bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological markers of smoking and their relation to coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial.
Authors: Knoke J D , Hunninghake D B , Heiss G
Published: June 2011

Several physiological variables which have previously been found to be associated with extent of cigarette smoking were investigated in a population selected to be free of existing coronary heart disease yet having high circulating cholesterol levels. Of these variables, white blood cell count had the strongest association with the extent of smoking. The addition of hematocrit and heart rate to white blood cell count strengthened the association. Given these three variables, however, other physiological variables had a minor effect on the association. Finally, the combination of these three physiological variables was more strongly predictive of subsequent coronary heart disease than was self-reported smoking level.
Insulin resistance and impaired glucose tolerance in the atherosclerosis-prone LA/N corpulent rat.
Authors: Russell J C , Ahuja S K , Manickavel V , Rajotte R V , Amy R M
Published: June 2011

The LA/N-cp rat is, when homozygous for the cp gene, hyperphagous, hyperlipidemic, and corpulent. The corpulent males develop atherosclerotic disease and myocardial lesions while corpulent females and lean rats do not. The fasting plasma glucose concentrations of corpulent rats are in the normal range, but insulin concentrations are mildly elevated in corpulent females and markedly elevated in corpulent males. Glucose tolerance testing reveals a glucose intolerance in corpulent rats in the presence of very high insulin concentrations, and this deficiency is more severe in the male rats. Glucagon concentrations are higher in corpulent rats than lean rats at 3 months of age and decrease progressively with age. In contrast, glucagon concentrations increase with age in lean rats and are higher than those in corpulent rats at 9 months. The islets of Langerhans of corpulent rats exhibit marked hyperplasia that increases with age. The hyperplasia is less extreme in corpulent female rats. The abnormalities suggest that this strain of rats has an insulin resistance leading to impaired glucose tolerance and progressive pancreatic disturbance. This process may be related to an accompanying defect causing elevated concentrations of very low density lipoproteins and correlates with the development of atherosclerotic disease.
Effects of selective breeding on the cholesterolemic responses to dietary saturated fat and cholesterol in baboons.
Authors: McGill H C , McMahan C A , Mott G E , Marinez Y N , Kuehl T J
Published: June 2011

Positive assortative mating of baboons (Papio sp.) based on elevation of serum cholesterol concentrations in response to a cholesterol- and saturated fat-enriched diet produced 64 progeny (30 high line; 34 low line). When the animals were 3 to 4 years of age, we tested their lipoprotein cholesterol responses to dietary cholesterol and fat in a factorial experiment with two levels of dietary cholesterol (1.7 and less than 0.01 mg/kcal) and two types of fat, coconut oil (P/S 0.1) and corn oil (P/S 3.5), each providing 40% of total calories from fat; we also tested their responses to chow. The high line animals had significantly higher very low density plus low density lipoprotein (VLDL + LDL) and high density lipoprotein (HDL) cholesterol levels on all diets. The effects of dietary cholesterol on VLDL + LDL cholesterol concentrations were greater in high line animals than in low line animals, but dietary cholesterol's effects on HDL cholesterol were similar in both lines. The effects of saturated fat, compared to unsaturated fat, on both VLDL + LDL and HDL cholesterol levels were similar in both lines. Selective breeding produced lines diverging in lipoprotein cholesterol concentrations by acting on several different genetically mediated processes that control serum lipoprotein levels. At least one of these processes involves responsiveness of serum VLDL + LDL cholesterol concentration to dietary cholesterol.
Role of phosphoinositides in the regulation of endothelial prostacyclin production.
Authors: Halldórsson H , Kjeld M , Thorgeirsson G
Published: June 2011

To elucidate the role of the phosphoinositide signal transduction system in endothelial endothelial prostacyclin production, endothelial cells from human umbilical veins previously labelled with 3H-inositol were incubated with thrombin or histamine. Water-soluble inositol phosphates were separated on anion exchange columns. Both agonists evoked transient bursts of inositol phosphate production with inositol trisphosphate peaking at 15 seconds in histamine-stimulated cells and at 60 seconds in thrombin-stimulated cells. The inositol phosphate production was closely linked to prostacyclin production. After stimulation, there was concurrent desensitization to prostacyclin production and formation of inositol phosphates. Arachidonic acid and the Ca2+-ionophore A23187 did not affect inositol phosphate production in concentrations sufficient to increase prostacyclin production 20-fold, and they did not affect desensitization to a subsequent thrombin stimulation. The phorbol ester 12-o-tetradecanoyl phorbol 13-acetate, a stimulator of protein kinase C, inhibited thrombin-induced generation of inositol phosphates, enhanced A23187-mediated prostacyclin production, and had complex effects on thrombin-mediated prostacyclin production, but had no effect on its production from extrinsic arachidonic acid. The current data suggest that production of inositol phosphates is a link in receptor stimulation of endothelial cells to produce prostacyclin and that associated activation of protein kinase C affects both the generation of second messengers and the release of arachidonic acid.
Mortality and cholesterol metabolism in familial hypercholesterolemia. Long-term follow-up of 96 patients.
Authors: Miettinen T A , Gylling H
Published: June 2011

