PT - JOURNAL ARTICLE AU - Pasquale Mone AU - Raffaele Izzo AU - Giuseppe Marazzi AU - Maria Virginia Manzi AU - Paola Gallo AU - Giuseppe Campolongo AU - Luca Cacciotti AU - Domenico Tartaglia AU - Giuseppe Caminiti AU - Fahimeh Varzideh AU - Gaetano Santulli AU - Valentina Trimarco TI - L-Arginine Enhances the Effects of Cardiac Rehabilitation on Physical Performance: New Insights for Managing Cardiovascular Patients During the COVID-19 Pandemic AID - 10.1124/jpet.122.001149 DP - 2022 Jun 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 197--203 VI - 381 IP - 3 4099 - http://jpet.aspetjournals.org/content/381/3/197.short 4100 - http://jpet.aspetjournals.org/content/381/3/197.full SO - J Pharmacol Exp Ther2022 Jun 01; 381 AB - Cardiac rehabilitation (CR) following acute myocardial infarction (AMI) improves physical capacities and decreases hospitalizations and cardiovascular mortality. L-arginine is the substrate used by nitric oxide (NO) synthase to generate NO and it has been shown to exert its beneficial effects on endothelium driving vasodilatation, reducing inflammation, and ameliorating physical function. We hypothesized that L-arginine could enhance physical capacities in patients who underwent CR after AMI. We designed a study aimed to assess the effects of L-arginine administration on the physical capacity of patients who underwent coronary revascularization after AMI. The trial was carried out amid the COVID-19 pandemic. Patients were assigned, with a 2:1 ratio, to add to their standard therapy one bottle containing 1.66 g of L-arginine or one bottle of identical aspect apart from not containing L-arginine, twice a day orally for 3 weeks. Patients performed a 6-minute walking test (6MWT), and their Borg modified 0–10 rating of perceived exertion (BRPE) was assessed before starting and at the end of the treatment. Seventy-five patients receiving L-arginine, and 35 receiving placebo successfully completed the study. The 6MWT distance increased significantly in the L-arginine group compared with both baseline and placebo (P < 0.0001). Additionally, we observed a significant improvement in the BRPE in patients treated with L-arginine but not in the placebo group. Taken together, our data indicate that L-arginine potentiates the response to CR independently of age, sex, baseline functional capacity, and comorbid conditions.SIGNIFICANCE STATEMENT This study shows for the first time that oral supplementation of L-arginine potentiates the response to cardiac rehabilitation after myocardial infarction and cardiac revascularization. Indeed, we observed a significant improvement in two fundamental parameters, namely, the 6-minute walking test and the Borg modified 0–10 rating of perceived exertion. Strikingly, the beneficial effects of L-arginine were independent of age, sex, comorbid conditions, and baseline functional capacity.