bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous 12-lead ST-segment recovery analysis in the TAMI 7 study. Performance of a noninvasive method for real-time detection of failed myocardial reperfusion.
Authors: Krucoff M W , Croll M A , Pope J E , Granger C B , O'Connor C M , Sigmon K N , Wagner B L , Ryan J A , Lee K L , Kereiakes D J 
Published: June 2012

BACKGROUND
If a practical, reliable, noninvasive marker of failed reperfusion was available in real time, the benefits of further therapy in this patient subgroup could be tested. We developed a method of 12-lead ST-segment recovery analysis using continuously updated reference points to provide such a marker.

METHODS AND RESULTS
In this study, our method was prospectively tested in 144 patients given thrombolytic therapy early in myocardial infarction. All patients had 12-lead continuous ST-segment monitoring and acute angiography, each analyzed in an independent, blinded core laboratory. ST-segment recovery and re-elevation were analyzed up to the moment of angiography, at which time patency was predicted. Predictions were correlated to angiographic infarct artery flow, with TIMI flow 0 to 1 as occluded and TIMI flow 2 to 3 as patent. Infarct artery occlusion was seen on first injection in 27% of patients. The positive predictive value of incomplete ST recovery or ST re-elevation by our method was 71%, negative predictive value 87%, with 90% specificity and 64% sensitivity for coronary occlusion. ST recovery analysis predicted patency in 94% of patients with TIMI 3 flow versus 81% of patients with TIMI 2 flow and predicted occlusion in 57% of patients with collateralized occlusion versus 72% of patients with non-collateralized occlusion. In a regression model including other noninvasive clinical descriptors, ST recovery alone contained the vast majority of predictive information about patency.

CONCLUSIONS
In a blinded, prospective, angiographically correlated study design, 12-lead continuous ST-segment recovery analysis shows promise as a practical noninvasive marker of failed reperfusion that may contribute substantially to currently available bedside assessment. Our data also suggest that patients with TIMI 2 flow or with collateralized occlusions may represent a physiological spectrum definable with ST-segment recovery analysis.
Comparison of native prothrombin antigen with the prothrombin time for monitoring oral anticoagulant prophylaxis.
Authors: Kornberg A , Francis C W , Pellegrini V D , Gabriel K R , Marder V J 
Published: June 2012

BACKGROUND
Oral anticoagulation is most frequently monitored using the prothrombin time, but an alternative approach is measurement of native, fully carboxylated, prothrombin antigen (NPA). We have correlated results of the prothrombin time and NPA with development of venous thrombosis or bleeding complications in a clinical trial of warfarin prophylaxis following total hip arthroplasty to determine the potential value of NPA measurement for monitoring oral anticoagulation.

METHODS AND RESULTS
Patients in one arm of a prospective, randomized trial received warfarin prophylactically beginning 10 to 14 days before total hip arthroplasty in a dose adjusted to prolong the international normalized ratio (INR) to 1.5 on the day of surgery and 2.5 after surgery. NPA was measured by ELISA, and the prothrombin time was measured using rabbit brain thromboplastin. Samples were tested from 97 patients, and data from 81 patients who had adequate venography were analyzed to correlate test results with occurrence of thrombosis. The prothrombin time and INR were less sensitive than NPA to the lowest intensities of anticoagulation, with the prothrombin time index increasing from 1.0 to 1.3 and the INR increasing from 1.0 to 2.0, whereas the NPA concentration decreased fourfold, from 200 to 50 micrograms/mL. There was little correlation between either the prothrombin time index or the INR and the development of thrombosis, whereas NPA concentrations were significantly higher on the day of surgery and on postoperative days 1, 3, 5, and 7 in patients who developed venous thrombosis. Higher concentrations of NPA were associated with an increased risk of venous thrombosis, but there was no relation between thrombosis and the prothrombin time index or INR. There was no significant correlation between surgical blood loss and prothrombin time index, INR, or NPA concentration. However, patients who received the largest number of transfusions on the day of surgery had significantly lower NPA concentrations than patients who required no transfusion.

