bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis.
Authors: Friedrich S P , Lorell B H , Rousseau M F , Hayashida W , Hess O M , Douglas P S , Gordon S , Keighley C S , Benedict C , Krayenbuehl H P 
Published: June 2012

BACKGROUND
Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction.

METHODS AND RESULTS
We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV micromanometer pressure and dimensions, (2) LV regional wall motion analyzed by the area method, and (3) Doppler flow-velocity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atrial natriuretic peptide. In patients with aortic stenosis, LV end-diastolic pressure declined from 25 +/- 2 to 20 +/- 2 mm Hg (P < .05). LV pressure-volume and LV pressure-dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating improved diastolic distensibility. Regional area change during isovolumic relaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of isovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac output, or right atrial pressure, excluding alterations in right ventricular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22 +/- 2 to 18 +/- 2 mm Hg (P < .05) was accompanied by a significant fall in right atrial pressure (9 +/- 1 to 6 +/- 1 mm Hg), implicating alterations in pericardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensibility.

CONCLUSIONS
Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of intracoronary enalaprilat on diastolic function were not observed in patients with dilated cardiomyopathy who did not have concentric hypertrophy. These observations support the hypothesis that the cardiac renin-angiotensin system is activated in patients with concentric pressure-overload hypertrophy and that this activation may contribute to impaired diastolic function.
Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST).
Authors: Anderson J L , Platia E V , Hallstrom A , Henthorn R W , Buckingham T A , Carlson M D , Carson P E 
Published: June 2012

BACKGROUND
The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular ectopy with antiarrhythmic drugs after a myocardial infarction reduces the incidence of sudden arrhythmic death. Patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The encainide and flecainide arms of the study were discontinued in 1989 (CAST-I) and the moricizine arm in 1991 (CAST-II) because of excess mortality. To explore the mechanisms of these adverse outcomes, we examined the interaction of baseline characteristics with the hazard of therapy with encainide, flecainide, or moricizine compared with their respective placebos.

METHODS AND RESULTS
CAST-I comprised 755 patients assigned to flecainide or encainide and 743 patients assigned to placebo, whereas in CAST-II, 502 patients received moricizine and 491 patients received placebo. Clinical and laboratory baseline variables of patients receiving active drug and those receiving placebo were similar. In CAST-I patients, there was a significant interaction of active therapy with both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest for non-Q-wave myocardial infarction (total mortality hazard ratios, 1.8 versus 7.9 for Q-wave versus non-Q-wave infarction, P = .03). Ventricular premature depolarization (VPD) frequency > or = 50/h and heart rate > or = 74 beats per minute each interacted significantly with total mortality/cardiac arrest only. In the sicker CAST-II patients (ejection fraction < or = 40%), only diuretic use at baseline interacted significantly with moricizine use for both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest (total mortality hazard ratios, 1.9 versus 0.7 for diuretic use versus no use, P = .01).

CONCLUSIONS
Although active treatment in CAST-I was associated with greater mortality than placebo with respect to almost all baseline variables, the therapeutic hazard was more than expected in patients with non-Q-wave myocardial infarction and (for total mortality) frequent premature VPDs and higher heart rates, suggesting that the adverse effect of encainide or flecainide therapy is greater when ischemic and electrical instability are present. The relative hazard of therapy with moricizine in the sicker CAST-II population was greater in those using diuretics. Thus, although these drugs have the common ability to suppress ventricular ectopy after myocardial infarction, their detrimental effects on survival may be mediated by different mechanisms in different populations, emphasizing the complex, poorly understood hazards associated with antiarrhythmic drug treatment.
Surgery for aortic stenosis in elderly patients. A study of surgical risk and predictive factors.
Authors: Logeais Y , Langanay T , Roussin R , Leguerrier A , Rioux C , Chaperon J , de Place C , Mabo P , Pony J C , Daubert J C 
Published: June 2012

BACKGROUND
Aortic stenosis is the most common valvular lesion occurring among elderly patients and has become extremely frequent because of changing demographics in industrialized countries. Surgical risk after the age of 70 has increased. The increasing older age of patients having surgery justifies an analysis of mortality predictive factors.

