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Faiez Zannad

Publications and source records attributed to Faiez Zannad.

At least 37 records · Page 2Linked to original sources
PubMed2006

Clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: The EFICA study.

BACKGROUND: Little is known about the epidemiology of acute decompensated heart failure (ADHF) in patients admitted to intensive and coronary care units (ICU/CCU). Observational data may improve disease management and guide the design of clinical trials. AIMS: EFICA is an observational study of the clinical profile, management and survival of ADHF patients admitted to ICU/CCU. METHODS: The study included 599 patients admitted to 60 ICU/CCUs across France. Relevant data was recorded during hospitalisation. Survival was assessed at 4 weeks and 1 year. RESULTS: The main cause of ADHF was ischaemic heart disease (61%); 29% of patients had cardiogenic shock. Mortality was 27.4% at 4 weeks and 46.5% at 1 year, increasing to 43.2% and 62.5%, respectively, when including pre-admission deaths. Shock patients had the highest [57.8% vs. 15.2% without shock (p < 0.001)] and patients with hypertension and pulmonary oedema had the lowest 4-week mortality: (7%). Pre-admission NYHA class III-IV heart failure, not initial clinical presentation, influenced 1-year mortality. CONCLUSION: ADHF is a heterogeneous syndrome. Based on initial clinical presentation, three entities with distinct features and outcome may be described: cardiogenic shock, pulmonary oedema with hypertension, and 'decompensated' chronic heart failure. This should be taken into account in future observational studies, guidelines and clinical trials.

Aged↗
PubMed2006

Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction.

AIMS: To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). METHODS: The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and/or LVSD. AF was assessed at presentation and at randomization (median 4.9 days after symptom onset). Primary outcomes were risk of death and major CV events 3 years following acute MI. RESULTS: A total of 1812 with current AF (AF between presentation and randomization), 339 patients with prior AF (history of AF without current AF), and 12,509 without AF were enrolled. Patients with AF were older; had more prior HF, angina, and MI, and received beta-blockers and thrombolytics less often than those without AF. Three-year mortality estimates were 20% in those without AF, 37% with current AF, and 38% with prior AF. Compared with patients without AF, the multivariable adjusted HR of death was 1.25 (1.03-1.52; p=0.03) for prior AF and 1.32 (1.20-1.45; p<0.0001) for current AF. HR for major CV events was 1.15 (0.98-1.35; p=0.08) and 1.21 (1.12-1.31; p<0.0001). CONCLUSION: AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD.

Acute Disease↗
PubMed2006

Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction <or=30%.

AIMS: Because of the prognostic importance of LV dysfunction following an AMI and the increasing use of electrical and/or mechanical interventions in patients with LV systolic dysfunction, this retrospective analysis of EPHESUS patients with LVEF <or=30% at baseline was conducted to determine the value of eplerenone in this setting. METHODS AND RESULTS: In EPHESUS, 6,632 patients with LVEF <or=40% and clinical heart failure (HF) post-AMI who were receiving standard therapy were randomized to eplerenone 25 mg/day titrated to 50 mg/day or placebo for a mean follow-up of 16 months. Treatment with eplerenone in the subgroup of patients with LVEF <or=30% (N=2106) resulted in relative risk reductions of 21% versus placebo in both all-cause mortality (P=0.012) and cardiovascular (CV) mortality/CV hospitalization (P=0.001), and 23% for CV mortality (P=0.008). The relative risk of sudden cardiac death (SCD) was reduced 33% (P=0.01) and HF mortality/HF hospitalization was reduced 25% (P=0.005) with eplerenone compared with placebo. Within 30 days of randomization, eplerenone resulted in relative risk reductions of 43% for all-cause mortality (P=0.002), 29% for CV mortality/CV hospitalization (P=0.006), and 58% for SCD (P=0.008). CONCLUSIONS: Treatment with eplerenone plus standard therapy in patients with post-AMI HF and LVEF <or=30% provided significant incremental benefits in reducing both early and late mortality and morbidity.

Adult↗
PubMed2006

The challenge of acute decompensated heart failure.

