The term cardioprotective agents (cytoprotectors), which is a term used in cardiology, means medicinal products, which can cure myocardial dysfunction and prevent irreversible damage to the myocardium. Since the ischemia pathogenesis is multiple-factor, majority of cardioprotective products prevent the imbalance of energy metabolism and maintain ATP stores and promote survival of cardiomyocytes. Trimethazidine (preductal) is considered an reference cardioprotective agent, however, national and international literature has emphasized more than once that cardioprotection can be adequate when metabolitic and plant products are used. Positive hemodynamic and clinical effects of those compounds are due to their low toxicity and protective effects on not only the myocardium, but also on tissues of other vital organs and systems (liver, kidney, and nerve tissues).

Cardioprotective mechanisms are versatile: energy saving or more efficient energy production,,   "training by ischemia" leading to opening ATP-dependent channels, inhibition of Na + - H + -exchange; modulation of the function of the cell membrane (changes in the viscosity, functioning of ion channels), antioxidant and antiradical effects (provided a patient with coronary artery disease does not have any significant disorders of lipid metabolism, high levels of polyunsaturated fatty acids and free cholesterol in plasma lipoproteins and cell membranes). Current approaches to cardioprotection, in particular in patients with ischemia and reperfusion, are associated with the optimization of energy metabolism and energy production in the myocardium, and efficient function of the heart. Clinicians emphasize that even though the use of basic antianginal agents reducing myocardial oxygen demand and improving blood circulation eliminates anginal pain, it does not always prevent ischemic events leading to recurrent myocardial infarction and sudden death.

Therefore, the formulation and production of the domestic product Cratal, which is both a plant and metabolitic medicinal product, is of great importance.

CRATAL is manufactured by PJSC SIC “Borshchahivskiy Chemical Pharmaceutical Plant”. Cratal tablets contain taurine - 0.867 g; thick extract of haws  -  0,043 g; thick extract of motherwort - 0,087 g

Medicinal products derived from hawthorn are very popular: liquid extract and tincture, which contain triterpene acids (oleanolic acid, ursolic acid, crategic acid), improve coronary and cerebral circulation, and increase the sensitivity of the myocardium to cardiac glycosides. Hawthorn products slightly increase contractility of the myocardium, and reduce myocardial irritability. Hawthorn berries contain flavonoids, acetylcholine, tannins, phytosterols, which may provide a wider range of actions, e.g., anti-oxidant effect, and its ability to normalize sleep and exert beneficial effect on general condition. The motherwort tincture produced by the pharmaceutical industry also contains alkaloids and tannins, which have a sedative action. The mechanism of action of motherwort is similar to the effects of valerian. Its sedative effect may be associated with the increase in the inhibitory processes and decrease in CNS excitability. We can assume that motherwort, like valerian, may inhibit sodium channels and GABA.

Taurine is known to the pharmacy and general public in Ukraine by its use for the production of the domestic eye drops Taufon, which is used for the treatment of degenerative diseases of the retina and penetrating corneal wounds.

Taurine is a mild direct-acting cardiotonic agent, which not only saves energy required for myocardial contractility, but it also directly affects the contractile proteins of the myocardium, increases the level of calcium ions, and simultaneously prevents calcium overload of the mitochondria. Taurine reduces the toxicity of cardiac glycosides and potentiates the action of cardiac glycosides normalizing energy metabolism.

Cratal improved blood flow and functional status of ischemia in experimental animals, it lowered plasma lactate concentrations by half, and changes in the redox potential of the lactate-pyruvate system, increased coronary blood flow velocity, oxygen supply to the myocardium and oxygen concentrations in the blood flowing through the coronary sinus, thus, increasing the coronary reserve. Cratal demonstrated a protective action on myocardial contractility and energy metabolism in experimental rats with pituitrin-isadrine induced cardiomyopathy, it prevented  death of the animals. Cratal also increased myocardial contractility, prevented tachycardia in experimental rats with coarctation of the aorta,.

Taurine has multiple effects on adrenergic structures. It can reduce the release of mediators, accelerate catabolism, slow down the consumption rate, and it can have alpha-adrenoblocking action. Vasodilatory properties of taurine are associated with the increased level of prostacyclin, and the acceleration of the blood flow is associated with its antiplatelet action. The hypocholesteremic action of taurine is equally important: cholesterologenesis control and acceleration of cholesterol elimination of the body.

