Melatonin Improves Quality of Life, Oxidative Stress, and Cardiovascular Function in Pulmonary Arterial Hypertension

Figure 1. Experimental design. Study timeline showing assessments at baseline (BT) and treatment Months 2–6 (T2–T6), including serial evaluations of patient wellness through echocardiography, 6‐min walking test (6MWT), and blood tests measuring both plasma antioxidant capacity as melatonin levels. Source:Figure created with BioRender.

Figure 2. Flowchart illustrating the study and patients' follow‐up. The study enrolled 24 patients with pulmonary arterial hypertension, of whom 19 (79.2%) completed the 6‐month protocol. Five participants discontinued participation due to adverse events, melatonin intolerance (n = 1), fatal massive hemoptysis (n = 1), or loss to follow‐up (n = 3). Serial evaluations were conducted at baseline (BT) and monthly intervals (T2 through T6 months) with assessments including echocardiography, 6‐min walk testing, and plasma biomarkers analysis.

Figure 3. Heart rate during the 6MWT. Bar graph representing the 6 min walking test (6MWT) heart rates (HR) grouped according to the different acquisition times (initial, final, and after 1 and 5 min of recovery) during the examination of PAH patients at baseline (BT; white bars), and after 3‐ (T3; gray bars) and 6‐ (T6; black bars) month of melatonin treatment. Significant differences (Dunnett's multiple comparisons, p ≤ 0.05): *versus BT (at same acquisition time).

Figure 4. Plasma reducing and antioxidant capacity. Histograms representing the total antioxidant capacity (TAC; A) and the ferric reducing ability (FRAP; B) of the plasma in patients with pulmonary arterial hypertension at baseline (BT; white bars), and after 3‐ (T3; gray bars) and 6‐ (T6; black bars) month melatonin treatment. Values are expressed as average ± SEM, for BT, T3, and T6. Statistical difference (ANOVA, p ≤ 0.05): *versus BT; †versus T3.

Figure 5. PAH‐SYMPACT outcomes. Histograms display: first, cardiovascular symptoms (A); second, cardiopulmonary symptoms (B); third, physical impact (C); and fourth, cognitive/emotional impact (D) domains, along with total composite (E) scores of patients with pulmonary arterial hypertension at baseline (BT), and after 2‐ (T2), 3‐ (T3), 4‐ (T4), 5‐ (T5), and 6‐ (T6) month melatonin treatment. Data represent mean ± SEM. *p ≤ 0.05 versus BT by ANOVA with post hoc correction.

Figure 6. Plasma melatonin levels and relationship with antioxidant capacity. Histogram of plasma melatonin levels at baseline (BT), 3 months (T3), and 6 months (T6) of treatment (A). Data represent mean ± SEM. *p ≤ 0.05 versus BT by ANOVA with post hoc correction. XY‐plot of individual melatonin levels versus total plasma antioxidant capacity (TAC) in all patients (B). The dashed trend line represents the monotonic relationship (Spearman's p = 0.6090, *p ≤ 0.05), with the linear equation superimposed.