Hemodynamic Defects Research Articles

Arterial stiffness as therapeutic target for smokers with comorbidity

Cigarette smoking has long been considered a risk factor for cardiovascular disease and a major preventable cause of death and disability in developed and developing countries. It is known that smoking can cause endothelial dysfunction and hemodynamic defects such as arterial stiffness. Among various surrogate markers of cardiovascular risk, arterial stiffness plays a central role and is a strong independent predictor of cardiovascular events, in addition to classical cardiovascular risk factors. This review presents the main mechanisms that explain the development of arterial stiffness during smoking, presents various treatment options for arterial stiffness as a therapeutic target for smokers with cardiorespiratory comorbidity.

Treatment of Vascular Injury During Balloon Pulmonary Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension.

Treatment strategy for vascular injury during balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) was uncertain. This study aimed to identify an optimal therapeutic strategy for vascular injury during BPA in patients with CTEPH. This study reviewed 207 patients with CTEPH and 956 BPA procedures between November 1, 2012 and November 30, 2015. Patients who were diagnosed with vascular injury during BPA, which was defined as angiographic signs or sudden respiratory and hemodynamic defects were included in this study. The study investigated the safety and efficacy of the hierarchically systematic treatment strategy including gelatin sponge embolization (GSE). More than one-half of the 79 patients and 133 procedures with vascular injury were improved by general treatment with reversal of heparin and high-flow oxygen administration. The investigators performed conventional treatment of proximal vessel occlusion using a guiding or balloon catheter in 47 procedures (35%) in which the culprit vessels could be detected under patients' stable conditions. In 32 procedures (24%) without detected culprit lesions or improvement by conventional treatment, GSE could significantly improve patient condition. The treatment strategy obtained successful bailout in 98% of procedures with vascular injury. No patients who underwent GSE died within 30days after the treatment. There was no significant difference in cumulative mortality rate (median follow-up: 6.6years) between groups with or without GSE (15.6% vs 8.2%; adjusted HR: 1.47; 95%CI: 0.25-8.69; P = 0.67). Treatment strategy including GSE would be promising for vascular injury during BPA in patientswith CTEPH.

Pathophysiology, Risk Factors, and Management of Atrial Fibrillation in Adult Congenital Heart Disease.

A confluence of clinical and epidemiologic factors has provoked a steep increase in the prevalence of atrial fibrillation in adults with congenital heart disease. Atrial fibrillation is the most common presenting arrhythmia. Much remains to be unraveled about the mitigating role congenital heart disease, residual hemodynamic defects, surgical ramifications, and shunts and cyanosis on new-onset and recurrent atrial fibrillation in this population. Catheter ablation is increasingly performed for atrial fibrillation. This synopsis provides an overview of current knowledge on atrial fibrillation in adults with congenital heart disease, addresses clinical management, and discusses knowledge gaps and areas for future research.

The study of systemic hemodynamic disorders of patients with varicose and post-thrombotic diseases

