Cardioprotective Effect of Reamberin in Ischemic — Reperfusion Injury

Материалы и методы. Провели анализ результатов лечения 61#го пациента (36 мужчин и 25 женщин) с протезированием клапанов сердца и пластикой дефектов межпредсердной и межжелудочковой перегород# ки. Больных разделили на 2 группы. В 1#й группе (основной), 35 больных после проведенного кардиохирур# гического вмешательства получали препарат Реамберин: в первые 6 часов послеоперационного периода 400 мл, внутривенно, капельно со скоростью 60—90 кап./мин. Во 2#й группе (контрольной), 26 больных полу# чали стандартный комплекс интенсивной терапии. Помимо стандартного клинико#лабораторного обследо# вания определяли содержание: тропонина I, лактатдегидрогеназы, креатинкиназы, изофракции креатинки# назы МВ, трансаминаз (аланинаминотрансферазы и аспартатаминотрансферазы).


Introduction
In 1975 G. R. Heyndrickx et al. first described the phenomenon of reversible post ischemic left ven tricular failure, and E. Braunwald and R. I. Kloner called this syndrome «stunned myocardium» to define reversible myocardial dysfunction in response to myocardial reperfusion after restoration of normal or subnormal blood flow in the coronary arteries.Histological severity of damage was related to the duration of the period of ischemia [1][2][3][4][5].
Currently, during surgical procedures on the fibrillated heart to preserve the natural blood flow in coronary vessels the three phase time -depen dent model of ventricular fibrillation (VF) is employed.It includes: electric phase (first 4-5 minutes), during which an effective method of removing fibrillation is the electrical defibrilla tion; circulatory phase (prolonged VF) for the next 5-10 minutes, with a pre compression of the chest and following the electrical defibrillation; metabolic phase, for which it is necessary to carry out metabolic therapy [6,7].Electrical defibrilla tion can cause damage to the heart, both reversible and irreversible [8].Cpntemporary understanding of myocardial alterations by electric shock is based on the concept of electroporation, i.e. increased permeability of cell membranes after exposure to a strong electric field that initiates the excessive calcium intake and development of contractures including muscle contractions followed by severe cell damage with death [9].The metabolic theory suggests that repeated defibrillation discharges cause transient depression of cellular respiration that are developing on the background of an ade quate oxygen saturation of arterial blood and an increases in blood flow in the myocardium.Similar changes in stunned myocardium were detected using the model of ischemia reperfusion injury.In addition, the main effect was to reduce any hypox ic cellular energy production [1].
Methods to affect the metabolic processes in the myocardium include the use of succinic acid drugs, specifically, Reamberin («NTFF POLYSAN «, St. Petersburg, Russia).Mechanisms of the drug action is associated with the effect of succinate on the neurotransmitter amino acid transport, catalytic action on oxygen utilization in the Krebs cycle, acti vation of aerobic metabolism, restoration of redoxmitochondrial status, as well as increased utilization of fatty acids, ketone bodies, glucose and lactate [10].[11].
The aim of the study was to evaluate the effec tiveness of the drug Reamberin in complex intensive threatment of patients with cardiac surgery in heart fibrillation and remodeling of prosthetic heart valves and plastic defects of atrial and ventricular septa.

Materials and Methods
The studies were performed in of 61 patients admitted to the «Dnipropetrovsk Regional Center for Cardiac Surgery and Cardiology».
for the cardiac surgery on the heart that included valve replacement and plastic surgery of atrial and ventric ular septa The patients were divided into two groups: the first group -treatment group (TG) (n=35: 21 men and 14 women, mean age 48,4±1,4 years) that received infusion therapy with the «Reamberin» infusion solution («NTFF POLYSAN» St. Petersburg, Russia) during the first 6 hours of the postoperative period (800 ml, intravenous drip at a rate of 60 -90 drops/min).The second group was employed as a control group (CG) (n=26: 15 men and 11 women, mean age 46.3±2,3 years).Patients of the latter group received the standard complex of intensive therapy, including inotropic and vasopressor support, analgoseda tion, transfusion of packed red cells and fresh frozen plas ma, infusion solutions of colloids and crystalloids.
Surgical intervention was carried out on the back ground of fibrillated heart with cardiopulmonary bypass (CB) using alfa STAT methods (with no CO 2 added to the oxygenator), temperature was at 28-30°C, duration of the period CB averaged 52.1±1.3 min in the TG and 60,1±1,6 minutes -in the CG), followed by reduction of hemody namically effective rate through an electrical defibrillation usingthe biphasic defibrillator «DI 03» (Ukraine).
ducted in the dynamics: during the initial 12 hours on admittance and 24 hours after cardiac surgery.
To assess the reliability of the obtained results, all data were statistically processed and analyzed according to gen eral rules of variation statistics using Statistica 10 software package [12].

Results and Discussion
Analysis of the dynamics of hemodynamic parameters in the two groups showed no signifi cant differences.Electrolyte composition of the blood in the control group (sodium and potassium levels) at a baseline (140±0.9 and 4.4±0.8mmol/l, respectively), and 12 hours after surgery at (145±0.5 and 4.3±0.3mmol/l, respectively) were within the normal range.Next day of observation there was a reduction of 4.2% of studied parame terss and of 11.4% (134±1,2 and 3.9±0.7 mmol/l, respectively) that correspond to the lower limit of norm (P 0.05).However, patients who received Reamberin after 24 hours of observation revealed increased sodium and potassium levels of 2.1% and 7.7% (141±1.2and 3.9±0.1 mmol/l), respectively, relative to a baseline (138±0.4 and 3.6±0.2mmol/l) (P 0.05).These changes if considering the known loss of intracellular potassium during electroporation cardiomyocytes under the influ ence of a defibrillation, may be due to cardiopro tective effects of Reamberin.
Analysis of red blood reveal similar alterations in both groups: decline in the 12 hours after surgery, which was associated with intraoperative blood loss, and the beginning of recovery level of performance after 24 hours due to ongoing transfusion therapy.
Анализ кардиоспецифических ферментов, от ражающих функциональное состояние миокарда, выявил их различия в группах (табл.3).Так, у боль ных, получивших Реамберин, содержание тропони Analysis of cardiac enzymes that reflect the func tional state of the myocardium revealed differences in the dynamics depending on the treatment (Table 3).Patients with infusion Reamberin, troponin I, a mark er of ischemia -reperfusion myocardial injury, changed within the normal range (from 0.2±0.03ng/ml to 0.7±0.026ng/ml, P 0.05), while increasing index was 66.7% in the control group, and go beyond the normal values (from 0.4±0.05ng/ml to 0.05±1.2ng/ml, P 0.05).There was a significant increase in creatine kinase levels in both groups, but the patients who received Reamberin, the intensity of the process was less pronounced: increase in the by the end of 24 hours of observation was 50.4% (from 596±1.6 g/l to 1204±3.3 g/l, P 0.05), whereas in CG -53.8% (from 598±0.7 g/l to 1295±1.5, P 0.05).
On myocardial damage as evidenced by a sig nificant increase in lactate dehydrogenase levels by the end of the first day of observation in the control group by 23.9% (from 102±1,6 U/l to 134±1.5 U /l, P 0.05), whereas changes in the study group were less significant -up to 7.1% (from 104±2.9U/l to 112±2,1 U/l, P 0.05).
Analysis of levels of amino transaminases dynamics revealed a slight increase in ALT levels in both groups in 12 hours after surgery with a subse quent decline (P 0.05), and increased AST in both groups, more prominent in the control group: 14.7% (29±3.5 U/l to 36±5.8 U/l).In patients who received Reamberin these changes were less prominent -3.9% (from 27±4.0U/l to 28.1±5.4U/l P 0.05).Таблица 1. Динамика показателей красной крови (M±m).Table 1.Dynamics of the red blood variables (M±m).
Therefore, in patients with cardiac surgery on fibrillated heart, during first 6 hours after the surgery an imbalance of acid base status (subcompensated metabolic acidosis), and arterial blood gas were revealed, followed by an adverse effect on the recov ery of the operated myocardium functions in the face of declining compensatory possibilities of the heart that resulted in damage to the myocardium (as dis covered by elevated cardiac biomarkers such as crea tine kinase, creatine kinase MB and troponin I).Inclusion in the complex post operative intensive care protocols the succinate -containing infusion solution Reamberin resulted in a significantly posi tive effects on (a) the acid -base status of the body (in the form of reduction of signs of metabolic acido sis and increased by the end of the first postoperative day sodium levels by 2.1% and potassium by 7.7% potassium in the blood) and (b) through reducing the signs of myocardial damage as demonstrated by the dynamics of alterations of cardiac enzymes con centrations in circulation.

Conclusion
Inclusion in the early postoperative period of complex intensive care of infusion of the solution of Reamberin in patients after cardiac surgery on the fibrillated heart with cardiopulmonary bypass fol lowed by electrical defibrillation increased the effec tiveness of the treatment.Therse results were evi denced by signs of recovery of the functionality of the myocardium, improving the dynamics of cardiac enzyme changes and normalization of blood acid base status.These changes were accompanied by improved clinical course of the early postoperative period and reduced risk of complications and early mortality.The efficacy and good tolerability of the Reamberin infusions allow to recommend its inclusion in the pro tocols of post operative therapy in cardiac surgery.
1 2 ; 4 54 w w w .r e a n i m a t o l o g y .c o m w w w .r e a n i m a t o l o g y .c o m Литература