bluuebunny/crossref_metadata_2025 huggingface dataset:
Passage of low density lipoproteins through monolayers of human arterial endothelial cells. Effects of vasoactive substances in an in vitro model.
Authors: Langeler E G , Snelting-Havinga I , van Hinsbergh V W
Published: June 2011

The endothelium controls the influx of lipoproteins into the arterial wall, a process that may be disturbed in arteriosclerotic blood vessels. We have used an in vitro model to investigate the characteristics of the passage of low density lipoproteins (LDL) through monolayers of human arterial endothelial cells. Umbilical artery, aorta, or carotid artery endothelial cells were cultured on polycarbonate filters and formed a tight monolayer in which the cells were connected by tight junctions. Passage of 125I-LDL through these monolayers proceeded linearly over a 24-hour period. It was threefold lower through monolayers of aorta or carotid artery cells than through monolayers of umbilical artery cells. The LDL passage process did not show saturation with LDL concentrations up to 800 micrograms/ml LDL-protein (i.e., 1.6 nmol/ml apolipoprotein B) between 2 and 4 hours after addition. However, during the first 30 to 60 minutes after addition of high concentrations of LDL, a reduction of the passage rate of both LDL and peroxidase, resulting in an apparent saturation of the passage process, was observed. The passage rate of the negatively charged acetylated LDL was twofold lower than that of native LDL. Addition of histamine to the endothelial monolayer resulted in a large, but transient, increase in permeability paralleled by a decrease in electrical resistance. The effects of histamine were mediated via an H1 receptor. Thrombin and Ca++ ionophore also induced an increase in permeability of the monolayer, while bradykinin did not. The effects of histamine and thrombin were paralleled by a rapid and marked increase in cytoplasmatic Ca++ concentration of the endothelial cells, while bradykinin induced only a small increase. Although the cyclic adenosine 5'-monophosphate-elevating agent, forskolin, markedly decreased the basal rate of LDL passage through the endothelial cell monolayers, it did not change the relative increase in permeability induced by histamine. Thus, histamine induces small, but significant, increases in the permeability of tight endothelial cell monolayers.
Immune mechanisms in atherosclerosis.
Authors: Hansson G K , Jonasson L , Seifert P S , Stemme S
Published: June 2011

To summarize, it is possible that T cell activation in the plaque has four different effects: a direct inhibition of smooth muscle proliferation mediated by IFN-gamma, an indirect stimulation of smooth muscle proliferation via IFN-induced macrophage activation, an induction of responsiveness to PDGF by induction of PDGF receptor expression, and finally, an up-regulation of HDL receptors. The net effect of T cell activation during the vascular response to injury may, therefore, depend on the balance between these mechanisms in any given situation during lesion development. T cell activation may itself be regulated by apolipoprotein E-containing LDL, which thus could form a direct link between lipoprotein accumulation and immune activation. We have recently tried to assess the effect of T cell activation during the response to experimental arterial injury with the use of a drug model. Cyclosporin A is a drug that specifically inhibits T cell activation. Rats treated with cyclosporin A for a short period had significantly smaller intimal lesions than did controls after balloon injury. This could be due to an inhibition of T cell activation, resulting in an inhibition of monocyte-macrophage activation and thereby loss of an important stimulus for intimal cell proliferation. When interpreting these results, one must, however, bear in mind that cyclosporin A could exert as yet unknown nonimmune vascular effects. It is also worth stressing that cell proliferation in the human atherosclerotic plaque may not be as high as in experimental animal lesions. In fact, cell replication may be a very rare event in the average advanced atherosclerotic plaque. Cell proliferation may, however, be associated with an episodic growth of lesions, and growth factor-mediated responses could, therefore, be important for the eventual clinical outcome in the individual patient. In conclusion, cytokines produced during the immune response affect growth and differentiation of vascular cells and could modulate both the response to injury and the local lipid metabolism in an atherosclerotic plaque There is indirect support for paracrine secretion of several of these factors in the atherosclerotic plaque, and activated T lymphocytes and macrophages are abundant in the plaque. This points to the possibility that specific immune responses are associated with the development of atherosclerosis. It is unknown, however, to what extent such immune responses occur or which antigens may elicit these responses.
Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients.
Authors: Rath M , Niendorf A , Reblin T , Dietel M , Krebber H J , Beisiegel U
Published: June 2011

The aim of this study was to determine the extent of accumulation of lipoprotein(a) [Lp(a)] in human arterial wall and to define its potential role in atherogenesis. Biopsies routinely taken from the ascending aorta of 107 patients undergoing aortocoronary bypass surgery were analyzed for lipid and lipoprotein parameters, which were then correlated to serum values. A significant positive correlation was established between serum Lp(a) and arterial wall apolipoprotein (apo)(a) by enzyme-linked immunosorbent assay. High serum Lp(a) also led to a significant increase of apo B in the arterial wall. No significant correlation was found between apo B in serum and aortic tissue. Apo B was found to be partially linked to apo(a) in the aortic extract. Furthermore, apo(a) was found to be intact, as determined by its molecular weight in sodium dodecyl sulfate electrophoresis. This technique also revealed that the apo(a) isoform pattern of aortic homogenate was comparable to the individual serum pattern. Immunohistochemical methods demonstrated a striking colocalization of apo(a) and apo B in the arterial wall, predominantly located extracellularly. Both proteins were increased in atherosclerotic plaques. With density gradient ultracentrifugation, Lp(a)-like particles could be isolated from plaque tissue. This initial study showed that Lp(a) accumulates in the arterial wall, partly in the form of lipoprotein-like particles, therefore contributing to plaque formation and coronary heart disease.
Low density lipoprotein subfractions and relationship to other risk factors for coronary artery disease in healthy individuals.
Authors: Swinkels D W , Demacker P N , Hendriks J C , van 't Laar A
Published: June 2011

