Biomedical subjects

M M Redfield

Publications and source records attributed to M M Redfield.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effects of natriuretic peptides on load and myocardial function in normal and heart failure dogs.

The effects on myocardial function and loading conditions of clinically relevant doses of the natriuretic peptides (NP) have not been established. The actions of single doses (100 ng x kg(-1) x min(-1) iv over 30 min) of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) were studied in conscious normal dogs and in dogs with pacing-induced heart failure. All three NP reduced end-diastolic pressure in normal dogs, and ANP and BNP reduced end-diastolic volume. In heart failure ANP and BNP reduced EDP, and ANP reduced EDV. Arterial elastance was unchanged in normal dogs and in dogs with heart failure. ANP increased end-systolic elastance (E(es)) in normal dogs, whereas BNP tended to increase E(es) (P = 0.06). In dogs with heart failure, no inotropic effect was seen. In normal dogs, all NP reduced the time constant of isovolumic relaxation (tau), and ANP and BNP reduced tau in dogs with heart failure. Increases in plasma cGMP in dogs with heart failure were blunted. The NP reduced preload and enhanced systolic and diastolic function in normal dogs. Effects of ANP and BNP on preload and diastolic function were maintained in heart failure. Lack of negative inotropic effects in heart failure supports the validity of the NP as therapeutic agents.

Animals↗

PubMed2000

Effects of adrenomedullin on load and myocardial performance in normal and heart-failure dogs.

Myocardial actions of the vasodilator peptide adrenomedullin (ADM) in the intact animal are unknown. Negative and positive inotropic actions have been reported in ex vivo experiments. Myocardial and load-altering actions of ADM in dogs before and after development of heart failure were studied. With controlled heart rate (atrial pacing) and after beta-blockade, ADM was administered to five normal dogs in doses of 20 ng. kg(-1). min(-1) iv, 100 ng. kg(-1). min(-1) iv, and 200 ng. kg(-1). min(-1) into the left ventricle (LV). LV peak systolic pressure and end-systolic volume decreased with each dose of ADM. End-systolic pressure decreased with the two higher doses. At the highest dose, arterial elastance and the time constant of LV isovolumic relaxation (tau) decreased, and LV end-systolic elastance (E(es)) increased. LV end-diastolic pressure and volume were unchanged. In five additional normal dogs receiving only the highest dose of ADM (200 ng. kg(-1). min(-1) intra-LV), to control for increased heart rate and sympathetic activation observed with the cumulative infusion, ADM produced arterial vasodilation but no change in E(es) or tau. In four dogs with pacing-induced heart failure, ADM (200 ng. kg(-1). min(-1) intra-LV) was without effect on tau, E(es), and systolic or diastolic pressure and volume. In vivo, ADM appears to be a selective arterial dilator without inotropic or lusitropic effects. The vasodilatory actions are attenuated in heart failure.

Adrenomedullin↗

PubMed2000

Activation of cardiorenal and pulmonary tissue endothelin-1 in experimental heart failure.

Endothelin-1 (ET-1) is a peptide that has been implicated in congestive heart failure (CHF). Although increased concentrations of circulating ET-1 have been repeatedly demonstrated, the activation of local ET-1 in target tissues of CHF remains poorly defined. Our objective was to characterize ET-1 tissue concentrations and gene expression of prepro ET-1 in myocardial, renal, and pulmonary tissue in rapid ventricular pacing-induced canine CHF. Progressive rapid ventricular pacing (38 days) resulted in impaired cardiovascular hemodynamics, increased atrial and left ventricular mass, decreased renal sodium excretion, and increased ET-1 plasma concentrations (all P < 0.05). Tissue analysis revealed significant increases in local ET-1 during CHF in left ventricular, renal, and pulmonary tissue, whereas a moderate increase in left atrial ET-1 did not reach statistical significance. In contrast, prepro-ET-1 gene expression was increased more than threefold in pulmonary tissue and more than twofold in left atrial myocardium with no increase in left ventricular or renal gene expression. The present studies demonstrate a differential pattern of ET-1 activation in cardiorenal and pulmonary tissue with a strong accumulation of ET-1 in kidney and lung during CHF. Although the observed increase in left ventricular and renal ET-1 in association with unaltered gene expression is consistent with increased uptake, pulmonary and atrial tissue may contribute to increased circulating and local ET-1 in CHF.

