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Biomedical subjects

David L Hare

Publications and source records attributed to David L Hare.

At least 19 recordsLinked to original sources
PubMed2006

Subclavian artery occlusion causing acute myocardial infarction in a patient with a left internal mammary artery graft.

Although atherosclerotic disease of the subclavian artery has previously been reported to cause coronary-subclavian steal syndrome, acute myocardial infarction because of occlusion of the subclavian artery in a graft-dependent coronary circulation is an uncommon and previously unreported mode of clinical presentation. Increasingly, patients undergoing high-risk cardiopulmonary procedures have comorbidities with extensive atherosclerotic disease of many vascular beds including coronary, cranial, and peripheral. Our discussion reviews the clinical presentation of such a case and highlights some of the important treatment options available when confronted with such a finding. The successful outcome achieved by percutaneous stenting of the subclavian artery and salvage of the graft may indicate that this modality is the initial treatment of choice in such cases.

Aortography↗
PubMed2006

Depression following acute coronary syndromes: a comparison between the Cardiac Depression Scale and the Beck Depression Inventory II.

OBJECTIVE: This study compared the Cardiac Depression Scale (CDS) and the Beck Depression Inventory II (BDI-II). METHOD: Depression was assessed in 81 participants, 2 weeks post-ACS, using the BDI-II and the Composite International Diagnostic Interview. RESULTS: The CDS had a strong concurrent validity with the BDI-II (r=.69). Cross-validation of the BDI-II and the CDS with the structured interview demonstrated the ability of both measures to detect severe symptoms. More patients were classified as depressed using the CDS. The CDS also had a significantly higher correlation with a trait anxiety measure than the BDI-II did. CONCLUSION: The CDS is a more suitable scale for assessing the less severe depressive symptoms typically seen in a cardiac population.

Acute Disease↗
PubMed2006

Cardiovascular biomarkers in CKD: pathophysiology and implications for clinical management of cardiac disease.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with all forms of chronic kidney disease (CKD). The underlying pathological state is caused by a complex interplay of traditional and nontraditional risk factors that results in atherosclerosis, arteriosclerosis, and altered cardiac morphological characteristics. This multifactorial disease introduces new challenges in predicting and treating patients with CVD sufficiently early in the course of CKD to positively alter patient outcome. Asymptomatic individuals with progressive CVD are a group of patients that deserve focused attention because early detection and intervention may provide the best opportunity for improved outcome. However, identifying CVD in asymptomatic patients with CKD or end-stage renal disease remains a significant hurdle in the management of these patients. Recently, a number of cardiovascular biomarkers were identified as predictors of patient outcome in individuals with CVD and, with additional research, may be used to guide the early diagnosis of and therapy for CVD in patients with CKD. This review examines the pathophysiological characteristics and potential clinical role of these novel cardiovascular biomarkers in risk stratification, risk monitoring, and selection of preventive therapies for patients with CKD.

Biomarkers↗
PubMed2006

Cardiac troponin levels in asymptomatic patients on the renal transplant waiting list.

AIMS: Cardiac troponin levels predict mortality and cardiovascular events in asymptomatic patients receiving dialysis and may be a useful clinical tool to stratify high-risk asymptomatic individuals. METHODS: The present study examined levels of troponins I (cTnI) and T (cTnT) in patients with chronic renal impairment, patients receiving dialysis and renal transplant recipients. Patients receiving dialysis on the renal transplant waiting list were compared with those excluded from the list based on medical criteria. Median levels were compared using the Kruskal-Wallis test and proportions compared by chi-squared. RESULTS: Median troponin levels were higher in patients on dialysis than transplant recipients. Comparing patients receiving dialysis not listed compared with those listed for renal transplant, median cTnI levels were significantly higher (0.03 versus 0.02 microg/L, P < 0.01) whereas median cTnT levels were not. Patients listed for transplantation were younger, had less clinical cardiovascular disease and lower C-reactive protein than those awaiting renal transplantation. The proportion of patients with elevated cTnT was not substantially different between patients awaiting renal transplantation (38%) and those excluded (52%). Levels of cTnI and cTnT were inversely related to renal function in predialysis and transplant patients, but were not related to time on dialysis for those receiving dialysis therapy. CONCLUSION: As patients awaiting renal transplantation are clinically screened for cardiovascular disease but have frequently elevated cardiac troponin levels, troponin may be a useful clinical tool to identify high-risk asymptomatic patients on dialysis prior to renal transplantation. The influence of renal function on the interpretation of cardiac troponin and risk prediction requires further evaluation.

Adult↗
PubMed2005

CD34 Class III positive cells are present in atherosclerotic plaques of the rabbit model of atherosclerosis.

CD34 is a positive marker for haematopoietic stem cells and endothelial cells. Recent evidence suggests that haematopoietic progenitor cells are involved in atherogenesis. CD34-positive haematopoietic progenitor cells have never been described in rabbit atherosclerotic tissues. The aim of this study is to identify CD34-positive haematopoietic progenitor cells in rabbit atherosclerotic tissues, and to compare this with macrophage (RAM-11), alpha smooth muscle cell actin and fibroblast (prolyl-4-hydroxylase) immunoreactive cells. Sixteen Male New Zealand White rabbits were divided into two groups: Group 1, control diet (Con); group 2, 0.5% cholesterol diet, and killed after 12 weeks. Immunohistochemistry was used to detect CD34 haematopoietic progenitor cells. CD34-positive haematopoietic progenitor cells were identified both within and overlying atherosclerotic plaques. As well, these haematopoietic progenitor cells also stained for RAM-11, CD45, prolyl-4 hydroxylase and alpha smooth muscle cell actin. These findings suggest that in the rabbit model of atherosclerosis, the previously identified macrophages, smooth muscle cells and fibroblasts within and overlying atherosclerotic plaques might be of haematopoietic origin.

Animals↗
PubMed2005

Immunolocalization of ACE2 and AT2 receptors in rabbit atherosclerotic plaques.

Evidence suggests that angiotensin type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2) play a protective role in atherogenesis. These factors have not been identified in rabbit atherosclerotic plaques. Our goal was to localize ACE2 and AT2R in rabbit atherosclerotic tissues, and determine which cell types express these factors. New Zealand White rabbits were fed either a control diet or a 0.5% cholesterol diet (n=8/group) for 12 weeks. Paraffin-fixed thoracic aorta were serially sectioned and processed for immunohistochemistry using commercially available antibodies to ACE2, AT2R, RAM 11 (to identify macrophages), and alpha smooth muscle cell actin (alphaSMC) to identify smooth muscle cells and myofibroblasts. AT2R immunoreactivity, but not ACE2 immunoreactivity, was clearly present in endothelia overlying normal wall. However, both AT2R and ACE2 immunoreactivity were clearly present in endothelia overlying neo-intima formation and atherosclerotic plaques. Within plaques, both AT2R and ACE2 immunoreactivity were observed in macrophages and alphaSMC actin-positive cells. Examination of serial sections showed that the majority of cells were both ACE2- and AT2R-positive. Macrophages and alphaSMC actin-positive cells produce ACE2 and the AT2R in atherosclerotic plaques. Determining a role for these factors in the control of atherosclerosis will require additional studies.

Actins↗
PubMed2005

The combination of high dietary methionine plus cholesterol induces myocardial fibrosis in rabbits.

UNLABELLED: Limited evidence suggests that myocardial fibrosis might be associated with dietary cardiovascular risk factors. OBJECTIVE: To investigate the effects of high dietary cholesterol, methionine (the precursor to homocysteine), and the combination of the two diets on myocardial fibrosis. METHODS: Rabbits were randomly allocated into four dietary groups for 12 weeks: control (Con), 1% methionine (Meth), 0.5% cholesterol (Chol) or 1% methionine plus 0.5% cholesterol (MethChol). RESULTS: Myocardial fibrosis was not significantly increased in Chol or Meth. However, interstitial fibrosis increased by 85% (p = 0.03) and perivascular fibrosis 28-fold (p < 0.01) in the MethChol group compared to Con. CONCLUSIONS: These results suggest that high levels of dietary cholesterol or methionine alone do not significantly increase myocardial collagen content. However, the combination of the two diets does cause myocardial fibrosis. Therefore, excessive cholesterol and methionine intake may be an important pathogenic factor in the development of myocardial fibrosis.

Animals↗
PubMed2005

The immunoquantification of caveolin-1 and eNOS in human and rabbit diseased blood vessels.

