bluuebunny/crossref_metadata_2025 huggingface dataset:
Tricarboxylic acid cycle activity in postischemic rat hearts.
Authors: Weiss R G , Kalil-Filho R , Herskowitz A , Chacko V P , Litt M , Stern M D , Gerstenblith G
Published: June 2012

BACKGROUND

Although myocardial oxidative tricarboxylic acid (TCA) cycle activity and contractile function are closely linked in normal cardiac muscle, their relation during postischemic reperfusion, when contractility often is reduced, is not well defined.

METHODS AND RESULTS

To test the hypothesis that oxidative TCA cycle flux is reduced in reperfused myocardium with persistent contractile dysfunction, TCA cycle flux was measured by analyzing the time course of sequential myocardial glutamate labeling during 13C-labeled substrate infusion with 13C nuclear magnetic resonance spectroscopy in beating isolated rat hearts at 37 degrees C. Total TCA cycle flux, indexed by both empirical and mathematical modeling analyses of the 13C data, was not reduced but rather increased in hearts reperfused after 17-20 minutes of ischemia (left ventricular pressure, 73 +/- 5% of preischemic values) compared with flux in developed pressure-matched controls (e.g., total flux, 2.5 +/- 0.4 versus 1.6 +/- 0.1 mumol.min-1.g wet wt-1, respectively; p < 0.01). No TCA cycle activity was detectable by 13C nuclear magnetic resonance in hearts reperfused after 40-45 minutes of ischemia, which lacked contractile recovery and had ultrastructural evidence of irreversible injury.

CONCLUSIONS

These results suggest that TCA cycle activity is not persistently decreased in dysfunctional reperfused myocardium after a brief ischemic episode and therefore cannot account for the reduced contractile function at that time.
The St. Jude valve. Thrombolysis as the first line of therapy for cardiac valve thrombosis.
Authors: Silber H , Khan S S , Matloff J M , Chaux A , DeRobertis M , Gray R
Published: June 2012

BACKGROUND

Thrombolytic therapy is a promising alternative to valve replacement in the management of prosthetic valve thrombosis. We sought to determine the short- and long-term results of treating thrombosed St. Jude heart valves with thrombolytic therapy as the primary treatment modality.

METHODS AND RESULTS

Between March 1978 and December 1991, 988 patients underwent implantation of St. Jude prosthetic valves at our medical center, and all patients with thrombosed valves were identified prospectively. During this period, 17 patients (13 women; mean age, 66.8 +/- 19.0 years) developed prosthetic valve thrombosis (11 aortic, six mitral). In six patients, Coumadin was stopped in preparation for elective surgery. The clinical presentation was congestive heart failure in 13, syncope and fatigue in two, and a cerebrovascular accident in one; one patient was asymptomatic. The average duration of symptoms was 11.7 +/- 12.0 days (range, 1-45 days). Anticoagulation was subtherapeutic in all but one patient at the time of presentation. Cinefluoroscopy was the primary method used for diagnosis and was also used to follow the response to therapy. Twelve patients were treated medically (10 with thrombolytic therapy and two with heparin), three were treated surgically, and two were diagnosed at autopsy. Of the 12 medically treated patients, 10 had marked improvement in leaflet movement and symptoms within 12 hours. Thus, 10 of 12 patients (83%) had a satisfactory response to medical therapy alone. No medically treated patient died or had a major complication resulting in permanent damage. However, four of the 12 medically treated patients had minor complications, including a transient episode of facial weakness in one patient, hematomas in two, and epistaxis in one. Late rethrombosis recurred in two patients in the medically treated group and was successfully retreated with thrombolytic therapy. At 3 months, all patients were alive and well.

CONCLUSIONS

Thrombolytic therapy can be used as the first line of therapy for thrombosed St. Jude valves with a low risk of permanent side effects and excellent chances of success. In most cases, surgery can be reserved for patients who do not respond to thrombolytic therapy.
Hemoglobin inhibits endothelium-dependent relaxation to acetylcholine in human coronary arteries in vivo.
Authors: Collins P , Burman J , Chung H I , Fox K
Published: June 2012

BACKGROUND

The endothelium can regulate vascular tone by releasing both endothelium-derived relaxing factor (EDRF or nitric oxide) and contracting factors. To date, there has only been circumstantial evidence to indicate EDRF activity in vivo in human coronary arteries. Using human hemoglobin as a specific inhibitor, the hypothesis that acetylcholine-induced coronary vasodilation is due to EDRF release was tested.

METHODS AND RESULTS

We studied the response of normal coronary arteries to acetylcholine (an endothelium-dependent vasodilator) and isosorbide dinitrate (an endothelium-independent vasodilator) in seven patients. The specificity of any vasodilator response was assessed by the infusion of reduced free human hemoglobin. Hemoglobin 10(-5) M infusion alone had no effect on coronary artery diameter. Drugs were infused into the coronary artery, and the diameter changes were assessed by quantitative angiography. Acetylcholine 10(-7) M increased left anterior descending coronary artery diameter from control: 2.30 +/- 0.12 mm to 2.79 +/- 0.20 mm (mean +/- SEM, n = 7, p < 0.01). Hemoglobin both in a concentration of 10(-6) M and 10(-5) M reversed this vasodilator effect, causing constriction to 2.11 +/- 0.18 mm (p < 0.001 compared with acetylcholine 10(-7) M) and 2.29 +/- 0.14 mm (p < 0.05 compared with acetylcholine 10(-7) M). Isosorbide dinitrate in the presence of hemoglobin caused dilatation of the coronary artery in all cases to 3.04 +/- 0.24 mm (p < 0.001 compared with acetylcholine 10(-7) M and hemoglobin 10(-6) M).

