bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography.
Authors: De Bruyne B , Baudhuin T , Melin J A , Pijls N H , Sys S U , Bol A , Paulus W J , Heyndrickx G R , Wijns W 
Published: June 2012

BACKGROUND
Experimental studies have shown that fractional flow reserve (defined as the ratio of maximal achievable flow in a stenotic area to normal maximal achievable flow) can be calculated from coronary pressure measurements only. The objectives of this study were to validate fractional flow reserve calculation in humans and to compare this information with that derived from quantitative coronary angiography.

METHODS AND RESULTS
Twenty-two patients with an isolated, discrete proximal or mid left anterior descending coronary artery stenosis and normal left ventricular function were studied. Relative myocardial flow reserve, defined as the ratio of absolute myocardial perfusion during maximal vasodilation in the stenotic area to the absolute myocardial perfusion during maximal vasodilation (adenosine 140 micrograms.kg-1 x min-1 intravenously during 4 minutes) in the contralateral normally perfused area, was assessed by 15O-labeled water and positron emission tomography (PET). Myocardial and coronary fractional flow reserve were calculated from mean aortic, distal coronary, and right atrial pressures recorded during maximal vasodilation. Distal coronary pressures were measured by an ultrathin, pressure-monitoring guide wire with minimal influence on the trans-stenotic pressure gradient. Minimal obstruction area, percent area stenosis, and calculated stenosis flow reserve were assessed by quantitative coronary angiography. There was no difference in heart rate, mean aortic pressure, or rate-pressure product during maximal vasodilation during PET and during catheterization. Percent area stenosis ranged from 40% to 94% (mean, 77 +/- 13%), myocardial fractional flow reserve from 0.36 to 0.98 (mean, 0.61 +/- 0.17), and relative flow reserve from 0.27 to 1.23 (mean, 0.60 +/- 0.26). A close correlation was found between relative flow reserve obtained by PET and both myocardial fractional flow reserve (r = .87) and coronary fractional flow reserve obtained by pressure recordings (r = .86). The correlations between relative flow reserve obtained by PET and stenosis measurements derived from quantitative coronary angiography were markedly weaker (minimal obstruction area, r = .66; percent area stenosis, r = -.70; and stenosis flow reserve, r = .68).

CONCLUSIONS
Fractional flow reserve derived from pressure measurements correlates more closely to relative flow reserve derived from PET than angiographic parameters. This validates in humans the use of fractional flow reserve as an index of the physiological consequences of a given coronary artery stenosis.
Reflex versus tonic vagal activity as a prognostic parameter in patients with sustained ventricular tachycardia or ventricular fibrillation.
Authors: Hohnloser S H , Klingenheben T , van de Loo A , Hablawetz E , Just H , Schwartz P J 
Published: June 2012

BACKGROUND
The autonomic nervous system has been demonstrated to play a decisive role in the genesis of sudden cardiac death. The loss of protective vagal reflexes, in particular, appears to be associated with an increased incidence of malignant ventricular tachyarrhythmias. Two clinically applicable methods for assessment of cardiac autonomic control have been developed: determination of heart rate variability and evaluation of baroreflex sensitivity.

METHODS AND RESULTS
To compare the potential predictive value of both methods, two groups of patients were studied. Group 1 comprised 14 postinfarction patients who had experienced at least one episode of ventricular fibrillation or sustained ventricular tachycardia and who were studied after this event. Group 2 consisted of 14 postinfarction patients without tachyarrhythmic events after their infarct. Both groups were carefully matched with respect to age, sex, infarct location, extent of coronary artery disease, left ventricular ejection fraction, blood pressure, and heart rate at rest. Heart rate variability was assessed from 24-hour Holter recordings, and baroreflex sensitivity was determined by means of the phenylephrine method. Indices of heart rate variability were not significantly different between the two groups (SD of the mean RR interval, 84 +/- 30 milliseconds versus 103 +/- 20 milliseconds; proportion of adjacent RR intervals > 50 milliseconds different, 2.8 +/- 3.2% versus 5.0 +/- 4.1% in group 1 versus 2). Baroreflex sensitivity, however, showed a striking difference: Group 1 patients had a mean value of 1.75 +/- 1.63 ms/mm Hg compared with 9.17 +/- 5.40 ms/mm Hg in group 2 (P = .0002). Eleven of 14 group 1 patients had a baroreflex sensitivity < or = 3.0 ms/mm Hg. By contrast, only 1 of 14 group 2 patients had such a depressed value.

