bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased HDL2 and HDL3 cholesterol, Apo A-I and Apo A-II, and increased risk of myocardial infarction.
Authors: Buring J E , O'Connor G T , Goldhaber S Z , Rosner B , Herbert P N , Blum C B , Breslow J L , Hennekens C H
Published: June 2012

BACKGROUND

A large and consistent body of evidence supports the judgment that elevation of total plasma blood cholesterol is a cause of myocardial infarction (MI) and that high levels of low density lipoprotein (LDL) cholesterol have a positive relation and high levels of high density lipoprotein (HDL) cholesterol an inverse relation with MI. At present, however, the roles, if any, of the major subfractions of HDL, namely, HDL2 and HDL3, have not been clarified. In addition, the relation of plasma apolipoprotein concentrations to MI and whether they provide predictive information over and above their lipoprotein cholesterol associations is unknown.

METHODS AND RESULTS

We evaluated these questions in a case-control study of patients hospitalized with a first MI and neighborhood controls of the same age and sex. Cases had significantly lower levels of total HDL (p less than 0.0001) as well as HDL2 (p less than 0.0001) and HDL3 (p less than 0.0001) cholesterol. These differences persisted after controlling for a large number of demographic, medical history, and behavioral risk factors and levels of other lipids. There were significant (p less than 0.0001) inverse dose-response relations with odds ratios for those in the highest quartile relative to those in the lowest of 0.15 for total HDL, 0.17 for HDL2, and 0.29 for HDL3 cholesterol levels. Levels of LDL and very low density lipoprotein cholesterol and triglycerides were also higher among cases than controls, but only for triglycerides was the difference statistically significant after adjustment for coronary risk factors and other lipids (p = 0.044). Apolipoproteins A-I and A-II were both significantly (p less than 0.0001) lower in cases, and differences remained even after adjustment for coronary risk factors and lipids. There were significant dose-response relations for both apolipoprotein A-I (p = 0.026) and A-II (p = 0.002). Neither apolipoprotein B nor E was significantly related to MI after adjustment for lipids and other coronary risk factors. When all four apolipoproteins were taken together, there was an increased level of prediction of MI over the information provided by the lipids and other coronary risk factors (p = 0.003), but this appeared present only for the individual apolipoproteins A-I (p = 0.027) and A-II (p = 0.011).

CONCLUSIONS

These data indicate that both HDL2 and HDL3 cholesterol levels are significantly associated with MI. They also raise the possibility that apolipoprotein levels, especially A-I and A-II, may add importantly relevant information to determination of risk of MI.
Capillary recruitment and pain relief on leg dependency in patients with severe lower limb ischemia.
Authors: Ubbink D T , Jacobs M J , Slaaf D W , Tangelder G J , Reneman R S
Published: June 2012

BACKGROUND

Patients suffering from severe lower limb ischemia may experience pain relief on leg dependency despite the fact that dependency normally results in arteriolar vasoconstriction. To clarify this possible paradox, skin microcirculation of the limb was investigated in 75 patients with different stages of lower limb ischemia and in 12 asymptomatic subjects.

METHODS AND RESULTS

Using nailfold capillary video microscopy, red blood cell-perfused capillary density and diameter and red blood cell velocity were assessed in supine and sitting positions. Capillary density increased by changing from the supine to the sitting position, especially in patients with limb-threatening ischemia (showing a 4.5-fold increase versus a 1.5-fold increase in asymptomatic subjects). In subjects without or with mild ischemia, capillary perfusion was two to four times lower in the sitting than in the supine position. In patients with limb-threatening ischemia, perfusion was strongly reduced, being slightly higher in the sitting position. Patients with relief of pain while sitting did not always have a higher capillary perfusion but did have a higher capillary density in the sitting position.

CONCLUSIONS

The arteriolar postural vasoconstrictive mechanism at the nutritive level is still intact in subjects without or with mild ischemia but not in patients with severe ischemia. Capillary recruitment rather than disturbed arteriolar vasoconstriction could explain why patients with severe leg ischemia prefer leg dependency.
Myocardial catecholamine and neuropeptide Y depletion in failing ventricles of patients with idiopathic dilated cardiomyopathy. Correlation with beta-adrenergic receptor downregulation.
Authors: Anderson F L , Port J D , Reid B B , Larrabee P , Hanson G , Bristow M R
Published: June 2012

BACKGROUND

Myocardial adrenergic neurotransmitters and beta-adrenergic receptor levels were measured in left and right ventricular myocardial specimens obtained from 30 patients with biventricular failure resulting from idiopathic dilated cardiomyopathy.

METHODS AND RESULTS

Nonfailing myocardium obtained from 12 organ donors provided control data. Norepinephrine, dopamine, and neuropeptide Y concentrations were significantly decreased in failing compared with nonfailing control hearts. The mean ratio of dopamine to norepinephrine and of dopamine to neuropeptide Y in failing hearts was also significantly decreased compared with nonfailing control hearts. Compared with nonfailing control hearts, Bmax and beta 1-receptor density were significantly decreased in failing hearts and there were weak but significantly positive correlations of Bmax and beta 1-adrenergic receptors with norepinephrine, dopamine, and neuropeptide Y.