CONCLUSIONS

Using a specific inhibitor of nitric oxide, reduced free hemoglobin, we have demonstrated that basal EDRF release does not appear to play an important role in the maintenance of human epicardial coronary artery diameter in vivo but is responsible for the acetylcholine-induced dilatation.
Echocardiographic correlates of left ventricular structure among 844 mildly hypertensive men and women in the Treatment of Mild Hypertension Study (TOMHS).
Authors: Liebson P R , Grandits G , Prineas R , Dianzumba S , Flack J M , Cutler J A , Grimm R , Stamler J
Published: June 2012

BACKGROUND

Echocardiography provides a noninvasive means of assessing left ventricular (LV) structure and evidence of LV wall remodeling in hypertensive persons. The relation of demographic, biological, and other factors with LV structure can be assessed.

METHODS AND RESULTS

LV structure was assessed by M-mode echocardiograms for 511 men and 333 women with mild hypertension (average blood pressure, 140/91 mm Hg). Measurements of LV wall thicknesses and internal dimensions were made, and estimates of LV mass indexes and other derivations of structure were calculated. LV hypertrophy criteria were based on previously reported echocardiographic population studies of normal subjects. These measures were compared by age, sex, race, body mass index, systolic blood pressure, antihypertensive drug use, physical activity, alcohol intake, cigarette smoking, and urinary sodium excretion. Despite virtual absence of ECG-determined LV hypertrophy, 13% of men and 20% of women had echocardiographically determined LV hypertrophy indexed by body surface area (g/m2), and 24% of men and 45% of women had LV hypertrophy indexed by height (g/m). Black participants had slightly higher mean levels of wall thickness than nonblack participants but similar LV mass. Systolic blood pressure and urinary sodium excretion were significantly and independently associated with LV mass index and LV hypertrophy using both g/m2 and g/m. Body mass index was significantly related to LV mass index and LV hypertrophy using g/m. Smoking was significantly associated with LV mass index, i.e., using continuous measurement but not using the dichotomy for LV hypertrophy.

CONCLUSIONS

This study of a large population of men and women with mild primary hypertension, largely without ECG evidence of LV hypertrophy, showed a substantial percentage of participants with echocardiographically determined LV hypertrophy. LV mass indexes correlated positively with systolic blood pressure, body mass index, urinary sodium excretion, and smoking.
Augmentation of coronary blood flow by intra-aortic balloon pumping in patients after coronary angioplasty.
Authors: Kern M J , Aguirre F , Bach R , Donohue T , Siegel R , Segal J
Published: June 2012

BACKGROUND

Controversy exists regarding the ability of intra-aortic balloon pumping to increase coronary blood flow in patients with obstructive coronary artery disease. To assess the effects of intra-aortic balloon pumping on coronary hemodynamics, we measured coronary blood flow velocity with a 0.018-in. Doppler-tipped angioplasty guide wire in 15 patients who received an intra-aortic balloon pump for typical clinical indications.

METHODS AND RESULTS

Intra-aortic balloon pumping augmented diastolic pressure 83 +/- 35%. In nine patients before angioplasty, peak diastolic coronary flow velocity beyond the stenosis (mean diameter narrowing, 95 +/- 7%) was 5.3 +/- 9.6 cm/sec and was unaffected by intra-aortic balloon pumping. After angioplasty, the improved coronary luminal diameter narrowing (n = 12; mean narrowing, 18 +/- 12%) was associated with increased distal diastolic flow velocity integral and peak diastolic and mean velocities (13.3 +/- 8.4 units: 36.4 +/- 18.3 and 24.0 +/- 11.4 cm/sec, respectively; all p < 0.01 versus before angioplasty), which were further augmented (36 +/- 37%, 54 +/- 49%, and 26 +/- 17%, respectively; all p < 0.01) with intra-aortic balloon pumping. Intra-aortic balloon pumping did not significantly increase the distal systolic velocity integral (10 +/- 59%) or peak systolic velocity (3 +/- 33%). Similar degrees of balloon pump augmentation of distal coronary flow velocity values were observed in five angiographically normal reference arteries in four patients.

CONCLUSIONS

These data demonstrate lack of significant flow improvement beyond most critical stenoses with intra-aortic balloon pumping and the unequivocal restoration and intra-aortic balloon pump-mediated augmentation of both proximal and distal coronary blood flow velocities after amelioration of severe coronary obstructions in patients after successful coronary angioplasty.
Effect of anti-CD18 antibody on myocardial neutrophil accumulation and infarct size after ischemia and reperfusion in dogs.
Authors: Tanaka M , Brooks S E , Richard V J , FitzHarris G P , Stoler R C , Jennings R B , Arfors K E , Reimer K A
Published: June 2012

BACKGROUND

Polymorphonuclear neutrophils (PMNs) accumulate in postischemic myocardium and may cause injury to myocardium or to vessels by production of oxygen free radicals or by release of proteases and lipases. PMN accumulation is dependent on adherence to endothelium, which is mediated by a family of glycoproteins on the PMN surface, each of which has a common beta-subunit (CD18). The purpose of this study was to determine whether an antibody (IB4) against the CD18 protein could attenuate PMN accumulation and limit myocardial infarct size.

