cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLCcardiovascular-2124Research ArticleКАРДИОМИОПАТИИCARDIOMYOPATHYНебиволол улучшает резерв коронарного кровотока у пациентов с идиопатической дилатационной кардиомиопатиейNebivolol improves coronary flow reserve in patients with idiopathic dilated cardiomyopathyErdoganDoganErdoganDoganaydoganer@yahoo.comGulluHakanGulluHakanCaliskanMustafaCaliskanMustafaCiftciOzgurCiftciOzgurBaycanSemraBaycanSemraYildirirAylinYildirirAylinMuderrisogluHaldunMuderrisogluHaldunCardiology Department, Konya Teaching and Medical Research Center, Baskent University, KonyaCardiology Department, Konya Teaching and Medical Research Centre, Baskent University, Konya201020102010955965Copyright © Erdogan D., Gullu H., Caliskan M., Ciftci O., Baycan S., Yildirir A., Muderrisoglu H., 20102010Erdogan D., Gullu H., Caliskan M., Ciftci O., Baycan S., Yildirir A., Muderrisoglu H.Erdogan D., Gullu H., Caliskan M., Ciftci O., Baycan S., Yildirir A., Muderrisoglu H.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/2124

Актуальность. Нарушение резерва коронарного кровотока (РКК) — достоверный предиктор неблагоприятного прогноза у пациентов с идиопатической дилатационной кардиомиопатией (ИДКМП). Небиволол способен снижать заболеваемость и смертность у больных с сердечной недостаточностью (СН) и дисфункцией левого желудочка (ЛЖ), в т.ч. у пациентов с ИДКМП. Цель. Оценить эффект небиволола на РКК у больных ИДКМП. Материал и методы. У 21 больного — основная группа (ОГ) с клинически стабильным течением ИДКМП (среднее значение фракции выброса ЛЖ 35,7 (6,2)) РКК оценивался исходно и через 1 мес. от начала терапии небивололом (однократный прием препарата в сут.). В контрольную группу (ГК) вошли относительно здоровые лица, сопоставимые по возрасту и полу с пациентами ОГ. Коронарный кровоток в покое и в условиях гиперемии измерялся при помощи трансторакальной Допплер-эхокардиографии с удвоением частоты принимаемого сигнала (second-harmonic). Никто из участников не страдал сопутствующей системной патологией. Результаты. Через 1 мес. терапии небивололом достоверно уменьшилась частота сердечных сокращений (ЧСС) (р<0,001). Уровень артериального давления (АД) также достоверно снизился (р<0,001). Статистически значимой динамики конечно-диастолического диаметра ЛЖ и ударного объема зарегистрировано не было. В то же время, конечно-систолический диаметр достоверно уменьшился (р<0,05). На фоне приема небиволола сократилась величина двойного произведения (ЧСС•АД) в покое. На увеличение двойного произведения после введения дипиридамола терапия небивололом существенного влияния не оказывала. Небиволол достоверно уменьшал скорость коронарного кровотока в покое (р<0,02), увеличивая ее после введения дипиридамола (р<0,02), что приводило к статистически значимому увеличению РКК 2,02 (0,35) vs 2,61 (0,43); (p<0,001). Небиволол увеличивал показатели РКК на ≥ 6 % у 17 из 21 больного (80,9 %). Заключение. У пациентов с ИДКМП прием небиволола в течение 1 мес. ассоциируется с достоверным увеличением РКК.

Background: Impaired coronary flow reserve (CFR) is a significant predictor of poor prognosis in patients with idiopathic dilated cardiomyopathy (IDC). Nebivolol reduces mortality and morbidity in patients with heart failure and left ventricular dysfunction, including cases caused by IDC. Objective: To assess the effects of nebivolol on CFR in patients with IDC. Methods: CFR was measured in the main group (MG), including 21 clinically stable patients with IDC (mean (SD) ejection fraction 35,7 (6,2)), at baseline and after 1 month of treatment with nebivolol once daily. A control group (CG) of apparently healthy subjects who were matched for age and sex was used for comparison. Resting and hyperaemic coronary flows were measured using transthoracic second-harmonic Doppler echocardiography. None of the subjects had any systemic disease. Results: After 1 month of treatment, heart rate (HR) was reduced significantly (p<0,001). The blood pressure (BP) was decreased significantly (p<0,001). The left ventricular end-diastolic diameter and stroke volume were not changed significantly, but end-systolic diameter was decreased significantly (p<0,05). Resting rate–pressure product was lower after treatment with nebivolol, but dipyridamole-induced change was not influenced by the treatment. Nebivolol treatment significantly reduced coronary velocities at rest (p<0,02) and also caused a significant increase in coronary velocities after dipyridamole (p<0,02), leading to a greater CFR (2,02 (0,35) vs. 2,61 (0,43); p<0,001). Nebivolol induced an absolute increase of at least 6% in the CFR in 17 of 21 patients (80,9%). Conclusions: In patients with IDC, 1 month of treatment with nebivolol induces a marked increase in CFR.

