L-Arginine Project:
BACKGROUND: Nitric oxide (NO)-dependent factors (serotonin, activated platelets, acetylcholine) cause vasodilation in normal coronary arteries but vasoconstrict atherosclerotic vessels. This experiment tested the hypothesis that intravenous systemic infusions of L-Arginine (L-ARG), a precursor for NO production, dilates the coronary vascular bed of patients undergoing CABG surgery.
METHODS: 20 patients scheduled for CABG surgery were studied in a prospective, blinded, randomized clinical trial. Saphenous vein graft blood flow (GBF) was measured with a transit time flow probe and coronary vascular resistance (CVR) was calculated. After weaning from bypass, patients were given a venous infusion (placebo or 10% arginine hydrochloride (30 g)) over 15 minutes. Arterial blood samples for the determination of L-ARG and L-citrulline levels were drawn prior to, 10 minutes after starting infusion, and 10 minutes after end of infusion.
RESULTS: The placebo group experienced an increase in mean arterial pressure (MAP) and CVR and a decrease in GBF. Patients in the L-ARG group maintained their baseline values. MAP (L-ARG, 88 ± 17 to 92 ± 13 mmHg) vs (Placebo, 80 ± 12 to 92 ± 9 mmHg), p=0.021), CVR (L-ARG, 97,000 ± 60,000 to 99,600 ± 51,000 dynes*sec* cm-5) vs (Placebo, 81,000 ±69,000 to 117,000 ± 64,000 dynes*sec* cm-5), (p = 0.05), and GBF (L-ARG, 55 ± 25 to 50 ± 19 ml/min) vs (Placebo, 60 ± 34 to 46 ± 18), (p=0.05) remained more stable in the L-ARG treated patients.
CONCLUSIONS: Systemic L-ARG infusion reduced post bypass coronary vasoconstriction. There were no adverse events associated with the drug infusion.
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