Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardiovascular effects of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride), a novel water-soluble forskolin derivative, were investigated in dogs. Intravenous (i.v.) injections of NKH477 (1-30 micrograms/kg) caused dose-related increases in left ventricular dP/dtmax (LVdP/dtmax), coronary and femoral artery blood flow (CBF, FBF), heart rate (HR), and myocardial oxygen consumption (MVO2) and a dose-related decrease in blood pressure (BP) in anesthetized dogs. The regression analysis between CBF and MVO2 showed that NKH477 did not influence substantially the balance of oxygen supply and demand. Infusions of NKH477 (0.15-0.6 microgram/kg/min i.v.) also increased LVdP/dtmax, cardiac output (CO), and HR and decreased BP, pulmonary arterial diastolic pressure, and total peripheral resistance (TPR) in a dose-dependent manner. In contrast to forskolin, NKH477 administered intraduodenally (0.05-0.2 mg/kg) and orally (0.15 and 0.3 mg/kg) clearly exhibited cardiovascular actions, as it did in i.v. administration, indicating that NKH477 is orally active. No arrhythmias were induced by NKH477 in any study. NKH477, like forskolin, showed adenylate cyclase stimulant activity in guinea pig ventricular membrane but did not inhibit Na+, K(+)-ATPase or phosphodiesterase (PDE) activity. Thus, NKH477 can be characterized as a potent, orally active, water-soluble forskolin derivative, which suggests that NKH477 is a useful inodilator for treatment of heart failure, especially in the severe stage with beta-adrenoceptor downregulation.
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PMID:Cardiovascular and adenylate cyclase stimulant properties of NKH477, a novel water-soluble forskolin derivative. 138 Jun 7

The pharmacokinetics of synthetic atrial natriuretic factor (ANF) and its effects on cyclic GMP, urinary sodium excretion, and hemodynamics were compared in 18 control subjects with normal hemodynamics and 12 patients with severe heart failure. Human 99-126 ANF was administered intravenously (0.2 micrograms/kg i.v. followed by 0.07 micrograms/kg/min for 30 min). As compared with controls, baseline plasma ANF concentration was higher in the heart failure group (329.2 +/- 166.1 vs. 33.6 +/- 17.3 pg/ml in controls, means +/- SD, p less than 0.01). Synthetic ANF increased plasma ANF concentration by similar amounts, but the elimination half-life (t 1/2) for synthetic ANF was longer in the heart failure group (6.5 +/- 2.6 vs. 3.8 +/- 0.8 min, p less than 0.05). Baseline plasma cyclic GMP concentration was higher in the heart failure group (13.8 +/- 6.8 vs. 4.2 +/- 2.2 pmol/ml, p less than 0.01) but ANF increased plasma cyclic GMP concentration to a lesser degree (14.4 +/- 7.6 pmol/ml, p less than 0.05 vs. 24.9 +/- 10.1 pmol/ml, p less than 0.001). Baseline urinary sodium excretion was less in the heart failure group (13.3 +/- 14.0 vs. 53.7 +/- 37.3 mumol/min, p less than 0.01) and ANF induced a smaller increase in urinary sodium excretion (22.1 +/- 32.3 mumol/min, p less than 0.05 vs. 305.7 +/- 242.9 mumol/min, p less than 0.001). Baseline plasma norepinephrine (NE), renin, and aldosterone were higher in the heart failure group. Synthetic ANF increased plasma NE only in the control group, had no effect on renin, and decreased aldosterone in both groups. Hemodynamic responses were similar in both groups except the decreased arterial blood pressure (BP) was accompanied by increased heart rate (HR) only in the controls. Therefore, in heart failure, the t 1/2 of ANF is prolonged and there appears to be a limit for further increase in cyclic GMP. These changes may explain in part the blunted renal response to ANF.
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PMID:Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure. 138 66