METHODS AND RESULTS
Between 1976 and February 1993, we performed 2871 operations for aortic stenosis. This study concerns 675 patients (278 men and 397 women) who were > or = 75 years old. Mean age was 78.5 +/- 3 years. Associated lesions were found in 226 patients. A bioprosthesis was implanted in 632 patients (93.6%). Concomitant surgical procedures were performed in 133 patients. Surgical mortality was 12.4% (84 deaths). A longitudinal analysis has been carried out over four successive time periods to evaluate population evolution during these 17 years. Statistical analysis was performed on 46 variables. Multivariate analysis found age (P < .0001), left ventricular failure (P < .0001), lack of sinus rhythm (P < .01), and emergency status (P < .02) to be presurgical independent predictive factors of mortality.

CONCLUSIONS
Risk-reducing strategy should both favor relatively early surgery to avoid cardiac failure and emergency situations and pay careful attention to the use of myocardial protection and cardiopulmonary bypass. Indications for surgery should remain broad since analysis failed to determine specific high-risk groups to be eliminated, and surgery remains the only treatment for aortic stenosis.
End-systolic volume and long-term survival after coronary artery bypass graft surgery in patients with impaired left ventricular function.
Authors: Hamer A W , Takayama M , Abraham K A , Roche A H , Kerr A R , Williams B F , Ramage M C , White H D 
Published: June 2012

BACKGROUND
Left ventricular function is the main predictor of long-term survival in patients with coronary artery disease. In patients with impaired left ventricular function after myocardial infarction, end-systolic volume is a better predictor than the global ejection fraction. We analyzed long-term follow-up of patients with impaired left ventricular function undergoing coronary artery bypass graft surgery to evaluate preoperative predictors of survival.

METHODS AND RESULTS
Consecutive patients with ejection fractions < or = 40% (n = 193) who had undergone surgical revascularization were followed to assess the predictive value of preoperative baseline characteristics and catheterization findings for long-term survival. Patients were followed for 133 +/- 30.7 months. At the time of surgery, patient age was 56 +/- 7.9 years and 169 patients (87.6%) had a history of previous myocardial infarction. Thirty-one patients (16%) were female. The ejection fraction was 32 +/- 7%, and the end-systolic volume was 147.4 +/- 52.6 mL. One hundred sixty-four patients (84.9%) had three-vessel disease, and 44 (22.8%) had a left main stenosis with > 50% diameter loss. Follow-up was complete in 99%. Fourteen patients died (7.3%) within the first 30 days after surgery. Twelve-month actuarial survival was 86%, 4-year survival was 80%, and 10-year survival was 40%. Predictors of poor long-term survival on multivariate analysis were end-systolic volume index (chi 2 = 14.02, P = .002), number of previous myocardial infarctions (chi 2 = 6.47, P = .001), preoperative stenosis score (chi 2 = 4.97, P = .02), and age at the time of surgery (chi 2 = 4.45, P = .03).

CONCLUSIONS
End-systolic volume index is the major predictor of survival after coronary artery bypass graft surgery in patients with impaired left ventricular function. Strategies to prevent ventricular dilatation, such as angiotensin-converting enzyme inhibitors, may improve the long-term outcome in these patients.
Reduction in reperfusion-induced myocardial necrosis in dogs by RheothRx injection (poloxamer 188 N.F.), a hemorheological agent that alters neutrophil function.
Authors: Schaer G L , Hursey T L , Abrahams S L , Buddemeier K , Ennis B , Rodriguez E R , Hubbell J P , Moy J , Parrillo J E 
Published: June 2012

BACKGROUND
Reperfusion after prolonged coronary artery occlusion may be followed by additional myocardial necrosis persisting for hours to days. Potential mechanisms include neutrophil-mediated injury and compromised flow within the microcirculation of the reperfused myocardium. Poloxamer 188 is a nonionic surfactant with beneficial hemorheological and neutrophil-inhibitory properties. The purpose of the present study was to determine if poloxamer 188 is capable of reducing the myocardial injury associated with sustained reperfusion and to examine the effect of treatment duration.