CONCLUSIONS
The results of this study indicate that postmyocardial infarction patients who develop life-threatening ventricular tachyarrhythmias, compared with carefully matched postinfarction patients without major arrhythmic episodes, differ strikingly in terms of baroreflex sensitivity but not in terms of heart rate variability. This finding may have implications for the risk stratification of postinfarction patients and may lead to a differential therapeutic strategy based on autonomic testing.
Relation of regional cross-fiber shortening to wall thickening in the intact heart. Three-dimensional strain analysis by NMR tagging.
Authors: Rademakers F E , Rogers W J , Guier W H , Hutchins G M , Siu C O , Weisfeldt M L , Weiss J L , Shapiro E P 
Published: June 2012

BACKGROUND
The mechanism by which small amounts of myofiber shortening lead to extensive wall thickening is unknown. When isolated fibers shorten, they thicken in the two orthogonal directions. In situ fibers, however, vary in their orientation through the wall, and each is tethered to near or distant neighbors, which allows shortening to occur both in the direction of the fibers and also perpendicular to them. This "cross-fiber" shortening may enable the wall to shorten in two directions and thereby thicken extensively in the third.

METHODS AND RESULTS
Nuclear magnetic resonance tagging is a noninvasive method of labeling and tracking myocardium of the entire heart in three dimensions that does not interfere with myocardial motion. To investigate the presence and importance of cross-fiber shortening in the intact left ventricle, 10 closed-chest dogs were studied by nuclear magnetic resonance tagging. Five short-axis and four long-axis images were acquired to reconstruct 32 cubes of myocardium in each dog at end diastole and end systole. Pathological dissection was performed to determine the fiber direction at the epicardium, midwall, and endocardium of each cube. Strain was computed from the three-dimensional cube coordinates in the fiber and cross-fiber directions for epicardial and endocardial surfaces, and thickening of the full wall and its epicardial and endocardial halves was determined. Shear deformations were also calculated. Fiber strain at the epicardium and endocardium was -6.4 +/- 0.7% and -8.5 +/- 0.6% (mean +/- SEM), respectively (difference, P > .05). Cross-fiber strain at epicardium and endocardium was -0.6 +/- 0.5% and -25 +/- 0.6%, respectively (difference, P < .05). Thickening of the full wall reached 32.5 +/- 1.0%, composed of epicardial thickening of 25.5 +/- 0.6% and endocardial thickening of 43.3 +/- 1.0% (difference, P < .05). Fiber/cross-fiber shear strain was small (< 3%). Significant regional differences were present in all strains. A significant correlation was found between the extents of regional thickening and cross-fiber shortening.

CONCLUSIONS
Cross-fiber shortening at the endocardium, therefore, far exceeds cross-fiber shortening at the epicardium and fiber shortening at both epicardium and endocardium. Since no active shortening can occur locally in the cross-fiber direction, the extensive endocardial cross-fiber shortening must result from interaction with differently aligned fibers at a distance. The correlation between regional thickening and cross-fiber shortening supports the hypothesis that this interaction is the mechanism for amplifying small amounts of fiber shortening to cause extensive endocardial thickening.
Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels.
Authors: Seo B , Oemar B S , Siebenmann R , von Segesser L , Lüscher T F 
Published: June 2012

BACKGROUND
Endothelin (ET)-1 has potent vascular effects. Two endothelin receptors have been cloned, namely, the ETA receptor, which preferentially binds ET-1, and the ETB receptor, which equally binds ET-1 and ET-3 and preferentially sarafotoxin S6c. We characterized endothelin receptor subtypes on vascular smooth muscle and endothelium of isolated human internal mammary artery (IMA) and vein (IMV) and porcine coronary artery (PCA) using the ETA antagonists FR139317 and BQ-123, the ETB ligand sarafotoxin S6c, and the ETA/ETB antagonist Ro 47-0203 (bosentan).

METHODS AND RESULTS
In endothelium-denuded IMA and PCA and less so in IMV, FR139317 and BQ-123 (in PCA only) shifted the concentration-contraction curves to ET-1 parallel to the right. However, even at 10(-5) mol/L, FR139317 did not inhibit a high-sensitivity portion of the concentration-contraction curve. Moreover, the ETB receptor agonist sarafotoxin S6c induced contraction in vessels preincubated with FR139317. IMV was significantly more sensitive to the contractile effect of ET-1 and sarafotoxin S6c than was IMA (P < .05). Prolonged incubation with sarafotoxin S6c (to downregulate ETB receptors) and FR139317 eliminated the contraction resistant to FR139317. The ETA/ETB receptor antagonist bosentan caused a parallel shift of the concentration-contraction curve to the right at all concentrations of endothelin. ETB receptor mRNA was detected by Northern blot analysis in IMA and aortic smooth muscle cells. In precontracted IMA and PCA with endothelium, sarafotoxin S6c did not cause endothelium-dependent relaxations, whereas transient responses occurred in IMV.

