Prothrombotic changes occurring in the prodromal stages of carbohydrate-induced laminitis were investigated. Hemostatic alterations were evaluated by determining platelet counts, platelet survival, activated partial thromboplastin time, one-stage prothrombin time, and monocyte procoagulant activity. Thrombosis of vessels in the hoof wall was evaluated by contrast arteriography and histologic examination. Of 5 horses, 4 became lame between 28 and 52 hours after carbohydrate administration. Mean platelet count in laminitis-affected horses was lower throughout the prodromal stages of laminitis, compared with that in control horses, but differences were not statistically significant. However, survival of indium-111-labeled platelets was less than the value in control horses by 6 hours after carbohydrate administration. Arteriography of disarticulated feet revealed marked reduction in blood supply to hooves in laminitis-affected horses. Histologic examination of the laminar dermis disclosed microthrombi in venules of the laminar dermis in 2 of 4 affected horses. Statistically significant changes in prothrombin time were not observed, and changes in activated partial thromboplastin time were slight and occurred only at the onset of lameness. Statistically significant changes in monocyte procoagulant activity were not observed. Plasma endotoxin-like activity was not detected in laminitis-affected horses. These data indicate that platelet survival was decreased within the first 6 hours after induction of carbohydrate-induced laminitis, but systemic activation of the coagulation system was not detected.

Forty-five claw lamed cows with pododermatitis circumscripta, hyperplasia interdigitalis, and dermatitis verrucosa were treated surgically through resection of necrotic tissues, currettage, antibiotics application, and compressive bandage, under retrograde intravenous regional anesthesia of claw. At 7 days postoperation were showed lameness score 0, absense of swelling of extremitis, without fistulation and purulent exudate in wound. Mean duration time of action of local anesthetic drug was 75 minutes and mean operation time for treatment of pododermatitis circumscripta, hyperplasia interdigitalis, and dermatitis verrucosa was 35 minutes, 20 minutes, and 21 minutes, respectively.

Loline and ergot alkaloids found in endophyte-infected (Acremonium coenophialum) tall fescue (EITF) cause vasoconstriction of equine vessels in vitro. An aggregate risk study was used to evaluate the association between horses exposed to EITF and development of laminitis. Veterinary teaching hospitals participating in the Veterinary Medical Data Base were grouped by whether equine accessions were likely to have been at high, moderate, or low risk for exposure to EITF. From 1980-1990, there were 185,781 accessions, of which 5,536 had diagnosis of laminitis. Proportion of equine accessions with laminitis reported by veterinary teaching hospitals for high, moderate, and low risks, were 3.41, 3.04, and 2.00 cases/100 accessions, respectively (P < 0.0001). Comparison of the proportion of accessions with laminitis in the high- and moderate-risk groups with that in the low-risk group revealed significant differences between risk groups over all months (P = 0.063) and differences from month to month within risk groups (P = 0.0001). If the difference among risk groups is attributed entirely to exposure to EITF, the population-attributable risk is 7 cases/1,000 admissions, or 15% of all admissions for laminitis at veterinary teaching hospitals in our data base. Preliminary data support an association between hoses exposed to EITF and increased risk of laminitis; however, studies at the individual animal level are indicated to confirm this hypothesis.