The aim of this prospective study was to explore the association of different prognostic factors including parameters of cholesterol metabolism with coronary morbidity and mortality in a study group of 96 patients who were heterozygous for familial hypercholesterolemia. During a 15-year follow-up period, 27% of the patients (44% of the men and 10% of the women, p less than 0.01) died from coronary disease, and an additional 4% died of noncoronary causes. Of the baseline characteristics, male gender, previous myocardial infarction, and smoking were the classical risk factors significantly associated with poor cardiac prognosis. In addition, a low bile acid synthesis predicted enhanced coronary mortality both in univariate and multivariate analysis, and in men bile acid synthesis was significantly correlated with cardiac mortality. Further analysis indicated that also in subjects without baseline myocardial infarction, low bile acid, cholesterol synthesis, or both predicted increased risk of coronary events. In multivariate analysis, male gender, previous myocardial infarction, and low bile acid synthesis at baseline explained 5%, 15%, and 5% (25%), respectively, of the variability of survival. Age, serum total cholesterol, and triglyceride values were unrelated to survival.
Binding of apolipoprotein A-I and apolipoprotein A-IV to cultured bovine aortic endothelial cells.
Authors: Savion N , Gamliel A
Published: June 2011

Adult bovine aortic endothelial (ABAE) cells specifically bound 125I-labelled high density lipoprotein3 (125I-HDL3), and saturation of the binding was observed at a concentration of about 50 to 100 micrograms protein/ml. The binding of purified apolipoproteins (apo) A-I and A-IV to cultured ABAE cells and the correlation of this binding with the binding of HDL to the cells was studied. ABAE cells bound 125I-labelled apo A-I (125I-apo A-I) and after a 3-hour exposure to the ligand, most of the radioactivity (82%) was associated with the cell surface and was accessible for trypsinization. Saturation of 125I-apo A-I binding was observed at a concentration of 3 micrograms/ml; each cell possessed 1.38 X 10(5) high affinity binding sites (Kd = 2.04 X 10(-8) M). The cultures also bound 125I-labelled apo A-IV (125I-apo A-IV), and saturation of the binding was observed at a concentration of 2 micrograms/ml. Each cell possessed 5.4 X 10(4) high affinity binding sites for apo A-IV (Kd = 1.45 X 10(-8) M). Addition of either excess unlabelled apo A-I or excess unlabelled apo A-IV competed with the binding of both iodinated apo A-I and apo A-IV. It suggests that apo A-I and A-IV share the same binding site on endothelial cells. HDL also successfully competed with the binding of apo A-I and A-IV to ABAE cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Fibronectin in platelet adhesion to human collagen types I and III. Use of nonfibrillar and fibrillar collagen in flowing blood studies.
Authors: Nievelstein P F , D'Alessio P A , Sixma J J
Published: June 2011

Platelet deposition at high wall shear rates on collagen type I and type III purified from human umbilical arteries is dependent on the presence of fibronectin and von Willebrand factor (VWF). The role of fibronectin at low wall shear rates (less than or equal to 500 s-1), where platelet deposition was independent of VWF, was studied with purified collagen I and III. Platelet deposition on nonfibrillar collagen I was fibronectin-dependent at all wall shear rates. Platelet deposition on nonfibrillar collagen type III was fibronectin-dependent at 300 s-1 and higher shear rates. By using a mixture of nonfibrillar type I and III, platelet deposition was found to be fibronectin-dependent at the tested wall shear rates (20, 100, and 300 s-1). This dependency was less than with nonfibrillar type I only, but more than with nonfibrillar type III. For platelet deposition on reconstituted type I or type III collagen fibrils, no fibronectin dependency was observed up to the highest wall shear rate tested (1800 s-1). The same results were obtained with a mixture of native type I and III fibrils. Thus, the dependence of platelet deposition on fibronectin is determined by the collagen type and the wall shear rate. The dependence on the fibronectin concentration was tested with nonfibrillar collagen type I at a wall shear rate of 300 s-1. Platelet deposition increased with increased fibronectin concentration up to a level of 700 micrograms/ml and leveled off above this concentration.
Very low density lipoprotein triglyceride metabolism in relatives of hypertriglyceridemic probands. Evidence for genetic control of triglyceride removal.
Authors: Sane T , Nikkilä E A
Published: June 2011

The production and catabolism of very low density lipoprotein triglycerides (VLDL-TG) were determined in 11 index patients with primary hypertriglyceridemia and in their 70 first-degree relatives. In the probands the mean value for VLDL-TG production rate was twice normal, and the mean fractional catabolic rate (FCR) was reduced to 50% from normal. A similar kinetic pattern was also observed in most hypertriglyceridemic relatives. In the normotriglyceridemic relatives the mean values of both kinetic parameters were comparable to those of controls. No kinetic differences were observed between families with familial hypertriglyceridemia, familial combined hyperlipidemia, or genetically unclassified hypertriglyceridemia (all diagnosed by lipoprotein phenotypes). Thus, no explanation for the phenotypic differences between the two forms of familial hyperlipoproteinemia was found in plasma VLDL-TG metabolism. When the families were grouped according to the VLDL-TG production rate of the proband, there was no significant difference between the VLDL-TG production rates of relatives of "overproducer" probands and relatives of the probands with normal VLDL-TG production rate. In contrast, relatives of low FCR probands had significantly lower mean FCR than the relatives of probands with a normal FCR. This difference in FCR was present both in hypertriglyceridemic and normotriglyceridemic relatives. These results suggest that the catabolism (lipolysis) of VLDL-TG is under genetic control, whereas the VLDL-TG production rate is mainly related to obesity. It is likely that hypertriglyceridemia often develops on the basis of VLDL overproduction in individuals who have a genetically low VLDL triglyceride removal (lipolytic) capacity.
Antiatherogenic effect of olive and corn oils in cholesterol-fed rabbits with the same plasma cholesterol levels.
Authors: Leth-Espensen P , Stender S , Ravn H , Kjeldsen K
Published: June 2011

Two groups of 18 rabbits were fed isocaloric, cholesterol-enriched diets for 8 weeks. The diet for one group was supplemented with 5% corn oil. The concentration of cholesterol in plasma was determined weekly and the amount of cholesterol in the diet was adjusted individually so that each rabbit had a mean plasma cholesterol concentration of about 45 mM during the experimental period. The aortic cholesterol concentrations were 122 +/- 29 and 193 +/- 38 (mean +/- SEM) mumol/g protein for the corn-oil group and the control group, respectively (p less than 0.05). In a similar experiment, each of 36 rabbits was given a mean plasma cholesterol level of about 20 mM over a period of 12 weeks. One-third of the rabbits received 10% to 15% corn oil, another third 10% to 15% olive oil, while the last third served as a control group. The aortic cholesterol concentrations were 98 +/- 25, 57 +/- 9, and 131 +/- 32 mumol/g protein, respectively. The value for the olive-oil group was significantly (p less than 0.01) lower than the value for the control group. The triglyceride concentrations and the distributions of cholesterol between HDL, LDL, and VLDL in plasma showed no significant differences between the plant-oil groups and their control groups. This suggests that plant oils have a direct effect on the aortic cholesterol metabolism.
Identification of Apo B-100 segments mediating the interaction of low density lipoproteins with arterial proteoglycans.
Authors: Camejo G , Olofsson S O , Lopez F , Carlsson P , Bondjers G
Published: June 2011

The interactions of low density lipoprotein (LDL) and apolipoprotein (apo) B-100 segments with chondroitin-6-SO4 rich aortic proteoglycans aggregate (CSPG) were studied by using quantitative frontal elution affinity chromatography. The affinity of the agarose-CSPG was higher for LDL than for very low density lipoprotein and high density lipoprotein was not bound. LDL from different individuals had dissociation coefficients (Kd) from 28 to 179 nM. Experiments with tryptic hydrolysates of apo B suggested that the capacity of LDL to bind with CSPG resides in the protein. Nine apo B-100 hydrophilic peptides, 12 to 26 amino acids long, were selected, and three were found to interact with the agarose-bound CSPG: apo B P-1 (LRKHKLIDVISMYRELLKDLSKEA, residues 4230 to 4254), apo B P-2 (RLTRKRGLKLATALSLSNK, residues 3359 to 3377), and apo B P-11 (RQVSHAKEKLTALTKK, residues 2106 to 2121). These peptides competed with LDL for binding to the agarose-bound and soluble CSPG; apo B P-2 was the most effective. This correlates with Kd values: 63, 86, and 82 microM for apo B P-2, P-1, and P-11, respectively. The peptides shared an excess of positive-charged side chains. Apo B P-2 belongs to the lys- and arg-rich, LDL-receptor domain. Apo E also binds to the agarose-proteoglycan. The results suggest that apo B regions with sequences and charge distributions analogous to those of residues 3359 to 3377, 4230 to 4254, and 2106 and 2121 are among those responsible for the interaction of LDL with intima-media CSPG.
Human aortic fibrolipid lesions. Immunochemical localization of apolipoprotein B and apolipoprotein A.
Authors: Bocan T M , Brown S A , Guyton J R
Published: June 2011

Comparative localization of apolipoproteins (apo) B and A in small, raised fibrolipid lesions was performed to determine whether low density lipoproteins (LDL) and high density lipoproteins (HDL) may be involved in the formation of the earliest identifiable lipid-rich core regions found in atherosclerotic fibrous plaques. Apo B was observed associated with the superficial layer of foam cells in collagenous areas of the lesion cap and within the lipid-rich core region. The lipid-rich core region was well-circumscribed by an intense band of apo B staining along both luminal and medial aspects. Apo A staining was confined to the noncellular elements of the fibrolipid lesion. Collagenous areas were speckled with fine, punctate granules of immunoreactive apo A. A homogeneous, granular apo A staining pattern was characteristic throughout the core region. With these data from a relatively early lesion in the development of the atherosclerotic fibrous plaque, we conclude that: 1) both LDL and HDL can accumulate in the lipid-rich core region since no preferential staining for apo B over apo A was observed in this region, and 2) the paucity of cell-associated apo A staining in small fibrolipid lesions suggests that HDL interacts with the arterial wall differently than does HDL.
Association between retinopathy and impaired peripheral arterial circulation in insulin-dependent diabetic patients.
Authors: Riccardi G , Vaccaro O , Rivellese A , Romano G , Cambri V , Rubba P , Pauciullo P , Greco G , Iovine C , Mancini M
Published: June 2011