Treatment of male rabbits with adriamycin at a cardiotoxic dose (1 mg/kg intravenously, i.v., twice a week for 9 weeks) caused cardiovascular disturbances characteristic of chronic heart failure. The severity of symptoms varied, indicating differences in the individual sensitivity of the animals to adriamycin. Thus, cardiac output (CO) was decreased by greater than 40% in only 4 of the 7 animals in which it was measurable at 9 weeks. Elevated levels of atrial natriuretic factor (ANF) and plasma renin activity (PRA), as well as pulmonary congestion, hydrothorax, and ascites were also evident. The baroreflex response to sodium nitroprusside (NPS) was blunted. The response to the inotropic drug dobutamine was depressed by 50% as compared with the control animals. Right ventricular beta-adrenoceptor density was significantly reduced in these animals (22.9 +/- 3.1 as compared with 31.8 +/- 1.0 fmol/mg protein in control animals) owing to a selective downregulation of the beta 1-adrenoceptor population. The loss of beta-adrenoceptors was highly correlated with severity of heart failure symptoms: i.e., baroreflex dysfunction as indicated by the NPS slope (r = 0.91), decrease in CO during the previous weeks (r = 0.88), and plasma norepinephrine (NE) levels (r = 0.96). However, when all adriamycin-treated animals were compared collectively regardless of the severity of heart failure, with the controls, no difference in the beta-adrenoceptor density was detectable, a finding in agreement with previous observations in this model. Chronic treatment of rabbits with adriamycin thus causes low-output failure, reflecting some of the findings reported for the human disease; however, individual sensitivity to adriamycin varies considerably between rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic adriamycin treatment and its effect on the cardiac beta-adrenergic system in the rabbit. 138 76

Twenty-nine patients with severe heart failure (NYHA III) were randomly assigned to receive therapy with an angiotensin converting enzyme inhibitor (ACE inhibitor), either captopril or enalapril. The mean daily dosage of captopril was 56 +/- 5 mg and of enalapril 9.5 +/- 0.4 mg. After a mean of 8 +/- 1 days, the influence of both ACE inhibitors on hemodynamics and renal function was compared. The mean arterial pressure in the group treated with captopril (Group A) fell by 9 +/- 3 mmHg (p less than 0.01), and in the group treated with enalapril (Group B) it fell by 12 +/- 3 mmHg (p less than 0.001). The difference between the groups was not significant. Heart rate decreased in both groups; however, the change was significant (p less than 0.05) only in patients treated with enalapril (-11 +/- 3 bpm in Group B vs. -7 +/- 4 bpm in Group A). Stroke volume index increased by 6 +/- 3 ml/m2 in Group A (p less than 0.05) vs. 10 +/- 2 ml/m2 in Group B (p less than 0.01). The increase in stroke volume index was not significantly different between the two groups. Mean decreases in pulmonary artery and right atrial pressure were also comparable in both groups. Thus, hemodynamic improvements were similar during therapy with either captopril or enalapril. Serum sodium and potassium before therapy were 137 +/- 1 mmol/l and 4.1 +/- 0.1 mmol/l, respectively, in group A and 139 +/- 1 mmol/l and 4.0 +/- 0.1 mmol/l, respectively, in group B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of captopril with enalapril in the treatment of heart failure: influence on hemodynamics and measures of renal function. 139 Mar 31

Fifty patients of grade III & IV malnutrition with diarrhoeal dehydration were rehydrated using the WHO recommended ORS. Serum sodium and potassium levels were estimated at admission and 24 hours later. Forty seven patients were successfully rehydrated orally. In 7 patients the level of dehydration at initial assessment was overestimated. Periorbital edema developed in 25.5% of the patients rehydrated. No patient had cardiac failure or convulsions during therapy. Though persistent hyponatremia and hypokalemia were found in 10.6% and 19.15% cases respectively after rehydration, the incidence decreased as compared to the pre-hydration levels and was comparable to that found in malnourished children without diarrhea who served as controls in the present study. Oral rehydration was discontinued in three patients due to development of excessive vomiting in one case and paralytic ileus in two. Thus WHO ORS can be used safely in children with severe malnutrition but constant monitoring is required.
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PMID:Oral rehydration therapy in severely malnourished children with diarrheal dehydration. 139 64

