Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two peptides consisting of amino acids 1-30 and 31-67 of the N-terminus of the prohormone of atrial natriuretic factor (pro-ANF) that have vasodilatory and natriuretic properties were investigated to determine if they circulate in humans. Specific and sensitive radioimmunoassays were developed to amino acids 1-30, 31-67, and 99-126 of pro-ANF. Evaluation of human plasma that had been subjected to reverse-phase high-pressure liquid chromatography suggested that pro-ANFs 1-30 and 31-67 as well as ANF were distinct peaks in human plasma corresponding exactly to pure synthetic peaks of these peptides on high-pressure liquid chromatography. Molecular weight determination of the endogenous immunoreactive peptides measured in plasma by G-50 Sephadex gel permeation chromatography revealed that the pro-ANF 1-30 radioimmunoassay recognized a peptide of 10,000 MW, which is consistent with it measuring the whole N-terminus of pro-ANF (amino acids 1-98) but without ANF (C-terminus) attached to it. The pro-ANF 31-67 radioimmunoassay recognized mainly (more than 95%) a peptide of 3,900-4,000 MW, which corresponds closely with its actual molecular weight of 3,878. Our ANF radioimmunoassay recognizes a peptide in plasma of 3,000 MW with the known molecular weight of ANF being 3,081. The mean circulating concentrations of immunoreactive pro-ANF 1-98, pro-ANF 31-67, and ANF in 54 control subjects were 531 +/- 25, 371 +/- 18, and 22 +/- 1 fmol/ml (+/- SEM), respectively. Thirty patients with varying severity of congestive heart failure were also studied. The N-terminus, C-terminus, and pro-ANF 31-67 increased: twofold for New York Heart Association functional Class II, threefold to ninefold for Class III, and 10- to 20-fold for Class IV patients with congestive heart failure. Thus, the N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of pro-ANF as well as ANF circulate normally and increased proportionately to the increasing severity of congestive heart failure. However, because the pro-ANF 31-67 radioimmunoassay was the only assay that discriminated between patients with Class I congestive heart failure and control subjects, this assay may be the most useful to accurately classify the severity of congestive heart failure.
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PMID:The N-terminus and a 4,000-MW peptide from the midportion of the N-terminus of the atrial natriuretic factor prohormone each circulate in humans and increase in congestive heart failure. 252 42

The feedback control of neuroendocrine activity by cardiopulmonary blood volume is disturbed in congestive heart failure. By analyzing plasma catecholamine kinetics, we tested in 11 chronically instrumented conscious dogs whether attenuations in the sympathoadrenal inhibition induced by atrial natriuretic peptide (ANP) contributed to this disturbance. Low-output failure was brought about by continuous ventricular pacing at 265 beats/min for 2 weeks. This resulted in a decline in aortic flow by 37 +/- 5% (SEM), an increase in peripheral vascular resistance by 48 +/- 4%, a 13 +/- 3-fold elevation in plasma ANP, a 9 +/- 3-fold elevation in plasma renin activity, and an augmentation of the norepinephrine-release rate into plasma by 132 +/- 17%. During ANP infusion, the epinephrine-release rate declined by 26 +/- 5% per 10-fold elevation in plasma ANP before pacing and by 31 +/- 7% (not significantly different) after 2 weeks of pacing. Before pacing, ANP attenuated plasma renin activity and caused hypotension without a rise in norepinephrine-release rate. After 2 weeks of pacing, ANP lowered norepinephrine release (by 16 +/- 6%) without affecting blood pressure or plasma renin activity, and vascular nonresponsiveness to ANP was verified under autonomic blockade. These data indicate that, during the development of heart failure, an inhibitory action of ANP on norepinephrine release is unmasked by an ANP-specific vascular desensitization, whereas the inhibition of epinephrine release is observed throughout. It is concluded that ANP-induced sympathoadrenal inhibition is not attenuated and, therefore, does not contribute to the disturbed regulation observed early in the development of failure.
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PMID:Sympathoadrenal inhibition by atrial natriuretic peptide is not attenuated during development of congestive heart failure in dogs. 253 76

