bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplexing studies of effects of rapid atrial pacing on the area of slow conduction during atrial flutter in canine pericarditis model.
Authors: Shimizu A , Nozaki A , Rudy Y , Waldo A L 
Published: June 2012

BACKGROUND
We report that rapid atrial pacing interrupts atrial flutter when the orthodromic wave front from the pacing impulse is blocked in an area of slow conduction in the reentry circuit. To characterize the area of slow conduction during atrial flutter and rapid pacing, we studied 11 episodes of induced atrial flutter, mean cycle length 157 +/- 20 msec, in eight dogs with sterile pericarditis.

METHODS AND RESULTS
Atrial electrograms were recorded simultaneously from 95 pairs of right atrial electrodes during the interruption of atrial flutter by rapid atrial pacing, mean cycle length 139 +/- 21 msec. Areas of slow conduction during atrial flutter were demonstrated at one to three sites in the reentry circuit. After rapid pacing captured the reentry circuit, one area of slow conduction either disappeared (10 episodes) or the degree of slow conduction in an area of slow conduction decreased (one episode). Both changes were in association with activation of the region by a wave front from the pacing impulse that arrived from a direction different than that during the induced atrial flutter. Interruption of atrial flutter during rapid pacing occurred when the orthodromic wave front from the pacing impulse blocked in an area of slow conduction that had either newly evolved during rapid pacing (seven episodes) or that was previously present (four episodes).

CONCLUSIONS
Areas of slow conduction present during atrial flutter and rapid pacing of atrial flutter are functional and depend on both the atrial rate and the direction of the circulating wave fronts. Interruption of atrial flutter by rapid pacing results from block of the orthodromic wave front of the pacing impulse in an area of slow conduction in the reentry circuit.
Xanthine oxidase inhibition does not limit canine infarct size.
Authors: Werns S W , Grum C M , Ventura A , Hahn R A , Ho P P , Towner R D , Fantone J C , Schork M A , Lucchesi B R 
Published: June 2012

BACKGROUND
Evidence supporting the role of xanthine oxidase in myocardial reperfusion injury is based on studies with pharmacological interventions used to inhibit enzyme function. Controversy exists, however, regarding the true role of xanthine oxidase in reperfusion injury. This study was performed to determine whether xanthine oxidase inhibition limits myocardial injury due to coronary artery occlusion and reperfusion.

METHODS AND RESULTS
Anesthetized dogs underwent coronary artery occlusion (90 minutes) and reperfusion (6 hours). Oxypurinol (28 mg/kg) or amflutizole (30 mg/kg), chemically unrelated inhibitors of xanthine oxidase, or vehicle was infused intravenously 15 minutes before and 3 hours after reperfusion. Regional myocardial blood flow was determined with radiolabeled microspheres. Infarct size was determined with the tetrazolium method. Myocardial infarct size (percent of risk region) was less in oxypurinol-treated dogs, 32 +/- 16%, compared with that of the control group, 46 +/- 15%. Infarct size for the amflutizole-treated dogs, 40 +/- 21%, was not significantly different from that of the control group. There were no differences in rate-pressure product or collateral blood flow to account for differences in infarct size. Uric acid concentration in the coronary venous plasma increased after reperfusion in the dogs treated with vehicle but not in the drug-treated dogs. Xanthine oxidase inhibition was demonstrated in each of the drug treatment groups, but only oxypurinol limited the extent of myocardial injury.

CONCLUSIONS
Previously reported cardioprotective effects of allopurinol, noted to occur only when the drug was administered chronically, may be related to a property of oxypurinol, a major metabolite of allopurinol. The beneficial effect of oxypurinol is unrelated to inhibition of superoxide formation during xanthine oxidase-catalyzed oxidation of xanthine and hypoxanthine.
Logistic discriminant analysis improves diagnostic accuracy of exercise testing for coronary artery disease in women.
Authors: Robert A R , Melin J A , Detry J M 
Published: June 2012

BACKGROUND
Diagnostic accuracy of the exercise electrocardiogram in women has been shown to be limited for the detection of coronary artery disease. New diagnostic methods based on computer analysis of the exercise electrocardiogram and multivariate analysis have improved the diagnostic value of exercise testing in male subjects. The aim of the present study was to assess whether the diagnostic value of exercise testing can be enhanced in women by using multivariate analysis of exercise data.