METHODS AND RESULTS

F(ab')2 fragments of a mouse monoclonal antibody to human adherence-promoting leukocyte glycoprotein (CD18) were used. Infarct size after 90 minutes of ischemia and 3 hours of reperfusion was compared in dogs with (n = 8) and without (n = 8) the anti-CD18 treatment. Myocardial PMN accumulation was assessed with 111In-labeled autologous PMNs. Anti-CD18 treatment significantly reduced the number of PMNs in the ischemic region (19,123 +/- 5,352/mg versus 5,204 +/- 927/mg in the control and treated groups, respectively; p < 0.05). In addition, the ratio of myocardial blood flow (ischemic/nonischemic wall) at 45 minutes into reperfusion was higher in the treated than in the control group (1.18 +/- 0.18 versus 0.69 +/- 0.09; p < 0.05). Nevertheless, infarct size was similar between the control and treated groups (40.5 +/- 7.4% versus 48.5 +/- 4.4% of the area at risk; p = NS). Transmural mean collateral blood flow to the ischemic myocardium was similar between the two groups, and the inverse relation between infarct size and collateral blood flow was not shifted by anti-CD18 therapy.

CONCLUSIONS

Although PMN accumulation contributed to reduced postischemic microvascular perfusion, it caused insufficient additional myocardial cell death to measurably affect infarct size in this model.
SIN-1 reduces platelet adhesion and platelet thrombus formation in a porcine model of balloon angioplasty.
Authors: Groves P H , Lewis M J , Cheadle H A , Penny W J
Published: June 2012

BACKGROUND

Nitric oxide inhibits platelet adhesion and platelet aggregation in vivo. In this study, we investigated the effects of the nitric oxide donor SIN-1 on platelet adhesion and platelet-thrombus formation following experimental angioplasty.

METHODS AND RESULTS

Bilateral carotid angioplasty was performed in 20 anesthetized pigs. Animals received either SIN-1 (3-morpholino-sydnonimine; 10 micrograms/kg/min; n = 8) or placebo (n = 8) before and during angioplasty. An additional control group of pigs received trimetaphan (n = 4), which induced hemodynamic changes similar to those that followed treatment with SIN-1. Platelet deposition was quantified by the injection of autologous 111In-labeled platelets. SIN-1 reduced platelet deposition after deep arterial injury compared with placebo (mean +/- SEM, 10.870 +/- 2.415 versus 40.326 +/- 9.889 platelets x 10(6)/cm2, p < 0.05). SIN-1 reduced platelet adhesion after superficial injury compared with both placebo and trimetaphan (2.231 +/- 0.333 versus 5.278 +/- 0.606 versus 5.022 +/- 1.136 platelets x 10(6)/cm2, respectively; p < 0.005). Scanning electron microscopy confirmed that platelets were deposited in the form of an adherent monolayer following superficial endothelial denudation and were reduced in number following treatment with SIN-1. The effects of SIN-1 on platelet function were associated with a significant increase in platelet cyclic GMP concentration from baseline (3.15 +/- 0.88 versus 1.58 +/- 0.73 pmol/10(9) platelets, p < 0.005).

CONCLUSIONS

SIN-1 reduces platelet adhesion and platelet-thrombus formation following experimental angioplasty. The antiadhesive effects of SIN-1 are independent of changes in systemic hemodynamics. These results imply that the administration of a nitric oxide donor may prove effective in modifying the pathophysiological response to angioplasty injury.
Thrombolytic profiles of clot-targeted plasminogen activators. Parameters determining potency and initial and maximal rates.
Authors: Holvoet P , Dewerchin M , Stassen J M , Lijnen H R , Tollenaere T , Gaffney P J , Collen D
Published: June 2012

BACKGROUND

Targeting of plasminogen activators to the thrombus by means of fibrin-specific monoclonal antibodies may enhance their thrombolytic potency. The kinetics of clot binding of two human fibrin-specific monoclonal antibodies (MA-12B3 and MA-15C5) and of clot lysis with their chemical 1:1 stoichiometric complexes with recombinant single-chain urokinase-type plasminogen activator (rscu-PA) (rscu-PA/MA-12B3 and rscu-PA/MA-15C5) were determined in hamsters and rabbits. Thrombolytic potencies, maximal rates of clot lysis, and the duration of the lag phases before clot lysis of the antibody/rscu-PA conjugates were compared with those of rscu-PA and tissue-type plasminogen activator (rt-PA).

METHODS AND RESULTS

Bolus injection of 7.5 micrograms of 125I-labeled antibody in rabbits with an extracorporeal arteriovenous loop containing a 0.3-mL human plasma clot produced clot-to-blood ratios of 6.6 +/- 1.0 (mean +/- SEM) for MA-12B3 and 1.1 +/- 0.15 for MA-15C5 (p < 0.001 versus MA-12B3) within 6 hours. Progressive digestion of the clot did not alter the binding of MA-12B3 but resulted in as much as a 10-fold increase of the binding of MA-15C5. The conjugates infused intravenously over 90 minutes in hamsters with a human plasma clot in the pulmonary artery produced dose-related in vivo clot lysis. Thrombolytic potencies (maximal slope of the percent lysis versus dose in milligrams of u-PA equivalent per kilogram body weight) were 2,500 +/- 440 for rscu-PA/MA-12B3, 3,600 +/- 640 for rscu-PA/MA-15C5 (p = NS vs. rscu-PA/MA-12B3), 60 +/- 8 for rscu-PA (p < 0.001 versus both conjugates), and 380 +/- 66 for rt-PA (p < 0.001 versus both conjugates). The plasma clearances of the conjugates were fourfold to sixfold slower than those of rscu-PA and rt-PA. Maximal rates of clot lysis, determined by continuous external radioisotope scanning over the thorax, were 0.90 +/- 0.13%, 0.91 +/- 0.17%, 0.84 +/- 0.12%, and 1.1 +/- 0.16% lysis per minute for rscu-PA/MA-12B3, rscu-PA/MA-15C5, rscu-PA, and rt-PA, respectively; these maximal rates were obtained with 0.016, 0.016, 1.0, and 0.25 mg/kg, respectively, and were associated with minimal lag phases of 18 +/- 3.2, 28 +/- 4.9, 34 +/- 3.7, and 25 +/- 3.9 minutes, respectively.

