The way to prevent early recurrence of angina and consequences of respiratory distress syndrome in adult patients undergoing surgery coronary artery bypass surgery


(57) Abstract:

The invention relates to medicine, namely to surgery, and for the prevention of early recurrence of angina and consequences of respiratory distress syndrome in adult patients undergoing surgery coronary artery bypass surgery. To do this in the immediate postoperative period to impose anti-inflammatory drugs, disaggregants and hypolipidemic drugs. It is also prescribed angiotensin converting enzyme inhibitors in therapeutic dose within 12 months. The method allows to increase the effectiveness of prevention.

The invention relates to medicine, namely to surgery, and can be used to prevent early recurrence of angina and consequences of respiratory distress syndrome in adults (rdsw) in patients undergoing surgery coronary artery bypass graft (CABG).

Many years of experience in the use of CABG showed that the duration of effect is determined by the duration of patency of autovenous graft (1). The main purpose of the further treatment is the prevention of the return strokes. According to the literature, the main cause of recurrent angina was the ATA and its atherosclerotic lesions (2). The risk of thrombosis coronary artery bypass grafts is increased if CABG is complicated by rdsw, which, in addition, some patients have long-term consequences in the form of development of pulmonary fibrosis, pulmonary hypertension, disorders of respiratory function, which also affects the results of the operation. Known methods of prevention of the recurrence of angina, including receiving antiplatelet (aspirin) and means preventing the development of atherosclerosis (1), indirect anticoagulants (3).

As the prototype used a method of preventing recurrence of angina, which is that used precision training autovenous graft, the rate of anti-inflammatory therapy in the immediate postoperative period, a lifelong receiving antiplatelet and prevention of progression of atherosclerosis, including medicamentous correction of hyperlipidemia (4). However, satisfactory methods for the prevention of late effects rdsw and impaired patency autovenous graft (coronary artery bypass grafts) not found. Sustainable effectiveness of CABG surgery is only observed in 70-80% of cases, when steadfastly maintained patency of the anastomoses (3), which is clearly not sufficient and requires a search for ACTICE early recurrence of angina and consequences rdsw patients undergoing surgery CABG.

This task is achieved by taking anti-inflammatory drugs in the immediate postoperative period, antiplatelet and lipid-lowering drugs with an additional appointment of angiotensin-converting enzyme in therapeutic dose for a period of 12 months.

There is a commonality in the pathogenesis of development of recurrent angina and consequences rdsw. The basis of the pathological process is the defeat of the vascular wall of the shunt or pulmonary capillaries, respectively. The results of morphological studies autovenous graft taken action to re-CABG, showed the number of patterns in the development of pathological changes. Their essence lies in the development of reactive aseptic inflammation of all layers of the vascular wall. In an intim revealed the development of its uneven fibrous thickening often with stenosis or obliteration of the lumen of the shunt and secondary thrombosis. In the media noted the proliferation of collagen fibers of varying degrees of maturity with the reduction of muscle cells and fragmentation of elastics. In adventitia took place sclerosis, hyalinosis vasa vasorum and focal inflammatory infiltration with the prevalence of tominskogo shunt (4).

In the pathogenesis of rdsw in recent years leading role assign endothelial theory: the defeat of the endothelium of the capillaries of the lungs aggressive mediators of inflammation with increased vascular permeability (5). Develops aseptic inflammation and subsequent fibrosis of the alveolar-capillary membrane of the lungs, which leads to deterioration of its diffusion capacity for oxygen (6). In the long term in some patients is the reduction of the capillary bed due to fibrous proliferation and subsequent thrombosis of the vessels, and the development of fibrosis in the interstitium of the lungs. As a consequence, developed long-term consequences in the form of disturbances of respiratory function predominantly restrictive nature, reduced diffusion capacity for oxygen, pulmonary hypertension.

Assigning inhibitors angiotensin-converting enzyme (ACE) inhibitors for long term (12 months) have primarily their antiproliferative effect and the ability to improve blood rheology. The main localization of ACE vascular endothelium. A particularly large amount of enzyme is produced in the endothelium of the capillaries of the lungs (7). The contents of the APF in the circulating blood is relatively small compared to its Sodom, translating in the blood angiotensin I into a highly active angiotensin II. Angiotensin II is mitogenic and growth-modulating role in some tissues: an intim, the smooth muscle cells of blood vessels, masanga, myocardial and vascular fibroblasts (9,10). In an intim damaged vessels increases the number of receptors for angiotensin II (11). When ACE inhibitors increase the levels of angiotensin I and bradykinin (ACE accelerates the disintegration of bradykinin), which increase the secretion and synthesis of prostaglandins (endogenous vasodilator), including prostacyclin, which is a potent antiaggregatory factor (12). ACE inhibitors prevent the development of pulmonary fibrosis, which is proved in the experiment (13).

