Lily Of The Valley

LILY OF THE VALLEY (Convallaria majalis L.), a perennial plant of the Liliaceae family, commonly found in deciduous forests (especially of temperate climate) in all parts of the world except Africa. The plant has a creeping rhizome, no above-ground stem, and two broad, oblong-oval leaves between which on a rounded scape are located from 6 to 12 white, fragrant flowers of a bitter, unpleasant taste. The leaves themselves are odorless, with a sweet-bitter, sharp taste.

In folk medicine since ancient times, various species of L. were considered a good therapeutic agent, especially for cardiac and nervous diseases and dropsy.--The specific active substances of L., of the glycoside type, were discovered by Walz in 1853. Of these, convallamarin (empirical formula C₂₃H₄₄O₁₂), which acts on the heart, is of greatest importance. It is a crystalline powder of bitter taste, readily soluble in water. Another glycoside, convallarin (C₃₄H₆₂O₁₁), has mainly a laxative effect. The roots and leaves of lily of the valley contain less convallamarin compared to the flowers.

The physiological action of L. was first studied in 1867 by Marme, but was mainly studied both experimentally on animals and in the clinic in the 1880s by a number of Russian authors, mostly students of Botkin (Troitsky, Bogoyavlensky, Isaev, Ksenzenko and others), as well as abroad (Reuss, Paul, Sée and others.). It turned out that the effect on the heart of various preparations of L., as well as its glycoside convallamarin, very much resembles the action of glycosides of the digitalis group.--The action of L. on the heart, depending on the dose, consists of various phases. The most characteristic phenomena of the first phase are: slowing of the heart rate, resp. pulse, and strengthening of systole. The slowing of the heart rate is explained mainly by an increase in the tone of the vagus nerve, which also explains the observed greater diastolic relaxation of the heart. The passage of impulses through the bundle of His is hindered due to vagal influence (see Digitalis, Dromotropic action).

The next, 2nd phase--toxic--at large doses is characterized by an increased pulse rate and an even greater strengthening of systole. In this phase, the difficulty of conduction through the bundle of His increases; sometimes partial and complete heart block are observed (see).--The final, 3rd phase, inevitably leading to cardiac arrest, is the completion of the second. The heart block becomes partial to complete, the dissociation of rhythm becomes more pronounced, the parts of the heart work under the influence of their own nerve nodes. In the final phase, an even greater increase in pulse rate, extrasystoles, and fibrillation and flutter of the atria and ventricles are observed, and finally cardiac arrest.--On the vessels of the splanchnic area, preparations of L., like other cardiac glycosides, act in a constricting manner; other vessels, such as cutaneous, muscular, cerebral and probably coronary and renal, dilate. The constriction of vessels should be attributed to the direct action on the smooth muscles of the vessels and only partly to the excitation of the vasomotor center.

In the first phase, which is the only therapeutic phase, blood pressure either does not change, or slightly increases, or even decreases, depending on the state of excitability and the nature of the work of the heart, vessels, vasomotor center, and vagus center before the introduction of L. preparations (for details, see Digitalis). The diuretic effect observed in cardiac patients when treated with L. should be attributed mainly to the regulation of blood circulation as a whole. On the gastrointestinal tract, the glycosides of L. and especially convallarin act to one degree or another irritantly; in pronounced cases, the irritation can manifest as increased peristalsis, diarrhea, vomiting. The emetic effect is explained, as with other cardiac glycosides, in addition to the reflex, also by the central action on the vomiting center. By analogy with other cardiac glycosides, the increase in tone and peristalsis of the smooth muscles of the intestine should be attributed, in addition to the action through the intestinal mucosa, also to the direct action of L. glycosides on smooth muscle tissue (through the blood), and possibly also through the vagus center.

On the central nervous system, besides the mentioned vagus centers and partly the vasomotor center, L. preparations have no special action, but of course can act on it through changes, resp. regulation of blood circulation as a whole. The local action (e.g., on mucous membranes, as well as when introduced into the skin and under the skin) of convallamarin, like other cardiac glycosides (digitoxin, strophanthin, adonidin, etc.), leads to a more or less pronounced irritation (pain, hyperemia, tissue edema), which is replaced by a more or less prolonged anesthesia (anaestheticum dolorosum); convallamarin has not received therapeutic application for purposes of local anesthesia.--The strength of the action of convallamarin on the heart can be judged by comparing convallamarin with other cardiac glycosides. Thus, to achieve systolic arrest of the frog's heart with subcutaneous injection, the following absolute (minimal) amounts of various cardiac glycosides were found necessary (in grams, per 1 g of body weight of the frog): K-Strophanthin (Merck)-0.0000011; Digitoxinum crystallis. (Merck)-0.0000085; Convallamarinum (Merck)-0.0000047; Digitaleinum (Merck)-0.000024 (Straub). From the comparison of these and similar figures, it is clear that convallarin itself is a very potent cardiac agent.

Practically, however, the lower toxicity and weaker cardiac action of L. preparations with usual administration per os compared, for example, with preparations of digitalis (especially digitoxin) should be attributed mainly to the lower stability, faster destructibility of convallamarin. This also explains why this glycoside does not accumulate in the heart, does not give cumulation. The therapeutic indications follow from the above. Indeed, L. is either a temporary replacement or an aid in the treatment with foxglove both for organic and functional diseases of the cardiovascular system. Furthermore, in tachycardias, 'nervous' heart palpitations, 'nervous' excitability of the heart, the resulting slowing of the pulse, decrease in sensitivity of the automatic centers of the heart, and slowed conduction through the bundle of His are of great importance. The third most important moment is the effect of L. preparations on the vessels: increase in vascular tone in the abdominal cavity and better blood filling of the brain, heart, kidneys, skin and muscles. Finally, the reputation of L. as an anti-nervine agent attributed to it by some clinicians should find its explanation in the regulation of general as well as local circulation.

Main contraindications: acute - catarrhal conditions of the gastrointestinal tract, liver, far-advanced degeneration of the cardiac muscle.--Preparations. 1) Tinctura Convallariae majalis (Ph. VII), tincture of L., lily of the valley drops, tincture of freshly collected herb of flowering lily of the valley on 90° alcohol (100 parts herb, 120 parts alcohol). Specific gravity 0.926-0.930. A transparent, greenish-brown liquid of bitter, aromatic taste, acidic reaction on litmus. Highest single dose - 1.25 g, daily - 3.75 g. 2) Convallamarin (C₂₃H₄₄O₁₂), a white crystalline powder, readily soluble in water and alcohol. Subcutaneous doses 0.005-0.01; per os single dose up to 0.05, daily - up to 0.25.