bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT-III) study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK)
Authors: Neuhaus K L , von Essen R , Tebbe U , Jessel A , Heinrichs H , Mäurer W , Döring W , Harmjanz D , Kötter V , Kalhammer E 
Published: June 2012

BACKGROUND
Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinant hirudin (HBW 023) with heparin. The primary end point was the incidence of death or reinfarction.

METHODS AND RESULTS
Seven thousand patients with acute myocardial infarction and a duration of symptoms of less than 6 hours were to be randomized to receive intravenous heparin (70 IU/kg body wt bolus and 15 IU.kg-1.h-1) or hirudin (0.4 mg/kg body wt bolus and 0.15 mg.kg-1.h-1) infused over 48 to 72 hours and adjusted to an activated partial thromboplastin time of 2 to 3.5 times baseline values. In a pilot phase, 1000 patients receiving front-loaded alteplase for thrombolysis were to be recruited by 93 German centers. After enrollment of 302 patients, the trial was stopped after an increased rate of intracranial bleeding was observed in the hirudin group (5 of 148, 3.4%) compared with the heparin group (0 of 154). The overall stroke rate was 3.4% in the hirudin group and 1.3% in the heparin group. Other major bleeding occurred in five versus three patients and ventricular rupture occurred in three versus one patient in the hirudin and heparin groups, respectively. There were 19 in-hospital deaths, with 13 of them from the hirudin group.

CONCLUSIONS
Although the number of patients was too small for a definite benefit-risk assessment, at the dosage tested, hirudin in combination with front-loaded alteplase and aspirin may be associated with an increased rate of intracranial hemorrhage. Our findings are consistent with the observations of the GUSTO-II and TIMI-9 trials, where higher doses of another recombinant hirudin were used. Therefore, the therapeutic range of hirudin as an adjunct to thrombolysis may be smaller than previously thought, and reappraisal of dose finding should be considered.
Beneficial effects of metoprolol treatment in congestive heart failure. Reversal of sympathetic-induced alterations of immunologic function.
Authors: Maisel A S 
Published: June 2012

BACKGROUND
Little information is available to explain why beta-blockers are beneficial in certain patients with congestive heart failure (CHF). Since catecholamines alter immune function, we asked whether beta-blocker treatment leads to enhancement of immune function.

METHODS AND RESULTS
Fifteen patients with New York Heart Association class III-IV CHF secondary to dilated cardiomyopathy were titrated to a minimum dose of metoprolol 25 mg BID on a background therapy of digoxin, diuretic, and angiotensin-converting enzyme inhibitors. Cardiac and immunologic studies were done before and 6 months to 1 year after treatment. While these patients served as their own controls, an additional population of patients with heart failure was followed for a similar time period on traditional medications. A panel of seven delayed hypersensitivity skin tests were placed at 6- to 12-month intervals on the patient's forearm. Seventy percent of all CHF patients were anergic (unable to respond to more than 1 antigen). The 30% who could respond averaged 2.2 antigens. After treatment with metoprolol, only 20% remained anergic (P < .001). The 80% of responders averaged 4.2 antigens (P < .001). Additionally, patients treated with metoprolol had an increased percentage of T cells, natural killer cells, and increased interleukin-2 receptor density upon stimulation with concanavalin A. These changes correlated to increases in ejection fraction. Patients not treated with metoprolol remained anergic and had no beneficial immunologic changes.

CONCLUSIONS
It appears that patients with dilated cardiomyopathy who are treated with metoprolol have enhancement of cell-mediated immunity and improvement of T-cell function; these improvements are correlated to improvement in ejection fraction.
New aspects in ultrasound-guided compression repair of postcatheterization femoral artery injuries.
Authors: Schaub F , Theiss W , Heinz M , Zagel M , Schömig A 
Published: June 2012

BACKGROUND
This study was undertaken to expand the understanding of ultrasound-guided compression repair (UGCR) of postcatheterization femoral artery injuries.