By a recently developed sensitive density gradient ultracentrifugation method, the distribution of low density lipoprotein (LDL) subfractions was studied in the serum of healthy blood donors (20 to 62 years old). For each subject, we observed a specific LDL subfraction distribution characterized by the relative contribution of the three major LDL subfractions, LDL-1 (1.020 to 1.028 g/ml), LDL-2 (1.027 to 1.034 g/ml), and LDL-3 (1.033 to 1.039 g/ml), to total LDL. Statistical analysis was performed by using the LDL density variable defined as: (% of LDL-1) x 1.024 + (% of LDL-2) x 1.0305 + (% of LDL-3) x 1.036 as a continuous variable. Controlling for age, smoking habits, relative body weight and, when appropriate, for gender, it appeared that: 1) dense LDL subfraction patterns characterized by a predominant LDL-3 subfraction and a decreased LDL particle size were more likely to be found among men than among women, 2) with increasing density of LDL, the levels of serum triglycerides increased, whereas the concentration of HDL cholesterol and the ratio of LDL cholesterol to LDL apolipoprotein (apo) B decreased, and 3) the best model with significant contribution in the prediction of the LDL subfraction distribution was the three-variable model: total cholesterol, serum triglycerides, and LDL apo B (R2 = 0.40), whereas the best two-variable model consisted of serum triglycerides and high density lipoprotein cholesterol (R2 = 0.37). These data are consistent with results from a study described previously in which a different approach based on LDL subfraction quantification by gradient gel electrophoresis of whole plasma was used.
Alimentary lipemia-induced redistribution of cholesteryl ester between lipoproteins. Studies in normolipidemic, combined hyperlipidemic, and hypercholesterolemic men.
Authors: Dullaart R P , Groener J E , van Wijk H , Sluiter W J , Erkelens D W
Published: June 2011

Alimentary lipemia stimulates the transfer of cholesteryl ester between lipoproteins in vitro and may alter lipoprotein cholesteryl ester distribution in vivo. The effect of a single, large oral fat load on lipoprotein cholesteryl ester redistribution and the activity of cholesteryl ester transfer protein was investigated in six normolipidemic men (Group A), six combined hyperlipidemic men (Group B), and six hypercholesterolemic men (Group C). Fasting triglyceride-rich lipoprotein cholesteryl ester was high in Group B, low in Group A, and intermediate in Group C (A less than C less than B, p less than 0.05). After an oral fat load, total plasma cholesteryl ester was unchanged in all groups. In Group A, cholesteryl ester increased in smaller triglyceride-rich lipoproteins and remained so at 24 hours. Conversely, low density and high density lipoprotein cholesteryl ester decreased and returned to fasting values at 24 hours. In Group B, cholesteryl ester increased in large triglyceride-rich lipoproteins. Low density and high density lipoprotein cholesteryl ester (expressed as percentage of plasma cholesteryl ester) decreased. By contrast, in Group C, triglyceride-rich lipoprotein and low density lipoprotein cholesteryl ester remained unaltered, and only high density lipoprotein cholesteryl ester decreased. The activity of cholesteryl ester transfer protein increased in all groups and returned to fasting values at 24 hours. No differences in response were observed among the three groups. It is concluded that an oral fat load can induce a shift in lipoprotein cholesteryl ester distribution from high and low density lipoproteins to triglyceride-rich lipoproteins without affecting total plasma cholesteryl ester.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced lipoprotein lipase secretion from human monocyte-derived macrophages caused by hypertriglyceridemic very low density lipoproteins.
Authors: Ishibashi S , Mori N , Murase T , Shimano H , Gotohda T , Kawakami M , Akanuma Y , Takaku F , Yamada N
Published: June 2011

We studied the effects of very low density lipoprotein (VDL) obtained from hypertriglyceridemic subjects on the secretion of lipoprotein lipase and lipid accumulation in human monocyte-derived macrophages. The incubation of macrophages with VLDL obtained from different subjects caused different effects on the secretion of lipoprotein lipase (6.8 to 137.7 nM free fatty acid/min/mg cell protein) and triglyceride accumulation (184 to 507 micrograms/mg cell protein) in human monocyte-derived macrophages. VLDL from subjects with marked hypertriglyceridemia (approximately 1000 mg/dl) had a fourfold greater effect on lipoprotein lipase activity and a twofold greater effect on cellular triglyceride accumulation when compared with the effects of VLDL from normolipidemic subjects. Both lipoprotein lipase activity and triglyceride accumulation correlated positively with plasma VLDL triglyceride levels (r = 0.50 and 0.45, respectively, p less than 0.05). From these data, we suggest that the activity of lipoprotein lipase secreted from macrophages incubated with VLDL was dependent on triglyceride concentrations, and that the secretion of lipoprotein lipase enhanced by hypertriglyceridemic VLDL was closely related to the intracellular accumulation of triglyceride.
Effect of alteration in triglyceride levels on factor VII-phospholipid complexes in plasma.
Authors: Skartlien A H , Lyberg-Beckmann S , Holme I , Hjermann I , Prydz H
Published: June 2011

