ABSTRACT
The aim of this study was to characterize cardiac features of patients with neurofibromatosis 1 (NF1) and large deletions of the NF1 gene region. The study participants were 16 patients with large NF1 deletions and 16 age- and sex-matched NF1 patients without such deletions. All the patients were comprehensively characterized clinically and by echocardiography. Six of 16 NF1 deletion patients but none of 16 non-deletion NF1 patients have major cardiac abnormalities (p = 0.041). Congenital heart defects (CHDs) include mitral insufficiency in two patients and ventricular septal defect, aortic stenosis, and aortic insufficiency in one patient each. Three deletion patients have hypertrophic cardiomyopathy. Two patients have intracardiac tumors. NF1 patients without large deletions have increased left ventricular (LV) diastolic posterior wall thickness (p < 0.001) and increased intraventricular diastolic septal thickness (p = 0.001) compared with a healthy reference population without NF1, suggestive of eccentric LV hypertrophy. CHDs and other cardiovascular anomalies are more frequent among patients with large NF1 deletion and may cause serious clinical complications. Eccentric LV hypertrophy may occur in NF1 patients without whole gene deletions, but the clinical significance of this finding is uncertain. All patients with clinical suspicion for NF1 should be referred to a cardiologist for evaluation and surveillance.
Subject(s)
Gene Deletion , Genes, Neurofibromatosis 1 , Heart Defects, Congenital/etiology , Neurofibromatosis 1/complications , Neurofibromatosis 1/genetics , Adolescent , Adult , Child , Echocardiography , Female , Heart Defects, Congenital/diagnosis , Humans , Male , Young AdultABSTRACT
BACKGROUND: Diabetic patients with acute myocardial infarction (AMI) may have diminished pain or a higher frequency of asymptomatic infarctions. This appears to be a common clinical perception. METHODS: Data from two registries of AMI patients presenting in hospital (MITRA PLUS with 18786 patients; North German Registry, NGR, 1042 patients with detailed symptom interviews) were analyzed concerning symptoms of acute myocardial infarction in patients with diabetes mellitus (DM) and without diabetes (non-DM). RESULTS: DM patients were significantly older and more often female than non-DM. There were no differences in the frequency of pre-infarction angina between DM and non-DM (Mitra Plus). In NGR, severe angina during AMI occurred in 49.8% of DM and 46.3% of non-DM (n. s.). No chest pain was reported in 16.9% of DM and 15.0% of non-DM (n. s.). Extra-thoracic pain, dizziness, nausea, sweating, palpitations, radiation of angina and localization of radiating pain was not different between DM and non-DM patients. Severe dyspnea occurred in 29.5% of DM and 19.5% of non-DM patients (p = 0.003). CONCLUSIONS: Apart from a higher frequency of severe dyspnea in diabetics, there appears to be no difference in the clinical symptoms of AMI patients with and without diabetes mellitus. AMI with little or no angina was also frequently found in non-diabetics. In the hospital, diabetics with suspected AMI do not appear to need a special judgement of symptoms. This could accelerate access of diabetics to standard therapeutic procedures.
Subject(s)
Angina Pectoris/diagnosis , Diabetic Angiopathies/diagnosis , Myocardial Infarction/diagnosis , Pain Measurement , Aged , Female , Germany , Humans , Male , Middle Aged , Pain Measurement/statistics & numerical data , Prospective Studies , Psychometrics/statistics & numerical data , RegistriesABSTRACT
While a circadian rhythm in the onset of acute myocardial infarction (AMI) is well established, little is known about the variability of prehospital delay and decision processes. Seven hundred and thirty-nine consecutive AMI patients (median age 65.3 years; 30.2% women) with a median decision time of 60 min and a total prehospital delay of 180 min were studied. In 30.9% of patients onset of AMI symptoms was at night (10.00 p.m.-06.00 a.m.). At night patient decision time was significantly longer than during daytime (120 vs 45 min, difference 75 min; p < 0.001), total prehospital delay was prolonged accordingly (240 vs 170 min, difference 70 min; p < 0.001). The relative risk (RR; 95% confidence interval, CI) for a late decision (> 1 h) to seek medical care at night was significantly increased in females (RR 1.96; CI 1.07-3.61, p = 0.028), non-smokers (RR 2.49; CI 1.42-4.39, p = 0.001) and patients with radiation of anginal pain (RR 2.34; CI 1.32-4.15; p = 0.003). Of all patients with a late decision to seek medical care at night, 95.6% belonged to one of these groups. These variables were not significant for early or late decisions during daytime. Decision processes of AMI patients may be different during daytime and at night. In conclusion, in AMI patients, decision time to seek medical help is prolonged at night. Simple clinical variables (female sex, non-smokers, radiation of anginal pain) identify patients at high risk for a late decision at night. This information should be included into public and individualized education campaigns.
