Color Doppler ultrasonography was used to compare blood flow characteristics in the caudal artery of heifers fed diets with endophyte (Neotyphodium coenophialum) infected (E+) or noninfected (E-) tall fescue seed. Eighteen crossbred (Angus x Brangus) heifers were assigned to 6 pens and were fed chopped alfalfa hay for 5 d and chopped alfalfa hay plus a concentrate that contained E-tall fescue seed for 9 d during an adjustment period. An 11-d experimental period followed, with animals in 3 pens fed chopped alfalfa hay plus a concentrate with E+ seed and those in the other 3 pens fed chopped hay plus concentrate with E E- seed. Color Doppler ultrasound measurements (caudal artery area, peak systolic velocity, end diastolic velocity, mean velocity, heart rate, stroke volume, and flow rate) and serum prolactin were monitored during the adjustment (baseline measures) and during the experimental period. Three baseline measures were collected on d 3, 5, and 6 during the adjustment period for comparison to post E+ seed exposure. Statistical analyses compared the proportionate differences between baseline and response at 4, 28, 52, 76, 100, 172, and 268 h from initial feeding of E+ seed. Serum prolactin concentrations on both diets were lower (P <0.001) than baseline beginning at 4 h from the start of the experimental period. However, trends in serum prolactin concentrations for heifers on the E- diet suggested ambient temperature was affecting these concentrations. Caudal artery area in E+ heifers had declined (P <0.10) from baseline by 4 h and was consistently lower (P <0.05) for the remainder of the period. Heart rates for E+ heifers were lower than the baseline rate from 4 (P <0.10) to 100 (P <0.001) h, but were similar (P >0.10) to the baseline for 172 and 268 h measures. Blood flow in E+ heifers was consistently lower than the baseline from 4 (P <0.05) to 172 (P <0.001) h, but was similar to the baseline at 268 h when heart rate was similar to the baseline rate. Caudal artery areas for the E- diet were similar to baseline areas except at 100 h when it was greater than baseline. Heart rates and flow rates for E- heifers did not differ (P >0.10) from baseline measures during the experimental period. Results indicated that onset of toxicosis was within 4 h of cattle exposure to E+ tall fescue and is related to vasoconstriction and reduction in heart rate.
Various alkaloids found in endophyte-infected tall fescue have been shown to elicit different effects in the grazing animal. As part of an ongoing characterization of vascular response generated by different alkaloids, the objective of this study was to examine the vasoconstrictive potentials of ergonovine (a simple lysergic acid derivative) and alpha-ergocryptine, ergocristine, and ergocornine (all ergopeptine alkaloids) using bovine lateral saphenous veins (cranial branch) biopsied from fescue-naïve cattle. Segments (2 to 3 cm) of vein were surgically biopsied from healthy crossbred yearling cattle (n = 18; 274 +/- 8 kg of BW). Veins were trimmed of excess fat and connective tissue, sliced into 2 to 3 mm sections, and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O(2)/5% CO(2); pH = 7.4; 37 degrees C). Tissue was allowed to equilibrate at 1 g of tension for 90 min before initiation of treatment additions. Increasing doses of each alkaloid (1 x 10(-10) to 1 x 10(-4) M) were administered every 15 min after buffer replacement. Data were normalized as a percentage of contractile response induced by a reference dose of norepinephrine (1 x 10(-4) M). Exposure of vein segments to increasing concentrations of ergocryptine, ergocristine, and ergonovine did not result in a contractile response until 1 x 10(-7) M, and ergocornine was even less potent (P < 0.05). Ergonovine had a greater maximal contractile intensity than ergocristine and ergocryptine (P < 0.05), with the 1 x 10(-4) M responses of ergonovine, ergocristine, ergocryptine, and ergocornine reaching maximums of 68.5 +/- 4.1, 45.5 +/- 4.5, 42.9 +/- 4.1%, and 57.2 +/- 9.9% of the norepinephrine maximum, respectively. The contractile response to increasing concentrations of ergonovine vs. ergocryptine, ergocristine, and ergocornine were opposite from previous evaluations of ergoline (e.g., lysergic acid) and ergopeptine (e.g., ergovaline) alkaloids using this bioassay, where the ergopeptine generated the greater contractile intensity. These data indicate that ergopeptines structurally different only at a single position of the peptide moiety do not exhibit differing contractile responses when considering contractile intensity. This difference may alter the potency when considering ergocornine was less potent than ergocryptine or ergocristine. These alkaloids may need to be considered when evaluating causative agents vasoconstriction associated with tall fescue-induced toxicosis.
