bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitroglycerin-induced coronary vasodilation in cardiac transplant recipients. Evaluation with in vivo intracoronary ultrasound.
Authors: Pinto F J , St Goar F G , Fischell T A , Stadius M L , Valantine H A , Alderman E L , Popp R L 
Published: June 2012

BACKGROUND
Coronary artery vasomotion is altered after cardiac transplantation. The impact of accelerated transplant coronary atherosclerosis and myocardial rejection on vasomotion is not well understood. Intravascular ultrasound is a new imaging method with the ability to study real-time changes in coronary artery dimensions.

METHODS AND RESULTS
Epicardial coronary artery response to nitroglycerin was studied in 32 cardiac transplant recipients (age, 47 +/- 11 years) 3 weeks to 10 years after transplantation with intracoronary ultrasound. Cross-sectional luminal area and diameter were measured at a fixed position in the left anterior descending artery immediately before and every 30 seconds for 5 minutes after 0.4 mg of sublingual nitroglycerin. Cross-sectional area increased from a baseline of 13.1 +/- 3.9 mm2 to 15.8 +/- 3.9 mm2 at maximal vasodilation; luminal diameter increased from 4.0 +/- 0.6 mm to 4.5 +/- 0.6 mm. This increase reached statistical significance (p less than 0.001) at 1.5 minutes after administration of nitroglycerin; mean maximum increase occurred at 4.5 minutes (24% for cross-sectional area and 11% for luminal diameter). Patients with biopsy-proven mild or moderate concurrent rejection had a significantly blunted vasodilatory response versus the nonrejection group (9% versus 27% for cross-sectional area, p less than 0.04), although a vasodilatory effect was still present. Nitroglycerin response was well preserved in patients up to 10 years after transplantation; however, there was a trend toward a decreased response in patients studied immediately after transplantation (21% versus 29%, p = 0.37). Coronary intimal thickness, as measured by ultrasound, had no impact on the vasodilatory response (R = 0.23, p = 0.34).

CONCLUSIONS
Vasodilatory response to nitroglycerin in cardiac transplant recipients is attenuated during episodes of cardiac rejection. This response is preserved in long-term survivors and is independent of the degree of intimal thickening. Intravascular ultrasound provides a new method to document real-time epicardial coronary vasomotion.
Pharmacokinetics of tissue-type plasminogen activator during acute myocardial infarction in men. Effect of a prostacyclin analogue.
Authors: Kerins D M , Roy L , Kunitada S , Adedoyin A , FitzGerald G A , Fitzgerald D J 
Published: June 2012

BACKGROUND
Coronary reocclusion complicates the thrombolytic therapy of acute myocardial infarction despite the routine use of aspirin. This is consistent with experimental studies demonstrating that multiple agonists, in addition to thromboxane A2, mediate the platelet activation underlying reocclusion. Consequently, a more potent antiplatelet therapy with a broader spectrum of activity than aspirin may be required in this setting. Prostacyclin and its more stable analogue, iloprost, inhibit platelet aggregation to all known agonists and exert an additional effect over aspirin alone. Experiments in animal models have demonstrated, however, that iloprost increases the clearance of tissue-type plasminogen activator (t-PA) and impairs thrombolysis in vivo. This study examines whether a similar interaction occurs in humans.

METHODS AND RESULTS
Twelve patients with acute myocardial infarction received t-PA intravenously, 60 mg in the first hour and a maintenance infusion of 13.3 mg/hr for 3 hours. Patients were assigned in a double-blind fashion to iloprost (2 ng/kg/min) or placebo following the initial 90 minutes of the maintenance infusion of t-PA. Iloprost decreased mean arterial blood pressure (-10 +/- 2.9 mm Hg, p less than 0.05) but did not alter heart rate. Steady-state plasma iloprost concentration was 591 +/- 64 pmol/l. At this concentration, iloprost markedly inhibited platelet aggregation in vitro, particularly in the presence of aspirin. Steady-state clearance of t-PA was unchanged by iloprost (454 +/- 65 versus 443 +/- 136 ml/min in controls, p = NS). Furthermore, neither elimination kinetics nor plasma protein binding of t-PA was altered by iloprost.