Subject(s)
Circadian Rhythm , Emergency Medical Services/statistics & numerical data , Myocardial Infarction/epidemiology , Aged , Analysis of Variance , Diagnosis, Differential , Female , Germany , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/therapy , Sex Factors , Task Performance and Analysis , Time FactorsABSTRACT
BACKGROUND: Early reperfusion treatment in acute myocardial infarction (AMI) preserves ventricular function and saves lives. After onset of AMI symptoms, patients often delay for hours until the decision to seek medical help. AIM: Of the MI-heart (Myocardial Infarction--HElp seeking And ReacTions) study was to identify factors determining patient decision delay. METHODS: 739 consecutive patients with confirmed AMI (median age 65.3 years, 30.2% females) were studied after transfer from the intensive care unit. A standardized interview covered AMI symptoms, attitudes toward symptoms, coping strategies, and clinical and sociodemographic variables. RESULTS: Of patients, 93.3% knew an AMI could be deadly. 43.9% of the patients who suspected an AMI, and knew it could be deadly, decided late (> 1 hour) to seek medical help. In univariate analyses, attitudes toward symptoms and coping strategies had the highest impact on a late decision. Stepwise logistic regression identified the following independent contributors to a late decision to seek medical help (relative risk, 95% confidence interval): wanting to wait and see (3.53; 2.32-5.39), not taking symptoms seriously (2.47; 1.64-3.72), not wanting to bother anybody (2.14; 1.29-3.57), symptoms improving at first (2.33; 1.52-3.56), asking others for advice (0.46; 0.30-0.71), taking pain medication (2.01; 1.01-4.03), age > 65 years (1.69; 1.17-2.44), very strong intensity of angina (0.60; 0.42-0.87). CONCLUSIONS: Emotional attitudes to AMI symptoms and inadequate coping strategies are the major determinants of patient decision delay. They should be considered as a key factor in patient and public education. Modification of these emotional factors might best be achieved by an individualized approach.
Subject(s)
Attitude to Health , Myocardial Infarction/psychology , Myocardial Infarction/therapy , Patient Acceptance of Health Care , Adaptation, Psychological , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Decision Making , Emotions , Female , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Regression Analysis , Risk , Surveys and Questionnaires , Time FactorsABSTRACT
Hyperthyroidism is usually associated with tachycardia, hypothyroidism with bradycardia. After observing clinically inapparent hyperthyroidism in patients requiring pacemaker implantation, we studied the occurrence of hyperthyroidism in patients receiving a first permanent pacemaker. Of 237 patients (age 71.4 +/- 8.9 years; 54.9% females), 16 (6.75%) had subclinical (TSH < 0.1 mE/l and fT3 < or = 9.0 pmol/l) and 4 (1.69%) overt hyperthyroidism (TSH < 0.1 mE/l and fT3 > 9.0 pmol/l). Prevalence of hyperthyroidism was similar to that in the general population. Compared to euthyroid patients, in the patients with subclinical or overt hyperthyroidism there were significantly more females (n = 16) than males (n = 4; p = 0.018). Hyperthyroid patients were older (75.0 +/- 9.6 vs. 70.7 +/- 8.9 years; p = 0.015). At follow-up, all patients had a relevant proportion of pacemacer-induced beats. Clinical signs of hyperthyroidism or cardiac symptoms were not different between groups. In conclusion, bradycardia does not exclude the presence of hyperthyroidism. Temporary pacing is recommended in thyreotoxicosis with bradycardia. In contrast, primary implantation of a permanent pacemaker appears to be adequate in patients with bradycardia, cardiovascular disease and an additional diagnosis of hyperthyroidism.