CONCLUSIONS

The thrombolytic potency of the rscu-PA/antifibrin conjugates is determined by their clearance, as well as by rate and extent of initial binding to clots and by changes in binding during clot lysis. Clot targeting of rscu-PA with fibrin-specific antibodies increases its thrombolytic potency but does not alter the maximal rate or the minimal lag phase of clot lysis. These parameters appear to be independent of the nature of the plasminogen activator and of targeting.
Radiofrequency catheter ablation of Mahaim fibers at the tricuspid annulus.
Authors: Klein L S , Hackett F K , Zipes D P , Miles W M
Published: June 2012

BACKGROUND

The purpose of this study was to test the feasibility of radiofrequency catheter ablation of Mahaim fibers at the tricuspid annulus.

METHODS AND RESULTS

Four patients who fulfilled criteria for having Mahaim fibers and preexcited reciprocating tachycardia underwent radiofrequency catheter ablation. Three patients had atriofascicular connections, and one patient had an atrioventricular connection. The mean age was 27 years (age range, 11-48 years). All patients had highly symptomatic tachycardias, producing syncope in one patient and presyncope in the remaining three patients. Symptoms were present for a mean of 13 years (range, 4-23 years). All pathways conducted only anterogradely, and preexcitation resulted in a left bundle branch block QRS morphology. Adenosine caused block in the accessory pathway in the three patients in whom it was tested. The stimulus to delta interval increased by 75 msec (range, 35-90 msec) during rapid atrial pacing. The atrial insertion of the Mahaim fiber was in the right lateral atrium in one patient, right posterolateral atrium in two patients, and right posterior atrium in one patient. The ventricular insertion was in the distal right bundle branch in three patients and in the posterolateral right ventricle near the tricuspid annulus in the patient with an atrioventricular connection. Stimulus to delta wave mapping was used to help localize the atrial insertion of the atriofascicular connections. A mean of 15 radiofrequency pulses (range, 10-19 pulses) delivered to the tricuspid annulus in the posterior to lateral regions eliminated accessory pathway conduction in all patients. No complications occurred. Tachycardia did not recur during a mean follow-up of 8 months (range, 2-15 months).

CONCLUSIONS

Radiofrequency current applied to the tricuspid annulus can safely eliminate tachycardia in patients with Mahaim fibers.
Quantitative ultrasonic analysis of myocardium in patients with thalassemia major and iron overload.
Authors: Lattanzi F , Bellotti P , Picano E , Chiarella F , Mazzarisi A , Melevendi C , Forni G , Landini L , Distante A , Vecchio C
Published: June 2012

BACKGROUND

Patients with beta-thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac dysfunction has been documented even in thalassemics without clinical manifestations of heart failure as well as by conventional echocardiographic-Doppler techniques. The purpose of this study was to assess the acoustic quantitative properties of myocardium in patients with iron overload.

METHODS AND RESULTS

Thirty-eight patients with beta-thalassemia major, without clinical signs of cardiac failure, and 20 age- and sex-matched young controls were studied by echocardiography. An on-line analysis of the ultrasonic radiofrequency signal was performed to obtain quantitative operator-independent measurements of the integrated backscatter (IB) signal of the ventricular septum and the posterior wall. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent (IB%). Thalassemic patients had been receiving transfusion therapy for 16 +/- 5 years and had received 313 +/- 138 transfusion units; they all had received chelation treatment (desferroxiamine) for 9 +/- 2 years. Patients and controls showed comparable values of echocardiographically assessed percent fractional shortening (32 +/- 3% versus 36 +/- 4%, p = NS), whereas thalassemics showed higher values of left ventricular mass index (118 +/- 30 versus 98 +/- 15 g/m2, p < 0.05). The IB% values were higher in patients with thalassemia major than in controls for both septum (35 +/- 14% versus 21 +/- 6%, p < 0.001) and posterior wall (16 +/- 6% versus 11 +/- 3%, p < 0.001). In thalassemic patients, no significant correlation was found between the septum IB% value and hematological parameters, such as the total number of transfusions (r = 0.2, p = NS) or the mean ferritin value (r = 0.1, p = NS). No significant correlation was also found between the septum IB% value and the echocardiographically assessed left ventricular mass index (r = 0.2, p = NS).

CONCLUSIONS

These data demonstrate that myocardial reflectivity is abnormally increased in patients with thalassemia major under transfusion treatment, probably due to myocardial iron deposits and/or secondary structural changes. These quantitatively assessed abnormalities in regional reflectivity can be detected when conventional echocardiographic parameters of systolic left ventricular function are undistinguishable from normal controls.
Infarct artery patency predicts outcome of serial electropharmacological studies in patients with malignant ventricular tachyarrhythmias.
Authors: Hii J T , Traboulsi M , Mitchell L B , Wyse D G , Duff H J , Gillis A M
Published: June 2012

BACKGROUND

Surviving myocardial cells near the infarct border zone form the arrhythmogenic substrate for sustained ventricular tachycardia (VT) in humans. Infarct-related artery (IRA) patency may modulate the electrophysiological function of this arrhythmogenic substrate and its response to antiarrhythmic drug therapy. We postulated that effective antiarrhythmic drug therapy selected during serial electrophysiological studies in patients with VT after a myocardial infarction would be identified more frequently when the IRA is patent than when chronically occluded.