ReferencesInoue T, Sakai Y, Morooka S, et al. Coronary flow reserve in patients with dilated cardiomyopathy. Am Heart J 1993; 125: 93-8.Inoue T, Sakai Y, Morooka S, et al. Coronary flow reserve in patients with dilated cardiomyopathy. Am Heart J 1993; 125: 93-8.Inoue T, Sakai Y, Morooka S, et al. Vasodilatory capacity of coronary resistance vessels in dilated cardiomyopathy. Am Heart J 1994; 127: 376-81.Inoue T, Sakai Y, Morooka S, et al. Vasodilatory capacity of coronary resistance vessels in dilated cardiomyopathy. Am Heart J 1994; 127: 376-81.Cannon RO 3rd, Cunnion RE, Parrillo JE, et al. Dynamic limitation of coronary vasodilator reserve in patients with dilated cardiomyopathy and chest pain. JACC 1987; 10: 1190-200.Cannon RO 3rd, Cunnion RE, Parrillo JE, et al. Dynamic limitation of coronary vasodilator reserve in patients with dilated cardiomyopathy and chest pain. JACC 1987; 10: 1190-200.Neglia D, Michelassi C, Trivieri MG, et al. Prognostic role of myocardial blood flow impairment in idiopathic left ventricular dysfunction. Circulation 2002; 105: 186-93.Neglia D, Michelassi C, Trivieri MG, et al. Prognostic role of myocardial blood flow impairment in idiopathic left ventricular dysfunction. Circulation 2002; 105: 186-93.Mohri M, Egashira K, Tagawa T, et al. Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure. Hypertension 1997; 30(1 Pt 1): 50-6.Mohri M, Egashira K, Tagawa T, et al. Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure. Hypertension 1997; 30(1 Pt 1): 50-6.Smith CJ, Sun D, Hoegler C, et al. Reduced gene expression of vascular endothelial NO synthase and cyclooxygenase-1 in heart failure. Circ Res 1996; 78: 58-64.Smith CJ, Sun D, Hoegler C, et al. Reduced gene expression of vascular endothelial NO synthase and cyclooxygenase-1 in heart failure. Circ Res 1996; 78: 58-64.Lerman A, Burnett JC Jr, Higano ST, et al. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 1998; 97: 2123-8.Lerman A, Burnett JC Jr, Higano ST, et al. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 1998; 97: 2123-8.Kuroedov A, Cosentino F, Luscher TF. Pharmacological mechanisms of clinically favorable properties of a selective beta1- adrenoceptor antagonist, nebivolol. Cardiovasc Drug Rev 2004; 22: 155-68.Kuroedov A, Cosentino F, Luscher TF. Pharmacological mechanisms of clinically favorable properties of a selective beta1- adrenoceptor antagonist, nebivolol. Cardiovasc Drug Rev 2004; 22: 155-68.Ignarro LJ, Byrns RE, Trinh K, et al. Nebivolol: a selective beta (1)-adrenergic receptor antagonist that relaxes vascular smooth muscle by nitric oxide-and cyclic GMP-dependent mechanisms. Nitric Oxide 2002; 7: 75-82.Ignarro LJ, Byrns RE, Trinh K, et al. Nebivolol: a selective beta (1)-adrenergic receptor antagonist that relaxes vascular smooth muscle by nitric oxide-and cyclic GMP-dependent mechanisms. Nitric Oxide 2002; 7: 75-82.Wisenbaugh T, Katz I, Davis J, et al. Long-term (3-month) effects of a new beta blocker (nebivolol) on cardiac performance in dilated cardiomyopathy. JAСC 1993; 21: 1094-100.Wisenbaugh T, Katz I, Davis J, et al. Long-term (3-month) effects of a new beta blocker (nebivolol) on cardiac performance in dilated cardiomyopathy. JAСC 1993; 21: 1094-100.Erdogan D, Gullu H, Caliskan M, et al. Coronary flow reserve in white-coat hypertension. Heart 2006; 92: 1109-12.Erdogan D, Gullu H, Caliskan M, et al. Coronary flow reserve in white-coat hypertension. Heart 2006; 92: 1109-12.Caiati C, Montaldo C, Zedda N, et al. New noninvasive method for coronary flow reserve assessment: contrast-enhanced transthoracic second harmonic echo Doppler. Circulation 1999; 99: 771-8.Caiati C, Montaldo C, Zedda N, et al. New noninvasive method for coronary flow reserve assessment: contrast-enhanced transthoracic second harmonic echo Doppler. Circulation 1999; 99: 771-8.Hozumi T, Yoshida K, Akasaka T, et al. Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique. JACC 1998; 32: 1251-9.Hozumi T, Yoshida K, Akasaka T, et al. Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique. JACC 1998; 32: 1251-9.Saraste M, Koskenvuo J, Knuuti J, et al. Coronary flow reserve: measurement with transthoracic Doppler echocardiography is reproducible and comparable with positron emission tomography. Clin Physiol 2001; 21: 114-22.Saraste M, Koskenvuo J, Knuuti J, et al. Coronary flow reserve: measurement with transthoracic Doppler echocardiography is reproducible and comparable with positron emission tomography. Clin Physiol 2001; 21: 114-22.Van den Heuvel AF, van Veldhuisen DJ, van der Wall EE, et al. Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy. JACС 2000; 35: 19-28.Van den Heuvel AF, van Veldhuisen DJ, van der Wall EE, et al. Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy. JACС 2000; 35: 19-28.Nitenberg A, Foult JM, Blanchet F, et al. Multifactorial determinants of reduced coronary flow reserve after dipyridamole in dilated cardiomyopathy. Am J Cardiol 1985; 55: 748-54.Nitenberg A, Foult JM, Blanchet F, et al. Multifactorial determinants of reduced coronary flow reserve after dipyridamole in dilated cardiomyopathy. Am J Cardiol 1985; 55: 748-54.Galderisi M, Cicala S, D’Errico A, et al. Nebivolol improves coronary flow reserve in hypertensive patients without coronary heart disease. J Hypertens 2004; 22: 2201-8.Galderisi M, Cicala S, D’Errico A, et al. Nebivolol improves coronary flow reserve in hypertensive patients without coronary heart disease. J Hypertens 2004; 22: 2201-8.Rossen JD, Winniford MD. Effect of increases in heart rate and arterial pressure on coronary flow reserve in humans. JACC 1993; 21: 343-8.Rossen JD, Winniford MD. Effect of increases in heart rate and arterial pressure on coronary flow reserve in humans. JACC 1993; 21: 343-8.Sugioka K, Hozumi T, Takemoto Y, et al. Early recovery of impaired coronary flow reserve by carvedilol therapy in patients with idiopathic dilated cardiomyopathy: a serial transthoracic Doppler echocardiographic study. JACC 2005; 45: 318-9.Sugioka K, Hozumi T, Takemoto Y, et al. Early recovery of impaired coronary flow reserve by carvedilol therapy in patients with idiopathic dilated cardiomyopathy: a serial transthoracic Doppler echocardiographic study. JACC 2005; 45: 318-9.Vyssoulis GP, Marinakis AG, Aznaouridis KA, et al. The impact of thirdgeneration beta-blocker antihypertensive treatment on endothelial function and the prothrombotic state: effects of smoking. Am J Hypertens 2004; 17: 582-9.Vyssoulis GP, Marinakis AG, Aznaouridis KA, et al. The impact of thirdgeneration beta-blocker antihypertensive treatment on endothelial function and the prothrombotic state: effects of smoking. Am J Hypertens 2004; 17: 582-9.Kalinowski L, Dobrucki LW, Szczepanska-Konkel M, et al. Third-generation betablockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action. Circulation 2003; 107: 2747-52.Kalinowski L, Dobrucki LW, Szczepanska-Konkel M, et al. Third-generation betablockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action. Circulation 2003; 107: 2747-52.Brehm BR, Bertsch D, von Fallois J, et al. Beta-blockers of the third generation inhibit endothelin-1 liberation, mRNA production and proliferation of human coronary smooth muscle and endothelial cells. J Cardiovasc Pharmacol 2000; 36: S401-3.Brehm BR, Bertsch D, von Fallois J, et al. Beta-blockers of the third generation inhibit endothelin-1 liberation, mRNA production and proliferation of human coronary smooth muscle and endothelial cells. J Cardiovasc Pharmacol 2000; 36: S401-3.Mundhenke M, Schwartzkopff B, Kostering M, et al. Endogenous plasma endothelin concentrations and coronary circulation in patients with mild dilated cardiomyopathy. Heart 1999; 81: 278-84.Mundhenke M, Schwartzkopff B, Kostering M, et al. Endogenous plasma endothelin concentrations and coronary circulation in patients with mild dilated cardiomyopathy. Heart 1999; 81: 278-84.

The authors declare that there are no conflicts of interest present.