Mechanisms of Benefit in the Ischemic Myocardium due to Heart Rate Reduction

Guth, Brain D.; Indolfi, Ciro; Heusch, Gerd; Seitelberger, Rainald; Ross, John

doi:10.1007/978-3-662-11038-6_13

Cited by 7 publications

(6 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several different mechanisms have been proposed to elucidate the beneficial effect of ␤-blockers under such conditions (4,23). Importantly, the most vital role of the ␤-blockers (including AT) in restoration of LV function was ascribed to reduction in heart rate (14,25). For instance, studies on the ischemic myocardium of conscious dogs revealed that AT-induced reduction in heart rate was associated with the concurrent improvement in coronary blood flow and contractile performance.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, studies on the ischemic myocardium of conscious dogs revealed that AT-induced reduction in heart rate was associated with the concurrent improvement in coronary blood flow and contractile performance. Most importantly, when electrical pacing was used concurrently with AT treatment to increase heart rate to baseline levels, the improvement in blood flow as well as in cardiac function was eliminated (14,32). In our present study, as well as in a previous study (22), we also found a dual beneficial role of chronic bradycardia 1) on LV contractile performance, as indicated by an attenuation of the drop in ejection fraction, and 2) on coronary perfusion indexes, as indicated by normalized CPR.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Reduction of heart rate by chronic β₁-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart

Dedkov¹,

Christensen²,

Weiß³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Dedkov, Eduard I., Lance P. Christensen, Robert M. Weiss, and Robert J. Tomanek. Reduction of heart rate by chronic ␤1-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart. Am J Physiol Heart Circ Physiol 288: H2684 -H2693, 2005. First published January 28, 2005 doi:10.1152/ajpheart.01047.2004.-Adequate growth of coronary vasculature in the remaining left ventricular (LV) myocardium after myocardial infarction (post-MI) is a crucial factor for myocyte survival and performance. We previously demonstrated that post-MI coronary angiogenesis can be stimulated by bradycardia induced with the ATP-sensitive K ϩ channel antagonist alinidine. In this study, we tested the hypothesis that heart rate reduction with ␤-blockade may also induce coronary growth in the post-MI heart. Transmural MI was induced in 12-mo-old male Sprague-Dawley rats by occlusion of the left anterior descending coronary artery. Bradycardia was induced by administration of the ␤-adrenoceptor blocker atenolol (AT) via drinking water (30 mg/day). Three groups of rats were compared: 1) control/sham (C/SH), 2) MI, and 3) MI ϩ AT. In the MI ϩ AT rats, heart rate was consistently reduced by 25-28% compared with C/SH rats. At 4 wk after left anterior descending coronary ligation, infarct size was similar in MI and MI ϩ AT rats (67.1 and 61.5%, respectively), whereas a greater ventricular hypertrophy occurred in bradycardic rats, as indicated by a higher ventricular weight-to-body weight ratio (3.4 Ϯ 0.1 vs. 2.8 Ϯ 0.1 mg/g in MI rats). Analysis of LV function revealed a smaller drop in ejection fraction in the MI ϩ AT than in the MI group (ϳ24 vs. ϳ35%). Furthermore, in MI ϩ AT rats, maximal coronary conductance and coronary perfusion reserve were significantly improved compared with the MI group. The better myocardial perfusion indexes in MI ϩ AT rats were associated with a greater increase in arteriolar length density than in the MI group. Thus chronic reduction of heart rate induced with ␤-selective blockade promotes growth of coronary arterioles and, thereby, facilitates regional myocardial perfusion in post-MI hearts. myocardial infarction; angiogenesis; coronary circulation; resistance vessels; capillaries A LARGE TRANSMURAL MYOCARDIAL infarction (MI) of the left ventricle (LV) causes the sudden loss of a substantial number of cardiac myocytes, which leads to increased diastolic wall stress and chronic functional overload of the remaining portion of LV myocardium. As a result, the LV undergoes progressive structural remodeling, consisting of thinning and scarring of the infarcted region, chamber dilation, and eccentric hypertrophy of the surviving portion of the LV myocardium (1,27,30).Because scar tissue is not capable of contracting, LV function after MI is entirely dependent on the hypertrophied portion of the surviving LV myocardium. However, to accommodate an increased O 2 demand in the surviving overloaded cardiac myocytes, an adaptation of the vascular bed is necessary. Two basic me...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reduction of heart rate by chronic β₁-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart

Dedkov¹,

Christensen²,

Weiß³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Studies performed on anesthetized swine and in conscious, exercising dogs have indicated that heart rate reduction produced by zatebradine was an essential mechanism to improve regional contractile function and subendocardial blood flow during ischemia [106][107]; this was accompanied by a decrease of the subepicardial perfusion in the ischemic zone of anesthetized dogs, indicating a regional redistribution of myocardial perfusion [108].…”

Section: Zatebradine (Ul-fs49) and Cilobradine (Dk-ah269)mentioning

confidence: 99%

Molecular Regulation and Pharmacology of Pacemaker Channels

Bois¹,

Guinamard²,

Chemaly³

et al. 2007

CPD

View full text Add to dashboard Cite

The spontaneous activity of cardiac tissue originates in specialized pacemaker cells in the sino-atrial node that generate autonomous rhythmic electrical impulses. A number of regions in the brain are also able to generate spontaneous rhythmic activity to control and regulate important physiological functions. The generation of pacemaker potentials relies on a complex interplay between different types of currents carried by cation channels. Among these currents, the hyperpolarization-activated current (termed I(f), cardiac pacemaker "funny" current, and I(h) in neurons) is the major component contributing to the initiation of cardiac and neuronal excitability and to the modulation of this excitability by neurotransmitters and hormones. I(f) is an inward current activated by hyperpolarization of the membrane potential and by intracellular cyclic nucleotides such as cAMP. The identification at the end of the 1990s of a family of mammalian genes that encode for four Hyperpolarization-activated Cyclic Nucleotide-gated channels, HCN1-4, has made analysis of the location of these channels and the study of their biophysical properties an obtainable goal. As a result, specific agents have been developed for their ability to selectively reduce heart rate by lowering cardiac pacemaker activity where f-channels are their main natural target. These drugs include alinidine, zatebradine, cilobradine, ZD-7288 and ivabradine. Recent data indicate that pharmacological tools such as W7 and genistein, which have been used to identify some intracellular pathways involved in ionic channel modulation, also have the ability to inhibit I(f) directly. This opens new perspectives for the future development of other specific rhythm-lowering agents.

show abstract

“…Так, было показано, что снижение ЧСС вследствие абляции синусово-го узла или фармакологическими агентами (ББ, ивабрадин) приводит к уменьшению уровня оксидативного стресса, эндотелиальной дисфункции, предупреждению прогрессии атеросклероза у мышей с дефицитом Апо-Е [76], регрессу уже имеющихся каротидного и коронарного атеросклеро-тических повреждений [77], улучшению кровоснабжения ишемизированного миокарда [78], снижению уровня нор-адреналина, уменьшению плотности коллагена, увеличению плотности капилляров и, как следствие, улучшению систо-лической функции ЛЖ при экспериментальной ХСН [79].…”

Section: Discussionunclassified

Reduction of increased heart rate in arterial hypertension: clinical and predictive practicability