METHODS AND RESULTS
Between 1978 and 1984, 135 infarct-free women underwent exercise testing and coronary angiography. Significant coronary artery disease was present in 41% of the patients. In this first group, maximal exercise variables were submitted to a stepwise logistic analysis. Work load, heart rate, and ST60X were selected to build a diagnostic model. The model was tested in a second group of 115 catheterized women (significant coronary artery disease in 47%) and of 76 volunteers. We compared the present model with conventional analysis of the exercise electrocardiogram, with ST changes adjusted for heart rate, and with a previously described analysis. In both groups, sensitivity was better with the present model (66% and 70%) than by conventional (68% and 59%) and by the previously described analysis (57% and 44%) without a loss of specificity (85% and 93%). Receiver-operator characteristic curves showed also a better diagnostic accuracy with the present model.

CONCLUSIONS
In women, logistic analysis of exercise variables improves the diagnostic value of exercise testing. It yields a significantly better sensitivity without a loss of specificity.
Significance of a negative exercise thallium test in the presence of a critical residual stenosis after thrombolysis for acute myocardial infarction.
Authors: Sutton J M , Topol E J 
Published: June 2012

BACKGROUND
After thrombolytic therapy for acute myocardial infarction, increasing emphasis is placed on early submaximal exercise testing, with further intervention advocated only for demonstrable ischemia. Although significant residual coronary artery lesions after successful thrombolysis are common, many patients paradoxically have no corresponding provokable ischemia.

METHODS AND RESULTS
The relation between significant postthrombolytic residual coronary artery disease and a negative early, submaximal exercise thallium-201 tomogram was studied among 101 consecutive patients with uncomplicated myocardial infarction and at least 70% residual stenosis of the infarct artery. A negative test occurred in 49 (48.5%) patients with a mean 88% residual infarct artery stenosis. Further characteristics of the group were as follows: mean time to treatment was 3.1 hours; mean age was 54 +/- 10 years; 80% were male; 47% had anterior infarction; 39% had multivessel disease; mean left ventricular ejection fraction was 53 +/- 14%; and mean peak creatine kinase level was 3,820 +/- 3,123 IU/ml. A similar group of 52 (51.5%) patients, treated within 3.3 hours from symptom onset, with a mean postthrombolysis stenosis of 90%, had a positive exercise test. Characteristics of this group were as follows: age was 58 +/- 10 years; 92% were male; 56% had anterior infarction; 40% had multivessel disease; and mean left ventricular ejection fraction was 54 +/- 15%. The peak creatine kinase level associated with the infarction, however, was lower: 2,605 +/- 1,805 IU/ml (p = 0.04). There was no difference in performance at exercise testing with respect to peak systolic pressure, peak heart rate, or time tolerated on the treadmill between the two groups. By multivariate logistic regression, only peak creatine kinase level predicted a negative stress result in the presence of a significant residual stenosis (odds ratio, 4.2; 95% confidence interval, 1.1-16.3).

CONCLUSIONS
The explanation for the relatively frequent finding of a negative early stress 201Tl tomogram after apparently successful reperfusion appears to be more extensive myocardial necrosis and not delay in therapy or inadequate exercise performance.
Effect of volume loading, pressure loading, and inotropic stimulation on left ventricular torsion in humans.
Authors: Hansen D E , Daughters G T , Alderman E L , Ingels N B , Stinson E B , Miller D C 
Published: June 2012

BACKGROUND
The transmural distribution of fiber angles and the extent of shortening among obliquely oriented fibers are likely to be major determinants of the twisting motion that accompanies left ventricular (LV) ejection. As such, measurements of torsion may provide useful information about LV contractile function, but other factors, such as ventricular loading conditions, may also regulate this motion.

METHODS AND RESULTS
Torsion angles (theta i) of midventricular and apical regions were measured relative to a reference minor axis near the base in seven human cardiac allografts from biplane radiographic images of metallic midwall markers. Pressure loading with methoxamine (5-10 muk/kg/min) increased LV end-systolic pressure by 41 +/- 14 mm Hg (p less than 0.0001). Volume loading with normal saline raised LV end-diastolic pressure from 9.9 +/- 5.2 to 19.6 +/- 4.9 mm Hg (p less than 0.0001). These alterations in LV loading conditions were associated with no change in theta i (difference not significant) for any marker site. Inotropic stimulation with dobutamine (5 micrograms/kg/min) increased values of theta i by as much as twofold (p less than 0.05); this response varied considerably depending on marker location, with the middle and apical inferior wall and the apical lateral wall being the most sensitive. When the marker site associated with the largest torsion angle (theta max) was considered in each patient, dobutamine increased theta max in all cases (25.2 +/- 10.5 degrees versus 15.8 +/- 7.7 degrees, p less than 0.001), whereas pressure and volume loading had negligible effects. This 59% increase in theta max was greater than that of conventional load-dependent indexes of LV systolic performance such as stroke volume (16%), ejection fraction (22%), and maximum rate of LV pressure rise (52%).