METHODS AND RESULTS

Consecutive patients (n = 64) with documented coronary artery disease and remote myocardial infarction presenting with spontaneous sustained VT or ventricular fibrillation (VF) were studied. These patients underwent 4 +/- 2 electropharmacological studies identifying effective antiarrhythmic drug therapy in 16 (25%) patients. Drug responders did not differ significantly from nonresponders in demographic, electrocardiographic, angiographic, or hemodynamic measurements. A patent IRA was associated with antiarrhythmic drug response significantly more frequently than was an occluded IRA (45% versus 9%, p = 0.001). Patency of the IRA was the only independent predictor of response to antiarrhythmic drug therapy in this study population. The sensitivity and specificity of using a patent IRA to predict successful drug testing were 81% and 67%, respectively.

CONCLUSIONS

The outcome of electropharmacological studies was predicted by the patency of the IRA. A patent IRA was associated with a greater probability of finding effective drug therapy.
Long-term clinical follow-up in patients with angiographic restudy after successful angioplasty.
Authors: Weintraub W S , Ghazzal Z M , Douglas J S , Liberman H A , Morris D C , Cohen C L , King S B
Published: June 2012

BACKGROUND

Restenosis remains a critical limitation after coronary angioplasty. There is little information comparing long-term prognosis in patients who suffer from restenosis and others who do not. The purpose of this paper is to determine the clinical events in patients with restenosis or continued patency documented by restudy coronary arteriography.

METHODS AND RESULTS

The source of data was the clinical data base at Emory University. Patients who had previous coronary surgery and patients who underwent angioplasty in the setting of acute myocardial infarction were excluded. A total of 3,363 patients undergoing angiographic restudy 4 months to 1 year after angioplasty were compared with 3,858 not undergoing restudy. In the restudy population, 1,570 had restenosis and 1,793 had patent arteries at all sites dilated. The restenosis patients were older and had more hypertension, more diabetes, more severe angina, more multivessel coronary artery disease, more severe stenoses, and less satisfactory original results. At restudy, in patients without restenosis, 38.7% had angina versus 70.7% in patients with restenosis (p < 0.0001). There were few deaths in the first 6 months. At 6 years, the survival rate was 0.95 without restenosis and 0.93 with restenosis (p = 0.16). At 6 months and 6 years, freedom from myocardial infarction was 0.97 and 0.88 without restenosis and 0.93 and 0.85 with restenosis (p = 0.0001). On multivariate analysis, restenosis was an independent correlate of myocardial infarction but not mortality. At 6 months and 6 years, freedom from coronary bypass surgery was 0.99 and 0.94 without restenosis and 0.91 and 0.78 with restenosis (p < 0.0001). At 6 months and 6 years, freedom from repeat angioplasty was 0.96 and 0.76 without restenosis and 0.44 and 0.20 with restenosis (p = 0.0001). The highest event rates were noted in the patients with restenosis with recurrent chest pain. Patients not undergoing restudy differed somewhat from the study group, and there were far fewer repeat revascularization procedures in the group not undergoing restudy.

CONCLUSIONS

Patients with restenosis are more likely to have recurrent angina pectoris. Although there is no or little difference in survival, there is a difference in myocardial infarction rate in the patients with and without restenosis. The low myocardial infarction and death rates in the group suffering restenosis may be related to repeat revascularization in these patients; the principal events in the restenosis population are frequent repeat revascularization procedures.
Effect of selective angiotensin II receptor antagonism and angiotensin converting enzyme inhibition on the coronary vasculature in vivo. Intravascular two-dimensional and Doppler ultrasound studies.
Authors: Sudhir K , MacGregor J S , Gupta M , Barbant S D , Redberg R , Yock P G , Chatterjee K
Published: June 2012

BACKGROUND

Although angiotensin converting enzyme (ACE) inhibitors have been reported to increase coronary blood flow, the effect of selective angiotensin II (AT1)-receptor antagonism on the coronary circulation has not been defined.

METHODS AND RESULTS

We examined the effects of the AT1-receptor antagonist Losartan (DuP 753, 0.2-3.2 mg/kg) on coronary arteries in vivo in 11 dogs, using a combination of intravascular two-dimensional and Doppler ultrasound. In six dogs, a 30-MHz, 4.3F ultrasound imaging catheter was placed in the midsegment of the circumflex coronary artery to measure cross-sectional area (CSA), and a 0.018-in. Doppler wire was placed alongside to measure coronary flow velocity. At peak effect (1.6 mg/kg), Losartan increased mean coronary CSA from 7.9 +/- 0.5 to 9.5 +/- 0.8 mm2 and average peak velocity (APV) from 32 +/- 10 to 56 +/- 18 cm/sec, resulting in an increase in coronary blood flow from 74 +/- 19 to 151 +/- 36 mL/min. The maximal effect of the ACE inhibitor enalaprilat (5 mg) was an increase in CSA from 7.7 +/- 0.7 to 8.4 +/- 0.8 mm2 and an increase in APV from 36 +/- 10 to 53 +/- 20 cm/sec, with an increase in coronary blood flow from 82 +/- 25 to 122 +/- 41 mL/min. Relative to maximal hyperemia with adenosine (6 mg i.c.), the magnitude of flow increase from baseline was 0.37 with the AT1-receptor antagonist and 0.19 with the ACE inhibitor (p < 0.05). These effects were seen without changes in heart rate or systemic arterial pressure. In an additional five dogs, the ultrasound imaging catheter was introduced directly over a 0.014-in. Doppler wire, and the effects of indomethacin, propranolol, and N omega-nitro-L-arginine methylester (L-NAME) on the vasodilator effect of Losartan (1.6 mg/kg) were examined. Indomethacin and propranolol had no effect on Losartan-induced vasodilation, suggesting that it was not mediated via prostaglandins or beta-adrenoceptors. However, Losartan-induced epicardial vasodilation was partially inhibited by L-NAME, suggesting an action partly dependent on endothelial release of nitric oxide.