The intrarenal renin-angiotensin system (RAS) may contribute to the pathophysiology of heart failure by the generation of angiotensin II at local sites within the kidneys. Angiotensin II may directly influence renal hemodynamics, glomerular contractility, and tubular sodium reabsorption, thereby promoting sodium and fluid retention in this syndrome. In the present study, we examined components of the circulating RAS as well as the intrarenal expressions of renin and angiotensinogen mRNA in rats with stable compensated heart failure (HF) 12 wk after experimental myocardial infarction. Renal angiotensinogen mRNA level in vehicle-treated HF rats increased 47%, as compared with sham control rats (P = 0.001). The increase in angiotensinogen mRNA levels was more pronounced in animals with medium (46%, P < 0.05) and large (66%, P < 0.05) infarcts than in those with small infarcts (31%, P = NS). There were no differences in liver angiotensinogen mRNA, circulating angiotensinogen, angiotensin II, plasma renin concentration (PRC), kidney renin content (KRC), and renal renin mRNA level between sham and HFv. In addition, in a separate group of rats with heart failure, we demonstrated that renal angiotensin II concentration increased twofold (P < 0.05) as compared with that of age-matched sham operated controls. A parallel group of heart failure rats (HFe, n = 11) was treated with enalapril (25 mg/kg per d) in drinking water for 6 wk before these measurements. Blood pressure decreased significantly during treatment (91 vs. 103 mm Hg, P < 0.05). Enalapril treatment in HF rats increased renin mRNA level (2.5-fold, P < 0.005), KRC (5.6-fold, P = 0.005), and PRC (15.5-fold, P < 0.005). The increase in renal angiotensinogen mRNA level observed in HFv rats was markedly attenuated in enalapril treated HF rats (P < 0.001), suggesting a positive feedback of angiotensin II on renal angiotensinogen synthesis. These findings demonstrate an activation of intrarenal RAS, but no changes in the circulating counterpart in this model of experimental heart failure, and they support the concept that the intrinsic renal RAS may contribute to the pathophysiology in this syndrome.
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PMID:Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure. 140 Oct 84

Isolated systolic hypertension (ISH) is generally defined as a systolic pressure of 160 mmHg or more, with a diastolic pressure cut-off point below 95 mmHg in some studies and 90 mmHg in others. Its prevalence and incidence vary from 3 to 30% depending on the definition applied, methodology of measurement, as well as the population and the age and sex of the patients. Mechanisms that could lead to the development of isolated systolic hypertension are discussed, especially the role of atherosclerosis and sodium intake. Comparing results from different countries, the Intersalt study showed that the age related rise in systolic pressure was positively related to the mean sodium excretion in that country. A post-hoc analysis of data from 4 Belgian groups could not show such a correlation within our country. The risks of systolic hypertension on mortality and morbidity in the elderly are considered. The need for further studies to quantify the risk and to establish the effect of treatment is emphasized. Three such studies in patients above the age of 60 years with ISH were started. The studies are double-blind, placebo-controlled trials and the main purpose is to examine the influence of treatment on morbidity, mortality, and general well-being. In the American SHEP study the patients of the actively treated group received a diuretic and possibly a beta-blocker or reserpine. The results indicate a significant reduction in non fatal stroke, heart failure and myocardial infarction without a significant reduction in fatal stroke, fatal myocardial infarction, cardiovascular or all cause mortality. Studies in other continents are still in progress, such as the Syst-Chin in China and the Syst-Eur trial in Europe. They may indicate whether the results obtained in the U.S.A. can be extrapolated to other continents and whether the use of other drugs without metabolic disturbances, such as calcium entry blockers and angiotensin converting enzyme inhibitors, produce a similar reduction in events. Additional studies are needed to establish the effect of reducing salt intake in younger age groups on the prevalence of ISH and of the related morbidity and mortality.
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PMID:[Isolated systolic hypertension in persons older than 60]. 141 81