Animals↗

PubMed2000

Left ventricular diastolic dysfunction in patients with hypertension and preserved systolic function.

OBJECTIVE: To assess prospectively diastolic function in hypertensive patients with preserved left ventricular function, particularly focusing on the limitation of the transmitral flow velocity curve alone to detect diastolic dysfunction. PATIENTS AND METHODS: Comprehensive Doppler analysis was performed in 51 hypertensive patients with preserved left ventricular systolic function. RESULTS: The ratio of the peak early diastolic filling wave velocity to the peak velocity of filling wave at atrial contraction was less than the age-adjusted mean value minus 2 SD in 16 patients, and the other 35 patients had a "normal" transmitral Doppler signal. However, the combined transmitral and pulmonary venous Doppler analysis revealed that 12 of these 35 patients had a "pseudonormal" pattern. The prevalence of diastolic dysfunction was estimated at 31% with use of transmitral Doppler alone but increased to 55% when comprehensive Doppler analysis was used (P < .05). CONCLUSION: The presence of diastolic dysfunction has been frequently overlooked in hypertensive patients with transmitral Doppler analysis alone, and an assessment of diastolic function with a comprehensive Doppler analysis is needed in patients at risk for diastolic dysfunction.

Aged↗

PubMed2000

Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation.

OBJECTIVE: To determine the frequency of tachycardia-related cardiomyopathy in patients with atrial fibrillation and systolic dysfunction referred for atrioventricular node ablation. PATIENTS AND METHODS: This prospective multicenter cohort study was conducted at 16 tertiary care centers. The ejection fraction was measured before and 3 and 12 months after atrioventricular node ablation. Patients with reduced systolic function (ejection fraction < or = 45%) before atrioventricular ablation were included in this study. Patients whose ejection fraction increased by at least 15 percentage points and to higher than 45% were considered to have tachycardia-related cardiomyopathy. RESULTS: Of 63 patients with systolic dysfunction, 48 had at least 1 adequate follow-up echocardiographic study. Sixteen (25%) of the 63 had marked improvement in the ejection fraction (mean +/- SD change, 27 +/- 8 percentage points) to a value higher than 45% after ablation. CONCLUSIONS: Tachycardia-related cardiomyopathy is common in patients with atrial fibrillation and systolic dysfunction referred for atrioventricular node ablation. This diagnosis should be considered in all patients in whom systolic dysfunction occurs subsequent to or concomitant with onset of atrial fibrillation.

Atrial Fibrillation↗

PubMed1999

Renal response to acute neutral endopeptidase inhibition in mild and severe experimental heart failure.

BACKGROUND: Neutral endopeptidase 24.11 (NEP) is a metalloprotease that is localized in the greatest abundance in the kidney and degrades natriuretic peptides, such as atrial natriuretic peptide (ANP). Mild congestive heart failure (CHF) is characterized by increases in circulating ANP without activation of the renin-angiotensin-aldosterone system (RAAS) or sodium retention. In contrast, severe CHF is characterized by sodium retention and coactivation of both ANP and the RAAS. METHODS AND RESULTS: We defined the acute cardiorenal actions of the NEP inhibitor candoxatrilat (8 microg. kg(-1). min(-1)) in 4 groups of anesthetized dogs (normal, n=8; mild CHF, n=6; severe CHF, n=5; and severe CHF with chronic AT(1) receptor antagonism, n=5). Mild CHF was produced by rapid ventricular pacing at 180 bpm for 10 days and severe CHF at 245 bpm for 10 days. In mild CHF, urinary sodium excretion and glomerular filtration rate were greatest in response to acute NEP inhibition compared with the response in either control animals or those with severe CHF. Furthermore, an increase in glomerular filtration rate was observed only in mild CHF in association with increases in renal blood flow and decreases in renal vascular resistance and distal tubular sodium reabsorption. Urinary ANP and cGMP excretion, markers for renal biological actions of ANP, were greatest in mild CHF. The renal actions observed in mild CHF were attenuated in severe CHF and not restored by chronic AT(1) receptor antagonism. CONCLUSIONS: The results of the present study demonstrate that acute NEP inhibition in mild CHF results in marked increases in renal hemodynamics and sodium excretion that exceed that observed in control animals and severe CHF. These studies underscore the potential therapeutic role for NEP inhibition to enhance renal function in mild CHF, an important phase of CHF that is marked by selective activation of endogenous ANP in the absence of an activated RAAS.

