Mone Pasquale, Izzo Raffaele, Marazzi Giuseppe, Manzi Maria Virginia, Gallo Paola, Campolongo Giuseppe, Cacciotti Luca, Tartaglia Domenico, Caminiti Giuseppe, Varzideh Fahimeh, Santulli Gaetano, Trimarco Valentina
Departments of Medicine (Cardiology) and Molecular Pharmacology - Wilf Family Cardiovascular Research Institute, Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Neuroimmunology and Inflammation, Einstein-Sinai Diabetes Research Center, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (P.M., F.V., G.S.); Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy (R.I., M.V.M., P.G., G.S.); IRCCS San Raffaele, Rome, Italy (G.M., G.Cami.); San Carlo di Nancy Hospital, Rome, Italy (G.Camp.); Madre Giuseppina Vannini Hospital, Rome, Italy (L.C.); and ASL AV, Avellino, Italy (D.T.); Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy (V.T.), New York, New York (P.M., F.V., G.S.); University of Naples Federico II, Naples, Italy (R.I., M.V.M., P.G., G.S., V.T.); IRCCS San Raffaele, Rome, Italy (G.M., G.Cami.); San Carlo di Nancy Hospital, Rome, Italy (G.Camp.); Madre Giuseppina Vannini Hospital, Rome, Italy (L.C.); and ASL AV, Avellino, Italy (D.T.).
Departments of Medicine (Cardiology) and Molecular Pharmacology - Wilf Family Cardiovascular Research Institute, Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Neuroimmunology and Inflammation, Einstein-Sinai Diabetes Research Center, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (P.M., F.V., G.S.); Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy (R.I., M.V.M., P.G., G.S.); IRCCS San Raffaele, Rome, Italy (G.M., G.Cami.); San Carlo di Nancy Hospital, Rome, Italy (G.Camp.); Madre Giuseppina Vannini Hospital, Rome, Italy (L.C.); and ASL AV, Avellino, Italy (D.T.); Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy (V.T.), New York, New York (P.M., F.V., G.S.); University of Naples Federico II, Naples, Italy (R.I., M.V.M., P.G., G.S., V.T.); IRCCS San Raffaele, Rome, Italy (G.M., G.Cami.); San Carlo di Nancy Hospital, Rome, Italy (G.Camp.); Madre Giuseppina Vannini Hospital, Rome, Italy (L.C.); and ASL AV, Avellino, Italy (D.T.)
J Pharmacol Exp Ther. 2022 Jun;381(3):197-203. doi: 10.1124/jpet.122.001149. Epub 2022 Mar 26.
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 ( < 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.
急性心肌梗死(AMI)后的心脏康复(CR)可改善身体机能,减少住院次数并降低心血管疾病死亡率。L-精氨酸是一氧化氮(NO)合酶用于生成NO的底物,并且已显示其对内皮发挥有益作用,促进血管舒张、减轻炎症并改善身体功能。我们假设L-精氨酸可以增强AMI后接受CR治疗的患者的身体机能。我们设计了一项研究,旨在评估给予L-精氨酸对AMI后接受冠状动脉血运重建患者身体机能的影响。该试验在新冠疫情期间进行。患者按2:1的比例分组,在标准治疗基础上,一组每天口服两瓶含1.66 g L-精氨酸的制剂,另一组每天口服两瓶外观相同但不含L-精氨酸的制剂,持续3周。患者在治疗开始前和结束时进行6分钟步行试验(6MWT),并评估其Borg改良0-10级主观用力程度评分(BRPE)。75例接受L-精氨酸治疗的患者和35例接受安慰剂治疗的患者成功完成了研究。与基线水平和安慰剂组相比,L-精氨酸组的6MWT距离显著增加(<0.0001)。此外,我们观察到接受L-精氨酸治疗的患者BRPE有显著改善,而安慰剂组没有。综上所述,我们的数据表明,L-精氨酸可增强对CR的反应,且不受年龄、性别、基线功能能力和合并症的影响。意义声明:本研究首次表明,口服补充L-精氨酸可增强心肌梗死后和心脏血运重建后对心脏康复的反应。事实上,我们观察到两个基本参数有显著改善,即6分钟步行试验和Borg改良0-10级主观用力程度评分。引人注目的是,L-精氨酸的有益作用不受年龄、性别、合并症和基线功能能力的影响。