Purified fumonisin B1 decreases cardiovascular function but does not alter pulmonary capillary permeability in swine

Abstract

Fumonisins are mycotoxins produced by Fusarium verticillioides, which induce acute pulmonary edema in swine. We previously reported that ingestion of fumonisin-containing culture material decreases cardiovascular function in swine (1996,a,b; Fundam. Appl. Toxicol. 31, 169-172; 33, 140-148; 1999, Am. J Vet. Res. 60, 1291-1300). The main purpose of this study was to confirm that fumonisin B1 was responsible for the observed cardiovascular changes. Treated pigs (n = 6) were given daily intravenous injections of purified fumonisin B1 at 1 mg/kg for 4 days, while controls (n = 6) were injected with equal volumes of saline. On day 5, pigs were anesthetized with butorphanol-chloralose and instrumented for hemodynamic studies. Terminally, bronchoalveolar lavage was performed on each pig to determine the relative permeability index of the pulmonary endothelium. Fumonisin B1-treated pigs had marked decreases in the maximal rate of change of left ventricular pressure (dP/dt(max)), mean aortic pressure, cardiac output, and arterial pO2, accompanied by increases in mean pulmonary artery pressure, oxygen extraction ratio, and blood hemoglobin concentration. Plasma and left ventricular sphingosine and sphinganine concentrations were markedly increased in treated pigs at day 5; however, there was no difference in the relative permeability index between groups. Serum cholesterol concentrations and activities of hepatic-derived enzymes were increased, and hepatocyte apoptosis and mitoses were present in the livers of fumonisin-treated pigs. In the lungs of treated pigs, there was proteinaceous edema and membranous accumulations in capillary endothelial cells. These results indicate that cardiovascular function is altered by fumonisin B1, and that fumonisin- induced pulmonary edema is caused by left-sided heart failure and not by altered endothelial permeability. Because of the potential for contamination of human foodstuffs by fumonisins, the cardiovascular toxicity of these compounds must be taken into consideration.