CONCLUSIONS

Norepinephrine and its cotransmitter neuropeptide Y are depleted in failing human ventricular myocardium. Decreased norepinephrine stores correlate weakly with beta 1-adrenergic receptor downregulation consistent with the hypothesis that norepinephrine depletion occurs in response to increased adrenergic drive. Decreased dopamine relative to norepinephrine implies that an abnormality of dopamine conversion to norepinephrine is not present in failing human heart.
Control of arteriolar resistance in heart failure. Partial attenuation of specific phosphodiesterase inhibitor-mediated vasodilation by digitalis glycosides.
Authors: Jondeau G , Klapholz M , Katz S D , Maher M , Galvao M , Levato P , LeJemtel T H
Published: June 2012

BACKGROUND

The vasodilatory response to local specific type III phosphodiesterase inhibition with amrinone was evaluated before and immediately after local administration of digoxin in 14 patients with severe congestive heart failure (CHF).

METHODS AND RESULTS

A 3F polyethylene catheter was inserted into the common femoral artery for drug administration and pressure monitoring. Mean blood flow velocity (MBFV) was continuously determined in the superficial femoral artery by transcutaneous Doppler ultrasonography. After intra-arterial administration of 10 mg amrinone, group MBFV increased from 7.7 +/- 1.4 to 16.0 +/- 2.1 cm/sec (p less than 0.05, n = 10). Local administration of 20 micrograms digoxin, which was infused over 20 minutes, did not alter group MBFV (i.e., 8.2 +/- 1.6 versus 7.6 +/- 1.5 cm/sec; p = NS, n = 10). The second administration of 10 mg amrinone, which immediately followed completion of local digoxin infusion, increased group MBFV but to a lesser extent than that produced by the first amrinone administration (i.e., 11.9 +/- 1.9 versus 16.0 +/- 2.1 cm/sec; p less than 0.05, n = 10). When placebo was administered instead of digoxin, group MBFV was similar after the first and second administrations of amrinone (i.e., 15.3 +/- 3.3 versus 15.6 +/- 3.8 cm/sec; p = NS, n = 4).

CONCLUSIONS

Although local administration of digoxin did not significantly alter baseline vascular tone in patients with CHF, it substantially decreased the direct vasodilatory effect induced by specific type III phosphodiesterase with amrinone.
Quantitative angiographic morphology of the coronary artery lesions at risk of thrombotic occlusion.
Authors: Taeymans Y , Théroux P , Lespérance J , Waters D
Published: June 2012

BACKGROUND

Coronary angiography in acute myocardial infarction has revealed complicated atherosclerotic plaque and a high rate of thrombotic occlusion. However, the characteristics of lesions at high risk of subsequent occlusion are not well known.

METHODS AND RESULTS

In the present study, the qualitative and quantitative angiographic features of 38 coronary artery lesions that occluded within 3 years to cause an acute myocardial infarction were compared with 64 control segments from the same patients that did not occlude. Compared with control lesions, the lesions that occluded were more likely to have a division branch originating within the stenosis (76% versus 52%, p less than 0.05). The percent lumen diameter reduction was more severe (47.5 +/- 17.8% versus 41 +/- 12.5%, p less than 0.05) and the inflow (21 +/- 10 degrees versus 16 +/- 7 degrees, p less than 0.05) and outflow (20 +/- 10 degrees versus 16 +/- 8 degrees, p less than 0.05) angles of the stenosis were steeper. Time to myocardial infarction after the angiogram interacted with the importance of these features (p less than 0.02). Thus, paired analysis of the lesions that occluded within 3 months and of the most severe control lesion from each patient showed percent lumen diameter reduction of 62.1 +/- 11.5% and 46.4 +/- 11.4%, respectively (p less than 0.001). The length of the stenosis, its asymmetry, and the irregularity of the contours did not help differentiate occlusive from control segments.

CONCLUSIONS

Coronary artery lesions at high risk of thrombotic occlusion share common characteristics that favor higher shear stress and flow separation.
One-year results of the Thrombolysis in Myocardial Infarction investigation (TIMI) Phase II Trial.
Authors: Williams D O , Braunwald E , Knatterud G , Babb J , Bresnahan J , Greenberg M A , Raizner A , Wasserman A , Robertson T , Ross R
Published: June 2012

BACKGROUND

The Thrombolysis in Myocardial Infarction (TIMI) Phase II Trial randomized 3,339 patients to either an invasive (INV, n = 1,681) or a conservative (CON, n = 1,658) strategy after intravenous recombinant tissue-type plasminogen activator (rt-PA) for acute myocardial infarction.

METHODS AND RESULTS

The patients assigned to the INV strategy routinely underwent cardiac catheterization, and when anatomically appropriate, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting 18-48 hours after infarction. CON patients had these procedures only in response to the occurrence of spontaneous or provoked ischemia. One-year follow-up data are available in 3,316 patients (99.3%). The primary trial end point, death and nonfatal reinfarction, occurred in 14.7% of INV patients and in 15.2% of CON patients (p = NS). When analyzed individually, there was no difference (p = NS) in death (INV, 6.9%; CON, 7.4%) or recurrent infarction (INV, 9.4%; CON, 9.8%) between the two groups. Anginal status at 1 year was also similar. Cardiac catheterization and PTCA were performed more often in INV (98.0% and 61.2%, respectively) compared with CON (45.2% and 20.5%, respectively) patients. At 1 year, the cumulative number of patients who underwent coronary bypass surgery (INV, 17.5%; CON, 17.3%) was similar in the two groups.

CONCLUSIONS

The INV and CON strategies resulted in similar favorable outcomes at 1 year of follow-up. In particular, the rates of mortality and reinfarction were not different and were impressively low in both groups. One possible advantage of the INV strategy was detected in subgroup analyses. In patients with a history of myocardial infarction, the data are suggestive that 1-year mortality was lower in INV patients (10.3%) than in CON patients (17.0%) (p = 0.03).
Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure.
Authors: Beuckelmann D J , Näbauer M , Erdmann E
Published: June 2012

BACKGROUND

Experiments were performed in human ventricular myocytes to investigate properties of excitation-contraction coupling in patients with terminal heart failure. Myocytes were isolated from left ventricular myocardium of patients with cardiac failure caused by dilated or ischemic cardiomyopathy undergoing transplantation. These results were compared with those obtained from cells of healthy donor hearts that for technical reasons were not suitable for transplantation.

METHODS AND RESULTS

[Ca2+]i transients and Ca2+ currents were recorded from isolated cells under voltage clamp perfused internally with the Ca2+ indicator fura 2. In cells that were stimulated externally, the cell-permeant form of the indicator, fura 2-AM, was used. When action potentials were to be recorded, cells were stimulated in current clamp mode. Unstimulated Ca2+ current densities were not significantly different in myopathic and control cells. In diseased myocytes, resting [Ca2+]i levels were 165 +/- 61 nmol/l, compared with 95 +/- 47 nmol/l in normal cells. With 5 mmol/l Na+ in the pipette, peak [Ca2+]i transients were 367 +/- 109 and 746 +/- 249 nmol/l, respectively. The decline of [Ca2+]i during diastole was significantly slower in myopathic cells than in control cells. This was a result of a prolongation of the action potential and of a reduced Ca2+ sequestration by the sarcoplasmic reticulum.

CONCLUSIONS

These results may partly explain the alterations of contractility in vivo in patients with heart failure.
Contrasting effects of propranolol on sympathetic nerve activity and vascular resistance during orthostatic stress.
Authors: Jacobsen T N , Converse R L , Victor R G
Published: June 2012

BACKGROUND

Previous studies in humans advanced the concept that cardiac filling pressure and contractility, the primary determinants of ventricular mechanoreceptor discharge, are important determinants of sympathetic outflow during orthostatic stress. Thus, intravenous propranolol greatly attenuated forearm vasoconstrictor response to venous pooling with lower body negative pressure (LBNP). The aim of this study was to reevaluate the experimental support for this concept by using direct measurements of sympathetic nerve activity.

METHODS AND RESULTS

In 11 healthy humans, we recorded muscle sympathetic nerve activity (MSNA) with microelectrodes (peroneal nerve), as well as blood flow in the forearm and calf (venous occlusion plethysmography) at baseline and during graded LBNP. The same experiments were repeated after administration of propranolol (0.15 mg/kg i.v.), which is thought to decrease ventricular mechanoreceptor discharge. The major new findings are that propranolol neither increased baseline MSNA nor attenuated the increases in MSNA during graded orthostatic stress even though in the same subjects, propranolol simultaneously increased the baseline level of vascular resistance in both the forearm and calf and substantially attenuated the increases in regional vascular resistance during orthostatic stress.

CONCLUSIONS

Systemic beta-blockade causes a marked dissociation between sympathetic outflow and vascular resistance that invalidates the use of intravenous propranolol as an experimental model to examine the reflex effects of ventricular mechanoreceptors on peripheral vascular resistance in humans.
Lipoproteins and blood pressure as biological pathways for effect of moderate alcohol consumption on coronary heart disease.
Authors: Langer R D , Criqui M H , Reed D M
Published: June 2012

BACKGROUND

Several epidemiological studies have shown light-to-moderate alcohol consumption to have a net protective effect on the incidence of coronary heart disease (CHD).

METHODS AND RESULTS

Major components of this effect, both positive and negative, may be explored using models that include both alcohol and variables expected to mediate the observed alcohol effect. Such modeling in a cohort of men of Japanese descent followed in the Honolulu Heart Program indicates that about half of the observed protection against CHD afforded by moderate alcohol consumption is mediated by an increase in high density lipoprotein cholesterol. An additional 18% of this protection is attributable to a decrease in low density lipoprotein cholesterol, but it is counterbalanced by a 17% increase in risk due to increased systolic blood pressure. The explanation for the residual 50% benefit attributable to alcohol is unknown but may include interference with thrombosis. The results in this population replicate those in the Lipid Research Clinics cohort studied earlier with the same analytic technique.

CONCLUSIONS

The consistency of these findings across populations, along with the demonstration of reasonable biological pathways for this effect of alcohol, provides strong support for the hypothesis that light-to-moderate alcohol intake is protective against heart disease in men.
Double-blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary angioplasty.
Authors: Bairati I , Roy L , Meyer F
Published: June 2012

BACKGROUND

Previous studies suggest that recurrence of coronary stenosis after percutaneous transluminal coronary angioplasty (PTCA) might be prevented with dietary supplements rich in omega-3 fatty acids. The purpose of the present study was to evaluate this hypothesis. In addition, the relation between usual dietary consumption of omega-3 fatty acids and restenosis was assessed.