Acute Disease↗

PubMed1999

Adenylate kinase-catalyzed phosphotransfer in the myocardium : increased contribution in heart failure.

Although the downregulation of creatine kinase activity has been associated with heart failure, creatine kinase-deficient transgenic hearts have a preserved contractile function. This suggests the existence of alternative phosphotransfer pathways in the myocardium, the identity of which is still unknown. In this study, we examined the contribution of adenylate kinase-catalyzed phosphotransfer to myocardial energetics. In the isolated mitochondria/actomyosin system, which possesses endogenous adenylate kinase activity in both compartments, substrates for adenylate kinase promoted the rate and amplitude of actomyosin contraction that was further enhanced by purified adenylate kinase. Inhibition of adenylate kinase activity diminished both actomyosin contraction and mitochondrial respiration, which indicated reduced energy flow between mitochondria and myofibrils. In intact myocardium, the net adenylate kinase-catalyzed phosphotransfer rate was 10% of the total ATP turnover rate as measured by 18O-phosphoryl labeling in conjunction with gas chromatography and mass spectrometry. In pacing-induced failing heart, adenylate kinase-catalyzed phosphotransfer increased by 134% and contributed 21% to the total ATP turnover. Concomitantly, the contribution by creatine kinase dropped from 89% in normal hearts to 40% in failing hearts. These phosphotransfer changes were associated with reduced levels of metabolically active ATP but maintained overall ATP turnover rate. Thus, this study provides evidence that adenylate kinase facilitates the transfer of high-energy phosphoryls and signal communication between mitochondria and actomyosin in cardiac muscle, with an increased contribution to cellular phosphotransfer in heart failure. This phosphotransfer function renders adenylate kinase an important component for optimal myocardial bioenergetics and a compensatory mechanism in response to impaired intracellular energy flux in the failing heart.

Actomyosin↗

PubMed1999

Congestive heart failure in the community: trends in incidence and survival in a 10-year period.

OBJECTIVE: To compare the incidence of congestive heart failure and the survival in patients with congestive heart failure in Rochester, Minn, in 1981 with that observed in 1991. METHODS: Population-based, descriptive epidemiological study with ecological and individual level comparisons over time. Olmsted County, Minnesota, where the Rochester Epidemiology Project provides passive surveillance of the population for health outcomes. All 248 patients fulfilled the Framingham criteria, 107 patients presenting with the new onset of congestive heart failure in 1981 and 141 patients in 1991. The community inpatient and outpatient medical records of all incident cases were reviewed to evaluate the presenting characteristics of patients at diagnosis. RESULTS: The incidence of congestive heart failure after adjustment for age and sex to the US population was not significantly different in the 1991 cohort compared with that in 1981 (3.0 per 1000 person-years; 95% confidence interval, 2.5-3.5 vs 2.8 per 1000 person-years; 95% confidence interval, 2.2-3.3; P = .55). The survival of patients with new diagnosis of congestive heart failure was similar in the 2 cohorts (P = .53). Survival adjusted for age, sex, and New York Heart Association functional class was not significantly different in patients with congestive heart failure in 1981 and 1991 (relative risk, 0.907; P = .55). CONCLUSIONS: These data suggest that recent advances in management of cardiovascular disease, as used in the community, had not yet impacted incidence or survival of patients with congestive heart failure in the community during the 10-year study period. This highlights the need to continue efforts to ensure that advances in diagnosis and therapy are incorporated into the care of patients with congestive heart failure in the community.

Age Distribution↗

PubMed1999

Doppler echocardiographic-guided diagnosis and therapy of heart failure.

