SUPPLEMENTAL L-ARGININE DURING CARDIOPLEGIC ARREST AND REPERFUSION AVOIDS REGIONAL POSTISCHEMIC INJURY

Unenhanced hypothermic cardioplegia does not prevent postischemic endo thelial and contractile dysfunction in hearts subjected to antecedent regional or global ischemia. This study tested the hypothesis that sup plementing blood cardioplegic solution and reperfusion with the nitric oxide precursor L-arginine would preserve endothelial function, reduc e infarct size, and reverse postcardioplegia regional contractile dysf unction by the L-arginine-nitric oxide pathway. In 23 anesthetized dog s, the left anterior descending coronary artery was ligated for 90 min utes, after which total bypass was established for surgical ''revascul arization.'' In 10 dogs, unsupplemented multidose hypothermic blood ca rdioplegic solution was administered for a total of 60 minutes of card ioplegic arrest. In eight dogs, L-arginine was given intravenously (4 mg/kg per minute) and in blood cardioplegic solution (10 mmol) during arrest. In five dogs, the nitric oxide synthesis blocker N omega-nitro -L-arginine (1 mmol) was used to block the L-arginine-nitric oxide pat hway during cardioplegia and reperfusion. Infarct size (triphenyltetra zolium chloride) as percent of the area at risk was significantly redu ced by L-arginine compared with blood cardioplegic solution (28.2% +/- 4.1% versus 40.5% +/- 3.5%) and was reversed by N omega-nitro-L-argin ine to 68.9% +/- 3.0% (p < 0.05). Postischemic regional segmental work in millimeters of mercury per millimeter (sonomicrometry) was signifi cantly better with L-arginine (92 +/- 15) versus blood cardioplegic so lution (28 +/- 3) and N omega-nitro-L-arginine (26 +/- 6). Segmental d iastolic stiffness was significantly lower with L-arginine (0.46 +/- 0 .06) compared with blood cardioplegic solution (1.10 +/- 0.11) and was significantly greater with N omega-nitro-L-arginine (2.70 +/- 0.43)>. In ischemic-reperfused left anterior descending coronary arterial vas cular rings, maximum relaxation responses to acetylcholine, the stimul ator of endothelial nitric oxide, was depressed in the blood cardiople gic solution group (77% +/- 4%) and was significantly reversed by L-ar ginine (92% +/- 3%), Smooth muscle function was unaffected in all grou ps, We conclude that cardioplegic solution supplemented with L-arginin e reduces infarct size, preserves postischemic systolic and diastolic regional function, and prevents arterial endothelial dysfunction via t he L-arginine-nitric oxide pathway.