Subject(s)
Bradycardia/therapy , Hyperthyroidism/epidemiology , Pacemaker, Artificial , Age Factors , Aged , Bradycardia/diagnosis , Cross-Sectional Studies , Female , Humans , Hyperthyroidism/diagnosis , Male , Middle Aged , Sex FactorsABSTRACT
In the years after 1989 major political and socioeconomic changes have taken place in East Germany. In parallel, emergency medical services (EMS) were restructured according to western standards. In Stralsund the EMS was restructured from a single to a two tier system with implementation of a second ambulance base in 1990. The number of household telephone extensions more than doubled. To analyze the effects of these changes, patients receiving advanced life support (ALS) for out-of-hospital cardiac arrest of cardiac origin (OHCA) between 1984 and 1988, and from 1991 to 1997 were studied. Adjusted per 100,000 inhabitants, the number of OHCA patients receiving ALS increased from 11 per year before 1989 to 52 per year after 1990 (P < 0.01). Survival without relevant neurologic defects was achieved in 3.7% (2/53) of patients before 1989 and in 8.1% (22/273) after 1990. Response time of the ALS unit shortened from 11.0 +/- 1.4 to 9.0 +/- 0.4 min (n.s.), while response time of any EMS shortened from 11.0 +/- 1.4 to 6.1 +/- 0.3 min (P < 0.005). Adjusted for observation period and population served, there was a 10-fold increase in the number of resuscitations attempted at home and an 8-fold increase in the absolute number of OHCA survivors without relevant neurological defects. In parallel to socioeconomic changes, the restructuring of the EMS in Stralsund and the rapid expansion of the telephone network led to a significant increase in the number of patients successfully resuscitated from OHCA. If the present results can be transferred to other former socialist countries of East and Middle Europe, they may have important implications for the EMS in these regions.
Subject(s)
Heart Arrest/therapy , Resuscitation/statistics & numerical data , Emergency Medical Services/statistics & numerical data , Germany/epidemiology , Heart Arrest/mortality , Humans , Middle Aged , Resuscitation/methods , Socioeconomic Factors , Urban Health Services/statistics & numerical dataABSTRACT
Since angiotensin II is an established target of pharmacological interventions, there is an increasing interest in the biological effects and metabolism of other vasoactive peptides like atrial natriuretic factor (ANF) and endothelin (ET). Exogenous administration of the vasodilatory and natriuretic ANF and of its analogues improved haemodynamics and renal function in cardiovascular disease, including congestive heart failure (CHF). Effects of natriuretic peptides appeared to be attenuated during prolonged infusion and in more severe disease. Promising results were obtained in animal experiments and initial patient studies concerning haemodynamics and kidney function with inhibition of ANF metabolism by inhibitors of the neutral endopeptidase 24.11 (NEP). With further clinical studies, moderately relevant effects of acute intravenous or oral NEP inhibition were observed, but these effects were blunted with prolonged drug administration. There is increasing evidence that NEP inhibitors such as candoxatril, expected to exhibit vasodilatory activity at least at certain doses and in certain clinical settings, even induce vasoconstriction. As well as natriuretic peptides, NEP also metabolises the vasoactive peptides ET, angiotensin II and bradykinin. It now appears to be evident, especially from human experiments on forearm blood flow after intra-arterial infusion of agents, that NEP inhibitor--induced vasoconstriction is mediated by increased ET-1 rather than by angiotensin II. The hypothesis that concurrent ACE inhibition would unmask the benefits of NEP inhibitors was not supported by a recent 10-week study in CHF; with ecadotril given to ACE inhibitor-pretreated patients, there were no clear hints towards improvement of symptoms but troublesome aspects on mortality. Future clinical studies on dual inhibitors of NEP and ACE will have to reveal the place of NEP inhibition in cardiovascular disease in the presence of established therapeutic standards. Remarkable haemodynamic and cardioprotective effects have been obtained with antagonists of the ET receptor. Specific inhibitors of the endothelin converting enzyme (ECE) have only recently been introduced, inhibiting ET generation from its precursor, big ET. If the results previously obtained with ET receptor antagonists can be reproduced with ECE inhibitors, and transferred to clinical medicine, endopeptidase inhibition might open new horizons in cardiovascular treatment strategies.
Subject(s)
Cardiovascular Diseases/drug therapy , Drugs, Investigational/therapeutic use , Endopeptidases/metabolism , Neurotransmitter Agents/physiology , Protease Inhibitors/therapeutic use , Animals , Atrial Natriuretic Factor/physiology , Cardiovascular Diseases/physiopathology , Endothelins/physiology , HumansABSTRACT
Patients with paroxysmal supraventricular tachycardia (SVT) may have a polyuria after termination of tachycardia. There is increasing evidence that the renal peptide urodilatin (ANP (95-126))--and not plasma ANP (ANP (99-126))--is the member of the natriuretic peptide family mediating natriuresis and diuresis in man. In patients with SVT we, therefore, analyzed the relationship between diuresis, natriuresis, plasma ANP, urinary urodilatin excretion and renal excretion of cyclic GMP, the second messenger in the ANP system. During and after clinical presentation with spontaneously occurring SVT, two patients with AV-nodal and one patient with atrioventricular reentry tachycardia (heart rate 160 to 200 bpm) were studied. Urinary urodilatin excretion was correlated to diuresis (r = 0.73) and natriuresis (r = 0.93); similarly urinary cyclic GMP excretion was related to diuresis (r = 0.80) and natriuresis (r = 0.87; p < 0.001, respectively). In contrast, there was no significant correlation between plasma ANP concentrations and diuresis (r = 0.28, n.s.) or natriuresis (r = 0.11, n.s.). As an explorative analysis, stepwise multiple linear regression identified urinary urodilatin as the most important contributor to diuresis and natriuresis after SVT. These data on polyuria after spontaneous SVT further support the view that in man urodilatin is the member of the natriuretic peptide family participating in kidney physiology.
Subject(s)
Atrial Natriuretic Factor/urine , Diuresis/physiology , Natriuresis/physiology , Peptide Fragments/urine , Tachycardia, Paroxysmal/urine , Tachycardia, Supraventricular/urine , Adult , Atrial Natriuretic Factor/blood , Cyclic GMP/urine , Female , Glomerular Filtration Rate/physiology , Humans , Male , Middle Aged , Polyuria/urine , Regression AnalysisABSTRACT
Accumulating evidence suggests that urodilatin, a kidney-derived member of the natriuretic peptide family, contributes as a major mediator of sodium excretion to body fluid regulation in healthy men. In contrast to other members of the natriuretic peptide family, pathophysiological data for the renal natriuretic peptide have still been missing. The present study compares renal synthesis of urodilatin in patients with congestive heart failure (CHF) and healthy volunteers. Because urodilatin excretion, considerably increases with increasing nutritive sodium intake (p<0.004), the CHF patients (15 NYHA I/II, 8 NYHA III/IV) were kept on a 165 mmol/day sodium diet and 6 healthy volunteers on a identical nutritive sodium intake level were selected as proper controls. Although urodilatin excretion significantly increased (p<0.027) with increasing severity of CHF and was therefore significantly higher in mild CHF (40.7 +/- 2.5 fmol/min) and severe CHF (54.7 +/- 6.6 fmol/min) than in healthy controls (3.2 +/- 4.2 fmol/min), both groups of CHF patients retained sodium and had significantly lower sodium excretion rates (NYHA I/II 79.0 +/- 6.9 micromol/min, NYHA III/IV 97.9 +/- 12.7 micromol/min) than the healthy controls (139 +/- 3.4 micromol/min). Our data suggest that renal urodilatin synthesis, may not be involved in the etiology of sodium retention in CHF, but may rather be stimulated to counteract antinatriuresis during CHF.