In this study, caveolin-1 (cav-1), an inhibitor of endothelial nitric oxide synthase (eNOS), was semi-quantified in diseased human and rabbit blood vessels. New Zealand White rabbits were fed, for 12 weeks, a high methionine diet (to induce intimal hyperplasia), 0.5% cholesterol diet, a normal diet, or the combination of both experimental diets. Excess segments of human internal mammary arteries (IMA) and radial arteries (RA) were obtained from patients undergoing coronary artery bypass surgery. eNOS and cav-1 were localized throughout both human and rabbit vessels. In rabbit arteries, eNOS was significantly increased in the endothelium overlying intimal thickening and atherosclerotic plaques compared with the adjacent endothelium overlying normal media. Interestingly, the endothelial cav-1:eNOS ratio increased 5-fold only in endothelium overlying plaques but decreased in endothelium overlying vessels with neo-intimal thickening. In human tissue, there was no difference between RA and IMA eNOS immunoreactivity in endothelium, intima, or media; however, RA endothelial, intimal, and medial cav-1 immunoreactivity increased 4-fold (p<0.02), 8-fold (p<0.001), and 4-fold (p<0.004), respectively, compared with IMA. Furthermore, the cav-1:eNOS immunostaining ratio in the media correlated with intimal thickening (r2 = 0.5). Our results suggest a close relationship between increased cav-1 and diseased blood vessels.

Animals↗
PubMed2005

Do angiographic results from symptom-directed studies reflect true graft patency?

BACKGROUND: Coronary artery graft patency results have been obtained from repeat angiograms in patients who presented with evidence of ischemia. The purpose of this study is to compare protocol-directed angiographic results from a randomized clinical trial with symptom-directed angiography in nontrial patients. METHODS: Repeat angiography after primary isolated coronary artery bypass grafting was performed in 337 of 2,259 patients between July 1996 and September 2004. Patients were divided into two groups: 596 graft angiograms in 192 trial patients were compared with 389 graft angiograms in 142 nontrial patients. The mean interval from surgery was 1,306 +/- 800 days versus 1,119 +/- 777 days, respectively. Grafting techniques were similar in both groups except that the right internal thoracic artery was used almost exclusively as a free graft in the trial patients. Angiographic outcomes were defined as patent (stenosis <80%) or failure (stenosis > or =80%, occlusion, or the string sign). Comparisons of trial versus nontrial grafts were made using a generalized linear mixed model. Five-year estimates of graft patency were made using survival analyses accounting for interval censoring. RESULTS: The odds ratio for graft failure for nontrial compared with trial patient grafts was 2.6 (95% confidence interval, 1.6 to 4.3; p < 0.001). Cumulative patency estimates for all grafts at 5 years were trial 91% versus nontrial 83%, p = 0.004. Five-year estimates for individual conduits were left internal thoracic artery, 99% versus 92%, p = 0.002; right internal thoracic artery, 86% versus 87%, p = 0.8; radial artery, 87% versus 86%, p = 0.6; and saphenous vein, 86% versus 56%, p = 0.003. CONCLUSIONS: Graft patency rates were superior in the trial compared with nontrial patients. Symptom-directed graft failure rates were approximately double those of trial patients.

Clinical Protocols↗
PubMed2005

Has the in situ right internal thoracic artery been overlooked? An angiographic study of the radial artery, internal thoracic arteries and saphenous vein graft patencies in symptomatic patients.

OBJECTIVE: The right internal thoracic artery is being used infrequently despite favorable observational angiographic data. Conversely, the radial artery utilization has increased with only limited data available. The purpose of this paper is to re-evaluate the roles of the right internal thoracic artery and the radial artery grafts. METHODS: We reviewed all ischemia-directed coronary angiographic procedures from January 1996 to December 2003. A total of 219 patients had primary coronary artery bypass grafting with an internal thoracic artery and a radial artery as two of the bypass grafts. Six hundred and seventy-nine (679) graft angiograms (45 saphenous vein, 363 radial artery, 54 right internal thoracic artery and 217 left internal thoracic artery) were studied. The mean period from operation to re-angiogram was 1104+/-761 days. Angiographic outcomes were divided into groups as: (1) patent (<50% stenosis) or (2) failed (>or=50% stenosis, string sign or occluded). A generalized linear mixed model was used to analyze predictors of graft patency. Turnbull's estimates of cumulative patency were used to compare graft failure rates over time. RESULTS: A total of 632/679 (93%) grafts were patent and 47/679 (7%) grafts had failed. Empirical saphenous vein graft patency was 40/45 (89%), radial artery patency 329/363 (91%), right internal thoracic artery patency 51/54 (94%) and left internal thoracic artery patency 212/217 (98%). Pairwise comparisons of patency from the generalized linear mixed model were: LITA>RITA, OR=1.5 (P=0.5); LITA>RA, OR=5.7 (P<0.001); LITA>SV, OR=6.5 (P<0.001); RITA>RA, OR=3.9 (P=0.01); RITA>SV, OR=4.4 (P=0.01); RA>SV, OR=1.1 (P=0.7). Five-year patency estimates from the Turnbull's model were the left internal thoracic artery (95.9%), right internal thoracic artery (91.2%), the radial artery (90.6%) and the saphenous vein (81.8%). CONCLUSIONS: Consideration should be given to the routine use of both internal thoracic arteries for coronary artery bypass grafting. When additional grafts are required, there is no evidence to suggest that either the radial artery or saphenous vein is superior.

