bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasminogen activator inhibitor-1 suppresses endogenous fibrinolysis in a canine model of pulmonary embolism.
Authors: Reilly C F , Fujita T , Hutzelmann J E , Mayer E J , Shebuski R J 
Published: June 2012

BACKGROUND
Plasminogen activator inhibitor-1 (PAI-1), the specific, fast-acting inhibitor of tissue-type plasminogen activator (t-PA), binds to fibrin and has been found in high concentrations within arterial thrombi. These findings suggest that the localization of PAI-1 to a thrombus protects that same thrombus from fibrinolysis. In this study, clot-bound PAI-1 was assessed for its ability to suppress clot lysis in vivo.

METHODS AND RESULTS
Autologous, canine whole blood clots were formed in the presence of increasing amounts of activated PAI-1 (0-30 micrograms/ml). Approximately 6-8% of the PAI-1 bound to the clots under the experimental conditions. Control and PAI-1-enriched clots containing iodine-125-labeled fibrin (ogen) were homogenized, washed to remove nonbound elements, and delivered to the lungs of anesthetized dogs where the homogenates subsequently underwent lysis by the endogeneous fibrinolytic system. 125I-labeled fibrin degradation products appeared in the blood of control animals within 10 minutes and were maximal by 90 minutes. PAI-1 reduced fibrin degradation product release in a dose-responsive manner at all times between 30 minutes and 5 hours (greater than or equal to 76% inhibition at 30 minutes, PAI-1 greater than or equal to 6 micrograms/ml). PAI-1 also suppressed D-dimer release from clots containing small amounts of human fibrin (ogen). t-PA administration attenuated the effects of PAI-1, whereas latent PAI-1 (20 micrograms/ml) had no effect on clot lysis. Blood levels of PA and PAI activity remained unaltered during these experiments.

CONCLUSIONS
The results indicate that PAI-1 markedly inhibits endogenous fibrinolysis in vivo and, moreover, suggest that the localization of PAI-1 to a forming thrombus is an important physiological mechanism for subsequent thrombus stabilization.
Diastolic perfusion time at ischemic threshold in patients with stress-induced ischemia.
Authors: Ferro G , Spinelli L , Duilio C , Spadafora M , Guarnaccia F , Condorelli M 
Published: June 2012

BACKGROUND
To evaluate the relevance of diastolic perfusion time on the mechanisms underlying stress-induced ischemia, 16 patients with coronary artery disease and seven patients with syndrome X underwent five randomized stress tests (upright and supine exercise with and without therapy, transesophageal atrial pacing).

METHODS AND RESULTS
Exercise duration Time to 0.1 mV ST segment depression, heart rate, rate-pressure product, and diastolic perfusion time were evaluated for each patient during stress tests. In both groups, variability coefficients of the above-mentioned parameters were not different at rest. At ischemic threshold (0.1 mV ST segment depression) in patients with coronary artery disease, the variability coefficient of exercise duration (40.1 +/- 22.2) was significantly higher (p less than 0.0001) than those of heart rate (12.8 +/- 2.9), rate-pressure product (14.8 +/- 3.3), and diastolic perfusion time (0.39 +/- 0.1). The variability coefficient of diastolic perfusion time was also significantly (p less than 0.0001) lower than those of heart rate and rate-pressure product. Similarly, the variability coefficient of diastolic perfusion time (0.44 +/- 0.1) in syndrome X patients was significantly lower (p less than 0.0001) than those of exercise duration (28.2 +/- 9.4), heart rate (12 +/- 1.4), and rate-pressure product (14.6 +/- 1.3).

CONCLUSIONS
Fixed diastolic perfusion time at ischemic threshold, despite different kinds of stress tests and variability of heart rate and rate-pressure product, indicates the relevant role of diastolic perfusion time in determining myocardial ischemia.
Hemodynamics and coronary blood flow during exercise after coronary artery bypass grafting with internal mammary arteries in children with Kawasaki disease.
Authors: Kawachi K , Kitamura S , Seki T , Morita R , Kawata T , Hasegawa J , Kameda Y 
Published: June 2012

BACKGROUND
Saphenous vein grafts (SVG) and internal mammary artery (IMA) grafts have been used for coronary artery bypass grafting. In adult patients with bypass grafting for atherosclerotic coronary artery disease, IMA grafts have been reported to have long-term patency; however, results are conflicting on whether the graft is sufficient to meet increased myocardial oxygen demand during exercise. There have been no studies on hemodynamics and blood flow during exercise after bypass grafting with IMA in pediatric patients with Kawasaki disease.