The effects of low bolus dose (70 +/- 6 micrograms [mean +/- SEM]) atrial natriuretic factor (ANF) administration was assessed in 16 patients with chronic congestive heart failure. Measurements were made for at least 60 minutes before and after the dose of ANF. There was a significant increase in urine flow rate (0.81 +/- 0.06 to 1.81 +/- 0.23 ml/min, p less than 0.01), sodium excretion rate (56 +/- 14 to 80 +/- 23 microEq/min, p less than 0.01), fractional excretion of sodium (1.23 +/- 0.49 to 1.63 +/- 0.60 percent, p less than 0.01) and potassium excretion rate (35 +/- 7 to 42 +/- 6 microEq/min, p less than 0.02). However, no significant alterations in renal plasma flow or glomerular filtration rate were observed. Furthermore, there was no significant correlation between the change in urine flow rate or sodium excretion rate and the change in renal plasma flow or glomerular filtration rate, respectively. In addition, there was no significant effect on cardiac index, mean aortic or left ventricular filling pressures, or systemic vascular resistance. There also was no discernible relationship between the response to ANF and the baseline concentrations of plasma ANF, aldosterone, or plasma renin activity. Thus, in patients with congestive heart failure, low dose ANF boluses may produce an increase in urine flow rate and sodium excretion rate that is independent of renal plasma flow or glomerular filtration rate. This suggests a meaningful direct renal tubular effect of exogenous ANF in this setting.
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PMID:Cardiorenal effects of atrial natriuretic factor administration in congestive heart failure: natriuresis and diuresis without hemodynamic alterations. 256 86

The effects of oral milrinone treatment in cardiomyopathic hamsters with severe congestive heart failure (CHF) were evaluated. Strict criteria based on increase in body weight were established to define day no 1 of treatment. Survival rate of non-treated hamsters (group 1) ranged between 9 and 16 d, mean 12.9 (SEM 0.8) d, after entering the study. Hamsters treated with milrinone in drinking water (group 2a: 0.3 mg.ml-1, or group 2b: 0.6 mg.ml-1) survived between 6 and 36 d, mean 15.0(2.1) d, NS, for group 2a, and between 6 and 47 d, mean 19.6(4.0) d, NS, for group 2b. There was a significant difference between the number of hamsters that survived longer than 16 d between untreated hamsters (group 1, n = 0/12) and hamsters treated with milrinone (groups 2a, b, n = 7/24). There was no significant correlation between survival duration and milrinone daily dose nor between survival and milrinone plasma concentration at death. Milrinone treatment also significantly decreased pulmonary congestion as measured by the number of pigment containing macrophages per alveolus. No other pathological findings were modified by milrinone. It was concluded that, in addition to exerting a beneficial effect on pulmonary congestion, milrinone improved survival in some CHF hamsters. However, more studies are needed to evaluate the possibility of an arrythmogenic potential that might explain why some treated hamsters died earlier than non-treated hamsters.
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PMID:Effects of milrinone treatment in cardiomyopathic hamsters (CHF 147) with severe congestive heart failure. 259 16

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients. Mean heart period variability (+/- SEM) was significantly lower (p less than 0.05) in the heart failure groups (22 +/- 3 ms for medicated and 17 +/- 3 ms for nonmedicated) than in the transplant patients (41 +/- 5 ms) or control subjects (58 +/- 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p less than 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation (R2 = 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 +/- 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p less than 0.001). These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.
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PMID:Subnormal heart period variability in heart failure: effect of cardiac transplantation. 266 25

The results of surgical treatment of post-infarction left ventricular aneurysms in 49 patients with congestive heart failure preoperatively were analyzed. Average patient age was 55 years. Preoperative total ejection fraction averaged 30.5 +/- 1.5% (mean +/- SEM), contractile segment ejection fraction was 42.5 +/- 1.1% and end-diastolic volume of aneurysm was 81.4 +/- 10.4 ml. Seventy eight percent of patients underwent coronary artery bypass grafting concomitantly with aneurysmectomy. Mean follow-up after operation was 41.5 +/- 3.5 months. Hospital mortality was 8.2%, the 5 year survival rate was 70 +/- 7% and the 5 year complication free rate was 52 +/- 8%. Mean functional class of dyspnea improved significantly from 2.9 +/- 0.1 preoperatively to 1.6 +/- 0.1 at late follow-up (p less than 0.001). Likewise, isotopic ejection fraction at rest increased from 13.7 +/- 1.3% preoperatively to 30.9 +/- 3.0% postoperatively (p less than 0.0001). Logistic regression analysis isolated two factors which influenced postoperative survival independently: contractile segment ejection fraction (p = 0.045) and myocardial score of left anterior descending coronary artery (p = 0.035). Combining these two risk factors, it was possible to identify a low risk group of patients with a 5 year survival probability of 93 +/- 6%, contrasting with a high risk group of patients having a 5 year survival of 57 +/- 9% (p less than 0.02). Thus, resection of left ventricular aneurysms complicated by congestive heart failure provides improvement in left ventricular function and clinical status.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Left ventricular aneurysm complicated by congestive heart failure: an analysis of long-term results and risk factors of surgical treatment. 278 22

