Fumonisins (FB) are mycotoxins produced by Fusarium moniliforme that induce acute pulmonary edema in swine. Fumonisins inhibit sphingosine N-acyltransferase, a key component in the pathway for de novo sphingolipid biosynthesis, resulting in increased sphingosine and sphinganine in vivo. One potential mechanism for FB-induced pulmonary edema is direct inhibition of myocardial L-type Ca2+ channels by sphingosine, resulting in negative inotropic and chronotropic effects. In this study we evaluated the cardiovascular effects of short-term fumonisin exposure in swine. Pigs were fed FB at 0 (n=6; Group C) or 20 (n=6; Group FB) mg/kg/day for 3 days. On day 4, pigs were anesthetized with butorphanol-chloralose and instrumented for left-ventricular pressure-volume loop studies. Cardiac inotropic and chronotropic state was assessed at baseline and following graded infusions of isoproterenol, esmolol, nitroprusside, phenylephrine, and calcium gluconate. Fumonisin-treated pigs had significant decreases in end-systolic elastance (FB:0.69±0.33; C:1.46±0.58 mmHg/ml), heart rate (FB:94±5; C:110±15 bpm) and cardiac output (FB:3.45±0.5; C:4.70±1.0 L/min) at baseline when compared to controls, and reduced inotropic and chronotropic responsiveness to isoproterenol and calcium gluconate. These findings suggest that the development of fumonisin-induced pulmonary edema in swine is cardiogenic in origin, possibly resulting from sphingosine-mediated left-sided heart failure.
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology