bluuebunny/crossref_metadata_2025_split huggingface dataset:
Balloon mitral commissurotomy after previous surgical commissurotomy. The National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry participants.
Authors: Davidson C J , Bashore T M , Mickel M , Davis K 
Published: June 2012

BACKGROUND
Mitral restenosis after surgical mitral commissurotomy often occurs within 5-15 years, necessitating a repeat procedure. Balloon mitral commissurotomy (BMC) has been advocated as an alternative to repeat surgery for mitral restenosis.

METHODS AND RESULTS
The purposes of this study are to determine the short- and intermediate-term outcomes of patients undergoing BMC after previous surgical commissurotomy, to compare these patients with those undergoing balloon mitral commissurotomy as an initial procedure, and to elucidate the multivariate determinants of acute procedural and clinical outcome. Of 738 patients undergoing BMC as part of the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry, 133 underwent BMC after previous surgical mitral commissurotomy. Prospective data obtained included demographic, hemodynamic, echocardiographic, and clinical follow-up. BMC after previous surgical commissurotomy produced a significant reduction in transvalvular gradient from 13 +/- 5 to 6 +/- 3 mm Hg (p less than 0.0001) and an increase in mitral valve area from 1.0 +/- 0.3 to 1.8 +/- 0.8 cm2 (p less than 0.0001). BMC as an initial procedure increased valve area from 1.0 +/- 0.4 to 2.0 +/- 0.8 cm2 (p less than 0.0001) (p = 0.03 versus prior surgery). Baseline characteristics including mitral valve echo score were similar for both groups. Comparing 6-month status in patients with prior surgery to those without, 80% versus 90% were New York Heart Association (NYHA) functional class I or II (p = 0.004). Mortality was similar. In patients with previous mitral valve surgery, multivariate predictors of improvement in 6-month clinical status included the experience of the center (p = 0.006), lower echocardiographic score (p = 0.001), and lower left ventricular end-diastolic pressure (p = 0.008). Multivariate determinants of a final mitral valve area greater than or equal to 1.5 cm2 were a lower baseline NYHA functional class (p = 0.003) and lower mitral valve echocardiographic score (p = 0.008).

CONCLUSIONS
BMC after previous surgical mitral commissurotomy results in similar hemodynamic changes as in patients undergoing BMC as an initial procedure. Symptomatic improvement at 6 months is slightly less frequent in prior commissurotomy patients. Patients with favorable valvular morphology and preserved left ventricular function who undergo BMC in experienced centers are most likely to achieve symptomatic improvement after previous surgical commissurotomy. In general, BMC is an effective treatment for mitral restenosis after previous surgical commissurotomy.
Cardiac persistence of cardioviral RNA detected by polymerase chain reaction in a murine model of dilated cardiomyopathy.
Authors: Kyu B , Matsumori A , Sato Y , Okada I , Chapman N M , Tracy S 
Published: June 2012

BACKGROUND
In our model of dilated cardiomyopathy (DCM), cardiac dilatation and hypertrophy developed after inoculation of encephalomyocarditis virus (EMCV), but the infectious virus was isolated only early after infection. In this study, we investigated whether viral RNA could be detected at later times using the polymerase chain reaction (PCR).

METHODS AND RESULTS
In the in vitro study, FL (human amnion) cells infected with EMCV were harvested for RNA extraction, and viral cDNA was synthesized by reverse transcription with random hexamers. Using oligonucleotide primers with homology to the 5' noncoding region of EMCV, we enzymatically amplified a 121-base pair band, which was homologous to a probe specific for EMCV as demonstrated by Southern blot hybridization. The sensitivity of this PCR technique was at the level of about 10(2)-10(3) copies of viral RNA genome. In the in vivo study, four-week-old DBA/2 mice were inoculated with EMCV intraperitoneally (10 pfu/mouse) and killed on days 1,2,3,5,7,10,14,18,28,60, and 90. The hearts were divided into three parts for purification of total RNA, histopathological examination, and to culture for infectious virus. The infectious virus was isolated from the heart after the second day but never after the 14th day. The viral genome was detectable by PCR on the second day, when very little mononuclear cell infiltration around the blood vessels was histologically visible. Positive PCR signals were observed in all hearts through day 14. Viral RNA was also detected in four of six 28-day samples, four of six 60-day samples, and two of seven 90-day samples when diffuse myocardial fibrosis was prominent, but myocardial necrosis or cellular infiltration had disappeared.

CONCLUSIONS
The persistence of EMCV RNA was shown by PCR in the chronic stage of EMCV-induced myocarditis, a time when the inflammatory reaction had largely subsided. The PCR is a potentially useful method to test possible viral etiologies in idiopathic heart muscle disease or DCM.
PEG-SOD and myocardial protection. Studies in the blood- and crystalloid-perfused rabbit and rat hearts.
Authors: Galiñanes M , Qiu Y , Ezrin A , Hearse D J 
Published: June 2012

BACKGROUND
Polyethylene glycol, covalently linked to superoxide dismutase (PEG-SOD), has a long plasma half-life (greater than 30 hours) and has been proposed as an effective agent for reducing free radical-mediated injury ischemia and reperfusion.

METHODS AND RESULTS
Using an isolated rabbit heart perfused with arterial blood from a support rabbit, we have demonstrated that pretreatment with PEG-SOD (30,000 units/kg, intravenous bolus, 12-24 hours before 60 minutes of normothermic global ischemia), combined with addition of PEG-SOD to the blood perfusion circuit (30,000 units/kg to the support rabbit) and inclusion of PEG-SOD (150 micrograms/ml) in a cardioplegic solution, enhanced the postischemic recovery of left ventricular developed pressure (LVDP) from 51 +/- 6 to 74 +/- 9 mm Hg (p less than 0.05; n = 9 per group). In further studies we showed that, whereas maximum protection was obtained when PEG-SOD was given as a combined pretreatment and additive to both the cardioplegic and the reperfusate solutions (postischemic LVDP recovery increased from 44 +/- 4% in the control group to 70 +/- 3% in the PEG-SOD group), the administration of PEG-SOD during pretreatment plus cardioplegia or during reperfusion alone also resulted in a significant improvement in postischemic function (62 +/- 7% and 60 +/- 3%, respectively). However, the use of PEG-SOD as a cardioplegic additive alone failed to afford protection (47 +/- 4% recovery of LVDP). In dose-response studies (with 0, 3,000, 6,000, 12,000, 30,000, or 60,000 units/kg; n = 8 per group), maximum recovery of LVDP was obtained with the administration of 12,000 units/kg of PEG-SOD. Studies of the plasma activity of PEG-SOD confirmed its long half-life and showed that the treatment with PEG-SOD either 1 hour or 12-24 hours before the study resulted in similar levels of plasma activity. In an attempt to assess any involvement of blood-borne elements in the protection afforded by PEG-SOD, studies were also carried out in the crystalloid-perfused rabbit heart, and no protection was observed. Similarly, no protection was observed at any one of a variety of doses in the crystalloid-perfused rat heart.

CONCLUSIONS
PEG-SOD can afford protection in the blood-perfused rabbit heart; this protection is dose dependent and probably involves some action of PEG-SOD on blood-borne elements, possibly leukocytes.
Adenosine infusion for the reversal of pulmonary vasoconstriction in biventricular failure. A good test but a poor therapy.
Authors: Haywood G A , Sneddon J F , Bashir Y , Jennison S H , Gray H H , McKenna W J 
Published: June 2012

BACKGROUND
Elevation of pulmonary vascular resistance is an important determinant of right ventricular function in patients with end-stage biventricular heart failure. Vasodilator drug therapy directed at the pulmonary vasculature is used in the hemodynamic assessment of patients for orthotopic heart transplantation, and therapy aimed at decreasing pulmonary vascular resistance and transpulmonary pressure gradient has been advocated in patients awaiting heart transplantation. Adenosine infusion has been shown to cause selective pulmonary vasodilatation in normal subjects and in patients with primary pulmonary hypertension but has not been assessed in patients with biventricular heart failure.

METHODS AND RESULTS
Using two infusion doses, we studied the pulmonary and renal hemodynamic effects of adenosine on patients referred for heart transplantation (n = 21) and compared it with sodium nitroprusside (n = 18). Patients received 30% oxygen via face mask throughout the study. Adenosine at 100 micrograms/kg min achieved the same percentage fall in pulmonary vascular resistance as nitroprusside (41 +/- 6% versus 42 +/- 4%) and a greater and more consistent fall in transpulmonary pressure gradient (35 +/- 6% versus 9 +/- 30%, p less than 0.02). The mean arterial blood pressure fell by 16 mm Hg with nitroprusside but was unchanged by adenosine, indicating that in contrast to nitroprusside, adenosine acted as a selective pulmonary vasodilator. Despite this, cardiac index showed only a modest increase with adenosine (1.73 +/- 0.09 to 1.89 +/- 0.16 l.m-2, p less than 0.05), and there was a rise in pulmonary capillary wedge pressure from baseline at the higher dose (29.7 +/- 2.5 to 33.4 +/- 3.4 mm Hg, p less than 0.05). Renal blood flow was unchanged during adenosine infusion.

