Biomedical subjects

E Nunez

Publications and source records attributed to E Nunez.

At least 19 recordsLinked to original sources

PubMed2001

Effect of combined aspirin and angiotensin-converting enzyme inhibitor therapy versus angiotensin-converting enzyme inhibitor therapy alone on readmission rates in heart failure.

An adverse interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors is suspected in patients with heart failure, but the effect of combined therapy with these agents on hospital readmission rates is unknown. Our study found that combining aspirin with ACE inhibitors is associated with higher early readmission rates than use of ACE inhibitors alone, particularly in patients with depressed ejection fraction and in those without coronary artery disease.

Aged↗

PubMed2000

Does left ventricular shape influence clinical outcome in heart failure?

BACKGROUND: Left ventricular (LV) shape tends to become spherical in patients with dilated cardiomyopathy of diverse etiology. Clinical and echocardiographic factors which affect the degree of LV spherical distortion and the impact of altered LV shape on prognosis have not been studied adequately. HYPOTHESIS: This study was undertaken to investigate the prognostic implications of altered LV shape on clinical outcome in dilated cardiomyopathy. METHODS: In 112 patients with depressed LV ejection fraction (19 +/- 9%) and symptomatic heart failure, and in 10 age- and gender-matched normal controls, we performed 2-dimensional echocardiography to assess LV shape using the eccentricity index. Eccentricity index was defined as the ratio of the LV long axis to the LV transverse diameter, measured at end systole and end diastole in the apical four-chamber view. We sought univariate and multivariate clinical and echocardiographic correlates of LV shape. Further, we sought correlations between eccentricity index and clinical outcomes (death and composite outcome of death or emergent heart transplant). RESULTS: Compared with controls, patients with cardiomyopathy had significantly lower systolic (2.04 vs. 1.56; p = 0.001) and diastolic (1.75 vs. 1.53; p = 0.003) eccentricity index, implying a more spherical LV shape. Of all clinical and echocardiographic variables tested, mitral regurgitation, right ventricular dysfunction, and increased LV mass were independently associated with spherical LV shape. At a follow-up period of 17 +/- 12 months, no correlation was found between eccentricity index and the occurrence of death or the combined endpoint of death or emergent heart transplant, in univariate or multivariate analysis. CONCLUSIONS: In patients with dilated cardiomyopathy, the degree of spherical distortion of the LV does not correlate with prognosis.

Age Factors↗

PubMed2000

Does gender bias exist in the medical management of heart failure?

INTRODUCTION: The purpose of this study was to ascertain the presence of gender bias in the medical management of heart failure, and to assess its association with the specialty of the caregiver physician. METHODS: In 309 patients with documented left ventricular systolic dysfunction (ejection fraction <45%) and at least one hospitalization for heart failure, we assessed the frequency of use of effective medical therapy for heart failure among male (n=187) and female (n=122) patients at the time of hospital discharge. We constructed multivariate models relating patient gender and caregiver specialty to utilization of each class of medications (angiotensin-converting enzyme inhibitors, effective vasodilator therapy (i.e., angiotensin-converting enzyme inhibitors or hydralazine-nitrate therapy), diuretics, digoxin), and combination therapy (i.e., vasodilator plus diuretic plus digoxin). RESULTS: In crude analyses, we did not find any difference in utilization of medications between male and female patients. Multivariate analyses involving adjustment for age, race, coronary artery disease, ejection fraction, and other relevant variables, revealed higher utilization of combination therapy by cardiologists in male versus female patients (adjusted odds ratios=2.07; 95%CI=1.09-3.95), and higher utilization of digoxin therapy by non-cardiologists in female versus male patients (adjusted odds ratio=5.5; 95%CI=1.4-22.2). No gender or caregiver specialty differences were seen in models relating to the other classes of medications. CONCLUSIONS: Our findings suggest the presence of gender bias in the medical management of heart failure, and identify an interesting interaction between caregiver specialty and gender bias.

Aged↗

PubMed2000

The incremental prognostic importance of body fat adjusted peak oxygen consumption in chronic heart failure.

OBJECTIVES: We sought to assess whether the adjustment of peak oxygen consumption (PkVO2) to lean body mass would yield a more accurate discriminator of outcomes in the chronic heart failure population. BACKGROUND: Peak oxygen consumption is traditionally used to risk stratify patients with congestive heart failure (CHF) and to time cardiac transplantation. There is, however, considerable variability in body fat content, which represents metabolically inactive mass. METHODS: In 225 consecutive patients with CHF, the percentage of body fat was determined by the sum of skinfolds technique. All underwent CPX using a ramping treadmill protocol. Mean follow-up duration was 18.9+/-11.3 months. RESULTS: There were 14 cardiovascular deaths and 15 transplants. Peak oxygen consumption lean, both as a continuous variable and using a cutoff of < or =19 ml/kg/min, was a better predictor of outcome than unadjusted PkVO2 (p = 0.003 vs. 0.027 for the continuous variables and p = 0.0006 vs. 0.055 for < or =19 ml/kg/min and < or =14 ml/kg/min unadjusted body weight, respectively). Using partial correlation index R statistics, the Cox model using PkVO2 lean < or =19 ml/kg/min, in addition to age and etiology of CHF as covariates, yielded the strongest predictive relationship to the combined end point (chi-square value 24.32). Especially in the obese patients and in women, there was considerably better correlation of PkVO2 lean with outcome than the unadjusted PkVO2. CONCLUSIONS: The adjustment of PkVO2 to lean body mass increases the prognostic value of cardiopulmonary stress testing in the evaluation of patients with chronic heart failure. The use of <19 ml O2/kg of lean body mass/min as a cutoff in PkVO2 should be used for timing transplantation, particularly in women and the obese.

Adipose Tissue↗

PubMed1999

The prognostic implications of outpatient diuretic dose in heart failure.

In 111 patients with left ventricular ejection fraction < or =30% who required hospitalization for heart failure, we examined the association between outpatient dose of diuretic agents and all-cause mortality. In comparison to patients who were not on treatment with diuretics prior to hospitalization, patients being treated with 'low' doses of diuretics (<80 mg/day of furosemide) and those being treated with 'high' doses of diuretics (> or =80 mg/day of furosemide) were more likely to die during follow-up after adjustment for other clinical parameters (adjusted relative risks, RR, 3.1 and 4.6).

Aged↗

PubMed1999

The independent effects of left ventricular ejection fraction on short-term outcomes and resource utilization following hospitalization for heart failure.

BACKGROUND: While depressed left ventricular ejection fraction is clearly associated with poor long-term outcome in heart failure (HF), the effect of ejection fraction on short-term outcomes and resource utilization following hospitalization for HF remains unclear. HYPOTHESIS: We evaluated the independent effect of depressed ejection fraction (< or = 40%) on short-term outcomes and resource utilization following hospitalization for HF. METHODS: The study population included 443 consecutive patients hospitalized for DRG 127 (HF and shock) with known ejection fraction. For each patient, we assessed the hospitalization cost (1995 US$), length of stay, in-hospital mortality, 30-day mortality, and 30-day readmission rates. RESULTS: Despite similar disease severity at admission, patients with ejection fraction < or = 40% (Group 1) had longer length of stay (4.0 vs. 3.7 days; p = 0.03), a tendency toward higher hospitalization cost ($3,054 vs. $2,770; p = 0.08), more readmissions for any cause (0.4 vs. 0.3; p = 0.05) and for HF (0.2 vs. 0.1; p = 0.01), but similar in-hospital (2.5 vs. 2.6%) and 30-day mortality (4.0 vs. 4.6%) compared with patients with ejection fraction > 40% (Group 2). In multivariate analyses, Group 1 patients were more likely to have higher than median hospitalization cost [odds ratio (OR) = 1.98; 95% confidence intervals (CI) = 1.02-3.91] and longer than median hospital stay (OR = 1.68; CI = 1.08-3.91); they were also more likely to be readmitted for any cause (OR = 2.07; CI = 1.15-3.78) or for HF (OR = 5.71; CI = 1.64-21.94), and they tended to have a higher 30-day incidence of death or readmission (OR = 1.65; CI = 0.96-2.84). CONCLUSIONS: Depressed left ventricular ejection fraction is associated with higher resource utilization and readmission rates following hospitalization for HF. Greater focus on patients with depressed ejection fraction may increase cost savings from HF disease management programs.

Aged↗

PubMed1999

Primary stenting in acute myocardial infarction: influence of diabetes mellitus in angiographic results and clinical outcome.

BACKGROUND: The outcome of patients with diabetes after myocardial infarction (MI) has traditionally been worse than in their nondiabetic counterparts before and during the thrombolytic therapy era. Whether the fate of patients with diabetes might improve with mechanical intervention, particularly with primary stenting, has not previously been studied. METHODS: We compared the angiographic and clinical outcome of 76 nondiabetic patients (aged 61 +/- 14 years; 66% male) and 28 patients with diabetes (aged 65 +/- 12 years; 64% male) consecutively treated with primary stenting for acute MI. Coronary Thrombolysis In Myocardial Infarction grade 3 flow was restored in 96% of diabetic and 97% of nondiabetic patients. RESULTS: Angiographic results after stent deployment were similar in the 2 groups. At 1-month follow-up, all patients in both groups were alive. Patients with diabetes had a much higher incidence of stent thrombosis (18% vs 1%; P =.003), which accounted for the majority of the major cardiac events at 1 month (21% vs 4%; P =.009). At a mean follow-up of 315 +/- 13 days, 99% of nondiabetic and 89% of patients with diabetes were alive (P =.04). Overall freedom from a major cardiac event (death, MI, target vessel revascularization) at 315 +/- 13 day follow-up was 88% for nondiabetics and 54% for patients with diabetes (P =.0003). By multivariate analysis, diabetes mellitus was the most important predictor for development of 1-month (RR 9.89; 95% confidence interval, 1.6-30) and late major cardiovascular events (RR 8.39; 95% confidence interval, 2.93-24). CONCLUSIONS: Primary stenting in acute MI is highly effective in restoring immediate TIMI 3 coronary flow in nondiabetic patients and patients with diabetes. This procedure may improve benefit in terms of mortality rate to both groups, particularly in patients with diabetes, compared with previous reports with thrombolytic therapy. Nevertheless, stent thrombosis and major cardiovascular events at 1 month and late follow-up are more frequent in patients with diabetes.

Aged↗

PubMed1998

Efferent projection from the rostral ventrolateral medulla to the area postrema in rats.

The rostral ventrolateral medulla (RVLM) is a region of the brain primarily involved in cardiovascular control. It receives information from several areas of the brainstem, among which the area postrema (AP) and the nucleus of the solitary tract (NTS). The medial subnuclei of the solitary tract (TS) project towards the RVLM, providing cardiopulmonary information, and the AP serves information about circulatory hormones. Although the efferent pathways are well known, it is not the case for the connections from the RVLM towards the AP and the NTS. The present study was designed to examine the efferent connections from the RVLM onto the dorsal structures of the medulla: quantitatively by means of anatomical techniques, and functionally by means of electrophysiological techniques. Morphologically, Biocytin or Biotinylated dextran amine microinjections into the RVLM were followed by labelling of many fibres running towards the bulbar dorsomedial structures, with some pathways lying in the AP itself, or located in its caudal vicinity. Conversely, when microinjections of Fast Blue (FB) were made into the AP, FB-labelled cells could be observed within the RVLM. Electrophysiologically, single shock stimulation carried on AP allowed identification of axonal fibres issuing from somata located into the cardiovascular neuronal pool in the RVLM. From these results, we can assume: (1) the existence of dense efferent projection from RVLM to aspects of the dorsal vagal complex, including the AP and, among this dense projection, (2) the existence of some fibres terminating in, or crossing through the AP, and identified as conveying baroreceptor-related information, in the rat.

Amidines↗

PubMed1998

Coronary hemodynamics in aging spontaneously hypertensive and normotensive Wistar-Kyoto rats.

OBJECTIVE: To delineate hypertension-related and age-related changes in coronary hemodynamics and to assess the role of myocardial (i.e. left ventricular) hypertrophy and cardiac fibrosis in inducing progressive deterioration of coronary flow reserve associated both with hypertension and with aging. METHODS: Systemic and coronary hemodynamics (using radionuclide-labeled microspheres), right ventricular, left ventricular, and aortic mass indexes, and ventricular hydroxyproline concentrations (an estimate of collagen) in normotensive Wistar-Kyoto and spontaneously hypertensive rats aged 22, 35, and 65 weeks were determined. RESULTS: Spontaneously hypertensive rats of all ages had greater left ventricular and aortic masses, greater collagen concentrations in both ventricles, a lower coronary flow reserve, and greater minimal coronary vascular resistance after administration of dipyridamole than did Wistar-Kyoto rats. Despite spontaneously hypertensive rats having only left ventricular hypertrophy, coronary hemodynamics were impaired to the same extent in both ventricles. Progressive increases in myocardial collagen concentration, decreases in coronary flow reserve, and increases in minimal coronary vascular resistance were observed in rats of both strains with aging. A positive correlation and linear regression between myocardial collagen concentration and minimal vascular resistance were found for both ventricles of rats of both strains. CONCLUSIONS: Both aging and hypertension adversely affected the coronary circulation; furthermore, these effects appeared to be additive. Cardiac fibrosis, but not hypertrophy, might play a role in progressive deterioration of coronary hemodynamics in aging and hypertension and could provide an explanation for the diastolic dysfunction encountered clinically in older patients with hypertension.

Aging↗

PubMed1997

Cardiovascular effects of a trandolapril/verapamil combination in patients with mild to moderate essential hypertension.

The cardiovascular effects of a combination of trandolapril and verapamil were evaluated in 14 patients with mild to moderate essential hypertension. This combination therapy decreased arterial pressure mainly through a decrease in total peripheral resistance without causing an increase in heart rate or cardiac output: left ventricular mass was significantly reduced, cardiac systolic function improved, and plasma volume and renal blood flow remained unchanged.

Aged↗

PubMed1997

Disparate effects of ACE-inhibitors and calcium antagonists on left ventricular structure and function in essential hypertension.

The present study was designed to compare the effects of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists-the two drug classes thought to be most effective in reducing left ventricular hypertrophy-on arterial pressure, left ventricular structure and function in patients with essential hypertension. After a placebo period of 4 weeks, a population of 96 patients were treated either with one of five different ACE inhibitors or one of six different calcium antagonists. Cardiac structure and function was assessed by 2D-guided M-mode echocardiography. Whereas both drug classes lowered arterial pressure to the same extent, ACE inhibitors had a more pronounced effect on posterior and septal wall thickness and left ventricular mass index than calcium antagonists. Diastolic function, as measured by peak filling rate and duration of rapid filling, improved in both treatment groups to the same extent. However, systolic performance, as assessed by midwall fractional fibre shortening, was significantly improved by ACE inhibitors only. Myocardial contractility (end-systolic wall stress/end-systolic volume index) showed no significant change in the ACE inhibitor group but decreased after treatment with calcium antagonists. We conclude that both calcium antagonists and ACE inhibitors lower arterial pressure and increase left ventricular filling to the same extent. However, compared with calcium antagonists, ACE inhibitors had a more pronounced effect on left ventricular mass and improved systolic ventricular performance in patients with essential hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

ACE inhibition reduces left ventricular mass independent of pressure without affecting coronary flow and flow reserve in spontaneously hypertensive rats.

