Biomedical subjects

Robert D Brook

Publications and source records attributed to Robert D Brook.

22 records · Page 2Linked to original sources

PubMed2003

Hypertension and triglyceride catabolism: implications for the hemodynamic model of the metabolic syndrome.

OBJECTIVE: We sought to determine if hypertensive adults have a blunted triglyceride catabolic rate (TG K(2)) and if related hemodynamic and vascular alterations are determinants of TG K(2). METHODS: Fasting levels of insulin, glucose, lipoproteins and plasma catecholamines were measured in 10 normotensive and 10 hypertensive adults. TG K(2) was determined by an intravenous fat tolerance test. Forearm blood flow, maximum forearm blood flow and minimal forearm vascular resistance were determined by strain gauge plethysmography. Vascular compliance and systemic hemodynamics were measured by computerized arterial pulse waveform analysis. RESULTS: Compared to normotensives, hypertensives had a significantly elevated blood pressure (145 +/- 8/94 +/- 11 versus 111 +/- 15/74 +/- 14 mm Hg, p < 0.001), systemic vascular resistance (1695 +/- 441 versus 1172 +/- 430 dynes x sec x cm(-5), p = 0.02) and reduced large vessel compliance (11.7 +/- 3.6 versus 15.1 +/- 3.1 ml/mm Hg x 100, p = 0.04). There were no significant group differences in TG K(2) (3.07 +/- 2.01 versus 2.88 +/- 2.12 mg/dL/min, p = 0.85) or other metabolic and anthropometric variables. TG K(2) was not predicted by the forearm vascular measures or the hemodynamic variables, but was correlated to waist/hip ratio (r = -0.71, p = 0.001), fasting triglycerides (r = -0.64, p = 0.003), and male gender (r = 0.56, p = 0.012). An enhanced TG K(2) was independently predicted by a reduced small vessel compliance (r = -0.61, p = 0.006). CONCLUSIONS: Elevated blood pressure per se and hypertension-related hemodynamic and vascular alterations are not associated with reduced TG K(2) or other metabolic abnormalities. Rather, aspects of the insulin resistance syndrome are closely related to abdominal adiposity. The independent association between small vessel compliance and TG K(2) deserves further investigation.

Adult↗

PubMed2003

Interactive effects of the ACE DD polymorphism with the NOS III homozygous G849T (Glu298-->Asp) variant in determining endothelial function in coronary artery disease.

The products of nitric oxide synthase (NOS) and angiotensin-converting enzyme (ACE) play a critical role in determining vessel wall structure and function. Polymorphisms in both genes have been independently demonstrated to influence propensity to cardiovascular events. The purpose of this study was to determine the influence of the homozygous G849T (Glu298-->Asp) polymorphism in NOS III on peripheral conduit artery endothelial function and to elucidate the modifier role, if any, of a common ACE polymorphism. Three hundred and ninety-seven consecutive subjects presenting to the cardiac catheterization laboratory of the University of Michigan over a period of 18 months were recruited. DNA was extracted and polymerase chain reaction (PCR) analysis for ACE and NOS polymorphisms performed. Patients with homozygosity for G849T at both loci (TT) who belong to DD and II ACE genotype (groups 1 and 2) and those who are negative for this polymorphism (GG) and belong to either DD or II genotype (groups 3 and 4) were identified. The four groups then underwent determination of conduit endothelial function. Heterozygosity of Glu298-Asp or the ID variant of the ACE were not studied. Median FMD value in the TT-DD group was 0.20 (-3.17, 2.01) compared with 2.23% (-0.29, 4.17) in the GG-II group. Median values in the TT-II and the GG-DD groups were 3.04 (-1.16, 6.61) and 2.46% (-1.83, 6.52) respectively. These values were not statistically significant (p > 0.05 by one-way ANOVA). Median nitroglycerin-mediated dilation in the four groups did not differ between the four groups (p = NS by ANOVA). Atherosclerosis burdens as assessed by angiography were not different across the groups. In conclusion, the homozygous NOS III variant (GG) status does not seem to interact additively with the ACE homozygous DD genotype in determining flow-mediated vasodilation in individuals with established atherosclerosis and pre-existent endothelial dysfunction.

Aged↗

PubMed2002

Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults.

BACKGROUND: Fine particulate air pollution and ozone are associated with increased cardiovascular events. To help explain the mechanism behind these observations, we investigated the effect of air pollution exposure on vascular function. METHODS AND RESULTS: Twenty-five healthy adults underwent a randomized, double-blind, crossover study comparing the vascular response to the 2-hour inhalation of approximately 150 microg/m(3) of concentrated ambient fine particles (CAP) plus ozone (120 ppb) versus the response to the inhalation of filtered air. High-resolution vascular ultrasonography was used to measure alterations in brachial artery diameter, endothelial-dependent flow-mediated dilatation (FMD) and endothelial-independent nitroglycerin-mediated dilatation (NMD). Exposure to CAP plus ozone caused a significant brachial artery vasoconstriction compared with filtered air inhalation (-0.09+/-0.15 mm versus +0.01+/-0.18 mm, P=0.03). There were no significant differences in FMD (+0.29+/-4.11% versus -0.03+/-6.63%, P=0.88), NMD (+3.87+/-5.43% versus +3.46+/-7.92%, P=0.83), or blood pressure responses between exposures. CONCLUSIONS: Short-term inhalation of fine particulate air pollution and ozone at concentrations that occur in the urban environment causes acute conduit artery vasoconstriction.

Adult↗

PubMed2002

Management of intermittent claudication.

Medical management of PAD is a considerable challenge. Although patients typically present with IC, there is a substantial pool of subclinical PAD patients. PAD, whether symptomatic or not, confers a marked cardiovascular risk; with affected patients dying of heart attack or stroke, identification of index patients and aggressive medical treatment can offer health benefits far in excess of improvement in IC or related symptoms. Management of risk factors, lifestyle interventions, and pharmacologic treatment with agents to provide symptomatic relief have a central role in improving function and quality of life and slowing the progression to advanced endpoints, such as the rest pain, nonhealing ulcers, gangrene, and cardiac death. Surgical or percutaneous revascularization for aorto-iliac disease provides durable treatment for individuals with disabling symptoms. Newer treatments, such as angiogenic growth factor treatments, are being tested in clinical trials and seem promising. There are limited treatment choices for individuals with predominant infra-popliteal disease. In the future, the availability of newer stents and therapies to prevent re-stenosis may extend the applicability of endovascular treatment to difficult-to-treat infra-inguinal lesions.

Disease Susceptibility↗