Acute heart failure syndromes (AHFS) is a broad spectrum of heterogeneous conditions including pulmonary oedema, hypertensive crisis, worsening exacerbated CHF and cardiogenic shock. HF hospitalizations have steadily risen with more than one million in 2004 in the United States and a similar number has been reported in Europe. Each year heart failure accounts for 6.5 million days spent in hospital in the USA and 1.4 million days in France. Mortality data are derived from registries or clinical trials. Registry data in patients admitted to general or cardiology wards such as in Euroheart Failure Survey and ADHERE provide a far more optimistic picture compared with data from consecutive unselected patients in the most acute situation. such as in EFICA. Four-week mortality was higher than 25% in this case. A great pathophysiologic understanding of the different features of the various AHFS is needed in order to identify targets for therapy and research. This includes hemodynamics, the role of myocardial injury, neurohormonal and cytokine abnormalities and the cardiorenal syndromes. So far, very little progress has been made in developing new, effective therapies and implementing management guidelines in this patient population. Future clinical trial endpoints should be better designed and tailored to the various pathophysiological conditions of this complex syndrome. The goal of AHFS therapy is not only to prevent disease progression but also to have a beneficial effect on an acute event that exacerbates disease progression. A combined endpoint assessing survival and rehospitalisation rates is becoming increasingly popular for acute therapies. Specific trials may also need to be designed according to the time of access to the patient.

Acute Disease↗
PubMed2006

Metabolic syndrome, new onset diabetes, and new end points in cardiovascular trials.

Metabolic syndrome affects approximately 44% of the US population over the age of 50 years. Although conflicting definitions exist, the syndrome is typically characterized by abdominal obesity, dyslipidemia, hypertension, and insulin resistance. Thus, it is a major risk factor for both coronary heart disease and type 2 diabetes. Furthermore, the risk of cardiovascular (CV) death is significantly increased in patients with diabetes and/or the metabolic syndrome. Although very few studies exist in patients with the metabolic syndrome, lifestyle changes and drug intervention targeted at the individual components have been shown to reduce the risk of developing diabetes and the incidence of CV disease in high-risk patients. Because many of the conventional antihypertensive drugs may affect the development of new onset diabetes, both positively and negatively, the choice of therapy is particularly important in this population. However, the long-term clinical trials to date have either not included new onset diabetes as a protocol end point or used various different criteria, making comparisons difficult. This review assesses the need for future research into metabolic syndrome and discusses whether clinical surrogates for CV end points, such as new onset diabetes, should be included in clinical trials of new drugs, new regimens, or new indications.

Animals↗
PubMed2005

Retinoic acid amplifies the host immune response to LPS through increased T lymphocytes number and LPS binding protein expression.

Vitamin A deficiency is associated with increased susceptibility to infection but the effects of Vitamin A supplementation on host response to pathogens are controversial. This study investigated the mechanisms by which all-trans retinoic acid (atRA) modulates the host immune response in an experimental model of Vitamin A supplementation before and after challenge with LPS in rats. We show here that a supplementation with five daily injections of 10mg/kg atRA increased the number of T lymphocytes in the peripheral blood. In addition, we show that atRA increased the expression of the LPS binding protein (LBP), a component of the LPS recognition system. The retinoic acid receptor (RAR)alpha agonist Ro 4060-55 but not the pan-retinoid X receptors (RXRs) agonist Ro 2573-86 mimicked the effects of atRA on LBP expression suggesting that atRA enhances LBP expression through a RARalpha-mediated pathway. In order to investigate the significance of increased LBP expression we challenged atRA-supplemented rats with the Gram-positive bacteria Listeria monocytogenes (LM) that activates the immune response independently from LBP. In sharp contrast to our previous observations that atRA supplementation enhances IFN-gamma expression and NOS2 pathway activation in LPS-challenged rats [Devaux, Y., Grosjean, S., Seguin, C., David, C., Dousset, B., Zannad, F., Meistelman, C., de Talancé, N., Mertes, P.M., Ungureanu-Longrois, D., 2000. Retinoic acid and host-pathogen interactions: effects on inducible nitric oxide synthase in vivo. Am. J. Physiol. 279, E1045-E1053], atRA did not increase the LM-induced IFN-gamma expression and NOS2 pathway activation. Overall, these data demonstrate that although atRA induces a "priming" of the immune system characterized by increased T lymphocytes number and LBP expression, the profile of the immune response depends on the inflammatory/infectious stimulus. These results could explain why Vitamin A supplementation could have beneficial/neutral or deleterious effects according to the identity of the infectious pathogen.