METHODS AND RESULTS
In a series of 62 patients with pseudoaneurysms (n = 53) or arteriovenous (AV) fistulas (n = 9), UGCR was performed as a nonsurgical method in the treatment of postcatheterization femoral artery injuries. When the communicating channel could be visualized (43 cases), pressure was focused on it; otherwise (10 cases) the extraluminal cavity itself was compressed. In 45 cases, the elimination of flow in the pseudoaneurysm and/or the communicating channel could be achieved only with simultaneous temporary complete occlusion of the femoral artery. UGCR was successfully performed in 25 of 27 cases of false aneurysms (93%) in patients without anticoagulation and in 14 of 26 patients (54%) on anticoagulants. Three of 9 AV fistulas could be repaired by this method. No apparent correlation could be found between the therapeutic success and the size of the pseudoaneurysm or the age of the lesion.

CONCLUSIONS
In patients on anticoagulants and in patients with AV fistulas, the detection of a communicating channel that could be obliterated by direct mechanical compression was discerned as a discriminant factor of success.
Characterization of ATP-induced vasodilation in the human forearm vascular bed.
Authors: Rongen G A , Smits P , Thien T 
Published: June 2012

BACKGROUND
Animal data indicate that ATP derived from aggregating thrombocytes or endothelium induces an endothelium-dependent vasodilator response that is mediated by P2y-purinergic receptors and is reduced when high dosages are administered. This reduced vasodilator response to high ATP doses has been associated with the concomitant release of endothelium-derived contracting factors. In contrast to the endothelium-dependent vasodilator response, ATP as released from sympathetic nerve endings induces a P2x-purinergic receptor-mediated vasoconstrictor response that may contribute to the attenuated vasodilator response to high dosages of luminally applied ATP. The dual action of ATP might be important in the pathophysiology of disease states characterized by an impaired endothelial function and increased thrombocyte aggregation. This study was performed to characterize the vascular response to ATP in humans.

METHODS AND RESULTS
The brachial artery was cannulated in 50 healthy male volunteers (age, 18 to 44 years) for drug infusion and measurement of mean arterial pressure. Forearm blood flow was recorded by venous occlusion strain-gauge plethysmography. ATP induced a dose-dependent vasodilator response that was significantly higher than the effect of equimolar adenosine infusion and that was not reduced by concomitant infusion of the P1-purinergic receptor antagonist theophylline. The infusion of the NO synthase antagonist NG-monomethyl-L-arginine (L-NMMA) reduced the average fall in forearm vascular resistance (FVR) to acetylcholine (-59 +/- 6% [mean +/- SEM] versus -42 +/- 8%; P < .05; N = 10) but did not affect the vasodilator response to ATP (-68 +/- 3% versus -64 +/- 6%; P > .1; N = 10) or sodium nitroprusside (SNP; -53 +/- 3% versus -49 +/- 4%; P > .01; N = 6). The L-NMMA-induced increase in FVR appeared to be related to the type of vasodilator pretreatment, being 94.7 +/- 16.7%, 44.9 +/- 8.7%, and 40.8 +/- 7.3% for acetylcholine, ATP, and SNP pretreatment, respectively (P < .01 for acetylcholine versus ATP and SNP; P > .1 for ATP versus SNP). In contrast to animal data, high dosages of intra-arterially infused ATP (up to 1000 micrograms.100 mL forearm-1.min-1) did not reveal a reduction in the forearm vasodilator response but appeared to be similar to the maximal forearm vasodilation as observed during postocclusive reactive hyperemia.

CONCLUSIONS
These observations indicate that ATP induces a potent dose-dependent vasodilator response that is not mediated by P1-purinergic receptor stimulation or by the release of nitric oxide. Moreover, in healthy volunteers, the vasodilator response to high intra-arterial dosages of ATP is not reduced by the release of endothelium-derived contracting factors or by the stimulation of P2x-purinergic receptors on the smooth muscle cells.
Platelet-induced vascular smooth muscle cell proliferation is modulated by the growth amplification factors serotonin and adenosine diphosphate.
Authors: Crowley S T , Dempsey E C , Horwitz K B , Horwitz L D 
Published: June 2012

BACKGROUND
Platelet-mediated mechanisms have been implicated in intimal lesion formation following vascular injury. Although the participation of peptide growth factors has been suspected in this process, little has been known about the possible mitogenic role of other platelet factors that are released at sites of vascular injury.

