Inhibition of carnitine synthesis protects against left ventricular dysfunction in rats with myocardial ischemia.
During myocardial ischemia, inhibition of the carnitine-mediated transportation of fatty acid may be beneficial because it facilitates glucose utilization and prevents an accumulation of fatty acid metabolites. We orally administered 3-(2,2,2-trimethyl hydrazinium) propionate (MET), an inhibitor of carnitine synthesis, for 20 days to rats. Then we evaluated left ventricular (LV) function during brief ischemia by using a buffer-perfused isovolumic heart model. After 15 min of reoxygenation after the transient ischemia, LV peak systolic pressure (PSP) almost completely returned to the baseline level in rats given MET (96 +/- 4%), whereas it was only partially (77 +/- 16%) recovered in the placebo-treated rats. We induced myocardial infarction in other rats by ligating the left anterior descending coronary artery. Then the animals were given MET for 20 days, and LV function was compared. In the placebo-treated rats (with myocardial infarction, but without drug treatment), LVPSP was lower than that in the sham group [108 +/- 19 (n = 10) vs. 136 +/- 15 mm Hg (n = 13); p < 0.05], and the time constant (T) of LV pressure decay was elongated (36 +/- 4 vs. 30 +/- 7 ms; p < 0.05). In MET-treated groups, however, neither PSP nor T differed from those in the sham group. In conclusion, inhibition of the carnitine-mediated transportation of fatty acid by MET protected against left ventricular dysfunction in acute and chronic myocardial ischemia.
Aoyagi
T
T
University of Tokyo, Japan.
Sugiura
S
S
Eto
Y
Y
Yonekura
K
K
Matsumoto
A
A
Yokoyama
I
I
Kobayakawa
N
N
Omata
M
M
Kirimoto
T
T
Hayashi
Y
Y
Momomura
S
S
D000818:Animals; D002331:Carnitine / Q000037:antagonists & inhibitors* / Q000097:blood; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left
D002331:Carnitine