This study was undertaken to investigate whether, in insulin-dependent diabetic patients, an association exists between microangiopathy (evaluated as retinopathy) and macroangiopathy (evaluated as impaired arterial circulation of the lower limbs). A total of 38 diabetic outpatients with either background (n = 25) or proliferative (n = 13) retinopathy, plus 18 diabetic outpatients of similar age (46.8 +/- 13.4 vs. 43.0 +/- 11.0 yrs) and duration of diabetes (16.8 +/- 5.8 vs. 14.8 +/- 15.1 yrs) without retinopathy were studied. Retinopathy was defined according to fluorescein angiography. The arterial circulation of the lower limbs was evaluated by the ankle/arm systolic pressure index with ultrasonic Doppler end-point detection and echo-Doppler examination of the pelvic vessels. The ankle/arm index was significantly lower in diabetic patients with retinopathy (0.98 +/- 0.16 vs. 1.12 +/- 0.11, p less than 0.002) and the percentage of persons with definitely impaired arterial circulation of the legs (ankle/arm systolic blood pressure less than 0.95) was significantly higher in this group (36.8% vs. 5.5%, p = 0.038). Of 14 patients with retinopathy and peripheral arterial disease, only three (21%) had detectable stenoses of the pelvic vessels. The overall profile of cardiovascular risk factors was similar in the two groups. The multivariate analysis indicated that retinopathy was the best correlate of impaired peripheral arterial circulation. In conclusion, in our study population, an association between retinopathy and impaired peripheral arterial circulation of the legs existed independently of major cardiovascular risk factors.
Balloon catheter injury to rabbit carotid artery. I. Changes in smooth muscle phenotype.
Authors: Manderson J A , Mosse P R , Safstrom J A , Young S B , Campbell G R
Published: June 2011

Stereology was used to investigate the changes in ultrastructure of smooth muscle cells during the formation of an experimental intimal thickening induced by injury with an inflated balloon catheter. The volume density of myofilaments in the cell cytoplasm was measured in smooth muscle cell-lined areas (which are freely permeable to Evans blue dye and, hence, stain blue) and in re-endothelialized areas (which remain white after injection of Evans blue) of the rabbit carotid artery. Two weeks after injury, the volume densities of myofilaments in the intimal smooth muscle cells in both white and blue areas were significantly less than that for control medial smooth muscle (67.9% +/- 3.6%; mean +/- SE), being 38.8% +/- 1.0% and 35.9 +/- 3.3%, respectively. By 6 weeks after injury, the volume density had increased significantly in both white (55.1% +/- 3.4%) and blue areas (53.5% +/- 3.0%), and these values did not change significantly by 18 weeks. The volume density of myofilaments in the luminal (lining) smooth muscle cells in the blue areas was significantly less than that of control medial cells and remained low (26.7% +/- 2.1%) up to 18 weeks after injury. The initial balloon-induced injury caused considerable damage to the smooth muscle cells in the media, and the remaining medial cells underwent similar changes in ultrastructure to the cells in the neointima. At 2 weeks, the cells had a low volume density of myofilaments (44.9% +/- 2.4%), which returned to a level not significantly different from the control artery by 6 weeks after injury. There were no differences in the estimates of the volume density of myofilaments between the inner and outer media of the injured arteries. These findings suggest that, after injury produced by a balloon catheter, the smooth muscle cells in both the media and the resultant intimal thickening undergo a reversible change in ultrastructure.
Apolipoprotein, low density lipoprotein subfraction, and insulin associations with familial combined hyperlipidemia. Study of Utah patients with familial dyslipidemic hypertension.
Authors: Hunt S C , Wu L L , Hopkins P N , Stults B M , Kuida H , Ramirez M E , Lalouel J M , Williams R R
Published: June 2011

Familial dyslipidemic hypertension (FDH) is a syndrome recently described from sibships selected for early familial hypertension and found to have one or more of three fasting lipid abnormalities [high triglycerides, low high density lipoprotein (HDL) cholesterol, high low density lipoprotein (LDL) cholesterol]. In further analyses of these same 131 hypertensive subjects, apolipoprotein A-I and B, fasting plasma insulin (adjusted for body mass index), and detailed anthropometrics were different in two subgroups of FDH. Of 63 FDH patients, 19 met the criteria for familial combined hyperlipidemia (FCHL); 44 did not, but still had high triglyceride and/or low HDL cholesterol levels. When compared to 20 normolipidemic hypertensive patients, the 19 hypertensive patients with FCHL had 196% higher very low density lipoprotein cholesterol (p = 0.0001), 33% higher apolipoprotein B (p = 0.0002), smaller LDL particles (p = 0.007), and 73% higher fasting insulin (p = 0.003), but no significant differences in body mass index or skinfold thicknesses. The other 44 FDH patients without FCHL had 33% lower HDL (p = 0.0001), with only 8% lower apolipoprotein A-I levels (p = 0.20); significantly higher subscapular skinfolds (p = 0.02), weights (p = 0.002), body mass index (p = 0.006), knee widths (p = 0.0007), and wrist circumferences (p = 0.0009); smaller, denser LDL subfractions (p = 0.001); and increased apolipoprotein B levels (p = 0.01) compared to the normolipidemic hypertensive group. Increased fasting insulin levels were similar to the normolipidemic group and significantly lower than the FCHL group after adjustment for body mass index, suggesting a relationship between obesity and fasting insulin levels only in the non-FCHL group. We conclude that FDH consists of at least two subgroups: 1) FCHL with high apolipoprotein B, small LDL particles, and increased fasting plasma insulin levels, and 2) a less well-defined residual having upper central obesity with low HDL cholesterol and high triglyceride levels. Elevated insulin levels found in both groups, but possibly originating through different physiological mechanisms, may provide the pathophysiological connections between dyslipidemia, obesity, and hypertension.
Differential distribution of apolipoprotein E isoforms in human plasma lipoproteins.
Authors: Steinmetz A , Jakobs C , Motzny S , Kaffarnik H
Published: June 2011

