L-arginine, prostaglandin, and white cell filtration equally improve myocardial protection in stressed neonatal hearts.
OBJECTIVE
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.
Kronon
M T
MT
Division of Cardiovascular Surgery, The Heart Institute for Children, Hope Children's Hospital, Oak Lawn, Illinois, USA.
Allen
B S
BS
Halldorsson
A
A
Rahman
S
S
Wang
T
T
Ilbawi
M
M
D000527:Alprostadil / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002306:Cardiac Volume / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D002315:Cardiopulmonary Bypass; D003331:Coronary Vessels / Q000187:drug effects; D003971:Diastole; D005609:Free Radicals / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology; D007937:Leukapheresis / Q000295:instrumentation; D007962:Leukocytes / Q000502:physiology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D016877:Oxidants / Q000378:metabolism; D009195:Peroxidase / Q000187:drug effects; D013312:Stress, Physiological / Q000503:physiopathology; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D013599:Systole; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
D002314:Cardioplegic Solutions; D005609:Free Radicals; D009566:Nitrates; D016877:Oxidants; D014665:Vasodilator Agents; C039642:peroxynitric acid; D009569:Nitric Oxide; D001120:Arginine; D009195:Peroxidase; D000527:Alprostadil