Subject(s)
Atrial Natriuretic Factor/urine , Diuretics/urine , Heart Failure/urine , Peptide Fragments/urine , Adolescent , Adult , Child , Child, Preschool , Cyclic GMP/urine , Female , Humans , Male , Middle Aged , Sodium/urine , Sodium, Dietary/metabolismABSTRACT
Primary chylopericardium is a rare disease with a highly variable clinical course. We report on a 24-year old female with chylopericardium detected during a pulmonary infection. Despite successful treatment of the infectious disease, the chylopericardium persisted and led to cardiac tamponade. From this case, as well as from the literature, it is intriguing to postulate an inflammatory injury of preexisting anomalous lymphatic vessels leading to onset or aggravation of primary chylopericardium. The clinical hallmark of chylopericardium is a milky white, but odorless pericardial fluid at pericardiocentesis. For cases where conservative treatment and pericardiocentesis fail, we newly introduced the method of pericardio-peritoneal shunting by a pericardial window. With postoperative reaccumulation of pericardial fluid, total parenteral nutrition followed by medium chain triglyceride diet was successfully reinitiated. This combined surgical and conservative approach was performed for the first time and may have helped to avoid the more aggressive treatment of thoracic duct ligation and resection. During 2 years of follow-up the patient was asymptomatic and had no recurrence of pericardial effusion.
Subject(s)
Pericardial Effusion/diagnosis , Adult , Cardiac Tamponade/diagnosis , Cardiac Tamponade/etiology , Cardiac Tamponade/surgery , Combined Modality Therapy , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Parenteral Nutrition, Total , Pericardial Effusion/etiology , Pericardial Effusion/surgery , Postoperative Care , RecurrenceABSTRACT
OBJECTIVES: Inhibition of neutral endopeptidase 24.11 (NEP) prevents degradation of plasma atrial natriuretic peptide (ANP), a substance with vasodilatory and natriuretic properties. The aim of the study was to investigate the haemodynamic and endocrine effects of the NEP inhibitor candoxatril in patients with congestive heart failure (CHF). METHODS: In a randomized double-blind, parallel group study design, 24 patients with CHF received a 10-day oral drug treatment with candoxatril (25, 100 or 400 mg b.i.d.) or placebo. Invasive haemodynamics and laboratory parameters were measured on days 1 and 10. RESULTS: On the first treatment day, candoxatril produced a dose-dependent increase in plasma cyclic GMP, the second messenger of ANP. At doses of 100 and 400 mg, candoxatril induced an increase (!) in systemic vascular resistance (SVR) and a decrease in cardiac index (CI), which was not observed with placebo and the lower candoxatril dose. CONCLUSION: Despite significant activation of the ANP system, reflected by a dose-dependent increase in plasma cyclic GMP concentrations, high doses of candoxatril induced systemic vasoconstrictory rather than vasocilatory effects in patients with CHF. Therefore NEP inhibition by candoxatril may not exhibit beneficial haemodynamic effects in CHF.
Subject(s)
Heart Failure/drug therapy , Hemodynamics/drug effects , Indans/therapeutic use , Neprilysin/antagonists & inhibitors , Propionates/therapeutic use , Protease Inhibitors/therapeutic use , Aldosterone/blood , Atrial Natriuretic Factor/blood , Cyclic AMP/analysis , Double-Blind Method , Heart Failure/physiopathology , Humans , Indans/pharmacology , Middle Aged , Propionates/pharmacologyABSTRACT
Examples for the effective teaching of core knowledge and skills of advanced life support courses are given. Didactive requirements of the skill stations for emergency treatment of cardiac arrest scenarios are discussed. A standardized course concept based on the recommendations of the American Heart Association (AHA) (1) and European Resuscitation Council (ERC) (2) as well as valid and mandatory certification and recertification procedures are deemed necessary for physicians active in emergency medical systems.
Subject(s)
Education, Medical , Problem-Based Learning , Resuscitation/education , Certification , Emergency Medicine/education , Germany , Heart Arrest/therapy , HumansABSTRACT
The effects of a continuous i.v. infusion of urodilatin at a dose of 30 ng kg-1 min-1 were studied in a patient with congestive heart failure. After 30 min, urodilatin had induced a marked stimulation of plasma cyclic GMP concentrations. In parallel haematocrit increased. No significant diuresis and no change of invasive haemodynamics was observed. After 2 h the patient developed a profuse perspiration. Eighty minutes later he suffered from dizziness due to hypotension (blood pressure 80/40 mmHg) and a sudden bradycardia (50 bpm). Urodilatin was discontinued and symptoms were relieved by bed tilt and rapid infusion of isotonic saline solution. Mechanisms contributing to these adverse effects may be fluid extravasation to the third space and sympathoinhibitory effects known to occur with natriuretic peptide infusion.
