title: [The physiopathological aspects and new therapeutic approaches in cardiac-circulatory failure].
abstract: Pathophysiological mechanisms are reviewed concerning the onset and the perpetuation of the clinical features of congestive heart failure. This syndrome is a severe condition of poor prognosis and bad life quality which in the last decades has reached, in the western industrial countries, the highest levels of general mortality, mainly due to the high prevalence of hypertensive and ischaemic myocardiopathies in the last years. To the clinical features of heart failure mainly contributes a deregulation of the physiological compensatory mechanisms contemporarily and concurrently activated following the primary deficiency of the heart pump function. In physiological conditions, following the myogenic adapting mechanisms reflex mechanisms intervene, activated by intracardiac and aortic and carotid-sinus mechanoreceptors following the variations in intracardiac and intravascular pressure and generally evoking negative feed-back effects. In patients with heart failure arterial high pressure mechanoreceptors respond to the reduction in effective arterial pressure thus provoking a deactivation of the tonic inhibition on the sympathetic cardiovascular drive. This leads to an activation of peripheral and renal vasoconstrictor tone, to a raised medullary catecholamine incretion, to heart rate and inotropism stimulation, and to an increase in pituitary gland ADH production as well as to an activation of renin-angiotensin-aldosterone system (RAAS). Analogous vasoconstrictive, and sodium and water retentive effects can be elicited by endothelin produced by endothelial cells and found in high plasma levels in CHF. These excitatory effects, leading to a rise in systemic vascular resistance and to hydro-electrolytic retention with volume expansion, are not efficiently counteracted by the opposite effects triggered by cardiopulmonary vagally mediated mechanoreceptors activated by the raised cardiac filling pressure and leading to sympathetic nervous inhibition, peripheral and renal vasodilation, ADH and RAAS inhibition. Analogous effects should be provoked by the raised production, due to enhanced heart wall distension, of atrial natriuretic factor leading to vasodilation, natriuresis and diuresis. Reduced sensitivity of cardiopulmonary baroreceptors and lowered production of ANF due to structural cardiac changes could represent, according to most opinions, the main factors responsible for the prevailing sympathetic activation and hydro-saline retention in CHF. The activation of cardiopulmonary sympathetic positive-feed back afferents, could be also involved in the characteristic alteration of the vago-sympathetic balance in heart failure. The persistent reduction in heart pump function could lead to the instauration of vicious circles among the various regulatory systems and create an overcompensation condition.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Dipartimento di Medicina Intena, Università degli Studi di Roma Tor Vergata.
authors.forename: G
authors.initials: G
authors.lastname: Peruzzi
authors.forename: P
authors.initials: P
authors.lastname: Di Nardo
authors.forename: G
authors.initials: G
authors.lastname: Raimondi
authors.forename: J M
authors.initials: JM
authors.lastname: Legramante
authors.forename: F
authors.initials: F
authors.lastname: Iellamo
authors.forename: M
authors.initials: M
authors.lastname: Massaro
authors.forename: F
authors.initials: F
authors.lastname: Bellegrandi
authors.forename: M
authors.initials: M
authors.lastname: Minieri
authors.forename: M
authors.initials: M
authors.lastname: Pafi
authors.forename: F
authors.initials: F
authors.lastname: Castrucci
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans
chemical_list: D002317:Cardiovascular Agents
vernacular_title: Aspetti fisiopatologici e nuovi indirizzi terapeutici nell'insufficienza cardio-circolatoria.