Evaluation of subclinical atherosclerosis by computed tomography coronary angiography and its association with risk factors in familial hypercholesterolemia

Background: Increasing age and cholesterol levels, male gender, and family history of early coronary heart disease (CHD) are associated with early onset of CHD in familial hypercholesterolemia (FH). Objective: Assess subclinical atherosclerosis by computed tomography coronary angiography (CTCA) and its association with clinical and laboratorial parameters in asymptomatic FH subjects. Methods: 102 FH subjects (36% male, 45 +/- 13 years, LDL-c 280 +/- 54 mg/dL) and 35 controls (40% male, 46 +/- 12 years, LDL-c 103 +/- 18 mg/dL) were submitted to CTCA. Plaques were divided into calcified, mixed and non-calcified; luminal stenosis was characterized as >50% obstruction. Results: FH had a greater atherosclerotic burden represented by higher number of patients with: plaques (48% vs. 14%, p = 0.0005), stenosis (19% vs. 3%, p = 0.015), segments with plaques (2.05 +/- 2.85 vs. 0.43 +/- 1.33, p = 0.0016) and calcium scores (55 perpendicular to 129 vs. 38 perpendicular to 140, p = 0.0028). After multivariate analysis, determinants of plaque presence were increasing age (OR = 2.06, for age change of 10 years, CI95%: 1.38-3.07, p < 0.001) and total cholesterol (OR = 1.86, for cholesterol change by 1 standard deviation, CI95%: 1.09-3.15, p = 0.027). Coronary calcium score was associated with the presence of stenosis (OR = 1.54; CI95%: 1.27-1.86, p < 0.001, for doubling the calcium score). Male gender was directly associated with the presence of non-calcified plaques (OR: 15.45, CI95% 1.72-138.23, p = 0.014) and inversely with calcified plaques (OR = 0.21, CI95%: 0.05-0.84, p = 0.027). Family history of early CHD was associated with the presence of mixed plaques (OR = 4.90, CI95%: 1.32-18.21, p = 0.018). Conclusions: Patients with FH had an increased burden of coronary atherosclerosis by CTCA. The burden of atherosclerosis and individual plaque subtypes differed with the presence of other associated risk factors, with age and cholesterol being most important. A coronary calcium score of zero ruled out obstructive disease in this higher risk population. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of Sleep Apnea on Nocturnal Free Fatty Acids in Subjects with Heart Failure

Study Objectives: Sleep apnea is common in patients with congestive heart failure, and may contribute to the progression of underlying heart diseae. Cardiovascular and metabolic complications of sleep apnea have been attributed to intermittent hypoxia. Elevated free fatty acids (FFA) are also associated with the progression of metabolic, vascular, and cardiac dysfunction. The objective of this study was to determine the effect of intermittent hypoxia on FFA levels during sleep in patients with heart failure. Design and interventions: During sleep, frequent blood samples were examined for FFA in patients with stable heart (ejection fraction < 40%). In patients with severe sleep apnea (apnea-hypopnea index = 15.4 +/- 3.7 events/h; average low SpO(2) = 93.6%). In patients with severe sleep apnea, supplemental oxygen at 2-4 liters/min was administered on a subsequent night to eliminate hypoxemia. Measurements and Results: Prior to sleep onset, controls and patients with severe apnea exhibited a similar FFA level. After sleep onset, patients with severe sleep apnea exhibited a marked and rapid increase in FFA relative to control subjects. This increase persisted throughout NREM and REM sleep exceeding serum FFA levels in control subjects by 0.134 mmol/L (P = 0.0038) Supplemental oxygen normalized the FFA profile without affecting sleep architecture or respiratory arousal frequency. Conclusion: In patients with heart failure, severe sleep apnea causes surges in nocturnal FFA that may contribute to the accelerated progression of underlying heart disease. Supplemental oxygen prevents that FFA elevation.