Aged↗
PubMed2005

A Cardiac Depression Visual Analogue Scale for the brief and rapid assessment of depression following acute coronary syndromes.

OBJECTIVE: A Cardiac Depression Visual Analogue Scale (CD-VAS) was developed as a rapid and easy method of assessing depressed mood in a cardiac population. The CD-VAS was contrasted against the Cardiac Depression Scale (CDS) and the Beck Depression Inventory-II (BDI-II). METHOD: Depression was assessed in 58 participants, 2 weeks postacute coronary syndrome (ACS), using the BDI-II and the CDS. Participants then completed the six-item CD-VAS for 14 consecutive days. RESULTS: Using mean weekly scores, the CD-VAS had strong internal reliability (.91) and strong test-retest reliability that ranged from .85 to .97. Principal components analyses found that the CD-VAS only measured one component. The CD-VAS had strong concurrent validity with the BDI-II (r=.81) and the CDS (r=.82) and was able to differentiate between depressed and nondepressed participants. CONCLUSION: The CD-VAS is a valid and reliable measure for brief and rapid repeated assessments of depressive symptoms in a cardiac population.

Adult↗
PubMed2004

High dietary methionine plus cholesterol exacerbates atherosclerosis formation in the left main coronary artery of rabbits.

UNLABELLED: Although mild hyperhomocysteinemia is a risk factor for cardiovascular events and mortality, there is no evidence to suggest that mild hyperhomocysteinemia stimulates coronary artery atherosclerosis formation. OBJECTIVE: To compare the development of coronary artery atherosclerosis in rabbits following the induction of hyperhomocysteinemia and hypercholesterolemia through diet, and whether the combination of these risk factors exacerbated atherosclerosis formation. METHODS: New Zealand White rabbits were fed for 12 weeks either a control diet, a 1% methionine diet (Meth), a 0.5% cholesterol diet (Chol) or the combination of the two diets (MethChol). Using volumetric stereological techniques, we quantitated the volume of intima, media and lumen of the left main coronary artery (LMCA). RESULTS: Atherosclerosis was present in the Chol group, and increased in the MethChol group. There was no atherosclerosis in the control or Meth groups. CONCLUSIONS: These results underscore the difference in the atherogenicity of hypercholesterolemia alone and mild hyperhomocysteinemia alone. Thus, we suggest that isolated mild hyperhomocysteinemia is not a risk factor for the initiation of coronary artery atherosclerosis formation over a short period of time, but may act in conjunction with other risk factors to further increase plaque formation.

Animal Feed↗
PubMed2004

Reduced exercise tolerance in CHF may be related to factors other than impaired skeletal muscle oxidative capacity.