The duration of the prevention of ACE inhibitors during the 12 months is substantiated by the fact that the closure of shunts is mainly observed in the first 2 to 3 months after CABG surgery (3). About 80 % of all recurrent strokes occur in the first year - the period of most pronounced reparative processes.

The method is as follows:

In the first two days after CABG surgery patient is prescribed prednisolone parenterally in a dose of 1 - 1.5 mg/kg/day ( 50 mg, 2 times in the Oze 0,25 - 0.5 mg/kg/day) or nonsteroidal anti-inflammatory drugs for 2 to 3 weeks. Prednisolone thus normalize blood picture, the disappearance of biochemical markers of inflammation and pathological immune responses (reduction to normal levels of circulating immune complexes).

Appointment of glucocorticoids (GC), prednisolone, achieve

1) anti-inflammatory effect, suppression of hyperimmune reactions and prevention of autocannibalism (normalization of increased capillary permeability, inhibition of the synthesis of mediators of inflammation, suppression of the function of T - and B - lymphocytes, monocytes);

2) increase the diffusion capacity of the alveolar-capillary membrane for oxygen;

3) reduce the development of fibrosis.

It is also prescribed ACE inhibitor at 5-7 days after CABG in therapeutic dose (capoten dose 25 - 50 mg/day, enam 5 - 10 mg/day, and others) and continue taking this drug for 12 months.

They also conventional therapy desagregants, according to testimony type of lipid-lowering means.

A specific example of the method.

Patient Riabovol N. N. , 42 years old, underwent surgical treatment for ischemic and three autovenous shunts. The postoperative course was hard, accompanied by the development of postoperative pericardial effusion, severe disorders of the hemostatic system, rdsw. Pulmonary hypertension (up to 36 mm RT, senior), and long-term persistence of fluid in the pleural cavity (28 days) required the appointment of SC at a dose of 30 mg/ day orally for 14 days and ACE inhibitors at a dose of 37.5 mg/ day. Within one month of the normalized pressure in the pulmonary artery, disappeared effusion in the pleural cavity, improved spirography. Later we have extended the patient receiving ACE inhibitors up to one year in order to prevent aseptic inflammation of shunts and possible fibrotic changes in the lungs due to rdsw. In the course of further surveillance of recurrence of angina was not observed, the function of external respiration, according to spirography, remained within normal limits.

An example where the inventive method is not used.

Patient Krupin Y. C., 49, was held surgical treatment for ischemic heart disease and cerebral atherosclerosis clinical hospital N 1, Arkhangelsk with 14.02.96 on 19.03.96 . The operation took place revascularization three autovenous shunts and one mammarocoronary, and carotid endarterectomy on the right. In the VA, posthemorrhagic anemia. However, severe disorders of the respiratory system were observed (indicators of blood gas composition, spirography, the pressure in the pulmonary artery were within normal limits). In the postoperative period was conducted traditional therapy, while the CC and ACE inhibitors the patient was not prescribed. 2 months after the operation the patient with the clinic angina was re-admitted for examination and treatment. Exercise ischemic test was positive. On re-koronaroangiografii (CAG) and sonography revealed occlusion of two coronary venous grafts, third autovenous shunt function has two stenosis in the proximal 2 cm and the distal 1.5 cm more than 50 % . Thus, the patient had an early recurrence of angina due to obstruction of autovenous graft.

A positive effect.

Clinical hospital N 1, Arkhangelsk, which is the base of the Department of faculty therapy ASMA, has completed 150 of CABG operations. We selected a group of 12 patients who underwent CABG surgery, the postoperative period was complicated rdsw. All of these patients were taking ACE inhibitors during progestone. Using a special questionnaire and conducting exercise tests have determined that none of the patient from this group gave no recurrence of angina, there was also the restoration of disturbed spirographis metrics and normalization of pressure in the pulmonary artery, which occurred in the early postoperative period. To compare the analyzed group of patients after CABG 16, which in the first year after surgery, there was a relapse of angina, which was confirmed by the data of the survey, positive ischemic test during Bicycle ergometry and some patients with CAG and sonographies revealed obstruction of the venous coronary artery bypass grafts. Retrospective analysis showed that none of the patient from the second group did not receive prophylactic treatment by the present method.

