bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure.
Authors: Mancini D M , Walter G , Reichek N , Lenkinski R , McCully K K , Mullen J L , Wilson J R 
Published: June 2012

BACKGROUND
The purpose of this study was to investigate the prevalence of skeletal muscle atrophy and its relation to exercise intolerance and abnormal muscle metabolism in patients with heart failure (HF).

METHODS AND RESULTS
Peak VO2, percent ideal body weight (% IBW), 24-hour urine creatinine (Cr), and anthropometrics were measured in 62 ambulatory patients with HF. 31P magnetic resonance spectroscopy (MRS) and imaging (MRI) of the calf were performed in 15 patients with HF and 10 control subjects. Inorganic phosphorus (Pi), phosphocreatine (PCr), and intracellular pH were measured at rest and during exercise. Calf muscle volume was determined from the sum of the integrated area of muscle in 1-cm-thick contiguous axial images from the patella to the calcaneus. A reduced skeletal muscle mass was noted in 68% of patients, as evidenced by a decrease in Cr-to-height ratio of less than 7.4 mg/cm and/or upper arm circumference of less than 5% of normal. Calf muscle volume (MRI) was also reduced in the patients with HF (controls, 675 +/- 84 cm3/m2; HF, 567 +/- 112 cm3/m2; p less than 0.05). Fat stores were largely preserved with triceps skinfold of less than 5% of normal and/or IBW of less than 80% in only 8% of patients. Modest linear correlations were observed between peak VO2 and both calf muscle volume per meter squared (r = 0.48) and midarm muscle area (r = 0.36) (both p less than 0.05). 31P metabolic abnormalities during exercise were observed in the patients with HF, which is consistent with intrinsic oxidative abnormalities. The metabolic changes were weakly correlated with muscle volume (r = -0.42, p less than 0.05).

CONCLUSIONS
These findings indicate that patients with chronic HF frequently develop significant skeletal muscle atrophy and metabolic abnormalities. Atrophy contributes modestly to both the reduced exercise capacity and altered muscle metabolism.
Intermittent ST depression and mortality after myocardial infarction.
Authors: Ruberman W , Crow R , Rosenberg C R , Rautaharju P M , Shore R E , Pasternack B S 
Published: June 2012

BACKGROUND
We conducted a case-control analysis to determine the contribution made to mortality by intermittent ST depression (STD) among patients enrolled in the already completed Beta Blocker Heart Attack Trial.

METHODS AND RESULTS
STD was determined by computer analysis of 24-hour ECG tapes as a change in ST level by +/- 0.1 mV or more from the median value of ST of all normally conducted complexes for greater than or equal to 1 minute. All computer-detected ST events were verified by trained readers. To estimate risk of dying associated with STD, 261 deaths were compared with controls matched for age, sex, drug status, and time elapsed since acute myocardial infarction. In a model including relevant covariates, STD had a relative risk (RR) of 1.73 (95% confidence interval, 1.09-2.73). The RR was 2.56 (1.39-4.71) in untreated patients and 0.98 (0.48-2.00) in propranolol-treated patients. A history of angina, although not independently significant, was found to enhance these RRs. A gradient of risk was shown in the placebo group by a RR of 1.91 in those with 1-30 minutes of STD and 4.33 in those with greater than 30 of STD (p = 0.001, trend test).

CONCLUSIONS
The findings in this large study show a significant contribution to mortality among untreated early post-myocardial infarction survivors from transient STD on 24-hour monitoring. The absence or reduction of effect in the treated group also suggests an anti-ischemic mechanism by which propranolol exerts a protective effect on mortality. Trials to determine whether reduction of STD improves survival would be warranted.
Influence of dietary fat on the pharmacodynamics of propafenone in isolated, perfused rabbit hearts.
Authors: Gillis A M , Keashly R , Watson P A , Mathison H J , Parsons H G 
Published: June 2012

BACKGROUND
The fatty acid composition of the phospholipids in sarcolemma may significantly influence cell membrane functions. We evaluated the effects of dietary fat on the pharmacodynamics of the antiarrhythmic drug propafenone in isolated, perfused rabbit hearts.

