Purified fumonisin B-1 decreases cardiovascular function but does not alter pulmonary capillary permeability in swine

Fumonisins are mycotoxins produced by Fusarium verticillioides, which induc e 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. Bes. 60, 1291-1300). The main purpose of this study was to confirm that fumonisin B-1 was responsible for the observed cardiovascular changes. Treated pigs (n = 6) were given daily intravenous injections of purified f umonisin B-1 at 1 mg/kg for 4 days, while controls (n = 6) were injected wi th equal volumes of saline. On day 5, pigs were anesthetized with butorphan ol-chloralose and instrumented for hemodynamic studies. Terminally, broncho alveolar lavage was performed on each pig to determine the relative permeab ility index of the pulmonary endothelium. Fumonisin B-1-treated pigs had ma rked decreases in the maximal rate of change of left ventricular pressure ( dP/dt(max)), mean aortic pressure, cardiac output, and arterial pO(2), acco mpanied by increases in mean pulmonary artery pressure, oxygen extraction r atio, and blood hemoglobin concentration. Plasma and left ventricular sphin gosine and sphinganine concentrations were markedly increased in treated pi gs at day 5; however, there was no difference in the relative permeability index between groups. Serum cholesterol concentrations and activities of he patic-derived enzymes were increased, and hepatocyte apoptosis and mitoses were present in the livers of fumonisin-treated pigs. In the lungs of treat ed pigs, there was proteinaceous edema and membranous accumulations in capi llary endothelial cells. These results indicate that cardiovascular functio n is altered by fumonisin B-1, and that fumonisin-induced pulmonary edema i s caused by left-sided heart failure and not by altered endothelial permeab ility. Because of the potential for contamination of human foodstuffs by fu monisins, the cardiovascular toxicity of these compounds must be taken into consideration.