The method allows to:

1) to reduce the frequency of stenosis coronary artery bypass grafts and thereby reduce the number of patients requiring re-CABG;

2) in patients undergoing rdsw, to improve during the early postoperative period (faster subside the symptoms of pericarditis, resolved effusion in the pleural cavity, decreases pulmonary hypertension, faster than normal pok which decreases the likelihood of developing serous mediastinitis, declining terms of patient stay in hospital on average 2 weeks);

3) long-term (first year) to fully normalize in patients spirographic indices, x-ray picture of the lungs, reduce pulmonary hypertension, to reduce or prevent the development of hypertrophy of the right ventricle;

4) to increase exercise tolerance;

5) to reduce the dose of aspirin (due to the property of ACE inhibitors improve blood rheology), which is especially important for patients suffering from peptic ulcer disease or gastroduodenitis.

All this allows to speed up the rehabilitation of patients, to improve their quality of life and improve performance. First of all the method can be used in patients undergoing rdsw, with prolonged fever in the postoperative period, with a marked inflammatory syndrome, endothelial and immune disorders have a tendency to autocannibalism, in patients with insulinorezistentne syndrome.

Sources of information

1. Akchurin, R. S., Borisenko A. P., Burakovsky Century. And. heart Disease and blood vessels : a Guide for physicians. Ed. by E. I. Chazov. 4 so-So 2 - M.: Medicine, 1992.

2. I. Zhbanov Century, Shabalkin B. C. Surgical is engelsk: 1996, S. 27 and 28.

3. Amosov N. N., Bendat J. A. Therapeutic aspects of cardiac surgery. - Kiev: Health, 1990, 288 S.

4. I. Zhbanov Century, Minkin S. M., Shabalkin B. C. the Fate of autovenous graft after coronary artery bypass surgery. In Proc.: Actual problems of cardiovascular surgery. - Arkhangelsk: 1996, S. 26 and 27.

5. Silber, A. P. Medicine critical conditions: common challenges. - Petrozavodsk: publisher PSU, 1995, 360 S.

6. Bone R. C. et al. Adult respiratory distress-syndrome - sequence and impotance of development of multiple organ failure. Chest 101, 2: 320 - 326.

7. Karpov, O. I. Modern cardiac drugs. Pharmacology of angiotensin converting enzyme inhibitors. St. Petersburg medical bills. 1995, No. 11-12, 1995, S. 39-45.

8. Fyhrquist F. , Tikkanen I. Atrial natriuretic peptide in congestive heart failure. Amer. J. Cardiol. the 1988 - vol. 62, No. 2, p. 20A - 24A.

9. Schelling, P., Fischer, H., Ganten D. Angiotensin and cell growth : a link to cardiovascular hypertrophy ? J. Hypertens. - 1991, 9: 3 - 15.

10. Heagerty A. M. Angiotensin II: vasoconstrictor or growth factor ? - J. Cardiovasc. Pharmacol. 1991, 18 (suppl 2): 14 - 19.

11. Pratt R. E., Wang D., Hein L., Dzan V. J. AT The2isoform of the angiotensin receptor mediates miointimal hyperplasia following vascular ingury (abstract). Hypertension. -1992, 20: 432.

12. Small L. G., Hump Y. G., Rachinsky I. D. Chronic circulatory insufficiency. -Kiev: Health 4 so So 4 - M.: Medicine, 1990.

The way to prevent early recurrence of angina and consequences of respiratory distress syndrome in adult patients undergoing surgery coronary artery bypass surgery, including the use of anti-inflammatory drugs in the early postoperative period, antiplatelet and lipid-lowering drugs, characterized in that it further prescribe angiotensin-converting enzyme inhibitor in a therapeutic dose within 12 months.


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FIELD: medicine; pharmaceutical engineering.

SUBSTANCE: pharmaceutical composition COMPRISES 5-(2-pyrazinyl)-4-methyl-1,2-dithyol -3-thion (oltipraze) and dimethyl-4,4'-dimetoxi-5,6,5',6'-dimethylene-dioxybiphenyl-2,2' dicarboxilate (DDB) as the main components. Oltipraze: DDB proportion is preferentially equal to 50-1:1-50, the most preferential being 5:1.

EFFECT: enhanced effectiveness of treatment.

6 cl, 6 dwg, 9 tbl