In two groups of anesthetized (sodium pentobarbital), mature Sprague-Dawley rats, 1) aged 2 years and weighing 300-400 grams, 2) aged 6 months weighing 200-300 grams, baroreflex-induced circulatory responses to pressor (graded doses phenylephrine) and depressor (graded doses nitroglycerine) agents were compared to those occurring during progressive hemorrhage in the same animals. Graded withdrawals of blood from the femoral artery elicited progressive hypotension accompanied by bradycardia rather than expected tachycardia. Graded doses of phenylephrine (2.5 ug to 40 ug bolus, via femoral vein) regularly induced elevations in arterial blood pressure with associated reflex bradycardia. Similarly graded doses of nitroglycerine induced a marked decline in arterial blood pressure, without expected tachycardia. As hypotension became more severe (during hemorrhage), atrioventricular conduction slowed and A-V block developed, resulting in statistically greater slowing in ventricular than in atrial excitation and contractile cycles. Heart failure during hemorrhage in the rat is characterized sequentially by severe bradycardia, depressed atrial contractile force, impaired conduction and A-V block, terminating in ventricular, atrial, and finally, in pacemaker failure. Baroreceptor reflexes were blunted or even absent in both young and old animals during induced hypotension.
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PMID:Baroreflex responses to the stress of severe hemorrhage in the rat. 141 67

Patients with congestive heart failure (CHF) have impaired peripheral vasodilation during exercise. Hyperosmolality is one local stimulus that produces vasodilation during exercise in normal subjects. This study addressed the hypothesis that vasodilation to hyperosmolal stimuli is impaired in patients with CHF. Forearm blood flow responses to intrabrachial artery infusions of isoosmolar (280 mosm/kg) and hyperosmolal (480 and 660 mosm/kg) solutions of saline and glucose were compared in 9 patients with CHF and 13 normal subjects. Forearm blood flow was measured by strain gauge plethysmography. In the normal subjects, hyperosmolal infusions of 480 and 660 mosm/kg increased forearm blood flow by 3.12 +/- 0.40 and 6.80 +/- 0.67 ml/min/100 ml forearm volume, respectively (both p < 0.001 compared with isoosmolal infusions). In contrast, in the patients with CHF, these infusions increased forearm blood flow by 2.19 +/- 0.44 and 4.06 +/- 0.92 ml/min/100 ml forearm volume (p < 0.05 normal vs CHF). The impaired forearm blood flow responses in heart failure occurred despite significantly greater (p < 0.05, normal vs CHF) increases in venous osmolality (17.3 +/- 6.5 vs 9.6 +/- 1.3 mosm/kg for the 660 mosm/kg infusion). There were no differences between groups in forearm venous hematocrit, calcium, and sodium or potassium changes during hyperosmolal infusions. It is concluded that peripheral vasodilation to hyperosmolal stimuli is impaired in patients with CHF.
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PMID:Impaired forearm vasodilation to hyperosmolal stimuli in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy. 144 84

Intravenous drip of sodium pentobarbital 6 mg/kg per min induced obvious heart failure of anesthetic dogs (n = 11) followed by an infusion of 0.25 mg/kg per min to maintain the heart failure state. The Chinese-made vesnarinone 3 mg/kg was injected, followed by an infusion of 0.1 mg/kg per min, or the solvent in the same volume, for 30 min. Vesnarinone increased significantly and instantly the cardiac output and left ventricular maximum + dp/dt, which almost recovered to normal at the end of the infusion and also significantly increased 30 min after administration. The positive inotropic effect of vesnarinone was not accompanied by an increase in the heart rate and the blood pressure. The results of our experiment reveal that the Chinese-made vesnarinone has a potent and relatively selective positive action on heart failure of dogs.
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PMID:[Effect of Chinese-made vesnarinone on experimental heart failure of dog]. 145 53


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