METHODS AND RESULTS
We studied 17 pediatric patients with Kawasaki disease (average age, 7.5 +/- 3.1 years), who underwent coronary artery bypass grafting with the IMA. The average number of coronary artery bypass grafts was 2.1 +/- 0.7/patient. For all patients, the left IMA was anastomosed to the left anterior descending coronary artery; for eight patients, the right IMA was also anastomosed to the right coronary artery. In addition, 11 SVGs were used. The postoperative patency rates after 1 month were 100% with the IMA graft and 91% with SVG. One year after the operation, the patency rates were 100% with IMA and 50% with SVG. Hemodynamics during exercise were measured with a bicycle ergometer, and coronary sinus blood flow was measured by the continuous thermodilution method in six patients. The relation between delta LVEDP (the difference between left ventricular end-diastolic pressure at rest and during exercise) and delta SVI (the difference between the stroke volume index at rest and during exercise) was analyzed. Four of six patients had reduced cardiac function before operation (delta LVEDP, positive; delta SVI, negative). However, after the operation, all patients demonstrated improvements in cardiac function during exercise (delta LVEDP, positive; delta SVI, positive). Coronary sinus flow per left ventricular mass increased after operation from 70 +/- 46 to 87 +/- 56 ml/min at rest (p less than 0.05) and from 139 +/- 118 to 183 +/- 150 ml/min during exercise (p less than 0.05).

CONCLUSIONS
In conclusion, this study reveals improvements in both hemodynamics and coronary blood flow during exercise after coronary artery bypass grafting with IMA grafts in pediatric patients with Kawasaki disease.
Relation of stenosis morphology and clinical presentation to the procedural results of directional coronary atherectomy.
Authors: Ellis S G , De Cesare N B , Pinkerton C A , Whitlow P , King S B , Ghazzel Z M , Kereiakes D J , Popma J J , Menke K K , Topol E J 
Published: June 2012

BACKGROUND
Directional coronary atherectomy has recently become available to treat coronary stenoses. This study was performed to determine the relation of patient characteristics and stenosis morphology to procedural outcome with directional coronary atherectomy to gain insight into which patients might be best treated with this device.

METHODS AND RESULTS
Four hundred stenoses from 378 patients consecutively treated at six major referral institutions were analyzed. Angiographic data were assessed at a central angiographic laboratory using standardized morphological criteria and computer-assisted quantitative dimensional analyses. Procedural success was achieved in 87.8% of stenoses, and major ischemic complications (death, myocardial infarction, and emergency bypass surgery) occurred in 6.3% of patients. Lesion success and complications were closely correlated with recognized modified American College of Cardiology/American Heart Association Task Force lesion morphological criteria. Observed for type A stenoses were 93% success and 3% complication rates; for type B1 stenoses, 88% success and 6% complication rates; and for type B2 stenoses, 75% success and 13% complication rates, respectively. There were too few type C stenoses treated to analyze. Furthermore, multivariate testing demonstrated stenosis angulation (multivariate p less than 0.001), proximal tortuosity (p less than 0.001), decreased preatherectomy minimum lumen dimension (p = 0.032), and calcification (p = 0.041) to correlate independently with adverse outcome and complex, probably thrombus-associated stenoses to have a favorable outcome (p = 0.055). Operator experience (p = 0.020) and a history of restenosis (p = 0.022) also favorably influenced outcome.

CONCLUSIONS
The procedural outcome of directional coronary atherectomy is highly associated with coronary stenosis morphology. Furthermore, after appropriate stratification for morphology and clinical presentation, overall atherectomy procedural outcome may be similar to that achieved with coronary angioplasty. However, specific subsets of patients may have relatively better outcome with either atherectomy or balloon angioplasty.
Electrode system influence on biphasic waveform defibrillation efficacy in humans.
Authors: Bardy G H , Troutman C , Johnson G , Mehra R , Poole J E , Dolack G L , Kudenchuk P J , Gartman D M 
Published: June 2012

BACKGROUND
Several clinical studies have demonstrated a general superiority of biphasic waveform defibrillation compared with monophasic waveform defibrillation using epicardial lead systems. To test the breadth of utility of biphasic waveforms in humans, a prospective, randomized evaluation of defibrillation efficacy of monophasic and single capacitor biphasic waveform pulses was performed for two distinct nonthoracotomy lead systems as well as for an epicardial electrode system in 51 cardiac arrest survivors undergoing automatic defibrillator implantation.

