bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo lymphocyte-mediated myocardial injuries demonstrated by adoptive transfer of experimental autoimmune myocarditis.
Authors: Kodama M , Matsumoto Y , Fujiwara M 
Published: June 2012

BACKGROUND
To elucidate the mechanisms of immune-related myocardial injuries, we examined whether autoimmune myocarditis was passively transferable by use of humoral or cellular factors.

METHODS AND RESULTS
Active myocarditis was elicited in Lewis rats by immunization with human cardiac myosin fraction in complete Freund's adjuvant. This experimental myocarditis was characterized by macroscopic features such as pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac surface. Histologically, extensive myocardial necrosis and numerous inflammatory cell infiltrations were observed. Interestingly, multinucleated giant cells were frequently observed in the lesions. Transfer of the disease by the humoral factor was examined by use of fresh sera and immunoglobulin fraction of pooled sera from rats with severe myocarditis, and transfer by the cellular factor was tested by use of spleen cells and lymph node cells from the diseased rats. When naive Lewis rats were given 15.75 mg of immunoglobulin fraction, no particular change was observed in the hearts. Fresh sera also could not elicit myocarditis in recipient rats. In contrast, intravenous injection of spleen cells or lymph node cells that were cultured for 3 days in the presence of 1 microgram/ml of concanavalin A elicited severe myocarditis. The macroscopic and microscopic findings of passively transferred myocarditis are essentially the same as those found in actively induced myocarditis. Multinucleated giant cells were also observed in the lesions of transferred myocarditis.

CONCLUSIONS
This study demonstrates direct evidence for in vivo lymphocyte-mediated myocardial injuries.
Cost and health implications of cholesterol lowering.
Authors: Goldman L , Gordon D J , Rifkind B M , Hulley S B , Detsky A S , Goodman D W , Kinosian B , Weinstein M C 
Published: June 2012

BACKGROUND
A broad, scientific consensus supports the role of cholesterol as a risk factor for coronary heart disease and agrees that lowering cholesterol levels will reduce coronary heart disease incidence. Cost-effectiveness analysis is a potentially powerful method for measuring the benefits to be achieved by expenditures of health care dollars.

METHODS AND RESULTS
The literature related to the effectiveness and cost-effectiveness of cholesterol lowering was reviewed. Application of cost-effectiveness methodology to the question of cholesterol reduction generally supports the use of population-wide educational programs and the aggressive use of cholesterol-lowering therapy for the secondary prevention of subsequent coronary events in persons with preexisting coronary heart disease. For primary prevention, however, therapy with medication has a favorable cost-effectiveness ratio only in identifiable high-risk persons, and the different costs of the various available medications should be taken into account. Therapy with medications, especially for primary prevention, would be more appealing if the price of the available medications were lower.

CONCLUSIONS
High priority should be given to research that could validate these cost-effectiveness projections as well as to further studies of the elderly and women, in whom direct data on the precise costs, risks, and benefits of interventions to lower cholesterol remain sparse.
In vivo assessment of vascular pathology resulting from laser irradiation. Analysis of 23 patients studied by directional atherectomy immediately after laser angioplasty.
Authors: Isner J M , Rosenfield K , White C J , Ramee S , Kearney M , Pieczek A , Langevin R E , Razvi S 
Published: June 2012

BACKGROUND
The pathological consequences of cardiovascular laser irradiation have been studied extensively in vitro. Previous in vivo studies of laser-induced injury have included analyses of acute and/or chronic findings in experimental animals. Little information, however, is available regarding the acute effects of laser irradiation of human vascular tissues in vivo.

METHODS AND RESULTS
To determine the acute pathology resulting from laser irradiation of human vascular tissue in vivo, specimens retrieved from 23 patients by directional atherectomy immediately after laser angioplasty (19 peripheral and four coronary) were examined by light microscopy. Of the 23 patients, three (13.0%) were treated with a metal-capped ("hot-tip") fiber coupled to a continuous-wave neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using up to 18 W power and 18-305 seconds of cumulative exposure time; in all three patients (100%), thermal injury, including frank charring several cell layers thick, was seen along the luminal borders of the atherectomy specimen. In eight of the 23 patients (34.5%), laser angioplasty was performed using a 250-microseconds holmium:YAG laser at fluences up to 2,300 mJ/mm2, a repetition rate of 5 Hz, and 25-200 seconds of cumulative exposure; in seven of eight patients (85.5%), the atherectomy specimen showed signs of vacuolar injury consisting of central and satellite Alcian-blue-negative vacuoles. In two patients (25.0%), there was a "smudged" or "shredded" edge, whereas in one patient, frank signs of thermal injury were observed. Finally, in 12 of the 23 patients (52.2%), laser angioplasty was performed using a 120-nsec excimer laser at fluences up to 60 mJ/mm2, a repetition rate of 25 Hz, and a cumulative exposure time of 21-315 seconds. Pathological findings among these 12 patients were limited to nine patients (75%) in whom a weakly basophilic, smudged, and/or shredded appearance approximately one cell layer thick was observed along the luminal border of the atherectomy specimen and two patients (16.7%) with small foci of vacuolar injury. None of the atherectomy specimens retrieved after excimer laser angioplasty disclosed signs of thermal injury.

CONCLUSIONS
These findings document that acute pathological alterations resulting from in vivo laser angioplasty are variable, depending on the laser source used, and are similar to that predicted by experimental studies performed previously in vitro. The prognostic implications of these varying pathological features remain to be clarified.
Suppression of longitudinal versus transverse conduction by sodium channel block. Effects of sodium bolus.
Authors: Turgeon J , Wisialowski T A , Wong W , Altemeier W A , Wikswo J P , Roden D M 
Published: June 2012

BACKGROUND
Arrhythmias resulting from treatment with sodium channel-blocking antiarrhythmic drugs have been successfully treated with sodium infusion, although the mechanism underlying this effect is uncertain.

METHODS AND RESULTS
In this study, we used a multielectrode array to examine the effects of O-desmethyl encainide (ODE), a potent sodium channel-blocking metabolite of encainide, on conduction in canine ventricle. ODE depressed both longitudinal and transverse conduction velocities in a plasma concentration-related fashion (r = -0.74, -0.60; p less than 0.001). At ODE concentrations less than or equal to 300 ng/ml (n = 34), conduction velocity was depressed to the same extent in the longitudinal (-21.9 +/- 8.4%, SD) and transverse orientations (-22.0 +/- 8.8%). However, at concentrations greater than 300 ng/ml (n = 17), conduction was significantly more impaired longitudinally than transversely (-44.5 +/- 11.7% versus -34.4 +/- 13.7%, p less than 0.02). In 12 animals with high concentrations (mean, 432 +/- 32 ng/ml), a 5-meq/kg bolus of sodium chloride over 1 minute immediately increased conduction velocity; this effect was significantly greater and longer lasting in the longitudinal orientation. In two animals, conduction block in the longitudinal orientation was documented at high plasma ODE and was immediately reversed by sodium bolus.

CONCLUSIONS
We conclude that the major effect of sodium in animals with excess sodium channel block is improvement of longitudinal propagation; this effect may underlie the antiarrhythmic action of sodium in the analogous clinical setting.
Microinjection of antibodies and expression vectors into living myocardial cells. Development of a novel approach to identify candidate genes that regulate cardiac growth and hypertrophy.
Authors: Shubeita H E , Thorburn J , Chien K R 
Published: June 2012

BACKGROUND
Microinjection approaches in the cardiac cell context have allowed delivery of various calcium dyes and monitoring of short-term physiological responses. However, unlike other cell types, it has proved difficult to microinject myocardial cells without the concomitant loss of long-term cell viability.

METHODS AND RESULTS
An analysis of experimental variables was conducted to adapt microinjection techniques to the neonatal rat ventricular cell context. Among the variables optimized were the selection of culture dishes, plating substrate, microinjection parameters, and a variety of maneuvers to inhibit myocyte hypercontracture, injury, and consequent death after micropuncture. With the modified technique, the percentage of injected cells that maintained long-term viability (48 hours) increased from less than 1% to 30%. Similarly, an increased efficiency of gene transfer and expression (measured as the percentage of injected cells that express the delivered gene) was obtained after either cytoplasmic or nuclear injection of a beta-galactosidase expression vector into cardiac myocytes. Microinjection of marker immunoglobulin G does not interfere with the induction of the hypertrophic response or the expression of a coinjected atrial natriuretic factor promoter-luciferase reporter fusion gene construct.