METHODS AND RESULTS
Three groups of weanling rabbits (n = 9 each group) were fed diets of 10% wt/wt lard, fish oil, or safflower oil for 40 days. Differences in electrophysiological variables were assessed at baseline and during propafenone perfusion. Myocardial concentration-effect relations were determined by plotting electrophysiological effects versus coronary sinus propafenone concentrations. The linoleic acid content of isolated sarcolemma was higher in the safflower group (33.4 +/- 11.4%) than in the lard (13.4 +/- 2.3%, p less than 0.01) and fish oil (8.5 +/- 1.4%, p less than 0.01) groups, whereas the omega-3 fatty acid content was higher in the fish oil group (p less than 0.01). During propafenone perfusion, greater changes in ventricular conduction time were observed in the lard group (22 +/- 11 msec) than in the safflower oil group (10 +/- 7 msec, p less than 0.05), whereas changes in ventricular conduction time in the fish oil group (16 +/- 7 msec) were intermediate between the lard and safflower oil groups. The slopes of the linear myocardial concentration-effect relations describing changes in QRS duration were steeper in the lard group (0.22 +/- 0.07 msec/micrograms/ml) than in the safflower oil group (0.13 +/- 0.04 msec/micrograms/ml, p less than 0.01) but not in the fish oil group (0.17 +/- 0.08 msec/microgram/ml, p = NS). Strength-interval curves were similar at baseline in all three groups. During propafenone perfusion, the threshold current was increased significantly at long coupling intervals (250-380 msec) in the lard group (1.8 +/- 1.0 mA) compared with the safflower oil group (0.8 +/- 0.6 mA, p less than 0.05) but not compared with the fish oil group (1.2 +/- 0.6 mA, p = NS).

CONCLUSIONS
Dietary fat significantly alters the fatty acid composition of the phospholipids in sarcolemma. Propafenone effects on ventricular conduction time and ventricular excitability are significantly influenced by the type of dietary fat.
Successful and reproducible myocardial opacification during two-dimensional echocardiography from right heart injection of contrast.
Authors: Villanueva F S , Glasheen W P , Sklenar J , Jayaweera A R , Kaul S 
Published: June 2012

BACKGROUND
Myocardial contrast echocardiography currently involves intro-arterial injection of contrast. For this technique to have a broader application, it is necessary that myocardial opacification be achieved from a venous injection of contrast.

METHODS AND RESULTS
To achieve myocardial opacification after right-side injection of contrast, two groups of open-chest anesthetized dogs were studied. Group 1 included nine dogs in whom microbubbles of various sizes, concentrations, and volumes were injected into the left atrium to determine microbubble characteristics that influence myocardial opacification. Group 2 included eight dogs in whom the effect of the combination of microbubble characteristics and myocardial blood flow on myocardial opacification was evaluated after right atrial injection of contrast. Background-subtracted time-intensity plots were generated from the myocardium to measure peak videointensity. In the group 2 dogs, digital subtraction and color coding were used to further highlight the contrast effect. The number, concentration, and size of the microbubbles all independently affected (p less than 0.01) peak myocardial videointensity after left atrial injection of contrast on multivariate analysis. Highly concentrated microbubbles (4.4 to 5.1 billion/ml) given during dipyridamole-induced coronary hyperemia was most frequently (88%) associated with myocardial opacification after right atrial injection of contrast and was the best predictor of this result on multivariate analysis (chi 2= 9.01, p = 0.003). No changes were noted in left atrial, left ventricular, and pulmonary artery pressures despite injection of large numbers of microbubbles into the right atrium.

CONCLUSIONS
Successful and reproducible myocardial opacification can be achieved during myocardial contrast echocardiography after right atrial injection of contrast. These findings could have far-reaching implications in the use of myocardial contrast echocardiography in acute and chronic ischemic syndromes in humans.
Influence of aortic pressure on effective regurgitant orifice area in aortic regurgitation.
Authors: Caguioa E S , Reimold S C , Vélez S , Lee R T 
Published: June 2012

BACKGROUND
The regurgitant volume in aortic regurgitation is determined by the diastolic filling period, the pressure gradient between the left ventricle and aorta, and the hemodynamic size of the regurgitant orifice area.