Abnormalities of diastolic function play a major role in producing the signs and symptoms of heart failure. In patients with heart failure and reduced left ventricular systolic function, concomitant diastolic dysfunction is invariably present. In addition, it is now well established that as many as 40% to 50% of patients with well-documented episodes of heart failure have preserved systolic function. Doppler echocardiography provides one of the most useful clinical tools for assessing left ventricular diastolic function and can provide diagnostic and prognostic information. The Doppler assessment of diastolic function should be part of the routine echocardiographic evaluation of patients suspected of having heart failure. This review focuses on the use of Doppler echocardiographic techniques to assess diastolic function. The Doppler patterns of diastolic filling observed and their progression over time in patients with myocardial disease are described and related to changes in the physiology of diastolic filling. In addition, Doppler echocardiographic-guided treatment strategies for heart failure are discussed.

Aged↗

PubMed1999

Use of echocardiography in the management of congestive heart failure in the community.

OBJECTIVES: We evaluated the use and the impact of echocardiography in patients receiving an initial diagnosis of congestive heart failure in Olmsted County, Minnesota, in 1991. BACKGROUND: The American College of Cardiology/American Heart Association clinical practice guidelines recommend echocardiography in all patients with suspected congestive heart failure. No data are available on use and impact of echocardiography in management of congestive heart failure in a community. METHODS: The medical records linkage system of the Rochester Epidemiology Project was used to identify all 216 patients who satisfied the Framingham criteria for congestive heart failure. Of these, 137 (63%) underwent echocardiography within 3 weeks before or after the episode of congestive heart failure (Echo group), and the other 79 patients constitute the No-Echo group. RESULTS: The No-Echo group patients were older (p=0.022), were more likely to be female (p=0.072), had milder symptoms (p=0.001) and were less often hospitalized at diagnosis (p=0.001). Fewer patients in the No-Echo group were treated with angiotensin-converting enzyme inhibitors (p=0.001). Advanced age (> or = 80 years), lower New York Heart Association functional class, absence of a fourth heart sound on examination, absence of cardiomegaly or signs of congestive heart failure on chest radiography and absence of known valve disease were independently related to the decision not to obtain an echocardiogram. Survival after adjustment for age, functional class and gender was lower in the No-Echo group than the Echo group (risk ratio=0.607, p=0.017). CONCLUSIONS: The underuse of echocardiography appears to be associated with poorer survival and underuse of angiotensin-converting enzyme inhibitor therapy.

Adult↗

PubMed1999

Left ventricular systolic and diastolic function after pericardiectomy in patients with constrictive pericarditis: Doppler echocardiographic findings and correlation with clinical status.

OBJECTIVES: The study assessed changes in left ventricular systolic and diastolic function after pericardiectomy in patients with constrictive pericarditis and correlated postoperative Doppler echocardiographic findings with clinical status. BACKGROUND: Despite the efficacy of pericardiectomy, some patients with constrictive pericarditis fail to improve postoperatively. Data on serial evaluation of systolic and diastolic function after pericardiectomy and its relation to clinical status are not available. METHODS: From 1985 to 1995, a total of 58 patients with constrictive pericarditis underwent pericardiectomy and had at least one follow-up Doppler echocardiographic study with a respirometer: 23 patients had one examination within 3 months postoperatively, 19 had a study within 3 months and another one more than 3 months postoperatively, and 16 had one study more than 3 months postoperatively. RESULTS: In the early postoperative period, diastolic function was normal in 17 patients (40.5%), restrictive in 17 (40.5%), and constrictive in 8 (19%). Among 19 patients who had serial Doppler echocardiography, in 2 patients with restrictive physiology and 5 with constrictive physiology the results had become normal, and 1 patient who had had constrictive physiology had restrictive findings. In late follow-up, left ventricular end-diastolic diameter increased compared with preoperative measurement (p = 0.0009). Diastolic filling pattern at late follow-up was normal in 20 patients (57%), restrictive in 12 (34%) and constrictive in 3 (9%). There was a significant relationship between diastolic filling patterns and symptomatic status (chi2 = 20.9, p < 0.0001). Patients with persistent abnormal diastolic filling on Doppler echocardiography had had symptoms for a longer time preoperatively than did patients with normal diastolic physiology (p = 0.0471). CONCLUSIONS: Diastolic filling characteristics remain abnormal in a substantial number of patients with constrictive pericarditis after pericardiectomy. These abnormalities may resolve gradually but can persist. Diastolic filling abnormalities after pericardiectomy correlate well with clinical symptoms and tend to occur in patients who have had symptoms longer preoperatively. This finding supports the recommendation that pericardiectomy be performed promptly in symptomatic patients with constrictive pericarditis.