CONCLUSIONS
To the best of our knowledge, this study provides the first description of the efficient microinjection of neonatal cardiac muscle cells with maintenance of long-term cell viability. The microinjection technique is now a viable approach to examine cause-and-effect relations between specific gene products and any defined feature or response of cardiac myocytes that can be assayed at a single-cell level.
Preconditioning does not attenuate myocardial stunning.
Authors: Ovize M , Przyklenk K , Hale S L , Kloner R A 
Published: June 2012

BACKGROUND
Despite numerous reports that one or more episodes of brief coronary artery occlusion preconditions the myocardium and dramatically reduces myocardial infarct size produced by a subsequent prolonged ischemia, we recently demonstrated that preconditioning does not attenuate contractile dysfunction in the peri-infarct tissue. However, the specific effects of preconditioning on myocardium in which wall motion has not been compromised by the preconditioning regimen per se and is further submitted to a short ischemic insult (that is, not confounded by necrosis) remain unknown.

METHODS AND RESULTS
We addressed these issues in the canine model of myocardial stunning. Eighteen anesthetized dogs underwent 15 minutes of coronary occlusion followed by 3 hours of reperfusion. Before the 15-minute coronary occlusion, each dog received one of three treatments: no intervention (control group, n = 6), one episode of 5-minute coronary occlusion/5-minute reperfusion (PC5 group, n = 6), or one episode of 2.5-minute coronary occlusion/5-minute reperfusion (PC2.5 group, n = 6). Segment shortening (SS) in the ischemic/reperfused midmyocardium was monitored by sonomicrometry, and myocardial blood flow was assessed by injection of radiolabeled microspheres. All three groups were equally ischemic during the 15-minute coronary occlusion: Midmyocardial blood flow averaged 0.05 +/- 0.02, 0.07 +/- 0.04, and 0.08 +/- 0.03 ml/min/g in control, PC2.5, and PC5 groups, respectively. Before the 15-minute coronary occlusion, PC5 dogs exhibited significant stunning (SS = 55% baseline; p less than 0.01 versus control), whereas PC2.5 dogs did not (SS = 91% baseline; p = NS versus control). However, segment shortening during the subsequent 15-minute coronary occlusion was equally depressed at -25% to -42% of baseline values among the three groups. Furthermore, all three groups demonstrated a similar degree of stunning after reperfusion: SS at 3 hours after reflow averaged 24 +/- 12%, 34 +/- 16%, and 48 +/- 12% of baseline in control, PC2.5, and PC5 groups, respectively (p = NS). The degree of recovery of function after reperfusion correlated with the amount of midmyocardial blood flow during coronary artery occlusion. However, this relation was not different among the three groups: Specifically, for any given collateral flow during ischemia, preconditioning did not reduce the degree of stunning.

CONCLUSIONS
Preconditioning neither preserves contractile function during a reversible ischemic insult nor prevents myocardial stunning during the initial hours of reflow.
Effect of pulse separation between two sequential biphasic shocks given over different lead configurations on ventricular defibrillation efficacy.
Authors: Johnson E E , Alferness C A , Wolf P D , Smith W M , Ideker R E 
Published: June 2012

BACKGROUND
Two sequential biphasic shocks delivered over separate lead configurations markedly improve defibrillation efficacy compared with a single shock alone. We investigated the effect of varying the intershock interval between sequential biphasic shocks on defibrillation.

METHODS AND RESULTS
Defibrillation thresholds (DFTs) were obtained in six dogs for shock separations ranging from 0.2 to 125 msec. The first shock was given from a catheter electrode in the right ventricular apex to a patch on the left lateral thorax; the second was from a small patch on the left ventricular apex to a catheter electrode in the right ventricular outflow tract. When the interval between shocks was less than or equal to 10 msec or greater than or equal to 75 and less than or equal to 125 msec, the mean DFTs were less than that previously found for the first shock by itself (4.2 versus 7.4 J, p = 0.002). At a separation of 50 msec, however, there was a marked rise in the DFT to 27 J. The mean DFT for the second shock at a delay of 50 msec was not different from the mean DFT previously found for the second shock by itself (7.2 versus 7.0 J). These results were confirmed in another six dogs using defibrillation probability-of-success curves. In 12 other dogs, probability-of-success curves were generated for delays between shocks as a percentage of the activation interval during ventricular fibrillation. Minimum defibrillation energy requirements were at two separations, 0.2 msec and 90% of the activation interval.

CONCLUSIONS
The optimal intershock interval between two sequential biphasic shocks is either less than or equal to 10 msec or greater than or equal to 75 and less than or equal to 125 msec. The marked rise in the DFT at a shock separation of 50 msec, requiring more energy than that for the first shock alone, suggests that the second shock at this time delay is likely to reinduce fibrillation after it is halted by the first shock until the second shock is strong enough to defibrillate independently of the first shock.
Doppler assessment of prosthetic valve orifice area. An in vitro study.
Authors: Baumgartner H , Khan S S , DeRobertis M , Czer L S , Maurer G 
Published: June 2012

BACKGROUND
Although Doppler echocardiography has been shown to be accurate in assessing stenotic orifice areas in native valves, its accuracy in evaluating the prosthetic valve orifice area remains undetermined.

METHODS AND RESULTS
Doppler-estimated valve areas were studied for their agreement with catheter-derived Gorlin effective orifice areas and their flow dependence in five sizes (19/20-27 mm) of St. Jude, Medtronic-Hall, and Hancock aortic valves using a pulsatile flow model. Doppler areas were calculated three ways: using the standard continuity equation; using its simplified modification (peak flow/peak velocity); and using the Gorlin equation with Doppler pressure gradients. The results were compared with Gorlin effective orifice areas derived from direct flow and catheter pressure measurements. Excellent correlation between Gorlin effective orifice areas and the three Doppler approaches was found in all three valve types (r = 0.93-0.99, SEE = 0.07-0.11 cm2). In Medtronic-Hall and Hancock valves, there was only slight underestimation by Doppler (mean difference, 0.003-0.25 cm2). In St. Jude valves, however, all three Doppler methods significantly underestimated effective orifice areas derived from direct flow and pressure measurements (mean difference, 0.40-0.57 cm2) with differences as great as 1.6 cm2. In general, the modified continuity equation calculated the largest Doppler areas. When orifice areas were calculated from the valve geometry using the area determined from the inner valve diameter reduced by the projected area of the opened leaflets, Gorlin effective orifice areas were much closer to the geometric orifice areas than Doppler areas (mean difference, 0.40 +/- 0.31 versus 1.04 +/- 0.20 cm2). In St. Jude and Medtronic-Hall valves, areas calculated by either technique did not show a consistent or clinically significant flow dependence. In Hancock valves, however, areas calculated by both the continuity equation and the Gorlin equation decreased significantly (p less than 0.001) with low flow rates.

CONCLUSIONS
Doppler echocardiography using either the continuity equation or Gorlin formula allows in vitro calculation of Medtronic-Hall and Hancock effective valve orifice areas but underestimates valve areas in St. Jude valves. This phenomenon is due to localized high velocities in St. Jude valves, which do not reflect the mean velocity distribution across the orifice. Valve areas are flow independent in St. Jude and Medtronic-Hall prostheses but decrease significantly with low flow in Hancock valves, suggesting that bioprosthetic leaflets may not open fully at low flow rates.
Coronary reserve and exercise ECG in patients with chest pain and normal coronary angiograms.
Authors: Camici P G , Gistri R , Lorenzoni R , Sorace O , Michelassi C , Bongiorni M G , Salvadori P A , L'Abbate A 
Published: June 2012

BACKGROUND
Coronary vasodilator reserve is reduced in some patients with a history of chest pain and angiographically normal coronary arteries. ECG changes suggestive of myocardial ischemia during exercise also can be demonstrated in a subset of these patients.

