Drugs that improve electrolyte and energy metabolism of the heart

The problem of urgent correction of the disrupted fundamental properties of 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 is known, 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 under hypoxic conditions, meanwhile, it is under these conditions that the lactate content in the blood increases significantly, and the tension of the sympathoadrenal system in shock and myocardial infarction leads to a pronounced mobilization of FFA due to intensive lipolysis (activated by CA and ACTH) in adipocytes of adipose tissue. Thus, a significant increase in the concentration of lactate and FFA in the blood contributes to their greater extraction by the myocardium and the dominance of these sources over glucose in the overall final oxidation pathway. In addition, the heart's own small glycogen pool is quickly used up. Long-chain fatty acids also have a damaging detergent effect on the membranes of cardiac fibers and organelles, which adds up to the negative impact of membrane lipid peroxidation.

Therefore, one of the tasks of improving energy metabolism is to inhibit lipolysis in adipose tissue (partly achieved by stress-protective agents) and "impose" on the heart a more productive energy metabolism based on glucose in hypoxic conditions (the output of ATP per unit of consumed O2 is 15-20% higher). Since glucose has a threshold for penetrating the myocardium, it should be administered with insulin. The latter also delays the degradation of myocardial proteins and promotes their resynthesis. If there is no renal failure, potassium chloride is added to the glucose solution with insulin, since in AHF of various genesis (general hypoxia, prolonged hypotension, condition after cardiac arrest, myocardial infarction, etc.) the content of K+ in the myocardium decreases, which significantly contributes to the development of arrhythmias and reduces tolerance to glycosides and other inotropic agents. The use of glucose-insulin-potassium ("repolarizing") solution was proposed by G. Labori (1970) and it has become very widespread, including in cardiogenic shock and for its prevention. Massive glucose loading is carried out using a 30% solution (more advantageous than 40%, but it can cause phlebitis) at 500 ml twice a day at a rate of about 50 ml/h. 50-100 U of insulin and 80-100 mEq of potassium are added to 1 liter of glucose solution; infusions are carried out under ECG control. To eliminate a possible potassium overdose, its antagonist, calcium chloride, should be ready. Sometimes the composition of the repolarizing solution for insulin and potassium is slightly modified. Infusion of the repolarizing solution quickly results in a 2-3-fold increase in glucose extraction by the heart, elimination of K+ deficiency in the myocardium, inhibition of lipolysis and absorption of free fatty acids by the heart, and a decrease in their blood level to a low level. As a result of changes in the free fatty acid spectrum (an increase in the proportion of arachidonic acid and a decrease in the content of linoleic acid, which inhibits prostacyclin synthesis), the concentration of prostacyclin, which inhibits platelet aggregation, increases in the blood. It is noted that 48-hour use of the repolarizing solution in several doses helps to reduce the size of the myocardial necrosis focus, increases the electrical stability of the heart, as a result of which the frequency and severity of ventricular arrhythmias decrease, as well as the number of episodes of pain syndrome resumption and mortality of patients in the acute period.

The use of glucose-insulin-potassium solution is currently the most accessible and well-tested method in the clinic for correcting the energy metabolism of the heart and replenishing the intracellular potassium reserve. Of even greater interest in the critical period is the use of macroergic compounds. Creatine phosphate, which is apparently a transport form of the macroergic phosphorus bond between intra- and extramitochondrial ADP, has proven itself well in experiments and clinical practice (so far in a few observations). Although reliable measurements of the amount of exogenous creatine phosphate penetrating into cardiac fibers have not been carried out (exogenous ATP practically does not enter the cells), empirical experience shows a favorable effect of the substance on the course, size and outcome of myocardial infarction. Repeated intravenous administration of large doses of creatine phosphate is necessary (about 8-10 g per injection). Although the optimal regimen for using creatine phosphate has not yet been developed, this method of correcting the energy deficit of the heart in acute heart failure is considered promising (“Creatine phosphate,” 1987).

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

Removal of a patient from the state of acute heart failure of various genesis and cardiogenic shock is a temporary therapeutic success, if it is not secured by eliminating the cause of acute heart failure and early rehabilitation therapy. Elimination of the cause, of course, is the main guarantee against relapses of acute heart failure, including a pharmacotherapeutic approach aimed at lysis of a freshly formed thrombus (streptokinase, streptodecase, urokinase, fibrinolysin). Here it is appropriate to evaluate the existing approaches to pharmacological rehabilitation therapy. As is known, the process of morphological and functional restoration of tissue with reversible pathological shifts (in the heart - these are mainly cells of the border zone with necrosis, as well as the so-called healthy areas of weakened muscle), regeneration of specific tissue or replacement of necrotic foci with a scar biochemically necessarily occurs through primary syntheses of nucleic acids and various types of proteins. Therefore, drugs that activate the biosynthesis of DNA and RNA with subsequent reproduction of structural and functional proteins, enzymes, membrane phospholipids and other cellular elements that require replacement are used as means of rehabilitation pharmacotherapy.

Below are the means - stimulators of recovery and reparative processes in the myocardium, liver and other organs, which are used in the immediate rehabilitation period:

• biochemical precursors of purine (riboxin or inosine G) and pyrimidine (potassium ororate) nucleotides used in the biosynthesis of DNA and RNA bases and the entire sum of macroergs (ATP, GTP, UTP, CTP, TTP); the use of riboxin parenterally in the acute period of heart failure, in acute liver dysfunction in order to improve the energy status of cells requires additional justification and the development of an optimal administration regimen;
• multivitamins with the inclusion of vitamins of plastic metabolism (for example, "aerovit") and microelements in moderate doses with the beginning of enteral nutrition; parenteral administration of individual vitamins in the acute period is unsafe and does not solve the problem of maintaining vitamin balance;
• nutrition that is complete in terms of energy composition (caloric content), a set of amino acids and essential fatty acids; all restorative biosynthesis are very energy-intensive processes and nutrition (enteral or parenteral) that is sufficient in terms of caloric content and composition is a necessary condition. No specific means have yet been created that stimulate reparative processes in the heart, although research is being conducted in this direction.

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