Acute Cardiovascular and Inflammatory Toxicity Induced by Inhalation of Diesel and Biodiesel Exhaust Particles

Analysis of fuel emissions is crucial for understanding the pathogenesis of mortality because of air pollution. The objective of this study is to assess cardiovascular and inflammatory toxicity of diesel and biodiesel particles. Mice were exposed to fuels for 1 h. Heart rate (HR), heart rate variability, and blood pressure were obtained before exposure, as well as 30 and 60 min after exposure. After 24 h, bronchoalveolar lavage, blood, and bone marrow were collected to evaluate inflammation. B100 decreased the following emission parameters: mass, black carbon, metals, CO, polycyclic aromatic hydrocarbons, and volatile organic compounds compared with B50 and diesel; root mean square of successive differences in the heart beat interval increased with diesel (p < 0.05) compared with control; low frequency increased with diesel (p < 0.01) and B100 (p < 0.05) compared with control; HR increased with B100 (p < 0.05) compared with control; mean corpuscular volume increased with B100 compared with diesel (p < 0.01), B50, and control (p < 0.001); mean corpuscular hemoglobin concentration decreased with B100 compared with B50 (p < 0.001) and control (p < 0.05); leucocytes increased with B50 compared with diesel (p < 0.05); platelets increased with B100 compared with diesel and control (p < 0.05); reticulocytes increased with B50 compared with diesel, control (p < 0.01), and B100 (p < 0.05); metamyelocytes increased with B50 and B100 compared with diesel (p < 0.05); neutrophils increased with diesel and B50 compared with control (p < 0.05); and macrophages increased with diesel (p < 0.01), B50, and B100 (p < 0.05) compared with control. Biodiesel was more toxic than diesel because it promoted cardiovascular alterations as well as pulmonary and systemic inflammation.

Relation between visceral fat and coronary artery disease evaluated by multidetector computed tomography

Visceral abdominal fat has been associated to cardiovascular risk factors and coronary artery disease (CAD). Computed tomography (CT) coronary angiography is an emerging technology allowing detection of both obstructive and nonobstructive CAD adding information to clinical risk strati. cation. The aim of this study was to evaluate the association between CAD and adiposity measurements assessed clinically and by CT. We prospectively evaluated 125 consecutive subjects (57% men, age 56.0 +/- 12 years) referred to perform CT angiography. Clinical and laboratory variables were determined and CT angiography and abdominal CT were performed in a 64-slice scanner. CAD was defined as any plaque calcified or not detected by CT angiography. Visceral and subcutaneous adiposity areas were determined at different intervertebral levels. CT angiography detected CAD in 70 (56%) subjects, and no association was found with usual anthropometric adiposity measurements (waist and hip circumferences and body mass index). Otherwise, CT visceral fat areas (VFA) were significantly related to CAD. VFA T12-L1 values >= 145 cm(2) had an odds ratio of 2.85 (95% CI 1.30-6.26) and VFA L4-L5 >= 150 cm(2) had a 2.87-fold (95% CI 1.31-6.30) CAD risk. The multivariate analysis determined age and VFA T12-L1 as the only independent variables associated to CAD. Visceral fat assessed by CT is an independent marker of CAD determined by CT angiography. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Intrapericardial Ranolazine Prolongs Atrial Refractory Period and Markedly Reduces Atrial Fibrillation Inducibility in the Intact Porcine Heart

Introduction: Extensive experimental studies and clinical evidence (Metabolic Efficiency with Ranzolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction-36 [MERLIN TIMI-36] trial) indicate potential antiarrhythmic efficacy of the antianginal agent ranolazine. Delivery of agents into the pericardial space allows high local concentrations to be maintained in close proximity to myocardial tissue while systemic effects are minimized. Methods and Results: The effects of intrapericardial (IPC) administration of ranolazine (50-mg bolus) on right atrial and right ventricular effective refractory periods (ERP), atrial fibrillation threshold, and ventricular fibrillation threshold were determined in 17 closed-chest anesthetized pigs. IPC ranolazine increased atrial ERP in a time-dependent manner from 129 +/- 5.14 to 186 +/- 9.78 ms (P < 0.01, N = 7) but did not significantly affect ventricular ERP (from 188.3 +/- 4.6 to 201 +/- 4.3 ms (NS, N = 6). IPC ranolazine increased atrial fibrillation threshold from 4.8 +/- 0.8 to 28 +/- 2.3 mA (P < 0.03, N = 6) and ventricular fibrillation threshold (from 24 +/- 3.56 baseline to 29.33 +/- 2.04 mA at 10-20 minutes, P < 0.03, N = 6). No significant change in mean arterial pressure was observed (from 92.8 +/- 7.1 to 74.8 +/- 7.5 mm Hg, P < 0.125, N = 5, at 7 minutes). Conclusions: IPC ranolazine exhibits striking atrial antiarrhythmic actions as evidenced by increases in refractoriness and in fibrillation inducibility without significantly altering mean arterial blood pressure. Ranolazine`s effects on the atria appear to be more potent than those on the ventricles.