CONCLUSIONS

Thus, these acute studies in anesthetized dogs suggest that inhibition of AT1-receptors in the coronary circulation results in vasodilator responses greater in magnitude than ACE inhibition and partly endothelium dependent. The exact role for AT1-receptors in human coronary physiology and pathology remains to be defined.
Cholinergic modulation of the coronary vasoconstriction induced by cocaine in conscious dogs.
Authors: Shannon R P , Stambler B S , Komamura K , Ihara T , Vatner S F
Published: June 2012

BACKGROUND

The effects of cocaine on the coronary circulation were examined in conscious dogs chronically instrumented to measure arterial and left ventricular pressures, coronary blood flow, and arterial and coronary sinus oxygen content.

METHODS AND RESULTS

With heart rate held constant, the peak effects of cocaine (1 mg/kg i.v.) occurred within 2 minutes, when mean arterial pressure increased by 42 +/- 5 mm Hg, coronary blood flow increased by 13 +/- 3%, and coronary vascular resistance increased by 24 +/- 3%. The arterial oxygen content increased significantly (by 2.8 +/- 0.3 vol%), the arterial-coronary sinus oxygen difference increased by 2.5 +/- 0.6 vol%, and myocardial oxygen consumption increased by 41 +/- 9%. The increase in coronary vascular resistance induced by cocaine was attenuated (p < 0.05) in the presence of cholinergic blockade (12 +/- 3%) despite a similar increase in MVO2 (49 +/- 8%). The increase in coronary vascular resistance was enhanced (p < 0.05) in the presence of beta-adrenergic receptor blockade (46 +/- 8%), whereas the MVO2 response was less (28 +/- 3%). Again, the addition of cholinergic blockade to beta-blockade attenuated the increase in coronary vascular resistance (23 +/- 6%) without affecting the increase in MVO2 (25 +/- 4%). Combined alpha-, beta-, and cholinergic blockades abolished the systemic hemodynamic and coronary vasoconstrictor response to cocaine.

CONCLUSIONS

In conscious dogs, cocaine induces coronary vasoconstriction, which competes with coronary vasodilator responses to increases in myocardial oxygen consumption. The mechanisms of cocaine's coronary vascular effects are mediated via adrenergic stimulation, and the intensity of the vasoconstrictor effects was reduced significantly by cholinergic blockade, in both the presence and absence of beta-adrenergic receptor blockade.
Effect of prosthetic valve malfunction on the Doppler-catheter gradient relation for bileaflet aortic valve prostheses.
Authors: Baumgartner H , Schima H , Kühn P
Published: June 2012

BACKGROUND

Considerable discrepancies between Doppler and catheter gradients caused by localized gradients and pressure recovery have been reported for normal bileaflet aortic valve prostheses.

METHODS AND RESULTS

To examine whether this Doppler-catheter gradient relation is affected by prosthetic valve malfunction, a 19-mm CarboMedics aortic valve was simultaneously studied with continuous-wave Doppler and catheter technique in normal function and in various states of malfunction ranging from slightly restricted opening to total occlusion of one leaflet. For each functional status, peak and mean gradients were measured at eight different flow rates (cardiac output, 2.0-6.0 L/min). Excellent correlation between Doppler and catheter gradients was found regardless of the valve function (r = 0.99, SEE = 1.0-3.3 mm Hg). However, the relation between Doppler and catheter gradient was highly dependent on the function of the valve as shown by a variation of slopes from 1.08 to 2.08. For the normally functioning valve (angle between flow axis and leaflet 5 degrees), peak and mean Doppler gradients were approximately twice the catheter gradients (slope, 2.08 and 2.03 for peak and mean gradients, respectively). Slightly restricted opening of one leaflet (22 degrees) significantly altered the Doppler-catheter gradient relation, and slopes decreased to 1.69 (p < 0.01) and 1.52 (p < 0.001) for peak and mean gradients, respectively. The differences between Doppler and catheter gradients significantly decreased with further restriction of valve opening, and slopes ranged from 1.25 to 1.41 for angles between 34 degrees and 52 degrees. When one leaflet was totally occluded, the slope finally dropped to 1.08 for both peak and mean gradients, and Doppler gradients were only slightly greater than catheter gradients. Gradients increased with malfunction of the valve caused by reduction of the effective orifice area. However, the increase of Doppler gradients was considerably smaller than the increase of simultaneous catheter gradients.

CONCLUSIONS

The discrepancies between Doppler and catheter gradients that have been reported for normally functioning bileaflet aortic valve prostheses may be reduced or even disappear in patients with malfunctioning valves. Furthermore, the increase of Doppler gradients caused by malfunction of the valve may underestimate the true hemodynamic changes.
Effect of increased availability of endothelium-derived nitric oxide precursor on endothelium-dependent vascular relaxation in normal subjects and in patients with essential hypertension.
Authors: Panza J A , Casino P R , Badar D M , Quyyumi A A
Published: June 2012

BACKGROUND

Patients with essential hypertension have a deficit in the endothelium-derived nitric oxide system that results in impaired endothelium-dependent vascular relaxation. The objective of this study was to determine whether this abnormality is caused by a deficiency of substrate for nitric oxide synthesis.

