bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular and endocrine effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations in conscious dogs.
Authors: Donckier J E , Hanet C , Berbinschi A , Galanti L , Robert A , Van Mechelen H , Pouleur H , Ketelslegers J M 
Published: June 2012

BACKGROUND
Increased plasma concentrations of endothelin-1, a potent vasoconstrictor produced by the endothelium, have been reported in various pathological conditions. This study was conducted to evaluate effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations.

METHODS AND RESULTS
Endothelin-1 was infused at increasing doses (2.5, 5, 10, and 20 ng/kg.min for 1 hour each) in nine conscious dogs. During endothelin-1 infusion, plasma endothelin-1 rose from a basal value of 1.8 +/- 0.4 pmol/l to 5.8 +/- 1.1 (pathophysiological), 20.8 +/- 3.9 (pathophysiological), 85.4 +/- 18.9 (pharmacological), and 311.4 +/- 55.7 (pharmacological) pmol/l at each dose, respectively. Heart rate increased at 2.5 ng/kg.min (from 129 +/- 7 to 146 +/- 12 beats/min) but decreased at 20 ng/kg.min (97 +/- 7 beats/min) (p less than 0.001). Such a biphasic response was also observed for peak (+)dP/dt and (dP/dt)/DP40 (p less than 0.005). Left ventricular systolic pressures, mean aortic pressure, and left atrial pressure increased over time (p less than 0.05, p less than 0.005, and p less than 0.001, respectively). The time constant of early isovolumic relaxation rose progressively (p less than 0.001). The percent systolic shortening decreased at 10 and 20 ng/kg.min (p less than 0.005). Pressure-segment length loops showed a reduction in systolic shortening associated with an increase in left ventricular systolic pressure at 20 ng/kg.min. Atrial natriuretic factor rose after 5 ng/kg.min from 28.5 +/- 6.5 to 92.0 +/- 18.2 pmol/l (p less than 0.005). Angiotensin II and catecholamines did not change significantly. Serum urea and creatinine rose progressively (p less than 0.05), whereas glucose decreased (p less than 0.05). The above results differed significantly from measurements obtained in a time-control group of six dogs.

CONCLUSIONS
A fourfold increase of plasma endothelin-1 obtained after doubling the infusion rate suggests a reduction in endothelin-1 clearance or endothelin-1 endogenous production. The biphasic response of heart rate is consistent with baroreflex-mediated effects resulting from vasodilation at the pathophysiological level and vasoconstriction at the pharmacological level. Hemodynamic data suggest an increase followed by a decrease in contractility at both levels, respectively. Finally, endothelin-1 is a stimulator of atrial natriuretic factor.
Does myocardial stunning contribute to infarct size limitation by ischemic preconditioning?
Authors: Miura T , Goto M , Urabe K , Endoh A , Shimamoto K , Iimura O 
Published: June 2012

BACKGROUND
The mechanism through which ischemic preconditioning causes cardioprotection is unknown. The present study investigated the role of stunning in preconditioning.

METHODS AND RESULTS
We studied three different protocols of preconditioning: two cycles of 2-minute ischemia separated by 5-minute reperfusion (2'PC), one cycle of 5-minute ischemia by 5-minute reperfusion (5'PC1), and two cycles of 5-minute ischemia separated by 5-minute reperfusion (5'PC2). In the first series of experiments, the stunning associated with 2'PC, 5'PC1, or 5'PC2 was assessed using an epicardial Doppler transducer in anesthetized open-chest rabbits. The thickening fraction (percent baseline) of the preconditioned region was 76.8 +/- 7.2% (mean +/- SEM) after 2'PC but 31.4 +/- 9.2% and 34.3 +/- 9.7% after 5'PC1 and 5'PC2, respectively, which were significantly lower, thus indicating more severe stunning than that after 2'PC. In the second series of experiments, a branch of the left circumflex artery was occluded for 30 minutes and then reperfused for 72 hours in four groups of rabbits. One group was not preconditioned and three groups were preconditioned with 2'PC, 5'PC1, or 5'PC2 protocols before the 30-minute ischemia. In contrast to the differences observed in the stunning in the first series of experiments, histological infarct size was similar in the three preconditioned groups (21.1 +/- 3.0% of area at risk after 2'PC, 20.1 +/- 3.4% after 5'PC1, 16.4 +/- 4.2% after 5'PC2), all of which were significantly smaller than that in the unpreconditioned group (43.9 +/- 5.0%). The third series of experiments examined the degree of stunning by 2'PC, 5'PC1, or 5'PC2 and the size of infarct (tetrazolium staining) in the same animal after 30-minute ischemia/3-hour reperfusion; again, the results showed no significant correlation between degree of stunning and infarct size.

