C.C. Pollitt School of Veterinary Science, University of Queensland, St Lucia, Qld 4072
Proc. Aust. Equine Sc. Symp., Vol 1, 2006
Laminitis is the most serious disease of the equine foot and causes pathological changes in anatomy that lead to long lasting, crippling changes in function. Australia, with a dependency on pasture as a food source for horses has a high incidence of laminitis induced by grass consumption. Selective breeding for high fructan concentration, in pastures designed for ruminants, is increasing the incidence of grass founder in horses. Such pastures exposed to low nocturnal ground temperature and bright sunny days, as occurs in spring and autumn, rapidly accumulate dangerously high fructan levels, sufficient to trigger laminitis. Drought breaking rain is also linked to laminitis; new shoots are rich in fructan. Intuitively horse owners overgraze and reduce irrigation and fertilizer to control pasture fructan despite data showing these practices actually increase fructans in grass. Dosing horses with 3-4 kg of pure commercial grade fructan, extracted from plants as oligofructose (OF), causes experimental laminitis, almost without fail (van Eps and Pollitt, 2006). When consumed by horses, OF is rapidly fermented in the hindgut, where Streptococcal microorganisms proliferate exponentially and for 24h are the dominant microflora (Milinovich et al., 2006). The hindgut events that follow generate circulating laminitis trigger factors (LTFs) that initiate hoof lamellar lesions 24h post OF dosing. Laminitis is more severe if, during the developmental phase, the circulation of the foot is dilated (Pollitt and Davies, 1998). Enzymes (matrix metalloproteinases, MMPs) capable of destroying key components of the hoof lamellar attachment apparatus are upregulated and activated in hoof lamellar tissues exposed to LTFs (Kyaw-Tanner and Pollitt, 2004). The substrates of MMP activity are the very ultrastructural filaments (laminin-5) that attach the inner hoof wall lamellae to the distal phalanx. Not surprisingly a key lesion of laminitis is laminin-5 cleavage (French and Pollitt, 2004). Since discovering that laminitis pathogenesis is enzyme dependent we have successfully prevented the disease by prolonged cooling (2-5oC) of the distal limb (van Eps and Pollitt, 2004). Cooling not only dampens enzymatic activity it produces profound vasoconstriction and together this limits the pathological effect of LTF delivery to the feet. Fortunately, prolonged distal limb cryotherapy does no harm and horses ignore it (Pollitt and van Eps, 2004). Interestingly, despite the dogma of decades, no lesions due ischaemia or reperfusion injury can be found now that molecular investigative techniques are focused on laminitis (Belknap et al., 2006). Thus, we have discovered a pathway that links the metabolism of pasture grass (fructan production) to fermentative activity in the equine large bowel (Streptococcal proliferation) that triggers laminitis via uncontrolled MMP activation and attachment failure between hoof and bone. This new knowledge has led to an effective preventive strategy; prolonged distal limb cryotherapy. The task ahead is to discover the precise nature of LTFs so that their effect can be blocked and horses can at last be treated rationally and efficaciously. We also need to devise ways to manage horse pastures to reduce fructan production, manage horses to reduce pasture fructan consumption and manage fructan fermenting hindgut bacteria to prevent formation of laminitis trigger factors. Difficult, but not impossible.
BELKNAP, J.K., GIGU?RE, S., PETTIGREW, A., et al. (2006) Equine Vet. J., 38, (in press).
FRENCH, K.R. and POLLITT, C.C. (2004) Equine vet. J., 36, 242-7.
KYAW-TANNER, M. and POLLITT, C.C. (2004) Equine Vet J, 36, 221-225.
MILINOVICH, G.J., TROTT, D.J., BURRELL, P.C., et al. (2006) Environ. Microbiol. , 8, 885?898.
POLLITT, C.C. and DAVIES, C.T. (1998) Equine vet. J. Suppl., 26, 125-32.
POLLITT, C.C. and VAN EPS, A.W. (2004) Equine vet. J., 36, 216-220.
VAN EPS, A.W. and POLLITT, C.C. (2004) Equine vet. J., 36, 255-260.
VAN EPS, A.W. and POLLITT, C.C. (2006) Equine vet. J., 38, (in press). .