METHODS AND RESULTS
We tested the hypothesis that platelet products, which are not peptide growth factors, are important modulators of the platelet-induced smooth muscle cell (SMC) proliferative response by acting as growth amplification factors. In these studies, cell proliferation was assessed by [3H]thymidine incorporation, flow cytometry, and direct cell counting. We examined the potential mitogenicity of several platelet products, including serotonin, ADP, norepinephrine, histamine, platelet-activating factor, the thromboxane A2 mimetic U46619, and bradykinin. Of the platelet products tested, serotonin and ADP induced a synergistic response with peptide growth factors. This synergy was greatest at low growth-factor concentrations. Addition of nonaggregated platelets to quiescent SMC cultures strongly stimulated cell proliferation. Since the addition of suramin to platelet-treated cultures markedly inhibited SMC proliferation, peptide growth factors are most likely the primary mitogens mediating this response. However, platelet-induced proliferation was also markedly reduced by the serotonin antagonists ketanserin and LY53857 (44%), and by the ADP antagonist apyrase (35%).

CONCLUSIONS
Therefore, serotonin and ADP contribute significantly, in synergy with peptide growth factors, to the platelet-induced SMC proliferative response. We propose that in vivo serotonin and ADP act as amplification factors for SMC proliferation at sites of vascular injury.
An angiotensin II receptor antagonist reduces myocardial damage in an animal model of myocarditis.
Authors: Tanaka A , Matsumori A , Wang W , Sasayama S 
Published: June 2012

BACKGROUND
Recently, an angiotensin-converting enzyme inhibitor was shown to have a beneficial effect on virus-induced myocardial injury. We investigated the effect of a new angiotensin II type 1 receptor antagonist, (+-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-([2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl)-1H-benz imi dazole-7- carboxylate (TCV-116), in an animal model of viral myocarditis induced by encephalomyocarditis virus.

METHODS AND RESULTS
Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus. TCV-116 (in 5% gum arabic) was given 1 day before (1 or 10 mg/kg) or 2 days after virus inoculation (0.3 or 3 mg/kg). Control mice received the vehicle only. All drugs were administered orally on a daily basis, and the animals were killed on day 14. When treatment was started 1 day before inoculation, the survival of mice receiving 10 mg/kg of TCV-116 improved (17 of 20 [85%] versus 14 of 22 [64%] control mice), but the difference was not significant. Heart weight (106 +/- 24 mg versus 133 +/- 33 mg, P < .05), histological scores for myocardial necrosis (1.1 +/- 0.3 versus 2.3 +/- 1.2, P < .01), cellular infiltration (1.4 +/- 0.7 versus 2.6 +/- 1.3, P < .05), and calcification (1.1 +/- 0.3 versus 2.1 +/- 1.1, P < .01) were significantly decreased in mice given TCV-116 at 3 mg/kg compared with the vehicle control mice. The plasma angiotensin II level was significantly higher in infected mice than in noninfected mice (71.8 +/- 30.2 versus 31.8 +/- 22.5 pg/mL, P < .05). TCV-116 did not inhibit viral replication in the heart.

CONCLUSIONS
This study suggests that angiotensin II plays an important pathophysiological role in viral myocarditis. Treatment with TCV-116, an angiotensin II receptor antagonist, had a cardioprotective effect.
Plasma triglycerides and three lipoprotein cholesterol fractions are independent predictors of the extent of coronary atherosclerosis.
Authors: Drexel H , Amann F W , Beran J , Rentsch K , Candinas R , Muntwyler J , Luethy A , Gasser T , Follath F 
Published: June 2012

BACKGROUND
The lipoprotein system has manifold links to atherosclerotic disease. LDL cholesterol is related to lesion formation and growth. The cholesterol of HDLs is indicative of protection against atherosclerosis. The status of triglycerides and of subfractions of high-density lipoproteins as risk factors is less certain. Also, the magnitude of the atherogenic/protective power of these factors is not known.