CONCLUSIONS
The myocardial infarct size-limiting effect of preconditioning did not correlate with the degree of myocardial stunning accompanying preconditioning. Thus, it is unlikely that myocardial stunning contributes to the cardioprotective effect of ischemic preconditioning.
Epicardial potential mapping. Effects of conducting media on isopotential and isochrone distributions.
Authors: Green L S , Taccardi B , Ershler P R , Lux R L 
Published: June 2012

BACKGROUND
Epicardial excitation sequences, recovery sequences, and potential distributions are recorded from patients during surgery and from animals in the research laboratory for a variety of purposes. During such recordings, a portion of the cardiac surface is exposed to air, and the remainder of the epicardial surface variably is in contact with conductive tissue. No systematic studies document the degree to which these different conditions affect measured excitation times, potential distributions, and/or the configuration of epicardial electrograms.

METHODS AND RESULTS
Epicardial potential distribution was recorded from five isolated, perfused hearts using a 64-unipolar-lead sock. Data were recorded first with the heart suspended in air and then with the heart immersed in a heated tank filled sequentially to full and half-full levels with conductive Tyrode's solution and then NaCl-sucrose solution. These solutions had resistivity less than and more than that of blood, respectively, and air was assumed to have infinite resistivity. Epicardial potentials were recorded from two hearts before removal from the chest, both with and without a latex sheet insulating the heart from the pericardial cradle. Amplitude of recorded potentials from both intact and isolated hearts was markedly higher when the heart was surrounded by an insulating medium, but locations of positive and negative regions were less affected by surrounding medium. Isochrone activation maps calculated using the minimum derivative of the QRS (intrinsic deflection) were not affected by the conductivity of media surrounding the heart.

CONCLUSIONS
The present study provides evidence that isochrone maps recorded at surgery are not distorted by exposure of the cardiac surface to insulating air. Results suggest that epicardial isochrones recorded during cardiac surgery could be used in patients to assess the accuracy of "inverse" procedures that noninvasively compute epicardial electrograms and isochrones from body surface potentials.
Blood pressure control by the renin-angiotensin system in normotensive subjects. Assessment by angiotensin converting enzyme and renin inhibition.
Authors: Kiowski W , Linder L , Kleinbloesem C , van Brummelen P , Bühler F R 
Published: June 2012

BACKGROUND
The participation of the renin-angiotensin system in the control of blood pressure in normal, sodium-replete subjects is not clear. The use of a specific inhibitor of human renin should allow a better delineation of the importance of this system.

METHODS AND RESULTS
Blood pressure responses were measured 1 hour after randomized, double-blind administration of the renin inhibitor Ro 42-5892 (600 mg p.o.) or the angiotensin converting enzyme inhibitor captopril (50 mg p.o.) in 20 healthy men on an ad libitum sodium diet. Effective inhibition of the renin-angiotensin system by either compound was indicated by increases of immunoreactive renin associated with an increase of angiotensin I production rate of 67.8 +/- 33.6% after captopril and a decrease of 79.5 +/- 16.4% after Ro 42-5892. Furthermore, Ro 42-5892 decreased plasma renin activity by 64%. Whereas intra-arterial diastolic (60 +/- 5.1 to 51.4 +/- 7.2 mm Hg, p less than 0.01) and mean arterial (77.7 +/- 6.0 to 71.4 +/- 8.5 mm Hg, p less than 0.001) pressures decreased after captopril, they remained unchanged after Ro 42-5892. Captopril, but not Ro 42-5892, increased forearm blood flow (2.4 +/- 0.8 versus 1.9 +/- 0.8 ml/min/100 ml, p less than 0.01) and significantly enhanced the increase of forearm blood flow to brachial artery infusions of bradykinin (0.15, 1.5, 5, 15, and 50 ng/min/100 ml; 5 minutes each) from 744 +/- 632% to 1,383 +/- 514% (p less than 0.01). Furthermore, repeat bradykinin infusions resulted in further decreases of blood pressure (from mean pressure of 71.4 +/- 8.5 to 63.2 +/- 7.6 mm Hg, p less than 0.01) only after captopril. Changes of blood pressure after captopril were unrelated to baseline plasma renin activity but correlated with captopril-induced enhancement of vasodilation to bradykinin (r = 0.68, p less than 0.05).

