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The Journal of Cardiovascular Surgery 1998 June;39(3):321-9

Copyright © 2000 EDIZIONI MINERVA MEDICA

language: English

Cardioprotective effect of L-arginine in myocardial ischemia and reperfusion in an isolated working rat heart model

Izhar U., Schwalb H., Borman J. B., Merin C.

From the Cardiothoracic Surgery Department and Joseph Lunenfeld Cardiac Surgery Research Center Hadassah University Hospital, Jerusalem, Israel


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Background. Studies in myo­car­dial ische­mia ­and reper­fu­sion ­have dem­on­strat­ed dam­age to endo­the­li­um, ­impaired pro­duc­tion ­and ­release of vasoac­tive sub­stanc­es ­such as ­nitric ­oxide, ­and ­marked alter­a­tion in endo­the­li­um-depen­dent relax­atin of ­the cor­o­nary vas­cu­la­ture. This ­study ­was ­designed to exam­ine ­the car­diop­ro­tec­tive ­effect of ex­og­e­nous admin­is­tra­tion of L-argi­nine, a pre­cur­sor of ­nitric ­oxide, dur­ing ische­mia ­and reper­fu­sion, par­tic­u­lar­ly ­using oxy­gen­at­ed crys­tal­loid car­di­o­ple­gia.
Methods. Seventy ener­gy-deplet­ed iso­lat­ed work­ing ­rat ­hearts ­were arrest­ed by car­di­o­ple­gia ­and sub­ject­ed to 60 ­min norm­other­mic glo­bal ische­mia fol­lowed by 10 ­min non­work­ing ­and 30 ­min work­ing reper­fu­sion (Gr 1). L-argi­nine (3mM or 10mM) ­was add­ed to ­the car­di­o­pleg­ic solu­tion (Gr 2,3 respec­tive­ly), reper­fu­sion (Gr 6,7 respec­tive­ly), through­out ­the experi­ment (Gr 4,5 respec­tive­ly), ­and ­with Nw-­nitro-L-argi­nine meth­yl ­ester (L-­NAME), a com­pet­i­tive inhib­i­tor of ­nitric ­oxide syn­thase (Gr 8).
Results. At 30 ­min of work­ing ­heart reper­fu­sion, com­pared to con­trol, ­all argi­nine con­tain­ing ­groups (Gr 2-7) exhib­it­ed a sig­nif­i­cant ­improved recov­ery of car­diac out­put (64.7±21.2, 98.1±21.1, 90.9±11.7, 88.9±16.2, 83.1±7.4, ­and 90.8±10.6, ­mean ± SD% Gr 2 to 7 respec­tive­ly, vs Gr 1 36.3±20%, p<0.01). Significant recov­ery improve­ment ­was ­observed ­also in oth­er hemo­dy­nam­ic param­e­ters (cor­o­nary ­flow, aor­tic ­peak pres­sure), as ­well as bio­chem­i­cal recov­ery ­assessed by O2 con­sump­tion ­ratio, ­release of lac­tic dehy­drog­e­nase at reper­fu­sion ­and regen­er­a­tion of ­ATP. The L-­NAME ­group ­had a sig­nif­i­cant poor­er hemo­dy­nam­ic ­and bio­chem­i­cal recov­ery. L-argi­nine ­had no ­effect on ­the pre­is­chem­ic hemo­dy­nam­ic param­e­ters.
Conclusions. These ­results sup­port ­the cumu­la­tive ­data con­sid­er­ing L-argi­nine as a car­di­op­ro­tec­tive ­agent in post­is­chem­ic reper­fu­sion inju­ry.

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