L-arginine improves endothelial and myocardial function after brain death.

BACKGROUND: Recently, we showed that brain death (BD) leads to a severe impairment of endothelial function. METHODS: To test the hypothesis, that nitric oxide supply improves endothelial function, we infused L-arginine (40 mg/kg) in 6 dogs after BD induction (subdural balloon). Six vehicle-treated BD animals served as controls. Coronary blood flow (CBF), preload recruitable stroke work (PRSW), and plasma L-arginine and nitrite/nitrate levels were measured before and 6 hr after BD induction. In addition, endothelium-dependent vasodilatation after intracoronary application of acetylcholine (ACH) and endothelium-independent vasodilation after sodium nitroprusside (SNP) were assessed. RESULTS: Six hours after BD, CBF decreased significantly in the control group (38.2+/-3.5 vs. 26.8+/-3.1 ml/min, P<0.05), whereas the decrease was less pronounced in the L-arginine group (41.8+/-6.9 vs. 36.0+/-1.2 ml/min, P<0.05 vs. control). Before BD, ACH led to a similar vasodilative response in both groups (81+/-6 vs. 75+/-7%). After BD, a paradox vasoconstriction occurred after ACH in the control group, while the vasodilative response did not change in the L-Arginine group (36+/-6 vs. 69+/-7%, P<0.05). The response to SNP did not differ between the groups and over the time. After BD PRSW decreased in both groups, however, it was still significantly higher in the L-arginine group (56+/-7 vs. 71+/-7 kerg, P<0.05). L-arginine (711+/-144 vs. 234+/-54 microM P<0.05) and nitrite/nitrate (39+/-3 vs. 27+/-3 microM P<0.05) levels were significantly higher in the L-arginine group. CONCLUSION: L-arginine treatment prevents endothelial dysfunction and improves myocardial performance after BD via enhancement of endogenous nitric oxide synthesis.

Myocardial protection after systemic application of L-arginine during reperfusion.

The L-arginine-nitric oxide (NO) pathway plays an important role in ischemia-reperfusion injury. In the present study we investigated the role of NO-precursor L-arginine on cardiac and pulmonary function after reversible hypothermic ischemia. Twelve anesthetized dogs underwent cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started with application of either saline vehicle (control, n = 6) or L-arginine (40 mg/kg i.v. bolus then 3 mg/kg i.v. infusion during the first 20 minutes of reperfusion, n = 6). The vasodilative response to acetylcholine was significantly higher in the L-arginine group (P < 0.05). The preload recruitable stroke work of the left ventricle decreased significantly after reperfusion, however remained unchanged in the L-arginine group. Arterial blood gas analysis did not show any difference between the two groups. Plasma L-arginine concentration reached peak level at 20 minutes of administration (675.0 +/- 66.6 versus 207.7 +/- 14.5 in the L-arginine group, P < 0.05) and returned to baseline at 40 minutes, while in the control group remained unchanged during ischemia and reperfusion (276.2 +/- 71.6 versus 283.8 +/- 38.5, P < 0.05). Plasma nitrite concentration followed L-arginine changes parallel, however nitrate levels increased slower. Supplementation with L-arginine during reperfusion prevents myocardial and endothelial dysfunction, however does not have any overriding effect on pulmonary function. Considerably rapid elimination of plasma L-arginine was demonstrated during early reperfusion.