Acute-Phase Proteins↗
PubMed2005

Mortality and morbidity remain high despite captopril and/or Valsartan therapy in elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction: results from the Valsartan in Acute Myocardial Infarction Trial (VALIANT).

BACKGROUND: The elderly constitute an increasing proportion of acute myocardial infarction patients and have disproportionately high mortality and morbidity. Those with heart failure or impaired left ventricular left ventricular function after acute myocardial infarction have high complication and mortality rates. Little is known about outcomes with contemporary therapies in these patients. METHODS AND RESULTS: The Valsartan in Acute Myocardial Infarction Trial (VALIANT) randomized 14,703 patients with heart failure and/or left ventricular ejection fraction <40% to receive captopril, valsartan, or both. Mortality and a composite end point, including cardiovascular mortality, readmission for heart failure, reinfarction, stroke, and resuscitated cardiac arrest, were compared for the age groups of <65 (n=6988), 65 to 74 (n=4555), 75 to 84 (n=2777), and > or =85 (n=383) years. With increasing age, 3-year mortality almost quadrupled (13.4%, 26.3%, 36.0%, and 52.1%, respectively), composite end-point events more than doubled (25.2%, 41.0%, 52.3%, and 66.8%), and hospital admissions for heart failure almost tripled (12.0%, 23.1%, 31.3%, and 35.4%). Outcomes did not differ between the 3 study treatments in any age group. Adverse events associated with captopril and valsartan were more common in the elderly and in patients receiving combination therapy. With increasing age, use of aspirin, beta-blockers, and statins declined, and use of digoxin, calcium-channel blockers, and non-potassium-sparing diuretics increased. On 3-year multivariable analysis, each 10-year age increase was associated with a hazard ratio of 1.49 (95% CI, 1.426 to 1.557; P<0.0001) for mortality and an odds ratio of 1.38 (95% CI, 1.31 to 1.46; P<0.0001) for readmission with heart failure. CONCLUSIONS: Outcomes remained poor in elderly patients with heart failure and/or impaired left ventricular systolic function after acute myocardial infarction, although most received beta-blockers and all received an ACE inhibitor and/or an angiotensin receptor blocker. Better therapies and increased use of aspirin, beta-blockers, and statins are needed in this important and increasing patient group.

Age Factors↗
PubMed2005

Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes.

AIMS: Extracellular matrix (ECM) turnover is a major determinant of diastolic dysfunction and pumping capacity, thus potentially contributing to the progression of congestive heart failure (CHF). Patients with both arterial hypertension and diabetes have a high risk of heart failure. Whether these patients have changes in cardiac ECM has not been studied previously. Our objective was to compare blood markers of collagen turnover among patients with CHF, patients with hypertension and type II diabetes (HD), and healthy individuals. METHODS AND RESULTS: Measurements were performed in 239 CHF patients; 64 HD patients and 92 healthy subjects. We showed by adjusted ANOVA that PIIINP levels were significantly higher in CHF and HD patients than in controls, and higher in CHF patients than in HD patients. MMP1 levels were significantly lower in CHF and HD patients than in controls. Collagen type I markers (PICP and PINP) were not influenced by CHF but were lower in HD patients as compared to controls (p<0.05 for all comparisons). CONCLUSION: In heart failure, markers of cardiac collagen synthesis are increased and markers of degradation are decreased, potentially contributing to cardiac fibrosis and thus to poor outcome. Changes in collagen turnover may also occur early in the disease process in high-risk patients before heart failure is clinically detectable.

Aged↗
PubMed2005

Public awareness of heart failure in Europe: first results from SHAPE.

AIMS: Appropriate heart failure (HF) care and adequate resourcing require recognition of its clinical, social, and economic importance by the general public besides healthcare authorities and providers. The extent of public awareness in Europe is not known. METHODS AND RESULTS: A total of 7958 subjects were randomly selected from nine European countries (minimum 100/group per country). Each completed a 32-question survey on HF covering recognition, impact on health, comparative prevalence and severity, treatment, and costs. Although 86% of respondents had heard of HF, only 3% could correctly identify HF from a description of typical symptoms and signs, 31% correctly identified angina, and 51% identified transient ischaemic attack/stroke. Only 29% thought that HF signs and symptoms indicate a 'severe' condition. Most thought that HF patients should reduce all physical activity and 34% believed HF a normal consequence of ageing. Sixty-seven per cent thought that HF patients live longer than cancer patients. Only 9% believed that HF leads to greater healthcare expenditure than cancer, HIV, or diabetes. Overall, responses were comparable between countries. CONCLUSION: In Europe, community awareness of HF is low. Therefore, the general public is unlikely to demand appropriate measures by healthcare authorities and providers. A better understanding of HF could improve its prevention and management. Strategies to educate the public about HF are needed.

Adult↗
PubMed2005

Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure.

OBJECTIVES: This study sought to assess the impact of the selective aldosterone blocker eplerenone on mortality 30 days after randomization in patients after acute myocardial infarction (AMI) with a left ventricular ejection fraction (LVEF) < or =40% and clinical signs of heart failure. BACKGROUND: In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone reduced all-cause mortality by 15% (p = 0.008) over a mean follow-up of 16 months when used with standard therapy in patients after AMI with an LVEF < or =40% and clinical signs of heart failure. METHODS: We analyzed the effect of eplerenone 25 mg/day initiated 3 to 14 days after AMI (mean, 7.3 days) on the co-primary end points of time to death from any cause and the composite end point of time to death from cardiovascular (CV) causes or hospitalization for CV events, and the secondary end points of CV mortality, sudden cardiac death, and fatal/nonfatal hospitalization for heart failure, after 30 days of therapy in the EPHESUS trial. RESULTS: At 30 days after randomization, eplerenone reduced the risk of all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone and placebo-treated patients, respectively; p = 0.004) and reduced the risk of CV mortality/CV hospitalization by 13% (8.6% vs. 9.9% in eplerenone and placebo-treated patients, respectively; p = 0.074). Eplerenone also reduced the risk of CV mortality by 32% (p = 0.003) and the risk of sudden cardiac death by 37% (p = 0.051). CONCLUSIONS: Eplerenone 25 mg/day significantly reduced all-cause mortality 30 days after randomization (when initiated at a mean of 7.3 days after AMI) in addition to conventional therapy in patients with an LVEF < or =40% and signs of heart failure. Based on its early survival benefit, eplerenone should be administered in the hospital after AMI.

Aged↗
PubMed2005

Effect of rosuvastatin on outcomes in chronic haemodialysis patients - design and rationale of the AURORA study.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis. METHODS: More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event. CONCLUSION: Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population.

Journal Article↗
PubMed2005

Effect of MR blockade on collagen formation and cardiovascular disease with a specific emphasis on heart failure.

Collagen is the major extracellular matrix protein in the heart and represents a crucial target for anti-remodeling and cardioprotective therapy. Collagen quantity and quality have been shown to be regulated under various physiological and pathologic conditions. Excessive deposition of collagen, leading to cardiac fibrosis, is a major determinant of cardiac dysfunction and arrhythmogenecity associated with sudden death. Serological markers of collagen turnover were proven as a noninvasive reliable tool for monitoring from a distance cardiac tissue repair and fibrosis, both in experimental and clinical conditions. Some markers of collagen synthesis and degradation were shown to have a prognostic significance in myocardial infarction, cardiomyopathy and heart failure, and were reported as independent predictors of mortality. Aldosterone represents the end-product of the renin angiotensin aldosterone system and may play a role in cardiac collagen deposition independent of its effect on blood pressure. Production of aldosterone is mainly regulated by angiotensin II and is activated in the failing human ventricle in proportion to heart failure severity. Circulating or locally produced aldosterone stimulates fibrillar collagen accumulation in the heart directly via mineralocorticoid receptors or, indirectly, modifying angiotensine II receptors number and/or function. The use of mineralocorticoid receptor antagonists counters collagen deposition, even when used on top of classical RAAS inhibitors, such as ACE inhibitors and angiotensine II receptor blockers. There is now accumulating evidence from experimental and clinical studies showing antifibrotic and cardioprotective effect for aldosterone antagonists, spironolactone and eplerenone. In chronic heart failure and post myocardial infarction patients, aldosterone receptor blockade benefit was associated with decreased serum levels of collagen synthesis marker PIIINP (procollagen type III amino-terminal peptide), without affecting collagen degradation. Understanding various autocrine/paracrine mechanisms involved in extracellular matrix remodeling in heart failure represents a major challenge, essential for developing new cardioreparative and cardioprotective strategies.