METHODS AND RESULTS
To test the hypothesis that the aortic regurgitant orifice area is related to aortic pressure and aortic root size, 16 fresh calf heart and aorta specimens were studied in vitro using a continuous-flow system over a range of aortic pressures. Regurgitant orifice areas were calculated as the ratio of flow divided by peak velocity through the valve measured by image-guided continuous-wave Doppler, and aortic root areas were measured by two-dimensional echocardiography. When the defect was created at the edge of the noncoronary leaflet (n = 10), regurgitant orifice area gradually increased 51 +/- 33% when aortic pressure was increased from approximately 40 to 152 cm of water (29.6 to 112.5 mm Hg) (p less than 0.0001). Similarly, the aortic root size increased 82 +/- 29% when the defect was created at the leaflet edge (p less than 0.0001). In contrast, when defects were created at the center of the noncoronary leaflet (n = 6), only a small increase in regurgitant orifice area (9 +/- 7%) was observed with increasing pressure (p = 0.043). The aortic root area remained strongly pressure dependent in specimens with defects at leaflet centers (p less than 0.0001).

CONCLUSIONS
The aortic regurgitant orifice area is dependent on both aortic pressure and the nature of the defect in the valve. Because not all regurgitant aortic valves are alike, further study of the nature of the regurgitant orifice area in humans may allow identification of patients who would benefit most from aggressive pharmacological therapy.
Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.
Authors: Buxton D B , Mody F V , Krivokapich J , Phelps M E , Schelbert H R 
Published: June 2012

BACKGROUND
Prolonged metabolic abnormalities have been demonstrated previously in postischemic myocardium, including relative increases in glucose uptake and abnormal fatty acid kinetics. However, quantitative metabolic information is limited, and the time course of changes in MVO2 in postischemic myocardium is unknown. To address these issues, chronically instrumented dogs were studied serially over 1 month after transient left anterior descending coronary artery (LAD) occlusion, using positron emission tomography.

METHODS AND RESULTS
Dynamic imaging protocols were used in conjunction with tracer kinetic models to quantify blood flow and metabolic rates. Myocardial sectors were defined as normal, predominantly reversibly injured, and infarct-containing, based on occlusion blood flow images and postmortem histochemistry. Myocardial blood flow and metabolism were homogeneous at baseline. During LAD occlusion for 3 hours, myocardial blood flow in reversibly injured and infarct-containing sectors (determined with 13NH3) was decreased to 46% and 23%, respectively, of blood flow in normal tissue. MVO2, determined with [1-11C]acetate, was decreased less than myocardial blood flow, consistent with increased oxygen extraction in the ischemic tissue. After reperfusion, blood flow normalized rapidly in reversibly injured tissue but remained depressed in infarct-containing sectors. Regional myocardial function, assessed by two-dimensional echocardiography, was severely depressed during occlusion and did not improve significantly until 1 week after reperfusion. MVO2 remained depressed after reperfusion in both reversibly injured and infarct-containing sectors, did not improve from occlusion levels until 1 week after reperfusion, and remained significantly depressed 1 month after reperfusion even in reversibly injured sectors; [1-11C]palmitate kinetics were also abnormal in postischemic tissue. As reported previously, glucose metabolic rates were increased relative to baseline in normal but not in postischemic tissue 3 hours after reperfusion. Subsequently, glucose metabolism tended to be higher in postischemic relative to normal myocardium.

CONCLUSIONS
The results demonstrate decreased oxidative metabolism in postischemic tissue, with concomitant abnormalities in palmitate kinetics and glucose metabolism. Oxidative metabolism and regional function demonstrated a parallel recovery with time.
Three-dimensional potential gradient fields generated by intracardiac catheter and cutaneous patch electrodes.
Authors: Tang A S , Wolf P D , Afework Y , Smith W M , Ideker R E 
Published: June 2012

BACKGROUND
Defibrillation may be improved if electrode configurations can be found that create a larger and more even voltage gradient field across the heart. This study determined the magnitude of the shock gradient fields generated by four nonthoracotomy electrode configurations for defibrillation.

METHODS AND RESULTS
In six dogs, a catheter was inserted containing a right ventricular apical electrode (V) and a right atrial electrode (A). A cutaneous patch electrode (P) was placed on the left lateral thorax. Shock potentials were recorded simultaneously from 128 electrodes in the left ventricular and right ventricular subepicardium and subendocardium, ventricular septum, and atria. With the chest closed, 50-mA shocks were given during diastole via the following lead configurations: V----A (V, cathode; A, anode); V----P; V----A+P; and V+A----P. Potential gradients were calculated at the subepicardium and subendocardium in millivolts per centimeter per volt of shock. In most dogs, the V----A+P configuration produced higher gradients throughout the ventricles than did V----A, V----P, or V+A----P. The maximum potential gradient was smaller for the V+A----P configuration than for V----A, V----P, or V----A+P. The gradient fields for the configurations with the catheter alone or combined with P were uneven.