Кобалава¹,

Kiyakbaev²,

Shavarov³

2015

RHJ

View full text Add to dashboard Cite

П овышенная ЧСС является независимым ФР, увели-чивающим общую смертность, частоту внезапной сердечной смерти и смерти от ССЗ как в общей популя-ции, так и в отдельных подгруппах: пожилых больных, пациентов с АГ, ИМ, СД, больных с установленным диа-гнозом ИБС [1][2][3][4][5][6][7][8][9][10][11].В этой связи есть основание полагать, что замедление ЧСС будет оказывать положительное влияние на течение ССЗ. Действительно известно, что применение β-АБ (ББ) или верапамила у больных в разные сроки после перене-сенного ИМ сопровождалось снижением смертности и риска развития несмертельного ИМ [12][13][14][15][16][17][18][19][20][21][22]. При этом отмечена отчетливая связь этих эффектов со степенью уменьшения ЧСС [13]. На положительный эффект ББ также указывают результаты мета-анализа рандомизиро-ванных клинических исследований (РКИ), включавших больных СН [23]. В то же время данные о влиянии меди-каментозного снижения ЧСС на прогноз пациентов с АГ, для которых тахикардия является характерной особенно-стью, далеко не столь однозначны. Результаты некоторых исследований и мета-анализов инициировали дискуссию о месте ББ в ряду гипотензивных препаратов с точки зре-ния снижения риска общей и сердечно-сосудистой смерт-ности у данной категории пациентов [24][25][26].В настоящем обзоре представлены данные, отражаю-щие многообразие проблемы клинико-прогностической значимости повышенной ЧСС при АГ. Связь АГ со склонностью к тахикардииИзвестно, что почти 30 % больных с АГ имеют ЧСС более или равную 80 уд / мин [27][28][29]. В российских наблюдатель-ных исследованиях ЭКСТРА, ЭКСТРА-2 и КОНСТАНТА было установлено, что средний уровень ЧСС у амбулатор-ных пациентов с неконтролируемой АГ, более 40 % из кото-рых в рамках гипотензивной терапии принимали ББ, ока-зался достаточно высоким и составлял 74,6±10,7 уд / мин Кобалава Ж. Д., Киякбаев Г. К., Шаваров А. А. Резюме Повышенная ЧСС является независимым ФР, увеличивающим общую смертность, частоту внезапной сердечной смер-ти и смерти от ССЗ как в общей популяции, так и в отдельных подгруппах. Данные о влиянии медикаментозного снижения ЧСС на прогноз пациентов с АГ, для которых тахикардия является характерной особенностью, далеко не столь однозначны. Результаты некоторых исследований и мета-анализов инициировали дискуссию о месте β-АБ в ряду гипотензивных препаратов с точки зрения снижения риска общей и сердечно-сосудистой смертности у данной категории пациентов. В обзоре представле-ны данные, отражающие многообразие проблемы клинико-прогностической значимости повышенной ЧСС при АГ.Kobalava Zh. D., Kiyakbaev G. K., Shavarov A. A.Federal State Autonomous Educational Institution of Higher Education, "Russian University of Peoples' Friendship", Miklukho-Maklaya 6, Moscow 117198Reduction of increased heart rate in arterial hypertension: clinical and predictive practicability Keywords: arterial hypertension, heart rate, arterial stiffness, beta-adrenergic blocker agentsFor citation : Kobalava Zh. D., Kiyakbaev G. K., Shavarov A. A. Reduction of increased heart rate in arterial hypertension: clini...

show abstract

Mechanisms of Benefit in the Ischemic Myocardium due to Heart Rate Reduction

Cited by 7 publications

References 25 publications

Reduction of heart rate by chronic β₁-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart

Reduction of heart rate by chronic β₁-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart

Molecular Regulation and Pharmacology of Pacemaker Channels

Reduction of increased heart rate in arterial hypertension: clinical and predictive practicability

Contact Info

Product

Resources

About

Mechanisms of Benefit in the Ischemic Myocardium due to Heart Rate Reduction

Cited by 7 publications

References 25 publications

Reduction of heart rate by chronic β1-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart

Reduction of heart rate by chronic β1-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart

Molecular Regulation and Pharmacology of Pacemaker Channels

Reduction of increased heart rate in arterial hypertension: clinical and predictive practicability

Contact Info

Product

Resources

About

Reduction of heart rate by chronic β₁-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart

Reduction of heart rate by chronic β₁-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart