bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of and correction for left ventricular systolic long-axis shortening by magnetic resonance tissue tagging and slice isolation.
Authors: Rogers W J , Shapiro E P , Weiss J L , Buchalter M B , Rademakers F E , Weisfeldt M L , Zerhouni E A
Published: June 2012

BACKGROUND

Measurement of regional left ventricular (LV) function is predicted on the ability to compare equivalent LV segments at different time points during the cardiac cycle. Standard techniques of short-axis acquisition in two-dimensional echocardiography, cine computed tomography, and standard magnetic resonance imaging (MRI) acquire images from a fixed plane and fail to compensate for through-plane motion. The shortening of the left ventricle along its long axis during systole results in planar images of two different levels of the ventricle, leading to error in any derived functional measurements. LV systolic long-axis motion was measured in 19 normal volunteers using MRI.

METHODS AND RESULTS

With a selective radio frequency (RF) tissue-tagging technique, three short-axis planes were labeled at end diastole and standard spin-echo images were acquired at end systole in the two- and four-chamber orientations. Persistence of the tags through systole allowed visualization of the intersecting short-axis tags in the long-axis images and allowed precise quantification of long-axis motion of the septum, lateral, anterior, and inferior walls at the base, mid, and apical LV levels. The total change in position along the long axis between end diastole and end systole was greatest at the base, which moved toward the apex 12.8 +/- 3.8 mm. The mid left ventricle moved 6.9 +/- 2.6 mm, and the apex was nearly stationary, moving only 1.6 +/- 2.2 mm (p less than 0.001). Having quantified the normal range of long-axis shortening, we developed a technique that isolates a slice of tissue between selective RF saturation planes at end diastole. Combining this with a wide end-systolic image slice, end-systolic images were acquired without contamination of signal from adjacent tissue moving into the imaging plane. This technique was validated in a moving phantom and in normal volunteers.

CONCLUSIONS

Significant LV systolic long-axis shortening exists, and this effect is seen the most at the base and the least at the apex. At a given ventricular level, shortening varied significantly according to location. A method using selective saturation pulses and gated spin-echo MRI automatically corrects for this motion and thus eliminates misregistration artifact from regional function analysis.
Intermediate-term effectiveness of balloon valvuloplasty for congenital aortic stenosis. A prospective follow-up study.
Authors: O'Connor B K , Beekman R H , Rocchini A P , Rosenthal A
Published: June 2012

BACKGROUND

Percutaneous balloon valvuloplasty has proven to be acutely effective in the treatment of congenital valvar aortic stenosis; however, the intermediate- and long-term effectiveness of the procedure remain to be documented.

METHODS AND RESULTS

To assess the intermediate-term effectiveness of balloon valvuloplasty, repeat catheterization was performed in 27 of 30 children 1.7 +/- 0.1 years after balloon valvuloplasty for congenital aortic stenosis (AS). In 33 children the peak AS gradient was reduced acutely by 55% from 77 +/- 4 to 35 +/- 3 mm Hg (p less than 0.001), and left ventricular systolic pressure was reduced from 176 +/- 4 to 138 +/- 4 mm Hg (p less than 0.001). Despite a technically adequate valvuloplasty procedure, three patients had inadequate relief of obstruction and required complex surgical intervention. Twenty-seven of the 30 patients available for late reevaluation (90%) enrolled in the follow-up study. The peak AS gradient remained significantly reduced compared with that present before valvuloplasty (29 +/- 3 versus 77 +/- 4 mm Hg, p less than 0.001). Furthermore, there was no difference in peak AS gradient at follow-up compared with that immediately after valvuloplasty. The greatest increase in gradient at reevaluation was 14 mm Hg. Twenty of 27 patients (74%) had no change in the degree of aortic insufficiency at follow-up compared with that present before valvuloplasty. At follow-up, 16 patients had no aortic insufficiency at all, and only two had moderate-to-severe (3-4+) insufficiency. Femoral artery injury was documented in four patients, three of whom were under 12 months of age at valvuloplasty.

CONCLUSIONS

Balloon aortic valvuloplasty provides safe and effective intermediate-term gradient relief without early restenosis in children and adolescents with congenital AS.
Antithrombotic therapy for deep arterial injury by angioplasty. Efficacy of common platelet inhibition compared with thrombin inhibition in pigs.
Authors: Lam J Y , Chesebro J H , Steele P M , Heras M , Webster M W , Badimon L , Fuster V
Published: June 2012

BACKGROUND

Platelet-thrombus formation is a complication of arterial wall deep injury by balloon angioplasty that may lead to acute arterial occlusion and may contribute to restenosis.

METHODS AND RESULTS

Because common platelet-inhibitor drugs with a heparin bolus (100 units/kg) may be effective in inhibiting platelet-thrombus formation after arterial angioplasty, these were compared with a bolus of heparin alone (control), the specific thrombin inhibitor hirudin (1.0 mg/kg), and saline (hirudin control) in normal pigs after angioplasty of the common carotid arteries. In the presence of deep arterial wall injury (injury exposing the media), indium-111-labeled platelet deposition (x 10(6)/cm2) was 68.8 +/- 12.3 and 48.1 +/- 16.9 in the control animals. This was significantly reduced by pretreatment with low-dose aspirin (1 mg/kg/day), by high-dose aspirin (20 mg/kg/day) plus dipyridamole, and especially by thrombin inhibition with hirudin. Treatment regimens with aspirin alone (20 mg/kg/day), dipyridamole alone, or sulfinpyrazone were ineffective. Likewise, the incidence of mural thrombosis was 75% and 80% in deeply injured arteries of controls and was significantly reduced to 46% with aspirin plus dipyridamole, 25% with low-dose aspirin, and 0% with hirudin. The incidence of mural thrombosis was unchanged with high-dose aspirin (69%), dipyridamole (90%), or sulfinpyrazone (92%). This mural thrombosis could not be identified by angiography. In the presence of mild injury (deendothelialization), platelet deposition was low (less than 10 x 10(6)/cm2, a single layer) and was not changed by any therapy, including hirudin.

CONCLUSIONS

These therapies do not affect platelet adhesion to deeply or mildly injured artery. These data suggest a greater role for thrombin inhibition than with thromboxane or cyclooxygenase inhibition in the pathogenesis of platelet-rich mural thrombosis after deep injury during angioplasty. Antithrombotic therapy for arterial thrombosis by thrombin inhibition appears promising.
Left ventricular pressure-volume and Frank-Starling relations in endurance athletes. Implications for orthostatic tolerance and exercise performance.
Authors: Levine B D , Lane L D , Buckey J C , Friedman D B , Blomqvist C G
Published: June 2012

BACKGROUND

Endurance athletes have a high incidence of orthostatic intolerance. We hypothesized that this is related to an abnormally large decrease in left ventricular end-diastolic volume (LVEDV) and stroke volume (SV) for any given decrease in filling pressure.

METHODS AND RESULTS

We measured pulmonary capillary wedge (PCW) pressure (Swan-Ganz catheter), LVEDV (two-dimensional echocardiography), and cardiac output (C2H2 rebreathing) during lower body negative pressure (LBNP, -15 and -30 mm Hg) and rapid saline infusion (15 and 30 ml/kg) in seven athletes and six controls (VO2max, 68 +/- 7 and 41 +/- 4 ml/kg/min). Orthostatic tolerance was determined by progressive LBNP to presyncope. Athletes had steeper slopes of their SV/PCW pressure curves than nonathletes (5.5 +/- 2.7 versus 2.7 +/- 1.5 ml/mm Hg, p less than 0.05). The slope of the steep, linear portion of this curve correlated significantly with the duration of LBNP tolerance (r = 0.58, p = 0.04). The athletes also had reduced chamber stiffness (increased chamber compliance) expressed as the slope (k) of the dP/dV versus P relation (chamber stiffness, k = 0.008 +/- 0.004 versus 0.031 +/- 0.004, p less than 0.005; chamber compliance, 1/k = 449.8 +/- 283.8 versus 35.3 +/- 4.3). This resulted in larger absolute and relative changes in end-diastolic volume over an equivalent range of filling pressures.

CONCLUSIONS

Endurance athletes have greater ventricular diastolic chamber compliance and distensibility than nonathletes and thus operate on the steep portion of their Starling curve. This may be a mechanical, nonautonomic cause of orthostatic intolerance.
Left ventricular hypertrophy associated with chronic cocaine abuse.
Authors: Brickner M E , Willard J E , Eichhorn E J , Black J , Grayburn P A
Published: June 2012

BACKGROUND

This study was performed to determine whether chronic cocaine abuse is associated with left ventricular hypertrophy in humans.

METHODS AND RESULTS

A consecutive series of 40 chronic cocaine abusers 23-44 years old who were enrolled in an inpatient drug rehabilitation program were considered for the study. Subjects with elevated resting blood pressure (n = 4) or a history of hypertension (n = 3) were excluded. Technically adequate two-dimensional echocardiograms were obtained in 30 cocaine abusers and 30 age- and race-matched normal control subjects. All subjects were men, and the groups were similar with regard to resting blood pressure, height, weight, and body surface area. All echocardiograms were read in blinded fashion, and left ventricular mass was calculated by the area-length method. Left ventricular cavity dimensions and wall motion were normal in all subjects. Left ventricular mass index was higher in the cocaine group (103 +/- 24 versus 77 +/- 14 g/m2, p = 0.0001). Posterior wall thickness was increased (1.2 cm or more) in 13 cocaine abusers (43%) compared with four controls (p = 0.0099).

CONCLUSIONS

Chronic cocaine abuse is associated with increased left ventricular mass index and wall thickness. Left ventricular hypertrophy may provide a substrate facilitating the development of myocardial ischemia and/or arrhythmias in cocaine abusers.
The long QT syndrome. Prospective longitudinal study of 328 families.
Authors: Moss A J , Schwartz P J , Crampton R S , Tzivoni D , Locati E H , MacCluer J , Hall W J , Weitkamp L , Vincent G M , Garson A
Published: June 2012

BACKGROUND

The Long QT Syndrome (LQTS) is an infrequently occurring familial disorder in which affected individuals have electrocardiographic QT interval prolongation and a propensity to ventricular tachyarrhythmic syncope and sudden death. We prospectively investigated the clinical characteristics and the long-term course of 3,343 individuals from 328 families in which one or more members were identified as affected with LQTS (QTc greater than 0.44 sec1/2).

