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Biomedical subjects

David S Celermajer

Publications and source records attributed to David S Celermajer.

At least 19 recordsLinked to original sources
PubMed2005

Intimal thickening after arterial balloon injury is increased by intermittent repetitive hypoxia, but intermittent repetitive hyperoxia is not protective.

Hypoxia increases and hyperoxia decreases experimental atherosclerosis, but it is unclear if repetitive hypoxic and hyperoxic insults affect intimal thickening after arterial injury. Rabbits on 2% cholesterol diet for 6 weeks underwent balloon injury to the abdominal aorta (AA) after week 3, and were then exposed to normoxia (n = 6), or 12 h daily of intermittent repetitive hypoxia (n = 6) or hyperoxia (n = 6). After week 6, damaged AA and undamaged thoracic aorta (TA) were assessed for intimal thickening and lipid content. Compared with normoxia, hypoxia and hyperoxia did not alter the rise in serum cholesterol related to cholesterol feeding. However, compared to normoxia, hypoxia markedly increased the intima-to-media ratio in AA (1.18 +/- 0.09 versus 1.96 +/- 0.14, P < 0.01) and TA (0.15 +/- 0.02 versus 0.41 +/- 0.01, P < 0.01) whereas hyperoxia had no effect on AA disease and increased intimal thickening in TA (0.26 +/- 0.03, P < 0.01). Hyperoxia promoted positive arterial remodeling in both TA and AA, resulting in larger luminal size. The cholesterol content in AA was increased by hypoxia and decreased by hyperoxia, but decreased by both treatments in TA. Lipophilic antioxidants and the proportion of arterial lipids that was oxidized were not altered by hypoxia or hyperoxia. These results suggest that intermittent repetitive hyperoxia is not protective and intermittent repetitive hypoxia promotes arterial disease in normal and injured arteries independent of lipid peroxidation.

Animals↗
PubMed2005

Repetitive hypoxia increases lipid loading in human macrophages-a potentially atherogenic effect.

Obstructive sleep apnea (OSA) is characterized by repetitive episodes of hypoxia and is associated with an increase in cardiovascular disease. We, therefore, investigated the effect of repetitive hypoxia on two key early events in atherogenesis; lipid loading in foam cells and monocyte adhesion to endothelial cells. Human macrophages were loaded with acetylated low-density lipoproteins. During lipid loading, the cells were exposed to 30 min cycles of 2%/21% oxygen or control (room air, 5% CO(2) incubator). Human umbilical vein endothelial cells (HUVECs) were also exposed to 30 min cycles of repetitive hypoxia or control conditions and monocyte adhesion measured. Cell adhesion molecules E-selectin, ICAM-1 and VCAM-1 were measured by ELISA. Repetitive hypoxia increased cholesteryl ester uptake by macrophages (127+/-5% compared to controls; p=0.003). By contrast, monocyte adhesion to HUVECs and cell adhesion molecule expression were unchanged by exposure to repetitive hypoxia, compared to controls (p >0.1). Repetitive hypoxia, at levels relevant to tissues such as the arterial wall, enhances lipid uptake into human macrophages. This may contribute to accelerated atherosclerosis in OSA patients.

Arteriosclerosis↗
PubMed2005

Cerebrovascular events in young adults after surgical repair of tetralogy of Fallot.

Increasing numbers of children who have undergone intracardiac repair of tetralogy of Fallot have survived to adulthood, but often have residual haemodynamic and/or electrical abnormalities. We report the unusual observation of 4 instances of cerebrovascular accidents in young adults subsequent to surgical repair of tetralogy of Fallot.

Adult↗
PubMed2005

Central obesity is associated with reduced peripheral wave reflection in Indigenous Australians irrespective of diabetes status.

OBJECTIVE: To determine the influence of central obesity and type 2 diabetes on peripheral wave reflection in Indigenous Australians. DESIGN AND METHODS: A cross-sectional study of remote Indigenous Australians with (n = 43) and without (n = 54) type 2 diabetes of similar age (47 years) and sex; using anthropometric and bioelectrical impedance measures of obesity and applanation tonometry to determine the aortic augmentation index (AI) as an index of peripheral wave reflection. RESULTS: Indices of obesity were significantly higher in the diabetic than non-diabetic participants [body mass index (BMI): 27.3 versus 24.6 kg/m, P = 0.018; waist circumference: women 101 versus 94 cm, P = 0.008, men 102 versus 91 cm, P = 0.039]. AI was negatively related to obesity: BMI (r = -0.35, P = 0.0003), weight (r = -0.44, P < 0.0005), waist circumference (r = -0.34, P = 0.0003) and fat mass (r = -0.35, P < 0.0005). There was no significant difference in AI between the groups with and without diabetes. On multiple regression analysis, 66% of the variance in AI was explained with the following significant predictors: age, heart rate, male gender, fat mass and mean arterial pressure. Similar results were obtained when weight, waist circumference or BMI were substituted for fat mass. CONCLUSION: When compared with Indigenous Australians without diabetes, those with type 2 diabetes do not have greater aortic pressure augmentation from peripheral wave reflection. However, obesity, irrespective of the index used, was related to lower peripheral wave reflection in both those with and without type 2 diabetes.