Systemic and regional (including coronary) hemodynamics were studied in spontaneously hypertensive and normotensive Wistar Kyoto rats after 3 weeks of treatment with one of the three doses of the angiotensin converting enzyme inhibitor, ramipril. The effects of respective treatments on cardiovascular mass and systemic, coronary, and regional hemodynamics (at rest, during maximal treadmill exercise, and during dipyridamole infusion) then were evaluated in conscious rats using radiomicrosphere techniques. Low-dose ramipril (10 micrograms/kg/day by gavage) neither decreased arterial pressure nor reduced cardiac mass. However, medium (100 micrograms/kg/day) and high (1 mg/kg/day) doses reduced total cardiac and left ventricular masses to the same extent in spontaneously hypertensive rats, despite a much greater fall in arterial pressure with a high dose. Resting cardiac index, and myocardial and all other organ blood flows remained unchanged in both strains. When compared with Wistar Kyoto rats, coronary circulation was impaired in untreated spontaneously hypertensive rats (ie, reduced coronary flow and flow reserve and increased minimal coronary vascular resistance during dipyridamole infusion). This remained unchanged by ramipril. Furthermore, significant (and comparable) increases in cardiac index and myocardial blood flow and decreases in coronary vascular resistance were produced by maximal treadmill exercise in both strains. This also was unaffected by ramipril. These data showed that angiotensin converting enzyme inhibition with suboptimal and optimal hypotensive doses of ramipril reversed left ventricular hypertrophy in spontaneously hypertensive rats, but coronary flow, flow reserve, and minimal coronary vascular resistance remained unchanged despite left ventricular hypertrophy reversal.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Enalapril and losartan reduced cardiac mass and improved coronary hemodynamics in SHR.

Among the multiple mechanisms postulated for the increased risk of hypertensive left ventricular hypertrophy (LVH), coronary hemodynamic alterations remain a strong possibility. This study was designed to compare the effects of treatment with an ACE inhibitor (enalapril) and an angiotensin AT1 receptor antagonist (losartan) on systemic and coronary hemodynamics and to determine whether the combination of these two renin-angiotensin system (RAS) inhibitor would be as or more effective in reducing mean arterial pressure (MAP), left ventricular (LV) mass, and improving coronary hemodynamics than either regimen alone. Thus, 23 week old spontaneously hypertensive rats (SHR) were treated (12 weeks) with tap water (C), enalapril (30 mg.kg-1.d-1), losartan (30 mg.kg-1.d-1), or their combination (15 mg.kg-1.d-1). Age-matched Wistar-Kyoto (WKY) rats served as normotensive controls. After 12 weeks, systemic and coronary hemodynamics were determined (15 microns radiolabeled microspheres) at baseline, during maximal treadmill exercise, and during maximal dilation (dipyridamole). Enalapril and losartan equally reduced MAP and LV mass in association with a decreased total peripheral resistance. The RAS combination reduced MAP and LV mass more than either drug alone. Resting cardiac index and coronary blood flow (CBF) per unit of LV mass did not differ among the groups. Although enalapril did not improve coronary flow reserve (CFR), it diminished minimal coronary vascular resistance (MCVR); losartan improved both. However, the combination was more effective than either agent alone, reaching values close to normotensive WKY controls. In conclusion, these data demonstrated significantly impaired maximal CBF, CFR, and MCVR in untreated SHR, but losartan alone and in combination with enalapril improved systemic and coronary hemodynamics more than enalapril alone.

Angiotensin Receptor Antagonists↗

PubMed1996

Is maternal serum creatine kinase actually a marker for early diagnosis of ectopic pregnancy?

OBJECTIVE: Our purpose was to investigate whether serum creatine kinase (CK) levels could be used as an early marker of ectopic pregnancy. Student's t-test was used for statistical analysis. STUDY DESIGN: In a prospective study we therefore measured serum progesterone, beta hCG and CK levels in 30 women with ectopic pregnancies, 30 women with ongoing pregnancies and 30 women with missed abortion. RESULTS: The mean serum CK concentration for patients with an ectopic pregnancy, ongoing pregnancy, and the women with missed abortion was 81.4 +/- 66.2, 81.5 +/- 40.3, 84.8 +/- 49.3, respectively. No relationship was found between CK level and the location of the pregnancy. CONCLUSION: Conversely to the first report of Lavie et al. (Am J Obstet Gynecol 1993; 169: 1149), our data suggest that serum CK level is not discriminative in the early diagnosis of tubal pregnancy.

Abortion, Missed↗

PubMed1996

Losartan reduces cardiac mass and improves coronary flow reserve in the spontaneously hypertensive rat.