Clotting Factor VII activity emerges as a highly significant predictive factor for development of cardiovascular disease (CVD) in prospective trials. We have previously shown that in hypertriglyceridemic individuals a fraction of their clotting Factor VII molecules is present in an activated state in phospholipase C-sensitive complexes in plasma. These complexes may explain the increased Factor VII activity observed to be a predictive factor for CVD. We demonstrate here that the level of such complexes is amenable to dietary intervention and that the alteration in Factor VII complex levels correlates closely with the corresponding alteration in triglycerides.
Two distinct truncated apolipoprotein B species in a kindred with hypobetalipoproteinemia.
Authors: Krul E S , Kinoshita M , Talmud P , Humphries S E , Turner S , Goldberg A C , Cook K , Boerwinkle E , Schonfeld G
Published: June 2011

Two novel, distinct truncated forms of apolipoprotein B (apo B) designated as apo B-90 and apo B-40 were found in five members of a kindred with hypobetalipoproteinemia. Sodium dodecyl sulfate gels and immunoblots of plasma or low density lipoprotein (LDL) (d = 1.019 to 1.063 g/ml) of the affected members demonstrated the presence of one or both of the truncated apo B bands. Employing four monoclonal anti-LDL antibodies with defined regional specificities, we demonstrated that amino terminal epitopes of the truncated apo Bs were intact, but that 10% and 60%, respectively, of the carboxyl terminal regions were absent. Thrombin digestion of apo B-90 generated an abnormally small T2 fragment, confirming that approximately 550 amino acids had been deleted from the carboxyl terminus of apo B-100. Restriction fragment length polymorphism analysis and variable number of tandem repeat typing of the 3' flanking hypervariable region of the apo B gene made it possible to distinguish all four parental alleles and therefore to follow the inheritance of the apo B variants through the family. This pedigree analysis confirmed the inheritance of the apo B-90 and apo B-40 identified by monoclonal antibody binding studies. Siblings heterozygous for apo B-90 or apo B-40 exhibited greater than 65% lower concentrations of apo B-90 or apo B-40 relative to apo B-100 and had 5th percentile LDL cholesterol concentrations. Compound heterozygotes (apo B-90/apo B-40) had the lowest LDL levels, and their LDL particles were small in size.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma lipid secretion and clearance in hyperlipidemic JCR:LA-corpulent rats.
Authors: Russell J C , Koeslag D G , Amy R M , Dolphin P J
Published: June 2011

The JCR:LA-corpulent rat is an obese, hyperlipidemic, hyperinsulinemic strain that is atherosclerosis-prone and develops myocardial lesions. The hyperlipidemia is due to elevated plasma levels of a large relatively triglyceride-rich very low density lipoprotein (VLDL). Both corpulent and lean male and female rats were studied. Postheparin lipid clearance and apparent hepatic secretion rate after Triton WR1339 inhibition of lipoprotein lipase were determined. The concentrations of cholesterol and cholesteryl esters were not significantly altered by either treatment. Triglycerides showed rapid postheparin clearance in corpulent rats. The apparent hepatic secretion rate was markedly higher in corpulent male rats than in lean male rats, and the rate in corpulent females was again higher, reflecting the higher serum triglyceride concentrations in corpulent female rats. The relative secretion rate of C:48 triglyceride molecular species was lower than that of the C:50 to C:56 species, while the postheparin clearance of C:48 triglyceride molecular species was impaired compared to the C:50 species and those with higher carbon numbers. This effect was more marked in the male than in the female corpulent rats. The results indicate that VLDL hyperlipidemia in the corpulent rat is due to hepatic hypersecretion of VLDL and not to a defect in lipoprotein lipase. Further, the atherogenesis that is characteristic of the corpulent male rat may be related to the differential metabolism of fatty acids.
Unlikely association between clinically apparent herpesvirus infection and coronary incidence at older ages. The Framingham Heart Study.
Authors: Havlik R J , Blackwelder W C , Kaslow R , Castelli W
Published: June 2011

Experimental studies in chickens have shown a relationship of a herpesvirus to atherosclerosis. The hypothesis of an association in humans was tested by using data on the history of cold sores and other manifestations of herpes infections reported by 658 male and 919 female participants (ages 58 to 89) in the Framingham Heart Study from 1977 to 1979 and on the prevalence and subsequent 6-year incidence of coronary heart disease (CHD). Approximately 40% of the men and 52% of the women reported a history of ever having "fever blisters or cold sores." Overall, there was no association between a history of such oropharyngeal manifestations and prevalent CHD. Only in the subgroup of women with recurrent infections was there a suggestion of a possible relationship (relative risk = 1.5, 95% confidence interval 1.0 to 2.1). Among members of the cohort without CHD at baseline there was no association between the history of cold sores, chicken pox, shingles, or infectious mononucleosis and 6-year CHD incidence. However, a possible interaction among women with recurrent herpes, lower levels of serum cholesterol, and incidence of angina pectoris without myocardial infarction was suggested in post hoc analyses. These data from the Framingham cohort do not support the notion that any self-reported clinically manifest herpesvirus infection has a strong etiological role in older persons, but they do raise issues to be addressed in any further research.
Effect of dietary fat saturation and cholesterol on low density lipoprotein degradation by mononuclear cells of Cebus monkeys.
Authors: Kuo P C , Rudd M A , Nicolosi R , Loscalzo J
Published: June 2011

The mechanism by which dietary unsaturated fatty acids lower low density lipoprotein (LDL) cholesterol is unknown. Unsaturated fatty acids incorporated into the cell membrane can increase membrane fluidity and, as a result, dramatically alter membrane-dependent cell functions. Therefore, we examined the effect of long-term dietary consumption of corn oil and coconut oil with and without cholesterol in amounts equivalent to those of a typical Western diet on the degradation of human LDL by peripheral blood mononuclear cells in Cebus albifrons monkeys. Cellular LDL degradation was dramatically enhanced in the mononuclear cells isolated from animals fed corn oil in comparison with those from animals fed coconut oil. The addition of cholesterol to the diets resulted in a slight attenuation of LDL degradation in the corn oil group while no effect was noted in the coconut oil group. Crossover LDL binding and degradation experiments with LDL isolated from animals fed corn oil diets and coconut oil diets demonstrated increased binding and degradation of LDL in mononuclear cells from animals fed corn oil diets. Enhanced mononuclear cell LDL degradation was accompanied by increased cellular cis-unsaturated fatty acyl content, increased membrane fluidity, and decreased plasma cholesterol. Increased cellular cis-unsaturated fatty acyl content with its concomitant increase in membrane fluidity mirrored the dietary lipid profile of the host animal. A linear relationship was observed between cellular LDL degradation and both cellular cis-unsaturated fatty acyl content and membrane fluidity. These observations parallel results noted in whole-animal LDL catabolic studies with these same animals described elsewhere. These data suggest a novel mechanism by which dietary unsaturated fatty acids exert their LDL-lowering effect.
Hydralazine and isosorbide dinitrate: comparative central and regional hemodynamic effects when administered alone or in combination.
Authors: Leier C B , Magorien R D , Desch C E , Thompson M J , Unverferth D V
Published: June 2011

Central and regional hemodynamic studies were performed before and after the oral administration of 75 mg of hydralazine and/or 20 mg of isosorbide dinitrate in 15 patients with low-output congestive heart failure. Hydralazine increased mean cardiac output 17-25%, mean renal blood flow 19%, and limb blood flow 17% (all p < 0.05). Mean hepatic blood flow did not change significantly with hydralazine. Except for a small increase in cardiac output (6%, p < 0.05) at 30 minutes, isosorbide dinitrate did not significantly alter central, renal, hepatic or limb blood flow. Combining isosorbide dinitrate and hydralazine effected similar increases in cardiac output (17-24%, p < 0.05), renal (17%, p < 0.05) and limb (20%, p < 0.05) blood flow as those elicited by hydralazine alone. The combination did not significantly alter mean hepatic blood flow. Hydralazine, alone or combined with isosorbide dinitrate, increases renal and limb blood flow in congestive heart failure in proportion to the augmented cardiac output; isosorbide dinitrate alone does not alter blood flow to these regions. Neither drug (or combination) changes hepatic blood flow in this clinical setting.
Hormonal adaptation to the stresses imposed upon sodium balance by pregnancy and lactation in the Yanomama Indians, a culture without salt.
Authors: Oliver W J , Neel J V , Grekin R J , Cohen E L
Published: June 2011

The Yanomama Indians of northern Brazil and southern Venezuela have been identified as a "no-salt" culture. In this study, data were obtained to determine in this population the adjustments of sodium-related hormones to the stresses imposed upon sodium balance by pregnancy and prolonged lactation. Controls against the possibility that findings in the Yanomama were ethnic rather than dietary were provided by similar observations in the Guaymi Indians of Panama, who have free access to salt. Urinary concentrations of sodium were approximately 1 mEq/l in male and female Yanomama, with 24-hour excretion rates in the males averaging 1 mEq, similar to our prior observation. The pregnant Yanomama had exceeding high urinary concentrations of aldosterone. These were associated with higher plasma renin activities and serum aldosterone concentrations than in all other subjects. Although pregnant Guaymi had elevations of serum and urinary aldosterone, these were significantly lower (p < 0.001) than those of the Yanomama. Prolonged lactation in the Yanomama was associated with elevation of plasma renin activity and serum and urinary aldosterone concentration compared with the Guaymi, but were not higher than those in nonlactating Yanomama females. The findings suggest that pregnancy in a salt-poor environment is associated with an exaggerated augmentation of hormonal responses that enhance positive sodium balance.
M-mode and two-dimensional echocardiographic features in cardiac amyloidosis.
Authors: Siqueira-Filho A G , Cunha C L , Tajik A J , Seward J B , Schattenberg T T , Giuliani E R
Published: June 2011

