The Neurohumoral Axis in Congestive Heart Failure

Abstract

The incidence of congestive heart failure is increasing in the United States. This common syndrome is characterized not only by impaired ventricular function but also by an increase in some endogenous vasoconstrictor substances, including norepinephrine, angiotensin II, and arginine vasopressin. Although activation of the systems that release these substances is presumed to be compensatory (to maintain perfusion pressure during inadequate flow), the sympathetic nervous system, renin-angiotensin-aldosterone system, and arginine vasopressin may contribute to the pathogenesis of the syndrome. The excessive vasoconstriction present in heart failure likely produces a further burden on the failing myocardium. New strategies in therapy are being developed to counteract the activation of vasoconstrictor forces in congestive heart failure. Data indicate that selective blockade of the renin-angiotensin system is useful. Preliminary data suggest that inhibition of the sympathetic nervous system may be helpful, and inhibition of vasopressin in animals with heart failure is being studied. New and more selective therapy for heart failure may come from these studies.

Effects of myocardial alpha 1-adrenergic receptor stimulation and blockade on contractility in humans.

“…22,24 In contrast, myocardial a1-adrenergic receptor density is not decreased in heart failure.3-5 Our data show that the positive inotropic response that can be attributed to a-adrenergic receptor stimulation was reduced in the congestive heart failure group and was most reduced in the patients with the lowest left ventricular ejection fractions. This finding is consistent with a number of possibilities.…”

Role of heart rate in mechanisms of compensation and decompensation in patients with CHF and sinus rhythm or atrial fibrillation and methods for safe and effective control of the heart rhythm. Part 1. Sinus rhythm

“…Выживаемость пациентов с систолической ХСН (II-IV ФК) и разным основным ритмом в зависимости от ЧСС ОБЗОРЫ § их влияние на прогноз пока не установлено [54][55][56] Амиодарон обладает умеренной эффективностью [57] при наличии экстракардиальных побочных эффектов и, по данным подгруппового анализа SCD-HeFT, также повышает риск смерти у пациентов с ХСН III-IV ФК [58]. Поводом к использованию β-АБ в лечении пациен-тов с ХСН было не столько увеличение ЧСС, сколько негативная роль гиперактивации САС в прогрессирова-нии декомпенсации и повышении смертности больных [59,60]. Этот подход привел к достоверному улучше-нию прогноза больных с систолической ХСН [61][62][63][64] Снижение смертности больных ХСН при использова-нии β-АБ теоретически связывали со снижением акти-вации САС и, возможно, РААС, что, в частности, было продемонстрировано в работах нашей группы [61,65].…”

Heart failure: a hemodynamic disorder complicated by maladaptive proliferative responses

“…Clues regarding the importance of non-hemodynamic abnormalities in heart failure emerged in the early 1980s, when the neurohumoral response to low cardiac output was found to have a major adverse effect on long-term survival [28]. As pointed out in a landmark paper by Peter Harris, the neurohumoral response compensates for short-term hemodynamic challenges like exercise and hemorrhage, but has harmful effects when the response is sustained [29].…”