METHODS AND RESULTS

The vascular responses to acetylcholine (an endothelium-dependent vasodilator infused at 7.5, 15, and 30 micrograms/min) and sodium nitroprusside (a direct smooth muscle dilator infused at 0.8, 1.6, and 3.2 micrograms/min) were studied during combined administration of dextrose 5% or L-arginine (substrate for nitric oxide synthesis infused at 40 mumol/min) in 12 normal control subjects (seven men and five women; age, 49.3 +/- 7 years) and 14 hypertensive patients (nine men and five women; age, 48.4 +/- 7 years). In addition, the effect of D-arginine (stereoisomer of arginine that is not a precursor of nitric oxide) on the vascular responses to acetylcholine was studied in eight normal control subjects and seven hypertensive patients. Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain gauge plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypertensive patients compared with normal control subjects (maximum flow, 8.9 +/- 5 versus 15.7 +/- 6 mL.min-1.100 mL-1, respectively; p < 0.007); however, no difference was observed in the response to sodium nitroprusside (11.4 +/- 6 and 11.7 +/- mL.min-1.100 mL-1, respectively). L-Arginine did not significantly change basal blood flow or vascular resistance in either group. In normal control subjects, the infusion of L-arginine significantly augmented the vasodilator response to acetylcholine (maximum flow, 15.7 +/- 6 versus 21.4 +/- 8 mL.min-1.100 mL-1 before and after L-arginine, respectively; p < 0.001). In contrast, in hypertensive patients, the infusion of L-arginine did not alter the response to acetylcholine (maximum flow, 8.9 +/- 5 and 8.4 +/- 4 mL.min-1.100 mL-1 before and after L-arginine, respectively). The administration of L-arginine did not modify the response to sodium nitroprusside in either group. Similarly, the infusion of D-arginine did not alter the response to acetylcholine in either group.

CONCLUSIONS

In normal humans, availability of substrate for production of nitric oxide is a rate-limiting step for endothelium-dependent vascular relaxation. In contrast, increased availability of nitric oxide precursor does not modify endothelium-mediated vasodilation in hypertensive patients. These findings provide further evidence of a defect in the endothelium-derived nitric oxide system in hypertension and indicate that this abnormality is not related to decreased availability of substrate for nitric oxide production.
Analysis of creatine kinase, CK-MB, myoglobin, and troponin T time-activity curves for early assessment of coronary artery reperfusion after intravenous thrombolysis.
Authors: Zabel M , Hohnloser S H , Köster W , Prinz M , Kasper W , Just H
Published: June 2012

BACKGROUND

Thrombolysis has become the standard therapeutic approach in patients with acute myocardial infarction. To identify patients who may benefit from early invasive procedures, reliable noninvasive assessment of success or failure of thrombolytic therapy is mandatory.

METHODS AND RESULTS

In a prospective study in 63 consecutive patients undergoing thrombolysis for their first myocardial infarction, serial measurements of creatine kinase (CK), its isoenzyme CK-MB, myoglobin, and troponin T were done to determine their value for noninvasive prediction of coronary artery patency. Blood samples were drawn every 15 minutes during the first 90 minutes, every 30 minutes during the first 4 hours, every 4 hours during the first 24 hours, and every 8 hours during the first 72 hours. The perfusion status of the infarct-related artery was assessed angiographically 90 minutes after initiation of thrombolysis. For each marker, time to its peak concentration and its early initial slope (start of thrombolysis to 90 minutes thereafter) were determined. Areas under receiver operator characteristic (ROC) curves were 0.83, 0.76, 0.82, and 0.80 for maxima of CK, CK-MB, myoglobin, and troponin T, respectively (p = NS by univariate Z test). The corresponding values for early slopes of CK, CK-MB, myoglobin, and troponin T were 0.79, 0.82, 0.89, and 0.80 (p = 0.23 for comparison between myoglobin and CK-MB; p = 0.07 between myoglobin and CK). Sensitivity, specificity, and positive and negative predictive values regarding noninvasive prediction of coronary artery patency after 90 minutes were 80%, 82%, 95%, and 61% for time to CK maximum; 91%, 77%, 91%, and 77% for time to myoglobin maximum; 87%, 71%, 89%, and 67% for early CK slope; and 94%, 88%, 94%, and 82% for myoglobin slope, respectively. When myoglobin slope was assessed together with other clinical reperfusion markers (resolution of chest pain or ST segment elevation, occurrence of reperfusion arrhythmias) by logistic regression analysis, only the myoglobin slope was an independent predictor of coronary artery patency (p < 0.0001).

CONCLUSIONS

With regard to noninvasive prediction of coronary artery patency after thrombolytic therapy, measurement of the early initial slopes of the serum markers within only 90 minutes after the initiation of therapy is as accurate as the determination of the time to their peak concentration. Compared with the other markers examined, myoglobin appears to have advantages because of its earlier rise, yielding a better negative predictive value and a higher area under the ROC curve for determination of its early initial slopes.
The long QT syndrome in children. An international study of 287 patients.
Authors: Garson A , Dick M , Fournier A , Gillette P C , Hamilton R , Kugler J D , van Hare G F , Vetter V , Vick G W
Published: June 2012

BACKGROUND

The Pediatric Electrophysiology Society studied children with the long QT syndrome (LQTS) to describe the features of LQTS in patients less than 21 years old, define potential "low-risk" and "high-risk" subpopulations, and determine optimal treatment.

METHODS AND RESULTS

Patients less than 21 years old were included if either QTc was more than 0.44; they had unexplained syncope, seizures, or cardiac arrest preceded by emotion or exercise; or family history of LQTS. We found 287 patients from 26 centers in seven countries. Mean +/- SD age at presentation was 6.8 +/- 5.6; 9% presented with cardiac arrest, 26% with syncope, and 10% with seizures. Of those with symptoms, 67% had symptoms related to exercise. Family history was positive for long QT interval in 39% and for sudden death in 31%. Hearing loss was present in 4.5%. A normal QTc was present in 6%, and QTc of more than 0.60 was in 13%. Atrioventricular block occurred in 5%, but 13 of 15 patients had second-degree atrioventricular block (2:1), and only two of 287 had complete atrioventricular block. Ventricular arrhythmias were found on 16% of initial routine ECGs: 4% uniform premature ventricular contractions, 5% multiform premature ventricular contractions, 1% monomorphic ventricular tachycardia, and 6% torsade de pointes. Overall, treatment was effective for symptoms in 76% and for ventricular arrhythmias in 60%. There was no difference between propranolol and other beta-blockers in effective treatment. Left stellectomy was performed in nine patients, and defibrillators were implanted in four; no sudden death occurred in these 13 patients. In follow-up (duration, 5.0 +/- 4 years; age, 10.9 +/- 6.3 years), 5% had cardiac arrest, 4% had syncope, and 1% had seizures. The two multivariate predictors of symptoms at follow-up were symptoms at presentation and propranolol failure. Sudden death occurred in 8%; multivariate predictors of sudden death were length of QTc at presentation of more than 0.60 and medication noncompliance.

CONCLUSIONS

The appearance of 2:1 atrioventricular block, multiform premature ventricular contractions, and torsade de pointes are relatively more common in children with LQTS than other children and should raise the index of suspicion for LQTS. Because 9% of patients presented with cardiac arrest and no preceding symptoms, perhaps prophylactic treatment in asymptomatic children is indicated. Asymptomatic patients with normal QTc and positive family history may be a low-risk group. Patients with QTc of more than 0.60 are at particularly high risk for sudden death, and if treatment is not effective, consideration should be given to cardiac sympathetic denervation, pacemaker implantation, and perhaps implantation of a defibrillator.
HLA antigens in Turkish race with rheumatic heart disease [see comment].
Authors: Ozkan M , Carin M , Sönmez G , Senocak M , Ozdemir M , Yakut C
Published: June 2012

BACKGROUND

Rheumatic valvular disease has been reported to be associated with HLA antigens. To determine whether genetic factors could be involved in the pathogenesis of rheumatic heart disease (RHD), we analyzed the distribution of HLA-A, HLA-B, and HLA-DR antigens in Turkish patients with chronic rheumatic heart disease.

METHODS AND RESULTS

The association of class I and class II HLA antigens was examined in 107 ethnic Turkish patients with chronic RHD. The diagnosis was supported by echocardiography, cardiac catheterization, angioventriculography, and histological findings in patients who underwent valve replacement. Two hundred three control subjects, also of Turkish origin, were chosen. The phenotypes B16, DR3, and DR7 were encountered in a significantly higher frequency in patients with RHD compared with the control population (corrected p < 0.05, p < 0.00005, and p < 0.0005, respectively). There also was a decrease in the antigen frequency of DR5 in patients compared with controls (corrected p < 0.005).

CONCLUSIONS

The results are consistent with the hypothesis that susceptibility to RHD is genetically linked, and this in turn may be associated mainly with HLA class II antigens and weakly with class I antigens, with DR3, DR7, and B16 influencing susceptibility and DR5 conferring protection.
Correlation between scintigraphic evidence of regional sympathetic neuronal dysfunction and ventricular refractoriness in the human heart.
Authors: Calkins H , Allman K , Bolling S , Kirsch M , Wieland D , Morady F , Schwaiger M
Published: June 2012

BACKGROUND

Denervation supersensitivity has been proposed as a mechanism for the relation between ventricular arrhythmias and the sympathetic nervous system. Evaluation of this phenomenon in humans has become feasible only recently with the development of noninvasive scintigraphic methods for evaluating the pattern of sympathetic innervation. The purpose of this study was to determine if scintigraphic evidence of sympathetic neuronal dysfunction correlates with measurements of ventricular refractoriness and to evaluate the phenomenon of denervation supersensitivity in humans.

METHODS AND RESULTS

Eleven patients with a history of sustained ventricular tachycardia or sudden cardiac death who were referred for placement of an implantable defibrillator participated in this study (seven men and four women; age, 51 +/- 18 years). Preoperative scintigraphic evaluation of the pattern of sympathetic innervation was performed with 11C-hydroxyephedrine in conjunction with positron emission tomography. At the time of surgery, ventricular refractoriness was determined in regions of myocardium demonstrating normal and reduced 11C-hydroxyephedrine retention in the baseline state and during an infusion of norepinephrine. Scintigraphic evaluation demonstrated regions of reduced 11C-hydroxyephedrine retention in each patient. The effective refractory period in areas of myocardium that demonstrated reduced 11C-hydroxyephedrine retention was significantly longer than in areas of myocardium demonstrating normal 11C-hydroxyephedrine retention (273 +/- 32 versus 243 +/- 32 msec, p < 0.001). Norepinephrine shortened the effective refractory period in regions of myocardium demonstrating normal and reduced 11C-hydroxyephedrine retention to a similar degree.

CONCLUSIONS

There is a correlation between scintigraphic evidence of sympathetic neuronal dysfunction and ventricular refractoriness in the human heart. These observations help validate the use of scintigraphic techniques for evaluation of sympathetic innervation and may assist in the further evaluation of the relation between the sympathetic nervous system and ventricular arrhythmias.