METHODS AND RESULTS

A double-blind, randomized, controlled trial was conducted in which 205 patients undergoing a first PTCA received 15 capsules per day containing 1 g of either fish oil (2.7 g/day of eicosapentaenoic acid, 1.8 g/day of docosahexaenoic acid) or olive oil. The treatment was started 3 weeks before PTCA and continued for 6 months thereafter. Dietary intake was assessed by food frequency questionnaire. At 6 months after PTCA, patients underwent a control angiography. All angiographic lesions were measured by quantitative computer analysis. Four criteria were used to define restenosis. Restenosis occurred less often in the fish oil group (22.0-35.6% depending on the definition) than in the control group (40.0-53.3%). After controlling for other risk factors of restenosis, the association of fish oil supplementation with a lower frequency of restenosis was statistically significant (p = 0.03) for three of four definitions. After adjustment, a dietary intake of omega-3 fatty acids of more than 0.15 g/day was also associated with a lower frequency of restenosis (p less than or equal to 0.03).

CONCLUSIONS

This trial documented the protective effect of fish oil supplements on the recurrence of coronary stenosis 6 months after PTCA. The study results suggest that a dietary intervention could be useful in preventing restenosis.
Predictors of early morbidity and mortality after thrombolytic therapy of acute myocardial infarction. Analyses of patient subgroups in the Thrombolysis in Myocardial Infarction (TIMI) trial, phase II.
Authors: Mueller H S , Cohen L S , Braunwald E , Forman S , Feit F , Ross A , Schweiger M , Cabin H , Davison R , Miller D
Published: June 2012

BACKGROUND

Thrombolysis has altered treatment of acute myocardial infarction (AMI). Therefore, reevaluation of predictors of outcome and treatment strategies is appropriate.

METHODS AND RESULTS

Clinical variables collected prospectively for the 3,339 patients of the Thrombolysis in Myocardial Infarction II study were analyzed retrospectively to identify predictors of clinical events at 42 days and earlier and to identify subgroups in which an invasive or conservative strategy might be superior. Pulmonary edema/cardiogenic shock presented as the strongest independent correlate with death (relative risk, 6.0). In two subgroups, mortality differed between the invasive and conservative strategies: 1) Patients with versus without prior AMI had a higher mortality in the conservative strategy (11.5% versus 3.5%, p less than 0.001); in the invasive strategy, the mortality rates were similar (6.0% and 5.1%). 2) Patients with diabetes mellitus and no prior AMI had a higher mortality in the invasive than in the conservative strategy (14.8% versus 4.2%, p less than 0.001). Reinfarction was not independently correlated with baseline characteristics except with history of angina (relative risk, 1.9). Mortality was lower in current smokers and ex-smokers versus never-smokers (3.6% and 4.8% versus 8.0%, p less than 0.001). Current smokers had a lower risk profile (p less than 0.001), including age, pulmonary edema/cardiogenic shock, history of hypertension, and diabetes. The rate of reinfarction was lower in current smokers versus ex-smokers and never-smokers (4.6% versus 8.3% and 8.8%, p less than 0.001). "Not current smoker" was an independent correlate with reinfarction (relative risk, 1.9). The coronary anatomy did not differ among the current smokers, ex-smokers, and never-smokers.

CONCLUSIONS

The strong independent correlation of pulmonary edema/cardiogenic shock with death suggests that thrombolysis is not sufficient to improve survival in these patients. The higher mortality in patients with versus without prior AMI in the conservative strategy suggests that early catheterization and revascularization of these patients might be beneficial. Conversely, the higher mortality in diabetes without prior AMI in the invasive than in the conservative strategy suggests that early aggressive management might not be suitable in this subgroup except for clinical indications. Reinfarction was not predictable by clinical variables except by history of angina. The finding that "not current smoker" was an independent correlate with reinfarction was unexpected.
Can physical activity mitigate the effects of aging in middle-aged women?
Authors: Owens J F , Matthews K A , Wing R R , Kuller L H
Published: June 2012

BACKGROUND

Aging is associated with an increased risk of women dying from coronary heart disease as well as from all causes combined. Alterations in the major biological risk factors for early coronary heart disease and all-cause mortality are frequently seen in aging.

METHODS AND RESULTS

The present investigation tested the hypothesis that high levels of physical activity could protect against age-associated changes in biological risk factor levels. In the Healthy Women Study, 507 women were evaluated at study entry and 3 years later. Weekly physical activity level was measured at each examination via the Paffenbarger Physical Activity Questionnaire. During the 3-year period, women increased significantly in weight, blood pressure, levels of total and low-density lipoprotein cholesterol, triglycerides, and insulin and decreased significantly in levels of total high-density lipoprotein cholesterol (HDL-C) and HDL2-C.

CONCLUSIONS

Consistent with the study hypothesis, women who reported higher levels of activity at baseline had less weight gain over time. Furthermore, women who increased their activity during the 3-year interval had the smallest increases in weight and tended to have the smallest decreases in total HDL-C and HDL2-C. The changes in lipids due to activity were largely independent of changes in body weight.
Patients with evidence of coronary endothelial dysfunction as assessed by acetylcholine infusion demonstrate marked increase in sensitivity to constrictor effects of catecholamines.
Authors: Vita J A , Treasure C B , Yeung A C , Vekshtein V I , Fantasia G M , Fish R D , Ganz P , Selwyn A P
Published: June 2012

BACKGROUND

Studies in patients undergoing cardiac catheterization have demonstrated that normal coronary arteries dilate and atherosclerotic arteries constrict in response to exercise and the cold pressor test, but the mechanisms are unknown. These vasomotor responses are mirrored by the vasomotor response to the endothelium-dependent agent acetylcholine. Exercise and the cold pressor test are associated with adrenergic stimulation and increased circulating catecholamines. The present study tested the hypothesis that coronary arteries with intact endothelial function are relatively resistant to the constrictor effects of catecholamines, whereas arteries with loss of endothelial function have increased sensitivity to catecholamine-induced constriction.