Adolescent↗

PubMed1999

Reduced activity of enzymes coupling ATP-generating with ATP-consuming processes in the failing myocardium.

Coupling of ATP-generating with ATP-consuming processes is an essential component in the cardiac bioenergetics responsible for optimal myocardial function. Although a number of enzymatic systems have been implicated in securing proper intracellular energy communication, their integrative response in a failing myocardium has not been determined so far. Therefore, we measured catalytic activities of enzymes responsible for the communication between ATP-generating and ATP-consuming processes in ventricular samples obtained from normal dogs and dogs with tachycardia-induced heart failure. In the failing myocardium, phosphotransfer activities of creatine kinase, adenylate kinase, 3-phosphoglycerate kinase and pyruvate kinase, which collectively deliver ATP and remove ADP from myofibrillar ATPases, were depressed by 30, 21, 44 and 20%, respectively, when compared to normal controls. The activity of hexokinase, an enzyme which directs phosphoryls into the glycolytic phosphotransfer pathway, was unchanged. Also, the activity of glyceraldehyde-3-phosphate dehydrogenase, which may shuttle inorganic phosphate between ATPases and ATP-synthases, was not affected by heart failure. However, the CO2-hydration activity of carbonic anhydrase, which together with creatine kinase, is presumed responsible for removal of protons from ATPases, was diminished by 21%. As these enzymatic systems are collectively required for adequate delivery of high-energy phosphoryl to, and removal of end-products from, cellular ATPases, the cumulative deficit in their flux capacities may provide a bioenergetic basis for impaired contraction-relaxation in the failing heart.

Adenosine Diphosphate↗

PubMed1998

Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991.

BACKGROUND: Data are limited regarding the classification and prognosis of patients with congestive heart failure (CHF) in the community. METHODS AND RESULTS: Using the resources of the Rochester Epidemiology Project, we evaluated all patients receiving a first diagnosis of CHF in Olmsted County, Minnesota, in 1991 (n=216). Among these patients, 88% were >/=65 years and 49% were >/=80 years of age. The prognosis of patients with a new diagnosis of CHF was poor; survival was 86+/-2% at 3 months, 76+/-3% at 1 year, and 35+/-3% at 5 years. Of the 216 patients, 137 (63%) had an assessment of ejection fraction. In these patients, systolic function was preserved (ejection fraction >/=50%) in 59 (43%) and reduced (ejection fraction <50%) in 78 (57%). Survival adjusted for age, sex, NYHA class, and coronary artery disease was not significantly different between patients with preserved and those with reduced systolic function (relative risk, 0.80; P=0.369). ACE inhibitors were used in only 44% of the total population with CHF. CONCLUSIONS: The present study reports the clinical characteristics and natural history of CHF as it presents in the community in the vasodilator era. CHF is a disease of the "very elderly," frequently occurs in the setting of normal ejection fraction, and has a poor prognosis, regardless of the level of systolic function. Diagnostic and therapeutic methods are underused in the community.

Age Distribution↗

PubMed1998

The Ablate and Pace Trial: a prospective study of catheter ablation of the AV conduction system and permanent pacemaker implantation for treatment of atrial fibrillation. APT Investigators.