OBJECTIVES: To evaluate the effects of losartan administration on cardiovascular mass, systemic and coronary hemodynamics (rest, maximal treadmill exercise, and dipyridamole infusion) and on resting regional hemodynamics in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. RESULTS: Although losartan administration (two doses: 10 and 30 mg/kg per day for 3 weeks by gavage) reduced left ventricular mass at the higher dose in WKY rats and with both doses in SHR, only the higher dose reduced arterial pressure in SHR. Losartan administration did not affect cardiac index, myocardial or other organ flows (radiomicrosphere) at rest in both strains. Significant increases in cardiac index and coronary flow and decreases in coronary vascular resistance were observed during exercise in both strains and these responses were not affected by losartan administration. Compared with those in WKY rats, coronary flow and flow reserve (dipyridamole) were decreased and minimal coronary vascular resistance was increased in untreated SHR. Administration of a higher losartan dose increased coronary flow reserve and decreased minimal coronary vascular resistance (measured during dipyridamole infusion) in SHR. CONCLUSIONS: These data demonstrated that losartan administration reduced left ventricular mass, a response that did not seem to be solely dependent on afterload. Furthermore, cardiac and stroke indices and coronary flow reserve were not changed in SHR during maximal treadmill exercise after hypertrophy reversal, even with the lower dose of losartan and when the ventricular afterload was similar to that of untreated SHR.

Angiotensin II↗

PubMed1995

Early genes induction in spontaneously hypertensive rats left ventricle with angiotensin-converting enzyme inhibitors but not hydralazine.

Spontaneously hypertensive rats were given an angiotensin-converting enzyme (ACE) inhibitor (benazepril or quinapril) or hydralazine and were left for up to 6 hr. To examine whether administration of antihypertensive agents affects expression of immediate early genes in left ventricular myocardium, groups of rats were sacrificed at 1, 3, and 6 hr after dosing; total RNA was extracted from left ventricular tissue and analyzed by blot hybridization technique using labeled probes for c-myc, c-fos, and GAPDH mRNA. All three antihypertensive agents reduced pressure similarly, and treatment with the two ACE inhibitors increased c-fos and c-myc mRNA expression in left ventriculum. By contrast, hydralazine did not increase steady-state mRNA expression of either proto-oncogene. Thus, in parallel with the pressure fall, acute administration of the ACE inhibitors induced expression of c-fos and c-myc mRNAs in the left ventricle. Since the equidepressor dose of hydralazine did not affect expression of these proto-oncogenes, this effect of ACE inhibitors is independent of their hemodynamic action.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Role of fatty acids in signal transduction: modulators and messengers.

Many of the steps involved in signal transduction are regulated positively or negatively by fatty acids (FA) per se. FA have been shown to act both as modulators and messengers, particularly of signals triggered at the level of cell membranes. Enzymes and proteins of the cyclic AMP and the protein kinase C signalling pathways and those involving ion fluxes and mobilization are both activated and/or inhibited by FA. FA can also participate in a feedback control mechanism since phospholipases are themselves modulated by FA. FA, particularly arachidonic acid liberated from membrane phospholipids, are also second messengers in signal transduction, and a good example is the activation of protein kinase C by FA. FA play an important role in regulating the transmission of signals from the extracellular environment by acting as modulators and messengers within the complex intracellular network of relays.

Animals↗

PubMed1991

Effect of anticoagulants in vitro on the viability of lymphocytes and content of free fatty acids in plasma.

These authors attempted to test the effect of anticoagulants on lymphocytes viability by reproducing the procedure used for lymphocyte isolation for various immunologic tests in which blood specimens are allowed to stay at room temperature for 2 h before lymphocytes are isolated. Blood was obtained with three different anticoagulants i.e. heparin, citrate, and CPDA (citrate, phosphate, dextrose, and adenine). Plasma was lyophilized and extracted with ethanol. Dried ethanol extracts were suspended in medium (RPMI 1640 + 10% fetal bovine serum) and incubated with a lymphocyte cell line (MOLT-4). After 24 h of incubation the viability of cells was examined. The following death rates of the cells were observed: heparin -63 +/- 4.6% (mean +/- SEM), citrate -27 +/- 6.7%, and CPDA 6.2 +/- 0.6% (P less than 0.0005). A significant correlation was found between these results and changes in the concentrations of free fatty acids in the extracts. These results emphasize the importance of choosing the right anticoagulant when the viability of lymphocytes is obligatory.

Adenine↗