METHODS AND RESULTS

The vasomotor function of the coronary endothelium was assessed by serial acetylcholine infusions (final concentration, 10(-8) to 10(-6) M) in 30 segments in 15 patients with minimal or no evidence of coronary atherosclerosis. The acetylcholine responses were related to the vasomotor response to intracoronary phenylephrine infusion (final concentration, 10(-9) to 10(-6) M) in the same segments. In the group of 18 segments that constricted to acetylcholine, there was a constrictor response to phenylephrine at an approximately 100-fold lower concentration than the group of 12 segments that did not constrict to acetylcholine.

CONCLUSIONS

These results suggest that the endothelial dysfunction that characterizes early and late atherosclerosis is associated with a marked increase in sensitivity to the constrictor effects of catecholamines. This finding may explain the constrictor responses of atherosclerotic coronary arteries to exercise and the cold pressor test. In stenotic coronary arteries this mechanism may play a role in the production of myocardial ischemia.
Divergent kinetics of 201Tl and 99mTc-SESTAMIBI in cultured chick ventricular myocytes during ATP depletion.
Authors: Piwnica-Worms D , Chiu M L , Kronauge J F
Published: June 2012

BACKGROUND

Thallous chloride (201Tl) and hexakis(2-methoxyisobutyl isonitrile) technetium (I) (99mTc-SESTAMIBI) are myocardial perfusion imaging agents with biological properties that also reflect tissue viability. Initial myocellular uptake rates of 201Tl reflect activity of Na,K-ATPase, whereas those of 99mTc-SESTAMIBI reflect mean plasma membrane potential.

METHODS AND RESULTS

To better understand the mechanistic responses of these tracers to myocellular injury, cultured chick embryo cardiac myocytes were metabolically inhibited in iodoacetate (1 mM) and rotenone (10 microM) for up to 2 hours, and initial uptake rates of each agent were determined at successive intervals along with correlative cellular contents of ATP, sodium, and potassium and lactate dehydrogenase release. ATP content fell from 30.5 +/- 1.4 to 2.7 +/- 0.9 nmol.(mg protein)-1 within 2 minutes, whereas sodium and potassium contents ran down their thermodynamic gradients more slowly (t 1/2 approximately 60 minutes). Modestly severe cell injury was produced at 2 hours as estimated by lactate dehydrogenase release (18% of total). Initial uptake rates of 201Tl declined from 6.9 +/- 0.8 to 4.0 +/- 0.4 fmol.(mg protein)-1.(nMo)-1.(min)-1 by 20 minutes and remained depressed and ouabain (100 microM)-insensitive at 30 +/- 13% of control. Conversely, initial uptake rates of 99mTc-SESTAMIBI increased from 10.6 +/- 0.8 to 15.0 +/- 0.6 fmol.(mg protein)-1.(nMo)-1.(min)-1 within 10 minutes, remained elevated for 40-60 minutes, and later declined to low values. Injury-induced enhancement of initial uptake rates of 99mTc-SESTAMIBI were insensitive to ouabain (100 microM), carbonyl cyanide-m-chlorophenyl hydrazone (5 microM), and valinomycin (1 microgram/ml) but were significantly inhibited by 130 mM Ko buffer, Ba2+ (1 mM), glybenclamide (100 microM), and quinacrine (10 microM).

CONCLUSIONS

Uptake rates of 201Tl monotonically decline, correlating with Na-K pump inhibition from ATP depletion. Conversely, uptake rates of 99mTc-SESTAMIBI at first increase above control for 40-60 minutes, indicating a mean plasma membrane hyperpolarization possibly resulting from opening of ATP-sensitive and arachidonic acid-activated potassium channels, before declining to low values with more severe cell injury. Correlative non-flow-dependent relations between 201Tl and 99mTc-SESTAMIBI contain information regarding the degree of myocellular injury.
Sex differences in the determinants of left ventricular mass in childhood. The Medical College of Virginia Twin Study.
Authors: Goble M M , Mosteller M , Moskowitz W B , Schieken R M
Published: June 2012

BACKGROUND

Left ventricular (LV) hypertrophy is a predictor of cardiovascular events in adults and has been observed in children and adolescents with hypertension. We wanted to establish the determinants of LV mass in normotensive preadolescent children. Our objectives were 1) to produce a simplified and generalizable model of the clinical variables that determine normal cardiac growth during childhood and 2) to understand better why males have an increased LV mass relative to females, even as children.