METHODS AND RESULTS
The configurations tested consisted of a right ventricular-left ventricular (RV-LV) epicardial patch-patch system, an RV catheter-chest patch (CP) nonthoracotomy system, and a coronary sinus (CS) catheter-RV catheter nonthoracotomy system. For each configuration, the defibrillation current and voltage waveforms were recorded via a digital oscilloscope to measure defibrillation threshold voltage, current, resistance, and stored energy. Biphasic waveform defibrillation proved more efficient than monophasic waveform defibrillation for the epicardial RV-LV system (4.8 +/- 4.1 versus 6.7 +/- 4.9 J, p = 0.047) and the nonthoracotomy RV-CP system (23.4 +/- 11.1 versus 34.3 +/- 10.4 J, p = 0.0042). Biphasic waveform defibrillation thresholds were not significantly lower than monophasic waveform defibrillation thresholds for the CS-RV nonthoracotomy system (15.6 +/- 7.2 versus 20.0 +/- 11.5 J, p = 0.11). Biphasic waveform defibrillation proved more efficacious than monophasic waveform defibrillation in 13 of 20 patients (65%) with RV-LV epicardial patches, 10 of 15 patients (67%) with an RV-CP nonthoracotomy system, and nine of 16 patients (56%) with an RV-CS nonthoracotomy system.

CONCLUSIONS
Biphasic pulsing was useful with nonthoracotomy lead systems as well as with epicardial lead systems. However, the degree of biphasic waveform defibrillation superiority appeared to be electrode system dependent. Furthermore, for a few individuals, biphasic waveform defibrillation proved less efficient than monophasic waveform defibrillation, regardless of the lead system used.
Abnormal vascular responses to supine exercise in hypertrophic cardiomyopathy.
Authors: Counihan P J , Frenneaux M P , Webb D J , McKenna W J 
Published: June 2012

BACKGROUND
Exercise hypotension has been documented in hypertrophic cardiomyopathy. It is not the result of an inability to augment cardiac output but instead relates to an inappropriate and exaggerated decrease in systemic vascular resistance at high work loads.

METHODS AND RESULTS
To enable us to examine the behavior of the peripheral vasculature during exercise, 103 consecutive patients underwent maximal symptom-limited supine bicycle exercise with measurement of forearm blood flow. A minimum reduction of 12% from the basal value was defined as a normal response based on the study of 25 normal controls. In the patients, two patterns of forearm blood flow were observed. Sixty-four patients had an appropriate reduction in forearm blood flow of 40 +/- 16% from resting flow. In 39 patients, the forearm blood flow either failed to decrease or increased with exercise by 45 +/- 105% of the resting value. Patients with an abnormal forearm vasodilator response were younger (31 +/- 13 versus 46 +/- 14 years), and more of them had a family history of hypertrophic cardiomyopathy and sudden death than did those with a normal vasoconstrictor response (16 of 39 versus eight of 64). Left ventricular end-diastolic cavity dimensions were smaller in those with an abnormal forearm blood flow response, but other clinical, echocardiographic, and arrhythmic variables were similar. To assess the relation of abnormal peripheral vascular responses to erect exercise blood pressure response, patients underwent treadmill exercise testing with careful monitoring of systolic blood pressure response. Thirty-eight patients had significant exercise hypotension with failure of the systolic blood pressure to increase during progressive exercise (n = 6) or an abrupt decrease in systolic blood pressure (20-60 mm Hg) from the peak value (n = 32); 65 patients had a normal exercise blood pressure response, but 18 of these patients had an oscillation in systolic blood pressure of 10 mm Hg or more early in the recovery phase. Thirty-one of 39 patients with an abnormal forearm blood flow response demonstrated exercise hypotension during the erect exercise testing, and the remaining eight patients had a normal exercise blood pressure response; however, five of these eight had abnormal oscillations in blood pressure during recovery (r = 0.61, p less than 0.001).