Vasoconstriction is a response associated with consumption of toxic endophyte-infected tall fescue. It is not known if endophyte-produced alkaloids act alone or collectively in mediating the response. Therefore, the objective of this study was to examine the vasoconstrictive potentials of selected ergot alkaloids, individually or in paired combinations, using bovine lateral saphenous veins biopsied from fescue-naïve cattle. Segments (2 to 3 cm) of vein were surgically biopsied from healthy crossbred yearling heifers (n = 22; 330 +/- 8 kg of BW). Veins were trimmed of excess fat and connective tissue, sliced into 2- to 3-mm sections, and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O(2)/5% CO(2); pH = 7.4; 37 degrees C). Increasing doses of ergovaline, lysergic acid, and N-acetylloline individually or in combination were evaluated. Contractile data were normalized as a percentage of the contractile response induced by a reference dose of norepinephrine (1 x 10(- 4) M). Increasing concentrations of lysergic acid did not result in an appreciable contractile response until the addition of 1 x 10(- 4) M lysergic acid. In contrast, the vascular response to increasing concentrations of ergovaline was apparent at 1 x 10(- 8) M and increased to a maximum of 104.2 +/- 6.0% with the addition of 1 x 10(- 4) M ergovaline. The presence of N-acetylloline did not alter the onset or magnitude of vascular response to either lysergic acid or ergovaline. The presence of 1 x 10(- 5) M lysergic acid with increasing concentrations of N-acetylloline and ergovaline generated an increased contractile response during the initial additions compared with the responses of N-acetylloline and ergovaline alone. In the presence of 1 x 10(- 7) M ergovaline, the contractile response increased with increasing concentrations of N-acetylloline and lysergic acid. Neither N-acetylloline nor lysergic acid elicited an intense contractile response individually (maximum contractile responses of 1.9 +/- 0.3% and 22.6 +/- 4.1%, respectively), suggesting that this was the result of the repetitive addition of 1 x 10(- 7) M ergovaline. These data indicate that ergovaline is a more potent vascular toxicant than lysergic acid or N-acetylloline. The contractile responses of the ergovaline and lysergic acid combinations appeared to differ from the individual dose responses. These data support the possibility that an additive alkaloid exposure effect may exist and should be considered during evaluations of ergot alkaloids.
Ergot alkaloids have been associated with vasoconstriction in grazing livestock affected by the fescue toxicosis syndrome. Previous in vitro investigations studying how ergot alkaloids caused vasoconstriction have shown that ergovaline has a distinct receptor affinity and sustained contractile response. A similar contractile response has not been noted for lysergic acid. The objectives of this study were to determine if repetitive in vitro exposure of bovine lateral saphenous vein to lysergic acid or ergovaline would result in an increasing contractile response and if a measurable bioaccumulation of the alkaloids in the vascular tissue occurs over time. Segments of vein were surgically biopsied from healthy, Angus x Brangus cross-bred, fescue-naïve yearling heifers (n = 16) or collected from healthy mixed breed and sex cattle immediately after slaughter (n = 12) at a local abattoir. Veins were trimmed of excess fat and connective tissue, sliced into cross-sections, and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O(2)/5% CO(2); pH = 7.4; 37 degrees C). Contractile responses to repetitive additions of ergovaline (1 x 10(-9) and 1 x 10(-7) M) and lysergic acid (1 x 10(-5) and 1 x 10(-4) M) were evaluated using the biopsied veins. For the bioaccumulation experiments, veins collected at the abattoir underwent repetitive additions of 1 x 10(-7) M ergovaline and 1 x 10(-5) M lysergic acid and the segments were removed after every 2 additions and media rinses for alkaloid quantification via HPLC/mass spectrometry. Contractile data were normalized as a percentage of contractile response induced by a reference dose of norepinephrine (1 x 10(-4) M). Repetitive additions of 1 x 10(-9) M ergovaline and 1 x 10(-5) and 1 x 10(-4) M lysergic acid resulted in contractile response with a negative slope (P < 0.02). In contrast, repetitive addition of 1 x 10(-7) M ergovaline resulted in a contractile response that increased with each addition (P < 0.01). Lysergic acid and ergovaline were detected at all 4 exposure levels (2x to 8x), but only the 1 x 10(-7) M ergovaline treatment resulted in increased tissue content as the number of exposures increased (P < 0.05). These data indicate that ergovaline, but not lysergic acid, bioaccumulates with repetitive exposure in vitro. These results suggest that ergovaline may have a greater potential for inducing toxicosis in grazing animals than lysergic acid because of its potential to bioaccumulate at the cellular site of action.
Despite increasing public scrutiny of practices used in raising animals for food, there is little readily available information about how cattle handling is managed in feedyards. The purpose of this study was to score cattle handling in commercial feedyards using the most widely adopted program for managing cattle handling, and to make these scores available as evidence of producer commitment to proper care and handling of cattle. Our objectives were to estimate compliance with the Beef Quality Assurance Feedyard Assessment (BQA FA) for cattle handling, to validate 6 cattle handling categories of the BQA FA, and to document management practices and elements of facility design. Categories scored were electric prod use; chute operation; rates of cattle vocalizing, stumbling, and falling; and rate of cattle jumping and running. This study compiles findings for cattle handling scores in commercial feedlots using the BQA FA. Of 28 sites, average scores were in compliance with BQA FA for the following 4 categories: electric prod use, vocalization, stumbling, and falling. For the following 2 categories, average scores were not in compliance: a score of 4.2% versus the target of 0% was recorded for cattle caught improperly in the squeeze chute; and a score of 52% versus the target of 25% was recorded for cattle that jumped or ran from the squeeze chute exit. All but one site exceeded this target. Curved crowd systems were recorded for 89% of feedyards, 11% used Bud Box systems, and 78.5% had rubber mats at the squeeze chute exit.
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