METHODS AND RESULTS
Three groups of closed-chest dogs underwent 90 minutes of left anterior descending coronary artery occlusion (angioplasty balloon) and 72 hours of reperfusion. Poloxamer 188, formulated as RheothRx Injection (Burroughs Wellcome Co), was given as a 75 mg/kg IV bolus 15 minutes before reperfusion followed by a 150 mg.kg-1.h-1 continuous IV infusion for 4 hours (n = 13) or 48 hours (n = 13); control dogs (n = 12) received saline for 48 hours. The 48-hour infusion of poloxamer 188 resulted in a 42% reduction in infarct size (as a percent of the area at risk) compared with the control group (25.0 +/- 4.2% versus 43.3 +/- 4.3%, P D .01), whereas the 4-hour group demonstrated a 25% reduction in infarct size compared with the control group (32.4 +/- 4.3%, P = .08). ANCOVA demonstrated that the 48-hour infusion of poloxamer 188 reduced myocardial infarct size independent of differences in collateral blood flow (P = .002 versus control). A trend toward infarct size reduction was observed in the 4-hour infusion group (P = .098 versus control by ANCOVA). Plasma creatine phosphokinase concentration was lower in both poloxamer 188-treated groups (P < .05 versus control). Global left ventricular ejection fraction at 72 hours of reperfusion was improved in the 48-hour infusion group compared with the control group (43 +/- 3.1% versus 33 +/- 2.0%, P < .05), whereas ejection fraction in the 4-hour group was 37 +/- 1.3% (P = NS versus control). Regional ventricular function was also significantly better in the 48-hour infusion group compared with the control group. In vitro studies demonstrated that at concentrations comparable to those achieved in vivo, poloxamer 188 inhibited neutrophil chemotaxis. This finding may represent a beneficial mechanism of action.

CONCLUSIONS
A 48-hour infusion of poloxamer 188 reduced myocardial infarct size and improved left ventricular function in this dog model of 90 minutes of coronary artery occlusion and 72 hours of reperfusion. The finding that the 4-hour infusion of poloxamer 188 did not result in similar benefits suggests that additional reperfusion injury occurred between 4 and 48 hours.
Cyclosporine impairs release of endothelium-derived relaxing factors in epicardial and resistance coronary arteries.
Authors: Sudhir K , MacGregor J S , DeMarco T , De Groot C J , Taylor R N , Chou T M , Yock P G , Chatterjee K 
Published: June 2012

BACKGROUND
Cyclosporin A is reported to impair endothelium-mediated vasorelaxation and induce endothelin release in some noncoronary vascular beds. We wished to determine whether acute cyclosporine administration induces endothelial dysfunction in coronary conductance or resistance arteries.

METHODS AND RESULTS
We examined the effect of intracoronary acetylcholine, N omega-nitro-L-arginine methyl ester (L-NAME), L-arginine, nitroglycerin, and adenosine before and after acute cyclosporine administration (3 mg/kg IV over 30 minutes) in anesthetized dogs. Flow velocity was measured with a 0.014-in Doppler wire to assess resistance vessel responses, and epicardial coronary lumen area was simultaneously measured with a 4.3F, 30-MHz imaging catheter inserted over the Doppler wire. In 6 dogs, acetylcholine-induced increase in flow velocity was attenuated by cyclosporine in vehicle (137% to 55% at 10(-5) mol/L, P < .001), as was acetylcholine-induced epicardial vasodilation (14.1% to 6.7% at 10(-5) mol/L, P < .001). Vasodilation in response to intracoronary nitroglycerin (200 micrograms) and adenosine (6 mg) were unchanged by cyclosporine. Epicardial vasoconstriction with L-NAME (10(-4) mol/L) was reduced by cyclosporine (Pre, 7.4 +/- 0.9%; Post, 2.6 +/- 1.2%; P = .04), but L-arginine (10(-4) mol/L) had no effect after cyclosporine. In another 5 dogs, pure cyclosporine impaired acetylcholine-induced vasodilatation to the same degree as cyclosporine in vehicle (Cremophor); vehicle infusion did not impair endothelial function. In 5 more dogs, cyclosporine did not increase either arterial or coronary sinus concentrations of endothelin-1.

