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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chagasic patients with congestive heart failure are usually treated with digitalis and converting enzyme inhibitors. According to the neurogenic and dysautonomic theories, chagasic patients would not benefit from these drugs. To clarify this controversial issue, we have studied patients with congestive heart failure and suspected Chagas' heart disease. All patients received intravenous methyl-digoxin for 24 h and oral enalapril for 96 h. Blood samples for plasma norepinephrine, aldosterone and renin were taken at baseline, after acute digitalization and following enalapril. Based on the serology for Chagas' disease, the patients were divided into non-chagasic and chagasic patients. In the chagasic group three patients were in functional class III and 3 were in functional class IV. In the non-chagasic group five patients were in functional class III and 2 were in functional class IV. Both groups had a marked and quantitatively similar degree of neurohormonal activation. All patients improved at least one functional class and lost more than 5 kg of body weight with treatment. The chagasic patients had a statistically significant reduction in plasma norepinephrine (2262 +/- 1407 to 865 +/- 390, P < 0.008, pg/ml, M +/- S.D.), plasma aldosterone (330 +/- 168 to 155 +/- 75, P < 0.01, pg/ml, M +/- S.D.) and plasma renin activity (14 +/- 13 to 2 +/- 1.6 ng/ml per h, M +/- S.D., P < 0.05), with digitalis. Following enalapril, norepinephrine and aldosterone there was a further but non-significant reduction, when compared to postdigitalis values. These results indicated that chagasic patients do benefit from digitalis and enalapril. Furthermore, the prominent and significant reduction in all three neurohormones suggest that the parasympathetic and sympathetic systems of these chagasic and non-chagasic patients, are responding to the neuromodulatory effects of digitalis and enalapril.
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PMID:Acute effects of digitalis and enalapril on the neurohormonal profile of chagasic patients with severe congestive heart failure. 896 Sep 39

The delineation of the molecular mechanisms of cardiovascular disease is an important initial step in developing improved methods of screening and therapy. Recently, progress has been made in characterizing the molecular basis of several inherited cardiovascular diseases, particularly as to the diseases caused by defects in single gene. When the disease under study has a complex etiology with multiple genetic and environmental components, it becomes much more difficult to dissect out the genetic factors and to distinguish between causation and correlation. Gene targeting in mice provides a means to test the effect of a precise genetic change completely free from the effects of differences in any other genes. Models of several human genetic diseases have been produced by gene targeting and the resulting "knockout" mice have often confirmed that the disease is the consequence of the defect of a gene of interest. The review will focus on the how molecular genetic approach is useful to understand the basic mechanism of complex genetic diseases, including essential hypertension, atherosclerosis, congenital heart disease. Particular emphasis will be given to the renin angiotensin system because a large body of evidence indicates its greater role in the pathogenesis of many complex cardiovascular diseases than has been recognized.
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PMID:Molecular genetic approach to the pathophysiology of cardiovascular disease. 897 74

Angiotensin converting enzymes inhibitors are now regarded as the cornerstone of congestive heart failure therapy owing to established reduction in mortality and the symptomatic amelioration following their use. Although the response to converting enzyme inhibitor therapy may be influenced by race, we have reported a trend to reduce intra hospital mortality, the correction of hyponatremia and shortened hospitalization in Nigerians treated with converting enzyme inhibitors. We have now conducted an extended retrospective study, to evaluate the trends in the use of enalapril or captopril and its impact on prognosis in Nigerian patients with heart failure alone, admitted between January 1992 to December 1994. The proportion of heart failure treated with (captopril or enalapril) increased from 37pc in 1992, to 50pc in 1993, to 65pc in 1994. The demographic variables and cause of heart disease were similar in patients treated with converting enzyme inhibitors (n = 55) and those treated conventionally (n = 36). The cumulative mortality among converting enzyme inhibitors treated patients, was (8/55, 14pc) compared to patients not treated (17/36, 48pc) x2 = 12.4; p < 0.0001. There was no sex predilection in mortality (M = 25pc, F = 28pc, mean 27pc). However, initial serum Na+,125mmol was significantly (x2 = 11.1; p < 0.001) more common in the dead patients, 25pc compared to the survivors discharged home 7.5pc. The median hospital stay was 17 days in captopril treated survivors (range two to 44 days) and 19 days (range four to 67 days) in conventionally treated patients. Thus converting enzyme inhibitor therapy may reduce intra hospital mortality in Black Africans hospitalized for congestive heart failure and shorten hospital stay, despite the epidemiologically low plasma renin in Blacks. Hyponatremia may be a poor prognostic index in heart failure in our patients, and its reversal by converting enzyme inhibitors may reflect neurohormonal inhibitor. Earlier and more wide spread use of angiotensin converting enzyme inhibitors in Nigerian and Black Africans with chronic heart failure is now clearly indicated.
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PMID:A three year clinical review of the impact of angiotensin converting enzyme inhibitors on the intra hospital mortality of congestive heart failure in Nigerians. 899 May 72

