RT Journal Article
SR Electronic
T1 A nitric oxide donor reverses myocardial injury in rabbits with acute hypercholesterolemia.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 741
OP 746
VO 278
IS 2
A1 S Hoshida
A1 N Yamashita
A1 J Igarashi
A1 M Nishida
A1 M Hori
A1 T Kuzuya
A1 M Tada
YR 1996
UL http://jpet.aspetjournals.org/content/278/2/741.abstract
AB We evaluated the propagation of myocardial injury in a model of coronary artery occlusion and reperfusion in control and hypercholesterolemic rabbits. This was done by examining the differences in the infarct size and in the extent of leukocyte accumulation resulting from coronary artery occlusion (30 min) followed by reperfusion (2 or 48 hr) in rabbits fed 1% cholesterol for 4 days vs. controls not fed cholesterol. There was no significant difference in the infarct size in the 2-hr (45.7 +/- 6.7%, n = 8) vs. 48-hr (48.8 +/- 5.8%, n = 9) models of reperfusion in control rabbits. However, infarct size in the cholesterol-fed rabbits at 2 hr (64.0 +/- 4.1%, n = 6) or 48 hr (72.3 +/- 3.0%, n = 8) of reperfusion significantly exceeded that in the corresponding controls (P < .05). The infarct in cholesterol-fed rabbits at 2 hr of reperfusion was smaller than that at 48 hr of reperfusion, but not significantly. Treatment with S-nitroso-N-acetylpenicillamine, a nitric oxide donor, effectively reduced the size of infarct in the cholesterol-fed rabbits. However, treatment with N-acetylpenicillamine had no infarct-limiting effect. When we evaluated the extent of leukocyte accumulation in the ischemic myocardium, as assessed by myeloperoxidase activity, a positive correlation was observed between myeloperoxidase activity and infarct size at 48 hr of reperfusion. Results indicate that the propagation of myocardial ischemia and reperfusion injury in acutely hypercholesterolemic rabbits differed from that in controls. An exogenous nitric oxide donor effectively reduced the size of infarct associated with the reduction in the accumulation of leukocytes 48 hr after reperfusion, which suggests that a reduction in the production of endogenous nitric oxide during ischemia and reperfusion may aggravate the severity of myocardial injury in acutely hypercholesterolemic rabbits.