METHODS AND RESULTS

In a group of 243 eleven-year-old children, we analyzed anthropometric, hemodynamic, and echocardiographic data to define which variables were predictors of echocardiographically determined LV mass. Stepwise regression was used to predict LV mass overall, by sex, and by body size (body mass index). Overall, LV mass was directly related to weight, male sex, and systolic and diastolic blood pressure and inversely related to resting heart rate and skin-fold thicknesses. Systolic blood pressure was a determinant in boys but not in girls. Heart rate was a weak inverse correlate in both sexes. When the data were analyzed by body mass index quartile, weight was the sole predictor of LV mass in the largest children.

CONCLUSIONS

We conclude that in normotensive preadolescent children, 1) weight, but not pondersity, is a strong predictor of LV mass; 2) body fat is negatively associated with LV mass; 3) boys have an increased LV mass relative to girls; and 4) boys and girls have similar anthropometric determinants and may have different hemodynamic determinants. Our data suggest that body size, and in particular lean body mass, explains much of the variability in cardiac growth seen in children. The influence of hemodynamic variables seems to be more limited. Our findings are of general interest because, although hypertensive heart disease is well described, the early developmental stages are not well understood.
Platelet-dependent thrombin generation after in vitro fibrinolytic treatment.
Authors: Aronson D L , Chang P , Kessler C M
Published: June 2012

BACKGROUND

Fibrinolytic therapy is associated with frequent rethrombosis. There is evidence of both increased coagulation and platelet activation.

METHODS AND RESULTS

Platelet-rich plasma (PRP) or washed platelets were incubated with the fibrinolytic agents urokinase, recombinant tissue-type plasminogen activator (rt-PA), or plasmin at concentrations consistent with those in the plasma of patients treated for myocardial infarction. All of the fibrinolytic agents induced a more rapid generation of thrombin and decreased the clotting times of non-contact-activated PRP than in untreated PRP. This effect was not blocked by the inclusion of thrombin inhibitors during the fibrinolytic treatment. Washed platelets derived from rt-PA-treated PRP induced more rapid thrombin generation when resuspended in untreated plasma or treated plasma. Washed platelets were treated with plasmin, rt-PA, and urokinase and added to platelet-poor plasma. Platelets treated with either plasmin or rt-PA increased the ability of washed platelets to support thrombin generation, but urokinase was without significant effect.

CONCLUSIONS

These results indicate not only that plasmin can cause increased platelet support of prothrombin activation but also that rt-PA in the absence of plasminogen can have a direct effect on the platelet, which increases thrombin generation.
Quantitative assessment of coronary artery stenosis by intravascular Doppler catheter technique. Application of the continuity equation.
Authors: Nakatani S , Yamagishi M , Tamai J , Takaki H , Haze K , Miyatake K
Published: June 2012

BACKGROUND

Quantitative assessment of coronary artery stenoses plays a central role in clinical decision making. According to the continuity equation, the ratio of the time-velocity integral of prestenotic to stenotic flow velocities represents the ratio of the cross-sectional area of the stenotic to prestenotic segments. However, no data exist regarding the application of this method to clinical assessment of human coronary artery diseases. Therefore, we attempted to determine the severity of coronary artery stenoses by applying the continuity equation to the coronary circulation.

METHODS AND RESULTS

Nineteen patients with a stenosis of the proximal left anterior descending coronary artery (LAD) and one patient with a stenosis in an aortocoronary bypass graft to the LAD were studied. Coronary flow velocities at the prestenotic and stenotic segments were measured with an end-mounted Doppler catheter (3F, 20 MHz), and the time-velocity integral ratio was calculated. Percent area stenosis was calculated as (1-time-velocity integral ratio) x 100. In three patients with severe stenosis (greater than 90% in area stenosis), velocity at the stenosis could not be determined because of aliasing of Doppler signals, and in four, Doppler signals at the stenosis were not measurable because of technical difficulties. The stenotic flow velocity was successfully recorded in 13 patients (65%) with mild to moderate stenosis. The diastolic peak flow velocity at the stenosis was 90 +/- 36 cm/sec (mean +/- SD), and was significantly greater than the velocity at the prestenotic segment, 48 +/- 18 cm/sec (p less than 0.01). Percent area stenosis determined by Doppler continuity equation correlated closely with that by biplane coronary angiography (r = 0.83, y = 0.92x-0.45, p less than 0.01).

CONCLUSIONS

Application of the continuity equation to Doppler catheter measurement of coronary flow velocity can be used to successfully compute the severity of coronary stenoses. This may be a useful alternative method to estimate functional severity of coronary artery disease, although further technical developments will be necessary to improve the sensitivity.
Relation between ventricular repolarization duration and cardiac cycle length during 24-hour Holter recordings. Findings in normal patients and patients with long QT syndrome.
Authors: Merri M , Moss A J , Benhorin J , Locati E H , Alberti M , Badilini F
Published: June 2012

BACKGROUND

The interval from the R wave to the maximum amplitude of the T wave (RTm) contains the heart rate dependency of ventricular repolarization.

METHODS AND RESULTS

A computer algorithm was developed to quantify the RTm and preceding RR intervals for each of more than 50,000 beats on 24-hour ambulatory electrocardiographic (Holter) recordings to evaluate the dynamic relation between repolarization duration and cycle length. The relation of RTm to the preceding RR interval (RTm/RR slope) was determined by the best-fit linear regression equation between these two parameters. Eleven normal subjects and 16 patients with long QT syndrome (LQTS) were investigated. Six of the normal subjects had Holter recordings obtained before and after beta-blocker therapy. beta-Blockers were associated with a significant (p = 0.005) reduction in the RTm/RR slope from 0.13 +/- 0.02 to 0.10 +/- 0.02. The mean value of the RTm/RR slope was significantly (p = 0.003) larger in the LQTS patients (0.21 +/- 0.08) than in normal subjects (0.14 +/- 0.03).