Validation of a Cutoff Value on Echo Doppler Analysis to Replace Right Heart Catheterization During Pulmonary Hypertension Evaluation in Heart Transplant Candidates

Background. Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. Objectives. Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. Methods. One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >= 60 mm Hg; a mean transpulmonary gradient >= 15; or pulmonary vascular resistance >= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. Results. A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. Conclusions. The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Recovery of Renal Function in Heart Transplantation Patients After Conversion From a Calcineurin Inhibitor-Based Therapy to Sirolimus

Background. Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. Methods. The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance <50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 +/- 12.3 years and time since transplantation 8.7 +/- 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 +/- 0.9 to 1.69 +/- 0.5 mg/dL, P = .01) and CrCl (24.9 +/- 6.5 to 45.7 +/- 17.2 mL/min, P = .005) at 6 months follow-up. Conclusion. The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.

Biopsy-Proven Pulmonary Determinants of Heart Disease

Heart disease (HD) can stress the alveolar blood-gas barrier, resulting in parenchymal inflammation and remodeling. Patients with HD may therefore display any of the symptoms commonly attributed to primary pulmonary disease, although tissue documentation of corresponding changes through surgical lung biopsy (SLB) is rarely done. Intent on exploring the basis of HD-related alveolar-capillary barrier dysfunction, a retrospective analysis of SLB histopathology was conducted in patients with clinically diagnosed HD, diffuse pulmonary infiltrates, and no evidence of primary pulmonary disease. Patients eligible for the study had a clinical diagnosis of heart disease, acute or chronic, and presented with diffuse infiltrates on chest X-ray. All qualified subjects (N = 23) who underwent diagnostic SLB between January 1982 and December 2005 were subsequently examined. Specific biopsy parameters investigated included demonstrable edema, siderophage influx, hemorrhage, venous and lymphatic ectasia, vascular sclerosis, capillary congestion, and fibroblast proliferation. Based on observed alveolar-capillary barrier (ACB) alterations, three main morphologic groups emerged: one group (6 patients) with alveolar edema; a second group (11 patients) characterized by pulmonary congestion; and a final group (6 patients) showing microscopic foci of acute ACB lung injury. Alveolar-capillary stress due to acute high-pressure or volume overload often manifests as diffuse pulmonary infiltrates with variable but generally predictable histopathology. In patients with biopsy-proven alveolar edema, pulmonary congestion, or acute microscopic lung injury, the clinician must be alert for the possibility of primary heart disease, particularly if the patient is elderly or when a history of myocardial, valvular, or coronary vascular disease exists.

The Aging Process of the Heart: Obesity Is the Main Risk Factor for Left Atrial Enlargement During Aging The MONICA/KORA (Monitoring of Trends and Determinations in Cardiovascular Disease/Cooperative Research in the Region of Augsburg) Study

Objectives This prospective study evaluated the association of obesity and hypertension with left atrial (LA) volume over 10 years. Background Although left atrial enlargement (LAE) is an independent risk factor for atrial fibrillation, stroke, and death, little information is available about determinants of LA size in the general population. Methods Participants (1,212 men and women, age 25 to 74 years) originated from a sex-and age-stratified random sample of German residents of the Augsburg area (MONICA S3). Left atrial volume was determined by standardized echocardiography at baseline and again after 10 years. Left atrial volume was indexed to body height (iLA). Left atrial enlargement was defined as iLA >= 35.7 and >= 33.7 ml/m in men and women, respectively. Results At baseline, the prevalence of LAE was 9.8%. Both obesity and hypertension were independent predictors of LAE, obesity (odds ratio [OR]: 2.4; p < 0.001) being numerically stronger than hypertension (OR: 2.2; p < 0.001). Adjusted mean values for iLA were significantly lower in normal-weight hypertensive patients (25.4 ml/m) than in obese normotensive individuals (27.3 ml/m; p = 0.016). The highest iLA was found in the obese hypertensive subgroup (30.0 ml/m; p < 0.001 vs. all other groups). This group also presented with the highest increase in iLA (+6.0 ml/m) and the highest incidence (31.6%) of LAE upon follow-up. Conclusions In the general population, obesity appears to be the most important risk factor for LAE. Given the increasing prevalence of obesity, early interventions, especially in young obese individuals, are essential to prevent premature onset of cardiac remodeling at the atrial level. (J Am Coll Cardiol 2009; 54: 1982-9) (C) 2009 by the American College of Cardiology Foundation

Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine Heart

Introduction: In vitro studies and ambulatory ECG recordings from the MERLIN TIMI-36 clinical trial suggest that the novel antianginal agent ranolazine may have the potential to suppress atrial arrhythmias. However, there are no reports of effects of ranolazine on atrial electrophysiologic properties in large intact animals. Methods and Results: In 12 closed-chest anesthetized pigs, effects of intravenous ranolazine (similar to 9 mu M plasma concentration) on multisite atrial effective refractory period (ERP), conduction time (CT), and duration and inducibility of atrial fibrillation (AF) initiated by intrapericardial acetylcholine were investigated. Ranolazine increased ERP by a median of 45 ms (interquartile range 29-50 ms; P < 0.05, n = 6) in right and left atria compared to control at pacing cycle length (PCL) of 400 ms. However, ERP increased by only 28 (24-34) ms in right ventricle (P < 0.01, n = 6). Ranolazine increased atrial CT from 89 (71-109) ms to 98 (86-121) ms (P = 0.04, n = 6) at PCL of 400 ms. Ranolazine decreased AF duration from 894 (811-1220) seconds to 621 (549-761) seconds (P = 0.03, n = 6). AF was reinducible in 1 of 6 animals after termination with ranolazine compared with all 6 animals during control period (P = 0.07). Dominant frequency (DF) of AF was reduced by ranolazine in left atrium from 11.7 (10.7-20.5) Hz to 7.6 (2.9-8.8) Hz (P = 0.02, n = 6). Conclusions: Ranolazine, at therapeutic doses, increased atrial ERP to greater extent than ventricular ERP and prolonged atrial CT in a frequency-dependent manner in the porcine heart. AF duration and DF were also reduced by ranolazine. Potential role of ranolazine in AF management merits further investigation. (J Cardiovasc Electrophysiol, Vol. 20, pp. 796-802, July 2009).

A double-blind, placebo-controlled treatment trial of citalopram for major depressive disorder in older patients with heart failure: The relevance of the placebo effect and psychological symptoms

Background: Little is known about the treatment of depression in older patients with heart failure. This Study was developed to investigate the effectiveness of antidepressant treatment for major depressive disorder (MDD) in the elderly with heart failure. Methods: We enrolled 72 older outpatients with ejection fraction < 50 and diagnosed with MDD by the structured clinical interview for DSM-IV. Thirty-seven patients, 19 on citalopram and 18 on placebo, initiated an 8-week double-blind treatment phase. Measurements were performed with the 31-item Hamilton Rating Scale for Depression (Ham-D-31), the Montgomery-Asberg rating scale (MADRS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE). A psychiatrist followed up the patients weekly, performing a consultation for about 20 min to field complaints after the measurements. Results: A trend toward superiority of citalopram over placebo in reducing depression was observed in MADRS scores (15.05 + 9.74 vs 9.44 + 9.25, P = .082) but not on HAM-D scores. The depressive symptomatology significantly decreased in both groups (P < .001). The high rate of placebo response during the double-blind phase (56.3%) led us to conclude the study at the interim analysis with 37 patients. Conclusion: Citalopram treatment of MDD in older patients with heart failure is well-tolerated with low rates of side effects, but was not significantly more effective than placebo in the treatment of depression. Weekly psychiatric follow-up including counseling may contribute to the improvement of depression in this population. Scales weighted on psychological symptoms such as the MADRS are possibly better suited to measure depression severity and improvement in patients with heart failure. (C) 2009 Elsevier Inc. All rights reserved.

Aerobic training abolishes ambulatory blood pressure increase induced by estrogen therapy: A double blind randomized clinical trial