Subject(s)
Atrial Natriuretic Factor/adverse effects , Bradycardia/chemically induced , Heart Failure/drug therapy , Hypotension/chemically induced , Peptide Fragments/adverse effects , Atrial Natriuretic Factor/administration & dosage , Blood Pressure , Cardiac Output , Cyclic GMP/blood , Heart Rate , Hematocrit , Humans , Infusions, Intravenous , Male , Middle Aged , Peptide Fragments/administration & dosageABSTRACT
In man, chronic antihypertensive calcium antagonist treatment improves cardiac function and reduces plasma ANF concentrations. Physical exercise increases cardiac workload and plasma ANF levels. In the present study, we investigated the effects of acute administration of the dihydropyridine calcium antagonist BAY t 7207 (BAY) during bicycle exercise on plasma ANF and plasma cyclic GMP levels, on mean arterial pressure (MAP), heart rate (HR), and on natriuresis and urinary urodilatin excretion. In a randomized, double-blind placebo controlled cross-over trial, 8 patients (age 56.8 +/- 2.5 y) with documented coronary artery disease and mildly impaired left ventricular function (EF 50.0 +/- 1.3%), received oral BAY (20 mg) or placebo. Forty-five minutes after medication, patients underwent a standardised exercise bicycle test in the supine position (6 min 25 W, 6 min 50 W). Before exercise, MAP was lower after BAY (88.8 +/- 4.1 mmHg) than after placebo (95.7 +/- 3.5 mmHg; p = 0.024), and HR was higher after BAY (76.8 +/- 3.5 bpm) than after placebo (69.5 +/- 3.6 bpm; p = 0.049). Plasma ANF tended to be higher after BAY (31.2 +/- 5.6 pg/ml) than after placebo (26.7 +/- 5.0 pg/ml), and plasma cGMP was not different (BAY 3.4 +/- 0.3, placebo 3.8 +/- 0.3 pmol/ml). During exercise, the relative increases in HR (+43%) and MAP (+17%) were identical after BAY and placebo. In contrast, ANF levels during exercise increased by 130 +/- 28% after placebo but only by 36 +/- 11% after BAY (p = 0.011). In parallel, plasma cyclic GMP increased by 61 +/- 13% after placebo and by 20 +/- 8% after BAY (p = 0.013). At the end of exercise, the BAY-induced reduction in plasma cyclic GMP reflected the reduction in diastolic arterial pressure (r = 0.717; p = 0.045). Compared to placebo, BAY treatment increased the fractional excretion rate of sodium from 0.46 +/- 0.11 to 0.90 +/- 0.22% (p = 0.016), without relation to urinary urodilatin excretion. Thus, the calcium antagonist BAY t 7207 attenuated the exercise-induced increase in plasma ANF and cyclic GMP probably due to its vasodilator effect. The relationship between blood pressure and the ANF system during exercise, which parallels findings during chronic antihypertensive treatment, may open a perspective for early evaluation of long-term therapy with calcium channel blockers.
