Sodium nitroprusside exacerbates myocardial ischemia-reperfusion injury.
BACKGROUND
The role of nitric oxide in myocardial ischemia-reperfusion is controversial. Although many studies claim that nitric oxide ameliorates reperfusion injury, others suggest that it exacerbates such injury, possibly through peroxynitrite production. These discordant results may be attributable to a dose-dependent phenomenon.


METHODS
Isolated rabbit hearts sustained sequential periods of blood perfusion (20 minutes), warm ischemia (30 minutes), and reperfusion (20 minutes). During reperfusion, four groups underwent intracoronary infusion of saline solution (n = 6), or the nitric oxide donor sodium nitroprusside (100 nm/min [SNP100, n = 6], 1 nmol x L(-1)/min(-1) [SNP1, n = 6], or 0.01 nmol x L(-1) x min(-1) [SNP0.01]). Left ventricular-developed pressure and oxygen consumption were measured after preischemic perfusion and reperfusion. Levels of myocardial nitrotyrosine, a marker for peroxynitrite, were measured after reperfusion with an immunoradiochemical assay.


RESULTS
Postischemic-developed pressure and myocardial oxygen consumption were significantly higher in the saline group than all nitroprusside-reperfused groups (p < 0.01 for both parameters). However, there were no differences in either parameter between SNP100, SNP1, or SNP0.01. Nitrotyrosine levels were similar among the four groups (p = 0.43).


CONCLUSIONS
Nitroprusside exacerbates myocardial ischemia-reperfusion injury over a wide range of doses, although the mechanism does not appear to be mediated by peroxynitrite.
Cope
J T
JT
Department of Surgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Banks
D
D
Laubach
V E
VE
Binns
O A
OA
King
R C
RC
Richardson
R M
RM
Shockey
K S
KS
Tribble
C G
CG
Kron
I L
IL
D000818:Animals; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009599:Nitroprusside / Q000009:adverse effects*; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D013861:Thiocyanates / Q000097:blood; D014665:Vasodilator Agents / Q000009:adverse effects*; D017725:Ventricular Pressure / Q000187:drug effects
D013861:Thiocyanates; D014665:Vasodilator Agents; D009599:Nitroprusside; C031760:thiocyanate