Anthropometry↗
PubMed2005

Androgen receptor gene expression in leucocytes is hormonally regulated: implications for gender differences in disease pathogenesis.

OBJECTIVE: There is evidence that male sex hormones influence the rate of progression of inflammatory and cardiovascular diseases. We have previously shown that human leucocytes and arterial cells isolated from male donors express more androgen receptor (AR) than those from female cells, with potentially pro-atherogenic effects. We now investigate whether the gender difference in AR expression is due to genetic or hormonal regulation. DESIGN AND PATIENTS: The influence of hormones on AR expression were studied in hpg mice (a mouse model of androgen deficiency) treated with testosterone, oestradiol or dihydrotestosterone (DHT). Blood samples were obtained for leucocyte AR expression and hormone levels from 53 subjects, grouped into: 12 male [six young adult (27-45 years), six elderly (71-79 years)] and six female (young adult 25-45 years) healthy controls; six male-to-female transsexuals (M2F; 20-50 years) receiving stable pharmacological oral oestrogen treatment; six female-to-male transsexuals (F2M; 31-51 years) receiving stable androgen replacement therapy; five younger men (18-56 years) who had been receiving long-term androgen replacement therapy for hypogonadal disease; six elderly men (72-88 years) who had undergone medical castration for prostate cancer treatment; and 12 male bone marrow transplant recipients (BMT; 23-65 years) from either male or female donors. MEASUREMENTS: Serum testosterone and oestradiol concentrations were measured by established immunoflurometric assays from unextracted human serum. AR mRNA levels were measured by RT-PCR and AR protein levels by western blot (cell culture) or immunohistochemistry (mouse arteries). RESULTS: We found that AR mRNA levels were significantly down-regulated in the leucocytes of hpg mice that were treated with exogenous testosterone, oestradiol or DHT. AR protein levels were also lower in aortic tissue from the same mice. In humans, we found AR expression was significantly down-regulated by exogenous treatment with testosterone in F2M (31 +/- 13%, compared with control) or oestradiol in M2F (22 +/- 5%) but was significantly up-regulated by endogenous testosterone in BMT (128 +/- 17%). Low androgen levels measured in castrated older men were associated with markedly increased AR expression (207 +/- 26%, P < 0.05) compared with age-matched older male controls (100 +/- 2%). CONCLUSIONS: Our results indicate a regulated ability of vascular cells to respond to sex hormones, with the effects of exogenous therapies differing markedly from those due to endogenous sex hormones. We conclude that the gender difference in AR expression in vascular cells is hormonally, rather than genetically, controlled.

Adult↗
PubMed2005

Endothelial dysfunction occurs in peripheral circulation patients with acute and stable coronary artery disease.

Atherosclerosis is a diffuse, systemic process. In addition, acute coronary syndromes (ACS) are associated with inflammatory marker elevations that are hypothesized to affect the function of nonculprit coronary as well as peripheral vessels. We investigated whether femoral vascular reactivity and/or fibrinolytic capacity are impaired in ACS patients over and above any dysfunction associated with stable coronary artery disease. Patients undergoing diagnostic coronary angiography (n = 42 total, 14 patients/group) were recruited into three groups as follows: 1) stable coronary syndromes (SAP group), 2) ACS as defined by rest angina with ECG changes and troponin rise (ACS group), and 3) angiographically normal coronary arteries (control group). After diagnostic coronary angiography, femoral artery endothelial and smooth muscle function were assessed by infusing acetylcholine (ACh) and nitroglycerin (GTN), and tissue-type plasminogen activator (t-PA) release across the femoral circulation was measured as the difference between arterial and venous concentrations before and after ACh and GTN stimulation. There were no significant differences between groups in relevant baseline characteristics apart from significantly higher C-reactive protein levels and reduced net t-PA release in the ACS group at baseline (P < 0.05). The ACS and SAP groups had equivalent angiographic severity of coronary artery disease. Endothelium-dependent dilatation was significantly higher in control individuals (14.9 +/- 9.1%; P < 0.001) compared with either stable patients (2.3 +/- 8.1%) or those with unstable syndromes (2.6 +/- 8.9%, who were similar to each other; P = not significant). Although baseline t-PA release was impaired in the ACS patients (0.09 +/- 0.06 compared with 0.39 +/- 0.33 and 0.49 +/- 0.56 ng/ml; P = 0.03), stimulation of t-PA release by ACh and GTN occurred only in the control subjects and not in the ACS or SAP patients. Coronary artery disease is associated with impaired endothelium-dependent dilatation and impaired stimulation of t-PA release in the systemic circulation. These aspects of endothelial dysfunction, however, were equally severe in acute and chronic coronary syndrome patients.