CONCLUSIONS
Vascular smooth muscle cells of human IMA, IMV, and PCA contain both ETA and ETB receptors, whereas the endothelium of IMA and PCA does not express functional ETB receptors linked to nitric oxide and/or prostacyclin production. Hence, inhibition of endothelin-induced contraction in patients requires the use of combined ETA/ETB antagonists.
Endogenous adenosine does not activate ATP-sensitive potassium channels in the hypoxic guinea pig ventricle in vivo.
Authors: Xu J , Wang L , Hurt C M , Pelleg A 
Published: June 2012

BACKGROUND
The activation of ATP-sensitive K+ (K+ ATP) channels by K+ ATP openers, eg, pinacidil, hypoxia, and ischemia, is known to shorten the ventricular action potential. Since adenosine is released in increased amounts during cardiac hypoxia and ischemia, the hypothesis that endogenous adenosine activates K+ ATP channels was tested in vivo in a guinea pig model.

METHODS AND RESULTS
Anesthetized animals (n = 37) were subjected to transient acute global hypoxia by ventilation with 100% N2. Monophasic action potentials (MAP) were recorded in ventricular and atrial myocardium by use of custom-made Ag/AgCl electrode catheters. In addition, right atrial and left ventricular electrograms as well as systemic arterial blood pressure were monitored throughout the experiments. Under normoxic conditions, pinacidil (1.8 microgram/kg i.v., n = 8), a K+ ATP channel opener, shortened ventricular MAP duration (APD); this effect was reversed by glibenclamide, a potent K+ ATP channel blocker, but not by 8-cyclopentyl-1,3-dimethylxanthine (CPT), a potent A1-selective adenosine antagonist. Global hypoxia shortened atrial and ventricular APD. Glibenclamide but not CPT reversed this effect of hypoxia on ventricular but not atrial MAP. CPT but not glibenclamide reversed the effect of hypoxia on atrial MAP. In addition, CPT delayed the appearance of the atrioventricular (AV) nodal conduction block associated with global hypoxia. Finally, the ability of CPT to selectively attenuate A1-adenosine receptor-mediated effects of adenosine agonists in ventricular and supraventricular tissues was confirmed in 17 animals. CPT reversed the negative dromotropic effect of adenosine on AV nodal conduction and the antiadrenergic effect of N6-cyclopentyladenosine (CPA) mediated by A1-adenosine receptor but not the adenosine-induced decrease in systemic blood pressure caused by the vasodilatory action of the nucleoside mediated by A2-adenosine receptor.

CONCLUSIONS
(1) Endogenous adenosine released during global cardiac hypoxia mediates, in part, AV nodal conduction delay and shortening of atrial but not ventricular APD. (2) The action of adenosine on atrial APD is mediated by A1 adenosine receptors, probably via IK,Ado,Ach. (3) Endogenous adenosine apparently does not play an important role in the early stages of acute global hypoxia-induced activation of K+ ATP channels. The present results are consistent with the hypothesis that the shortening of ventricular APD in the hypoxic heart is due, in part, to activation of K+ ATP channels.
Infarct size-limiting effect of ischemic preconditioning is blunted by inhibition of 5'-nucleotidase activity and attenuation of adenosine release.
Authors: Kitakaze M , Hori M , Morioka T , Minamino T , Takashima S , Sato H , Shinozaki Y , Chujo M , Mori H , Inoue M 
Published: June 2012

BACKGROUND
We have previously reported that ischemic preconditioning increases 5'-nucleotidase activity and adenosine release during ischemia and reperfusion. However, its direct cause-and-effect relation has not been proven. To test the idea that the infarct size-limiting effect of ischemic preconditioning is blunted by inhibition of ectosolic 5'-nucleotidase activity, we assessed 5'-nucleotidase activity, adenosine release, and infarct size caused by sustained ischemia with and without an exposure to alpha,beta,-methylene adenosine 5'-diphosphate (AOPCP) in the ischemia-preconditioned myocardium.