BACKGROUND: The Ablate and Pace Trial (APT) prospectively assessed the effects of catheter ablation of the AV conduction system and permanent pacemaker implantation on health-related quality of life, survival, exercise capacity, and ventricular function in 156 patients with symptomatic atrial fibrillation. METHODS: All patients referred for catheter ablation and permanent pacemaker implantation because of medically-refractory atrial fibrillation at 16 centers were screened for enrollment in a prospective registry. Baseline assessment prior to ablation included measurement of quality of life, including the Health Status Questionnaire, the Quality of Life Index and the Symptom Checklist: Frequency and Severity. Exercise capacity was assessed with metabolic treadmill exercise testing and ventricular function was quantitated with echocardiography. The quality of life instruments, exercise capacity, and echocardiography were repeated at 3 and 12 months after catheter ablation. RESULTS: The APT population included 90 men and 66 women (66.1 +/- 11.5 years of age) with either chronic (n = 70), recurrent (n = 31), or paroxysmal atrial fibrillation (n = 55). Structural heart disease was present in 78.2% of patients. Successful ablation of AV conduction was achieved in 155 of 156 patients (99.4%). Survival at 1 year was 85.3%, with 5 of 23 deaths being sudden cardiac deaths. Survival over the first year of follow-up was significantly lower for patients with a baseline left ventricular ejection fraction (LVEF) < 0.45 (0.73) than for patients with a LVEF > or = 0.45 (0.88, p = 0.03). The NYHA functional class improved from 2.1 at baseline to 1.8 at 3 months and 1.9 at 12 months of followup (p = 0.0001). Significant improvement in quality of life scores were noted for all 8 subscales of the Health Status Questionnaire, for the overall rating of the Quality of Life Index, the Health and Function subscales; Arrhythmia-related symptoms were markedly reduced as measured by the Symptom Checklist: Frequency and Severity scale. The mean LVEF improved from 0.50 +/- 0.20 at baseline to 0.54 +/- 0.20 at 3 months (p = 0.03). The LVEF 12 months after ablation was 0.52 +/- 0.20, not statistically different from baseline. Individuals with reduced systolic function at baseline had the greatest improvement, from LVEF 0.31 +/- 0.20 at baseline to 0.41 +/- 0.20 at 3 months and 0.41 +/- 0.30 at 12 months (p = 0.0001). There were no significant changes in treadmill exercise duration (10.0 +/- 4.3 min at baseline and 11.6 +/- 3.6 min at 12 months) or VO2max (1467 +/- 681 ml O2 min baseline and 1629 +/- 739 ml O2 min at 12 months). CONCLUSIONS: Catheter ablation of the AV conduction system and permanent pacemaker implantation were associated with improved quality of life and left ventricular function in this population of highly symptomatic patients with atrial fibrillation refractory to medical therapy.

Aged↗

PubMed1998

Chronic oral endothelin type A receptor antagonism in experimental heart failure.

Endothelin-1 (ET-1) is a cardiovascular peptide that binds to two distinct receptors, ET(A) and ET(B), resulting in systemic and regional vasoconstriction, alteration in sodium excretion, mitogenesis, and release of other vasoactive peptides such as atrial natriuretic peptide (ANP). A role for ET-1 has been proposed in congestive heart failure (CHF) based on the increase in circulating ET-1 in this cardiovascular disease state. The present study determined the cardiorenal and endocrine responses to chronic selective oral ETA antagonism in experimental CHF. Two groups of conscious dogs underwent 21 days of pacing-induced CHF. These groups included a control untreated group (n = 6) and a group that received an orally active ET(A) receptor antagonist (A-127722, Abbott Pharmaceuticals, 5 mg/kg PO bid, n = 6). Each group was studied at baseline before the onset of CHF and after 14 and 21 days of CHF. Compared with the CHF control group, the ET(A) receptor antagonism group at 14 days of CHF showed lower mean arterial pressure and systemic vascular resistance. Similarly, ET(A) receptor antagonism markedly attenuated the increase in circulating ANP despite similar atrial pressures. At 21 days of CHF, ET(A) receptor antagonism lowered pulmonary artery pressure, pulmonary vascular resistance, and systemic vascular resistance in association with a higher cardiac output. Plasma ANP remained suppressed. Despite the lower mean arterial pressure and circulating ANP in the ET(A) receptor antagonist group, the absolute decrease in sodium excretion from baseline was less compared with the untreated CHF control group. The present investigation supports the conclusion that endogenous ET-1 participates in the systemic and pulmonary vasoconstriction, the elevation of ANP, and the sodium retention that characterize this model of experimental CHF, suggesting a potential therapeutic role for ET(A) receptor antagonism in CHF.

Administration, Oral↗

PubMed1997

Determination of left ventricular filling pressure by Doppler echocardiography in patients with coronary artery disease: critical role of left ventricular systolic function.