The polymorphism of apolipoprotein E (apo E) accounts for a substantial amount of the genetic variance of cholesterol levels in man. The epsilon-2 allele and the epsilon-4 allele raises plasma and low density lipoprotein cholesterol levels as compared to the epsilon-3 allele. Whereas the lower cholesterol levels in carriers of the epsilon-2 allele can, at least in part, be attributed to the grossly deficient binding of apo E-2 to the apo B,E receptor, apo E-3 and E-4 bind to the same degree. We used gel filtration and ultracentrifugation to separate lipoproteins and subsequent immunoblotting analysis to study the apo E isoform distribution. We always found lipoproteins of lower density relatively enriched in apo E-4 and high density lipoproteins relatively depleted of apo E-4 as compared to apo E-3. This was also seen in plasma of heterozygous subjects that simultaneously express two apo E isoforms. Also, the apo E-A-II complex was directly shown by immunoblotting. Furthermore, when purified iodinated apo E was incubated with plasma in vitro, apo E-4 also reassociated more with lipoproteins of lower density than apo E-3. We conclude that apo E-3 and apo E-4 have a different lipoprotein particle distribution in vivo. This differential lipoprotein distribution may account for differences in the metabolism between apo E-3 and E-4.
Effect of normolipemic and hyperlipemic serum on biosynthetic response to cyclic stretching of aortic smooth muscle cells.
Authors: Grande J P , Glagov S , Bates S R , Horwitz A L , Mathews M B
Published: June 2011

Arterial smooth muscle cells synthesize matrix macromolecules in response to mechanical stimulation. Exposure to serum lipids also stimulates connective tissue fiber accumulation. To assess the effect of serum lipids on the biosynthetic response to tensile stress, we subjected rabbit aortic smooth muscle cells that were cultured on purified elastin membranes to cyclic stretching and relaxation 50 times per minute in the presence of serum-free medium (SFM), normolipemic serum (NLS), or hyperlipemic serum (HLS). Incorporation of 14C-proline into proline and into hydroxyproline was taken as a measure of protein and collagen synthesis. When cells were grown in plastic Petri dishes, exposure to NLS or HLS increased both protein and collagen production to the same extent compared to synthesis in SFM (1.7 times for NLS and 1.6 times for HLS; p less than 0.001 compared to SFM). For cells grown on stationary elastin membranes, NLS and HLS also increased protein and collagen synthesis compared to SFM. The effect of NLS was 1.35 times that of HLS for protein and 1.43 times greater for collagen (p less than 0.03). Cyclic stretching in SFM doubled synthesis for both protein (p less than 0.002) and collagen (p less than 0.002) compared to stationary controls, but had no effect on synthesis in NLS. In HLS, however, cyclic stretching elevated synthesis to the same level as was found in NLS (p less than 0.003). We conclude that the relative inhibition of synthesis on stationary membranes by HLS was not due to a toxic effect, since HLS increased synthesis both in Petri dishes and on elastin membranes, and the amplifying effect of cyclic stretching in HLS was similar to that seen in SFM.(ABSTRACT TRUNCATED AT 250 WORDS)
Parental history of diabetes is associated with increased cardiovascular risk factors.
Authors: Haffner S M , Stern M P , Hazuda H P , Mitchell B D , Patterson J K , Ferrannini E
Published: June 2011

Serum insulin concentrations are higher in persons with a positive parental history of diabetes than in persons without such a history. Since hyperinsulinemia is associated with both an increased prevalence of hypertension and an atherogenic pattern of serum lipids and lipoproteins, we hypothesized that among nondiabetic persons, a parental history of diabetes would be associated with an atherogenic pattern of cardiovascular risk factors. In the San Antonio Heart Study, a population-based study of cardiovascular disease and diabetes, we examined 549 nondiabetic persons with a parental history of diabetes and 1167 nondiabetic persons without such a history. Compared to persons without a parental history of diabetes, those with such a history had a more atherogenic pattern of cardiovascular risk factors, including higher body mass index, higher systolic and diastolic blood pressures, higher serum insulin and triglyceride concentrations, and lower levels of high density lipoprotein cholesterol. After adjustment for serum insulin concentration, body mass index, and waist-to-hip ratio, the differences in lipids, lipoproteins, and blood pressure between the two parental history groups were no longer statistically significant. Since persons with a parental history of diabetes are more likely to be prediabetics, the present results suggest that prediabetics have an increased risk of coronary heart disease even before they become diabetic. This phenomenon may help explain why the duration of clinical diabetes is only weakly associated with the risk of coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Responsiveness of the coronary circulation to brief vs sustained alpha-adrenergic stimulation.
Authors: Williams D O , Most A S
Published: June 2011

The effects of brief and sustained pharmacologic alpha-adrenergic stimulation on the coronary arterial circulation were compared in awake pigs. Phenylephrine was administered into the left anterior descending coronary artery (LAD) either as a bolus (eight pigs) or as a 15-minute infusion (eight pigs), with myocardial blood flow measured by the radioactive microsphere technique. Flow in the distribution in the LAD was compared with flow in myocardium perfused by the left circumflex coronary artery (LCF) as the ratio LAD/LCF. This technique corrects for systemic factors capable of modifying oxygen demand, and hence myocardial blood flow, in both zones. After a phenylephrine bolus (50-100 microgram), LAD/LCF fell significantly, whereas no change was observed after the sustained infusion (5-10 and 50-100 microgram/min). Four additional pigs were pretreated with i.v. adenosine to raise myocardial blood flow in excess of demand before sustained stimulation. In this setting LAD/LCF fell significantly during the sustained phenylephrine infusion. Brief alpha-adrenergic stimulation could overcome normal flow regulatory mechanisms and resulted in constriction of coronary resistance vessels. Such changes did not occur after sustained stimulation and suggest an ability of the coronary circulation to offset chronic vasoconstrictive effects. When the myocardium is overperfused, sustained alpha-adrenergic stimulation does not jeopardize myocardial oxygenation and its vasoconstriction potential is unmasked.
Suprasternal notch echocardiography: a two-dimensional technique for evaluating congenital heart disease.
Authors: Snider A R , Silverman N H
Published: June 2011

Two-dimensional suprasternal notch echocardiography was performed in 1033 patients, ages 1 day to 18 years. For the long-axis suprasternal notch view, the transducer was positioned in the suprasternal notch and angled to obtain a plane passing between the right nipple and left scapular tip. In this view, the entire aortic arch, vessels to the head and neck, right pulmonary artery and right bronchus were imaged. The long-axis view was useful for evaluating coarctation and interruption of the aorta, hypoplastic left heart, aortic and pulmonic stenosis and cervical aortic arch. For the short-axis suprasternal notch view the transducer was positioned in the suprasternal notch and angled to obtain a coronal body plane. In this view the transverse aorta, right pulmonary artery, left atrium, innominate veins and superior vena cava were imaged. The short-axis view was useful in the evaluation of children with increased or decreased pulmonary blood flow, persistent left superior vena cava, total anomalous pulmonary venous return to the right superior vena cava, and superior vena caval obstruction after Mustard's operation. In the evaluation of children with congenital heart disease, the suprasternal notch views added significant information to the two-dimensional echocardiographic examination.
Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.
Authors: Naito M , Michelson E L , Kmetzo J J , Kaplinsky E , Dreifus L S
Published: June 2011

Ninety-nine adult mongrel dogs underwent acute ligation of the proximal left anterior descending coronary artery. Thirty minutes later, the occlusion was released to evaluate the effectiveness of five antiarrhythmic protocols in eliminating reperfusion ventricular fibrillation. The five protocols included: protocol 1 --i.v. lidocaine, preligation and prerelease (n = 19); protocol 2 -- i.v. lidocaine, prereperfusion only (n = 22); protocol 3 -- chronic, oral, daily amiodarone for 2 weeks preligation (n = 19); protocol 4 -- i.v. procainamide, preligation and prereperfusion (n = 21); and protocol 5 -- i.v. verapamil, prereperfusion (n = 18). Each regimen was evaluated with respect to the incidence of reperfusion ventricular fibrillation in dogs that survived to reperfusion, and the results were compared to 77 control dogs that underwent identical coronary artery occlusion and release procedures without drug therapy. The incidence of reperfusion ventricular fibrillation was as follows: protocol 1 -- seven of 15 dogs (47%); protocol 2 -- six of 18 (33%); protocol 3 -- 11 of 16 dogs (69%); protocol 4 -- eight of 17 dogs (47%); and protocol 5 -- 10 of 17 dogs (59%), compared with 36 of 60 (60%) in control dogs. Using chi-square analysis, protocol 2 was beneficial (p < 0.05). The dogs were then stratified into high- and low-risk subgroups based on the arrhythmic events of the antecedent coronary artery ligation periods, and predictive risk indexes for the occurrence of reperfusion ventricular fibrillation were developed. the Mantel-Haenszel method of statistical analysis revealed that none of these protocols resulted in a statistically significant reduction in the incidence of reperfusion ventricular fibrillation. Thus, use of these predictive indexes plus appropriate statistical methods has revealed, unexpectedly, limitations in the efficacy of a spectrum of antiarrhythmic agents in preventing reperfusion ventricular fibrillation.
The pathophysiology of failure in acute right ventricular hypertension: hemodynamic and biochemical correlations.
Authors: Vlahakes G J , Turley K , Hoffman J I
Published: June 2011

Acute right ventricular (RV) hypertension and failure occur clinically. In this study we examined the mechanism of RV failure. Adult dogs were studied acutely under anesthesia; dogs were instrumented for measurement of pressures and right coronary artery blood flow. Myocardial blood flow and cardiac output were determined with radionuclide-labeled microspheres, and the presence of ischemia was determined by biochemical analysis of ventricular biopsies. RV hypertension was produced by constricting the pulmonary artery and was increased until RV failure occurred, as evidenced by decreased aortic pressure and cardiac output and increased RV end-diastolic pressure. With increasing RV systolic pressure, RV myocardial blood flow failed to increase in proportion to demand. At the onset of RV failure, there was no reactive hyperemia of right coronary flow compared with control, indicating the absence of further coronary vascular reserve; biochemical analysis demonstrated that the RV free wall was ischemic; the LV free wall was not. Infusion of phenylephrine raised aortic pressure and hence, myocardial perfusion pressure; RV failure reversed as shown by decreased RV end-diastolic pressure and increased cardiac output and RV systolic pressure; reactive hyperemia of right coronary flow was restored and the biochemical indexes of ischemia were reversed, demonstrating that ischemia is the cause of failure in acute RV hypertension.
Hemodynamic effects of oral pirbuterol in chronic severe congestive heart failure.
Authors: Awan N A , Evenson M K , Needham K E , Evans T O , Hermanovich J , Taylor C R , Amsterdam E , Mason D T
Published: June 2011

The achievement of satisfactory ambulatory therapy of severe chronic congestive heart failure may be helped by the development of safe and orally effective cardiotonic agents. Therefore, we evaluated by cardiac catheterization and limb plethysmography the temporal cardiocirculatory responses of the new ingestible beta agonist pirbuterol in 10 coronary heart disease patients with severe congestive heart failure refractory to digitalis and diuretics. After a single oral dose of 0.4 mg/kg, ventricular dysfunction was considerably improved during 6 hours of hemodynamic monitoring. Cardiac index increased from a control of 1.7 l/min/m2 to 2.6 l/min/m2 (p < 0.001) at 1 hour and to 2.4 l/min/m2 (p < 0.005) at 3 hours and was 2.2 l/min/m2 (p < 0.001) at 6 hours; left ventricular filling pressure decreased from a control of 24 mm Hg to 19 mm Hg (p < 0.005) at 1 hour and to 18 mm Hg (p < 0.005) at 3 hours and was 22 mm Hg (p < 0.05) at 6 hours. Concomitantly, the peak increment in heart rate (6 beats/min) was minimal and without ectopy and mean arterial blood pressure decreased only 10 mm Hg. total systemic vascular resistance declined by 887 dyn-sec-cm-5, forearm venodilation occurred and the rate-pressure product was unaltered. Thus, oral pirbuterol provides beneficial hemodynamic effects in patients with severe left ventricular dysfunction and appears potentially useful for long-term management of low-output congestive heart failure.
Aortic valve replacement without myocardial revascularization in patients with combined aortic valvular and coronary artery disease.
Authors: Bonow R O , Kent K M , Rosing D R , Lipson L C , Borer J S , McIntosh C L , Morrow A G , Epstein S E
Published: June 2011

To test the hypothesis that coronary artery bypass grafting (CABG) is not routinely required in patients undergoing aortic valve replacement (AVR) who have coexistent coronary artery disease (CAD), we compared the results of operation in 55 consecutive symptomatic patients who had CAD and underwent AVR without CABG with results in another 142 patients without CAD who underwent AVR during the same period, and with published results from other centers in which CABG was used in patients with CAD who underwent AVR. Operative mortality was 4% in patients with CAD and 5% in patients without CAD. Late survival was not significantly different between the two groups when analyzed for the entire population (80% survival at 3 years in CAD patients, 82% for non-CAD patients), or for the subgroup of patients with aortic stenosis, aortic regurgitation or aortic stenosis plus regurgitation. Eight patients with CAD (15%) developed recurrent angina after AVR (mean follow-up 43 months); only three patients (6%) required CABG because of medically refractory angina (12-43 months). Operative mortality, operative infarction (9%), recurrent angina and long-term survival in patients with CAD after AVR were similar to those at other centers after AVR plus CABG. These data suggest that preoperative detection of CAD does not necessitate CABG in all patients at the time of AVR.
Effect of direct-current countershocks on regional myocardial contractility and perfusion. Experimental studies.
Authors: Kerber R E , Martins J B , Gascho J A , Marcus M L , Grayzel J
Published: June 2011

Very high energy electrical countershocks can cause morphologic damage to the myocardium. In this study we searched for functional correlates of these shock-induced morphologic changes. We used ultrasonic sonomicrometers to measure myocardial contractility and radiolabeled microspheres to assess perfusion. Acute and chronic experiments were conducted in 45 dogs, assessing the effect of both direct (epicardial) and transthoracic shocks on beating and fibrillating hearts. High-energy or rapidly repeated epicardial shocks caused subepicardial contraction abnormalities. This indicates that electrical current delivered to the myocardium in sufficiently high amounts and concentration can cause functional damage. Thus, in open-chest defibrillation during cardiac surgery, low energies (10-20 J) should be used initially and higher energies resorted to only if lower-energy shocks fail. However, single and multiple transthoracic shocks up to 460 J delivered energy caused no detectable contraction abnormalities. Myocardial perfusion did not fall after shocks. Thus, high-energy transthoracic shocks may have no deleterious effects on the contraction and perfusion of normal myocardium.
Hypertrophic cardiomyopathy with unusual locations of left ventricular hypertrophy undetectable by M-mode echocardiography. Identification by wide-angle two-dimensional echocardiography.
Authors: Maron B J , Gottdiener J S , Bonow R O , Epstein S E
Published: June 2011

Twenty-one patients without evidence of hypertrophy by M-mode echocardiography were studied by wide-angle two-dimensional echocardiography to determine if they had a form of hypertrophic cardiomyopathy that could not be detected by conventional M-mode echocardiography. Each patient was suspected clinically of having hypertrophic cardiomyopathy because of a distinctly abnormal ECG and either a family history of hypertrophic cardiomyopathy or cardiac symptoms. Patients were 5-49 years old (mean 16 years) and 16 of the 21 had no functional limitation. The most common electrocardiographic abnormalities were deep Q waves, T-wave inversion and right ventricular hypertrophy. Using wide-angle two-dimensional echocardiography to reconstruct the geometry of the left ventricular wall, 16 of the 21 patients (76%) were shown to have prominent but unusually located regions of left ventricular wall hypertrophy. In each instance, the hypertrophy involved regions of the left ventricular wall through which the M-mode ultrasound beam does not usually pass, i.e., posterior ventricular septum (seven patients), anterior or lateral left ventricular free wall (seven patients) and ventricular septum near the apex (two patients). There was no echocardiographic or hemodynamic evidence of left ventricular outflow tract obstruction in any patient. Hence, some patients with hypertrophic cardiomyopathy may have substantial hypertrophy present in unusual locations of the left ventricular wall. Although electrocardiographic abnormalities suggested the presence of myocardial disease, conventional M-mode echocardiography (performed from standard parasternal positions) did not reliably identify such sites of hypertrophy, which were limited to regions of the left ventricle not accessible to the M-mode beam. Only wide-angle two-dimensional echocardiography permits definitive identification of these unusually located regions of cardiac hypertrophy and confirmation of the diagnosis of hypertrophic cardiomyopathy.
Comparisons of the effects on survival after coronary artery surgery in subgroups of patients from the Seattle Heart Watch.
Authors: DeRouen T A , Hammermeister K E , Dodge H T
Published: June 2011

We compared the survival of medically and surgically treated coronary artery disease patients in subgroups of patients to determine those most or least likely to benefit from surgery after an average of 5.5 years of follow-up. Cox's regression model for survival analysis was used in conjunction with data from all patients to estimate and test for the significance of the effects of surgery on survival in subgroups of patients, defined by one or more of the following variables: number of stenotic vessels (greater than or equal to 70%), ejection fraction, age, heart murmur, diuretic therapy, ventricular arrhythmia on resting ECG, left main coronary artery stenosis greater than or equal to 50%, previous myocardial infarction, cardiomegaly, congestive heart failure, unstable angina, and functional class. The Cox model adjusts for differences between medical and surgical patients in variables shown to be predictive of survival. A statistically beneficial effect of surgery on survival was seen in patients with two- or three-vessel disease, ejection fraction greater than or equal to 30%, age greater than or equal to 48 years, no heart murmur, no diuretic therapy, no ventricular arrhythmia on resting ECG, left main coronary artery stenosis less than 50%, no cardiomegaly, and no congestive heart failure. The converse subgroups defined by these variables did not show a significant beneficial effect from surgery. However, patient subgroups defined by presence or absence of prior myocardial infarction or unstable angina and New York Heart Association functional class I-II vs III-IV all showed beneficial effects from surgery.
Diastolic sounds and murmurs associated with mitral valve prolapse.
Authors: Wei J Y , Fortuin N J
Published: June 2011

Although mitral valve prolapse is often associated with a systolic click or murmur, it is not widely appreciated that a sound or murmur may also occur in diastole. Nine patients with a systolic click or murmur and echocardiographic evidence of mitral prolapse had, in addition, a diastolic sound or an early diastolic murmur best heard at the apex or left sternal border. The sound, which was of high frequency and easily audible, followed A2 by 70-110 msec (mean 94 +/- 5 msec), and coincided with the point where the prolapsed posterior leaflet returned from the left atrium and recoapted with the anterior mitral leaflet. The diastolic sound occurred 40-60 msec (mean 53 +/- 4 msec) before the E point of the echocardiogram and O point of the apexcardiogram, and even longer before the rapid-filling wave. The diastolic murmur, also of high frequency, was brief and decrescendo, and simulated aortic regurgitation in two patients. Thus, mitral prolapse may be associated with a sound or murmur in diastole. When a diastolic sound or murmur is best heard apically, even if accompanied by a systolic murmur, mitral valve prolapse should be considered.
Antiarrhythmic efficacy of encainide in patients with refractory recurrent ventricular tachycardia.
Authors: Mason J W , Peters F A
Published: June 2011

Encainide is a new agent for treating ventricular arrhythmias. We attempted long-term oral therapy with encainide in 38 patients with recurrent, strikingly drug-refractory ventricular tachycardia. The usual daily dose of encainide ws 150-250 mg divided into four or six doses. The mean period until withdrawal of encainide or the date of follow-up was 4.2 months. Encainide completely eliminated recurrence of ventricular tachycardia in 54% of the patients for 6 months of therapy and in 29% of the patients for 18-30 months of therapy. Twelve patients (32%) had side effects possibly due to encainide; in four, the arrhythmia may have been worsened by encainide. During chronic therapy, encainide increased the PR interval by 18% and the QRS duration by 32%. There was no significant change in the corrected QT interval. The presence of QRS prolongation appeared to correlate with antiarrhythmic effect. We conclude that encainide is a safe, well-tolerated antiarrhythmic agent that is often effective against previously drug-refractory ventricular tachycardia.
Quantitative detection of regional left ventricular contraction abnormalities by two-dimensional echocardiography. I. Analysis of methods.
Authors: Moynihan P F , Parisi A F , Feldman C L
Published: June 2011

Different approaches to the quantification of regional left ventricular (LV) function from two-dimensional echocardiographic (2-D echo) images were assessed for their ability to optimize interobserver reproducibility in a heterogeneous patient population and to minimize the variability of regional function observed in a homogeneous normal population. Areas, hemiaxis and perimeter measurements were examined, as were the effect of the degree of image subdivision into halves, quadrants or octants. Each approach was also tested using both a fixed and a floating frame of reference for the definition of a regional-axis system. The area method was consistently superior to either linear method in optimizing both reproducibility and variability. Reproducibility decreased inversely with the degree of subdivision. The axis-system frame of reference had no effect on reproducibility. The floating-axis system yielded the same variability as the fixed system for short-axis sections at the mitral valve level, but slightly less variability for a papillary muscle level section. We conclude that area-based methods are superior for the evaluation of regional LV function with 2-D echo, but the degree of subdivision of the image and the frame of reference chosen do not greatly affect reproducibility or variability and should be chosen based on their performance in a well-defined clinical population.