METHODS AND RESULTS
In 67 open-chest dogs, the left anterior descending coronary artery was cannulated and perfused with an extracorporeal bypass tube from the carotid artery. After hemodynamic stabilization, the coronary artery was occluded four times for 5 minutes separated by 5 minutes of reperfusion (ischemic preconditioning, n = 10). After this procedure, the coronary artery was occluded for 90 minutes followed by 6 hours of reperfusion. Infarct size normalized by the risk area was smaller than the control group (n = 8, 41.0 +/- 2.6% versus 6.8 +/- 1.9%), although there were no significant differences in the endomyocardial collateral flow measured at 80 minutes of ischemia (8.5 +/- 1.1 versus 9.4 +/- 1.0 mL/100 g per minute). Ectosolic and cytosolic 5'-nucleotidase activity and adenosine release were increased during reperfusion in the ischemic preconditioning group compared with the control group, and the activity of ectosolic 5'-nucleotidase was markedly reduced by AOPCP (n = 10). AOPCP affected neither adenosine-induced coronary vasodilation nor increases in myocardial oxygen consumption during an intracoronary infusion of isoproterenol (n = 10). To test whether the increase in 5'-nucleotidase activity decreases infarct size, we infused AOPCP 10 minutes before the ischemic preconditioning procedure and continued for 60 minutes after the onset of reperfusion (n = 8). AOPCP blunted the infarct size-limiting effect (infarct size, 38.8 +/- 4.9%). AOPCP without ischemic preconditioning did not increase infarct size (n = 9). Furthermore, when AOPCP was infused during the ischemic preconditioning procedure (n = 6) or during 60 minutes of reperfusion (n = 6), the infarct size-limiting effect was partially blunted (infarct size, 21.3 +/- 2.5% and 19.5 +/- 2.4%, respectively).

CONCLUSIONS
Increases in ectosolic 5'-nucleotidase activity and adenosine release are primarily responsible for the infarct size-limiting effect of ischemic preconditioning. Exposures to adenosine during the ischemic preconditioning procedure and enhanced release of adenosine during reperfusion synergistically contribute to the infarct size-limiting effects.
Specific factor Xa inhibition reduces restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.
Authors: Ragosta M , Gimple L W , Gertz S D , Dunwiddie C T , Vlasuk G P , Haber H L , Powers E R , Roberts W C , Sarembock I J 
Published: June 2012

BACKGROUND
Balloon angioplasty of atherosclerotic arteries results in activation of the coagulation cascade. Several coagulation factors, including factor Xa and thrombin, are mitogenic for vascular smooth muscle cells in vitro and thus may play a role in restenosis after balloon angioplasty. Specific inhibition of factor Xa can be achieved with recombinant antistasin (rATS) or tick anticoagulant peptide (rTAP). We hypothesized that inhibition of Xa would limit restenosis after balloon angioplasty in an atherosclerotic rabbit model.

METHODS AND RESULTS
Focal femoral atherosclerosis was induced by air desiccation injury and a high-cholesterol diet in 38 New Zealand White rabbits. Recombinant antistasin (n = 20 arteries) or rTAP (n = 14 arteries) was administered by intravenous bolus at the time of balloon angioplasty and followed by a 2-hour infusion; controls (n = 21 arteries) received bolus heparin alone (150 U/kg). Therapeutic prolongation of the activated partial thromboplastin time occurred, and antithrombotic drug levels were achieved in all animals. Luminal diameter in millimeters by quantitative angiography did not differ between treatment groups before (1.1 +/- 0.2 for controls, 1.1 +/- 0.2 for rATS, and 1.1 +/- 0.3 for rTAP) or after balloon angioplasty (1.5 +/- 0.3 for controls, 1.4 +/- 0.2 for rATS, and 1.4 +/- 0.2 for rTAP). At 28 days, treatment with factor Xa inhibitors tended to result in arteries with larger luminal diameter than controls (1.2 +/- 0.3 for rATS, 1.2 +/- 0.3 for rTAP versus 1.0 +/- 0.3 for control, P = .09 by one-way ANOVA). Restenosis, defined as reduction in angiographic luminal diameter (in mm) from 2 hours after angioplasty to 28 days after angioplasty was less in the rATS group than in controls (-0.2 +/- 0.1 versus -0.5 +/- 0.4, P < .001) and tended to be less in the rTAP group (-0.3 +/- 0.2 versus -0.5 +/- 0.4, P = .07). Quantitative histopathological analysis showed less percent cross-sectional area narrowing by plaque in both rATS- and rTAP-treated arteries compared with controls (42 +/- 21%, 47 +/- 18%, and 63 +/- 14%, respectively; P < .01 by one-way ANOVA).