CONCLUSIONS
The lack of blood pressure effects of renin inhibition in contrast to angiotensin converting enzyme inhibition suggests that the renin-angiotensin system does not contribute significantly to blood pressure control in normotensive, sodium-replete subjects. The hypotensive activity of angiotensin converting enzyme inhibitors may result from additional hormonal effects, for example, inhibition of bradykinin degradation and/or subsequent increases of vasodilating prostaglandins or endothelium-derived relaxing factor(s).
Percutaneous transluminal coronary angioplasty of chronic total occlusions. Primary success, restenosis, and long-term clinical follow-up.
Authors: Ivanhoe R J , Weintraub W S , Douglas J S , Lembo N J , Furman M , Gershony G , Cohen C L , King S B 
Published: June 2012

BACKGROUND
Angioplasty of chronically totally occluded vessels has been associated with a success rate well below and restenosis rate well above that for angioplasty of stenosed segments. However, long-term clinical outcome after successful revascularization of a chronically totally occluded vessel has not been reported in detail.

METHODS AND RESULTS
Accordingly, data for 480 patients undergoing angioplasty for chronic total occlusion at Emory University Hospital, Atlanta, Ga., from 1980 to 1988 were analyzed for predictors of in-hospital procedural and clinical (procedural success and absence of in-hospital complications) success, restenosis, and 4-year clinical follow-up. The study population was grouped by procedural and clinical success and failure. The groups were then compared for outcome, both in hospital and long term. The initial clinical success rate was 66% (317 of 480 patients). Independent correlates of failure were the number of vessels diseased (p less than 0.001), vessel location of the lesion (p = 0.016), and absence of any distal antegrade filling (p = 0.002). Follow-up data revealed 98% cardiac survival and 96% overall survival at 4 years for the group as a whole. Freedom from myocardial infarction or cardiac death was significantly greater in patients with clinical success (93%) than with clinical failure (89%, p = 0.0044). In the successful group, 87% were free from coronary surgery after 4 years compared with 64% in the failure group (p less than 0.0001). Two thirds of the patients were free of angina at last follow-up. The presence of angina at follow-up was the same for patients successfully treated and for those with failed angioplasty, which may be related to the frequent use of coronary surgery in the failure group.

CONCLUSIONS
In well-selected cases, the success rate for angioplasty of chronic total occlusion is acceptable. Furthermore, long-term clinical benefit is suggested by the high freedom from coronary surgery, myocardial infarction, and death in the patients who underwent successful revascularization.
Two-dimensional echocardiographic phase analysis. Its potential for noninvasive localization of accessory pathways in patients with Wolff-Parkinson-White syndrome.
Authors: Kuecherer H F , Abbott J A , Botvinick E H , Scheinman E D , O'Connell J W , Scheinman M M , Foster E , Schiller N B 
Published: June 2012

BACKGROUND
In patients with the preexcitation syndrome who are undergoing transcatheter or surgical ablation, accurate localization of accessory pathways is critical. Because preexcitation is known to alter ventricular activation sequence and result in focal areas with presystolic contraction, we investigated whether phase analysis applied to two-dimensional echocardiographic cine loops objectively identifies these focal areas and can be used to localize ventricular insertion sites of accessory pathways.

METHODS AND RESULTS
We prospectively obtained phase images in 17 patients (11 males; age range, 11-35 years) during minimal preexcitation in normal sinus rhythm and during maximal preexcitation induced by right atrial pacing. A group of 11 normal subjects (six men; age range, 26-37 years) served as controls. Pathway locations predicted from phase imaging were compared with those predicted from routine 12-lead ECGs, from visual inspection of cine loop images, and from catheter-mounted electrode endocardial mapping. Cross-sectional views in a digital cine loop format were mathematically transformed using a first harmonic Fourier algorithm to obtain the corresponding phase images. Phase angle histograms were derived in eight wall segments. Mean and earliest phase angles were derived by computer analysis to quantitate contraction sequence. We found that during right atrial pacing, phase angles in focal areas markedly deviated from normal--mean phase angles from 33 degrees to 164 degrees, and earliest phase angles from 50 degrees to 180 degrees. Accessory pathways could be precisely localized in 53% of the patients by 12-lead ECG, in 59% by visual inspection of cine loop images, in 82% by phase imaging, and in 94% by a combination of the three methods.