Aim. Study of heart function in the patients with CVD. Materials and methods. 46 patients with varicosity (VD) and 34 patients with post-thrombotic disease (PTD) were examined; the control group was represented by 15 healthy volunteers. The diagnosis was established using the CEAP basic classification. The study did not include patients with a diagnosed arterial hypertension, diabetes mellitus, chronic lung disease, significant hemodynamic heart defects, coronary heart disease. Ultrasound examination of the heart and veins of the lower extremities was performed on a Saote My Lab Alpha, Acuson Sequoia 512 apparatus. In addition to the standard protocol of heart ultrasound examination, the parameters of the right heart were calculated: sizes of the right ventricle (RV), right atrium, thickness of the anterior wall of the pancreas; to assess the ejection fraction (EF) of the pancreas the mobility of the lateral edge of the tricuspid ring was calculated, and the pressure on the tricuspid valve (TV) was measured. Diastolic ventricular function was studied by spectrograms of tricuspid and mitral blood flow. Results. Most of the indicators of cardiac activity in patients with VD were within normal limits, but a tendency to increase increasing of the right heart size was noted. In addition, the thickness of the interventricular septum and the right ventricle (RV) anterior wall was found to increase from 0.8 to 1.1 cm and from 0.3 to 0.5 cm, respectively, according clinical classes from C2 to C6 (CEAP). Eject fraction (EF) of both the RV and the left ventricle (LV) were also within normal limits, but with a tendency to decrease (67.8 % – C2, to 62 % – C6). The growth of the clinical class is followed by the increasing of percentage of non-restrictive blood flow through the tricuspid valve (TV). The restrictive type of blood flow in patients with VD had not been identified. Patients with PTD also showed a tendency to increase the right heart. However, whereas the size of the RV, as a rule, did not exceed 3.0 cm, the size of the right atrium was slightly higher than normal one in the clinical class C4 and C5.6. All the patients had EF of LV within normal limits, but it slightly decreased by the growth of class. Only patient classes C3 and C4 had EF of RV within the normal range. The 18 % of patient class C5.6 had EF lower than normal with value 48%. Diastolic dysfunction (DD) of the RV was detected in 73.3% of patients with class C3 and 100% with classes C4 and C5.6. Moreover, a restrictive type of blood flow through TV appeared from class C4 and the percentage increased up to 27.2% (class C5,6). Conclusions. DD of the RV was the main hemodynamic disorder.

P6375Correlation between cytokine profile and ultrasonic characteristics of atherosclerotic plaques in patients with essential hypertension

Abstract Objective To study the association of serum cytokine concentrations (tumor necrosis factor-alpha (TNF-a) and interleukin-10 (IL-10)) with ultrasonic characteristics of atherosclerotic plaque and signs of its instability. Materials and methods We examined 166 patients (mean age 56.3±6.1 years). We used the generally accepted classification of Gray-Weale AC et al.(1988) to describe the structural characteristics of atherosclerotic plaque (ASP) and to determine local hemodynamic defects. There were 3 groups of patients. The 1st group included 48 patients with homogeneous hyperechoic plaques, the 2nd group included 56 patients with predominantly hyperechoic ASP (more than 50% of sites), the 3rd group included 13 patients with anechoic, low ultrasound density of ASP or with predominantly hypoechoic average density ASP (more than 50% of sites with average density). The control group consisted of 39 patients with essential hypertension (EH) without atherosclerotic lesions of the carotid arteries. All patients were subjected to general clinical examinations (measuring height, weight, waist, systolic and diastolic blood pressure, calculating body mass index), laboratory tests (lipid profile, fasting glucose, creatinine with glomerular filtration rate (eGFR), fibrinogen, TNF-a and IL-10). Mass determination of TNF-a and IL-10 was carried out by the method of enzyme-linked immunosorbent assay and ultrasound doppler sonography of the carotid arteries, common carotid artery scanned in longitudinal section using a wideband linear sensor with a frequency of 3–11 MHz, the image was synchronized with the R wave on the ECG). Results Patients of the 1st (7,26±0,64 pg/ml) and 2nd groups (8,93±0,98 pg/ml) who do not have ultrasonic signs of ASP instability TNF-a was significantly lower than in patients of the 3rd group (10,51±2,23 pg/ml, p<0,001) with ultrasound signs of ASP instability. Similar results were obtained in terms of the level of IL-10. The level of IL-10 in patients of the 1st and 2nd groups, having reached 14,7±3,5 pg/ml and 14,4±2,7 pg/ml, was significantly lower in comparison with patients of the 3rd group (17,1±5,3 pg/ml, p<0,025 and p<0,017, respectively). The logistic regression analysis showed that the independent factors associated with the presence of ultrasonic signs of ASP instability in patients with EH are: age (HR-1,20; 95% CI 1,03–1,38; p<0,02), concentration of triglycerides (HR-4,05; 95% CI 1,90–8,64; p<0,001) and TNF-a (HR-2,72; 95% CI 1,44–5,15; p<0,02). The influence of other factors, including IL-10, on the instability of ASP was less significant (p>0,05). Further statistical analysis showed that in patients with level of TNF-a more than 10 pg/ml, the risk of detecting an unstable ASP increased almost in 7 times (HR 6,81; 95% CI 2,17–21,6). Conclusions Increasing the concentration of tumor necrosis factor-alpha above 10 pg/ml is an independent risk factor for unstable atherosclerotic plaques in patients with essential hypertension