METHODS AND RESULTS

The first member of a family to be identified with LQTS, the proband, was usually brought to medical attention because of a syncopal episode during childhood or teenage years. Probands (n = 328) were younger at first contact (age 21 +/- 15 years), more likely to be female (69%), and had a higher frequency of preenrollment syncope or cardiac arrest with resuscitation (80%), congenital deafness (7%), a resting heart rate less than 60 beats/min (31%), QTc greater than or equal to 0.50 sec1/2 (52%), and a history of ventricular tachyarrhythmia (47%) than other affected (n = 688) and unaffected (n = 1,004) family members. Arrhythmogenic syncope often occurred in association with acute physical, emotional, or auditory arousal. The syncopal episodes were frequently misinterpreted as a seizure disorder. By age 12 years, 50% of the probands had experienced at least one syncopal episode or death. The rates of postenrollment syncope (one or more episodes) and probable LQTS-related death (before age 50 years) for probands (n = 235; average follow-up 54 months per patient) were 5.0% per year and 0.9% per year, respectively; these event rates were considerably higher than those observed among affected and unaffected family members.

CONCLUSIONS

Among 232 probands and 1,264 family members with prospective follow-up, three factors made significant independent contributions to the risk of subsequent syncope or probable LQTS-related death before age 50 years, whichever occurred first (Cox hazard ratio; 95% confidence limits): 1) QTc (1.052; 1.017, 1.088), 2) history of cardiac event (3.1; 1.3, 7.2), and 3) heart rate (1.017; 1.004, 1.031). The findings from this prospective longitudinal study highlight the clinical features, risk factors, and course of LQTS.
Adenosine as a vasodilator in primary pulmonary hypertension.
Authors: Morgan J M , McCormack D G , Griffiths M J , Morgan C J , Barnes P J , Evans T W
Published: June 2012

BACKGROUND

The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients.

METHODS AND RESULTS

The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner.

CONCLUSIONS

Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension.
Proximal regulatory domains of rat atrial natriuretic factor gene.
Authors: Rosenzweig A , Halazonetis T D , Seidman J G , Seidman C E
Published: June 2012

BACKGROUND

At least three cis-acting regulatory elements are required for expression of the rat atrial natriuretic factor (ANF) gene. One distal cis-acting regulatory element lies more than 640 base pairs from the transcription initiation site.

METHODS AND RESULTS

In this report, we identify two other proximal regulatory elements that lie within 609 base pairs of the transcription initiation site. One proximal regulatory element contains an activator protein-1 (AP-1)-like binding site and is recognized by the AP-1 protein, the c-fos/c-jun proto-oncogene heterodimer in vitro. The second regulatory element contains a cyclic AMP-responsive element (CRE)-like recognition site.

CONCLUSIONS

In vitro binding of the c-fos/c-jun heterodimer to ANF gene sequences suggests that the heterodimer may play a role in the regulation of gene transcription in vivo. This observation may also explain the correlation between c-fos/c-jun expression and ventricular ANF gene expression found in hypertrophic states. Nuclear extracts from normal cardiocytes contain proteins that bind these regulatory elements but do not appear to bind at the AP-1 site, suggesting that the levels of fos/jun heterodimer in nonhypertrophied cardiocytes are quite low.
Repolarization inhomogeneities in ventricular myocardium change dynamically with abrupt cycle length shortening.
Authors: Rosenbaum D S , Kaplan D T , Kanai A , Jackson L , Garan H , Cohen R J , Salama G
Published: June 2012

BACKGROUND

In single heart cells, abrupt changes in stimulation rate elicit complex alterations in repolarization. The effects of rate change on dispersion of repolarization, however, have not been well characterized.

METHODS AND RESULTS

To determine the effects of abrupt cycle length (CL) shortening on spatial inhomogeneity of repolarization in a syncytium of ventricular cells, 124 action potentials were simultaneously recorded from Langendorff-perfused guinea pig hearts using high-resolution optical mapping with voltage-sensitive dye. The distribution of ventricular action potential durations (APDs) mapped during each cardiac cycle was used to calculate mean APD and repolarization dispersion index (DI), defined as the variance of the distribution. After abruptly shortening CL from 500 to 300 msec, mean APD declined exponentially in normoxic controls (by 23 +/- 3 msec, p less than 0.0001). This response was characterized by beat-to-beat oscillations of APD that were synchronized at all ventricular sites. After 30 minutes of hypoxia, mean APD decreased from 175.0 +/- 13.3 to 76 +/- 25.7 msec. However, during hypoxia, abrupt CL shortening lowered mean APD by only an additional 6 +/- 6 msec, and APD oscillations were no longer synchronized throughout the ventricle. In controls, beat-to-beat DI decreased significantly (-51.0 +/- 6.8%, p less than 0.01) by the sixth post-CL shortening beat and then recovered (by 15-20 beats). In contrast, DI failed to decrease during hypoxia (+7.1 +/- 23%). Two mechanisms for the transient decline of DI in controls were identified: synchronous APD oscillations and transient diminution of the apical-to-basal ventricular APD gradient.

