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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the time-dependent changes in the secretion of atrial natriuretic peptide (ANP) in response to chronic stimulation by controlled increments in atrial pressure, we developed methodology for precise control of right atrial pressure (RAP) in dogs by employing an externally adjustable occluder around the pulmonary artery and a servo-control system. During 7 days of servo-control of RAP at 6.3 +/- 0.1 mmHg above control levels (1.3 +/- 0.1 mmHg), the 24-h coefficient of variation in RAP was 1/45 the variation that occurred under control conditions. After 30 min of increased RAP, mean arterial pressure (MAP) was reduced from 101 +/- 4 to 84 +/- 3 mmHg in association with increments in plasma renin activity (PRA) from 0.6 +/- 0.1 to 2.5 +/- 0.9 ng angiotensin I (ANG I).ml-1.h-1 and in the plasma concentrations of ANP, arginine vasopressin (AVP), and epinephrine from 93 +/- 18 to 484 +/- 61 pg/ml, from 0.5 +/- 0.1 to 9.2 +/- 2.4 pg/ml, and from 82 +/- 27 to 585 +/- 133 pg/ml, respectively. In comparison, on day 7 of servo-control of RAP, sodium balance was achieved and MAP remained depressed (82 +/- 4 mmHg) along with sustained increments in both plasma ANP concentration (482 +/- 67 pg/ml) and PRA (1.7 +/- 0.6 ng ANG I.ml-1.h-1); on the other hand, the plasma concentrations of AVP and epinephrine returned to control levels. This quantitative study indicates that ANP secretion does not chronically adapt to stimulation by increased atrial pressure and suggests that the plasma levels of ANP achieved in heart failure markedly increase renal excretory capability and allow fluid balance to be achieved at a substantial fall in renal perfusion pressure.
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PMID:Hormonal and circulatory responses to chronically controlled increments in right atrial pressure. 183 8

The renin-angiotensin system originally was thought to be responsible for only renovascular hypertension, but the development and use of various inhibitors of this system have produced much evidence for its participation in many forms of hypertensive disease. Tissue renin-angiotensin system also may play a major role in blood pressure control. Chronic clinical as well as animal use of converting enzyme inhibitors results in levels of angiotensin II that are equivalent to those found in the normotensive state and higher than those found in the very acute phase of treatment. The source of this conversion possibly may be due to enzymes unrelated to angiotensin converting enzyme. One such enzyme is a very highly specific serine protease isolated from human cardiac tissue. This enzyme exists in human ventricular tissue at levels four to five times that of angiotensin converting enzyme. During chronic treatment of patients with heart failure, angiotensin I levels become high, and heart tissue levels of angiotensin II may become elevated because of the conversion to angiotensin II by this serine protease. This conversion in turn may possibly increase inotropy of the heart, whereas the peripheral resistance remains low because of the reduction of angiotensin II in the circulation.
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PMID:Angiotensin I and II. Some early observations made at the Cleveland Clinic Foundation and recent discoveries relative to angiotensin II formation in human heart. 193 74

There is activation of the renin angiotensin system after both complicated and uncomplicated myocardial infarction. Angiotensin II increases myocardial oxygen consumption whilst reducing coronary flow and is also directly toxic to the myocardium. Angiotensin converting enzyme inhibitors produce beneficial haemodynamic and neuroendocrine changes in patients with acute left ventricular failure, and may have a role in selected patients with cardiogenic shock. There is evidence to suggest that they might prevent the development of late cardiac failure by limiting the extent of post infarction ventricular dilation. Further research is necessary to define their role in the treatment of acute myocardial infarction.
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PMID:Importance of RAA system and the treatment of patients with ACE inhibition after myocardial infarction. 201 17

Several changes in neuroendocrine activity follow failure of cardiac function to satisfy peripheral requirements and contribute to the clinical syndromes of heart failure. Afferent pathways are poorly understood and triggers are both central and peripheral, involving attenuation of atrial and arterial baroreceptor activity. Efferent sympathetic activity is generally increased with resulting vasoconstriction, but responses are organ-specific and differ among heart, kidney, lung and skeletal muscle. Changes in cardiac sympathetic activity are inadequately understood. Enhanced cardiac norepinephrine spillover contrasts with reduced tissue concentration and impaired activity of synthetic enzymes and neuronal catecholamine uptake. Beta-receptor down-regulation further complicates overall adrenergic responsiveness and the balance between enhancement of contractile function and reduction in arrhythmia threshold. Activation of the renin-angiotensin system is potentiated by the sympathetic nervous system and may contribute to vasoconstrictor hyporesponsiveness. Angiotensin II may in turn facilitate the central and peripheral effects of sympathetic activation and the release of vasopressin from the pituitary. Our understanding of the role of vasodilator peptides in heart failure remains rudimentary. It is likely that vasoconstrictor neuroendocrine response adversely influences optimal cardiac function in heart failure and may promote arrhythmogenesis. The neuroendocrine response in individual organs, however, requires intensive study.
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PMID:Neuroendocrine activation in congestive heart failure. 202 Nov 17

Cardiac hypertrophy is characterized by marked abnormalities in the contraction/relaxation pattern of the heart. For example, delayed relaxation is a prominent feature, impairing ventricular filling and coronary flow. In intact heart preparations the relative contribution of fibrosis and of the myocardial cell itself to these abnormalities cannot be correctly assessed. Biochemical studies on the mechanisms of impaired contraction and relaxation and hypertensive heart failure are hampered by the fact that 75% of all heart cells are non-myocytes. We therefore established the model of the isolated calcium-tolerant, adult rat cardiomyocyte as a new approach to the investigation of these problems. Contractility was measured using a videomicroscope system with high time resolution (1 ms). Angiotensin II induced a marked relaxation delay in the cardiomyocyte from normotensive rats and showed a moderate positive inotropic effect, whereas isoproterenol had a strong positive inotropic effect but accelerated relaxation. Therefore, angiotensin II is capable of inducing a relaxation delay even in the absence of coronary ischaemia or hypertension. These first results show that the isolated cardiomyocyte model may be a useful approach to investigating the mechanisms of hypertensive heart disease.
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PMID:Isolated myocardial cells: a new tool for the investigation of hypertensive heart disease. 214 54

The renin-angiotensin-aldosterone system (RAAS) has been implicated in the pathogenesis of congestive heart failure (CHF). Abnormal activation of the RAAS adversely affects cardiac performance and impairs functional status, increasing both afterload and preload through direct and indirect mechanisms. Conventional first-line therapy for CHF consists of diuretics and/or digitalis. Diuretics offer rapid relief of symptoms, effective volume control, and ease of administration, but are associated with a number of disadvantages, including further activation of neurohormonal systems resulting in augmented vasoconstriction. Angiotensin-converting enzyme (ACE) inhibitors, which block the RAAS by inhibiting production of angiotensin II from angiotensin I, are emerging as the vasodilators of choice in combination with diuretics with or without concomitant digitalis. Direct comparative studies have shown that ACE inhibitors provide acute and long-term symptomatic, hemodynamic, and exercise-related benefits as well as improved functional class and, possibly, slowed progression of disease with enhanced survival in specific subgroups. Captopril was the first orally effective ACE inhibitor associated with improved exercise tolerance and functional class in large multicenter trials of patients with severe heart failure and mild to moderate heart failure. Enalapril reduced the probability of death in patients with severe heart failure in the CONSENSUS trial. The new ACE inhibitor quinapril has been shown to improve hemodynamic status both acutely and chronically and to produce dose-related improvements in exercise tolerance. ACE inhibitors have a favorable safety profile, although hypotension can occur with initial doses, particularly in volume-depleted patients or at times when excessive initial doses are administered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ACE inhibitors in the treatment of heart failure. 218 19

Stimulation of the renin angiotensin system, catecholamines and antidiuretic hormone causes prominent vasoconstriction in severe heart failure. Angiotensin converting enzyme inhibitors reverse these effects, and thus ameliorate cardiac function and reduce mortality in severe heart failure. Angiotensin II is an important regulator of renal function in diseases with renal hypoperfusion, and treatment with angiotensin converting enzyme inhibitors may cause a serious decrease in glomerular filtration and hyperkalemia. Asymptomatic heart failure, acute heart failure and acute myocardial infarction are areas where angiotensin converting enzyme inhibitors may prove beneficial in the future.
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PMID:[Treatment of heart failure with angiotensin converting enzyme inhibitors]. 221 71

The pharmacokinetics of the angiotensin-converting enzyme (ACE) inhibitors are difficult to assess for several reasons. First, these compounds exert their influence by inhibiting an intermediary enzyme of a cascade of enzymatic events, whose rate-limiting enzyme (renin) is not directly affected by ACE inhibition. Second, renin and angiotensin I accumulate during ACE inhibition and a change in the dose of an ACE inhibitor could produce sudden shifts of angiotensin I to angiotensin II. Third, components of the circulating renin system require the interaction of several organ systems and effector sites. Fourth, the kinetics of ACE inhibitors can be influenced by the organ systems responsible for drug absorption, metabolism and excretion, and the functional status of these systems can be affected by the heart failure process. Fifth, at least some portion of the cardiovascular effects of ACE inhibitors is influenced by the contributions of other systems whose physiologic effects may be of importance in some patients with congestive heart failure. Sixth, the potential impact of tissue-bound ACE is not yet fully understood. Finally, for appropriate drug dosing, the effects of aging on the heart failure process, the extent of renin system activity, and the disposition of ACE inhibitors need to be considered. Because of their complex pharmacokinetics, treatment with ACE inhibitors has been guided by their pharmacodynamic and clinical characteristics.
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PMID:Pharmacology of angiotensin-converting enzyme inhibitors as a guide to their use in congestive heart failure. 222 Jun 5

The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure.
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PMID:Inotropic effects of angiotensin II on human cardiac muscle in vitro. 224 22

Perindopril is an orally active, non-thiol angiotensin-converting enzyme (ACE) inhibitor, which in doses of 4 to 8mg is effective in the control of essential hypertension. As monotherapy it is as effective as once-daily atenolol and possibly more effective than twice-daily captopril. A synergistic response has been noted when perindopril is combined with a thiazide diuretic. Maximal pharmacodynamic effects (ACE inhibition, increase in plasma renin activity and angiotensin I, reduction in aldosterone and angiotensin II and blood pressure) are seen 4 to 6 hours after dosing, with substantial effects still present at 24 hours. Perindopril is a prodrug which requires de-esterification to perindoprilat for useful ACE inhibition. Maximal plasma perindoprilat concentrations are reached 2 to 6 hours after oral administration of perindopril, and 70% of the active metabolite is cleared by the kidneys. The other major metabolite of perindopril is an inactive glucuronide. Ageing is associated with increased serum perindoprilat concentrations, which are probably caused by a combination of enhanced conversion to the active metabolite and diminished renal clearance. Compensated cirrhosis does not appear to have an independent effect. There is little published experience of the use of perindopril in patients with cardiac failure or other cardiac disease, but preliminary evidence would support the general value of this class of agent as adjunctive therapy.
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PMID:Perindopril. A review of its pharmacokinetics and clinical pharmacology. 240 93


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