METHODS AND RESULTS
Five hundred patients (418 men and 82 women) were enrolled in an angiographic study. A total of 1006 coronary lesions with > or = 50% narrowing were recorded as study end points. By extent of atherosclerosis, defined as the number of > or = 50% lesions, the study subjects were allocated to one of four ordered categories with 0, 1 to 3, 4 to 6, or 7 to 10 lesions, respectively. Subfractions of HDL cholesterol were determined by a dual precipitation method. By a polychotomous logistic regression model, it was found that, besides age and sex, LDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, and triglycerides were independently predictive (P < .05) of the extent of coronary atherosclerosis. An increase in age by 10 years was associated with an increase of the odds ratio for falling into a higher-extent category by a factor of 1.64, and the same increase of the odds ratio was obtained by increasing LDL cholesterol by 0.92 mmol/L or triglycerides by 1.01 mmol/L and by decreasing HDL2 cholesterol by 0.20 mmol/L or HDL3 cholesterol by 0.46 mmol/L. The less sensitive coronary end point, presence of atherosclerosis (ie, observation of > or = 1 lesion of > or = 50%) depended significantly on age, sex, LDL cholesterol, and HDL2 cholesterol, but not on HDL3 cholesterol or triglycerides.

CONCLUSIONS
In addition to LDL, HDL2, and HDL3 cholesterol, triglycerides also proved independently predictive of the extent of coronary atherosclerosis.
Upper limit of vulnerability reliably predicts the defibrillation threshold in humans.
Authors: Hwang C , Swerdlow C D , Kass R M , Gang E S , Mandel W J , Peter C T , Chen P S 
Published: June 2012

BACKGROUND
The upper limit of vulnerability is the stimulus strength above which electrical stimulation cannot induce ventricular fibrillation even when the stimulus occurs during the vulnerable period of the cardiac cycle. The purpose of this study was to test the hypothesis that the upper limit of vulnerability can accurately predict the defibrillation threshold in patients undergoing implantable cardioverter-defibrillator (ICD) implantation using nonthoracotomy lead systems.

METHODS AND RESULTS
We studied 77 patients at the time of ICD implantation. Multiple endocardial-endocardial and endocardial-subcutaneous shock pathways were used. Two different protocols were used to test the upper limit of vulnerability. In protocol 1 (n = 17), the upper limit of vulnerability was tested with two shocks on the peak or the up-slope of the T wave of paced rhythm. The shocks were given randomly either at the peak and 20 milliseconds before the peak of T wave (n = 7) or at 20 and 40 milliseconds before the peak of T wave (n = 10). In protocol 2 (n = 60), the upper limit of vulnerability was tested with three shocks delivered at 0, 20, and 40 milliseconds before the peak of the T wave. The weakest shock that failed to induce ventricular fibrillation by a 5-J step-down or step-up method was defined as the upper limit of vulnerability. The defibrillation threshold was also determined by a 5-J step-down or step-up method. In protocol 1, the upper limit of vulnerability (9 +/- 6 J) was significantly lower than the defibrillation threshold (13 +/- 7 J) with a correlation coefficient of .87 and P < .001. In protocol 2, the upper limit of vulnerability (13 +/- 6 J) was not significantly different from the defibrillation threshold (13 +/- 6 J) with a correlation coefficient of .85 and P < .001. In 45 of the 60 patients, the upper limit of vulnerability was < or = 15 J; all had a defibrillation threshold of < or = 20 J. In 51 of the 60 patients, the upper limit of vulnerability was within 5 J of the defibrillation threshold. The upper limit of vulnerability overestimated the defibrillation threshold by > 10 J in 8 patients and underestimated the defibrillation threshold by > 10 J in only 1 patient. The overestimation and underestimation occurred only in patients with the upper limit of vulnerability > 15 J.

CONCLUSIONS
When tested with three shocks on and before the peak of the T wave, the upper limit of vulnerability accurately predicted the defibrillation threshold in patients undergoing ICD implantation using nonthoracotomy lead systems. This method required either one or no episodes of ventricular fibrillation in most patients.
Sudden death in the young. Is acute coronary thrombosis the major precipitating factor?
Authors: Corrado D , Basso C , Poletti A , Angelini A , Valente M , Thiene G 
Published: June 2012

BACKGROUND
Atherosclerotic coronary artery disease, complicated by acute thrombosis, is the usual cause of sudden death in adults. This study addresses the pathology of coronary arteries in sudden death in the young (< or = 35 years old).