CONCLUSIONS

These data demonstrate that inhomogeneity of ventricular repolarization, as measured by DI, changes dynamically with CL shortening. Furthermore, the hypoxic ventricle does not attenuate DI after abrupt CL shortening and thereby lacks a physiological response expected to diminish vulnerability to arrhythmias.
Effects of dietary omega 3 fatty acids on vascular contractility in preanoxic and postanoxic aortic rings.
Authors: Malis C D , Leaf A , Varadarajan G S , Newell J B , Weber P C , Force T , Bonventre J V
Published: June 2012

BACKGROUND

Vasomotor reactivity may contribute to the pathophysiology of ischemic injury. The atherosclerotic vessel may be particularly susceptible to vasoconstriction because of the damaged endothelial layer with resultant loss of vasodilatory factors. While dietary omega 3 fatty acids have been proposed to protect against vascular occlusion, it is not clear to what extent this results from alterations in the function of platelets or from changes intrinsic to the blood vessel itself.

METHODS AND RESULTS

The effects of dietary supplementation with fish oils on vascular contractility were examined in endothelialized and de-endothelialized aortic rings under pre- and postanoxic conditions. De-endothelialization was defined functionally by the loss of acetylcholine-induced vasodilation in norepinephrine-preconstricted aortic rings from rats fed normal rat chow. Three groups of rats were fed diets containing either 20% menhaden oil or 20% beef tallow, both supplemented with 3% corn oil or 23% corn oil for longer than 4 weeks. All animals received vitamin E. Under well-oxygenated conditions, de-endothelialized aortic rings from rats fed fish oil and corn oil contracted to similar extents with norepinephrine and vasopressin and less than rings from rats fed beef tallow. Endothelialized (intact) and de-endothelialized rings from rats fed fish oil relaxed more in response to acetylcholine than rings from rats fed beef tallow and corn oil. After anoxic exposure and reoxygenation, KCl-induced contraction of intact rings from rats fed fish oil and corn oil was similar and less than rings from rats fed beef tallow. Intact and de-endothelialized rings from rats fed fish oil relaxed more to acetylcholine than did rings from rats fed beef tallow and corn oil.

CONCLUSIONS

Under preanoxic or postanoxic conditions, rings from rats fed fish oil and corn oil contracted less than rings from rats fed beef tallow. The relaxation response to acetylcholine, however, was greater in rings from rats fed fish oil than from rats fed either corn oil or beef tallow. These vascular effects of fish oil feeding may result in increased blood flow to ischemic and reperfused tissues in vivo.
Relative importance of thrombin compared with plasmin-mediated platelet activation in response to plasminogen activation with streptokinase.
Authors: Winters K J , Santoro S A , Miletich J P , Eisenberg P R
Published: June 2012

BACKGROUND

Platelet activation occurs in vivo during pharmacologic thrombolysis and may contribute to recurrent thrombosis. Plasmin does not directly activate platelets except at high concentrations; thus, the mechanisms for platelet activation during thrombolysis remain undefined. Increases in thrombin activity also occur in patients treated with fibrinolytic agents and may contribute to activation of platelets. We have shown that one mechanism for increased thrombin activity is activation of the coagulation system by plasmin.

METHODS AND RESULTS

In the present study we sought to determine whether activation of platelets in response to pharmacologic activation of plasminogen in plasma is due primarily to plasmin or mediated by increased thrombin activity. Platelet-rich citrated plasma (PRP) was recalcified and incubated with 1,000 IU/ml of streptokinase or 1.0 caseinolytic units/ml of plasmin. Concentrations of fibrinopeptide A, a marker of thrombin activity, increased markedly over 10 minutes in plasma incubated with streptokinase or plasmin, but not in PRP incubated without plasminogen activator. Platelet activation characterized by the secretion of 14C-serotonin occurred within 2-4 minutes after thrombin activity increased. In stirred recalcified PRP, platelet aggregation was accelerated from 3.6 +/- 0.5 to 2.5 +/- 0.3 minutes (p less than 0.01) when incubated with 1,000 IU/ml of streptokinase. Leupeptin and aprotinin, inhibitors of plasmin activity, markedly attenuated platelet activation in response to pharmacologic activation of plasminogen. However, inhibition of thrombin with heparin, hirudin, or D-Phe-D-Pro-L-Arg-chloromethylketone was more effective in inhibiting the acceleration of platelet activation induced by plasminogen activation, despite the elaboration of plasmin activity.

CONCLUSIONS

Activation of platelets during coronary thrombolysis may be due in part to increased procoagulant activity induced by plasminogen activation as well as other factors that promote platelet activation in vivo.
Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity.
Authors: Sullivan M J , Green H J , Cobb F R
Published: June 2012

BACKGROUND

Exertional fatigue, which frequently limits exercise in patients with chronic heart failure, is associated with early anaerobic metabolism in skeletal muscle. The present study was designed to examine the skeletal muscle metabolic response to exercise in this disorder and determine the relation of reduced muscle blood flow and skeletal muscle biochemistry and histology to the early onset of anaerobic metabolism in patients.