The renin-angiotensin system is associated with a variety of pathophysiological processes in many organ systems, and is known to be involved in the normal regulation of blood pressure and in the pathogenesis of renovascular hypertension. Angiotensin II is a multifunctional hormone that manifests its properties by interacting with two major subtypes of cell surface receptors (AT1 and AT2). Angiotensin converting enzyme (ACE) inhibitors are able to modify the actions of the renin-angiotensin system, and are indicated for the treatment of hypertension and heart disease. The antihypertensive effects of ACE inhibiting drugs are related to their ability to block the conversion of the decapeptide, angiotensin I, to the potent pressor octapeptide, angiotensin II. ACE inhibitors have been implicated in fetopathies in humans and perinatal mortality in rats, rabbits, sheep and baboons. Human fetopathies were seen when ACE inhibitors were given around the 26th week of gestation. The major adverse effects in babies include: oligohydramnios, renal tubular dysgenesis, neonatal anuria, calvarial and pulmonary hypoplasia, mild to severe intrauterine growth retardation, persistent patent ductus arteriosus and fetal or neonatal death. These developmental anomalies are thought to be partly due to a direct action of ACE inhibitors on the fetal renin-angiotensin system and partly due to the ischemia resulting from maternal hypotension and decreases in fetal-placental blood flow and oxygen/nutrient delivery to the fetus. The purpose of this review is to briefly discuss the pathophysiological role of the renin-angiotensin system, the therapeutic uses of ACE inhibitors in pregnant patients and to focus primarily on the major fetotoxic effects of ACE inhibitors encountered in humans and animal models. I will also review our recent data which show that capozide (captopril + hydrochlorothiazide) not only produces oligohydramnios but also disturbs the balance of glucose and NaCl in the maternal plasma and amniotic fluid of the rat.
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PMID:An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development. 940 46

Prolonged Q-T interval predicts severe arrhythmias and sudden death, and has been shown to occur in alcoholic liver disease and cirrhotic patients who are candidates for liver transplantation. This study first evaluated the prevalence of prolonged Q-T interval in a large population of unselected patients with cirrhosis, and assessed the relationship between abnormal Q-T, etiology, and severity of liver disease and mortality of patients. Possible causes of Q-T abnormality were also explored. Ninety-four patients with cirrhosis without overt heart disease and 37 control subjects with mild chronic active hepatitis were enrolled. Rate-corrected Q-T interval (Q-Tc) was assessed along with routine liver tests, Child-Pugh score, serum bile salts, electrolytes and creatinine, plasma renin activity, aldosterone, norepinephrine, atrial natriuretic factor and, gonadal hormones. Q-Tc was longer in patients with cirrhosis than in controls (440.3 +/- 3.2 vs. 393.6 +/- 3.7 ms; P < .001) and prolonged (> 440 ms) in 44 patients (46.8%) and 2 controls (5.4%; P < .001). Q-Tc length was not influenced by the etiology of cirrhosis and correlated with Child-Pugh score (r = .53; P < .001), liver tests such as prothrombin activity, and serum concentrations of albumin and bilirubin, plasma bile salts, and plasma norepinephrine. Multivariate analysis showed that only Child-Pugh score and plasma norepinephrine were independently correlated with Q-Tc duration. Over a median follow-up period of 19 months (range, 2-33 months), patients with Q-Tc longer than 440 ms had a significantly lower survival rate than those with normal Q-Tc. Q-T interval is frequently prolonged in patients with cirrhosis, regardless the etiology of the disease, worsens in parallel with the severity of the disease, and may have an important prognostic meaning. In addition to other undefined factors related to the severity of cirrhosis, sympathoadrenergic hyperactivity may play a pathogenetic role.
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PMID:Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors. 942 13

Traditionally, the pathophysiology of heart failure was viewed as a derangement in hemodynamic factors. Impairment in cardiac function resulted in decreased cardiac output and end-organ hypoperfusion triggering compensatory increases in heart rate, blood pressure and cardiac contractility. While initially beneficial, these mechanisms placed additional stress on the failing heart. Unfortunately, pharmacologic therapies that restored hemodynamic balance failed to halt disease progression. The activation of neurohormonal responses, including those of the renin-angiotensin-aldosterone system, the sympathetic nervous system and the arginine vasopressin system, has been implicated in the progression of heart disease. In acute heart failure, their effects help to restore cardiovascular homeostasis. However, the chronic stimulation of these systems eventually leads to worsening left ventricular function. Drug treatments that activate neurohormonal systems may have long-term clinically deleterious outcomes, and therefore new pharmacological therapies for cardiovascular disease must take into account the interaction between neurohormonal activation and hemodynamic factors.
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PMID:Neurohormonal activation in the treatment of congestive heart failure: basis for new treatments? 969 63

