Abstract
Cardiovascular diseases are still the first leading cause of death and morbidity in developed countries. Experimental cardiology research and preclinical drug development in cardiology call for appropriate and especially clinically relevant in vitro and in vivo studies. The use of animal models has contributed to expand our knowledge and our understanding of the underlying mechanisms and accordingly provided new approaches focused on the improvement of diagnostic and treatment strategies of various cardiac pathologies.
Numerous animal models in different species as well as in small and large animals have been developed to address cardiovascular complications, including heart failure, pulmonary hypertension, and thrombotic diseases. However, a perfect model of heart failure or other indications that reproduces every aspect of the natural disease does not exist. The complexity and heterogeneity of cardiac diseases plus the influence of genetic and environmental factors limit to mirror a particular disease with a single experimental model.
Thus, drug development in the field of cardiology is not only very challenging but also inspiring; therefore animal models should be selected that reflect as best as possible the disease being investigated. Given the wide range of animal models, reflecting critical features of the human pathophysiology available nowadays increases the likelihood of the translation to the patients. Furthermore, this knowledge and the increase of the predictive value of preclinical models help us to find more efficient and reliable solutions as well as better and innovative treatment strategies for cardiovascular diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bauersachs J (2013) Eur Heart J 34(31):2426–2428
Bonderman D, Ghio S, Felix SB et al (2013) Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial (LEPHT) Study Group. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study. Circulation 128(5):502–511
Eisert WG, Hauel N, Stangier J et al (2010) Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Thromb Vasc Biol 30(10):1885–1889
Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HH, Stasch JP (2006) NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov 9:755–768
Feldman AM, Li YY, McTiernan CF (2001) Matrix metalloproteinases in pathophysiology and treatment of heart failure. Lancet 357:654–655
Francis GS, Wilson Tang WH (2003) Pathophysiology of congestive heart failure. Rev Cardiovasc Med 4(suppl 2):S14–S20
Galiè N, Hoeper MM, Humbert M et al (2009) Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 30(20):2493–2537
Gavras H, Brunner HR, Laragh JH et al (1975) Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes. Circ Res 36:300–309
Ghofrani HA, D’Armini AM, Grimminger F et al (2013a) Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 369(4):319–329
Ghofrani HA, Galiè N, Grimminger F et al (2013b) Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 369(4):330–340
Iyer A, Chan V, Brown L (2010) The DOCA-salt hypertensive rat as a model of cardiovascular oxidative and inflammatory stress. Curr Cardiol Rev 6:291–297
Kolkhof P, Delbeck M, Kretschmer A et al (2014) J Cardiovasc Pharmacol 64:69–78
Kubitza D, Perzborn E, Berkowitz SD (2013) The discovery of rivaroxaban: translating preclinical assessments into clinical practice. Front Pharmacol 4:145
Lang M, Kojonazarov B, Tian X et al (2012) The soluble guanylate cyclase stimulator riociguat ameliorates pulmonary hypertension induced by hypoxia and SU5416 in rats. PLoS One 7(8):e43433
Laux V, Perzborn E, Heitmeier S et al (2009) Direct inhibitors of coagulation proteins – the end of the heparin and low-molecular-weight heparin era for anticoagulant therapy? J Thromb Haemost 102:892–899
Perzborn E, Strassburger J, Wilmen A et al (2005) In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939 – an oral, direct Factor Xa inhibitor. J Thromb Haemost 3(3):514–521
Pfeffer MA, Braunwald E (1990) Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 81:1161–1172
Pfeffer MA, Pfeffer JM, Steinberg C, Finn P (1985) Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation 72:406–412
Pitt B, Filippatos G, Gheorghiade M et al (2012) Rationale and design of ARTS: a randomized, double-blind study of BAY 94–8862 in patients with chronic heart failure and mild or moderate chronic kidney disease. Eur J Heart Fail 14(6):668–675
Pitt B, Kober L, Ponikowski P et al (2013) Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94–8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J 34(31):2453–2463
Rubin LJ, Galiè N, Grimminger F et al (2015) Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J 45(5):1303–1313
Ryan JJ, Marsboom G, Archer SL (2009) Rodent models of group 1 pulmonary hypertension. In: Hofmann F, Schmidt HHHW, Stasch JP (eds) Handbook of experimental pharmacology: cGMP generators, effectors and therapeutic implications, vol 191. Springer, Berlin, pp 105–149
Schermuly RT, Stasch JP, Pullamsetti SS et al (2008) Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J 32(4):881–891
Simonneau G, Gatzoulis MA, Adatia I et al (2013) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 62(25 Suppl):D34–D41
Simonneau G, D’Armini AM, Ghofrani HA et al (2015) Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2). Eur Respir J 45(5):1293–1302
Stasch JP, Evgenov OV (2013) Soluble guanylate cyclase stimulators in pulmonary hypertension. In: Humbert M, Evgenov OV, Stasch JP (eds) Handbook of experimental pharmacology: pharmacotherapy of pulmonary hypertension, vol 218. Springer, Berlin, pp 279–313
Stasch JP, Hobbs AJ (2009) NO-independent, haem-dependent soluble guanylate cyclase stimulators. In: Hofmann F, Schmidt HHHW, Stasch JP (eds) Handbook of experimental pharmacology: cGMP generators, effectors and therapeutic implications, vol 191. Springer, Berlin, pp 277–308
Wienen W, Stassen JM, Priepke H et al (2007) Effects of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate, on thrombus formation and bleeding time in rats. Thromb Haemost 98(2):333–338
Wong PC, Watson CA, Crain EJ et al (2008) Arterial antithrombotic and bleeding time effects of apixaban, a direct factor Xa inhibitor, in combination with antiplatelet therapy in rabbits. J Thromb Haemost 6(10):1736–1741
Wong PC, Pinto DJ, Zhang D et al (2011) Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor. J Thromb Thrombolysis 31(4):478–492
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Fliegner, D., Gerdes, C., Meding, J., Stasch, JP. (2015). Translational In Vivo Models for Cardiovascular Diseases. In: Nielsch, U., Fuhrmann, U., Jaroch, S. (eds) New Approaches to Drug Discovery. Handbook of Experimental Pharmacology, vol 232. Springer, Cham. https://doi.org/10.1007/164_2015_31
Download citation
DOI: https://doi.org/10.1007/164_2015_31
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-28912-0
Online ISBN: 978-3-319-28914-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)