METHODS AND RESULTS

We evaluated leg blood flow, blood lactate, and skeletal muscle metabolic responses (by vastus lateralis biopsies) during upright bicycle exercise in 11 patients with chronic heart failure (ejection fraction 21 +/- 8%) and nine normal subjects. In patients compared to normal subjects, peak exercise oxygen consumption was decreased (13.0 +/- 3.3 ml/kg/min versus 30.2 +/- 8.6 ml/kg/min, p less than 0.01), whereas peak respiratory exchange ratio and femoral venous oxygen content were not different (both p greater than 0.25), indicating comparable exercise end points. At rest in patients versus normals, there was a reduction in the activity of hexokinase (p = 0.08), citrate synthetase (p less than 0.02), succinate dehydrogenase (p = 0.0007), and 3-hydroxyacyl CoA dehydrogenase (p = 0.04). In patients, leg blood flow was decreased at rest, submaximal, and maximal exercise when compared to normal subjects (all p less than 0.05), and blood lactate accumulation was accelerated. In patients, during submaximal exercise blood lactate levels were not closely related to leg blood flow but were inversely related to rest citrate synthetase activity in skeletal muscle (r = -0.74, p less than 0.05). At peak exercise there were no intergroup differences in skeletal muscle glycolytic intermediates, adenosine nucleotides, or glycogen, whereas in patients compared to normal subjects less lactate accumulation and phosphocreatine depletion were noted (both p less than 0.05), suggesting that factors other than the magnitude of phosphocreatine depletion or lactate accumulation may influence skeletal muscle fatigue in this disorder.

CONCLUSIONS

The results of the present study suggest that in patients with chronic heart failure reduced aerobic activity in skeletal muscle plays an important role in mediating the early onset of anaerobic metabolism during exercise. Our findings are consistent with the concept that reduced aerobic enzyme activity in skeletal muscle is, in part, responsible for determining exercise tolerance and possibly the response to chronic intervention in patients with chronic heart failure.
Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function.
Authors: Bonow R O , Lakatos E , Maron B J , Epstein S E
Published: June 2012

BACKGROUND

Many asymptomatic patients with aorta regurgitation and normal left ventricular systolic function remain clinically stable for many years, but others ultimately develop symptoms or left ventricular dysfunction and require operation. To identify indexes of left ventricular function predictive of symptomatic and functional deterioration during the long-term course of asymptomatic patients, we studied 104 asymptomatic patients with chronic severe aortic regurgitation and normal left ventricular ejection fraction at rest.

METHODS AND RESULTS

Serial echocardiographic (average, 7.8 per patient) and radionuclide angiographic (average, 5.0 per patient) studies were obtained over a mean follow-up period of 8 years (range, 2-16 years). By Kaplan-Meier life table analysis, 58 +/- 9% of patients remained asymptomatic with normal ejection fraction at 11 years, an average attrition rate of less than 5% per year; two patients died suddenly, four developed asymptomatic left ventricular dysfunction, and 19 underwent operation because symptoms developed. By univariate Cox regression analysis, many variables on initial study were associated with death, ventricular dysfunction, or symptoms, including age, left ventricular end-systolic dimension and end-diastolic dimension, fractional shortening, and both rest and exercise ejection fraction (all p less than 0.001). The average rates of change of rest ejection fraction, fractional shortening, and end-systolic dimension were also associated with death or symptoms by univariate Cox analysis (all p less than 0.01). However, when all variables were included in a multivariate Cox analysis, only age (p less than 0.05), initial end-systolic dimension (p less than 0.001), and rate of change in end-systolic dimension and rest ejection fraction during serial studies (both p less than 0.05) predicted outcome.

CONCLUSIONS

Thus, in addition to indexes of left ventricular function determined on initial evaluation, serial long-term changes in systolic function identify patients likely to develop symptoms and require operation. Patients have a higher risk of symptomatic deterioration if there is progressive change in end-systolic dimension or resting ejection fraction during the course of serial studies.
Regional control of atrial fibrillation by rapid pacing in conscious dogs.
Authors: Allessie M , Kirchhof C , Scheffer G J , Chorro F , Brugada J
Published: June 2012

BACKGROUND

In five chronically instrumented conscious dogs, we studied the effects of rapid pacing on sustained electrically induced atrial fibrillation.

METHODS AND RESULTS

Twenty-three unipolar atrial electrograms were recorded simultaneously from the bundle of Bachmann and the lateral wall of the right and left atria. During sustained atrial fibrillation, the surface electrocardiogram showed continuous irregularities of the baseline without P or F waves as well as an irregular ventricular rhythm with narrow QRS complexes. The atrial electrograms showed rapid irregular activity with a median cycle length of 85 +/- 8 msec and a range (P5-95) of 33 +/- 18 msec. Overdrive pacing of atrial fibrillation was performed using symmetric biphasic rectangular stimuli (2-msec duration, sixfold that of threshold) applied to a pair of stimulating electrodes at the left atrial appendage. Stimulation was started at pacing intervals of about 10 msec longer than the local median fibrillation interval and subsequently shortened in steps of 1 msec. At a critical pacing interval slightly shorter than the median fibrillation interval, the atrium around the pacing site was suddenly captured by the electrical stimuli. The area of local capture had a diameter of 6.1 +/- 1.6 cm. The time window of capture was 12 +/- 4 msec.

CONCLUSIONS

These observations show that during electrically induced atrial fibrillation in chronically instrumented conscious dogs, a short excitable gap is present, permitting regional control of the fibrillatory process by rapid pacing.
Evaluation of contractile state by maximal ventricular power divided by the square of end-diastolic volume.
Authors: Kass D A , Beyar R
Published: June 2012

BACKGROUND

Maximal ventricular power (PWRmax) reflects contractile state and has the potential to be noninvasively determined. However, its sensitivities to preload, afterload resistance, and inotropic state are incompletely defined. The present study determines these dependencies and proposes a novel power-based contractile index that is little altered by load.