The importance of the loss of ovarian function to the progression of hypertension and heart disease in women is controversial. We investigated whether ovariectomy would accelerate development of hypertension, congestive heart failure, and neurohumoral activation in adult spontaneous hypertension heart failure (SHHF) rats, a genetic model of heart failure. Six months after ovariectomy, no significant differences between control and ovariectomized rats were seen in systolic or diastolic blood pressure, left ventricular fractional shortening by echocardiography, or heart weight. Percent V1 myosin isozyme was significantly lower in ovariectomized rats. Northern blot analysis failed to show significant differences between groups in expression of hepatic angiotensinogen, renal renin, or left ventricular atrial or brain natriuretic peptide mRNA. In a second experiment, serial measures of systolic pressure and left ventricular shortening fractions failed to document a significant difference between control and ovariectomized rats as they developed heart failure, although there was a significant decline in shortening fraction in both groups at the age when regular estrous cycling naturally ceases. Survival time was similar between groups. In summary, ovariectomy of adult SHHF rats does not appear to affect the progression of genetically programmed hypertension and heart failure in this model.
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PMID:Effect of ovariectomy in heart failure-prone SHHF/Mcc-facp rats. 984 86

The autonomic nervous system is abnormal in patients with advanced Chagas'heart disease. Most researchers consider these autonomic abnormalities as primary, specific and irreversible. However, when and why do these abnormalities appear in the natural history of Chagas'disease, is still the subject of intense controversy. Recent morphological and functional studies strongly suggest that, the sympathetic and the parasympathetic abnormalities, are preceded by myocardial damage and left ventricular dysfunction. Consequently, the cardiac parasympathetic abnormalities and the activation of the sympathetic and of the renin-angiotensin-aldosterone systems of chagasic patients are very likely secondary and partially reversible. Therefore, neurohormonal activation, as postulated by the neurogenic theory could contribute to the progression of myocardial damage and left ventricular dysfunction. Additional clinical investigations are necessary to clarify this important issue.
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PMID:[Chagas cardiomyopathy and the autonomic nervous system. Clinical studies]. 1036 91

Heart failure has become the most widely studied syndrome in cardiology over the recent years. Despite the encouraging achievements by angiotensin converting enzyme (ACE) inhibitors, the mortality of patients with chronic heart failure remains high. There are several factors which can potentially be responsible for the fact that about 80% of patients with a failing heart defy protection by ACE inhibitors: different activation of tissue and systemic renin-angiotensin system (RAS) in a particular heart disease and the distinct ability of various ACE inhibitors to block cardiac ACE, alternative pathways for angiotensin II formation (chymase), genetic polymorphism of the RAS system and the complexity of neuroendocrine activation. Moreover, chronic heart failure can provoke disturbances in the reactivity of peripheral vessels and metabolism of striated muscles. These factors may then potentiate the vicious circle of heart failure. New therapeutic approaches, which could further reduce the mortality in patients with heart failure involve angiotensin II type 1 receptor antagonists, beta-blockers, aldosterone antagonists and blockers of the endothelin receptor. A number of questions associated with functions of the RAS still remain open and their solution could be of substantial benefit for patients with a failing heart.
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PMID:Heart failure and angiotensin converting enzyme inhibition: problems and perspectives. 1047 Aug 60

The renin-angiotensin system (RAS) plays a central role in cardiovascular homeostasis. Angiotensin is the key peptide of the RAS, and exerts its influence on the heart and blood vessels both through its haemodynamic effects (via its influence on after-load and pre-load and determining coronary vasoconstriction) and through its direct cellular effects (via its actions on cell proliferation). Numerous studies in the past 10 years have demonstrated that the pharmacological inhibition of angiotensin converting enzyme (ACE), one of the two critical enzymes of the RAS, improves the outcome in patients with several cardiovascular disorders (hypertension, heart failure, ischaemic heart disease). These studies suggest a role of the RAS as a major determinant of cardiovascular risk. Recent data suggest that genetics may in turn contribute to modulating the effects of angiotensin on coronary vascular biology and ischaemia. This paper reviews the physiologic characteristics of the RAS and recent research developments related to angiotensin cell biology and pathobiology in heart disease. In particular, this review will cover the genetic aspects of RAS and their implications in cardiovascular disease.
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PMID:Aspects of gene polymorphisms in cardiovascular disease: the renin-angiotensin system. 1142 97


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