A Five-Repeat Micro-Dystrophin Gene Ameliorated Dystrophic Phenotype in the Severe DBA/2J-mdx Model of Duchenne Muscular Dystrophy

Micro-dystrophins are highly promising candidates for treating Duchenne muscular dystrophy, a lethal muscle disease caused by dystrophin deficiency. Here, we report robust disease rescue in the severe DBA/2J-mdx model with a neuronal nitric oxide synthase (nNOS)-binding micro-dystrophin vector. 2 × 1013 vector genome particles/mouse of the vector were delivered intravenously to 10-week-old mice and were evaluated at 6 months of age. Saturated micro-dystrophin expression was detected in all skeletal muscles and the heart and restored the dystrophin-associated glycoprotein complex and nNOS. In skeletal muscle, therapy substantially reduced fibrosis and calcification and significantly attenuated inflammation. Centronucleation was significantly decreased in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles but not in the quadriceps. Muscle function was normalized in the TA and significantly improved in the EDL muscle. Heart histology and function were also evaluated. Consistent with the literature, DBA/2J-mdx mice showed myocardial calcification and fibrosis and cardiac hemodynamics was compromised. Surprisingly, similar myocardial pathology and hemodynamic defects were detected in control DBA/2J mice. As a result, interpretation of the cardiac data proved difficult due to the confounding phenotype in control DBA/2J mice. Our results support further development of this microgene vector for clinical translation. Further, DBA/2J-mdx mice are not good models for Duchenne cardiomyopathy.

Monocyte-derived extracellular Nampt-dependent biosynthesis of NAD(+) protects the heart against pressure overload.

Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in the salvage pathway for nicotinamide adenine dinucleotide (NAD+) biosynthesis, and thereby regulates the deacetylase activity of sirtuins. Here we show accommodative regulation of myocardial NAD+ by monocyte-derived extracellular Nampt (eNampt), which is essential for hemodynamic compensation to pressure overload. Although intracellular Nampt (iNampt) expression was decreased in pressure-overloaded hearts, myocardial NAD+ concentration and Sirt1 activity were preserved. In contrast, iNampt was up-regulated in spleen and monocytes, and circulating eNampt protein and nicotinamide mononucleotide (NMN), a key precursor of NAD+, were significantly increased. Pharmacological inhibition of Nampt by FK866 or depletion of monocytes/macrophages by clodronate liposomes disrupted the homeostatic mechanism of myocardial NAD+ levels and NAD+-dependent Sirt1 activity, leading to susceptibility to cardiomyocyte apoptosis and cardiac decompensation in pressure-overloaded mice. These biochemical and hemodynamic defects were prevented by systemic administration of NMN. Our studies uncover a crucial role of monocyte-derived eNampt in myocardial adaptation to pressure overload, and highlight a potential intervention controlling myocardial NAD+ against heart failure.

Comparative transcriptomic analysis between an artificially induced SIRS in healthy individuals and spontaneous sepsis

Sepsis is defined as a syndrome combining a systemic inflammatory response with a documented infection. It may progress to more serious cases such as septic shock following the failure of one or more organs and the emergence of hemodynamic defects. Assuming that the emergence of serious septic syndromes may be partially explained by the early loss of regulation of the inflammatory response, we decided to compare, in a transcriptomic perspective, the biological mechanisms expressed during an induced systemic inflammatory response with those expressed during severe septic syndromes. By using open-access transcriptomic databases, we first studied the kinetics of an induced inflammatory response. The use of functional analysis helped us identify discriminating biological mechanisms, such as the mTOR signaling pathway, between the pathological cases of sepsis and non-pathological (i.e., the artificially induced SIRS) cases.