CONCLUSIONS
We conclude that a 2-hour infusion of rATS or rTAP reduced angiographic restenosis and resulted in less luminal cross-sectional narrowing by plaque compared with controls.
Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. The Stanford Coronary Risk Intervention Project (SCRIP).
Authors: Haskell W L , Alderman E L , Fair J M , Maron D J , Mackey S F , Superko H R , Williams P T , Johnstone I M , Champagne M A , Krauss R M 
Published: June 2012

BACKGROUND
Recent clinical trials have shown that modification of plasma lipoprotein concentrations can favorably alter progression of coronary atherosclerosis, but no data exist on the effects of a comprehensive program of risk reduction involving both changes in lifestyle and medications. This study tested the hypothesis that intensive multiple risk factor reduction over 4 years would significantly reduce the rate of progression of atherosclerosis in the coronary arteries of men and women compared with subjects randomly assigned to the usual care of their physician.

METHODS AND RESULTS
Three hundred men (n = 259) and women (n = 41) (mean age, 56 +/- 7.4 years) with angiographically defined coronary atherosclerosis were randomly assigned to usual care (n = 155) or multifactor risk reduction (n = 145). Patients assigned to risk reduction were provided individualized programs involving a low-fat and -cholesterol diet, exercise, weight loss, smoking cessation, and medications to favorably alter lipoprotein profiles. Computer-assisted quantitative coronary arteriography was performed at baseline and after 4 years. The main angiographic outcome was the rate of change in the minimal diameter of diseased segments. All subjects underwent medical and risk factor evaluations at baseline and yearly for 4 years, and reasons for all hospitalizations and deaths were documented. Of the 300 subjects randomized, 274 (91.3%) completed a follow-up arteriogram, and 246 (82%) had comparative measurements of segments with visible disease at baseline and follow-up. Intensive risk reduction resulted in highly significant improvements in various risk factors, including low-density lipoprotein cholesterol and apolipoprotein B (both, 22%), high-density lipoprotein cholesterol (+12%), plasma triglycerides (-20%), body weight (-4%), exercise capacity (+20%), and intake of dietary fat (-24%) and cholesterol (-40%) compared with relatively small changes in the usual-care group. No change was observed in lipoprotein(a) in either group. The risk-reduction group showed a rate of narrowing of diseased coronary artery segments that was 47% less than that for subjects in the usual-care group (change in minimal diameter, -0.024 +/- 0.066 mm/y versus -0.045 +/- 0.073 mm/y; P < .02, two-tailed). Three deaths occurred in each group. There were 25 hospitalizations in the risk-reduction group initiated by clinical cardiac events compared with 44 in the usual-care group (rate ratio, 0.61; P = .05; 95% confidence interval, 0.4 to 0.9).

CONCLUSIONS
Intensive multifactor risk reduction conducted over 4 years favorably altered the rate of luminal narrowing in coronary arteries of men and women with coronary artery disease and decreased hospitalizations for clinical cardiac events.
Heparin neutralization by platelet-rich thrombi. Role of platelet factor 4.
Authors: Eitzman D T , Chi L , Saggin L , Schwartz R S , Lucchesi B R , Fay W P 
Published: June 2012

BACKGROUND
Platelets contain several factors that inhibit heparin. This study was designed to assess the heparin-neutralizing activity present in acute, platelet-rich arterial thrombi formed at sites of arterial injury in animals.

METHODS AND RESULTS
Platelet-rich thrombi (n = 3) were induced in pig coronary arteries by balloon catheter-mediated arterial injury. Soluble extracts were prepared from each thrombus and assayed for the capacity to inhibit heparin in an in vitro clotting assay (activated partial thromboplastin time). Mean heparin-neutralizing activity was 28 U of heparin neutralized per milliliter of thrombus, indicating that 1 vol of coronary thrombus completely inhibited the heparin present in 140 vols of therapeutically anticoagulated (0.2 U heparin/mL) plasma. In contrast, thrombus extracts had no effect on the anticoagulant activity of hirudin, a direct-acting thrombin inhibitor. The heparin-neutralizing activity present in coronary thrombi bound to heparin-agarose and was eluted from it by 1.4 mol/L NaCl, suggesting that platelet factor 4 mediated the antiheparin effect of thrombi. Consistent with this hypothesis, a murine monoclonal antibody to rabbit platelet factor 4 nearly completely inhibited the heparin-neutralizing activity present in rabbit thrombi (n = 3) generated by carotid artery injury.

CONCLUSIONS
Extracts prepared from platelet-rich arterial thrombi significantly inhibit the in vitro anticoagulant potency of heparin but not of hirudin. This antiheparin effect appears to be mediated by platelet factor 4. These results are consistent with the hypothesis that localized inhibition of heparin at sites of platelet activation may reduce its antithrombotic efficacy. In addition, they suggest an additional mechanism for the apparent superiority of hirudin over heparin as a thrombin inhibitor at sites of arterial injury.