L-ARGININE - EFFECT ON REPERFUSION INJURY AFTER HEART-TRANSPLANTATION

Global myocardial ischemia and reperfusion injury play a major role in early postoperative myocardial graft dysfunction. The aim of the pres ent study was to investigate the effects of the nitric oxide (NO) prec ursor L-arginine on myocardial and endothelial function after hypother mic ischemia and reperfusion in a heterotopic rat heart transplantatio n model. After 1 hour ischemic preservation, reperfusion was started a fter application of placebo (control, n = 12) or L-arginine (L-Arg 40 mg/kg, n = 12), a substrate of NO synthesis. Myocardial blood bow (MBF ) was assessed by the hydrogen clearance method. An implanted balloon was used to obtain pressure-volume relations of the transplanted heart . Left ventricular developed pressure (LVDP), rate of pressure develop ment (dP/dt), end-diastolic pressure (LVEDP), isovolumic relaxation co nstant (T-E), and MBF were measured after 60 minutes and 24 hours of r eperfusion. Endothelium-dependent vasodilatation in response to acetyl choline (ACh) and endothelium-independent vasodilatation in response t o sodium nitroprusside (SNP) were also determined. After 1 hour the MB F was significantly higher in the L-Arg group (3.6 +/- 0.6 vs. 1.9 +/- 0.2 ml/min/g, p < 0.05). The L-Arg group showed better recovery of sy stolic function and myocardial relaxation (LVDP 106 +/- 6 vs. 70 +/- 7 mmHg, p < 0.05; maximal dP/dt 5145 +/- 498 vs. 3410 +/- 257 mmHg/s, p < 0.05; T-E, 12.1 +/- 0.9 vs. 16.1 +/- 1.5 ms, p < 0.05, at an intrav entricular volume of 80 CLI). LVEDP was similar in the two groups. Aft er 24 hours no difference was found between the groups for basal MBF, LW, dP/dt, T-E,, LVEDP, or the response of MBF to SNP. However, ACh le d to a significantly higher increase in MBF in the L-Arg group (52 +/- 8% vs. 29 +/- 7%, p < 0.05). These results indicate that (1) NO donat ion improves myocardial and endothelial functional recovery during ear ly reperfusion after heart transplantation; and (2) initial treatment with L-Arg has a persisting beneficial effect against reperfusion-indu ced graft coronary endothelial dysfunction during late reperfusion.