Cerebral Abscess in a 8 years old with uncorrected tetralogy of Fallot: Anaesthetic challenge

Patients with cyanotic heart disease are prone to develop frequent brain abscesses. Tetralogy of Fallot is a leading cause of cyanotic congenital heart disease and is responsible for as many as 10 % of all causes of congenital heart diseases. Surgery for drainage of abscess under general anaesthesia in these children is considered a challenge. Hemodynamic instability, cyanotic spells, coagulation defects, electrolyte and acid base imbalance, and sudden cardiac arrest are among the major anaesthetic concerns during perioperative period. We are here by reporting anaesthetic management of such a case with good outcome.

ASSA13-15-26 Echocardiography Guided Endovascular Graft Exclusion For the Treatment of Stanford B Aortic Dissection

Objective This study was aimed to evaluate the feasibility, safety and efficacy of transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) guided endovascular graft exclusion (EVGE) for the treatment of Stanford B aortic dissection. Methods In 11 patients with Stanford B aortic dissection, TEE and TTE were used to determine the parameters for pre-surgery diagnosis and selection of a coated stent. During surgery, TEE and TTE provided real-time and dynamic monitoring and guiding for precise implantation of the coated stent to effectively seal the tear of the aortic dissection. After surgery, clinical efficacy and potential side effects of the implantation of the coated stent were evaluated. Results In all 11 patients, the coated stent was successfully implanted and morphologic and hemodynamic defects were corrected. Follow-up examinations performed at 1 year post-surgery showed neither displacement nor morphologic alternation of the implanted stent. An improvement of cardiac function and blood supply was observed. There was no main ductus arteriosus perforation or hematoma, vital organ failure, paraplegia or endoleak. Conclusions In our study with a limited number of patients, TEE and TTE guided EVGE treatment of Stanford B aortic dissection was safe and efficacious with reduced risk of complications. As echocardiography is real-time, dynamic, noninvasive, reproducible, non-radioactive and contrast media damage free, TEE and TTE guided EVGE offers a novel and viable clinical approach for the treatment of Stanford B aortic dissection.

Separating genetic and hemodynamic defects in neuropilin 1

Formation of the cardiovascular system is crucial for embryo growth and survival and the importance of proper blood flow even during these early stages is becoming increasingly clear. In recent years, there has been a debate regarding which aspects of early vascular formation are genetically predetermined, and which are governed by external stimuli, such as mechanical and biochemical signaling. Though the initial vascular network is patterned without knowledge of the functional requirements, it makes biological sense that a feedback mechanism with respect to physiological function would set in as soon as this information becomes available. We recently showed that physical forces created by blood flow are necessary for proper vascular development and remodeling. In this study, we show how to distinguish between genetic defects and biomechanical defects during vascular development. Using mouse embryo culture, we study hemodynamic defects in Nrp1−/− mice together with an analysis of the emerging vascular defects. The geometry of yolk sac blood vessels is altered and remodeling into yolk sac arteries and veins does not occur. To separate flow‐induced deficiencies from those caused by the nrp‐1 mutation, we arrested blood flow in cultured wild‐type and mutant embryos and followed their vascular development. This method allows genetic defects caused by loss‐of‐function of a gene important for cardiovascular development to be isolated even in the presence of hemodynamic defects.Grant Funding SourceNSERC

Relationships of the Thrombolysis in Myocardial Infarction Frame Count With Clinical, Hemodynamic and Medicine Variables in Syndrome X Patients