Aldosterone↗
PubMed2005

Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the Efficacy of Vasopressin antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST).

BACKGROUND: Hospitalizations for worsening heart failure due to fluid overload (congestion) are common. Agents that treat congestion without causing electrolyte abnormalities or worsening renal function are needed. Tolvaptan is an oral vasopressin (V 2 ) antagonist that decreases body weight and increases urine volume without inducing renal dysfunction or hypokalemia. The Efficacy of Vasopressin antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial is evaluating mortality, morbidity, and patient-assessed global clinical status in patients treated with tolvaptan compared with standard care. METHODS AND RESULTS: Patients are eligible for inclusion if they have a reduced left ventricular ejection fraction and are hospitalized for worsening heart failure with evidence of systemic congestion. Patients are randomized 1:1 to tolvaptan 30 mg/day or matching placebo for a minimum of 60 days. Time to all-cause mortality and time to cardiovascular mortality or heart failure hospitalization are the coprimary end points. Patient-assessed global clinical status and quality of life are also evaluated. EVEREST will be continued until 1065 deaths occur. As of April 18, 2005, 2260 patients have been enrolled. CONCLUSION: Tolvaptan has been shown to reduce body weight in patients with worsening heart failure without inducing renal dysfunction or causing hypokalemia. The results of EVEREST will determine whether these effects translate into improved clinical outcomes.

Antidiuretic Hormone Receptor Antagonists↗
PubMed2005

Impaired response of cardiac autonomic nervous system to glucose load in severe obesity.

OBJECTIVE: This study was undertaken to further analyze the response of the cardiovascular autonomic nervous system (ANS) to changes in plasma insulin concentration induced by an oral glucose load. We hypothesized that, as a consequence of insulin resistance, an inability of insulin to increase the sympathetic modulation of heart rate (HR) and blood pressure (BP) would be observed in normotensive obese patients. METHODS: We used spectral analysis to measure simultaneously the short-term variability of HR and BP in 23 never-obese subjects and in 70 normotensive overweight or obese patients subdivided into 3 subgroups: (1) overweight group (body mass index [BMI], 25-29.9 kg/m 2 ), n = 23; (2) class I-II obese group (BMI, 30-39.9 kg/m 2 ), n = 23; (3) class III obese group (BMI, > or =40 kg/m 2 ), n = 23. RESULTS: Oral glucose ingestion and the related increased insulinemia caused significant changes in the indices of sympathetic modulation (low-frequency [LF] power and LF/high-frequency ratio) of both HR and BP in normal weight, overweight, and obese subjects. However, the LF increments gradually decreased with the BMI classes, suggesting that sympathetic nervous system modulation in these subjects may be insulin-resistant. CONCLUSION: Obesity could develop resistance to the sympatho-excitatory effects of insulin that might play a role in the etiology of obesity. Spectral analysis of BP and HR can be used in research to evaluate the reactivity of the sympathetic nervous system in a manner that represents another feature of the obesity/insulin-resistance syndrome.

Adult↗
PubMed2005

Angiotensin receptor blockers: therapeutic targets and cardiovascular protection.