Twenty-eight patients with cardiac amyloidosis were studied by echocardiography -- 26 by M-mode and 13 by two-dimensional (2D) studies. All had heart failure and biopsy-proved amyloidosis, M-mode features included (1) normal left ventricular (LV) dimension in all; (2) thickened ventricular septum (88%), LV posterior wall (77%), and right ventricular (RV) anterior wall (79%); (3) decreased thickening of ventricular septum (96%) and of LV posterior wall (65%) and reduced LV global function (62%); (4) left atrial enlargement (50%); and (5) pericardial effusion (58%). Two-dimensional echocardiography provided additional features: (1) thickened papillary muscles (five of 13); (2) thickened valves (four of 13); (3) better appreciation of thickened RV wall; and (4) a characteristic "granular sparkling" appearance of thickened cardiac walls -- presumably secondary to the amyloid deposit -- which was noted in 12 of 13 patients. Thus, M-mode echocardiography is helpful in the recognition of cardiac amyloidosis. However, the better appreciation with 2D echocardiography of thickened cardiac walls with a "granular sparkling" appearance in patients with unexplained cardiac failure is virtually diagnostic of cardiac amyloidosis.
Detection of pericardial metastases by cross-section echocardiography.
Authors: Chandraratna P A , Aronow W S
Published: June 2011

Cross-sectional echocardiography was performed on 69 patients with pericardial effusion. The etiology of the pericardial effusion was malignant infiltration of the pericardium in nine patients; chronic renal failure in 10; postcardiac surgery in 31; viral pericarditis in three; tuberculous pericarditis in two; and undetermined in 14. Seven of the nine patients with pericardial metastases were noted to have irregular cauliflower-like masses protruding from the pericardium and the epicardium into the echo-free space of the pericardial effusion. These masses demonstrated a to-and-fro motion within the pericardial space during ventricular systole. The presence of pericardial metastases was confirmed at operation in four cases and the three others had intrathoracic or colonic malignancy with widespread metastases. None of the patients without pericardial metastasis showed the characteristic abnormality seen in patients with pericardial metastases. Six patients had dense linear echoes connecting the pericardium and epicardium that probably represented adhesions (confirmation at surgery in one, and confirmation at autopsy in another), with an appearance that was different from that seen in pericardial metastases. We conclude that cross-sectional echocardiography may be useful for detecting pericardial metastases.
Myocardial ultrastructure and the development of atrioventricular block in Kearns-Sayre syndrome.
Authors: Charles R , Holt S , Kay J M , Epstein E J , Rees J R
Published: June 2011

A right ventricular endomyocardial biopsy specimen from a 30-year-old male with chromic progressive external ophthalmoplegia, retinal pigmentation and complete atrioventricular block (Kearns-Sayre syndrome) was examined in the electron microscope. There was a proliferation of mitochondria between the myofibrils and beneath the sarcolemma. Many of the mitochondria showed morphologic abnormalities not previously described in this condition. There were associated accumulations of glycogen. A similarly affected female with left anterior hemiblock developed complete atrioventricular block at age 26 years, Despite the ultrastructural changes, clinically detectable myocardial disease is not a feature of Kearns-Sayre syndrome. However, intraventricular conduction defects show an unusually rapid progression to potentially fatal complete atrioventricular block and are an indication for prophylactic cardiac pacing.
Coexistence of sick sinus rhythm and atrial flutter-fibrillation.
Authors: Gomes J A , Kang P S , Matheson M , Gough W B , El-Sherif N
Published: June 2011

A 58-year-old man with hypertensive cardiovascular disease and atrial flutter underwent electrophysiologic studies, including multiple intra-atrial recordings and atrial stimulation. Although the surface ECG suggested the presence of atrial flutter, intra-atrial recordings demonstrated the presence of (1) sinus-like rhythm localized to an area of approximately 5 mm in and around the region of the sinus node, which was protected by entrance block; (2) flutter and/or fibrillation of the remaining parts of the right atrium; (3) fibrillation of the left atrium; and (4) transient degeneration of flutter into fibrillation at right atrial sites, with predominant flutter activity. Although a major part of the right atrium was in flutter and/or fibrillation, we could assess sinus node function by overdrive stimulation of the area of sinus node-activity. Sinus node function studied revealed an underlying sick sinus syndrome.
Exercise testing in children before and after surgical treatment of aortic stenosis.
Authors: Whitmer J T , James F W , Kaplan S , Schwartz D C , Knight M J
Published: June 2011

Twenty-three children with valvar or discrete subvalvar aortic stenosis underwent a controlled, progressive bicycle exercise test within 6 months before and 3-30 months after surgery for left ventricular outflow tract obstruction. The patients were divided into three groups according to the preoperative resting gradient of left ventricular to aortic peak systolic pressure: 30-69 mm Hg (group A), 70-99 mm Hg (group B), and greater than or equal to 100 mm Hg (group C). Preoperatively, 19 of 23 patients (83%) developed significant ST depression (greater than or equal to 1.0 mm) during exercise, whereas only seven (30%) had abnormal ST depression at rest. Postoperatively, mean exercise-induced ST depression regressed to less than 1 mm in all three groups. In the total population the frequency of ST depression greater than 1 mm was significantly reduced after surgical treatment and mean total work and peak exercise systolic blood pressure were significantly increased within 12 months after surgery. Total work increased significantly in group B within 12 months and in group C within 13-24 months after surgery, but remained unchanged on group A. Peak exercise heart rates were similar before and after surgery in each group. Peak exercise systolic pressures increased after surgery in all three groups, but the mean differences were statistically significant only in group C patients tested 13-24 months after surgery. The results of this study show that exercise testing is useful for quantifying the severity of aortic stenosis and documenting the clinical improvement (or lack thereof) after surgical treatment, and that properly supervised exercise testing can be performed at minimal risk to children with significant aortic stenosis.
Mechanism for improved cardiac performance with arteriolar dilators in aortic insufficiency.
Authors: Greenberg B H , DeMots H , Murphy E , Rahimtoola S H
Published: June 2011