Pharmacodynamic studies of taurine demonstrated the hypoglycemic effect in diabetic patients, hepatoprotective action in patients with alcohol intoxication and other disorders.

There are study results demonstrating that the hepatoprotective action of taurine exceeds that of legalon, and is slightly inferior to essentiale and heptral.

Neuroprotective effect of taurine has also been demonstrated: when it was used in combination with the basic therapy (trental, cinnarizine) for the treatment of patients with organic impairment of brain tissue, it improved cortical function, memory and mental performance, accelerated the reduction of neurosis and somatic and autonomic disorders. Some reports recommended using taurine in a combination therapy to treat children with neurogenic bladder dysfunction.

There are some reports on effects of taurine on hormonal homeostasis. In particular, this effect is seen in the decrease in the plasma thyroxine and triiodothyronine levels.

The synergic action of the three above-mentioned components of Cratal let them widen their pharmacodynamics. Cratal has an inhibitory effect on the renin-angiotensin and kallikrein-kinin system, it has positive affects on the production of cAMP, and inhibits lipid peroxidation.

Experiments and clinical use have demonstrated that Cratal has a mild cardiotonic action, antianginal and antiarrhythmic effects, antiplatelet and sedative effects.

Clinical studies have demonstrated the feasibility of using CRATAL in the scheme of treatment of patients with ischemic heart disease in combination with the basic therapy (calcium channel blockers, beta-blockers, nitrates, ACE inhibitors). CRATAL may also be recommended for the use as monotherapy for patients with neurocirculatory dystonia. The daily dosage is 1 - 2 tablets 3 times a day before meal. The treatment plan should be established by a doctor.

Clinical trials of CRATAL demonstrated that in patients with coronary heart disease accompanied with mild hypertension, Cratal lowered systolic and diastolic blood pressure and then stabilized them, and reduced the heart rate within 10 - 20 days from the initiation of treatment. This action is believed to be due to the more efficient use of oxygen by the myocardium when the patient has stable physical activity. In addition, CRATAL increased the ejection fraction. The efficacy of the basic therapy supplemented with CRATAL increases

Clinicians have reported that it is feasible to use CRATAL in combination therapy for CHD due to its properties to potentiate the actions of long-acting nitrates, vasodilators, cardiac glycosides and diuretics.

These effects of CRATAL were reported in patients with mild hypertension, who suffered from the Chernobyl accident. These patients also reported that headache, dizziness, chest pain, tachycardia disappeared; the levels of haemoglobin and white blood cells, and the activity of alkaline phosphatase were normalized. Cratal protected the membrane of human erythrocytes from deformation.

The results show that the use of CRATAL is feasible in patients with coronary heart disease and mild hypertension, who live or/and work in high-radiation areas.

The use of Cratal as monotherapy for the treatment of patients with neurocirculatory dystonia, and complaints of frequent vegetovascular paroxysms allowed to reduce the number and severity of sympathoadrenal crises, improve their general health condition. The patients demonstrated lower anxiety and irritation; they improved their sleep, and had fewer attacks of pain in the heart region, as well as headaches, and palpitations.

No side effects of Cratal were reported during the clinical trials. Cratal did not affect the parameters of complete blood count and biochemical analysis (total protein, bilirubin, uric acid, cholesterol, triglycerides, ALT, AST) in patients with coronary artery disease or/and hypertension, who did not live or work in high-radiation areas of the Chernobyl NPP accident.

As of today, no adverse effects resulted from the use of the product were registered; individual hypersensitive reactions, though, to its components may occur.

The product is contraindicated in patients with hypersensitivity to its components.

Therefore, the clinical and experimental findings demonstrate the efficacy of Cratal as a cardioprotective agent, therefore it is recommended for the use in cardiological and general clinics. Some literature data on effectiveness of taurine as a hepato- and neuroprotector, its effects on functioning of the endocrine system, and on its other pharmacological properties justify its further clinical studies in order to extend the therapeutic indications.

 
31.07.2003    N.Gorchakova, Professor of the National Medical University.