CONCLUSIONS
At plasma levels that exert a potent antiplatelet effect, iloprost did not alter the pharmacokinetics of t-PA in men. Prostacyclin analogues may prove useful as an adjunct to plasminogen activators, particularly in patients at high risk for thrombotic reocclusion.
Migratory activity of human smooth muscle cells cultivated from coronary and peripheral primary and restenotic lesions removed by percutaneous atherectomy.
Authors: Bauriedel G , Windstetter U , DeMaio S J , Kandolf R , Höfling B 
Published: June 2012

BACKGROUND
The successful cultivation of human smooth muscle cells (SMC) from coronary and peripheral atherosclerotic lesions removed by percutaneous directional atherectomy is described.

METHODS AND RESULTS
Sixty-seven patients in whom plaque material was obtained compose the study population. A total of 73 lesions from both coronary (n = 38) and peripheral (n = 35) arteries of primary (n = 50) and restenotic origin (n = 23) were studied. Successful cultivation was significantly (p less than 0.001) dependent on the quantity of plaque material submitted. Fifty-five percent of patients in whom atherectomy specimens were removed from coronary lesions yielded an adequate SMC population in comparison to 89% of those from peripheral arteries (p less than 0.01). Cultivation was not dependent on the age and sex of patients, lesion origin, risk factors, medications, or incidence of unstable angina. In an attempt to quantify SMC activity, migratory velocity was measured with a computer-assisted motion analysis system. SMC migratory velocity was found to be significantly (p less than 0.001) greater in restenotic than in primary plaque material. This finding was confirmed for both coronary and peripheral lesions.

CONCLUSIONS
Our data suggest that elevated SMC migratory activity may be an important mechanism in the development of restenotic lesions.
A low-sodium diet corrects the defect in beta-adrenergic response in older subjects.
Authors: Feldman R D 
Published: June 2012

BACKGROUND
One of the prominent cardiovascular abnormalities in the elderly is reduced beta-adrenoceptor responsiveness. Because dietary sodium restriction corrects the defect in vascular and lymphocyte beta-adrenoceptor responsiveness in hypertensive subjects, we postulated an analogous effect in the elderly. Thus, vascular and lymphocyte beta-adrenergic responsiveness were studied in 10 older normotensive subjects (age, 56 +/- 2 years) on either a 400- or 10-meq/day sodium diet.

METHODS AND RESULTS
In older subjects fed a high-sodium diet, maximal isoproterenol-mediated vasodilation was depressed compared with a group of normotensive younger subjects studied previously. When they were fed a low-sodium diet, however, maximal isoproterenol-mediated vasodilation in the elderly was increased significantly. Lymphocyte adenylyl cyclase sensitivity to isoproterenol was comparably increased. Blood pressure was significantly reduced on a low-sodium diet, and mean arterial pressure was significantly inversely correlated with the extent of isoproterenol-mediated vasodilation.

CONCLUSIONS
These studies indicate that a low-sodium diet corrects the defect in both vascular and lymphocyte beta-adrenergic responsiveness with aging. This suggests an important role for dietary modification in the adrenergic regulation of vascular tone in the elderly.
Evidence of genetic heterogeneity in five kindreds with familial hypertrophic cardiomyopathy.
Authors: Epstein N D , Fananapazir L , Lin H J , Mulvihill J , White R , Lalouel J M , Lifton R P , Nienhuis A W , Leppert M 
Published: June 2012

BACKGROUND
Recently, two families with hypertrophic cardiomyopathy have been shown to have mutations in the cardiac beta-myosin heavy chain gene (beta-MHC) located on the long arm of chromosome 14.

METHODS AND RESULTS
We have performed linkage analysis of five newly ascertained pedigrees with more than 50 chromosomal markers detecting polymorphisms. Our findings confirm the linkage to beta-MHC gene locus on chromosome 14 in one family (LOD score, 4.50) and suggest linkage to the same gene in another kindred. Chromosome 14 markers were not linked to the disease gene in the other three kindreds, however, and a test for genetic heterogeneity was statistically significant. Moreover, markers for the beta-MHC gene identified affected individuals who were recombinants with respect to this gene and the disease phenotype in these three kindreds.

