Abstract

Aim. Wе studiеd thе influеncе of Carvеdilol on thе indicеs hеmorhеology (еrythrocytе dеformability, fibrinogеn, and hеmatocrit) and thе hеmocoagulation statе (blood fibrinolitic activity, plasma rеcalcification timе, protrombin indеx, and spontanеous aggrеgation of thrombocytеs), plasma malondialdеhydе in patiеnts (pts) with chronic hеart failurе (CHF). Matеrial and mеthods. 30 pts with NYHA class II or III CHF aftеr myocardial infarction [agе 45 to 71 yеars] wеrе trеatеd with basic thеrapy (glycosidеs+ diurеtics+ ACЕ inhibitor) and Carvеdilol was addеd from 3,125 - 6, 25 mg twicе a day to 12,5 - 25 mg (twicе) for 12 wееks (3 months). Rеsults. Bеforе addition of Carvеdilol wе discovеrеd thе significant incrеasе of fibrinigеn by 20% and hеmatocrit by 7,6%; rеduction of еrythrocytе dеformability by 14,5%; complеtеly dеprеssеd blood fibrinilotic activity, dеcrеasе of plasma rеcalcification timе by 40%; incrеasе of protrombin indеx by 19%; spееding-up of spontanеous aggrеgation of thrombocytеs, incrеasе of plasma malondialdеhydе by 10,7% in pts with CHF. Af¬tеr 12 wееks (3 months) of trеat-mеnt with Carvеdilol thе indicеs wеrе changеd: thе fibrinogеn was dеcrеasеd by 40% and thе hеmatocrit dеcrеasеd by 16,1%; thе еrythrocytе dеformability incrеasеd by 24,5%; thе blood fibrinolytic activity incrеasеd by 50%; thе plasma rеcalcification timе incrеasеd by 50%; thе protrombin indеx dеcrеasеd by 33%; dеcrеasеd thе spontanеous aggrеgation of thrombocytеs and plasma malondialdеhydе by 8,9% dеcrеasеd in pts with CHF (0.05 > Pu < 0.01). Conclusion. Thе addition of Carvеdilol “abovе” basic thеrapy promotеd a pronouncеd improvеmеnt of hеmorhеology, hеmocoagulation statе and lipid mеtabolism, which rеsultеd in rеduction of hеart failurе dеgrее and improvеmеnt of thе rеmotе prognosis. Summary. Chronic hеart failurе (CHF) is accompaniеd by hеmorhеology, hеmocoagulation and lipid mеtabolism disturbancеs; thе most important of thosе arе thе following: incrеasе of fibrinogеn lеvеl, dеcrеasе of еrythrocytе dеformability and incrеasе of aggrеgativе propеrtiеs of blood cеlls, incrеasе of plasma malondialdеhydе.

Cover Letter

Despite improvements in the management of cardiovascular risk factors and disease over the last 50 years that have led to a reduction in mortality from myocardial infarction and stroke, hospital admissions with heart failure have risen unabated (1). The data of experimental and clinical studies testifying the important role of rheological indices of blood in formation of the heart failure were published a lot of years ago (2). Clinically, lipid peroxidation is revealed by an increase of malondialdehyde (MDA): high serum concentrations of MDA in patients with myocardial infarction are indirect evidence of oxygen free radicals toxicity in these conditions (3,4). Oxidative stress is also involved in the induction of apoptosis, a mechanism of physiological cell death (5) and, by this mechanism  may contribute to irreversible left ventricular (LF) dysfunction.
Treatment for heart failure has improved dramatically over a short space of time. It is well recognized that the neuroendocrine response, including the renin- angiotensin and the sympathetic system, are activated in CHF (6). Interestingly, only anti- neuroendocrine treatment with angiotensine- converting enzyme (ACE) inhibition,  - blockage and anti- aldosterone therapy may result in significant reduction in morbidity and mortality (7,8,9).
However, beta- blockers are pharmacologically a very heterogeneous class of agents. Carvedilol is not only unique in being the first beta- blocker for heart failure (and the only for which small doses required for initiation of treatment are available) but also has a unique pharmacological profile. Carvedilol, a multiple- action  1 + 2-adrenoceptor blocker, vasodilator (1- blockade) and antioxidant drug, is a potent cardioprotective agent as shown in a variety of experimental models of ischemic cardiac injury (10). In experimental models, carvedilol has been shown to inhibit oxygen free radicals production and apoptosis of the myocytes (11); therefore, carvedilol in CHF might be more effective than other   - blockers for its antioxidant and antiapoptotic activities which play a synergistic role with its non- specific  and 1- blocking effects.
The aim of the present investigation was to study the influence of Carvedilol on the indices of hemorheology, hemogoagulation and lipid metabolism at patients with chronic heart failure.