OBJECTIVES: This study was designed to determine the usefulness of transthoracic Doppler measurements in detecting increased left ventricular (LV) end-diastolic pressure in patients with coronary artery disease, specifically examining the influence of systolic function on the accuracy of these methods. BACKGROUND: Studies that have correlated Doppler indexes with LV filling pressures primarily involved patients with LV systolic dysfunction. The reliability of Doppler indexes in estimating filling pressures in patients with coronary artery disease and preserved systolic function is unclear. METHODS: Pulsed wave Doppler transmitral and pulmonary venous flow velocity curves and LV pressure were recorded in 83 patients with coronary artery disease. RESULTS: Conventional Doppler indexes (deceleration time of mitral E wave velocity, ratio of peak mitral E to A wave velocities and pulmonary venous systolic fraction) correlated with LV filling pressure in patients with an ejection fraction (EF) < or = 50% but not in those with an EF > 50%. Previously published regression analysis for prediction of LV filling pressure was accurate in patients with an EF < or = 50% but not in those with an EF > 50%. The difference between flow duration with atrial contraction in the pulmonary veins and transmitral flow duration with atrial contraction correlated with LV filling pressure in both groups. CONCLUSIONS: Analysis of the early diastolic portion of the transmitral or pulmonary venous flow velocity curves can be used to predict LV filling pressures in patients with systolic dysfunction, but are inaccurate in patients with preserved systolic function. The combined analysis of both flow velocity curves at atrial contraction is a reliable, feasible predictor of increased LV filling pressure, irrespective of systolic function.

Aged↗

PubMed1997

Effect of endogenous natriuretic peptide system on ventricular and coronary function in failing heart.

Ventricular concentrations of atrial, brain (BNP) and C-type natriuretic peptide are enhanced in congestive heart failure (CHF). Natriuretic peptide receptors are present on ventricular myocytes and stimulate guanosine 3',5'-cyclic monophosphate (cGMP) production. cGMP has been demonstrated to affect myocyte function in vitro. Thus we hypothesized that the intracardiac natriuretic peptide system may modulate myocardial and coronary function in CHF. To test this hypothesis, the effects of an intracoronary infusion of the natriuretic peptide receptor antagonist HS-142-1 on ventricular and coronary function were examined in anesthetized dogs with chronic CHF. To determine whether receptor stimulation had contrasting effects to those of receptor blockade, intracoronary BNP was infused in anesthetized normal and CHF dogs. Low-dose HS-142-1 delayed and slowed left ventricular (LV) relaxation and decreased coronary blood flow without changes in LV pressures. Higher doses further impaired LV relaxation without further decreases in coronary blood flow. In normal and CHF dogs, exogenous BNP produced the opposite effect with a quicker onset and faster rate of LV relaxation without effects on LV pressures or coronary blood flow. The endogenous natriuretic peptide system has an autocrine-paracrine role to modulate LV and coronary vascular function in CHF.

Adrenergic beta-Antagonists↗

PubMed1997

Adrenomedullin in experimental congestive heart failure: cardiorenal activation.

Adrenomedullin (ADM) is a new member of a family of vasodilating and natriuretic peptides that plays an important role in cardiorenal regulation. This study was designed to establish the plasma, urinary, cardiac, and renal tissue concentrations and immunohistochemical localizations of ADM in normal dogs and dogs with experimental congestive heart failure (CHF) produced by rapid ventricular pacing. Plasma ADM concentration was 5.6 +/- 0.4 pg/ml in normal dogs and significantly increased to 14.5 +/- 2.5 pg/ml in CHF dogs (P < 0.05). Ventricular and renal tissue ADM were significantly increased in CHF dogs compared with normals. Immunohistochemical examination revealed positive ADM immunostaining within the myocytes, and ventricular ADM immunoreactivity was significantly more intense in CHF dogs than in normals. ADM immunoreactivity was also observed in the glomerulus, distal tubules, and medullary collecting duct cells in the kidney, and the intensities of ADM immunoreactivity in these sites were increased in CHF dogs compared with normals. In addition, ventricular ADM was a powerful marker for left ventricular mass, and circulating ADM correlated positively with left ventricular end-diastolic pressure and inversely with cardiac output and ejection fraction. Despite an increase in renal tissue ADM, urinary ADM did not increase in CHF dogs. The current study demonstrates that plasma concentration of ADM is increased in experimental CHF and that ventricular and renal ADM is activated in the progression of CHF. Tissue and circulating ADM also are markers for the alterations in myocardial structure and function. This study supports a potential role for ADM in the neurohumoral activation in experimental CHF.

Adrenomedullin↗