Subject(s)
Atrial Natriuretic Factor/blood , Calcium Channel Blockers/pharmacology , Cyclic GMP/blood , Ventricular Dysfunction, Left/blood , Atrial Natriuretic Factor/urine , Cross-Over Studies , Diuretics/urine , Double-Blind Method , Exercise Test , Humans , Male , Middle Aged , Peptide Fragments/urine , Supine Position , Ventricular Dysfunction, Left/urineABSTRACT
Urodilatin (ANF(95-126)) is an analogue of the atrial natriuretic factor (ANF(99-126)), which has been isolated from human urine. Recently we have shown in healthy volunteers, that intravenous bolus injections of synthetic urodilatin produce more pronounced reductions of pulmonary arterial pressure than ANF(99-126). To compare haemodynamic and renal effects of synthetic urodilatin with those of ANF(99-126) in congestive heart failure (CHF), 12 patients (66.3 +/- 1.4 years) received either two high dose intravenous bolus injections of 4 micrograms kg-1 bw Urodilatin (URO) at a 30 min interval (n = 6) or the same doses of ANF(99-126) (n = 6). Prior to i.v. URO, no URO immunoreactivity was found in human plasma (specific RIA, no crossreactivity to ANF). Similar to ANF, the increase in diuresis (1.4 +/- 0.7 to 3.7 +/- 1.6 ml min-1) and natriuresis (169 +/- 114 to 430 +/- 197 mumol min-1) was moderate after URO in CHF. During the 90 min study period, mean plasma cyclic GMP levels increased much more after URO (by 53.4 +/- 15.1 nM) than after ANF (by 13.1 +/- 3.0 nM; P = 0.04). In contrast to ANF, i.v. bolus injections of URO produced sustained haemodynamic effects in CHF lasting up to 90 min: The average (0-90 min) reduction of systemic vascular resistance was more pronounced after URO (-578 +/- 148) than after ANF (-204 +/- 65 dyn*s*cm-5, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Atrial Natriuretic Factor/administration & dosage , Heart Failure/drug therapy , Peptide Fragments/administration & dosage , Aged , Amino Acid Sequence , Atrial Natriuretic Factor/blood , Atrial Natriuretic Factor/chemistry , Atrial Natriuretic Factor/pharmacology , Creatinine/blood , Cyclic GMP/blood , Diuretics/administration & dosage , Female , Heart Failure/physiopathology , Hemodynamics/drug effects , Humans , Injections, Intravenous , Kidney/drug effects , Kidney/physiopathology , Male , Middle Aged , Molecular Sequence Data , Peptide Fragments/blood , Peptide Fragments/chemistry , Peptide Fragments/pharmacologyABSTRACT
The effects of intravenous human atrial natriuretic factor ANF(99-126) administration on anterior pituitary hormone secretion have not been extensively investigated in humans. We repeatedly studied 10 healthy volunteers (5 female, 5 male, aged 28 +/- 2 years) on 2 occasions, 3 days apart. In randomized, single blind order, subjects received pretreatment with either placebo or intravenous ANF(99-126) (bolus 100 micrograms/kg, 30-min infusion of 0.1 micrograms/kg.min). Subsequently on both occasions subjects received a combined intravenous bolus injection of pituitary releasing hormones (200 micrograms thyrotropin releasing hormone, 100 micrograms gonadotropin releasing hormone and 100 micrograms human adrenocorticotropin releasing hormone; Bissendorf, Hannover, FRG). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), thyrotropin (TSH), prolactin, ANF and cyclic guanosine monophosphate (GMP) were determined by radioimmunoassay. ANF(99-126) treatment induced a significant reduction in basal ACTH plasma concentrations and tended to decrease basal plasma cortisol. The TSH response to combined releasing hormone administration was significantly diminished after ANF(99-126) pretreatment. In women, the releasing hormone induced prolactin increase was reduced after ANF(99-126) pretreatment. With the present study design, ANF(99-126) did not alter the basal or releasing hormone stimulated plasma concentrations of cortisol, LH, FSH and GH. Releasing hormone administration did not affect ANF and cyclic GMP plasma levels. In humans, effects of natriuretic peptides on anterior pituitary hormone secretion may have to be considered with investigational or therapeutic administration of ANF analogues or agents interfering with the ANF metabolism.