METHODS AND RESULTS
Among 200 consecutive cases of sudden death in youth in the Veneto region of Italy, 37 (33 men and 4 women, age 18 to 35 years; mean, 29.4 years) showed obstructive atherosclerotic coronary artery disease in the absence of other cardiac pathological conditions and causes of death. No patient had previous angina pectoris or myocardial infarction. Cardiac arrest occurred at rest in 30 subjects and was related to effort in 7. A histological study was carried out on the obstructive coronary plaques. Degree of lumen stenosis and extension of lipid core and intimal fibrocellular hyperplasia facing the lumen were calculated morphometrically. Immunohistochemistry and electron microscopy were used to further characterize the plaque cell population. Single-vessel disease was found in 33 patients and triple-vessel disease in 4, with an overall total of 45 obstructive plaques, 34 of which were located in the proximal left anterior descending coronary artery. At histological study, only 10 plaques from 10 patients showed acute thrombosis (occlusive in 5 and subocclusive in 5); the remaining 35 were uncomplicated. Thirty-one plaques were fibrous in nature, while the other 14 were atheromatous. Compared with the atheromatous lesions, the fibrous plaques were rarely complicated by thrombosis (3% versus 64%; P < .001) and distinctly exhibited a fairly well-preserved tunica media (81% versus 21%; P < .001) as well as a stratum of neointimal fibrocellular hyperplasia (68% versus 7%; P < .001), which on immunohistochemistry and electron microscopy appeared to be proliferating smooth muscle cells.

CONCLUSIONS
In our study population, sudden death was precipitated by acute coronary thrombosis in only 27% of patients with obstructive coronary atherosclerotic plaque. Most of the young victims of sudden death with obstructive coronary atherosclerosis showed single-vessel disease that affected the left anterior descending coronary artery and was due to fibrous plaques with neointimal smooth muscle cell hyperplasia and a preserved tunica media in the absence of acute thrombosis.
Oxygen uptake kinetics are determined by cardiac function at onset of exercise rather than peak exercise in patients with prior myocardial infarction.
Authors: Koike A , Hiroe M , Adachi H , Yajima T , Yamauchi Y , Nogami A , Ito H , Miyahara Y , Korenaga M , Marumo F 
Published: June 2012

BACKGROUND
Resting cardiac function does not necessarily affect exercise capacity. However, to determine whether it affects early dynamics of oxygen uptake (VO2) during exercise, we measured VO2 during a constant work rate and during incremental exercise testing in patients with a history of myocardial infarction. VO2 kinetics and exercise capacity were compared between patients with relatively high left ventricular ejection fractions (LVEF > or = 35%, group 1) and those with lower ejection fractions (LVEF < 35%, group 2).

METHODS AND RESULTS
Forty patients with a history of prior myocardial infarction (age, 57 +/- 10 years) were monitored during 6 minutes of moderate constant work rate testing (40 +/- 8 W) and during symptom-limited incremental exercise testing with a cycle ergometer. VO2 was calculated from respired gas analysis on a breath-by-breath basis. Cardiac output determinations were made with a computerized cadmium telluride detector every 10 seconds during exercise. The VO2 time constant during constant work rate exercise was slower in group 2 (58.0 +/- 7.6 seconds) compared with group 1 (45.8 +/- 10.5 seconds, P = .0002), indicating slower kinetics in group 2. The time constant for the rise in cardiac output during exercise was also slower in patients with lower EFs (63.0 +/- 12.8 versus 50.0 +/- 12.2 seconds). However, there were no differences in exercise capacity parameters, such as the VO2 or cardiac output at peak exercise, obtained during incremental exercise testing among the two groups.

CONCLUSIONS
The prolonged time constant of VO2, which is primarily determined during early parts of exercise, reflects delayed cardiac output response in patients with severely impaired LV function. The time constant of VO2 during submaximal constant work rate exercise can be used as a sensitive and discriminant measure of impaired cardiac reserve in these patients.