Mechanism of action

In isolated guinea pig heart models, both taxine A and B are potentially cardiotoxic, but taxine B is significantly more potent.² Taxine B has both negative inotropic and atrioventricular (AV) conduction delay effects.² Taxine B-induced AV conduction delay produces the classic increase in the electrocardiographic QRS complex duration that is observed in people, pigs, and guinea pigs with yew toxicosis.² The P wave may also be depressed or absent. Taxine B also acts as a class I antiarrhythmic drug and, thus, reduces cardiac contractility and the maximum rate of depolarization. Taxine cinnamate metabolites have an arrhythmogenic effect because of their ability to reduce coronary blood flow.

Taxines, particularly taxine B, are potent direct cardiac myocyte calcium and sodium channel antagonists that inhibit calcium and sodium currents in a manner similar to that of drugs such as verapamil, although taxines are more cardioselective. Potential cardiac effects associated with calcium channel blockade include increased coronary arterial vasodilation and blood flow and suppressed cardiac contractility, sinoatrial node automaticity, and AV node conduction. Like other calcium channel antagonists, taxines also suppress vascular smooth muscle contraction and can produce marked arterial vasodilation-mediated hypotension. Thus, the most common effect of taxine alkaloids in monogastric animals with yew toxicosis is peracute death due to diastolic cardiac standstill and possibly concurrent arterial vasodilation and hypotension.

Clinical signs

Often, the first evidence of yew toxicosis is unexpected death. Clinical signs or death may occur within minutes to several days after plant ingestion. Clinical signs, when observed, may include trembling, dyspnea, nausea, vomiting, and diarrhea. In a nonfatal case of T. cuspidata ingestion in a dog, clinical signs relating to central nervous system disturbance (particularly mydriasis, tetanic seizures, and increased aggressiveness) and gastroenteritis lasting one week were reported.³ Clinical signs in experimentally poisoned canaries and budgerigars included vomiting, regurgitation, dyspnea, depression, weakness, a wide-based stance, ataxia, cyanosis, and death.¹ As stated earlier, the most important electrocardiographic findings in poisoned mammals include bradycardia, depression or the absence of the P wave, and the increased QRS complex duration secondary to AV conduction delay.

Lesions, laboratory findings, and diagnosis

Gross and microscopic lesions are often absent in animals with yew toxicosis. Nonspecific findings at necropsy may include nonspecific pulmonary edema, congestion, and hemorrhage secondary to acute cardiovascular disturbance.^1,2 Evidence of acute gastroenteritis may be present if the animal survives long enough. Reported necropsy findings in subacutely poisoned ruminants also include myocardial hemorrhages and focal interstitial myocarditis.²

Diagnosis depends on a history of potential exposure, clinical signs, and the detection of either yew leaves in the gastric contents or taxines in gastric contents or blood by gas or liquid chromatography and mass spectroscopy.^1,2 The presence of 3,5-dimethoxyphenol, an agylactone of the taxine alkaloid taxicatine, in the gastric contents or blood has also been suggested as a marker for yew exposure. While the leaves of Taxus species are distinctive, submitting masticated samples to a plant identification laboratory for microscopic examination may be required for positive identification. Because of the small amount of leaves required for toxicosis, make sure to thoroughly and systematically examine the gastric contents.

Treatment

Sadly, death is often the first indication of yew toxicosis, and little opportunity for therapeutic intervention may be available. No specific antidote exists, and successful treatment has never been demonstrated experimentally.

Induce emesis within one hour (preferably within 30 minutes) after ingestion with due clinical prudence in asymptomatic animals in which electrocardiographic anomalies are not present. If large amounts of taxine alkaloids have already been absorbed, inducing emesis carries the potential risk of triggering cardiac and central nervous system complications. When emesis is contraindicated, consider gastric lavage. If emesis is induced or gastric lavage is performed, carefully examine the gastric contents for yew leaves, and submit samples for taxine alkaloid determination. Decontamination involving activated charcoal administration has been effective in some cases of subacute yew toxicosis in ruminants, so administer activated charcoal to potentially poisoned companion animals.