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Simple Summary: Pulmonary hypertension is a fatal comorbidity in dogs with left-sided heart disease. Various oral pulmonary vasodilators have been effective in treating canine pulmonary hypertension; however, no studies have compared their hemodynamic effects. This study compared the hemodynamic effects of selected pulmonary vasodilators (15 µg/kg beraprost, 1.0 mg/kg sildenafil, and their combination) in canine models of mitral regurgitation (the most common cardiac disease in dogs). Significant improvements in pulmonary hypertension were observed with all study drugs. Pulmonary vasodilating effects differed among the study's drugs. Sildenafil showed a more potent pulmonary vasodilating effect than beraprost; however, sildenafil significantly worsened the left-heart loading condition. Although beraprost showed a weaker pulmonary vasodilating effect than sildenafil, no significant worsening in the left-heart loading condition was observed. Combination therapy resulted in the strongest pulmonary and systemic vasodilating effects without worsening the left-heart loading condition. This study demonstrated the differences between beraprost and sildenafil in pulmonary and systemic vasodilating effects. Sildenafil involved the risk of worsening the left-heart load, although it was effective in treating pulmonary hypertension. Combination therapy with beraprost and sildenafil synergistically dilated the pulmonary and systemic vessels, indicating a more potent treatment option. Previous reports have shown that various oral pulmonary vasodilators are effective against canine pulmonary hypertension (PH). However, no studies have compared their hemodynamic effects. We aimed to compare the hemodynamic effects of 15 µg/kg beraprost sodium, 1.0 mg/kg sildenafil, and their combination, in dogs with experimentally induced mitral regurgitation. This experimental crossover study evaluated the hemodynamic and functional effects of oral pulmonary vasodilators by application of right-sided heart catheterization and echocardiography. Beraprost significantly decreased pulmonary and systemic vascular resistance. Additionally, beraprost increased right-ventricular stroke volume and left-ventricular cardiac output without worsening left-heart size and left-atrial pressure. The pulmonary vasodilatory effects of sildenafil were stronger, and its systemic vasodilatory effects were weaker than those of beraprost. However, sildenafil significantly increased the left-ventricular volume, left-atrial pressure indicator, and right-ventricular cardiac output. Combination therapy resulted in the strongest pulmonary and systemic vasodilating effects without worsening the left-heart size and left-atrial pressure indicators. Both beraprost and sildenafil were effective against canine PH; however, sildenafil was associated with the risk of worsening left-heart loading. Combination therapy with beraprost and sildenafil synergistically dilated pulmonary and systemic vessels, indicating a more potent treatment option for severe PH cases. [ABSTRACT FROM AUTHOR]

Introduction: The therapeutic efficacy of mesenchymal stromal cells (MSCs) in inflammatory bowel disease is not completely known and is not consistent. Priming with inflammatory cytokines has been proposed to adapt MSCs to an inflammatory environment to have them ready to counteract it, but may have undesirable effects on MSCs, such as increased immunogenicity. In this study, we hypothesized that priming MSCs with inflamed intestinal tissue would more effectively enhance their therapeutic effect on intestinal inflammation., Methods: The capacity of canine adipose-derived MSCs (cADSCs) primed with colon tissue homogenates from mice with experimentally induced colitis or a combination of tumor necrosis factor-α and interferon-γ to inhibit T-cell proliferation was analyzed, along with their own apoptosis, proliferation, cell surface marker expression, and transcriptome. In addition, colitis mice were treated with the primed cADSCs to assess colitis severity and immune cell profile., Results: Priming with cytokines induced apoptosis, decreased cell proliferation, and major histocompatibility complex-II gene expression in cADSCs, but these adverse effects were mild or absent with colitis-tissue priming. cADSCs primed with colitis tissue reduced the severity of colitis via the induction of M2 macrophages and T-regulatory cells and suppression of T-helper (Th)1/Th17-cell responses, and their effects were comparable to those of cytokine-primed cells., Discussion: Our results emphasize the importance of the activation of MSCs by the appropriate microenvironment to maximize their therapeutic effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yasumura, Teshima, Nagashima, Michishita, Taira, Suzuki and Matsumoto.)