Acetylcholine↗
PubMed2004

Meal-related increases in vascular reactivity are impaired in older and diabetic adults: insights into roles of aging and insulin in vascular flow.

A fatty meal induces vasodilatation (of both resting and stimulated forearm flow) in healthy young adults, an effect most likely mediated by the vasodilator actions of insulin. We therefore hypothesized that an impaired meal-related vascular response might be an in vivo marker of vascular insulin resistance, related to the presence of diabetes and/or higher age. Postprandial vascular responses were assessed in three groups of subjects: 15 Type 2 diabetic subjects (age 58 +/- 8 yr), 15 age-, gender-, and body mass index (BMI)-matched older control subjects (age 57 +/- 9 yr), and 15 healthy young control subjects (age 33 +/- 7 yr). Studies were carried out before and 3 and 6 h after a standardized high-fat meal (1,030 kcal, 61 g fat). Forearm microvascular flows were measured by strain gauge plethysmography and large-artery function by ultrasound. Resting blood flow and hyperemic area under curve (AUC) flow were not significantly different in diabetic subjects (resting 117 +/- 42% and AUC 134 +/- 46% of premeal values) compared with age-matched controls (resting 131 +/- 39% and AUC 134 +/- 47%); however, the response in diabetic subjects was blunted compared with young controls (resting 171 +/- 67% and AUC 173 +/- 99% of premeal values; P = 0.02 and P = 0.18, respectively). On multiple regression analysis, we found that increasing age (but not BMI or diabetes) was significantly associated with impaired postprandial vascular responses (resting: r = -0.4, P = 0.002; AUC: r = -0.4, P = 0.006). Therefore, meal ingestion results in impaired vasodilator responses in older nondiabetic and diabetic adults, related to aging rather than insulin resistance.

Adult↗
PubMed2004

Effects of diet and exercise on obesity-related vascular dysfunction in children.

BACKGROUND: The prevalence of obesity in both adults and children is increasing rapidly. Obesity in children is independently associated with arterial endothelial dysfunction and wall thickening, key early events in atherogenesis that precede plaque formation. METHODS AND RESULTS: To evaluate the reversibility of obesity-related arterial dysfunction and carotid intima-media thickening by dietary and/or exercise intervention programs, 82 overweight children (body mass index, 25+/-3), 9 to 12 years of age, were randomly assigned to dietary modification only or diet plus a supervised structured exercise program for 6 weeks and subsequently for 1 year. The prospectively defined primary end points were ultrasound-derived arterial endothelial function (endothelium-dependent dilation) of the brachial artery and intima-media thickness of common carotid artery. At 6 weeks, both interventions were associated with decreased waist-hip ratio (P<0.02) and cholesterol level (P<0.05) as well as improved arterial endothelial function. Diet and exercise together were associated with a significantly greater improvement in endothelial function than diet alone (P=0.01). At 1 year, there was significantly less thickening of the carotid wall (P<0.001) as well as persistent improvements in body fat content and lipid profiles in the group continuing an exercise program. Vascular function was significantly better in those children continuing exercise (n=22) compared with children who withdrew from the exercise program (n=19) (P<0.05). CONCLUSIONS: Obesity-related vascular dysfunction in otherwise healthy young children is partially reversible with diet alone or particularly diet combined with exercise training at 6 weeks, with sustained improvements at 1 year in those persisting with diet plus regular exercise.

Arteriosclerosis↗
PubMed2004

Deleterious impact of "high normal" glucose levels and other metabolic syndrome components on arterial endothelial function and intima-media thickness in apparently healthy Chinese subjects: the CATHAY study.