CONCLUSIONS
The relation of abnormal peripheral vascular responses to exercise hypotension confirms the observation of hemodynamic instability in patients with hypertrophic cardiomyopathy. The finding of abnormal vascular responses in patients known to be at increased risk (young age and a family history of hypertrophic cardiomyopathy and sudden death) suggests that hemodynamic mechanisms may be important in the occurrence of sudden death in hypertrophic cardiomyopathy.
Combination balloon-ultrasound imaging catheter for percutaneous transluminal angioplasty. Validation of imaging, analysis of recoil, and identification of plaque fracture.
Authors: Isner J M , Rosenfield K , Losordo D W , Rose L , Langevin R E , Razvi S , Kosowsky B D 
Published: June 2012

BACKGROUND
We investigated the hypothesis that an ultrasound transducer positioned within an angioplasty balloon could be used to perform quantitative assessment of arterial dimensions before and after percutaneous transluminal angioplasty (PTA) and to identify certain mechanical alterations consequent to PTA, including vascular wall recoil and the initiation of plaque fractures.

METHODS AND RESULTS
A combination balloon-ultrasound imaging catheter (BUIC) that houses a 20-MHz ultrasound transducer within and halfway between the proximal and distal ends of an angioplasty balloon was used to perform PTA in 10 patients with peripheral vascular disease. Each PTA site was also evaluated before and after PTA by standard (nonballoon) intravascular ultrasound (IVUS) technique. In eight patients in whom satisfactory images were recorded with the BUIC before PTA, luminal cross-sectional area (XSA) of stenotic sites (0.10 +/- 0.01 cm2) did not differ significantly from measurements of XSA by IVUS (0.09 +/- 0.01 cm2, p = NS). Likewise, minimum luminal diameter (Dmin) measured by BUIC (0.34 +/- 0.02 cm) was similar to that measured by IVUS (0.33 +/- 0.01 cm, p = NS). In nine patients in whom satisfactory images were recorded with the BUIC after PTA, XSA measured by BUIC (0.29 +/- 0.03 cm2) did not differ significantly from XSA measured by IVUS (0.30 +/- 0.03 cm2, p = NS). Dmin measured by BUIC after PTA (0.57 +/- 0.02 cm) was also similar to Dmin measured by IVUS (0.57 +/- 0.03 cm, p = NS). After PTA, XSA and Dmin measured immediately after deflation were significantly less than balloon XSA and diameter at full inflation, indicating significant elastic recoil of the dilated site. For the nine patients in whom post-PTA images were satisfactory for quantitative analysis, including four patients in whom recoil was 39%, 46%, 50%, and 61%, percent recoil measured 28.6 +/- 7.2%. Finally, plaque fractures were identified on-line in six of 10 patients (60%); in each case, initiation of plaque fracture was observed at inflation pressures of 2 atm or less.

CONCLUSIONS
The results of this preliminary human investigation indicate that an ultrasound transducer positioned within an angioplasty balloon can be used to perform quantitative and qualitative analyses of lumen-plaque-wall alterations immediately preceding, during, and immediately after PTA in patients with peripheral vascular disease.
Effects of milrinone on left ventricular remodeling after acute myocardial infarction.
Authors: Jain P , Brown E J , Langenback E G , Raeder E , Lillis O , Halpern J , Mannisi J A 
Published: June 2012

BACKGROUND
Left ventricular remodeling after an acute myocardial infarction may result in progressive left ventricular dilation that may be associated with increased mortality. We studied the effects of the phosphodiesterase inhibitor milrinone on left ventricular remodeling after acute myocardial infarction.

METHODS AND RESULTS
Rats (n = 90) were randomized to undergo either left coronary artery ligation or sham operation. Three weeks after surgery, rats received either no treatment or milrinone, which was continued until 2 days before the rats were killed. Ninety days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Compared with untreated infarcted rats, milrinone-treated infarcted rats had a lower left ventricular end-diastolic pressure (1.7 +/- 0.4 versus 4.3 +/- 1.4 mm Hg, p less than 0.05), a lower left ventricular volume (1.25 +/- 0.20 versus 2.37 +/- 0.30 ml/kg, p less than 0.001) and a lower left ventricular wall stress index (1.3 +/- 0.2 versus 1.7 +/- 0.1, p less than 0.05). Left ventricular chamber stiffness was higher in milrinone-treated infarcted rats than in untreated infarcted rats. Milrinone had no cardiac effect on uninfarcted animals.

