Page 894 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

850 SECTION | XIV Poisonous Plants

VetBooks.ir larkspur populations (D. nuttallianum and D. andersonii) cattle eat little or no tall larkspur before the plant has
elongated flowering racemes, and (2) weather patterns are
in Utah, Colorado, and Arizona (Gardner, unpublished
very important determinants of larkspur consumption
data). Reports of very high concentrations of MLA (up to
8.7 mg/g) in vegetative low larkspur (D. nuttallianum) (Pfister et al., 1999). Cattle often eat more tall larkspur
from Canada were contrasted with a concentration of during summer storms and reduce larkspur consumption
2 mg/g in flowering plants (Bai et al., 1994). Unlike tall during drought for reasons that are not clear. Another var-
larkspurs, concentrations of toxic alkaloids in low lark- iable that may play a role in the susceptibility of cattle to
spurs do not decline precipitously after senescence larkspur toxicosis is breed differences. Anecdotal observa-
(Gardner, unpublished data). MLA is the major toxic tions of differences in the susceptibility of different
alkaloid in plains larkspur (D. geyeri), with concentrations breeds of cattle to larkspur toxicosis have been supported
ranging from 1 to 4 mg/g in Wyoming and Colorado. We using a rodent model in which different strains of mice
emphasize that NUD is more toxic than MLA, and both had up to a twofold difference in LD 50 to MLA (Welch
alkaloids are frequently found together in low larkspurs et al., 2009a).
(Gardner, unpublished data). Thus, the potential lethality Cattle generally begin consuming tall larkspur after
of low larkspurs can be highly variable depending on flowering racemes are elongated, and consumption
alkaloid concentrations and plant density. increases as larkspur matures. Consumption usually peaks
The primary result of larkspur toxicosis is neuromus- during the pod stage of growth in late summer, when cat-
cular paralysis from blockage at the postsynaptic neuro- tle may eat large quantities (25 30% of diet as herd aver-
muscular junction (Benn and Jacyno, 1983). MLA also age; .60% on some days by individual animals).
elicits central effects in mice and rats (Stegelmeier et al., Because larkspur toxicity generally declines throughout
1998). Larkspur alkaloids compete as postsynaptic inhibi- the growing season and cattle tend to eat more larkspur
tors of acetylcholine particularly at α 1 nicotinic sites after flowering, the period of greatest danger has been
(Dobelis et al., 1999). MLA strongly competes with termed a “toxic window” (Pfister et al., 2002). This toxic
α-bungarotoxin at nicotinic acetylcholine receptors window extends from the flower stage into the pod stage,
(nAChRs). Larkspur alkaloid binding to nAChRs appears or approximately 5 weeks depending on temperature and
to be correlated with toxicity in various tissues and may elevation (Figure 61.3). Many ranchers typically defer
explain sheep tolerance to larkspur if larkspur toxins bind grazing on tall larkspur-infested ranges until the flower
less avidly to nAChRs in sheep (Stegelmeier et al., 1998). stage to avoid death losses. This approach wastes much
Clinical signs of intoxication include muscular weak- valuable forage and often places cattle into larkspur-
ness and trembling, straddled stance, periodic collapse infested pastures when risk of losses is high. An
into sternal recumbency, respiratory difficulty, and death
while in lateral recumbency. An effective dose of larkspur
causes labored breathing, rapid and irregular heartbeat, High High
Toxicity Palatability
and collapse but not death. The effective i.v. dose for
purified MLA is 2 mg/kg BW in calves versus 10 mg/kg
in sheep given a single injection (Panter, unpublished Toxic
data). Nation et al. (1982) reported that an effective window
dose of MLA in cattle receiving two i.v. injections was Relative toxicity Relative palatability
1.1 mg/kg. Conversely, the effective i.v. dose for deltaline
in both calves and sheep is 50 mg/kg (Panter, unpublished
data). Cattle typically show clinical signs (i.e., tremors
Low risk
and periodic collapse) when given an MLA DAN dose grazing window
(i.e., via ground plant) of 20 6 3 mg/ kg BW (Pfister
et al., 1994). Stress and/or exertion will reduce the effec- Low Low
tive dose. Assuming an MLA 1 DAN concentration of
Veg/Bud Flower Pod
5 mg/g (dry wt), a 450-kg cow may show clinical
Phenological stage
signs after rapidly eating 1.8 kg (dry wt) of tall larkspur
( 7.2 kg wet wt). FIGURE 61.3 Relationship between toxicity and palatability in tall
Key factors in larkspur intoxication are the amount larkspurs. Most cattle deaths are predicted to occur during the toxic win-
eaten and the rate of ingestion. Studies utilizing direct dow when the concentration of toxic alkaloids is relatively high and con-
observations of grazing animals have provided a number sumption by cattle begins to increase after flowering racemes elongate.
There is a low-risk grazing window early in the season before flowering
of insights into the amount and timing of tall larkspur
when larkspur is generally very toxic but risk is low because cattle typi-
ingestion. More than 10 such studies have been conducted cally eat little tall larkspur during this phenological stage. There is also a
since 1986 and have led to two major conclusions: (1) low-risk grazing window in late summer after pods shatter.