METHODS AND RESULTS

Seven open-chest, autonomically blocked dogs were instrumented with a proximal aortic flow probe, central aortic and ventricular micromanometers, and a conductance catheter for ventricular chamber volume. Preload was transiently reduced by left atrial hemorrhage, and afterload was increased by intra-aortic balloon inflation. Inotropic state was pharmacologically altered by lidocaine, dobutamine, propranolol, or verapamil. PWRmax was highly preload sensitive, altering 1.7 +/- 0.1-fold a given percent change in end-diastolic volume (EDV). This preload dependence was reduced by dividing PWRmax by EDV but was virtually eliminated when PWRmax was divided by EDV2. This latter index also displayed little change in response to as much as 60% increases in afterload resistance. PWRmax/EDV2 varied directly with inotropic state, correlating to both the slope (Ees) of the end-systolic pressure-volume relation (PWRmax x 1,000/EDV2 = 0.31 x Ees - 0.04, r = 0.82, p less than 0.001) and the slope (A) of the dP/dtmax-EDV relation (PWRmax x 1,000/EDV2 = 0.025 x A + 0.02, r = 0.86, p less than 0.001). PWRmax values determined from the product of ventricular pressure and flow versus central aortic pressure and flow were nearly identical over a broad loading range, indicating that PWRmax may be noninvasively assessed (i.e., without requiring left ventricular chamber pressure).

CONCLUSIONS

PWRmax divided by EDV2 provides a measure of contractile function that is little influenced by loading conditions and has potential for noninvasive clinical use.
Usefulness of transesophageal echocardiography in assessment of aortic dissection.
Authors: Ballal R S , Nanda N C , Gatewood R , D'Arcy B , Samdarshi T E , Holman W L , Kirklin J K , Pacifico A D
Published: June 2012

BACKGROUND

The value of transesophageal echocardiography in the assessment of patients with aortic dissection was studied.

METHODS AND RESULTS

Group 1 (34 patients) represented all patients studied at our institution with this technique in whom aortic dissection was proven by aortography, surgery, or autopsy. Group 2 (27 patients) represented all patients studied with this technique at our institution in whom aortic dissection was excluded by aortography. Transesophageal echocardiography made a correct diagnosis of aortic dissection in 33 of 34 patients (sensitivity, 97%; specificity, 100%). It also correctly demonstrated the type of dissection in all 29 patients with aortographic or surgical proof. On the other hand, computed tomography scanning, performed in 24 of 34 patients in group 1, made a correct diagnosis in only 67% of patients and misclassified the type of dissection in 33%. Transesophageal echocardiography correctly identified involvement of the coronary arteries by aortic dissection in six of seven patients as well as absence of both left and right coronary artery involvement in 10 patients with aortic dissection. This technique was also useful in detecting communications between the true and false lumens, presence of thrombi in the false lumen, and, in two patients, localized dissection rupture with formation of a false aneurysm. In both groups 1 and 2, transesophageal echocardiography correctly identified patients with moderate to severe aortic regurgitation.

CONCLUSIONS

Transesophageal echocardiography is very useful in the assessment of aortic dissection.
Skeletal muscle metaboreceptor exercise responses are attenuated in heart failure.
Authors: Sterns D A , Ettinger S M , Gray K S , Whisler S K , Mosher T J , Smith M B , Sinoway L I
Published: June 2012

BACKGROUND

Resting sympathetic nervous system activity is increased in heart failure. Whether sympathetic nervous system responses during exercise are increased is controversial. Furthermore, the role of muscle metaboreceptors and central command in regulating sympathetic outflow has been largely unexplored.

METHODS AND RESULTS

Muscle sympathetic nerve activity (MSNA, peroneal nerve) was measured in nine heart failure subjects and eight age-matched control subjects during static exercise (30% maximal voluntary contraction) for 2 minutes and during a period of posthandgrip regional circulatory arrest. This maneuver isolates the metaboreceptor contribution to sympathetic nervous system responses. MSNA responses were similar during static exercise in the two groups. During posthandgrip regional circulatory arrest we observed a marked attenuation in MSNA responses in the heart failure subjects (15% increase in heart failure versus 57% increase in control subjects). A cold pressor test demonstrated a normal MSNA response to a potent nonspecific stimulus in the heart failure subjects (heart failure subjects, 141% increase; control subjects, 215% increase; NS). Nuclear magnetic resonance spectroscopy studies in five separate heart failure subjects and five control subjects suggested that the attenuated metaboreceptor response in heart failure was not due to reduced H+ production.

CONCLUSIONS

Skeletal muscle metaboreceptor responses are impaired in heart failure. Because MSNA responses during static exercise are similar in the two groups, mechanisms aside from metaboreceptor stimulation must be important in increasing sympathetic nervous system activity.
Psychosocial factors impair vascular responses of coronary arteries.
Authors: Williams J K , Vita J A , Manuck S B , Selwyn A P , Kaplan J R
Published: June 2012

BACKGROUND

Four sets of monkeys were used to examine the effect of chronic psychosocial disruption and diet on dilator responses of coronary arteries.