1. Binding sites for atrial natriuretic peptide (ANP) with a specificity similar to that of vascular ANP receptors have been demonstrated previously in human platelets. The density of these binding sites for ANP on platelets is decreased after increased dietary sodium intake, when plasma ANP levels increase. ANP-binding sites were investigated in patients with severe congestive heart failure (CHF), a condition in which there is an increase in the concentration of ANP in plasma. 2. In 24 patients with a clinical diagnosis of functional class III-IV CHF, plasma ANP (90.3 +/- 13.4 fmol/ml, mean +/- SEM) was significantly higher (P less than 0.001) than in 16 age-matched patients without cardiac disease (15.4 +/- 2.0 fmol/ml). The density of ANP-binding sites on platelets was significantly lower (P less than 0.01) in the 24 CHF patients (6.3 +/- 0.8 fmol/10(9) cells) than in the non-cardiac patients (11.8 +/- 1.4 fmol/10(9) cells). There was no significant difference in affinity of the ANP-binding sites between both groups. There was a significant non-linear inverse correlation of the density of ANP-binding sites on platelets with plasma ANP concentration. These results could not be explained by prior receptor occupancy secondary to the elevated concentration of circulating ANP. 3. In conclusion, ANP-binding sites on platelets are decreased in patients with severe CHF and with significantly elevated concentration of ANP in plasma.
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PMID:Decreased density of binding sites for atrial natriuretic peptide on platelets of patients with severe congestive heart failure. 282 42

The number of putative calcium channels in cardiac muscle from young adult hamsters (60 days old) was compared in normal (F1B) hamsters and two different mutant strains (CHF 146 and Bio 14.6) which express cardiomyopathy and muscular dystrophy. Equilibrium binding assays of high affinity sites for [3H]-nitrendipine in ventricular homogenate preparations showed that the maximum number of [3H]-nitrendipine binding sites (Bmax), which corresponds to the number of putative calcium channels, was not significantly different in normal and cardiomyopathic hearts: 79(SEM 9), 64(14) and 69(10) fmol.mg-1 protein in 4-6 hearts from F1B, Bio 14.6 and CHF 146 hamster strains, respectively. Similar results were obtained with binding data after partial purification of the preparation. These data are in agreement with earlier studies comparing two normal strains (CHF 148 and random bred Syrian hamsters) with cardiomyopathic (CHF 146) hamsters, and conflict with other studies comparing normal and cardiomyopathic hamsters. Comparisons with the conflicting data suggest (a) that change in the number of high affinity [3H]-nitrendipine binding sites is not responsible for calcium overload and cell necrosis in cardiomyopathy, and (b) that increased numbers of low affinity [3H]-nitrendipine binding sites may emerge in cardiomyopathic hearts.
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PMID:[3H]-nitrendipine binding sites in normal and cardiomyopathic hamsters: absence of a selective increase in putative calcium channels in cardiomyopathic hearts. 285 22

Efficacy and safety of esmolol in the treatment of supraventricular tachyarrhythmias (SVT) was evaluated in this open-label, baseline-controlled, multicenter study. One hundred sixty patients with SVT received an intravenous infusion of esmolol in doses ranging from 25 to 300 micrograms/kg/min for up to 24 hours. All of the 160 patients were evaluated for safety, and 147 of them were eligible for evaluation of therapeutic response. Therapeutic response was defined as greater than or equal to 15% reduction in the average baseline heart rate of conversion to normal sinus rhythm. Seventy-nine percent (116 of 147) of the patients exhibited a therapeutic response. The cumulative percentage response increased significantly with increasing esmolol doses up to 200 micrograms/kg/min. The mean (+/- SEM) dose of esmolol producing a therapeutic response was 97.2 +/- 5.5 micrograms/kg/min. Among all patients (n = 160), 39% exhibited hypotension. In 58% of these patients, hypotension resolved with or without adjustment of the esmolol dose while the infusion continued; among almost all of the remaining patients, hypotension resolved within 30 minutes after esmolol was discontinued. Most patients at risk for adverse effects during beta blockade (i.e., those with diabetes mellitus, congestive heart failure, asthma, etc.) tolerated esmolol therapy, and there were no clinically important trends among the reported changes in laboratory variables. The results of the study indicate that esmolol is effective and well tolerated for the treatment of SVT.
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PMID:Intravenous esmolol for the treatment of supraventricular tachyarrhythmia: results of a multicenter, baseline-controlled safety and efficacy study in 160 patients. The Esmolol Research Group. 287 41

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.
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PMID:A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. 296 Aug 97


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