CONCLUSIONS
The present study shows that cyclosporine acutely impairs release of endothelium-derived relaxing factor in canine conductance and resistance coronary arteries and provides evidence for decreased epicardial nitric oxide release after cyclosporine. The potential contribution of acute cyclosporine-induced coronary endothelial dysfunction to posttransplant vasculopathy needs further study.
Effect of exercise on left ventricular mechanical efficiency in conscious dogs.
Authors: Nozawa T , Cheng C P , Noda T , Little W C 
Published: June 2012

BACKGROUND
We studied the effect of exercise (7.2 to 8.0 km/h) on the efficiency of the conversion of metabolic energy to external work or stroke work (SW) by the left ventricle (LV).

METHODS AND RESULTS
Energy use was calculated from LV myocardial oxygen consumption per beat (MVO2). LV volume was calculated from orthogonal dimensions and coronary flow measured with ultrasonic flow probes. The total mechanical energy of the LV was calculated as the pressure-volume area (PVA). At rest, the MVO2-PVA point fell on the MVO2-PVA relation determined by steady-state changes in arterial pressure produced by graded infusions of phenylephrine. Exercise increased the slope (Ees) of LV end-systolic pressure-volume (PV) relation by 29%. During exercise, the MVO2-PVA point shifted to the right only slightly above the control MVO2-PVA relation by 0.007 +/- 0.005 mL O2.beat-1.100 g LV-1. Despite the increase in ventricular contractility with exercise, the PVA/MVO2 ratio was unchanged because of the marked increase in PVA. During exercise, the transmission of total mechanical energy to external work (SW/PVA) increased from 65 +/- 5% to 72 +/- 4% (P < .01) as the ratio of the arterial end-systolic elastance to Ees decreased from 1.1 +/- 0.2 to 0.8 +/- 0.1 (P < .05). Thus, LV mechanical efficiency (SW/MVO2 = SW/PVA.PVA/MVO2) improved from 12.9 +/- 1.5% to 14.3 +/- 1.1% (P < .05) during exercise.

CONCLUSIONS
Exercise increases the efficiency of conversion of metabolic energy to external work by the LV due to alteration in LV arterial coupling resulting in increased production of mechanical energy and enhanced transmission of mechanical energy to external work, which more than offsets any increased metabolic cost of the enhanced contractility.
Observations of ventilation during resuscitation in a canine model.
Authors: Chandra N C , Gruben K G , Tsitlik J E , Brower R , Guerci A D , Halperin H H , Weisfeldt M L , Permutt S 
Published: June 2012

BACKGROUND
Fear of infection limits the willingness of laymen to do cardiopulmonary resuscitation (CPR). This study assessed the time course of change in arterial blood gases during resuscitation with only chest compression (no ventilation) in an effort to identify the time for which ventilation could be deferred.

METHODS AND RESULTS
Aortic pressures and arterial blood gases were monitored in seven 20- to 30-kg dogs in ventricular fibrillation (VF) at 2-minute intervals during chest compression alone (no ventilation) at 80 to 100 compressions per minute. Before the induction of ventricular fibrillation, all animals were intubated and ventilated with room air, 10 mL/kg. The endotracheal tube was removed when VF was induced. Pre-VF arterial pH, PCO2, and O2 saturation were (mean +/- SEM) 7.39 +/- 0.02, 27.0 +/- 1.5 mm Hg, and 97.5 +/- 0.5%, respectively, with aortic pressures being 143.2 +/- 5.7/116.2 +/- 4.6 mm Hg. At 4 minutes of chest compression alone, the corresponding values were 7.39 +/- 0.03, 24.3 +/- 3.1 mm Hg, and 93.9 +/- 3.0%, with an arterial pressure of 48.1 +/- 7.7/22.6 +/- 3.9 mm Hg. Mean minute ventilation during the fourth minute of CPR, measured with a face mask-pneumotachometer, was 5.2 +/- 1.1 L/min.

CONCLUSIONS
These data suggest that in the dog model of witnessed arrest, chest compression alone during CPR can maintain adequate gas exchange to sustain O2 saturation > 90% for > 4 minutes. The need for immediate ventilation during witnessed arrest should be reexamined.
Suppression of thrombolysis in a canine model of pulmonary embolism.
Authors: Marsh J J , Konopka R G , Lang I M , Wang H Y , Pedersen C , Chiles P , Reilly C F , Moser K M 
Published: June 2012

BACKGROUND
The brisk fibrinolytic response of canines has impaired efforts to develop a canine model of chronic thromboembolic pulmonary hypertension. Difficulties in retaining chronic embolic residuals were partially overcome by administration of tranexamic acid (TXA) (Circulation. 1991;83:1272-1279.). In this study, we used type 1 plasminogen activator inhibitor (PAI-1), a major inhibitor of the endogenous fibrinolytic system, to determine its efficacy in the suppression of thrombolysis in canines.

