We investigated the endogenous production of apelin and the cardiac and pulmonary effects of its chronic administration in monocrotaline (MCT)-induced pulmonary hypertension (PH). Male Wistar rats were injected with MCT (60 mg/kg sc) or vehicle ( day 0). One week later, these animals were randomly treated during 17 days with pyroglutamylated apelin-13 (Pyr-AP13; 200 μg·kg⁻¹·day⁻¹ ip) or a similar volume of saline, resulting in four groups: sham ( n = 11), sham-AP ( n = 11), MCT ( n = 16), and MCT-AP ( n = 13). On day 25, right ventricular (RV) and left ventricular (LV) hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis. When compared with sham, the MCT group presented a significant increase of RV mass (166 ± 38%), diameter of cardiomyocyte (40 ± 10%), myocardial fibrosis (95 ± 20%), peak systolic pressure (99 ± 22%), peak rate of ventricular pressure rise (dP/d t_max; 74 ± 24%), peak rate of ventricular pressure decline (dP/d t_min; 73 ± 19%), and time constant τ (55 ± 16%). In these animals, RV expression of apelin (−73 ± 10%) and its receptor APJ (−61 ± 20%) was downregulated, whereas mRNA expression of type B natriuretic peptide (9,606 ± 713%), angiotensinogen (191 ± 147%), endothelin-1 (RV, 497 ± 156%; and LV, 799 ± 309%), plasmatic levels of apelin (104 ± 48%), and angiotensin 1-7 (161 ± 151%) were increased. Chronic treatment with Pyr-AP13 significantly attenuated or normalized these changes, preventing apelin-APJ mRNA downregulation and PH-induced neurohumoral activation of several vasoconstrictors, which exacerbates apelin-APJ vasodilator effects. Therefore, apelin delayed the progression of RV hypertrophy and diastolic dysfunction. Together, these observations suggest that the apelin-APJ system may play an important role in the pathophysiology of PH, representing a potential therapeutic target since it significantly attenuates RV overload and PH-induced neurohumoral activation.

Introduction: Cardiac surgery is an aggressive procedure, inducing a great level of stress and disturbance to the homeostasis of the organism and underlying several postoperative complications. Surgical prehabilitation comprises pre-operative physical conditioning designed to improve the physiological and functional capacities of the individual, prepare the organism for surgical stress and reduce the risk of postoperative morbidity.Aim: This systematic review and meta-analysis is aimed at evaluating the ability of prehabilitation to prevent post-surgical complications in cardiac patients.Methods: We selected studies conducted among patients who were waiting for non-urgent cardiac surgical procedures, where a comparison between prehabilitation and standard treatment was made. A total of 3650 possible studies were researched, of which eight were selected for inclusion.Results: A reduction in the number of complications in the groups submitted to prehabilitation (odds ratio = 0.41; 95% confidence interval (CI): 0.28–0.62; p < 0.001; I²= 0%) was observed, as well as a significant increase in maximal inspiratory pressure (standard mean difference (SMD) = 0.66; 95% CI: 0.35–0.96; p < 0.001; I²= 58%), a non-significant decrease in the length of stay (SMD = –0.56; 95% CI: −1.13, 0.01; p = 0.05; I²= 93%), a non-significant increase in the distance walked by the intervention group in the six-minute walk test (SMD = 0.89; 95% CI −0.06, 1.84; p = 0.07) and a lack of effect on mechanical ventilation time (SMD = −0.03; 95% CI: −0.22, 0.16; p = 0.75; I²= 0%).Conclusion: Prehabilitation reduces the number of post-surgical complications and increases maximal inspiratory pressure; a reduction in the length of stay and an improvement of functional capacities are also probable.