CONCLUSIONS

These findings indicate that 1) quantification of the dynamic relation between ventricular repolarization and RR cycle length can be obtained on a large number of Holter-recorded heart beats; 2) beta-blockers reduce the RTm/RR slope in normal patients; and 3) LQTS patients have an exaggerated delay in repolarization at long RR cycle lengths.
Synchronized repolarization after defibrillation shocks. A possible component of the defibrillation process demonstrated by optical recordings in rabbit heart.
Authors: Dillon S M
Published: June 2012

BACKGROUND

It is currently believed that defibrillation shocks act primarily by stimulating excitable myocardium to abolish wave fronts. Recent studies have shown that shocks applied during pacing not only stimulate excitable myocardium but also prolong the depolarization and refractoriness of myocardium already in a depolarized state. This study investigates the effects of shocks on fibrillation action potentials.

METHODS AND RESULTS

Recordings of membrane action potentials free of shock artifact were obtained using the voltage-sensitive dye WW781 during defibrillation of isolated rabbit hearts. These records showed that the shocks caused an additional phase of depolarization beginning with an initial rapid depolarization of the optical signal followed by a slow phase of repolarization. This occurred throughout all phases of the fibrillation action potential from just after completion of the upstroke to a time of near maximal repolarization. Defibrillation shocks, however, had the additional effect of causing the myocardium to repolarize at a constant time after the shock regardless of its prior electrical activity--the constant repolarization time response. This effect was not dependent on the presence of D600 (methoxyverapamil) or continuous coronary perfusion. It was accompanied by a similar constancy in the return of myocardial excitability. Recordings taken from multiple adjacent recording sites also showed a constant repolarization time among them.

CONCLUSIONS

A simple model of reentry is used to illustrate how the constant repolarization response, in addition to wave front termination and refractoriness extension, could play a role in the successful termination of fibrillation by electrical shock.
Basic structure-function relations of the epicardial coronary vascular tree. Basis of quantitative coronary arteriography for diffuse coronary artery disease.
Authors: Seiler C , Kirkeeide R L , Gould K L
Published: June 2012

BACKGROUND

Quantitative coronary arteriography has been validated for stenotic segments of coronary arteries. However, it does not currently account for diffuse coronary artery disease, because the normal size of the coronary artery for its distal myocardial bed size is not known and cannot be measured directly with diffuse involvement of the artery.

METHODS AND RESULTS

From clinical coronary arteriograms of 12 patients without coronary artery disease (group 1) and in 17 patients with coronary artery disease (group 2), we determined by quantitative coronary arteriography 1) the relations among measured coronary artery cross-sectional lumen area, summed distal branch lengths, and regional myocardial mass distal to each point in each coronary artery; 2) the ratio of coronary artery lumen area between parent and daughter vessels at 50 bifurcations; and 3) which of three different theoretical physical principles could underlie the tree structure of the human coronary artery system, by comparing the coronary artery size, branch lengths, regional mass, and relations between parent-to-daughter lumen area ratios with those for the different theoretical physical principles to test which principle best fit the observed data and therefore which principle most probably characterizes the human coronary artery tree structure. The results showed that 1) there is a close correlation between the lumen area of a coronary artery at each point along its length and the corresponding summed distal branch lengths and regional myocardial mass in patients without and with coronary artery disease; 2) measured coronary artery lumen area in patients with coronary artery disease is diffusely 30-50% too small for distal myocardial bed size compared with normal subjects; and 3) the observed relations among coronary artery size, distal summed lengths, myocardial bed size, and parent-to-daughter size ratios are not consistent with the theoretical principle of constant mean blood flow velocity in the coronary circulation but are consistent with the principles of minimum viscous energy loss and of limited/adaptive vascular wall shear stress characterized by a 2/3 power law relating coronary artery lumen area to distal summed branch lengths and regional mass or parent-to-daughter branching ratios.

CONCLUSIONS

These observations provide a basis for quantifying diffuse coronary artery disease on clinical arteriograms.
Spectral analysis of signal-averaged electrocardiograms in patients with idiopathic ventricular tachycardia of left ventricular origin.
Authors: Kinoshita O , Kamakura S , Ohe T , Yutani C , Matsuhisa M , Aihara N , Takaki H , Kurita T , Shimomura K
Published: June 2012

BACKGROUND

The signal-averaged ECG has been used to detect late potentials, and it is considered a noninvasive marker for areas of slow conduction requisite for reentrant arrhythmia. Late potentials are not usually found in patients with idiopathic ventricular tachycardia (VT); nevertheless, fragmented electrograms are often recorded in those patients during endocardial mapping. The purpose of this study was to investigate the spectral content of the signal-averaged ECGs with use of fast Fourier transform analysis (FFT) in patients with idiopathic VT of left ventricular origin.