METHODS AND RESULTS
We have investigated the correlation between coronary vasodilator reserve, assessed with 13N-labeled ammonia and positron emission tomography, and the ECG during exercise stress in 45 patients with a history of chest pain, angiographically normal coronary arteries, and a negative ergonovine test. ST segment depression on the ECG during exercise was present in 29 of 45 patients. Mean resting left ventricular blood flow was 1.04 +/- 0.22 ml.min-1.g-1; it increased to 1.32 +/- 0.47 ml.min-1.g-1 (p less than 0.01 versus baseline value) during atrial pacing and to 2.52 +/- 0.96 ml.min-1.g-1 (p less than 0.01 versus baseline value) after dipyridamole (0.56 mg/kg i.v.). No regional flow defects could be demonstrated in any patient during pacing or after dipyridamole. Myocardial flows after dipyridamole, however, did not show a normal frequency distribution (Kolmogorov-Smirnov test), and two patient populations could be identified. Twenty-nine (67%) patients had a mean left ventricular flow of 3.02 +/- 0.33 ml.min-1.g-1 after dipyridamole (range, 2.13-5.46 ml.min-1.g-1), and 14 (33%) patients had a mean flow of 1.48 +/- 0.29 ml.min-1.g-1 (range, 1.06-2.04 ml.min-1.g-1, p less than 0.01 versus the "high-flow group").

CONCLUSIONS
Approximately one third of patients in our series showed a reduced coronary vasodilator reserve. Although 12 of 14 patients in the "low-flow group" had ST segment depression during exercise stress, 16 of 29 patients in the high-flow group also had ST segment depression during exercise stress. Therefore, despite a good sensitivity (86%) in identifying patients with a blunted increment of coronary flow, the ECG response during exercise stress appears to have a rather low specificity (45%). This suggests that factors other than reduced coronary reserve and myocardial ischemia may play a role in the genesis of the ST segment depression in these patients.
Lumen diameter of normal human coronary arteries. Influence of age, sex, anatomic variation, and left ventricular hypertrophy or dilation.
Authors: Dodge J T , Brown B G , Bolson E L , Dodge H T 
Published: June 2012

BACKGROUND
Precise knowledge of the expected "normal" lumen diameter at a given coronary anatomic location is a first step toward developing a quantitative estimate of coronary disease severity that could be more useful than the traditional "percent stenosis."

METHODS AND RESULTS
Eighty-three arteriograms were carefully selected from among 9,160 consecutive studies for their smooth lumen borders indicating freedom from atherosclerotic disease. Of these, 60 men and 10 women had no abnormalities of cardiac function, seven men had idiopathic dilated cardiomyopathy, and six men had left ventricular hypertrophy associated with significant aortic stenosis. Lumen diameter was measured at 96 points in 32 defined coronary segments or major branches. Measurements were scaled to the catheter, corrected for imaging distortion, and had a mean repeat measurement error of 0.12 mm. When sex, anatomic dominance, and branch length were accounted for, normal lumen diameter at each of the standard anatomic points could usually be specified with a population variance of +/- 0.6 mm or less (SD) and coefficient of variation of less than 0.25 (SD/mean). For example, the left main artery measured 4.5 +/- 0.5 mm, the proximal left anterior descending coronary artery (LAD) 3.7 +/- 0.4 mm, and the distal LAD 1.9 +/- 0.4 mm. For the LAD, lumen diameter was not affected by anatomic dominance (right versus left), but for the right coronary artery, proximal diameter varied between 3.9 +/- 0.6 and 2.8 +/- 0.5 mm (p less than 0.01) and for the left circumflex, between 3.4 +/- 0.5 and 4.2 +/- 0.6 mm (p less than 0.01). Women had smaller epicardial arterial diameter than men (-9%; p less than 0.001), even after normalization for body surface area (p less than 0.01). Branch artery caliber was unaffected by the anatomic dominance but increased with branch length, expressed as a fraction of the origin-to-apex distance (p less than 0.001). Lumen diameter was not affected by age or by vessel tortuosity but was significantly increased among men with left ventricular hypertrophy (+ 17%; p less than 0.001) or dilated cardiomyopathy (+ 12%; p less than 0.001).

CONCLUSIONS
This is a reference normal data set against which to compare lumen dimensions in various pathological states. It should be of particular value in the investigation of diffuse atherosclerotic disease.