CONCLUSIONS
It is possible to estimate shock gradient fields in three dimensions. Of the four configurations tested, V----A+P produced the highest gradients and V+A----P produced the lowest high gradient. The gradient fields were uneven throughout the ventricles.
Acute reduction of lipoprotein(a) by tissue-type plasminogen activator.
Authors: Hegele R A , Freeman M R , Langer A , Connelly P W , Armstrong P W 
Published: June 2012

BACKGROUND
Lipoprotein(a) [Lp(a)] is a low density lipoprotein-like particle whose apolipoprotein B (apo B) moiety is disulfide-linked to apo(a), a plasminogen-like inhibitor of fibrinolysis in vitro. We hypothesized that plasma concentrations of Lp(a) are acutely affected by intravenous tissue-type plasminogen activator (t-PA).

METHODS AND RESULTS
Patients with unstable angina were randomized to receive either intravenous t-PA (n = 15) or placebo (n = 11). Two-way ANOVA using repeated measures revealed a significant effect of t-PA on concentrations of Lp(a) (p = 0.026). There was a 48% fall in Lp(a) from baseline concentrations in the t-PA group at 12 hours (p = 0.031) but not at 72 hours. Lp(a) in the placebo group was unchanged.

CONCLUSIONS
We conclude that t-PA produces a sharp and substantial but reversible reduction in plasma Lp(a). These data suggest that Lp(a) concentration is not as static in vivo as had been believed and might be acutely modifiable through some mechanism that induces its removal from the freely circulating state.
Early mortality of acute myocardial infarction in patients with and without prior coronary revascularization surgery. A Coronary Artery Surgery Study Registry Study.
Authors: Davis K B , Alderman E L , Kosinski A S , Passamani E , Kennedy J W 
Published: June 2012

BACKGROUND
The Coronary Artery Surgery Study (CASS) Registry is used to evaluate the effect of various baseline clinical and angiographic factors on mortality after acute out-of-hospital myocardial infarction (MI) in patients with and without prior coronary bypass surgery.

METHODS AND RESULTS
Among the CASS Registry patients, there were 985 medical and 369 surgical patients who had an MI out of the hospital within 3 years after enrollment. In the medical group, 20% died before hospitalization. Medical patients with baseline three-vessel disease or left ventricular (LV) dysfunction were at high risk of immediate death. For medical patients who were hospitalized with MI, mortality was higher for older patients and those with severe angina as well as for those with extensive disease and LV dysfunction. The total 30-day mortality for medical patients was 36%. In the surgical group, 12% died before hospitalization. Surgical patients with LV dysfunction or prior MI were at highest risk of immediate death. For surgical patients hospitalized with MI, mortality was significantly increased only for patients with baseline LV dysfunction. Mortality was not significantly higher for surgical patients with multivessel disease. The total 30-day mortality for surgical patients was 21%. The prior use of aspirin or beta-blockers was not associated with reduced mortality from subsequent MI for either medical or surgical patients. Although the prevalence of cigarette smoking was high among patients who had an MI, cigarette smoking did not alter the infarct-related mortality rate.

CONCLUSIONS
The surgical group had lower mortality rates than the medical group both immediately (p = 0.001), after hospitalization (p less than 0.0001), and at 30 days (p less than 0.0001).
Are contraction and relaxation coupled in patients with and without congestive heart failure?
Authors: Eichhorn E J , Willard J E , Alvarez L , Kim A S , Glamann D B , Risser R C , Grayburn P A 
Published: June 2012

BACKGROUND
Although changes in contractility are often accompanied by changes in relaxation, a mathematical model of ventricular coupling has not been described. A model we examined suggests a hyperbolic relation between measurements of contraction and relaxation. We thus tested the hypothesis that relatively load-independent measurements of contractility (end-systolic elastance [Ees]) and relaxation (the slope of the tau-to-end-systolic pressure relation [R]) were coupled.

