012.10.173

Hill MR, Simon MA, Valdez-Jasso D, Zhang W, Champion HC, Sacks MS. (2014). Structural and mechanical adaptations of right ventricle free wall myocardium to pressure overload. Ann Biomed Eng. 42(12):2451-65. PMID:25164124. PMC4241140. doi: 10.1007/s10439-014-1096-3.

Meng Q, Lai YC, Kelly NJ, Bueno M, Baust JJ, Bachman TN, Goncharov D,Vanderpool RR, Radder JE, Hu J, Goncharova E, Morris AM, Mora AL, Shapiro SD, Gladwin MT. Development of a Mouse Model of Metabolic Syndrome, Pulmonary Hypertension, and Heart Failure with Preserved Ejection Fraction. Am J Respir Cell Mol Biol. 2017 Apr;56(4):497-505. doi: 10.1165/rcmb.2016-0177OC. PubMed PMID: 28118022; PubMed Central PMCID: PMC5449511.

Goncharov DA, Goncharova EA, Tofovic SP, Hu J, Baust JJ, Pena AZ, Ray A, Rode A, Vanderpool RR, Mora AL, Gladwin MT, Lai YC. Metformin Therapy for Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection Fraction versus Pulmonary Arterial Hypertension. Am J Respir Crit Care Med. 2018 Sep 1;198(5):681-684. doi: 10.1164/rccm.201801-0022LE. PubMed PMID: 29727194; PubMed Central PMCID: PMC6118018.

Kudryashova TV, Goncharov DA, Pena A, Kelly N, Vanderpool R, Baust J, Kobir A, Shufesky W, Mora AL, Morelli AE, Zhao J, Ihida-Stansbury K, Chang B, DeLisser H, Tuder RM, Kawut SM, Silljé HH, Shapiro S, Zhao Y, Goncharova EA. HIPPO-Integrin-linked Kinase Cross-Talk Controls Self-Sustaining Proliferation and Survival in Pulmonary Hypertension. Am J Respir Crit Care Med. 2016 Oct 1;194(7):866-877. PubMed PMID: 27119551; PubMed Central PMCID: PMC5074651.

Kelly NJ, Radder JE, Baust JJ, Burton CL, Lai YC, Potoka KC, Agostini BA, Wood JP, Bachman TN, Vanderpool RR, Dandachi N, Leme AS, Gregory AD, Morris A, Mora AL, Gladwin MT, Shapiro SD. Mouse Genome-Wide Association Study of Preclinical Group II Pulmonary Hypertension Identifies Epidermal Growth Factor Receptor. Am J Respir Cell Mol Biol. 2017 Apr;56(4):488-496. doi: 10.1165/rcmb.2016-0176OC. PubMed PMID: 28085498; PubMed Central PMCID: PMC5449510.

Pena A, Kobir A, Goncharov D, Goda A, Kudryashova TV, Ray A, Vanderpool R, Baust J, Chang B, Mora AL, Gorcsan J 3rd, Goncharova EA. Pharmacological Inhibition of mTOR Kinase Reverses Right Ventricle Remodeling and Improves Right Ventricle Structure and Function in Rats. Am J Respir Cell Mol Biol. 2017 Nov;57(5):615-625. doi: 10.1165/rcmb.2016-0364OC. PubMed PMID: 28679058; PubMed Central PMCID: PMC5705904.

Potoka KP, Wood KC, Baust JJ, Bueno M, Hahn SA, Vanderpool RR, Bachman T, Mallampalli GM, Osei-Hwedieh DO, Schrott V, Sun B, Bullock GC, Becker-Pelster EM, Wittwer M, Stampfuss J, Mathar I, Stasch JP, Truebel H, Sandner P, Mora AL, Straub AC, Gladwin MT. Nitric Oxide-Independent Soluble Guanylate Cyclase Activation Improves Vascular Function and Cardiac Remodeling in Sickle Cell Disease. Am J Respir Cell Mol Biol. 2018 May;58(5):636-647. doi: 10.1165/rcmb.2017-0292OC.  PubMed PMID: 29268036.

Rogers NM, Sharifi-Sanjani M, Yao M, Ghimire K, Bienes-Martinez R, Mutchler SM, Knupp HE, Baust J, Novelli EM, Ross M, St Croix C, Kutten JC, Czajka CA, Sembrat JC, Rojas M, Labrousse-Arias D, Bachman TN, Vanderpool RR, Zuckerbraun BS, Champion HC, Mora AL, Straub AC, Bilonick RA, Calzada MJ, Isenberg JS. TSP1-CD47 signaling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction. Cardiovasc Res.2017 Jan;113(1):15-29. doi: 10.1093/cvr/cvw218. Epub 2016 Oct 13. PubMed PMID: 27742621; PubMed Central PMCID: PMC5220673.

Lee VG, Johnson ML, Baust J, Laubach VE, Watkins SC, Billiar TR. The roles of iNOS in liver ischemia-reperfusion injury. Shock. 2001 Nov;16(5):355-60. PubMed PMID: 11699073.