CONCLUSIONS
This component of LV motion is relatively insensitive to alterations in preload and afterload, while changes in contractile state influence LV torsion in a regionally heterogeneous manner. Quantification of LV torsion may, therefore, provide a sensitive and relatively load-independent measure of contractile performance that may prove to be useful in the serial assessment of LV function.
Fibrocellular tissue response after percutaneous transluminal coronary angioplasty. An immunocytochemical analysis of the cellular composition.
Authors: Ueda M , Becker A E , Tsukada T , Numano F , Fujimoto T 
Published: June 2012

BACKGROUND
Restenosis after initial, successful percutaneous transluminal coronary angioplasty (PTCA) is due to fibrocellular proliferation.

METHODS AND RESULTS
The present study focused on the nature of fibrocellular tissue in humans by use of immunocytochemical techniques. Four hearts (five coronary arteries) were investigated; time lapse between PTCA and death varied between 20 days (two arteries) and 1 year 7 months. Proliferating cells stained positive with smooth muscle cell-specific monoclonal antibodies. Cells from early proliferative lesions (20 days) have a phenotypic expression different from cells in "old" lesions. Proliferating cells stained positive with vimentin but were negative with desmin, irrespective of the lesion's age.

CONCLUSIONS
The findings indicate a change in actin isoform expression of smooth muscle cells while adapting to a pathological state.
A1-adenosine receptor inhibition of adenylate cyclase in failing and nonfailing human ventricular myocardium.
Authors: Hershberger R E , Feldman A M , Bristow M R 
Published: June 2012

BACKGROUND
Receptors that couple via the stimulatory G protein, Gs, to adenylate cyclase and to a positive inotropic response have been extensively investigated in falling human heart. In contrast, much less is known about receptors, such as the A1-adenosine receptor, that couple to adenylate cyclase via the inhibitory G protein, Gi, to give a negative inotropic response. Activation of such Gi-coupled receptors might worsen heart failure. Furthermore, alpha Gi is increased in failing human ventricular myocardium, which may enhance inhibitory receptor coupling to adenylate cyclase.

METHODS AND RESULTS
A1-Adenosine receptor inhibition of adenylate cyclase was examined in crude particulate preparations derived from 12 nonfailing and 12 failing human left ventricles. Experimental conditions were designed for maximal inhibitory responses. Dose-response curves were performed with the selective A1-adenosine receptor agonist R-phenylisopropyl-adenosine (R-PIA). No differences in nonfailing versus failing heart were observed for basal adenylate cyclase activity (49.0 +/- 4.1 versus 45.7 +/- 2.6 pmol cyclic AMP/min/mg), maximal R-PIA-mediated inhibition (31.1 +/- 2.6 versus 30.2 +/- 1.6 pmol cyclic AMP/min/mg), ED50 (R-PIA x 10(-7) 1.28 +/- 0.10 versus 1.36 +/- 0.08), or slope (1.06 +/- 0.06 versus 1.03 +/- 0.10), respectively. Furthermore, fluoride, forskolin, and manganese adenylate cyclase activation were not different in failing heart, which is consistent with no change in the catalytic unit of adenylate cyclase. The inhibitory G protein alpha Gi, as quantitated by pertussis toxin-catalyzed ADP-ribosylation, was increased in failing heart (105.7 +/- 5.8 versus 132.7 +/- 3.4 optical density units, p less than 0.003). Basal adenylate cyclase activity was reduced in failing heart (7.8 +/- 0.8 versus 4.5 +/- 0.4 pmol cyclic AMP/min/mg, p less than 0.005) with assay conditions designed to assess G protein effects.

CONCLUSIONS
The A1-adenosine receptor pathway exerts a major inhibitory effect on human myocardial adenylate cyclase activity. Although alpha Gi was increased in failing heart, A1-adenosine receptor inhibition of adenylate cyclase was not altered in preparations of failing versus nonfailing human ventricular myocardium.
Early afterdepolarizations and triggered activity in rabbit cardiac Purkinje fibers recovering from ischemic-like conditions. Role of acidosis.
Authors: Rozanski G J , Witt R C 
Published: June 2012

BACKGROUND
The mechanisms underlying repetitive activity during reperfusion of ischemic myocardium are thought to include triggered responses elicited at short pacing cycle lengths. The potential to generate repetitive responses at longer pacing cycle lengths under similar conditions, however, has not been explored. Thus, the present study examined the role of cycle length on the cellular electrical changes produced during recovery from ischemic-like conditions and identified the major component precipitating nondriven, repetitive activity.

METHODS AND RESULTS
Transmembrane potentials were recorded in vitro from isolated rabbit Purkinje fibers exposed to hypoxia (defined as PO2 less than 30 mm Hg, high [K+]o, and zero glucose) plus lactic acidosis (pH 6.7) for 45 minutes and during recovery in normal Tyrode's solution (pH 7.4). Compared with control, action potential duration (90% repolarization) during recovery increased transiently by 40.9 +/- 11.8 and 241.0 +/- 51.1 msec at respective basic cycle lengths of 1,000 and 3,000 msec (both p less than 0.005). In 81% of preparations, action potential prolongation was accompanied by early afterdepolarizations and triggered activity generated from low (positive to -40 mV) or high (negative to -40 mV) membrane potentials. In 62% of experiments, brief periods of abnormal automaticity also occurred. Triggered responses were 1) unaffected by 1 microM ryanodine, 2) abolished by pacing at short basic cycle lengths or by exposing tissues to 2.5 micrograms/ml lidocaine, and 3) more easily induced at long basic cycle lengths or by superfusing 2.5 micrograms/ml quinidine. When tissues were conditioned with hypoxia alone (pH 7.4), action potential prolongation on recovery was comparatively small, and nondriven responses did not develop. Conversely, addition of 10-20 microM amiloride to the hypoxic, acidic test solution augmented recovery-induced action potential prolongation.

CONCLUSIONS
We conclude that acidosis, as a component of ischemia, plus slow pacing frequencies may mediate the genesis of early afterdepolarizations and triggered activity in Purkinje fibers on recovery, long after extracellular pH has been restored to normal. These data may have clinical relevance to the mechanisms of reperfusion arrhythmias in the intact human heart.
Interventricular coronary steal induced by stenosis of left anterior descending coronary artery in exercising pigs.
Authors: Crottogini A J , Guth B D , Barra J G , Willshaw P , Lascano E C , Pichel R H 
Published: June 2012

BACKGROUND
In pigs and humans, the left anterior descending coronary artery (LAD) supplies the left ventricular anterior wall (LVAW), anterior septum, and paraseptal band of the right ventricular anterior wall (RVAW). The purposes of our study were 1) to study the LAD flow distribution in these walls during preexercise, exercise, and exercise with LAD stenosis and 2) to analyze regional wall motion under these conditions.

METHODS AND RESULTS
Nine pigs were instrumented with sonomicrometers for measuring percent wall thickening (%WTh) in LVAW, RVAW, and lateral (control) walls of both ventricles, a hydraulic occluder at the LAD origin, an LV pressure transducer, and catheters for radioactive microsphere injection (left atrium) and blood withdrawal (aorta). One month later, regional %WTh and flows were measured during preexercise, exercise, and continuing exercise with LAD stenosis resulting in more than 50% reduction in systolic LVAW %WTh with regard to exercise. LAD stenosis caused a dramatic decrease in total mean +/- SD LVAW subendocardial flow with regard to exercise (28.7 +/- 8 to 9.1 +/- 3.2 ml.min-1, p less than 0.0001) but not significant changes in either LVAW subepicardial flow or RVAW flow. The transmural distribution of flows within the LAD bed (as percentages of the total LAD flow in each experimental condition) showed that LAD stenosis redistributed flows with regard to exercise such that the LVAW subendocardial flow decreased from 26.4 +/- 4.2% of the total LAD flow to 11.8 +/- 4.3% (p less than 0.0001), whereas LVAW subepicardial flow increased from 32.9 +/- 2.3% of the total LAD flow to 45.5 +/- 7.9% (p less than 0.0001) and RVAW increased from 12 +/- 4.9% of the total LAD flow to 18.7 +/- 7.2% (p less than 0.0005). With exercise plus LAD stenosis, LVAW %WTh decreased from 43.2 +/- 8.4% to 17.2 +/- 9.7% (p less than 0.0001), but RVAW %WTh did not change.

CONCLUSIONS
In the LAD bed of exercising pigs, LAD stenosis induces, in addition to transmural steal, an interventricular steal favoring the RVAW at the expense of the LVAW subendocardium. This steal results in preserved RVAW thickening despite severe LVAW hypokinesia.
Morphological changes and smooth muscle cell proliferation after experimental excimer laser treatment.
Authors: Hanke H , Haase K K , Hanke S , Oberhoff M , Hassenstein S , Betz E , Karsch K R 
Published: June 2012

BACKGROUND
Little is known about the mechanism(s) in the development of restenosis after excimer laser angioplasty. Thus, the rationale of this study was to determine the time course of intimal and medial smooth muscle cell (SMC) proliferation and histomorphological changes after experimental excimer laser treatment.

METHODS AND RESULTS
Laser ablation was performed in the right carotid artery of 34 New Zealand White rabbits after development of a fibromuscular plaque by repeated weak electrical stimulations. The vessels were excised 3, 7, 14, 21, 28, and 42 days after excimer laser treatment. Staining of alpha-actin was used to identify SMCs. In five rabbits (15%), a stenosis of more than 50% of luminal area was due to intimal proliferation of SMCs, and in four other rabbits, a total occlusion was due to organized thrombi. After the initial ablation of the performed plaque (13 +/- 6 intimal SMC layers) a continuous increase of intimal wall thickness was found from 7 +/- 6 SMC layers at 7 days to 28 +/- 5 intimal SMC layers at 28 days after excimer laser ablation (p less than 0.01). After 42 days, no additional increase of intimal thickening occurred. After bromodeoxyuridine labeling, the extent of cell proliferation (percent of cells undergoing DNA synthesis) in the intima and media was determined using a monoclonal antibody against bromodeoxyuridine. Immunohistological quantification of SMC proliferation in the intima revealed a significant increase of cells undergoing DNA synthesis at 3 (p less than 0.05) and 14 (p less than 0.01) days after laser treatment. Medial proliferation of SMCs was delayed and had a significant increase 7 days (p less than 0.05) after intervention. Twenty-one days after laser treatment, SMC proliferation in the intima as well as in the media was normalized.

CONCLUSIONS
The proliferative response of SMCs after experimental excimer laser treatment will occur as a dynamic process with a maximum of SMCs undergoing DNA synthesis during 14 days after laser ablation, resulting in an increase of intimal thickening within 4 weeks after laser treatment. The extent of intimal hyperplasia due to SMC proliferation after excimer laser treatment is comparable with the effect of transluminal balloon angioplasty in this experimental model.
Myocyte injury and contraction abnormalities produced by cytotoxic T lymphocytes.
Authors: Woodley S L , McMillan M , Shelby J , Lynch D H , Roberts L K , Ensley R D , Barry W H 
Published: June 2012

BACKGROUND
The mechanisms by which ventricular function is altered during cardiac transplant rejection are not well understood. Therefore, an in vitro model system has been developed to facilitate investigation of lymphocyte-mediated myocyte injury.

METHODS AND RESULTS
Splenic lymphoid cells were obtained from mice 8-10 days after placement of a vascularized abdominal cardiac allograft and were restimulated in vitro with irradiated donor-type splenocytes for 5 days. Cytotoxic effects of these allogenically stimulated lymphocytes on syngeneic and donor strain fetal cultured myocytes were determined by a 51Cr release assay at different lymphocyte to myocyte ratios. 51Cr release from donor strain myocytes was detectable within 1 hour of exposure, was maximal by 3-5 hours of coincubation with sensitized lymphocytes, and was allospecific. Cell injury manifest by 51Cr release was calcium dependent and was inhibited by pretreatment of lymphocytes with phorbol ester to deplete protein kinase C. Myocyte injury was also prevented by pretreatment of sensitized lymphocytes with anti-Thy 1.2 or anti-CD8 antibody plus complement but not by treatment with anti-CD4 antibody, indicating that CD8+ cytotoxic T cells are involved. Altered myocyte contractile motion preceded myocyte lysis (51Cr release), was characterized by an initial reversible decrease in amplitude of contraction, and was followed by rapid and irregular beating with eventual complete cessation of contraction. Contractile alterations induced by sensitized lymphocytes were inhibited by elimination of CD8+ cells.

CONCLUSIONS
Myocyte injury can be produced by sensitized cytotoxic T lymphocytes in vitro and is calcium and protein kinase C dependent. The contractile abnormalities produced appear to be similar to those observed in cardiac transplant patients undergoing rejection, and thus this model system promises to allow investigation of the mechanisms involved.