Abstract
Introduction: Animal models have been used to understand the pathophysiology of pulmonary hypertension, to describe the mechanisms of action and to evaluate promising active ingredients. The monocrotaline-induced pulmonary hypertension model is the most used animal model. In this model, invasive and non-invasive hemodynamic variables that resemble human measurements have been used. Aim: To define if non-invasive variables can predict hemodynamic measures in the monocrotaline-induced pulmonary hypertension model.
Materials and Methods: Twenty 6-week old male Wistar rats weighing between 250-300g from the bioterium of the Universidad del Valle (Cali - Colombia) were used in order to establish that the relationships between invasive and non-invasive variables are sustained in different conditions (healthy, hypertrophy and treated). The animals were organized into three groups, a control group who was given 0.9% saline solution subcutaneously (sc), a group with pulmonary hypertension induced with a single subcutaneous dose of Monocrotaline 30 mg/kg, and a group with pulmonary hypertension with 30 mg/kg of monocrotaline treated with Sildenafil. Right ventricle ejection fraction, heart rate, right ventricle systolic pressure and the extent of hypertrophy were measured. The functional relation between any two variables was evaluated by the Pearson correlation coefficient.
Results: It was found that all correlations were statistically significant (p <0.01). The strongest correlation was the inverse one between the RVEF and the Fulton index (r = -0.82). The Fulton index also had a strong correlation with the RVSP (r = 0.79). The Pearson correlation coefficient between the RVEF and the RVSP was -0.81, meaning that the higher the systolic pressure in the right ventricle, the lower the ejection fraction value. Heart rate was significantly correlated to the other three variables studied, although with relatively low correlation.
Conclusion: The correlations obtained in this study indicate that the parameters evaluated in the research related to experimental pulmonary hypertension correlate adequately and that the measurements that are currently made are adequate and consistent with each other, that is, they have good predictive capacity.
Keywords: Animal models, hemodynamic measures, left ventricle, MCT, pulmonary hypertension, right ventricle hypertrophy.
Graphical Abstract
[http://dx.doi.org/10.1055/s-0037-1606214] [PMID: 29032561]
[http://dx.doi.org/10.1093/eurheartj/ehv317] [PMID: 26320113]
[http://dx.doi.org/10.1183/16000617.0063-2015] [PMID: 26621976]
[http://dx.doi.org/10.1152/ajplung.00212.2011] [PMID: 21964406]
[http://dx.doi.org/10.1016/j.bcp.2013.08.026] [PMID: 24001556]
[http://dx.doi.org/10.1371/journal.pone.0150480] [PMID: 26937637]
[http://dx.doi.org/10.1007/s00380-018-1293-3] [PMID: 30386918]
[http://dx.doi.org/10.1016/j.chest.2017.06.013] [PMID: 28642105]
[http://dx.doi.org/10.1152/ajpregu.00358.2016] [PMID: 27784688]
[http://dx.doi.org/10.1016/j.jtcvs.2017.06.053] [PMID: 28755882]
[http://dx.doi.org/10.1016/j.jacc.2013.10.027] [PMID: 24355638]
[http://dx.doi.org/10.1136/jcp.39.4.459] [PMID: 3009559]
[http://dx.doi.org/10.1371/journal.pone.0204254] [PMID: 30235299]
[http://dx.doi.org/10.1152/ajpheart.00369.2006] [PMID: 16731643]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.653576] [PMID: 18347220]
[http://dx.doi.org/10.1016/j.amjcard.2007.11.077] [PMID: 18394460]
[http://dx.doi.org/10.1097/ACO.0b013e32833953fb] [PMID: 20386437]
[http://dx.doi.org/10.1371/journal.pone.0043433] [PMID: 22912874]
[http://dx.doi.org/10.3345/kjp.2016.59.6.262] [PMID: 27462355]
[http://dx.doi.org/10.1007/978-3-662-45805-1_12] [PMID: 24092345]
[http://dx.doi.org/10.1056/NEJMoa1209655] [PMID: 23883378]
[http://dx.doi.org/10.5603/AIT.a2016.0041] [PMID: 27689429]
[http://dx.doi.org/10.1021/acschemneuro.6b00415] [PMID: 28182397]
[http://dx.doi.org/10.1161/CIRCIMAGING.109.887109] [PMID: 20044514]
[http://dx.doi.org/10.1007/978-1-4939-8597-5_18] [PMID: 29987824]
[http://dx.doi.org/10.1016/j.jacc.2016.10.047] [PMID: 28081831]
[http://dx.doi.org/10.1164/ajrccm.164.2.2010150] [PMID: 11463607]
[http://dx.doi.org/10.1097/HJH.0000000000000511] [PMID: 25668353]
[PMID: 29146614]
[http://dx.doi.org/10.1007/s10741-016-9526-y] [PMID: 26833318]
[http://dx.doi.org/10.1111/j.1460-9568.2004.03707.x] [PMID: 15525283]
[http://dx.doi.org/10.1186/s12917-014-0198-3] [PMID: 25149627]