The thrombolysis in myocardial infarction (TIMI) frame count was reported to reflect coronary blood flow and have prognostic value. However, such data in syndrome X was lacking. The purpose of this study was to examine the prognostic value of the TIMI frame count in syndrome X patients, compared with the normal population. The TIMI frame count was measured in 2,049 consecutive patients referred for coronary angiography from March 2003 to February 2005. Among 308 patients with normal coronary angiograms, 44 undergoing the procedure for electrophysiologic studies or valvular heart disease surveys other than angina were designated normal controls. Another 155 patients with positive stress test results were diagnosed as syndrome X. Comparisons of the two groups showed that the syndrome X patients had higher frame counts in the left anterior descending artery (40.9 ± 15.7 vs. 47.8 ± 25.4; p < 0.05) and left circumflex artery (35.2 ± 11.7 vs. 42.0 ± 18.7; p < 0.05). A similar trend was found in the right coronary artery (29.3 ± 13.5 vs. 31.9 ± 15.9; p = 0.2). The TIMI frame count in each artery of the syndrome X group was related to the patients' variables (sex, age, and body mass index), clinical variables (medication use, diabetes, hypertension, hypercholesterolemia, smoking, and family history), and hemodynamic variables (aortic systolic blood pressure and left ventricular end-diastolic pressure). By multivariate analysis, the TIMI frame counts in all arteries were significantly higher in women and lower with angiotensin-converting enzyme inhibitor (ACEI) use (both p < 0.05). The frame count in the left anterior descending was associated with diuretics use ( p < 0.05). Our TIMI frame count data confirm the presence of slow coronary flow in syndrome X patients, especially women. ACEI use shortens the counts in these patients, suggesting that ACEIs have the potential to correct the underlying hemodynamic defects in such patients.

Separating genetic and hemodynamic defects in neuropilin 1 knockout embryos

Targeted inactivation of genes involved in murine cardiovascular development frequently leads to abnormalities in blood flow. As blood fluid dynamics play a crucial role in shaping vessel morphology, the presence of flow defects generally prohibits the precise assignment of the role of the mutated gene product in the vasculature. In this study, we show how to distinguish between genetic defects caused by targeted inactivation of the neuropilin 1 (Nrp1) receptor and hemodynamic defects occurring in homozygous knockout embryos. Our analysis of a Nrp1 null allele bred onto a C57BL/6 background shows that vessel remodeling defects occur concomitantly with the onset of blood flow and cause death of homozygous mutants at E10.5. Using mouse embryo culture, we establish that hemodynamic defects are already present at E8.5 and continuous circulation is never established in homozygous mutants. The geometry of yolk sac blood vessels is altered and remodeling into yolk sac arteries and veins does not occur. To separate flow-induced deficiencies from those caused by the Nrp1 mutation, we arrested blood flow in cultured wild-type and mutant embryos and followed their vascular development. We find that loss of Nrp1 function rather than flow induces the altered geometry of the capillary plexus. Endothelial cell migration, but not replication, is altered in Nrp1 mutants. Gene expression analysis of endothelial cells isolated from freshly dissected wild-type and mutants and after culture in no-flow conditions showed down-regulation of the arterial marker genes connexin 40 and ephrin B2 related to the loss of Nrp1 function. This method allows genetic defects caused by loss-of-function of a gene important for cardiovascular development to be isolated even in the presence of hemodynamic defects.