Subject(s)
Atrial Natriuretic Factor/pharmacology , Peptide Fragments/pharmacology , Pituitary Gland, Anterior/drug effects , Pituitary Hormone-Releasing Hormones/pharmacology , Pituitary Hormones, Anterior/metabolism , Adult , Atrial Natriuretic Factor/administration & dosage , Atrial Natriuretic Factor/toxicity , Blood Pressure/drug effects , Dyspnea/chemically induced , Female , Flushing/chemically induced , Heart Rate/drug effects , Humans , Infusions, Intravenous , Injections, Intravenous , Male , Nausea/chemically induced , Peptide Fragments/administration & dosage , Peptide Fragments/toxicity , Pituitary Gland, Anterior/metabolism , Pituitary Hormone-Releasing Hormones/administration & dosage , Pituitary Hormone-Releasing Hormones/toxicity , Secretory Rate/drug effects , Taste Disorders/chemically inducedABSTRACT
Urodilatin (ANF(95-126)), an analogue of the atrial natriuretic factor (ANF(99-126)), has recently been isolated from human urine. To study haemodynamic and renal effects of synthetic urodilatin, 18 healthy male volunteers (age 26.1 +/- 0.8 years; X +/- SEM) received i.v. bolus injections of urodilatin at doses of 1, 2 or 4 micrograms kg-1 body weight (bw) (n = 6 per dosage group). Urodilatin dose-dependently increased heart rate and cardiac index. A dose-dependent increase in plasma cyclic GMP levels was also observed. Urinary cyclic GMP excretion, urine flow and natriuresis increased 7-fold, 5-fold and 4-fold, respectively. Renal effects were not different between dosage groups. Compared with ANF(99-126), after urodilatin the reduction in mean pulmonary arterial pressure (PAP) was more pronounced (2 micrograms kg-1, n = 6; ANF -1.8 +/- 0.5, URO: -5.5 +/- 1.1 mmHg, P less than 0.05). Furthermore, after urodilatin the reduction of PAP lasted continuously from 2 up to 90 min after injection, while ANF(99-126) produced only a transient decrease of PAP. Similarly the reduction of pulmonary capillary wedge pressure (PCWP) by urodilatin from 9.3 +/- 1.2 to 3.8 +/- 0.9 mmHg (P less than 0.05) was also sustained up to 90 min post administration. These data in healthy volunteers suggest that, due to prolonged reduction of PAP and PCWP with increases of cardiac index and reduction of systemic vascular resistance, urodilatin might exhibit beneficial effects in cardiovascular disease.
Subject(s)
Atrial Natriuretic Factor/pharmacology , Diuretics/pharmacology , Hemodynamics/drug effects , Kidney/drug effects , Peptide Fragments/pharmacology , Adult , Atrial Natriuretic Factor/blood , Atrial Natriuretic Factor/urine , Cyclic GMP/blood , Diuresis/drug effects , Diuretics/blood , Diuretics/urine , Humans , Male , Natriuresis/drug effects , Peptide Fragments/blood , Peptide Fragments/urineSubject(s)
Critical Care/methods , Pre-Eclampsia/therapy , Acute Kidney Injury/physiopathology , Acute Kidney Injury/therapy , Combined Modality Therapy , Female , Heart/physiopathology , Hemodynamics/physiology , Humans , Infant, Newborn , Pre-Eclampsia/physiopathology , Pregnancy , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome, Newborn/physiopathology , Respiratory Distress Syndrome, Newborn/therapyABSTRACT
In malignant hyperthermia, dantrolene, a drug assumed to possess calcium channel blocking properties, effectively suppresses supraventricular and ventricular arrhythmias. To investigate antiarrhythmic properties of dantrolene, six patients (three women and three men, age 42 +/- 18 yr) with symptomatic atrioventricular (AV)-nodal reentry tachycardia were studied. Electrocardiographic measurements included sinus cycle length, PQ-interval, width of the QRS-complex, and QT- and rate-corrected QT-interval. During the electrophysiologic study, effective refractory periods of the right atrium, AV node, right ventricle, and AV-nodal conduction intervals were determined, and AV-nodal reentry tachycardia was induced in all patients. Dantrolene was administered intravenously over a period of 15 min at doses of 1.0, 1.5, or 3.0 mg/kg in two patients each. The dosage was not further increased because of side effects at the dose of 3.0 mg/kg. After the infusion of dantrolene, the electrocardiographic measurements and electrophysiologic study were repeated. The plasma concentrations of dantrolene ranged from 1.69 to 6.61 micrograms/ml at the time of the electrophysiologic study. After dantrolene administration, the sinus cycle length shortened from 686 +/- 80 to 622 +/- 55 ms (P less than 0.05). No significant changes of any other parameter could be demonstrated after intravenous dantrolene. AV-nodal reentry tachycardia remained inducible in all patients without change of the tachycardia cycle length and without change in coupling intervals of tachycardia-inducing extrastimuli. Antiarrhythmic properties of dantrolene could not be demonstrated in patients with AV-nodal reentry tachycardia at therapeutic doses.(ABSTRACT TRUNCATED AT 250 WORDS)