To determine how arteriolar dilation improves cardiac performance in aortic insufficiency, we evaluated the acute effects of hydralazine in 10 patients with chronic severe aortic insufficiency. Control measurements of intracardiac and intravascular pressures, cardiac output and left ventricular volumes were obtained at cardiac catheterization. Hydralazine, 0.3 mg/kg i.v. (maximal dose 20 mg), was administered and all measurements were repeated 30 minutes later. A reduction in systemic vascular resistance from 1264 to 710 dyn-sec-cm-5 was associated with significant increases in forward cardiac index (2.9 to 5.1 l/min/m2) and stroke volume index (37 to 55 ml/m2). Left ventricular end-diastolic pressure was reduced from 19 to 12 mm Hg. There was a significant reduction in mean arterial pressure (88 to 83 mm Hg) and a significant increase in heart rate (81 to 94 beats/min). Regurgitant stroke volume was reduced by more than 10 ml/m2 in seven patients and for the group was significantly reduced, from 65 to 53 ml/m2. Regurgitant fraction was reduced in all patients; the overall reduction from 0.64 to 0.48 was highly significant. Ejection fraction increased more than 0.10 in four patients, by 0.08 in an additional patient and for the group increased significantly from 0.50 to 0.57. Left ventricular end-diastolic volume decreased by more than 25 ml/m2 in four patients, by 19 ml/m2 in an additional patient and was decreased significantly, from 208 to 190 ml/m2, for the group. Arteriolar dilators improve cardiac performance in aortic insufficiency by reducing the amount of aortic regurgitation and, in some patients, by substantially improving systolic pump fraction. These data suggest a role for arteriolar dilators in the management of selected patients with aortic insufficiency.
Long-term vasodilator therapy for heart failure: clinical response and its relationship to hemodynamic measurements.
Authors: Massie B , Ports T , Chatterjee K , Parmley W , Ostland J , O'Young J , Haughom F
Published: June 2011

To assess the clinical efficacy of chronic vasodilator therapy for refractory congestive heart failure, the long-term follow-up (mean 13 months, range 3-30 months) was evaluated in 56 patients treated with hydralazine, usually in combination with nitrates. In the first 6 months, 73% improved subjectively and 59% improved by one or two New York Heart Association classifications; early improvement was usually sustained. Mortality was high, 22% at 6 months and 37% at 12 months, but was significantly lower in patients who had a clinical response to vasodilators (21% in responders vs 55% in nonresponders at 1 year). The only clinical indicator that differentiated responders from nonresponders was the presence or absence of symptomatic progression before initiation of vasodilator therapy. Pulmonary artery pressure, pulmonary capillary wedge (PCW) pressure and stroke work index (SWI) before and during vasodilator therapy correlated with clinical response and survival. Fifteen of 20 patients with PCW < 20 mm Hg and SWI greater than or equal to 30 g-m/m2 improved and survived, compared with two of 19 with PCS greater than or equal to 20 mm Hg and SWI < 30 g-m/m2. Patients who did not have acute hemodynamic improvement generally did not improve clinically, but neither the percentage change nor the absolute change in any hemodynamic variable predicted outcome in the remaining patients. The findings of this study indicate that vasodilators produce clinical improvement in many patients with refractory heart failure and that hemodynamic measurements are helpful in predicting the outcome of therapy.
Effects of coronary artery reperfusion on myocardial infarct size and survival in conscious dogs.
Authors: Baughman K L , Maroko P R , Vatner S F
Published: June 2011

The effects of coronary artery reperfusion at 1 and 3 hours after coronary artery occlusion were examined on myocardial infarct size and survival in conscious dogs. Left circumflex coronary artery occlusion was induced by inflating an hydraulic occluder and confirmed thereafter by measuring the absence of coronary blood flow. Of the 77 dogs that underwent coronary artery occlusion, 18 died within 1 hour. Of the 59 remaining dogs, permanent coronary artery occlusion was carried out in 31 dogs, 12 underwent reperfusion after 1 hour and 16 underwent reperfusion after 3 hours. Survival at 1 week was enhanced significantly (p < 0.01) by reperfusion carried out at either 1 or 3 hours; only 29% of dogs with permanent coronary artery occlusion survived, whereas 83% and 75% of dogs survived 1 week with reperfusion at 1 hour and 3 hours, respectively. Average infarct size at 1 week was smaller in dogs with reperfusion (NS). The inability to reach statistical significance was most likely the result of two factors: (1) There was a marked variation in infarct size in dogs with permanent coronary artery occlusion--infarcts averaged 21.3 +/- 7.5% and ranged from 0.7-72.6% of the left ventricle. (2) Dogs that died 1-7 days after coronary artery occlusion had significantly (p < 0.05) larger infarcts (40 +/- 4% of left ventricle) than those that survived 1 week in any of the three groups. Thus, if all dogs had survived 1 week, a beneficial effect on infarct size could have been demonstrated. Nevertheless, coronary artery reperfusion at either 1 or 3 hours after coronary artery occlusion induces a striking beneficial effect on survival, which is of the utmost clinical significance.
The first heart sound in left bundle branch block: an echophonocardiographic study.
Authors: Burggraf G W
Published: June 2011

