Cerqueira-Gomes M, Polónia J, Brandão F, Ramalhão C, da Faria D B
Unidade de Farmacologia Clínica do Serviço de Medicina 3/Cardiologia Serviço de Cardiologia do Hospital de S. João, Porto.
Rev Port Cardiol. 2001 May;20 Suppl 5:V-99-122; discussion V-123-5.
This review updates some recent advances of a new and exciting developments in basic and clinical cardiology: a) the role, in the congestive heart failure (CHF), of the neurohumoral systems (NHS) which act to maintain circulatory homeostatic equilibrium, and b) the therapeutic implications of such a role. Six NHS, acting in CHF, have presently been identified: three of them induce vasoconstriction and sodium retention (sympathetic nervous systems, renin-angiotensin-aldosterone system and arginine-vasopressine system); the remaining three offset or balance the former ones, acting, therefore as "counterregulators" (prostaglandins--PGE2 and PGI2--, dopaminergic system and atrial natriuretic factor). Each one of these NHS influences the "compensatory" mechanisms of heart failure, acting on the target-organs both by direct effects and by interaction with other NHS; consequently, in heart failure, all the NHS are stimulated with the respective increase in the plasma levels of their active agents. In asymptomatic stages of ventricular dysfunction the stimulation of the vasodilator-and-natriuretic systems appears to be predominant and able to maintain circulatory equilibrium. However, as the heart dysfunction increases and becomes symptomatic, the vasoconstrictor and sodium-retaining forces appear to predominate; this phenomenon becomes increasingly apparent as the functional class becomes more advanced. The hyperstimulation of these last systems has an extremely important role in the pathophysiology and clinical manifestations of congestive heart failure, as well as in its prognosis. Therefore, the attempts to correct these neurohormonal imbalance in patients with heart failure has a sound rational basis, not only to improve the symptoms and the exercise capacity but also to increase the survival of these patients. At the present time, amongst the potential pharmacological interventions acting on NHS in CHF, the blockade of the RAA system with ACE-inhibitors is generally accepted as the most feasible, the safest and the most effective therapeutic tool. In fact, its application has broadened from an earlier use in severe CHF to other symptomatic stages of cardiac failure, including the milder forms. In addition, preliminary data strongly suggest its unique usefulness in asymptomatic phase of ventricular dysfunction. Looking back at the medical therapy of heart failure, in can be concluded that we are starting a new era. Throughout 200 years (since the introduction of digitalis) the therapeutic goal in CHF has been the improvement of symptoms. With the developments of the present decade, a new and exciting goal is being offered to these patients, called by Packer "the second frontier", that is, the prolongation of their lives.
本综述更新了基础与临床心脏病学领域一些新的、令人振奋的进展：a）在充血性心力衰竭（CHF）中，神经体液系统（NHS）在维持循环稳态平衡方面所起的作用；b）这一作用的治疗意义。目前已确定在CHF中起作用的6种NHS：其中3种可诱导血管收缩和钠潴留（交感神经系统、肾素 - 血管紧张素 - 醛固酮系统和精氨酸加压素系统）；其余3种可抵消或平衡前三者，因此作为“反调节因子”发挥作用（前列腺素——PGE2和PGI2——、多巴胺能系统和心房利钠因子）。这些NHS中的每一种都通过直接作用以及与其他NHS的相互作用影响心力衰竭的“代偿”机制，作用于靶器官；因此，在心力衰竭时，所有NHS均被激活，其活性物质的血浆水平相应升高。在心室功能障碍的无症状阶段，血管舒张和利钠系统的激活似乎占主导地位，并能够维持循环平衡。然而，随着心脏功能障碍加重并出现症状，血管收缩和钠潴留力量似乎占主导；随着心功能分级进展，这种现象愈发明显。这些最后提到的系统的过度激活在充血性心力衰竭的病理生理学、临床表现及其预后中具有极其重要的作用。因此，试图纠正心力衰竭患者的这些神经激素失衡具有合理的依据，不仅可以改善症状和运动能力，还能提高这些患者的生存率。目前，在针对CHF中NHS的潜在药物干预措施中，使用ACE抑制剂阻断肾素 - 血管紧张素 - 醛固酮系统通常被认为是最可行、最安全且最有效的治疗手段。事实上，其应用范围已从早期在严重CHF中的使用扩展到心力衰竭的其他有症状阶段，包括较轻的形式。此外，初步数据强烈表明其在心室功能障碍无症状阶段具有独特的效用。回顾心力衰竭的药物治疗，可以得出结论，我们正在开启一个新时代。在200年（自洋地黄引入以来）里，CHF的治疗目标一直是改善症状。随着本十年的发展，一个新的、令人振奋的目标正在为这些患者呈现，被帕克称为“第二个前沿”，即延长他们的生命。
