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 microgram/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 <.001 vs group 1) and preload recruitable stroke work (100% vs 101% vs 101%; P <.001 vs group 1), minimal increase in diastolic stiffness (160% vs 162% vs 160%; P <. 001 vs group 1), and lowered conjugated diene production, myeloperoxidase activity, and coronary vascular resistance (P <.001 vs group 1 for each).
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.