METHODS AND RESULTS

One set consisted of monkeys consuming monkey chow and living in a stable social setting (nonatherosclerotic controls, n = 6). Three sets consumed an atherogenic diet for 14 months followed by one of three treatments for the next 16 months: 1) a high-cholesterol diet and housed in unstable social groups (n = 9); 2) a low-cholesterol diet and housed in unstable (n = 8); or 3) stable groups (n = 10). Quantitative coronary angiography revealed that intracoronary infusion of acetylcholine resulted in a change of diameter (versus infusion of 5% dextrose in water) of +4 +/- 1% in control monkeys and -11 +/- 4% in unstable monkeys consuming a high-cholesterol diet (p less than 0.05). In monkeys consuming the cholesterol-lowering diet, the change in artery diameter was +2 +/- 4% in stable and -10 +/- 4% in unstable social conditions (p less than 0.05) despite a similar plaque size (0.4 +/- 0.2 and 0.5 +/- 0.1 mm2) and total plasma cholesterol concentrations (179 +/- 9 and 172 +/- 6 mg/dl), respectively. The arterial response to nitroglycerin was similar among all groups of monkeys.

CONCLUSIONS

We conclude that chronic social disruption is associated with relative arterial constriction in response to acetylcholine in atherosclerotic monkeys consuming a cholesterol-lowering diet.
Predictors of survival in neonates with critical aortic stenosis.
Authors: Rhodes L A , Colan S D , Perry S B , Jonas R A , Sanders S P
Published: June 2012

BACKGROUND

Failure of infants with critical aortic stenosis to survive after adequate valvotomy despite a left ventricular size that appears to be adequate indicates that additional preoperative anatomic features may contribute to mortality.

METHODS AND RESULTS

Discriminant analysis was used to determine which of several echocardiographically measured left heart structures were independent predictors of survival after valvotomy for neonatal critical aortic stenosis. It was possible to predict outcome after classic valvotomy (two-ventricle-type repair) with 95% accuracy based on mitral valve area, long-axis dimension of the left ventricle relative to the long-axis dimension of the heart, diameter of the aortic root, and body surface area. Left ventricular volume was not a major determinant in this study, in part because patients who had initial valvotomy had been preselected in favor of an adequately sized left ventricle. Patients with multiple small left ventricular structures were found to have significantly improved survival after initial Norwood operation. In contrast, balloon valvotomy with subsequent Norwood procedure was usually unsuccessful.

CONCLUSIONS

The adverse effects of small inflow, outflow, and/or cavity size of the left ventricle are cumulative. The accuracy of prediction of outcome based only on preoperative anatomy indicates that adequacy of valvotomy is not generally a limiting factor for survival in this group of patients. It is possible to identify subjects whose chance of survival is better after a Norwood procedure rather than valvotomy, even if left ventricular volume is not critically small.
Protection against endocarditis due to Staphylococcus epidermidis by immunization with capsular polysaccharide/adhesin.
Authors: Takeda S , Pier G B , Kojima Y , Tojo M , Muller E , Tosteson T , Goldmann D A
Published: June 2012

BACKGROUND

Staphylococcus epidermidis is the principal pathogen in prosthetic valve endocarditis. The capsular polysaccharide adhesin (PS/A) has been shown to mediate attachment of bacteria to medical devices. In this study, we investigated the efficacy of active and passive immunization against PS/A in preventing S. epidermidis endocarditis in a rabbit model.

METHODS AND RESULTS

Aortic valve vegetations were produced by inserting a Teflon catheter into the left ventricle through the right carotid artery. Bacteremia and endocarditis were then established by implanting in the left jugular vein a catheter that was attached to an osmotic pump and contaminated with S. epidermidis strain RP62A. During a 3-week study period, of 64 blood cultures taken every second or third day from six nonimmune rabbits, 54 (84%) yielded strain RP62A. In rabbits actively immunized with PS/A, eight of 60 blood cultures (13%) were positive (odds ratio 5.0, 95% CI, 2.0-12.3, p = 0.005). At death, all six nonimmune rabbits had infected vegetations that yielded 10(6)-10(11) colony-forming units (cfu)/g of vegetation, whereas only one PS/A-immunized rabbit had an infected vegetation. Immunization protocols designed to elicit antibody to teichoic acid but not to PS/A afforded no protection against bacteremia or endocarditis. Infusion of monoclonal antibody to PS/A through a catheter in the right jugular vein provided a level of protection against both bacteremia and endocarditis comparable to that produced by active immunization. In vitro, antibody against PS/A was opsonic for S. epidermidis.

CONCLUSIONS

Immunoprophylaxis targeted at staphylococcal PS/A is a promising new approach to the prevention of prosthetic valve endocarditis.
Valvular heart disease in four patients with Maroteaux-Lamy syndrome.
Authors: Tan C T , Schaff H V , Miller F A , Edwards W D , Karnes P S
Published: June 2012

BACKGROUND

Maroteaux-Lamy syndrome is a lysosomal storage disease of mucopolysaccharide metabolism (MPS type VI) that may involve the mitral and aortic valves. Affected patients have other skeletal and oropharyngeal malformations that complicate anesthetic and surgical management.

METHODS AND RESULTS

The present report describes the clinical, echocardiographic, and pathological findings in four patients with Maroteaux-Lamy syndrome. Two of three siblings underwent successful double-valve replacement for aortic and mitral valve stenoses. The third sibling, whose aortic and mitral valves were thick and fibrotic, died from septicemia after hip surgery. A fourth, unrelated patient also had successful double-valve replacement.

