Can L-arginine improve myocardial protection during cardioplegic arrest? Results of a phase I pilot study.
BACKGROUND
L-arginine appears to improve myocardial protection during cardioplegic arrest in animal models.


METHODS
To study the clinical effect and safety of L-arginine in humans, a phase I pilot study was performed with 50 patients who underwent coronary artery bypass grafting. We randomly assigned half to a treatment group, which received 1 g of L-arginine administered during the first 30 minutes of cardioplegic arrest induced by either warm or cold blood cardioplegia, and half to a control group, which did not receive L-arginine supplementation.


RESULTS
Age, sex, and preoperative clinical status were similar in both groups. Seventeen patients of each group were administered intermittent warm antegrade blood cardioplegia, whereas the solution needed to be cooled to obtain complete standstill of the remaining eight hearts in each group. An internal thoracic artery graft to the left anterior descending coronary artery was performed in all patients. There was no death and no myocardial infarction in the treatment group, but there were one death and two infarctions in the control group. The amount of serial release of troponin I during the first 72 hours after the operation was similar between the L-arginine group and the control group (p > 0.05). Peak serum troponin levels averaged 4.9 +/- 1.0 microg/L in the arginine group and 3.9 +/- 1.0 microg/L in the control group (p > 0.05). A multivariate analysis of variance showed no effect of L-arginine (p > 0.05) but a significant effect of the temperature of the cardioplegic solution on the release of troponin I (p < 0.05). Serum troponin I levels averaged 2.2 +/- 0.4 microg/L, 4.5 +/- 0.4 microg/L, and 6.9 +/- 0.4 microg/L in the patients with cold cardioplegia and 1.4 +/- 0.3 microg/L, 2.4 +/- 0.3 microg/L, and 3.3 +/- 0.3 microg/L in the patients with warm cardioplegia 1, 2, and 6 hours, respectively, postoperatively.


CONCLUSIONS
The administration of 1 g of L-arginine during the first 30 minutes of blood cardioplegic arrest did not result in a decrease in the postoperative release of cardiac enzyme; however, cold cardioplegic arrest significantly increased the release of cardiac troponin I postoperatively. There was no significant side effect related to the addition of L-arginine to the cardioplegic solution.
Carrier
M
M
Department of Surgery, Montreal Heart Institute, Quebec, Canada. carrier@icm.umontreal.ca
Pellerin
M
M
Pagé
P L
PL
Searle
N R
NR
Martineau
R
R
Caron
C
C
Solymoss
B C
BC
Pelletier
L C
LC
D001120:Arginine / Q000627:therapeutic use*; D001769:Blood; D002314:Cardioplegic Solutions / Q000627:therapeutic use; D002423:Cause of Death; D003080:Cold Temperature; D001026:Coronary Artery Bypass; D003402:Creatine Kinase / Q000097:blood; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced; D006358:Hot Temperature; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology; D010865:Pilot Projects; D012449:Safety; D015996:Survival Rate; D013895:Thoracic Arteries / Q000637:transplantation; D019210:Troponin I / Q000097:blood
D002314:Cardioplegic Solutions; D007527:Isoenzymes; D019210:Troponin I; D001120:Arginine; D003402:Creatine Kinase