Material and methods
There were 30 patients with NYHA class II or III CHF (males- 20, females- 10) after myocardial infarction aged from 42 to 67 years examined during the investigation. The investigation was performed before and after treatment. The current degree of the patient's heart failure was assessed by echocardiography (registration on Aloka- SSD- 500) by use of the following parameters: left ventricular end- diastolic volume, left ventricular ejection fraction. All patients were treated with basic therapy (glycosides+ diuretics+ ACE inhibitor) and Carvedilol was added from 3,125- 6,25 mg twice a day to 12,5- 25 mg (twice) for 12 weeks (3 months). Dosage was selected individually. The use of other drugs was excluded. Clinical characteristics of the study group are shown in Table 1. Written informed consent was obtained from all patients. Approval was obtained from the local ethics committee.
Besides, the hematocrit was measured with the help of the microcentrifuge. Deformability of red blood cells was studied with the help of viscosimeter. The thrombocytes (platelet) aggregation and disaggregation was estimated by Zakhariya and Kinakh. Serum recalcification time was measured by W. Howel, Prothrombin index- by A, Quick, fibrinogen - by R. Rutberg, fibrinolytic activity of blood - by E. Kowalski. Serum concentrations of MDA were measured by L. Andreeva. Statistical processing of obtained data was performed with the help of standard statistical (non- parameters criterion) methods. The significance changes of hemorheology, hemogoaculation and lipid metabolism parameters after administration of carvedilol was examined by the Whylcoukson- Mann- Whythny U test.
On the day of investigation, oral medication (see Table 1) was continued. Carvedilol was added from 3,125- 6,25 mg twice a day to 12,5- 25 mg (twice) for 12 weeks (3 months).

RESULTS
Before administration carvedilol the study showed the distinct and significant changes of hemorheology, hemocoagulation and lipid metabolism parameters in patients with CHF. We discovered the significant increase of fibrinigen by 20 % and hematocrit by 7,6 %; reduction of erythrocyte deformability  by 14,5 %; completely depressed blood fibrinilotic activity, decrease of plasma recalcification time by 40 %; increase of protrombin index by 19 %; speeding-up of spontaneous aggregation of thrombocytes  and decreased of plasma MDA  by 10,7% in pts with CHF. After 12 weeks (3 months) of treatment with Carvedilol the indices  were  changed: the fibrinogen was decreased by 40% and the hematocrit by 16,1 %; the erythrocyte deformability increased by 24,5%; the blood fibrinolytic activity increased by 50%; the plasma recalcification time  increased by 50%; the protrombin index decreased by 33%; the spontaneous aggregation of thrombocytes  decreased  and decreased of plasma MDA by 8,9 % in pts with CHF (0.05 >Pu < 0.01) (Table 2).

Discussion and conclusion
A recent study has shown that carvedilol improves the rheology properties of blood and hemocoagulation index in pts with CHF. This effect of carvedilol seems to be specific and independent from its cardio- protective effect due to  -blockade; in fact, blood coagulation activity decreased after the course of treatment. The potent antioxidant activities of carvedilol can be attributed to the presence of a carbazole moiety in its chemical structure (12). In fact, plasma levels of MDA are significantly higher in CHF patients than in controls, both at rest and during exercise (13). Carvedilol protects against oxygen free radicals which are consistent plasma levels obtained clinically at doses between 25 to 50 mg/day. This activity results in organ protection from several oxygen free radicals mediated injuries (14-17). Thus, obtained data showed that pts with CHF has hemorheological disturbances; the main one is increase of fibrinogen level, decrease of erythrocyte deformability and increase of their aggregative properties. We can suppose that worsening of hemorheological properties of blood can predetermine the progressing of HF. In fact, the quantitative and qualitative alteration (changes) of fibrinogen is "keystone" in hemostasis and rheology of blood. At the same time, intensification precipitation of fibrinogen is the real means by completely depressed blood fibrinilotic activity in CHF pts (18). As well, the functional disturbances of thrombocytes during the HF pathogenesis are very important and limited by offences lipid metabolism in outcome hypercatecholaminemia.  The plenty of catecholamine in blood depresses the fibrinolitic activity which provocative intensified precipitation of fibrinogen and in result to show up the thrombonemia and disturbances of microcirculation (19). Simultaneously, the plenty of catetholamine is the powerful factor by peroxydation syndrome (18,19). Oxydativee stress is also involved in the induction of apoptosis; a mechanism of physiological cell death (5) and, by this mechanism may contribute to irreversible LV dysfunction. Thus, this mechanism arouses the "vicious circle" (18-19).  
In summary, sympathetic nervous system hyperactivity provides a short -term support to the failing heart. Conversely, prolonged sympathetic activity is recognized as a fundamental process contributing to the progression of heart failure (20,21). Carvedilol is a non- selective beta- adrenergic antagonist which also blocks alpha1- receptors and has antioxidant properties (22). In patients treated with carvedilol the response to catecholamine may be significantly inhibited as this agent blocks the receptors without increasing their density (23).
The addition of Carvedilol "above" basic therapy promoted a pronounced improvement of hemorheology and hemocoagulation state, lipid metabolism which resulted in reduction of heart failure degree and improvement of the remote prognosis. The improvement of rheological properties of blood, hemocoagulation and lipid metabolism with carvedilol   to eliminate the threat of thrombogenicity complication in patients with CHF. 

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Keywords

• chronic hеart failurе
• carvedilol
• hеmorhеology
• hеmocoagulation and lipid mеtabolism

References

Article Info:

Publication history

Published: 10.Apr.2012

DOI: https://doi.org/10.28942/acj.v1i1y2012.27

Copyright

© 2013-2025. Azerbaijan Society of Cardiology. Published by "Uptodate in Medicine" health sciences publishing. All rights reserved.

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