CONCLUSIONS
Adenosine is a potent selective pulmonary vasodilator in patients with biventricular heart failure and is preferable to sodium nitroprusside as a test for the reversibility of pulmonary vasoconstriction. However, its deleterious effects on left atrial pressure make it unsuitable as a therapeutic agent in patients awaiting heart transplantation.
Myocardial protective effects of adenosine. Infarct size reduction with pretreatment and continued receptor stimulation during ischemia.
Authors: Toombs C F , McGee S , Johnston W E , Vinten-Johansen J 
Published: June 2012

BACKGROUND
We hypothesized that 1) endogenous adenosine released during ischemia conferred an inherent cardioprotection, and 2) a pretreatment dose of adenosine before ischemia would provide additional protection independent of hemodynamic effects.

METHODS AND RESULTS
Thirty-six anesthetized New Zealand White rabbits underwent 30 minutes of regional ischemia produced by coronary occlusion followed by 2 hours of reperfusion. The adenosine group (ADO, n = 9) received a 5-minute pretreatment infusion of 140 micrograms/kg/min of adenosine before ischemia. A control group (SAL, n = 9) received saline before ischemia. To separate the effects of adenosine used as a pretreatment versus the effects during ischemia, a third group (ADO+SPT, n = 9) received adenosine as pretreatment followed by 10 mg/kg 8-p-sulfophenyl theophylline (8-SPT), an A1/A2-receptor antagonist given before ischemia, thus allowing pretreatment with adenosine but antagonizing its effects during ischemia. To preclude any protection from endogenous adenosine released during ischemia, the fourth group (SAL+SPT, n = 9) received saline as pretreatment and 8-SPT before ischemia. Area of necrosis within the area at risk (infarct size) was determined with tetrazolium and Evans blue stains, and transmural blood flow was measured using radioactive microspheres. Collateral blood flow in the area at risk was similar in all groups, as was the size of the area at risk. Infarct size was reduced by adenosine pretreatment (ADO, 8.4 +/- 7.2%) in contrast to saline vehicle (SAL, 27.8 +/- 6.3%; p less than 0.05 versus ADO). alpha 1/alpha 2-Receptor blockade after adenosine pretreatment abolished the ischemic protection provided by pretreatment adenosine (ADO+SPT, 42.7 +/- 8.3%; p less than 0.05 versus ADO). Finally, receptor blockade of endogenously released adenosine without adenosine pretreatment increased infarct size by 24% over the nonpretreated saline group (SAL+SPT, 51.5 +/- 9.0%; p less than 0.05 versus SAL).

CONCLUSIONS
We conclude that 1) endogenous adenosine building up during ischemia is cardioprotective, and 2) pretreatment with adenosine confers cardioprotection independent of hemodynamic effects. Whether pretreatment effects of adenosine subsequently modulate the effects of endogenous adenosine (through alterations in receptor population or sensitivity) or endogenous and exogenous adenosine represent additive compartments is unclear.
Loss of the coronary microvascular response to acetylcholine in cardiac transplant patients.
Authors: Treasure C B , Vita J A , Ganz P , Ryan T J , Schoen F J , Vekshtein V I , Yeung A C , Mudge G H , Alexander R W , Selwyn A P 
Published: June 2012

BACKGROUND
The coronary arteries of transplanted hearts frequently develop accelerated diffuse arteriosclerosis. The effects of this disease on resistance vessel function are unknown.

METHODS AND RESULTS
To investigate the integrity of endothelium-dependent small-vessel vasodilation in transplanted hearts, coronary blood flow (CBF) responses to the endothelium-dependent dilator acetylcholine (10(-8) to 10(-6) M) and the essentially endothelium-independent dilator adenosine (10(-6) to 10(-4) M) were assessed in 40 studies of 29 transplant patients 1-3 years after transplantation and in seven nontransplanted controls. CBF was measured at constant arterial pressure with a Doppler catheter in the left anterior descending coronary artery. Controls, year 1 transplant patients, and year 2 transplant patients had similar increases in CBF in response to acetylcholine (232 +/- 40%, 200 +/- 41%, and 201 +/- 54%, respectively; p = NS), whereas year 3 transplant patients had increased CBF of only 100 +/- 39% (p less than 0.05 versus controls). An index of the proportion of CBF reserve attributable to endothelium-dependent dilation was obtained by normalizing each patient's peak acetylcholine flow response by the peak adenosine flow response. In patients receiving both acetylcholine and adenosine, endothelium-dependent flow responses declined over time [57 +/- 9% in controls, 56 +/- 10% for year 1, 47 +/- 12% for year 2, and 29 +/- 9% for year 3 (p less than 0.05 versus controls)]. An increased mean cyclosporine level (range, 99-261 ng/ml) (r = 0.67, p = 0.004) and increased transplant recipient age (range, 20-63 years) (r = 0.51, p = 0.004) predicted a preserved endothelium-dependent microvascular response.