Emerging data reveal that oral estrogen therapy can increase clinic blood pressure (BP) in postmenopausal women; however, it is important to establish its effects on ambulatory BP, which is a better predictor for target-organ damage. Besides estrogen therapy, aerobic training is widely recommended for post-menopausal women, and it can decrease ambulatory BP levels. This study was designed to evaluate the effect of aerobic training and estrogen therapy on the ambulatory BP of post-menopausal women. Forty seven healthy hysterectomized women were randomly divided (in a double-blind manner) into 4 groups: placebo-control (PLA-CO = 12), estrogen therapy-control (ET-CO = 14), placebo-aerobic training (PLA-AT = 12), and estrogen therapy-aerobic training (ET-AT = 09). The ET groups received estradiol valerate (1 mg/day) and the AT groups performed cycle ergometer, 3x/week at moderate intensity. Hormonal status (blood analysis), maximal cardiopulmonary exercise test (VO(2) peak) and ambulatory BP (24-h, daytime and nighttime) was evaluated before and 6 months after interventions. A significant increase in VO(2) peak was observed only in women who participated in aerobic training groups (+4.6 +/- 1.0 ml kg(-1) min(-1), P=0.00). Follicle-stimulating hormone was a significant decreased in the ET groups (-18.65 +/- 5.19 pg/ml, P=0.00), and it was accompanied by an increase in circulating estrogen (56.1 +/- 6.6 pg/ml). A significant increase was observed in the ET groups for daytime (P=0.01) and nighttime systolic BP (P=0.01), as well as nighttime diastolic BP (P = 0.02). However, daytime diastolic BP was increased only in the ET-CO group (+3.4 +/- 1.2 mmHg, P=0.04), and did not change in any other groups. No significant effect was found in ambulatory heart rate. In conclusion, aerobic training abolished the increase of daytime ambulatory BP induced by estrogen therapy in hysterectomized, healthy, normotensive and postmenopausal women. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Local renin-angiotensin system regulates left ventricular hypertrophy induced by swimming training independent of circulating renin: a pharmacological study

Introduction. This study addressed the role of the local renin-angiotensin system (RAS) in the left ventriular hypertropy (LVH) induced by swimming training using pharmacological blockade. Materials and methods. Female Wistar rats treated with enalapril maleate (60 mg.kg(-1).d(-1), n = 38), losartan (20 mg.kg(-1).d(-1), n = 36) or high salt diet (1% NaCl, n = 38) were trained by two protocols (T1: 60-min swimming session, 5 days per week for 10 weeks and T2: the same T1 protocol until the 8(th) week, then 9(th) week they trained twice a day and 10(th) week they trained three times a day). Salt loading prevented activation of the systemic RAS. Haemodynamic parameters, soleus citrate synthase (SCS) activity and LVH (left ventricular/body weight ratio, mg/g) were evaluated. Results. Resting heart rate decreased in all trained groups. SCS activity increased 41% and 106% in T1 and T2 groups, respectively. LVH was 20% and 30% in T1 and T2 groups, respectively. Enalapril prevented 39% of the LVH in T2 group (p < 0.05). Losartan prevented 41% in T1 and 50% in T2 (P < 0.05) of the LVH in trained groups. Plasma renin activity (PRA) was inhibited in all salt groups and it was increased in T2 group. Conclusions. These data provide evidence that the physiological LVH induced by swimming training is regulated by local RAS independent from the systemic, because the hypertrophic response was maintained even when PRA was inhibited by chronic salt loading. However, other systems can contribute to this process.

Percutaneous Laser Ablation of Sacrococcygeal Teratoma in a Hydropic Fetus with Severe Heart Failure - Too Late for a Surgical Procedure?

Sacrococcygeal teratoma (SCT) is the commonest solid fetal tumor. Perinatal prognosis is usually favorable, but sometimes it can be complicated by fetal hydrops being responsible for high risk of mortality. Fetal therapy in such cases has so far not been established. We report a case with a giant solid SCT associated with fetal hydrops and severe heart failure. 2D- and 3D-Doppler ultrasonography revealed great vessels originated from the medial sacral artery. Percutaneous laser ablation of these vessels was performed at 24 weeks of gestation. During the procedure, severe anemia was also diagnosed (hemoglobin 4.3 g/dl). Two days later, the fetus died and pathological examination revealed local tumor necrosis and blood hemorrhage inside the mass. We suggest that in such cases, fetal surgery may not be enough, being too late, and perhaps fetal clinical therapy for anemia and heart failure could be the best option at a gestational age of less than 28 weeks. Copyright (C) 2009 S. Karger AG, Basel

Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside

Chantler PD, Nussbacher A, Gerstenblith G, Schulman SP, Becker LC, Ferrucci L, Fleg JL, Lakatta EG, Najjar SS. Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside. Am J Physiol Heart Circ Physiol 300: H1914-H1922, 2011. First published March 4, 2011; doi:10.1152/ajpheart.01048.2010.-The coupling between arterial elastance (E(A); net afterload) and lea ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium. nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, EA was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV): did not differ between old (70 +/- 8 yr. n = 15) and young (30 +/- 5 yr. n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 +/- 3.1 mmHg/ml) versus young (11.4 +/- 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 +/- 0.11) versus young (0.16 +/- 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.