Training programs in preclinical studies. The example of pulmonary hypertension. Systematic review and meta-analysis

BACKGROUND: Exercise and cardiopulmonary exercise testing are essential in the evaluation of physiological, biochemical, and molecular responses in the experimental studies on chronic diseases such as diabetes, heart failure and hypertension. The exercise tolerance and seem to be a valuable contribution to the experiments that are performed in animal models of pulmonary hypertension (PH), as well. The current survey uses detailed quantitative analyses to assess the advantages of exercise training programs performed in preclinical studies based on outcomes such as exercise capacity, cardiopulmonary hemodynamics, and mortality. METHODS: Articles were identified through search engines in the online electronic databases Pubmed/Medline, Web of Science following the PRISMA Protocol. Studies conducted between 1991 and 2022 without language restrictions were included in this study. Heterogeneity was assessed using the Cochrane Q-test and I2 test statistics. Subgroup analysis was employed with evidence of heterogeneity. Quality assessment was carried out using SYRCLE’s risk of bias tool for animal studies. Publication bias across studies was determined using the funnel plot and Egger’s regression test statistic. RESULTS: The available protocols typically included treadmill running, swimming, and voluntary wheel running with a different series of intensities, times and durations; these were also used in studies examining the efficacy of chronic training programs. In 66 interventions, PH induction reduced exercise endurance by half compared to healthy subjects, while exposure to tested medical agents normalized exercise capacity. The other 58 interventions demonstrated the advantages of various exercise training programs for PH. Induction of PH reduced exercise endurance by half compared to healthy subjects (R = 0.52; 0.48 − 0.55 95%CI; P<0.0001; I2 = 98.9%), while the exposure to tested medical agents normalized exercise capacity (R = 1.75; 1.61 − 1.91 95%CI; P<0.0001; I2 = 97.8%). CONCLUSION: Despite a wide spectrum of study protocols to measure exercise endurance in animals with PH, there is a significant correlation between worsening of exercise-related parameters and PH development, manifested by alterations in haemodynamic and remodeling parameters. Familiarization with exercise, training program schedule, method used for PH induction, or detailed training parameters such as slope, exercise intensity or individualization, can influence the final outcome. This in turn can impact on the diversity and reproducibility of results being obtained in particular experimental studies.