CONCLUSIONS
Thus, microvascular endothelium-dependent dilation deteriorates over time in the transplanted heart, which may reflect underlying graft arteriosclerosis and contribute to ischemic damage of the myocardium.
Endothelial dysfunction early after heart transplantation. Assessment with intravascular ultrasound and Doppler.
Authors: Mills R M , Billett J M , Nichols W W 
Published: June 2012

BACKGROUND
Allograft vasculopathy after heart transplantation is thought to represent a response to endothelial injury in the graft vessels. To assess endothelial function before the onset of anatomic disease, coronary vasomotor responses to adenosine, acetylcholine, and nitroglycerin were evaluated in transplant recipients by intravascular ultrasound imaging and Doppler flow studies.

METHODS AND RESULTS
Nine patients were studied 1 year after heart transplantation. Acetylcholine provoked significant vasoconstriction to 82% of maximal coronary diameter but was associated with an increase in mean coronary blood flow from 63.1 to 204 ml/min. Coronary blood flow increased fivefold in response to adenosine, a normal response.

CONCLUSIONS
The vasomotor response to acetylcholine at 1 year after heart transplantation is consistent with endothelial dysfunction in the epicardial conduit vessels. Microvascular function as judged by coronary flow reserve appears to be normal.
Endogenous fibrinolytic system in chronic large-vessel thromboembolic pulmonary hypertension.
Authors: Olman M A , Marsh J J , Lang I M , Moser K M , Binder B R , Schleef R R 
Published: June 2012

BACKGROUND
Chronic thromboembolic pulmonary hypertension (CTEPH) is a disorder characterized by pulmonary arterial hypertension as a consequence of organized thrombotic material in the central pulmonary arteries. Incomplete resolution of acute pulmonary emboli is believed to be pathogenically important; however, the mechanism for poor thrombus dissolution remains to be explained. We undertook this study to assess the major determinants of plasma fibrinolysis in patients with CTEPH (n = 32).

METHODS AND RESULTS
Immunological and functional levels of tissue-type plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) were quantified in platelet-poor plasma (PPP) from patients with CTEPH as well as age-matched controls. Although basal PPP t-PA antigen levels (CTEPH mean, 29.5 ng/ml; control mean, 2.7 ng/ml) and PAI-1 antigen levels (CTEPH mean, 55.8 ng/ml; control mean, 21.0 ng/ml) were higher in the CTEPH group, no between-group differences were detected in the enzymatic activities of these two molecules. The CTEPH group demonstrated a greater rise in t-PA antigen (CTEPH mean rise, 53.0 ng/ml; control mean rise, 5.6 ng/ml) and PA activity (CTEPH mean rise, 10.5 IU/ml; control mean rise, 1.2 IU/ml) than controls in response to an experimentally induced venous occlusion. Immunoprecipitation and fibrin autography of PPP from two patients with markedly elevated basal t-PA antigen levels demonstrate that the t-PA antigen was present in PPP primarily in complex with PAI-1.

CONCLUSIONS
Although abnormalities of the fibrinolytic system were detected, neither a high resting plasma PAI-1 activity nor a blunted response of t-PA to venous occlusion can be invoked as an etiology for CTEPH:
Multivariate genetic analysis of blood pressure and body size. The Medical College of Virginia Twin Study.
Authors: Schieken R M , Mosteller M , Goble M M , Moskowitz W B , Hewitt J K , Eaves L J , Nance W E 
Published: June 2012

BACKGROUND
In subjects of all ages, those who weigh the most often have the highest blood pressure. Thus, in epidemiological studies, weight is the most important correlate of blood pressure. Using the data from the Medical College of Virginia Twin Study, we asked these questions: 1) Do the same genetic paths that regulate body size also regulate systolic and diastolic blood pressure? 2) Are there distinct genetic pathways that regulate each of these variables? 3) Does environment play a major regulatory role? 4) Are the correlations among these variables mainly due to genetic or environmental effects? 5) Do genetic paths that regulate body size mediate the correlation between systolic blood pressure and diastolic blood pressure?