Starling forces and hemodynamics in the digits of 5 horses were studied during early laminitis induced by oral administration of an aqueous extract of black walnut (Juglans nigra). The black walnut extract was prepared from heartwood shavings and was administered by nasogastric tube. Heart and respiratory rates, rectal temperature, central venous and arterial pressures, digital pulses, and signs of lameness were monitored. Blood samples were collected for determination of WBC count, hemoglobin concentration, and PCV and for endotoxin and tumor necrosis factor assays. Total WBC count and central venous pressure were monitored until they decreased by 30 or 20%, respectively. These decreases in WBC count and central venous pressure were observed 2 to 3 hours after dosing with black walnut extract. Respiratory and heart rates, body temperature, systolic and diastolic blood pressures, PCV, and hemoglobin concentration did not change significantly. Anesthesia was induced, heparin (500 IU/kg of body weight) was administered IV, and a pump-perfused extracorporeal digital preparation was established. Digital arterial and venous pressures were maintained at 100 and 30 mm of Hg, respectively. Blood flow, capillary pressure, lymph and plasma protein concentrations, and weight of the isolated digit during rapid increase in venous pressure were measured. Isogravimetric capillary filtration coefficient, vascular compliance, vascular and tissue oncotic pressures, tissue pressure, osmotic reflection coefficient, and precapillary and postcapillary resistances were calculated. Mean digital blood flow was 14 ml/min/100 g, capillary pressure was 52 mm of Hg, and vascular compliance was 0.06 ml/mm of Hg. The vascular and tissue oncotic pressures were 21.49 and 4.93 mm of Hg, respectively. The osmotic reflection coefficient was 0.71, and tissue pressure was 41 mm of Hg. The precapillary and postcapillary resistances were 7 and 2 mm of Hg/ml, respectively. Capillary permeability to proteins was not significantly different from that previously measured in healthy horses, suggesting that the increased capillary filtration coefficient reflected increased capillary hydrostatic pressure and perfusion of previously nonperfused capillaries. Neither endotoxin nor serum tumor necrosis factor activity was detected in any samples. The hemodynamic and Starling forces observed in this study were similar to those observed after laminitis was induced by administration of a carbohydrate gruel. Significant differences between the 2 models were detected for total vascular resistance, postcapillary resistance, and capillary filtration coefficient. It is likely that these differences were identified because the horses administered the black walnut extract were at an earlier stage in the disease process. The findings of this study suggest that the increase in capillary pressure causes transvascular fluid movement, resulting in increased tissue pressure and edema. We hypothesize that further increases in tissue pressure may collapse capillary beds and lead to tissue ischemia.

The balance of coagulation and fibrinolysis was studied in 15 horses during the prodromal stages of acute laminitis induced by carbohydrate overload. Progression of the disease was stopped 12 to 24 hours before the expected onset of lameness in trial 1 (8 horses) and at the onset of lameness in trial 2 (7 horses). The end points in each trial were identified by specific changes in blood pressures (trial 1) and by changes in pulse, rectal temperature, and arterial pressure (trial 2) that were anticipated on the basis of original description of the experimental model. Blood samples for hemostasis evaluation were collected before and after carbohydrate overload in trial 1 and after carbohydrate overload in trial 2. Significant changes were not detected in platelet count, mean platelet volume, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, plasminogen concentration, alpha-2-antiplasmin, antithrombin III, protein C, thromboxane B2, or fibrin(ogen) degradation product concentration. We concluded that an imbalance in coagulation and fibrinolysis is not pathogenic in the onset of experimentally induced equine acute laminitis. Because several test methods used to evaluate hemostasis in these horses were new, reference values for 34 healthy adult horses were established.

Twelve horses, with acute laminitis (primarily in the forefeet) at 12 hours after intragastric dosing with an aqueous extract of black walnut (Juglans nigra) heartwood, were studied. The distribution of perfusion of blood to the foot and to outlined regions within the foot was quantified, using gamma scintigraphy of regionally 99mTC. labeled macroaggregated albumin, before and 12 hours after extract administration. Horses 1 to 3 were not studied further. Perfusion was quantified again for horses 4 to 12 at 84 hours after extract administration. At the onset of acute laminitis, horses 7 to 12 were administered a single dose of prazosin (0.025 mg/kg of body weight, IV) immediately after scintigraphy of the right forelimb and before scintigraphy of the left forelimb. When compared with baseline images, perfusion to the forefoot of horses after the development of acute laminitis was quantitatively decreased vs perfusion to the entire distal portion of the forelimb. Also with the onset of laminitis, perfusion also decreased to the dorsal laminar and coronary corium regions vs the distal portion of the forelimb. The acute laminitis-associated deficit in perfusion to the dorsal lamina was greater in magnitude than the deficit in perfusion to either the coronary corium or the entire forefoot. Equivalent deficits in the distribution of perfusion were not detected in forelimbs from horses with acute laminitis and which had been treated with prazosin. When compared with baseline images, perfusion to the dorsal lamina was increased in relation to perfusion to the distal portion of the limb at postdosing hour 84. Prazosin treatment did not influence that increase in perfusion to the dorsal lamina.