METHODS AND RESULTS
Thrombus was induced in the inferior vena cava of anesthetized mongrel dogs with thrombin and a special double-balloon catheter; 2 hours later, the thrombus was embolized. In one group of dogs, activated type 1 plasminogen activator inhibitor (PAI-1) (130 micrograms) was delivered directly into the forming thrombus; in another, TXA (110 mg/kg) was given intravenously before thrombus formation; in controls, thrombus was induced without inhibitors. Cross-linked fibrin degradation product (D-dimer) appeared in the blood of control animals within 1 hour of thrombus induction (176 +/- 62.5 versus 1.02 +/- 0.39 ng/mL baseline; mean +/- SEM), was maximal by 4 hours (413 +/- 110 ng/mL) and remained elevated at 24 hours (90.8 +/- 19.5 ng/mL). Compared with controls, PAI-1 and TXA suppressed D-dimer release by 80% and 85%, respectively, over the first 24 hours. One week later, animals were killed, and residual emboli were harvested. Perfusion scan defects persisted in all animals at this time, but there were no scan defect differences among groups. However, emboli recovered from animals receiving PAI-1 still harbored immunoreactive PAI-1 and were, on average, more than twofold greater in mass (393 +/- 56 mg) than emboli recovered from either controls (183 +/- 76 mg) or animals receiving TXA (180 +/- 80 mg).

CONCLUSIONS
Intravenous TXA and intrathrombus PAI-1 effectively suppress thrombolysis for 24 hours in canines. Thromboemboli enriched with PAI-1 appear to resist lysis for longer periods of time (up to 1 week). These findings are consistent with the hypothesis that PAI-1 remains associated with the embolus, where it continues to inhibit lysis, whereas TXA eventually diffuses out of the embolus, allowing lysis to ensue.
Value of physical signs in the diagnosis of ventricular tachycardia.
Authors: Garratt C J , Griffith M J , Young G , Curzen N , Brecker S , Rickards A F , Camm A J 
Published: June 2012

BACKGROUND
Although the use of physical signs for the diagnosis of ventricular tachycardia (VT) was described in the early 1900s, their value in this role has never been systematically assessed.

METHODS AND RESULTS
Using a blinded, randomized protocol, we examined the ability of 26 clinicians to detect ventriculoatrial (VA) dissociation during cardiac pacing in 21 patients with both atrial and ventricular pacing wires in situ after successful ablation of accessory pathways. In protocol 1 (10 patients), pacing was randomized to either ventricular pacing alone (simulating VT) or to atrioventricular sequential pacing (simulating supraventricular tachycardia or VT with intact VA conduction) at rates of 150 or 180 beats per minute. Each patients was examined by four clinicians blinded to the pacing mode. Clinicians were asked to make a diagnosis of "VA association" or "VA dissociation" after examining the patient for variability of the arterial pulse, jugular venous pulse (JVP), and first heart sound. In protocol 2 (11 patients), randomization of pacing mode was performed between examination of each of the three physical signs so that the value of each sign was assessed individually. In protocol 1, a diagnosis of VA dissociation (VT) was made in 21 of 40 observations, with a specificity of 75%, sensitivity of 70%, and a positive predictive value (PPV) of 71%. In protocol 2, from a total of 132 observations (44 for each sign), the sensitivity, specificity, and PPV for a diagnosis of VT were as follows: arterial pulse, 61%, 71%, 70%; JVP, 96%, 75%, 82%; and first heart sound, 58%, 100%, 100%.

CONCLUSIONS
It is concluded that, in patients with a regular tachycardia of uncertain origin, clinically detectable variations in the first heart sound and JVP are highly specific and sensitive indicators, respectively, of a diagnosis of VT. Assessment of the arterial pulse is of little value in this role.