CONCLUSIONS
These results provide conclusive evidence that hypertrophic cardiomyopathy in separate families is caused by mutations in disease genes at two or more locations in the genome.
Imaging the rejecting heart. In vivo detection of major histocompatibility complex class II antigen induction.
Authors: Isobe M , Narula J , Southern J F , Strauss H W , Khaw B A , Haber E 
Published: June 2012

BACKGROUND
Mice with abdominal heterotopic heart transplants were studied to determine whether scintigraphic detection of an increase in major histocompatibility complex (MHC) class II antigen expression could be used as a noninvasive method for diagnosing early rejection.

METHODS AND RESULTS
Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2d) recipients (n = 18). Two of the 18 allografted mice were treated with cyclosporine (15 mg/kg/day), and two isografted mice served as controls. Each mouse was injected intravenously with 100 microCi of 111In-labeled anti-MHC class II monoclonal antibodies (10-2-16 and 14-4-4S) 24 hours before scintigraphy. After imaging, the mice were killed for tissue counting and histopathology. Radiotracer uptake in the grafts reflected the severity of rejection as determined by histopathological criteria. The percent injected dose per gram of tissue in excised grafts was 4.8 +/- 1.8 (mean +/- SD) for normal grafts (n = 8), 11.1 +/- 9.7 for grafts with grade IA rejection (n = 3, NS), 18.0 +/- 3.8 for grafts with grade IIIA rejection (n = 4, p less than 0.001 versus normal), 18.7 +/- 3.2 for grafts with grade IIIB rejection (n = 3, p less than 0.001 versus normal), and 22.6 +/- 5.4 for grafts with severe rejection (grade IV) (n = 3, p less than 0.001 versus normal). Rejecting allografts with lymphocyte infiltration but without significant myocyte necrosis could be identified by this scintigraphic method. In the BALB/c donor-C57BL/6 (H2b, IE-) recipient combination, rejecting allografts were visualized by 14-4-4S (anti-IEk,d,p,r) antibody but not by 10-2-16 (anti-IAk,r,s,f) antibody. This difference shows that class II antigens induced on donor hearts are solely responsible for the antibody uptake in positive scintigrams of rejecting allografts.

CONCLUSIONS
We conclude that 111In-labeled anti-MHC class II antigen antibody imaging is a sensitive and noninvasive method for detecting cardiac allograft rejection.
Adenosine causes bradycardia in pacing-induced cardiac failure.
Authors: Belloni F L , Wang J , Hintze T H 
Published: June 2012

BACKGROUND
In normal, conscious dogs, systemic injection of adenosine causes arterial hypotension and a baroreceptor reflex tachycardia mediated in part by withdrawal of vagal tone from the sinoatrial node. After vagal section or muscarinic receptor blockade, however, adenosine injection causes bradycardia via a direct sinoatrial node inhibition. Because cardiac failure is marked by a loss of vagal tone, we hypothesized that adenosine injection in dogs with failing hearts would reduce heart rate.

METHODS AND RESULTS
Mongrel dogs were instrumented with indwelling catheters, manometers, and ventricular pacing electrodes. After the dogs had recovered from the surgery, the ventricles were paced continuously at 210 beats per minute for 3 weeks, followed by pacing at 240 beats per minute for an additional week. This regimen caused mild ventricular and more striking atrial hypertrophy and a gradual onset of physiological and clinical signs of congestive heart failure. Adenosine injections that caused large tachycardias before the pacing regimen began caused progressively smaller increments in heart rate during the first 2 weeks of pacing. After 3 and 4 weeks, adenosine injections caused overt reductions in heart rate despite the concomitant arterial depressor response.

CONCLUSIONS
We conclude that the loss of vagal tone associated with the development of cardiac failure unmasks the direct negative chronotropic effect of exogenous adenosine on the sinoatrial node.
Immediate and long-term outcome of percutaneous mitral valvotomy in patients 65 years and older.
Authors: Tuzcu E M , Block P C , Griffin B P , Newell J B , Palacios I F 
Published: June 2012

BACKGROUND
We analyzed the immediate and long-term outcome of percutaneous balloon mitral valvotomy (PMV) in 99 patients who were greater than or equal to 65 years of age (81 women and 18 men; mean +/- SEM age, 72 +/- 0.5 years).

