L-arginine, prostaglandin, and white cell filtration equally improve myocardial protection in stressed neonatal hearts.

Abstract Objectives: L-Arginine may improve cardioplegic protection by increasing nitric oxide production. However, L-arginine may also be detrimental because it generates the free radical peroxynitrite. It would, therefore, be advantageous if the benefits of L-arginine could be achieved by another means. Methods: Twenty neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8%-10%) followed by 20 minutes of ischemia on cardiopulmonary bypass (stress) and were then protected for 70 minutes with multiple doses of blood cardioplegic solution. In 5 piglets (group 1), the cardioplegic solution was not modified; in 5 (group 2), low-dose L-arginine (4 mmol/L) was added; in 5 (group 3), prostaglandin E 1 (alprostadil, 4 μg/L) was added; and in 5 (group 4), the cardioplegic solution was passed through a leukodepleting filter. Myocardial function was assessed by pressure volume loops and expressed as percentage of control, and coronary vascular resistance was measured with each cardioplegic infusion. Results: Unmodified blood cardioplegic solution (group 1) was unable to protect the severely stressed myocardium, resulting in depressed systolic function (39% ± 1%) and preload recruitable stroke work (40% ± 1%), increased diastolic stiffness (239% ± 3%), and high conjugated diene production, myeloperoxidase activity, and coronary vascular resistance. In contrast, cardioplegic solutions modified with L-arginine, prostaglandin E 1 , or leukodepletion, resuscitated the stressed myocardium, resulting in complete return of systolic function (100% vs 101% vs 101%; P P P P Conclusions: (1) Unmodified blood cardioplegic solution is unable to protect the severely stressed myocardium. (2) L-Arginine, prostaglandin E 1 , and leukocyte filtration all improve myocardial protection equally and appear to work by limiting a white blood cell–mediated injury. This reduces oxygen-derived free radical formation, maintains vascular function, and restores functional recovery. Since L-arginine may be detrimental, surgeons should consider using prostaglandin E 1 and/or a leukocyte filter instead. (J Thorac Cardiovasc Surg 1999;118:665-73)