Separating Genetic and Hemodynamics Effects In Nrp1 Knockout Embryos

Targeted inactivation of genes involved in murine cardiovascular development frequently leads to abnormalities in blood flow. Since blood fluid dynamics play a crucial role in shaping vessel morphology, the presence of flow defects generally prohibits the precise assignment of the role of the mutated gene product in the vasculature. In this study, we show how to distinguish between genetic defects caused by targeted inactivation of the Neuropilin‐1 (Nrp‐1) receptor, and hemodynamic defects occurring in homozygous knockout embryos. Using mouse embryo culture, we establish that hemodynamic defects are already present at E8.5 and continuous circulation is never established in homozygous mutants. The geometry of yolk sac blood vessels is altered and remodeling into yolk sac arteries and veins does not occur. To separate flow‐induced deficiencies from those caused by the nrp‐1 mutation, we arrested blood flow in cultured wild‐type and mutant embryos and followed their vascular development. We find that loss of nrp‐1 function rather than flow induces the altered geometry of the capillary plexus. This method allows genetic defects caused by loss‐of‐function of a gene important for cardiovascular development to be isolated even in the presence of hemodynamic defects.

Impact of Cardiac Rehabilitation on the Exercise Function of Children With Serious Congenital Heart Disease

The exercise capacity of children with congenital heart disease (CHD) is often depressed. This depression is thought to be attributable to (1) residual hemodynamic defects and (2) deconditioning secondary to physical inactivity. We hypothesized that this latter component would be ameliorated by a formal cardiac rehabilitation program designed specifically for children. The objective of this study was to characterize the effect of a cardiac rehabilitation program on the exercise performance of children with CHD and to define the physiologic mechanisms that might account for any improvements that are observed. Nineteen patients with CHD who were referred for exercise testing and found to have a peak oxygen consumption (VO2) and/or peak work rate <80% of predicted were enrolled in the study. Sixteen patients (11 Fontan patients, 5 with other CHD) completed the program and had postrehabilitation exercise tests, results of which were compared with the prerehabilitation studies. Improvements were found in 15 of 16 patients. Peak VO2 rose from 26.4 +/- 9.1 to 30.7 +/- 9.2 mL/kg per min; peak work rate from 93 +/- 32 to 106 +/- 34 W, and the ventilatory anaerobic threshold from 14.2 +/- 4.8 to 17.4 +/- 4.5 mL/kg per min. The peak heart rate and peak respiratory exchange ratio did not change, suggesting that the improvements were not attributable merely to an increased effort. In contrast, the peak oxygen pulse rose significantly, from 7.6 +/- 2.8 to 9.7 +/- 4.1 mL/beat, an improvement that can be attributed only to an increase in stroke volume and/or oxygen extraction at peak exercise. No patient experienced rehabilitation-related complications. Cardiac rehabilitation can improve the exercise performance of children with CHD. This improvement is mediated by an increase in stroke volume and/or oxygen extraction during exercise. Routine use of formal cardiac rehabilitation may greatly reduce the morbidity of complex CHD.

Developmental and neurologic outcomes late after neonatal corrective surgery

J Thorac Cardiovasc Surg 2002;124:425-7

Conduction system abnormalities in rat embryos induced by maternal hyperthermia.

Maternal hyperthermia induces severe malformations in the central nervous system (CNS) in both humans and laboratory animals. These phenomena are accompanied by apoptotic cell death, especially in the developing CNS. Cardiovascular malformations in conjunction with skeletal and CNS abnormalities have been reported in embryos of laboratory animals. In rats, hyperthermic treatment at 43 degrees C for 15 min at day 9 of pregnancy induced various severe external malformations in embryos, such as exencephaly, spina bifida, microphthalmia, anophthalmia, facial cleft or defect, generalized edema, and cardiovascular abnormalities. Examination of the embryonic heart revealed abnormal formation of the conduction system. Although hyperthermia causes marked hemodynamic defects, we could not obtain direct proof of a link between hemodynamic alteration by hyperthermia and malformations of the conduction system.

Respiratory muscle dysfunction in sepsis.