BACKGROUND: We sought to determine whether skeletal muscle oxidative capacity, fiber type proportions, and fiber size, capillary density or muscle mass might explain the impaired exercise tolerance in chronic heart failure (CHF). Previous studies are equivocal regarding the maladaptations that occur in the skeletal muscle of patients with CHF and their role in the observed exercise intolerance. Methods and results Total body O(2) uptake (VO(2peak)) was determined in 14 CHF patients and 8 healthy sedentary similar-age controls. Muscle samples were analyzed for mitochondrial adenosine triphosphate (ATP) production rate (MAPR), oxidative and glycolytic enzyme activity, fiber size and type, and capillary density. CHF patients demonstrated a lower VO(2peak) (15.1+/-1.1 versus 28.1+/-2.3 mL.kg(-1).min(-1), P<.001) and capillary to fiber ratio (1.09+/-0.05 versus 1.40+/-0.04; P<.001) when compared with controls. However, there was no difference in capillary density (capillaries per square millimeter) across any of the fiber types. Measurements of MAPR and oxidative enzyme activity suggested no difference in muscle oxidative capacity between the groups. CONCLUSIONS: Neither reductions in muscle oxidative capacity nor capillary density appear to be the cause of exercise limitation in this cohort of patients. Therefore, we hypothesize that the low VO(2peak) observed in CHF patients may be the result of fiber atrophy and possibly impaired activation of oxidative phosphorylation.

Adenosine Triphosphate↗
PubMed2004

Moderate-intensity resistance exercise training in patients with chronic heart failure improves strength, endurance, heart rate variability, and forearm blood flow.

BACKGROUND: Resistance exercise training was applied to patients with chronic heart failure (CHF) on the basis that it may partly reverse deficiencies in skeletal muscle strength and endurance, aerobic power (VO(2peak)), heart rate variability (HRV), and forearm blood flow (FBF) that are all putative factors in the syndrome. METHODS AND RESULTS: Thirty-nine CHF patients (New York Heart Association Functional Class=2.3+/-0.5; left ventricular ejection fraction 28%+/-7%; age 65+/-11 years; 33:6 male:female) underwent 2 identical series of tests, 1 week apart, for strength and endurance of the knee and elbow extensors and flexors, VO(2peak), HRV, FBF at rest, and FBF activated by forearm exercise or limb ischemia. Patients were then randomized to 3 months of resistance training (EX, n=19), consisting of mainly isokinetic (hydraulic) ergometry, interspersed with rest intervals, or continuance with usual care (CON, n=20), after which they underwent repeat endpoint testing. Combining all 4 movement patterns, strength increased for EX by 21+/-30% (mean+/-SD, P<.01) after training, whereas endurance improved 21+/-21% (P<.01). Corresponding data for CON remained almost unchanged (strength P<.005, endurance P<.003 EX versus CON). VO(2peak) improved in EX by 11+/-15% (P<.01), whereas it decreased by 10+/-18% (P<.05) in CON (P<.001 EX versus CON). The ratio of low-frequency to high-frequency spectral power fell after resistance training in EX by 44+/-53% (P<.01), but was unchanged in CON (P<.05 EX versus CON). FBF increased at rest by 20+/-32% (P<.01), and when stimulated by submaximal exercise (24+/-32%, P<.01) or limb ischemia (26+/-45%, P<.01) in EX, but not in CON (P<.01 EX versus CON). CONCLUSIONS: Moderate-intensity resistance exercise training in CHF patients produced favorable changes to skeletal muscle strength and endurance, VO(2peak), FBF, and HRV.

Aged↗
PubMed2003

High methionine and cholesterol diet abolishes endothelial relaxation.

OBJECTIVE: High plasma cholesterol or homocysteine is a risk factor for atherosclerosis. Cholesterol and methionine, the precursor of homocysteine, are rarely eaten separately. Thus, the aims of this study were to determine neointima formation, aortic reactivity, and factors involved in endothelial function in rabbits fed high dietary cholesterol, methionine, or a combination of the two for 12 weeks. METHODS AND RESULTS: Rabbit dietary groups were randomized into the following: control (Con), 0.5% cholesterol (Chol), 1% methionine (Meth), and 1% methionine+0.5% cholesterol (MethChol). Aortic reactivity was studied by isometric tension techniques, aortic volumetric analysis was determined by stereological techniques, and immunohistochemistry was used to localize endothelial and inducible NO synthases, superoxide dismutase, macrophages, and nitrotyrosine. Atherosclerosis was present in the Chol and MethChol groups. Endothelium-dependent relaxation was virtually abolished in the MethChol group compared with control. Such decrease in relaxation was not attributable to a vascular smooth muscle cell defect or to a decrease in endothelial NO synthase or superoxide dismutase content. Macrophages and inducible NO synthase immunoreactivity were present in Chol and MetChol groups. CONCLUSIONS: The combination of high dietary cholesterol plus methionine virtually abolishes endothelium-dependent relaxation, underscoring the importance of multiple risk factors in the development of cardiovascular disease.

Animals↗