CONCLUSION
Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation.
Cardiac epinephrine synthesis. Regulation by a glucocorticoid.
Authors: Kennedy B , Ziegler M G 
Published: June 2012

BACKGROUND
The heart can synthesize epinephrine. Homogenates of rat heart, which contain the enzymes phenylethanolamine N-methyltransferase (PNMT) and nonspecific N-methyltransferase (NMT), methylate norepinephrine to form epinephrine. The cardiac atrium contains primarily PNMT and the cardiac ventricle contains both PNMT and NMT.

METHODS AND RESULTS
Rats were given the glucocorticoid dexamethasone at doses ranging from 0.2 to 20 mg/kg. Twenty-four hours later, cardiac atria, ventricle, skeletal muscle, and adrenal had increases in PNMT activity to as much as 230% of baseline. NMT activity was unchanged. Longer-term treatment with 1 mg/kg dexamethasone daily for 12 days increased cardiac PNMT activity about fivefold and also increased atrial epinephrine levels. Dexamethasone did not alter ventricular epinephrine levels but increased levels of both PNMT and catechol-O-methyltransferase, the major catabolic enzyme for epinephrine. After dexamethasone treatment, greater volumes of anti-PNMT antiserum were needed to decrease PNMT enzymatic activity, indicating that dexamethasone treatment resulted in greater amounts of PNMT and did not just activate existing PNMT molecules. Denervation of the masseter muscle of rats by unilateral superior cervical ganglionectomy markedly diminished tissue norepinephrine and epinephrine levels but had no effect on masseter PNMT or NMT levels. We have previously shown that chemical sympathectomy with 6-hydroxydopamine increases cardiac PNMT levels. These findings suggest that PNMT is an extraneuronal enzyme in both cardiac and skeletal muscle.

CONCLUSIONS
Glucocorticoids have several cardiovascular effects, including increased cardiac output and blood pressure. Enhanced cardiac epinephrine synthesis may mediate some of these glucocorticoid effects.
Differences in beta-adrenergic neuroeffector mechanisms in ischemic versus idiopathic dilated cardiomyopathy.
Authors: Bristow M R , Anderson F L , Port J D , Skerl L , Hershberger R E , Larrabee P , O'Connell J B , Renlund D G , Volkman K , Murray J 
Published: June 2012

BACKGROUND
We measured the content and activities of components of the beta-adrenergic receptor-G protein-adenylate cyclase complex and adrenergic neurotransmitter levels in left and right ventricular myocardial preparations derived from 77 end-stage failing human hearts from patients with idiopathic dilated cardiomyopathy (IDC) or ischemic dilated cardiomyopathy (ISCDC).

METHODS AND RESULTS
The results were compared with data obtained in 21 nonfailing hearts removed from organ donors. Compared with ISCDC ventricles, IDC left and right ventricles exhibited a greater degree of total beta- or beta 1-receptor downregulation. In contrast, compared with IDC right ventricles, isolated tissue preparations of ISCDC right ventricles exhibited a greater degree of subsensitivity to the inotropic effect of isoproterenol, indicating a relatively greater degree of functional uncoupling of right ventricular ISCDC beta-receptors from mechanical response. In addition, relative to IDC left ventricles, preparations of ISCDC left ventricle exhibited greater subsensitivity to beta-agonist-mediated adenylate cyclase stimulation, indicating functional uncoupling of left ventricular ISCDC beta-receptors from cyclic AMP generation. The uncoupling of beta-receptors in ISCDC left and right ventricles may have been a result of abnormalities in G protein activation of adenylate cyclase; compared with age- and cardiac function-matched respective left or right IDC ventricles, ISCDC left ventricles exhibited less stimulation of adenylate cyclase by NaF or forskolin but no change in Mn2+ stimulation, whereas ISCDC right ventricles exhibited less stimulation by the nonhydrolyzable guanine nucleotide Gpp (NH)p. Also, IDC right ventricles exhibited a "selective" (not present in IDC left ventricles or ISCDC ventricles) decrease in stimulation of adenylate cyclase by Mn2+. Tissue neurotransmitter levels and pertussis toxin-catalyzed ADP ribosylation were altered to similar extents in IDC and ISCDC:

CONCLUSIONS
These data indicate that potentially important differences exist in the regulatory behavior of components of the beta-adrenergic receptor-G protein-adenylate cyclase complex in IDC versus ISCDC, differences that presumably relate to the distinct pathophysiologies of these two types of heart muscle disease.