CONCLUSIONS

Our experience emphasizes the potential difficulties in preoperative assessment and surgical treatment as well as the unique problems related to airway management in patients with this syndrome.
Are aortic aneurysms caused by atherosclerosis?
Authors: Reed D , Reed C , Stemmermann G , Hayashi T
Published: June 2012

BACKGROUND

The emerging controversy concerning the causal role of atherosclerosis in the development of aortic aneurysms was examined using the accumulated clinical and autopsy data obtained during a 20-year follow-up of a cohort of more than 8,000 men of Japanese ancestry in Hawaii.

METHODS AND RESULTS

Analyses of 174 clinical incident events indicated that there were two types of aneurysmal disease, 151 aortic aneurysms and 23 aortic dissections. The baseline risk factors that predicted the clinical aortic aneurysms were the same factors that predicted aortic atherosclerosis in the same cohort, namely, high blood pressure, high serum cholesterol, and cigarette smoking. These same risk factors were also significantly associated with the occurrence of 27 aortic aneurysms among 293 autopsied men. The less common aortic dissections had an age-specific incidence pattern indicative of an innate susceptibility precipitated by an exposure to another factor. This pattern was consistent with the findings that the incidence of aortic dissections was predicted mainly by baseline high blood pressure.

CONCLUSIONS

From the perspective of prevention, it appears that the risk factors for aortic atherosclerosis and probably atherosclerosis itself are necessary elements in the causal pathway for the great majority of aortic aneurysms in this cohort.
Treatment of prolonged ventricular fibrillation. Immediate countershock versus high-dose epinephrine and CPR preceding countershock.
Authors: Niemann J T , Cairns C B , Sharma J , Lewis R J
Published: June 2012

BACKGROUND

Early countershock of ventricular fibrillation has been shown to improve immediate and long-term outcome of cardiac arrest. However, a number of investigations in the laboratory and in the clinical population indicate that immediate countershock of prolonged ventricular fibrillation most commonly is followed by asystole or a nonperfusing spontaneous cardiac rhythm, neither of which rarely respond to current therapy. The use of epinephrine in doses greater than those currently recommended has recently been shown to improve both cerebral and myocardial perfusion during cardiopulmonary resuscitation (CPR). The purpose of this study was to compare cardiac resuscitation outcome between immediate countershock of prolonged ventricular fibrillation with high-dose epinephrine therapy and conventional CPR before countershock of prolonged ventricular fibrillation in a canine model.

METHODS AND RESULTS

After sedation, intubation, induction of anesthesia, and instrumentation, ventricular fibrillation was electrically induced in 28 dogs. After 7.5 minutes of ventricular fibrillation, animals were randomly allocated to two treatment groups: group 1, immediate countershock followed by recommended advanced cardiac life support (ACLS) interventions, or group 2, 0.08 mg/kg epinephrine and manual closed-chest CPR before countershock and ACLS. In both groups, ACLS was continued until a spontaneous perfusing rhythm was restored or for 20 minutes (total arrest time, 27.5 minutes). A spontaneous perfusing rhythm was restored in three of 14 group 1 animals and in nine of 14 group 2 animals (p = 0.014 by sequential analysis method of Whitehead). Coronary perfusion pressure (aortic minus right atrial pressure during CPR diastole) before countershock was significantly greater in group 2 (21 +/- 7 mm Hg) when compared with mean circulatory pressure in group 1 (9 +/- 8, p less than 0.01).

CONCLUSIONS

The findings of this study suggest that a brief period of myocardial perfusion before countershock improves cardiac resuscitation outcome from prolonged ventricular fibrillation.
Response of high-energy phosphates and lactate release during prolonged regional ischemia in vivo.
Authors: Schaefer S , Schwartz G G , Wisneski J A , Trocha S D , Christoph I , Steinman S K , Garcia J , Massie B M , Weiner M W
Published: June 2012

BACKGROUND

The functional impairment of persistently ischemic, or "hibernating," myocardium may serve to maintain myocardial cell viability through a reduction of energy requirements. Although previous studies have, in a variety of experimental models, independently shown variable responses in lactate metabolism and intracellular phosphates during prolonged ischemia, the responses of these metabolites under identical flow conditions have not been adequately described.

METHODS AND RESULTS

To examine the responses of high-energy phosphates and lactate metabolism to prolonged ischemia induced by partial coronary artery stenosis, 12 open-chest pigs were studied using 31P nuclear magnetic resonance spectroscopy. Concurrent measurements of blood flow, segment shortening, high-energy phosphates, and lactate release (in nine animals) were made during 2 hours of regional ischemia. Subendocardial blood flow and segment shortening were persistently depressed during ischemia, with parallel reductions in ATP, phosphocreatine (PCr), and the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Pi was persistently elevated during the ischemic period. In contrast, lactate release increased significantly from 0.23 +/- 0.04 to 1.34 +/- 0.28 mumol/ml after 15 minutes of ischemia (p less than 0.05) but then decreased to 0.73 +/- 0.17 mumol/ml at 2 hours (p less than 0.05 versus 15 minutes, p = NS versus control). Similarly, pH increased significantly from a nadir of 6.82 +/- 0.07 at 30 minutes of ischemia to 6.98 +/- 0.05 at 2 hours.

CONCLUSIONS

Changes in high-energy phosphates parallel changes in blood flow and function during prolonged ischemia, whereas there is a partial amelioration in lactate production and acidosis. These data support the concept that reduction of myocardial energy requirements during prolonged flow reduction results in signs of reduced ischemia.