RU2330663C2 - Method of operative myocardium protection using artificial circulation - Google Patents

Abstract

FIELD: medicine; cardiosurgery.

SUBSTANCE: within seven days before operative intervention in addition to standard therapy patient orally takes 5-oxymethyluracil (Immureg) in dose 500 mg 3 times a day.

EFFECT: prevention of myocardium damage caused by artificial circulation due to complex action of medicinal agent.

1 ex, 1 tbl, 1 dwg

Description

The present invention relates to medicine, namely to cardiac surgery, and can be used in operations using cardiopulmonary bypass.

At the present stage of development of cardiac surgery, a significant number of open heart operations are performed using cardiopulmonary bypass (IC). Despite the advances in IC technique, the success of anesthetic management, the improvement of methods for regulating the basic vital functions of the body, the extent of the negative effects of IC during cardiac surgery remain significant. This is primarily associated with the activation of free radical oxidation, which is due to the large volume of surgical intervention, ischemia-reperfusion syndrome during aortic clamping, prolonged contact of blood with foreign surfaces (oxygenator membranes, etc.), accompanying macrophage activation and the regular development of systemic inflammatory response. So, free radicals are a real link in the pathogenesis of damage to the heart muscle, manifested by its stunning syndrome, the phenomenon of unrestored blood flow ("no-reflow phenomenon"), which consists in the progressive deterioration of blood flow in those parts of the myocardium, which perfusion was adequate at the time of elimination of occlusion, what is a protective reaction of the myocardium from free-radical damage during restoration of coronary blood flow [M. Bilenko Ischemic and reperfusion damage to organs. - M .: Medicine, 1989.- 368 p.].

As a result, the restoration of myocardial function occurs several hours or even days after reperfusion, and in some cases is accompanied by an aggravation of myocardial damage, subsequent dilatation of the left ventricular cavity, heart failure [Braunwald E. Myocardial reperfusion limitation of infarct size, reduction of left ventricular dysfunction and improved survival. Should the paradigm be expanded? // Circulation. - 1989. - Vol. 79. - P. 441-444]. All of the above dictates the need for adequate protection of the myocardium, one of the effective methods of which is the use of antioxidants.

There is a method of protecting the myocardium when using cardiopulmonary by applying histochrom, which was administered intravenously at a dose of 1 mg / kg on the eve of surgery and 40 minutes before connecting the cardiopulmonary bypass [T.V. Lasukova, E.V.Uskina, S.A. , I.V. Ponomarenko, N.V. Outer, A.M. Chernyavsky, Yu.B. Lishmanov. The effect of emoxipin and histochrom on lipid peroxidation and the activity of serum MV creatine phosphokinase in patients with coronary heart disease in the dynamics of coronary artery bypass surgery. Experimental and clinical pharmacology. 1997. Volume 60. No. 5. S.51-53]. Researchers have shown that the use of histochrome allows more effective prevention of increased peroxidation processes and the release of the cardiospecific enzyme MV-KFK into the bloodstream, which are inherent in reperfusion injury of the myocardium.

The prototype of the invention is a method of protecting the myocardium using cardiopulmonary by using tanakan (ginkgo biloba extract) as a preoperative preparation for aortic valve replacement surgery [Pietri S., Seguin JR, d'Arbigny P., Drieu K., Culcasi M. Ginkgo biloba extract pretreatment limits free radical-induced oxidative stress in patients undergoing coronary bypass surgery. Cardiovasc Drugs Ther. 1997 Apr; 11 (2): 121-31]. Patients were given tanakan for 5 days (320 mg / day) in the preoperative period. In patients after aortic valve surgery, the manifestations of reperfusion-induced lipid peroxidation, tissue necrosis, and myocardial dysfunction were reduced.

The disadvantage of the proposed methods is that their cardioprotective effect is realized only through the strengthening of antioxidant processes without coronarolytic effects and effects on coronary blood flow, which is of great importance in the formation of the “no-reflow” phenomenon.

The technical result is an increase in the effectiveness of myocardial protection by enhancing antioxidant processes and increasing coronary blood flow.

The drawing shows the dynamics of the level of creatine phosphokinase in the blood serum of patients of the main and control groups.

The proposed method is as follows.

In addition to standard therapy, 5-hydroxymethyluracil (Immureg) at a dose of 500 mg 3 times a day is orally administered to the patient within seven days before surgery.

The preparation of 5-hydroxymethyluracil (5-OMU), a pyrimidine derivative, is a "minor" base, is found in significant amounts of transport RNA, as well as DNA, and plays a significant role in the functioning and metabolism of these polymers. High activity of 5-WMD as an antioxidant was noted. In addition to the antioxidant, 5-OMU revealed other important properties: antihypoxic, coronarolytic, cardiotonic. Oxymethyluracil is a direct-acting antioxidant, i.e. realizes its action both in vivo and in vitro. It is shown that the drug is a direct interceptor of the superoxide antiradical and normalizes the activity of antioxidant enzymes (SOD, GP, catalase). Another important property of 5-WMD is coronary vasodilation and an increase in the volumetric rate of coronary blood flow. In 2002, the use of 5-OMU (FSP 42-0415-2777-02) under the trade name Immureg was permitted.

After theoretical justification, the method has been tested and implemented in clinical practice. Using this method, 35 operations were performed using cardiopulmonary bypass (aortic valve replacement, mitral valve replacement, coronary artery bypass grafting). There are no complications associated with the use of this method. The comparison group consisted of 40 patients who received standard preoperative preparation. The groups were comparable in terms of the structure of operations, sex, age, disease duration, functional class, clinical and functional indicators, cardiopulmonary bypass, aortic clamping time, and duration of surgery. For the studied criterion, the dynamics of the creatine phosphokinase (CPK) enzyme in the serum of venous blood was taken as the most specific marker of myocardial damage. CPK was determined in the postoperative period on 1, 2, 3 days. As a result of comparing the two groups, it turned out that the level of CPK in the main group was significantly lower than in the control during the entire observation period, which indicates less damage to the myocardium in the group of patients taking 5-hydroxymethyluracil (Table 1, drawing).

The proposed method is illustrated by the following example.

Patient L., 61 years old, height 173 cm, weight 85 kg, was admitted to the hospital with complaints of pressing pain behind the sternum with little physical exertion, stopping by taking nitrates up to 5-7 times a day. Based on complaints, medical history, examination, data of additional research methods, a clinical diagnosis was established: Coronary heart disease. Postinfarction cardiosclerosis (1988, 1994). Angina pectoris FC 3.

Osl .: CHF 1. FC 3. Sop .: Hypertension 3, Article 3, risk 4.

In the preoperative period, the patient received 5-oxymethyluracil (Immureg) at a dose of 500 mg 3 times a day for seven days.

The operation was performed: Aortocoronary (posterior interventricular artery, branch of the obtuse margin), mammary coronary artery bypass grafting (anterior interventricular artery) under IR conditions in a planned manner. IR time 87 minutes, aortic occlusion 55 minutes, operation time 255 minutes. Cardiac activity recovered spontaneously, rhythm disturbances were not noted, inotropic support was not required.

The postoperative course is smooth. Angina attacks are not noted.

ECG without negative dynamics. The level of cardiospecific enzymes: on 1 day after ALT operation 43 U / L, ACT 52 U / L, LDH 459 U / L, KFK-MV - 834 U / L; on the 2nd day ALT 38 U / l, ACT 51 U / l, LDH 315 U / l, KFK-MV - 820 U / l; on the 3rd day ALT 30 U / l, ACT 42 U / l, LDH 280 U / l, KFK-MV - 470 U / l. Sutures were removed on the 10th day. The patient was discharged from the clinic on the 10th day.

At the control examination after 2 months: Angina attacks are not noted. It passes simultaneously 2500 m, per day 10000 m. It rises up the stairs to the 5th floor.

Claims (1)

A method of protecting the myocardium during operations using cardiopulmonary bypass, including the introduction of an antioxidant in the preoperative period against the background of standard therapy, characterized in that 5-hydroxymethyluracil is administered at 500 mg 3 times a day for 7 days.