It became evident in the past 12 years that venitlatory muscle contractile performance is significantly impaired during the course of septic shock. In animal models of septic shock, depression of ventilatory muscle contractile performance has been shown to cause hypercapneic ventilatory failure and respiratory arrest. Failure of ventilatory muscle contractility in septic shock has never been attributed to a single factor, but two groups of factors are likely to be involved: (a) increased ventilatory muscle metabolic demands due to augmentation of ventilation, hypoxemia and increased pulmonary impedance; and (b) specific cellular, metabolic, immune and hemodynamic defects which interfere with several processes necessary for normal force generation. These defects are mediated by complex interactions between several local and systematic mediator such a bacterial endotoxin, proinflammatory cytokines, prostaglandins, platelet activating factor, reactive oxygen species and nitric oxide. This is a summary of how these interactions are likely to interfere with ventilatory muscle contractile performance in septic shock with particular emphasis on the newly described role of nitric oxide.

Repair of Traumatic Ventricular Septal Defect and Associated Tricuspid Insufficiency: A Case Report

Penetrating cardiac trauma often results in serious and life-threatening sequelae. Traumatic ventricular septal defect and valvular insufficiency are among the rarest. The author presents a case of a young man who sustained cardiac arrest from ventricular tamponade secondary to a penetrating left ventricular stab wound. This patient was successfully resuscitated after open manual massage. A significant ventricular septal defect and associated tricuspid regurgitation were detected on the following day. Serial echocardiograms were used to evaluate the evolution of these two hemodynamic defects. The patient underwent operative repair for patch closure of a defect the size of a quarter and repair of the associated tricuspid papillary muscle dysfunction. His pulmonary status and right ventricular failure improved with resolution of his ascites. The operative and medical considerations are discussed for these unique traumatic intracardiac defects.

Reduced Postprandial Skeletal Muscle Blood Flow Contributes to Glucose Intolerance in Human Obesity*

While it is well accepted that the disposal of an oral glucose load (OGL) occurs primarily in skeletal muscle, the mechanisms by which this occurs are not completely elucidated. Glucose uptake (GU) in skeletal muscle follows the Fick principal, such that GU equals the products of the arteriovenous glucose difference (AVGd) across and the blood flow (BF) into muscle. It is widely believed that in the postprandial period both insulin and glucose increase GU by increasing the AVGd; however, a role for increments in BF in the disposal and tolerance of an OGL has not been established. To investigate this issue, whole body GU (isotope dilution), leg GU (leg balance technique), leg BF, and cardiac index (CI) were measured after an overnight fast and over 180 min after an OGL (1 g/kg) in 8 lean (ln) and 8 obese (ob) subjects [mean +/- SEM age, 36 +/- 2 vs. 37 +/- 2 yr (P = NS) and 60 +/- 1 vs. 99 +/- 5 kg (P less than 0.01), respectively]. Serum glucose levels were higher in the ob than in the ln subjects between 100 and 160 min, indicating reduced glucose tolerance. Fasting and post-OGL serum insulin levels were 2- to 3-fold higher in ob vs. ln at all times, indicating insulin resistance. Peak (40-80 min) incremental whole body GU above baseline was 32% lower in ob vs. ln, (P less than 0.05). Peak femoral AVGd was not different between ob and ln (0.55 +/- 0.16 vs. 0.66 +/- 0.14 mmol/L; P = NS). Peak leg BF increased 36% over baseline in ln (0.328 +/- 0.052 to 0.449 +/- 0.073 L/min; P less than 0.05), while ob subjects displayed no change in leg BF from baseline. Consequently, peak leg GU was 44% lower in ob vs. ln (P less than 0.05). CI increased 24% from baseline at 60 min in ln (P less than 0.05), but was unchanged in ob. In summary, after an OGL 1) femoral AVGd increases in both ln and ob subjects, but skeletal muscle BF and CI increase in ln only; 2) since peak femoral AVGd values were similar in ln and ob, differences in peak leg GU and (by inference) whole body GU are largely due to reduced BF to insulin-sensitive tissues; and 3) hemodynamics play an important role in the physiological disposal of an OGL, and therefore, hemodynamic defects can potentially contribute to reduced glucose tolerance and insulin resistance.