Tall fescue (Festuca arundinacea Shreb) hay from a source known to cause "fescue foot" in grazing cattle was extracted with 80% ethanol. The ethanolic extract was further refined and fractionated into cation,nion, and neutral f fractions by ion-exchange chromatography. The cation fraction was partitioned with alkaline-chloroform to give chloroform-extractable cation and residual cation fractions. All fractions plus the crude ethanolic extract were assayed for toxic activity by intraperitoneal injection into 12 calves (weighting 152.4 to 241.3 kg each) over a 14-day period. Clinical signs of fescue foot were observed on the 5th day in calves given the anion and crude ethanolic extracts. Lameness, swelling, and reddening of the rear coronary bands, discoloration of the tip of the tail, and other signs of fescue foot were seen. Microscopically, coronary bands and tail tips of affected calves had blood vessels with thick walls and small lumens.

Surface temperatures of hoofs of calves given toxic anion fractions of tall fescue were measured with an infrared sensitive camera. These changes expressed in terms of a weighted average coronary band temperature relate to clinical signs of fescue foot. The weighted average coronary band temperature values for control calves given saline solution were 27 to 31 C; those values of test calves given anion fractions of tall fescue were as low as 22 +/- 1 C. Videothermometry provides an independent, permanent, objective measure that is useful in assessing fescue-foot potential of tall fescue fractions by intraperitoneal injection. Videothermometry may also serve as a clinical means for determining progression of the total fescue foot syndrome.

The in vitro reactivity of vasoconstrictive mediators that are implicated in acute laminitis was determined in palmar and plantar digital arteries and veins obtained from healthy horses and in palmar digital vessels of horses with early laminitis (Obel grade I). To obtain baseline reactivity data, 3 experiments were conducted, using healthy horses: (1) the reactivity of palmar and plantar digital arteries and veins to angiotensin II, norephinephrine, and 5-hydroxytryptamine (serotonin) were compared; (2) the direct effects of bacterial endotoxin on vascular reactivity were assessed; and (3) the reactivity of palmar digital arteries and veins to angiotensin II, norepinephrine, prostaglandin F2 alpha (PGF2 alpha), sertonin, and a thromboxane-endoperoxide analog (U46619) were determined. The vascular reactivity of these same 5 vasoconstrictors then was determined in horses with early laminitis and was compared with data from healthy (control) horses. Obel grade-I laminitis was experimentally induced in horses using carbohydrate overload. Dose responses were conducted for each agent at concentrations between 10(-8)M and 10(-4)M. The potency of a drug was defined as the mean effective concentration necessary to induce 50% of maximal contraction (EC50). There were no differences in EC50 concentrations and in maximal contractions between forelimb and hind limb arteries and veins for angiotensin II, norepinephrine, and serotonin. Incubation with endotoxin had no effect on the reactivity of arteries and veins to angiotension II, norepinephrine, and serotonin. In healthy horses, serotonin and U46619 were more potent arterial constrictors than were norepinephrine PGF2 alpha, and angiotensin II. In veins, serotonin, U46619, and angiotension II were similar in potency, and all were significantly (P less than 0.05) more potent than were norepinephrine and PGF2 alpha. Serotonin induced greater arterial constriction than did all other agents tested. There were no differences in the maximal venoconstriction induced by norepinephrine, PGF2 alpha, serotonin, and U46619. Angiotensin II induced the least amount of arterial and venous constriction. Maximal contractions were significantly (P less than 0.05) greater for veins than for arteries for all agents evaluated, except for angiotensin II. In horses with early laminitis, angiotensin II and serotonin were the most potent (smallest EC50 values) constricting agents for the arterial and venous segments and norepinephrine and PGF2 alpha were the least potent. Serotonin and norepinephrine induced significantly (P less than 0.05) greater venoconstriction than did the other agents. Angiotensin II induced the least arterial and venous contraction. For all agonists except angiotensin II, the mean EC50 values for vessels from horses with early laminitis were either similar or greater than those for vessels from control horses. The EC50 values for norepinephrine and the thromboxane analog were significantly (P less than 0.05) greater for vessels from horses with early laminitis, compared with those from control horses. The mean maximal contractions for all vasoconstrictors, except angiotensin II, were significantly (P less than 0.05) less for vessels from horses with early laminitis. Significantly greater venous-to-arterial maximal contraction ratios were found for norepinephrine and serotonin in horses with laminitis, compared with those ratios in control horses. These data suggested that the digital vasculature of horses with early laminitis was not more sensitive to the vasoconstrictor substances tested and that the vessels were significantly less repsonsive than was vasculature from the control horses. However, the venous-to-arterial contraction ratios were either the same or significantly (P less than 0.05) greater in horses with laminitis.