OBJECTIVE: Endothelial vasodilator dysfunction and carotid intima-media thickening are useful surrogate markers of cardiovascular disease, a major cause of morbidity and mortality in type 2 diabetic patients. However, because most studies reporting the relationships between endothelial function, intima-media thickness (IMT), and hyperglycemia have compared diabetic patients with healthy controls, we report their relationship with glycemia as a continuum. METHODS AND RESULTS: Brachial artery endothelial function (flow-mediated dilatation [FMD]) and carotid IMT were measured noninvasively by high-resolution ultrasound B-mode imaging in 228 apparently healthy Chinese subjects recruited from Hong Kong and Macau. FMD and IMT were significantly associated with increasing levels of glycemia, particularly in the "high normal" glycemic range, with IMT increasing and endothelium-independent dilatation decreasing linearly across the glucose tertiles, and endothelium-dependent dilatation significantly lower in the upper glucose tertile compared with the other 2 groups (P<0.01). Using multiple linear regression, fasting glucose level was identified as an independent predictor of each of these markers of vascular function (P<0.004). Additionally, other conventional cardiovascular risk factors, including obesity, blood pressure, and an adverse lipid profile, were also related to levels of glycemia (P<0.05), further contributing to impaired vascular function. CONCLUSIONS: Increasing levels of glycemia and the coexistence of other cardiovascular risk factors in apparently healthy subjects are adversely associated with arterial endothelial dysfunction and intima-media thickening.

Adolescent↗
PubMed2003

Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-kappaB-dependent pathway.

There exists a striking gender difference in atherosclerotic vascular disease. For decades, estrogen was considered atheroprotective; however, an alternative is that androgen exposure in early life may predispose men to earlier atherosclerosis. We recently demonstrated that the potent androgen, dihydrotestosterone (DHT), enhanced the binding of monocytes to the endothelium, a key early event in atherosclerosis, via increased expression of vascular cell adhesion molecule-1 (VCAM-1). We now show that DHT mediates its effects on VCAM-1 expression at the promoter level through a novel androgen receptor (AR)/nuclear factor-kappaB (NF-kappaB) mechanism. Human umbilical vein endothelial cells were exposed to 4-400 nm DHT. DHT increased VCAM-1 mRNA in a dose- and time-dependent manner. The DHT effect could be blocked by the AR antagonist, hydroxyflutamide. DHT increased VCAM-1 promoter activity via NF-kappaB activation without affecting VCAM-1 mRNA stability. Using 5' deletion analysis, it was determined that the NF-kappaB sites within the VCAM-1 promoter region were responsible for the DHT-mediated increase in VCAM-1 expression; however, coimmunoprecipitation studies suggested there is no direct interaction between AR and NF-kappaB. Instead, DHT treatment decreased the level of the NF-kappaB inhibitory protein. DHT did not affect VCAM-1 protein expression and monocyte adhesion when female endothelial cells were tested. AR expression was higher in male, relative to female, endothelial cells, associated with increased VCAM-1 levels. These findings highlight a novel AR/NF-kappaB mediated mechanism for VCAM-1 expression and monocyte adhesion operating in male endothelial cells that may represent an important unrecognized mechanism for the male predisposition to atherosclerosis.

Adult↗
PubMed2003

Dehydroepiandrosterone, an adrenal androgen, increases human foam cell formation: a potentially pro-atherogenic effect.

OBJECTIVES: We studied the effects of dehydroepiandrosterone (DHEA), an abundant adrenal androgen on two key early events of atherogenenis: 1) human monocyte adhesion to vascular endothelium, and 2) human foam cell formation. BACKGROUND: In the U.S., where DHEA is available without prescription, there has recently been a rapid increase in unsupervised self-administration of DHEA. The vascular biologic effects of DHEA are largely unknown, however. METHODS: Regarding adhesion, human umbilical vein endothelial cells (HUVECs), exposed to either DHEA (42 or 420 nmol/l) or control, were incubated with human monocytes, and adhesion was measured by hemocytometry. Surface expression of endothelial cell adhesion molecules was measured by ELISA. Regarding foam cell formation, studies of lipid loading were performed on macrophages treated with DHEA or control and/or the androgen receptor antagonist hydroxyflutamide (HF) (4 micromol/l). Intracellular cholesterol and cholesteryl esters (CE) were quantified by high-performance liquid chromatography. Expression of foam cell formation-related genes was measured by reverse-transcription polymerase chain reaction. RESULTS: DHEA produced a dose-dependent receptor-mediated increase in the male macrophage CE content (up to 120 +/- 4% of control values, p = 0.015). DHEA upregulated messenger ribonucleic acid expression of the lipoprotein-processing enzymes acyl coenzyme A:cholesterol acyltransferase I and lysosomal acid lipase by 3.4- and 5.3-fold, respectively (p < 0.05 vs. control), but had no effect on scavenger receptor expression (p > 0.2). There was no significant effect of DHEA on monocyte-endothelial adhesion (<10% change in values, p = 0.56) or endothelial cell expression of cell adhesion molecules (p > 0.1). CONCLUSIONS: DHEA increases human macrophage foam cell formation, a potentially pro-atherogenic effect. This effect appears to be mediated via the androgen receptor and involves the upregulation of lipoprotein-processing enzymes.

