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

Objectives: L-Arginine may improve cardioplegic protection by increasing ni tric oxide production. However, L-arginine may also be detrimental because it generates the free radical peroxynitrite. It mould, therefore, be advant ageous if the benefits of L-arginine could be achieved by another means. Me thods: Twenty neonatal piglets underwent 60 minutes of ventilator hypoxia ( inspired oxygen fraction 8%-10%) followed by 20 minutes of ischemia on card iopulmonary bypass (stress) and were then protected for 70 minutes with mul tiple doses of blood cardioplegic solution. In 5 piglets (group 1), the car dioplegic 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 mu g/ L) was added; and in 5 (group 4), the cardioplegic solution was passed thro ugh a leukodepleting filter. Myocardial function was assessed by pressure v olume loops and expressed as percentage of control, and coronary vascular r esistance was measured with each cardioplegic infusion. Results: Unmodified blood cardioplegic solution (group 1) was unable to protect the severely s tressed myocardium, resulting in depressed systolic function (39% +/- 1%) a nd preload recruitable stroke work (40% +/- 1%), increased diastolic stiffn ess (239% +/- 3%), and high conjugated diene production, myeloperoxidase ac tivity, and coronary vascular resistance. In contrast, cardioplegic solutio ns modified with L-arginine, prostaglandin E-1, or leukodepletion, resuscit ated the stressed myocardium, resulting in complete return of systolic func tion (100% vs 101% vs 101%; P < .001 vs group 1) and preload recruitable st roke 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 lowere d conjugated diene production, myeloperoxidase activity, and coronary vascu lar resistance (P < .001 vs group 1 for each). Conclusions: (1) Unmodified blood cardioplegic solution is unable to protect the severely stressed myoc ardium. (2) L-Arginine, prostaglandin E-1, and leukocyte filtration all imp rove myocardial protection equally and appear to work by limiting a white b lood cell-mediated injury This reduces oxygen-derived free radical formatio n, maintains vascular function, and restores functional recovery Since L-ar ginine may be detrimental, surgeons should consider using prostaglandin E-1 and/or a leukocyte filter instead.