METHODS AND RESULTS
There were 84 patients in New York Heart Association (NYHA) class III or IV; 26 patients had previous surgical commissurotomy; 64 had one or more comorbidities; 73 had fluoroscopically visible mitral valve (MV) calcification; and 63 had echocardiographic score greater than 8 (mean +/- SEM score, 9.2 +/- 0.2). There were three procedural deaths, all occurring in our early experience. Pericardial tamponade occurred in five patients, thromboembolism in three, and transient atrioventricular block in one. After PMV, MV area was greater than or equal to 1 cm2 in 86 patients and greater than or equal to 1.5 cm2 in 56. A successful outcome (defined as MV area greater than or equal to 1.5 cm2 without a greater than or equal to 2-grade increase in mitral regurgitation and without left-to-right shunt with a pulmonary-to-systemic flow ratio of greater than or equal to 1.5:1) was achieved in 46 patients. The best multivariate predictor of success was the combination of echocardiographic score, NYHA functional class, and inverse of MV area. Mean follow-up was 16 +/- 1 months. Actuarial survival (79 +/- 7% versus 62 +/- 10%, p = 0.04), survival without MV replacement (71 +/- 8% versus 41 +/- 8%, p = 0.002), and survival without MV replacement and NYHA class III or IV (54 +/- 12% versus 38 +/- 8%, p = 0.01) at 3 years were significantly better in the successful group of 46 patients than in the unsuccessful group of 53 patients. Low echocardiographic score was the only independent predictor of survival. Lack of MV calcification and low NYHA class, low mean left atrial pressure, and low pulmonary artery pressure were the independent predictors of event-free survival.

CONCLUSIONS
PMV can be performed safely in selected patients greater than or equal to 65 years old with good immediate and long-term results. In addition to clinical examination, echocardiographic evaluation of the mitral valve and fluoroscopic screening for valvular calcification are the most important steps in patient selection for successful outcome.
Intracoronary ultrasound in cardiac transplant recipients. In vivo evidence of "angiographically silent" intimal thickening.
Authors: St Goar F G , Pinto F J , Alderman E L , Valantine H A , Schroeder J S , Gao S Z , Stinson E B , Popp R L 
Published: June 2012

BACKGROUND
Accelerated coronary atherosclerosis is a major factor limiting allograft longevity in cardiac transplant recipients. Histopathology studies have demonstrated the insensitivity of coronary angiography for detecting early atheromatous disease in this patient population. Intracoronary ultrasound is a new imaging technique that provides characterization of vessel wall morphology. The purpose of this study was to compare in vivo intracoronary ultrasound with angiography in cardiac transplant recipients.

METHODS AND RESULTS
The left anterior descending coronary artery was studied with intracoronary ultrasound in 80 cardiac transplant recipients at the time of routine screening coronary angiography 2 weeks to 13 years after transplantation. A mean and index of intimal thickening were obtained at four coronary sites. Intimal proliferation was classified as minimal, mild, moderate, or severe according to thickness and degree of vessel circumference involved. Twenty patients were studied within 1 month of transplantation and had no angiographic evidence of coronary disease. An intimal layer was visualized by ultrasound in only 13 of these 20 presumably normal hearts. The 60 patients studied 1 year or more after transplantation all had at least minimal intimal thickening. Twenty-one patients (35%) showed minimal or mild, 17 (28%) moderate, and 21 (35%) severe thickening. Forty-two of these 60 patients had angiographically normal coronary arteries, 21 (50%) of whom had either moderate or severe thickening. All 18 patients with angiographic evidence of coronary disease had moderate or severe intimal thickening, but there was no statistically significant difference in intimal thickness or index when compared with the patients with moderate or severe proliferation and normal angiograms (thickness, 0.53 +/- 0.35 mm versus 0.64 +/- 0.30 mm, p = NS; index, 0.28 +/- 0.10 versus 0.34 +/- 0.10, p = NS).

CONCLUSIONS
The majority of patients 1 or more years after cardiac transplantation have ultrasound evidence of intimal thickening not apparent by angiography. Intracoronary ultrasound offers early detection and quantitation of transplant coronary disease and provides characterization of vessel wall morphology, which may prove to be a prognostic marker of disease.
Nitroprusside and regional vascular capacitance in patients with severe congestive heart failure.
Authors: Risöe C , Simonsen S , Rootwelt K , Sire S , Smiseth O A 
Published: June 2012

BACKGROUND
This study investigates the effects of sodium nitroprusside on regional vascular capacitance in eight patients with severe congestive heart failure (New York Heart Association class IV) and pulmonary hypertension.

METHODS AND RESULTS
Regional relative blood volumes in the splanchnic and pulmonary region were determined by equilibrium blood pool scintigraphy. Hepatic venous wedge pressure and the mean of pulmonary artery and pulmonary capillary wedge pressure were used to represent the distending pressures of the splanchnic and pulmonary capacitance vessels, respectively. The dose of sodium nitroprusside was increased stepwise until systolic pulmonary artery pressure decreased below 50 mm Hg. This caused reductions in mean aortic pressure from 89 +/- 5 to 66 +/- 3 mm Hg (p less than 0.005), in pulmonary capillary wedge pressure from 31 +/- 1 to 16 +/- 2 mm Hg (p less than 0.001), and in hepatic venous wedge pressure from 10.0 +/- 1.0 to 5.9 +/- 0.6 mm Hg (p less than 0.005). Intestinal blood volume increased by 26 +/- 7% (p less than 0.005), whereas hepatic blood volume decreased by 9 +/- 3% (p less than 0.02). Pulmonary blood volume was unchanged. Analysis of intestinal and pulmonary vascular pressure-volume relations showed larger or equal blood volumes contained at lower distending pressures, indicating that sodium nitroprusside reduced smooth muscle tone of the capacitance vessels in these regions. The reduction of hepatic blood volume was compatible with passive expulsion of blood subsequent to reduced venous pressure. There was no change in the count rate from the spleen.

CONCLUSIONS
Nitroprusside reduced venous pressure in patients with congestive heart failure by active relaxation of intestinal and pulmonary capacitance vessels. Hepatic vascular volume was probably reduced by a passive mechanism.
Selective stimulation of parasympathetic nerve fibers to the human sinoatrial node.
Authors: Carlson M D , Geha A S , Hsu J , Martin P J , Levy M N , Jacobs G , Waldo A L 
Published: June 2012

BACKGROUND
In animals, parasympathetic nerve fibers that innervate the sinoatrial node can be selectively stimulated to increase atrial cycle length. These nerve fibers course through an epicardial fat pad at the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium. We hypothesized that similar nerves exist and can be selectively stimulated in humans.

METHODS AND RESULTS
Microscopic examination of fat pads excised from the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium during two human autopsies revealed the presence of nerve fibers and ganglia. We electrically stimulated this epicardial fat pad in 16 patients during cardiac surgery. The fat pads were stimulated with continuous-pulse trains for 15 seconds via a hand-held bipolar electrode using constant current (10-15 mA), constant pulse width (0.02-0.05 msec), and at 6.6, 10, 20, 25, and 30 Hz. The mean atrial cycle length +/- 1 SEM increased from 734 +/- 34 msec at baseline to a maximum of 823 +/- 61 msec at 6.6 Hz, 1,167 +/- 125 msec at 10 Hz, 1,734 +/- 281 msec at 20 Hz, 2,993 +/- 661 msec at 25 Hz, and 2,461 +/- 668 msec at 30 Hz during nerve stimulation. Linear regression analysis showed that the response of atrial cycle length to sinoatrial parasympathetic nerve stimulation was frequency dependent. The maximum response and complete decay of the response occurred within 4-8 seconds of initiation or termination of sinoatrial parasympathetic nerve stimulation. Atrioventricular conduction time and the PR interval did not change during sinoatrial parasympathetic nerve stimulation, even when the atria were paced at the baseline heart rate.

CONCLUSIONS
Electrical stimulation of parasympathetic nerve fibers in a fat pad near the sinoatrial node increased atrial cycle length without affecting atrioventricular nodal conduction. This is the first study in which such nerve fibers that innervate the sinoatrial node have been selectively stimulated in humans.