To examine the nature of the first heart sound in left bundle branch block (LBBB), 26 patients with LBBB were studied using echophonocardiography. Apexcardiograms and systolic time intervals were also obtained from these patients and the results were compared with 20 normal subjects. Mitral closure preceded tricuspid closure by 0.02-0.04 second in 19 of the 20 normal subjects. In contrast, in subjects with LBBB there was a variable delay in mitral closure so that in seven subjects the sequence of mitral and tricuspid closure was normal, in 11 it was reversed compared wih the normal group, and in eight closure of both valves was simultaneous. The interval from the onset of ventricular depolarization to mitral closure was 0.074 +/- 0.019 (mean +/- SD) for the patients with LBBB and 0.057 +/- 0.008 second for the normal group (p < 0.001). With LBBB the first sound tended to be of reduced intensity and separate mitral and tricuspid components could not be identified. Systolic time intervals and the apexcardiograms demonstrated a delayed onset of left ventricular contraction and an increased isometric contraction time in the LBBB group, both of which would contribute to a delayed mitral valve closure and decreased first heart sound intensity.
Effectiveness of a prehospital medical control system: an analysis of the interaction between emergency room physician and paramedic.
Authors: Pozen M W , D'Agostino R B , Sytkowski P A , Schneider R J , Berezin M M , Bremer L H , Riggen R J
Published: June 2011

Medical control for paramedics by means of radio and ECG telemetry is costly, time consuming, and of unproved value. We assessed the interaction between emergency room physicians and paramedics during ambulance transport of "seriously ill" cardiac patients (cardiac arrest, acute myocardial infarction, or new onset of crescendo angina pectoris) with paramedics in service. Thirty-five percent of all arrhythmias and 35% of potentially life-threatening arrhythmias were misclassified. Correct treatment was rendered in 74% of the cases, although only 65% were correctly diagnosed (p < 0.01). The principal predictive variable for misdiagnosing or incorrectly treating a patient was the presence of a potentially life-threatening arrhythmia, precisely the condition for which medical control and the paramedic system has the most to offer. Only 39% of patients with life-threatening arrhythmias were correctly diagnosed and correctly treated, whereas 64% of patients without life-threatening arrhythmias were correctly diagnosed and correctly treated (p < 0.001). Mortality reflected correct diagnosis and treatment. In-hospital and overall mortalities were 12% and 33%, respectively, for patients who were correctly diagnosed and treated (p < 0.06), compared with 20% and 43%, respectively, for patients who were incorrectly diagnosed or incorrectly treated (p < 0.04). More rigorous medical control is needed to improve the quality of patient care and outcome and to further integrate the advanced life support program into the health care system.
Two-dimensional echocardiographic features of atrial septal aneurysms.
Authors: Gondi B , Nanda N C
Published: June 2011

Aneurysms of the interatrial septum are rare. They have been associated with complications such as embolic phenomena and atrioventricular orifice obstruction. We describe two patients, one adult and one child, with atrial septal aneurysms that were diagnosed by real-time, two-dimensional echocardiography. Atrial septal aneurysms appeared as thin, localized outpouchings of the atrial septum that protruded into the right atrium and showed marked variations in their contour and size during the cardiac cycle. They could be differentiated from other intra-atrial structures such as tumor mass, large eustachian valve and intra-atrial baffle by their relatively low reflectance, relationship to the atrial septum, considerable alterations in their outline during the cardiac cycle and characteristic patterns during peripheral venous contrast echocardiography.
The anatomic evolution of coronary artery disease demonstrated by coronary arteriography in 256 nonoperated patients.
Authors: Bruschke A V , Wijers T S , Kolsters W , Landmann J
Published: June 2011

Coronary arteriography was performed twice in 256 nonoperated patients, including 92 surgical candidates who were recatheterized because of the long wait for surgery. Criteria to define progression and regression were established in advance. Analysis of separate segments, reflecting separate lesions, revealed that progression percentages increased proportionally with the degree of initial narrowing and the interval between catherizations, ranging from 1.2% to more than 20%. The highest progression percentages were shown by the proximal right coronary artery, the left anterior descending artery distal to the first septal and first diagonal branches, and the obtuse marginal branch of the circumflex artery. In 56.3% of the patients, progression was found in at least one segment, ranging from 40% in patients who were recatheterized within 1 year to 92% in patients who were recatheterized after 5 years or longer (p less than 0.025). In 12 patients (4.7%), regression had occurred; in two cases obstructions had reverted to less than 50% narrowing. Regression was associated with progression in other branches in three cases. Indications for recatheterization did not correlate significantly with progression, but a higher progression percentage was found in patients who had sustained a myocardial infarction during follow-up than in those who had not (p less than 0.05). Comparison of potential surgical procedures based on the first and second angiogram revealed that at the second catheterization more distal anastomoses were required to achieve complete revascularization in 29.3% of the patients and that left ventricular contractions had deteriorated markedly in 15.6%. These fractions correlated with the duration of the interval between catheterizations.
Detection and quantitation of myocardial infarction in vivo using transmission computed tomography.
Authors: Doherty P W , Lipton M J , Berninger W H , Skioldebrand C G , Carlsson E , Redington R W
Published: June 2011