METHODS AND RESULTS
We ascertained 253 Caucasian twin pairs living in the Commonwealth of Virginia. The average age was 11.2 +/- 0.2 years. We used multivariate path analyses to investigate the genetic relations among systolic blood pressure, diastolic blood pressure, and body size. We found that there was a highly significant genetic relation between systolic blood pressure and body size and between systolic and diastolic blood pressure. There are genetic paths that are shared within these two sets of variables, but in each case, the paths for each pair appear to be separate from one another.

CONCLUSIONS
These analyses provide a method to partition correlation coefficients found in epidemiological studies into genetic and environmental components. The correlations found among these three variables are in large part due to these genetic relations. We found no genetic relation between diastolic blood pressure and body size.
How does angioplasty work? Serial analysis of human iliac arteries using intravascular ultrasound.
Authors: Losordo D W , Rosenfield K , Pieczek A , Baker K , Harding M , Isner J M 
Published: June 2012

BACKGROUND
Previous studies regarding the mechanism by which balloon angioplasty increases luminal patency have generally used animal models or postmortem specimens from occasional fatal cases of angioplasty performed in human patients. In either case, conclusions regarding participatory mechanisms have relied exclusively on nonserial, postangioplasty histopathological examination.

METHODS AND RESULTS
In the present study, intravascular ultrasound examination was performed before and after balloon angioplasty in 40 consecutive patients with iliac artery stenoses. The areas of the arterial wall, plaque, lumen, and areas resulting from angioplasty-induced plaque fractures were measured immediately after angioplasty in vivo and compared with findings recorded immediately before angioplasty. Angioplasty increased luminal cross-sectional area (CSA) from 11.5 +/- 0.6 mm2 before angioplasty to 25.4 +/- 1.2 mm2 after angioplasty (p = 0.0001). CSA of the portion of the postangioplasty neolumen contained within angioplasty-induced plaque fractures measured 10.0 +/- 0.8 mm2; the neolumen excluding the area contributed by these plaque fractures measured 15.4 +/- 0.8 mm2. Thus, the area contained within plaque fractures accounted for 10.0 mm2 (71.9%) of the 13.9-mm2 increase in luminal CSA after angioplasty. Analysis of CSA occupied by atherosclerotic plaque disclosed that plaque CSA decreased from 33.8 +/- 1.8 mm2 before angioplasty to 22.5 +/- 1.5 mm2 after angioplasty (p = 0.0001). Plaque CSA was thus reduced ("compressed") by 11.3 +/- 1.1 mm2. Total artery CSA increased ("stretched") slightly from 45.3 +/- 2.6 mm2 before angioplasty to 47.8 +/- 2.0 mm2 after angioplasty (p = 0.0025).

CONCLUSIONS
In vivo analysis of iliac stenoses by intravascular ultrasound immediately before and after angioplasty demonstrates that plaque fractures and "compression" of atherosclerotic plaque are the principal factors responsible for increased luminal patency resulting from balloon angioplasty. "Stretching" of the arterial wall provides an additional, but minor, contribution.
Reentrant and focal mechanisms underlying ventricular tachycardia in the human heart.
Authors: Pogwizd S M , Hoyt R H , Saffitz J E , Corr P B , Cox J L , Cain M E 
Published: June 2012

BACKGROUND
To determine the mechanisms of ventricular tachycardia (VT) in humans, three-dimensional intraoperative mapping of up to 156 intramural sites was performed in 13 patients with healed myocardial infarction and refractory VT.

METHODS AND RESULTS
Mapping was of sufficient density to define the mechanism of 10 VTs in eight patients. In five of 10 cases, sustained VT was initiated in the subendocardium or epicardium by intramural reentry with marked conduction delay as well as functional and anatomic block most prominent in the subendocardium and midmyocardium. The initiating beats of reentrant VT induced by programmed electrical stimulation arose in the endocardium or midmyocardium by progressive slowing of conduction leading to unidirectional block. Multiple simultaneous reentrant circuits can be present. In contrast, five of the 10 sustained VTs were initiated by a focal mechanism as defined by the absence of electrical activity between the termination of one beat and the initiation of the next despite the presence of multiple intervening intramural electrode recording sites. Comparisons of the mapping data with results of histopathological analysis of tissue demonstrated that the location of infarction as well as that of adjacent fibrotic muscle determined sites of both fixed and functional conduction block during macroreentrant VT and that slowing of conduction occurred in a direction transverse rather than longitudinal to fiber orientation.

CONCLUSIONS
Both intramural reentry and a focal mechanism underlie sustained VT in patients with healed myocardial infarction.