METHODS AND RESULTS
To establish the validity of the model, an assessment of Ees and R was made in 30 subjects who underwent sequential digital ventriculography and micromanometer pressure measurements during atrial pacing (93 +/- 10 min-1) before and after graded doses of nitroprusside. To establish if a cyclic AMP (cAMP)-mediated intervention alters coupling, seven of the 30 subjects were studied before and after 3 months of beta-blockade. To determine if a non-cAMP-mediated intervention alters coupling, 12 other patients were studied before and after deslanoside. Nonlinear regression analysis for the initial 30 patients suggested a hyperbolic relation: (Ees) (R) = 1.05 (r = 0.79, p less than 0.001) with an inflection point near Ees = 1.02 mm Hg/ml. Thus, with normal or near-normal contractility, relaxation is normal and not load dependent (R is close to 0). With systolic dysfunction, relaxation becomes very afterload dependent and so must be normalized for load. After long-term beta-blockade in patients with severe left ventricular dysfunction, small improvements in contractility (elastance) occurred with larger changes in relaxation, but the curve describing the relation was not displaced. Acute administration of deslanoside resulted in a large increase in elastance and a smaller change in relaxation but did not alter coupling. However, the magnitude of the change in R was dependent on the predrug R value.

CONCLUSIONS
These data suggest contraction and relaxation may be physiologically coupled with relaxation relatively preserved in early heart failure and more rapid deterioration in relaxation as elastance falls under 1.02 mm Hg/ml. Both beta-blockers (which may act through cAMP) and digitalis (which is cAMP independent) improve contraction and relaxation, but both mechanisms appear to maintain coupling. The hyperbolic relation between contraction and relaxation may have important implications regarding therapeutic response and selection of patients for clinical trials in heart failure.
Early afterdepolarizations and triggered activity induced by cocaine. A possible mechanism of cocaine arrhythmogenesis.
Authors: Kimura S , Bassett A L , Xi H , Myerburg R J 
Published: June 2012

BACKGROUND
Cocaine may produce life-threatening cardiac arrhythmias, but it is not clear whether this is an indirect effect of coronary vasoconstriction and ischemia or a direct myocardial effect of the substance. Except for its effects on the Na+ current as a local anesthetic, little is known about the direct electrophysiological actions on cardiac cells. Therefore, we studied the effects of cocaine on action potentials and membrane currents in isolated feline ventricular myocytes to test the hypothesis that cocaine-induced arrhythmogenesis may be based on cellular and ionic mechanisms.

METHODS AND RESULTS
Action potentials and membrane currents were recorded using the patch clamp technique. Single cells were isolated from feline left ventricles by enzymatic digestion. Exposure to cocaine (10 or 50 microM) depressed the plateau phase of the action potential and prolonged action potential duration. Action potential duration measured at 90% repolarization (APD90) was increased from 280 +/- 12 msec to 325 +/- 17 msec (p less than 0.01) by 5-minute exposure to 10 mumol cocaine, when the cells were stimulated at 1 Hz. During exposure to 50 mumol cocaine, APD90 was markedly increased from 298 +/- 13 msec to 437 +/- 35 msec (p less than 0.01) in seven of 16 cells, and early afterdepolarizations (EADs) developed in these cells. The take-off potential and the amplitude of EADs were -28.3 +/- 2.3 mV and 16.8 +/- 1.2 mV, respectively. Triggered activity arising from EADs was induced in four of the seven cells. Addition of 1 nmol isoproterenol augmented EADs and induced sustained triggered activity, whereas they were suppressed by exposure to 2 microM verapamil. Whole-cell voltage clamp experiments revealed that cocaine (50 microM) reduced the peak L-type Ca2+ current from 1.03 +/- 0.13 nA to 0.79 +/- 0.11 nA (23% reduction, p less than 0.05). Cocaine also reduced the peak delayed rectifier K+ current from 362 +/- 51 pA to 113 +/- 32 pA (69% reduction, p less than 0.01). However, cocaine did not affect activation and inactivation kinetics of these channels. Cocaine had no effect on the inward rectifier K+ current.

CONCLUSIONS
We conclude that cocaine can prolong action potential duration and induce EADs and triggered activity by blocking the delayed rectifier K+ current, and that cocaine-induced abnormalities of repolarization, modulated by its inhibitory effects on catecholamine reuptake, may play a role in the potential of cocaine for induction of acute fatal arrhythmias.