In vivo studies were performed on 28 dogs to evaluate the usefulness of transmission computed tomography (CT) in the detection and quantitation of experimentally induced myocardial infarction. Intravenously administered contrast material was required to define the internal structure of the heart and to differentiate normal from infarcted tissue. Transmural infarcts with homogeneous central regions were visualized as areas of diminished contrast enhancement compared with the normal myocardium. All transmural infarcts of at least 24 hours' duration showed a surrounding border zone of patchy necrosis that was variable in size and had high CT numbers due to slow washout of the contrast material from this region. Infarct area determined from the images for individual slices correlated well (r = 0.976) with that calculated using pathology. The technique is very sensitive and can detect infarction within a papillary muscle. Nontransmural or patchy infarcts show up as areas of diffuse contrast enhancement without a central core of diminished enhancement. The distribution of the contrast material is similar to that of technetium-99m pyrophosphate in the border zone of the infarct in infusion studies, but in bolus studies it behaves more like thallium-201.
Experimental evaluation of the extent of myocardial dyssynergy and infarct size by two-dimensional echocardiography.
Authors: Wyatt H L , Meerbaum S , Heng M K , Rit J , Gueret P , Corday E
Published: June 2011

The extent of left ventricular (LV) dyssynergy was assessed noninvasively in 19 dogs with two-dimensional echocardiographic short-axis sections during myocardial ischemia and infarction. After coronary occlusion, two-dimensional echocardiography uniformly indicated an increase in LV end-diastolic volume and a decrease in LV ejection fraction. Two-dimensional echocardiographic measurements of dyssynergy were evaluated and compared in three subgroups against (1) the extent of LV dyssynergy determined by force-gauge mapping during 10 coronary occlusions of 30-60 minutes' duration in eight open-chest dogs, (2) infarct size delineated by nitroblue tetrazolium (NBT) staining of left ventricular slabs after 48 hours of left anterior descending coronary artery (LAD) occlusion in five closed-chest dogs, and (3) NBT infarct size after 3-hour LAD occlusion followed by 45 hours of reperfusion in six closed-chest dogs. Linear regression analysis of results from these three comparisons gave good correlations (r = 0.89) for groups 1 and 2; in group 2, the extent of dyssynergy by two-dimensional echocardiography was consistently greater than infarct size by NBT. In group 3, the correlation was poor (r = 0.39). These results suggest that an adequate estimate for the extent of LV dyssynergy or infarct size may be obtained with two-dimensional echocardiography during myocardial ischemia or infarction, but not in the presence of coronary reflow, which causes an acute discrepancy between myocardial viability and function.
Echocardiographic diagnosis of congenital sinus of Valsalva aneurysm with dissection of the interventricular septum.
Authors: Engel P J , Held J S , van der Bel-Kahn J , Spitz H
Published: June 2011

A case is reported in which a congenital aneurysm of the right coronary sinus of Valsalva ruptured and dissected into the interventricular septum. M-mode and cross-sectional echocardiographic examination allowed accurate preoperative assessment of the pathologic anatomy, which was confirmed by angiography, surgery and autopsy. Dissection of the interventricular septum by a congenital sinus of Valsalva aneurysm is a rare lesion, has a poor prognosis, and can be diagnosed noninvasively with echocardiography.
Natural history of contractile abnormalities after acute myocardial infarction in man: severity and response to nitroglycerin as a function of time.
Authors: Ramanathan K , Bodenheimer M M , Banka V S , Helfant R H
Published: June 2011

The natural history of contraction abnormalities and their response after acute myocardial infarction in man were studied using radionuclide angiography. Sixteen patients were studied before and after sublingual nitroglycerin within 24 hours, 5-7 days and 4-6 weeks after the onset of chest pain. Within 24 hours, central chord shortening in the zone of infarction was reduced to 13.1 +/- 9.8%, but improved 27.2 +/- 18.4% (p less than 0.001) after nitroglycerin. After 5-7 days, central chord shortening improved similarly, but less markedly, from 12.9 +/- 9.2% to 24.4 +/- 13.2% (p less than 0.001). After nitroglycerin 4--6 weeks after the acute myocardial infarction, the central chord showed no response to nitroglycerin; it was 13.9 +/- 10.9% before and 13.4 +/- 2.5% after nitroglycerin. Changes in the lateral chords paralleled changes in the central chords in the three studies. Nonischemic zone improvement after nitroglycerin in all three studies. Global ejection fraction improved and end-diastolic and end-systolic volumes decreased in all three studies after nitroglycerin. These data indicate that after acute myocardial infarction, there is a significant reduction in hemiaxis shortening in the central and lateral chords that remains essentially unchanged over 4-6 weeks. However, the asynergic ischemic area improves considerably after nitroglycerin within 24 hours and 5-7 days, but fails to improve after 6 weeks.