METHODS AND RESULTS

Signal-averaged ECGs were recorded in 12 patients with idiopathic VT originating from the left ventricle (group 1) and 25 age-matched normal volunteers (group 2). Frequency analysis with FFT was performed with a Blackman-Harris window in a segment length of 120 msec from 40 msec before the end of the QRS complex, and the frequency spectrum was displayed in a three-dimensional graph. Area ratio 1 (area of 20-50 Hz/area of 10-50 Hz) and area ratio 2 (area of 40-100 Hz/area of 0-40 Hz) were calculated in all subjects. Late potentials defined by the time domain were negative in all subjects. The area ratios of group 1 were significantly higher than those of group 2. High-frequency components in the three-dimensional graph were confined within the QRS complex.

CONCLUSIONS

These results suggest that frequency analysis of signal-averaged ECGs with FFT is an available method for detecting the high-frequency component within the QRS complex in some patients with idiopathic VT of left ventricular origin.
Implantable defibrillators for prevention of sudden death. Technology at a medical and economic crossroad.
Authors: Saksena S , Camm A J
Published: June 2012

Implantable cardioverter-defibrillator therapy is now widely used for the treatment of symptomatic patients with documented or suspected life-threatening VTs. Although sudden death recurrence in ICD recipients is virtually eliminated, the extent of benefit both with respect to cardiac mortality and total survival in this patient population remains to be accurately quantitated, particularly vis-à-vis alternative antiarrhythmic therapies. Advanced device and lead systems can be expected to further improve both patient survival and quality of life after implant. The economic impact of unrestrained proliferation in ICD therapy can be enormous; however, available cost-benefit analyses support judicious use of this therapy with comparable economic impact to other accepted cardiovascular therapies. Such prospective risk stratification becomes economically essential when considering expanding its application to asymptomatic or minimally symptomatic populations at potential risk for future cardiac arrest.
Regular physical exercise and low-fat diet. Effects on progression of coronary artery disease.
Authors: Schuler G , Hambrecht R , Schlierf G , Niebauer J , Hauer K , Neumann J , Hoberg E , Drinkmann A , Bacher F , Grunze M
Published: June 2012

BACKGROUND

Significant regression of coronary and femoral atherosclerotic lesions has been documented by angiographic studies using aggressive lipid-lowering treatment. This study tested the applicability and effects of intensive physical exercise and low-fat diet on coronary morphology and myocardial perfusion in nonselected patients with stable angina pectoris.

METHODS AND RESULTS

Patients were recruited after routine coronary angiography for stable angina pectoris; they were randomized to an intervention group (n = 56) and a control group on "usual care" (n = 57). Treatment comprised intensive physical exercise in group training sessions (minimum, 2 hr/wk), daily home exercise periods (20 min/d), and low-fat, low-cholesterol diet (American Heart Association recommendation, phase 3). No lipid-lowering agents were prescribed. After 12 months of participation, repeat coronary angiography was performed; relative and minimal diameter reductions of coronary lesions were measured by digital image processing. Change in myocardial perfusion was assessed by 201Tl scintigraphy. In patients participating in the intervention group, body weight decreased by 5% (p less than 0.001), total cholesterol by 10% (p less than 0.001), and triglycerides by 24% (p less than 0.001); high density lipoproteins increased by 3% (p = NS). Physical work capacity improved by 23% (p less than 0.0001), and myocardial oxygen consumption, as estimated from maximal rate-pressure product, by 10% (p less than 0.05). Stress-induced myocardial ischemia decreased concurrently, indicating improvement of myocardial perfusion. Based on minimal lesion diameter, progression of coronary lesions was noted in nine patients (23%), no change in 18 patients (45%), and regression in 13 patients (32%). In the control group, metabolic and hemodynamic variables remained essentially unchanged, whereas progression of coronary lesions was noted in 25 patients (48%), no change in 18 patients (35%), and regression in nine patients (17%). These changes were significantly different from the intervention group (p less than 0.05).

CONCLUSIONS

In patients participating in regular physical exercise and low-fat diet, coronary artery disease progresses at a slower pace compared with a control group on usual care.
Expression and localization of dystrophin in human cardiac Purkinje fibers.
Authors: Bies R D , Friedman D , Roberts R , Perryman M B , Caskey C T
Published: June 2012

BACKGROUND

Mutations in the dystrophin gene produce clinical manifestations of disease in heart, brain, and skeletal muscle in patients with Duchenne and Beckers muscular dystrophy (DMD/BMD). Conduction disturbances and heart block contribute to cardiac decompensation in these patients, which suggests an important role for dystrophia in the cardiac conduction system. We therefore examined the messenger RNA (mRNA) expression and protein localization of dystrophin in normal human cardiac Purkinje fibers.

METHODS AND RESULTS

Polymerase chain reaction amplification of isolated Purkinje fiber complementary DNA identified several alternatively spliced mRNA transcripts encoding for carboxy-terminal isoforms of the dystrophin protein. The predominant mRNA transcript detected was a splice form previously detected in the brain. Antipeptide antibodies specific for a carboxy-terminal dystrophin sequence were used for Western blot analysis and immunocytochemical localization. These antisera detect approximately 400,000-d immunoreactive band or bands on Western blot in normal heart and Purkinje fibers but not in DMD heart. Immunocytochemical staining showed that dystrophin was localized to the membrane surface of the Purkinje fiber.

CONCLUSIONS

These results suggest that dystrophin may be an important molecule for membrane function in the Purkinje conduction system of the heart and support the hypothesis that defective dystrophin expression contributes to the cardiac conduction disturbances seen in DMD/BMD: