Medications that improve electrolyte and energy metabolism of the heart

The problem of urgent correction of the disturbed fundamental properties of the heart cells and the organ as a whole is a very difficult task, and a reliable solution to it has not yet been found.

As you know, a healthy heart consumes relatively little glucose (about 30% of energy supply) and the main sources of energy are free fatty acids (FFA) and blood lactate. These sources are not the most economical in terms of hypoxia, meanwhile, the lactate content in the blood increases substantially, and the tension of the sympathetic adrenal system in shock and myocardial infarction leads to a marked mobilization of FFA due to intense lipolysis (CA and ACTH activation) in adipocytes of adipose tissue. Thus, a significant increase in the concentration of lactate and FFA in the blood promotes greater extraction of myocardium and the dominance of these sources over glucose in the overall final oxidation pathway. In addition, your own small glycogen pool in the heart is consumed quickly. FFAs with a long chain also have a detrimental effect on the membranes of cardiac fibers and organelles, which is summarized with the negative effect of peroxide oxidation of membrane lipids.

Consequently, one of the tasks of improving energy metabolism is to inhibit lipolysis in adipose tissue (partly achieved by stress protective means) and "imposing" the heart more productive in conditions of hypoxia (the yield of ATP per unit of 02 consumed by 15-20% higher) of glucose-based energy exchange. Since glucose has a threshold of penetration into the myocardium, it must be administered with insulin. The latter also delays the degradation of myocardial proteins and promotes their resynthesis. If there is no renal insufficiency, then potassium chloride is added to the glucose solution with insulin, as in the case of OCH of different genesis (general hypoxia, prolonged hypotension, condition after cardiac arrest, myocardial infarction, etc.), the content of K + decreases in the myocardium, promotes the development of arrhythmias and reduces tolerance to glycosides and other inotropic agents. The use of a glucose-insulin-potassium ("repolarizing") solution was proposed by G. Labori (1970) and it was very widely used, including with cardiogenic shock and for its prevention. Massive loading of glucose is carried out with a 30% solution (more than 40% solution, but it can cause phlebitis) 500 ml twice a day at a rate of about 50 ml / h. To 1 liter of glucose solution, 50-100 U of insulin and 80-100 meq of potassium are added; infusion is carried out under ECG monitoring. To eliminate a possible overdose of potassium at the ready there must be its antagonist - calcium chloride. Sometimes the composition of repolarizing solution on insulin and potassium is somewhat modified. The infusion of the repolarizing solution quickly leads to a 2-3-fold increase in the extraction of glucose by the heart, the elimination of K + deficiency in the myocardium, inhibition of lipolysis and absorption of FFA by the heart, and a decrease in their level in the blood to a low level. As a result of changes in the spectrum of FFA (an increase in the share of arachidonic and a decrease in the content of the inhibitory synthesis of prostacyclin linoleic acid), the concentration of prostacyclin, which aggregates platelets, increases in the blood. It is noted that the 48-hour application of the repolarizing solution in several ways helps to reduce the size of the focus of myocardial necrosis, increases the electrical stability of the heart, which decreases the frequency and severity of ventricular arrhythmias, reduces the number of episodes of renewed pain syndrome and the mortality of patients in the acute period.

The use of glucose-insulin-potassium solution is still the most accessible and well-approved in the clinic way of correction of energy metabolism of the heart and replenishment of intracellular potassium reserve. Even more interest in the critical period is represented by the use of macroergic compounds. In the experiment and clinic (so far in a few observations), creatine phosphate, which is apparently the transport form of the macroergic phosphorus bond between intra- and extra-mitochondrial ADP, has proved to be well established. Although no reliable measurements of the amount of exogenous creatine phosphate penetrating into the cardiac fibers were made (exogenous ATP into cells is practically not included), the empirical experience shows the beneficial effect of the substance on the course, size and outcome of myocardial infarction. It is necessary to re-inject large doses of creatine phosphate into the vein (about 8-10 g per injection). Although the optimal regimen for the use of creatine phosphate has not yet been developed, this method of correction of cardiac energy deficit with OSS is considered promising ("Creatine phosphate.", 1987).

The use of oxygen therapy in the complex treatment of DOS is self-evident, but its consideration goes beyond the scope of the chapter.

Removing a patient from the state of OCH of different genesis and cardiogenic shock is a temporary therapeutic success if it is not fixed by eliminating the cause of OCH and early rehabilitation therapy. Elimination of the cause, of course, is the main guarantee against the relapse of OCH, including the pharmacotherapeutic approach aimed at lysis of the newly formed thrombus (streptokinase, streptodeacase, urokinase, fibrinolysin). Here it is appropriate to evaluate the existing approaches to pharmacological rehabilitation therapy. As is well known, the process of morphological and functional restoration of tissue with reversible pathological shifts (in the heart - this is mainly the cells bordering on the necrosis of the zone, as well as the so-called healthy areas of the weakened muscle), regeneration of a specific tissue or replacement of necrosis foci by a scar, biochemically necessarily passes through primary syntheses nucleic acids and various proteins. Therefore, drugs that activate biosynthesis of DNA, RNA and subsequent reproduction of structural and functional proteins, enzymes, phospholipids of membranes and other cell elements that require replacement are used as remedies for rehabilitation pharmacotherapy.

Below are the means - stimulants of restorative and repair processes in the myocardium, liver and other organs that in the nearest rehabilitation period use:

• biochemical precursors of purine (riboxin or inosine G) and pyrimidine (potassium ororate) nucleotides used in the biosynthesis of DNA and RNA bases and the total amount of macroerges (ATP, GTP, UTP, CTF, TTF); the use of ribonxine parenterally in the acute period of heart failure, with acute violations of the liver in order to improve the energy status of cells requires additional justification and the development of an optimal mode of administration;
• multivitamins with the inclusion of vitamins of plastic metabolism (for example, "aerovit") and trace elements in moderate doses with the onset of enteral nutrition; parenteral administration of individual vitamins in an acute period is unsafe and does not solve the problem of maintaining the vitamin balance;
• high-grade on the energy composition (calories), a set of amino acids and essential fatty acids nutrition; all reductive biosynthesis are very energy intensive processes and sufficient nutrition and nutrition (enteral or parenteral) is a necessary condition. There are no specific drugs that stimulate reparation processes in the heart, yet it has not been created, although research is underway in this direction.

[1], [2], [3], [4]