Acyl Coenzyme A↗
PubMed2003

Androgens up-regulate atherosclerosis-related genes in macrophages from males but not females: molecular insights into gender differences in atherosclerosis.

OBJECTIVES: This study investigated the effects of androgens on gene expression in male- and female-donor macrophages. BACKGROUND: Men have more severe coronary disease than women. Androgen exposure increases foam cell formation in male but not female macrophages, and male macrophages express >4-fold more androgen receptor messenger ribonucleic acid than female macrophages. Therefore, androgen exposure may have gender-specific and potentially pro-atherogenic effects in macrophages. METHODS: Utilizing complementary deoxyribonucleic acid arrays, we studied the effects of a pure androgen (dihydrotestosterone, 40 nmol/l) on human monocyte-derived macrophages from healthy male and female donors (n = 4 hybridizations; 2 men, 2 women). Differential expression of atherosclerosis-related genes was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in five male and five female donors. Functional corroboration of foam cell formation-related findings was undertaken by experiments using (125)I-acetylated low-density lipoprotein (AcLDL). RESULTS: In male macrophages, androgen treatment produced differential up-regulation of 27 genes concentrated in five functional classes: 1) lipoprotein processing; 2) cell-surface adhesion; 3) extracellular signaling; 4) coagulation and fibrinolysis; and 5) transport protein genes. By contrast, none of 588 genes were up-regulated in female macrophages. By RT-PCR, we confirmed the gender-specific up-regulation of six of these atherosclerosis-related genes: acyl coenzyme A:cholesterol acyl transferase I, lysosomal acid lipase (LAL), caveolin-2, CD40, vascular endothelial growth factor-165 receptor, and tissue factor pathway inhibitor. Functionally, androgen-treated male macrophages showed increased rates of lysosomal AcLDL degradation, by 45% to 75% after 15 to 20 h of (125)I-AcLDL incubation (p = 0.001), consistent with increased LAL activity. CONCLUSIONS: Androgens increase expression of atherosclerosis-related genes in male but not female macrophages, with functional consequences. These findings may contribute to the male predisposition to atherosclerosis.

Adult↗
PubMed2003

Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease.

OBJECTIVES: We sought to assess the effects of raloxifene, a selective estrogen receptor modulator, on arterial physiology and biology in postmenopausal women with coronary artery disease (CAD). BACKGROUND: Raloxifene improves endothelial function and markers of vascular health in vitro in experimental animals and in healthy postmenopausal women. In women whose arteries are affected by advanced atherosclerosis, however, the vascular effects of estrogen receptor modulation are unknown. METHODS: We conducted a prospective, randomized, double-blinded, placebo-controlled, crossover trial of raloxifene, 60 mg/day for 8 weeks, in 33 consecutively eligible and consenting postmenopausal women age 50 to 75 years with known CAD. Parameters measured at the beginning and end of each treatment period included brachial artery flow-mediated dilation (FMD), the primary end point, as well as nitroglycerin-induced dilation, peripheral artery tonometry, serum lipoprotein levels, and markers of vascular function, including urinary prostaglandin, serum endothelin-1, and fibrinogen levels. RESULTS: Baseline FMD was impaired in these women, as expected (2.84 +/- 0.60%), but there was no significant difference between the effect of raloxifene (0.26 +/- 0.66% increase) and placebo (0.01 +/- 0.63% decrease) on this marker of endothelial function (p = 0.82). No significant raloxifene-related effects were observed on derived aortic pressure, pulse pressure, augmentation index, total cholesterol or low- and high-density lipoprotein subfractions, markers of thrombosis, or vasoconstrictor or vasodilator substances. CONCLUSIONS: In postmenopausal women with treated CAD, selective estrogen receptor modulation with raloxifene does not improve a comprehensive set of parameters examining vascular function and serum lipoprotein levels.

Aged↗
PubMed2003

Obstructive sleep apnea and cardiovascular disease.

Obstructive sleep apnea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension and has also been implicated in the pathogenesis of congestive cardiac failure, pulmonary hypertension, arrhythmias, and atherosclerosis. Obesity is strongly linked to an increased risk of OSA, and weight loss can reduce the severity of OSA. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnea and the ensuing acute hemodynamic changes during sleep. Long-term CPAP treatment studies have shown a reduction in nocturnal cardiac ischemic episodes and improvements in daytime blood pressure levels and left ventricular function. Despite the availability of effective therapy, OSA remains an underdiagnosed and undertreated condition. A lack of physician awareness is one of the primary reasons for this deficit in diagnosis and treatment.

Cardiovascular Diseases↗
PubMed2003

Probucol promotes functional reendothelialization in balloon-injured rabbit aortas.

BACKGROUND: Probucol remains the only conventional drug that reduces restenosis after coronary angioplasty. Apart from its weak cholesterol-lowering effect, probucol has antioxidant properties, but it remains unclear how this drug inhibits restenosis. METHODS AND RESULTS: Aortic balloon-injured New Zealand White rabbits were fed 2% (wt/wt) cholesterol-enriched or normal chow, with 0.75% (wt/wt) probucol (P) or without (controls, C) for 6 weeks. Endothelial denudation of the abdominal aorta was performed at week 3 with a 3F Fogarty embolectomy catheter. The arteries were harvested after week 6 and analyzed for histology, lipids and antioxidants, and endothelial regeneration and function. Probucol significantly decreased aortic intima-to-media ratio (cholesterol-fed: C, 1.10+/-0.08 versus P, 0.70+/-0.10; normal: C, 0.89+/-0.02 versus P, 0.83+/-0.05; P<0.05) and the numbers of proliferating intimal smooth muscle cells and lowered serum cholesterol without altering the proportion of aortic lipids that was oxidized. Probucol promoted endothelial regeneration in the injured aorta in cholesterol-fed rabbits (25% increase in reendothelialization, P<0.05) and in those on normal chow (37% increase, P<0.01). This was associated with both improved endothelial function as assessed by enhanced aortic ring relaxation and cGMP production in response to acetylcholine and decreased intimal thickening. CONCLUSIONS: Probucol inhibits intimal thickening in balloon-damaged arteries of rabbits by promoting the regeneration of functional endothelium, without affecting the proportion of aortic lipids that was oxidized. This novel in vivo finding helps explain how probucol inhibits restenosis after coronary angioplasty and highlights potential new targets for therapeutic intervention.

Angioplasty, Balloon↗
PubMed2003

Contrast echocardiography: potential for the in-vivo study of pediatric myocardial preservation.

BACKGROUND: Myocardial contrast echocardiography (MCE) has been used successfully during adult cardiac surgery to image myocardial perfusion. Recently it has been suggested this technique is capable of detecting microvascular injury and inflammation because sonicated albumin microbubbles adhere to activated neutrophils and, in the presence of denuded or inflamed endothelium, they persist within the microvasculature rather than passing unimpeded, which results in profound slowing of their transit rates. The technique has not previously been used during congenital heart surgery; however significant potential is suggested in this setting in which myocardial inflammation may contribute to postoperative myocardial dysfunction, a leading cause of morbidity and mortality. We have performed a preliminary study to assess the safety and feasibility of MCE in the pediatric intraoperative environment and to examine myocardial transit rates. METHODS: Sonicated albumin microbubbles were injected with cardioplegia during bypass in 16 children (aged 3 weeks to 8.5 years). Images were collected using transesophageal echocardiography. Complications, post-bypass electrocardiographic, echocardiographic, and outcome data were recorded. Myocardial transit rates were calculated using videointensity analysis, assessed for reproducibility and correlated with demographic and intraoperative variables and postoperative outcome. RESULTS: The technique was performed safely, with good reproducibility. Myocardial persistence of microbubbles, which occurred in 6 patients, was associated with crystalloid cardioplegia, prolonged preischemic bypass (r = 0.72, p = 0.004), or ischemic time (r = 0.69, p = 0.002). CONCLUSIONS: Intraoperative MCE shows potential as an in vivo technique for the study of pediatric myocardial preservation.

Albumins↗