CONCLUSIONS
Our results suggest that phase imaging, especially when used in combination with cine loop and 12-lead ECG, can be used to localize ventricular insertion sites of accessory pathways and may be clinically useful as a noninvasive adjunct to endocardial mapping in patients with Wolff-Parkinson-White syndrome.
Preventive administration of intravenous N-acetylcysteine and development of tolerance to isosorbide dinitrate in patients with angina pectoris.
Authors: Boesgaard S , Aldershvile J , Poulsen H E 
Published: June 2012

BACKGROUND
Development of tolerance to organic nitrates may be related to depletion of sulfhydryl groups in vascular smooth muscle. N-Acetylcysteine (NAC), a sulfhydryl donor, has been reported to potentiate the effect of nitroglycerin and reverse tolerance in humans. However, its ability to prevent or delay the development of nitrate tolerance in patients with angina pectoris has not been established.

METHODS AND RESULTS
Ten patients with stable angina pectoris were treated with intravenous isosorbide dinitrate (ISDN; 5 mg/hr) combined with NAC (2 g i.v. over 15 minutes followed by 5 mg/kg/hr) or matching placebo for 30 hours in a double-blind, randomized, crossover study with a washout interval of 8 days. Bicycle exercise tests were performed before and at 1 1/2, 8, 20, 24, and 30 hours after start of treatment. After 24 hours of infusion, exercise parameters were not significantly different from pretreatment values (p greater than 0.05) during ISDN plus placebo, indicating development of tolerance to ISDN. In contrast, time to onset of angina, time to 1-mm ST segment depression, and total amount of ST segment depression were still significantly improved after 24-hour infusion of ISDN plus NAC (p less than 0.05). In addition, compared with placebo, a significant difference (p less than 0.05) in favor of NAC was observed regarding time to angina (507 +/- 63 versus 445 +/- 69 seconds, mean +/- SEM), time to 1-mm ST segment depression (435 +/- 43 versus 407 +/- 45 seconds), and total ST segment depression (1.8 +/- 0.9 versus 3.1 +/- 0.4 mm).

CONCLUSIONS
These results suggest that infusion of high doses of NAC in combination with ISDN for 30 hours affects and partially prevents the development of tolerance to antianginal effects normally observed during infusion with ISDN.
Frequency domain measures of heart period variability and mortality after myocardial infarction.
Authors: Bigger J T , Fleiss J L , Steinman R C , Rolnitzky L M , Kleiger R E , Rottman J N 
Published: June 2012

BACKGROUND
We studied 715 patients 2 weeks after myocardial infarction to establish the associations between six frequency domain measures of heart period variability (HPV) and mortality during 4 years of follow-up.

METHODS AND RESULTS
Each measure of HPV had a significant and at least moderately strong univariate association with all-cause mortality, cardiac death, and arrhythmic death. Power in the lower-frequency bands--ultra low frequency (ULF) and very low frequency (VLF) power--had stronger associations with all three mortality end points than power in the higher-frequency bands--low frequency (LF) and high frequency (HF) power. The 24-hour total power also had a significant and strong association with all three mortality end points. VLF power was the only variable that was more strongly associated with arrhythmic death than with cardiac death or all-cause mortality. In multivariate Cox regression models using a step-up approach to evaluate the independent associations between frequency domain measures of heart period variability and death of all causes, ULF power was selected first (i.e., was the single component with the strongest association). Adding VLF or LF power to the Cox regression model significantly improved the prediction of outcome. With both ULF and VLF power in the Cox regression model, the addition of the other two components, LF and HF power, singly or together, did not significantly improve the prediction of all-cause mortality. We explored the relation between the heart period variability measures and all-cause mortality, cardiac death, and arrhythmic death before and after adjusting for five previously established postinfarction risk predictors: age, New York Heart Association functional class, rales in the coronary care unit, left ventricular ejection fraction, and ventricular arrhythmias detected in a 24-hour Holter ECG recording.

CONCLUSIONS
After adjustment for the five risk predictors, the association between mortality and total, ULF, and VLF power remained significant and strong, whereas LF and HF power were only moderately strongly associated with mortality. The tendency for VLF power to be more strongly associated with arrhythmic death than with all-cause or cardiac death was still evident after adjusting for the five covariates. Adding measures of HPV to previously known predictors of risk after myocardial infarction identifies small subgroups with a 2.5-year mortality risk of approximately 50%.
Evidence for the association of unexplained pulmonary hypertension in children with the major histocompatibility complex.
Authors: Barst R J , Flaster E R , Menon A , Fotino M , Morse J H 
Published: June 2012

BACKGROUND
A link between primary pulmonary hypertension (PPH) and autoimmune disorders has been postulated. To investigate this relation, we performed immunofluorescent antinuclear antibody tests (ANA) and serological human leukocyte antigen (HLA)-A, B, C, DR, and DQ typing on two groups of Caucasian children with unexplained pulmonary hypertension (PHT) and their parents.