In the prevention and treatment of cardiovascular disease, pharmacological treatment strategies should have several aims: (i) in individuals without overt cardiovascular disease, but with risk factors such as hypertension and/or diabetes, pharmacotherapy should prevent or delay disease development; (ii) in patients who have already progressed to cardiovascular disease, pharmacotherapy should help either to prevent or regress target organ damage (TOD); and (iii) in patients with TOD, pharmacotherapy should prevent events. Any medication intended for long-term therapy also should be well tolerated. Inhibiting the renin-angiotensin system has proven a successful therapeutic strategy in cardiovascular and renal medicine. Angiotensin-converting enzyme (ACE) inhibitors have demonstrated important advantages over conventional agents such as beta-blockers and thiazide diuretics, and have become a relevant part of treatment for heart failure post-myocardial infarction, left ventricular dysfunction and renal disease. Tolerability concerns may prevent their use in some patients, however. Angiotensin AT1 receptor blockers (ARBs) provide a different form of blockade of the renin-angiotensin system and a growing body of evidence suggests that this alternative approach may confer additional cardiovascular protection for some patient subgroups. In addition, ARBs generally are better tolerated than ACE inhibitors, enhancing patient compliance and persistence with long-term therapy. Furthermore, evidence in favour of combining an ACE inhibitor and an ARB in certain circumstances is continuously growing.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Aldosterone and telomere length in white blood cells.

BACKGROUND: Aldosterone accelerates cardiovascular aging by mechanisms that generate reactive oxygen species. Telomere length in white blood cells (WBCs) may be a bioindicator that registers the accruing burden of systemic oxidative stress. The aim of the present study was, therefore, to examine the relationship between plasma aldosterone and telomere length in WBCs. METHODS: We studied 75 normotensive and never-treated mildly hypertensive men whose blood was drawn for the measurements of plasma aldosterone concentration and the terminal restriction fragment (TRF) length in WBCs. RESULTS: The slope of the TRF-age relationship in the entire cohort showed a decrease in telomere length of 26 +/- 5 base pairs per year (r = -0.46, p <.001). Age-adjusted TRF length was the longest in the lowest aldosterone quartile (6.74 +/- 0.12 kb) and shortest in the highest aldosterone quartile (6.36 +/- 0.11 kb), with intermediate TRF lengths in the second and third aldosterone quartiles (analysis of variance [ANOVA] trend test, p =.025). In telomeric attrition equivalence, participants in the upper aldosterone quartile were 15 years older than their peers in the lowest quartile. CONCLUSIONS: The inverse relationship between aldosterone and WBC telomere length suggests not only that aldosterone is pro-oxidant but that elevated concentrations of this hormone might be linked to a higher rate of telomere attrition and perhaps increased biological aging in humans.

Adult↗
PubMed2005

Anaphylactic shock: a form of distributive shock without inhibition of oxygen consumption.

BACKGROUND: The pathophysiology of anaphylactic shock during anesthesia is incompletely characterized. It is described as distributive by analogy with septic shock (anaerobic metabolism, high tissue oxygen pressure [Ptio2] values). The Ptio2 profile and its metabolic consequences during anaphylaxis are not known. METHODS: Ovalbumin-sensitized anaphylactic shock rats (n = 11) were compared to nicardipine-induced hypotension rats (n = 12) for systemic hemodynamics, Ptio2, sympathetic nervous system activation, skeletal muscle blood flow, and interstitial lactate and pyruvate concentrations using combined microdialysis and polarographic Clark-type oxygen probes. RESULTS: In both groups, the time course and the magnitude of arterial hypotension were similar. The ovalbumin group but not the nicardipine group displayed decreased skeletal muscle blood flow (from 45 +/- 6.2 ml x 100 g(-1) x min(-1) to 24.3 +/- 5 ml x 100 g(-1) x min(-1); P < 0.0001) and Ptio2 values (from 42 +/- 5 to 5 +/- 2; P < 0.0001). The ovalbumin group had more intense sympathetic nervous system activation with higher plasma epinephrine and interstitial norepinephrine concentrations. For the ovalbumin group, there was skeletal muscle anaerobic metabolism (lactate concentration increased from 0.446 +/- 0.105 to 1.741 +/- 0.459 mm; P < 0.05) and substrate depletion (pyruvate concentration decreased from 0.034 +/- 0.01 mm to 0.006 +/- 0.002 mm; P < 0.05) leading to increased interstitial lactate/pyruvate ratios (from 17 +/- 6 to 311 +/- 115; P < 0.05). CONCLUSIONS: This profile suggests decreased skeletal muscle blood flow and oxygen delivery. Persistent energy consumption results in decreased Ptio2 and substrate depletion through anaerobic glycolysis leading to complete failure of cellular energy production. This could explain rapid organ dysfunction and resuscitation difficulties.

Anaphylaxis↗