METHODS AND RESULTS
Group 1 consisted of 17 children with PPH including two patients with familial PPH and three patients with trivial congenital pulmonary to systemic communications. Group 2 consisted of 13 children with advanced PHT and anatomically large congenital pulmonary to systemic communications (PHT + shunt). Both groups had comparably severe pulmonary vascular disease documented by cardiac catheterization. The following statistically significant data (p less than 0.05) were obtained when the study groups were compared with those published for normal controls. Although positive ANAs and varying titers of autoantibodies were found in both groups of children and mothers (not fathers), +ANAs were only significant for the maternal groups. The PPH (group 1) children had increased frequencies of HLA-DR3, DRw52, and DQw2 and decreased DR5, whereas the group 2 (PHT + shunt) children (also their parents) had no statistically significant alterations in any of the DR or DQ alleles. The PPH mothers had decreased DQw3, an allele in linkage disequilibrium with DR5.

CONCLUSIONS
These immunogenetic data suggest that childhood PPH appears to be associated with the major histocompatibility complex alleles HLA-DR3, DRw52, and DQw2. This newly found correlation of juvenile PPH with these alleles adds this disease to the DR3+ group of autoimmune diseases. Further studies are needed to determine whether there is also an immunological or autoimmune component in some children with PHT + shunt lesions because this group lacked an HLA association.
Imaging of thrombi with tissue-type plasminogen activator rendered enzymatically inactive and conjugated to a residualizing label.
Authors: Ord J M , Hasapes J , Daugherty A , Thorpe S R , Bergmann S R , Sobel B E 
Published: June 2012

BACKGROUND
Contemporary cardiovascular practice relies increasingly on thrombolysis as a therapeutic modality. Its optimal use requires prompt, noninvasive delineation of thrombotic occlusion in arterial beds and rapid detection of reocclusion after initially successful thrombolysis.

METHODS AND RESULTS
We have been developing an approach to noninvasively image thrombi in which plasminogen-activating properties of tissue-type plasminogen activator (t-PA) are attenuated by treatment with D-Phe-L-Pro-L-Arg-chloromethyl ketone (PPACK) and have shown that the inactive t-PA avidly and promptly binds to clots in vitro. In the present study, we conjugated this material to a residualizing label, radioiodinated dilactitol tyramine (*I-DLT), and characterized the potential use of the inactivated, conjugated t-PA as a radiopharmaceutical for imaging thrombi in vivo. The approach developed requires not only avid binding of the tracer to thrombi but also rapid clearance from plasma and a lack of prompt release of radiolabeled degradation products from the liver. The rapid clearance of unaltered or PPACK-treated t-PA was not influenced by conjugation to *I-DLT, but the release of radioiodinated degradation products into plasma after injection of *I-DLT-conjugated t-PA was markedly less than release of degradation products of directly radioiodinated t-PA. When 131I-DLT-PPACK-t-PA was infused for 15 minutes intravenously after a bolus injection of 20% in dogs with coronary, pulmonary, or carotid artery thrombi, clearance was rapid. Mean +/- SEM thrombus-to-blood ratios of radioactivity were high, ranging from 37 +/- 9:1 and 2.8 +/- 0.6:1 with carotid thrombi formed concomitantly or approximately 30 minutes before infusion of tracer, respectively, to 35:1 for concomitantly formed coronary thrombi, 42 +/- 7:1 and 8.1 +/- 0.8:1 for concomitantly formed and preformed pulmonary thrombi, respectively, and 18:1 for a preformed femoral artery thrombus. Thrombi were detectable by planar gamma scintigraphy even though image quality was affected adversely by low concentrations of radioactivity that in aggregate composed a relatively large amount of radioactivity in underlying and overlying tissues. This limitation was overcome by tomographic imaging, which was used to detect both femoral and pulmonary thrombi.

CONCLUSIONS
Use of enzymatically inactivated t-PA coupled to a residualizing label permits rapid detection and localization of thrombi in vivo.