CONCLUSIONS
These results indicate that the NPA concentration more accurately reflects the antithrombotic effect of warfarin than does prothrombin time and may be superior in monitoring prophylactic oral anticoagulation.
Exercise conditioning in older coronary patients. Submaximal lactate response and endurance capacity.
Authors: Ades P A , Waldmann M L , Poehlman E T , Gray P , Horton E D , Horton E S , LeWinter M M 
Published: June 2012

BACKGROUND
Older coronary patients are at high risk of cardiac disability. Exercise conditioning programs have been demonstrated to improve functional capacity, particularly in younger coronary patients. In this study, the effects of aerobic conditioning on submaximal and maximal indicators of exercise performance were examined in 45 older coronary patients.

METHODS AND RESULTS
Forty-five patients (mean age, 69 +/- 6 years; range, 62 to 82 years) entered 3-month and 12-month (n = 11) endurance training programs. Training effects were assessed during an exhaustive submaximal exercise protocol with measurement of endurance time, serum lactate, perceived exertion, and expired ventilatory measures. Exhaustive endurance time increased by more than 40% (30 +/- 10 to 41 +/- 10 minutes), with associated decreases in serum lactate, perceived exertion, minute ventilation, heart rate, and systolic blood pressure during steady-state exercise. Respiratory exchange ratio during steady-state exercise, an indicator of substrate utilization, decreased, indicating a shift toward greater use of free fatty acids as a metabolic fuel. In a subset of 10 patients, percent body fat was decreased (32 +/- 8% to 29 +/- 10%) over a period of 3 months.

CONCLUSIONS
Older coronary patients respond to aerobic conditioning with remarkable improvements in submaximal endurance capacity, out of proportion to the more modest increases in VO2max. Activities that were exhaustive before training became sustainable for extended periods of time at a lower perceived exertion. Measurements of serum lactate, respiratory exchange ratio, and ventilation during steady-state exercise document that at an identical absolute work load after conditioning, exercise is performed using aerobic substrate to a greater degree, and ventilatory response to a given work load is lessened.
Probucol decreases neointimal formation in a swine model of coronary artery balloon injury. A possible role for antioxidants in restenosis.
Authors: Schneider J E , Berk B C , Gravanis M B , Santoian E C , Cipolla G D , Tarazona N , Lassegue B , King S B 
Published: June 2012

BACKGROUND
Restenosis after percutaneous transluminal coronary angioplasty is the major limitation of the long-term success of this procedure. The process of restenosis is similar to an accelerated form of atherosclerosis. Thus, therapeutic interventions that limit the progression and initiation of atherosclerosis may be beneficial in the treatment of restenosis. One such intervention is the antioxidant drug probucol, which has demonstrated benefit in animal models of atherosclerosis.

METHODS AND RESULTS
Twenty-six female domestic swine were divided into three study groups (control, n = 9; low-dose probucol, n = 9; high-dose probucol, n = 8) before oversized balloon injury of the left anterior descending and left circumflex coronary arteries. Probucol (1 g/d, low-dose group; 2 g/d, high-dose group) was administered 2 days before balloon injury and was continued until the swine were killed 2 weeks after balloon injury. Morphometric analysis of the injured arteries included the intimal area (square millimeters), maximal intimal thickness (millimeters), and residual lumen (ratio of luminal to intimal plus luminal area). Treatment with high-dose probucol significantly reduced neointimal formation compared with control animals (decreases of 36% in intimal area, P = .007; 20% in maximal intimal thickness, P = NS; and an increase of 15% in residual lumen, P = .02).

CONCLUSIONS
The major finding of this study is that the antioxidant drug probucol reduces neointimal formation after oversized balloon injury in a swine model of restenosis. This suggests that active oxygen species may play a role in restenosis.
Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. Relevance of clinical characteristics and pacing modalities.
Authors: Sgarbossa E B , Pinski S L , Maloney J D , Simmons T W , Wilkoff B L , Castle L W , Trohman R G 
Published: June 2012

BACKGROUND
The goal of the report was to study the long-term incidence and the independent predictors for chronic atrial fibrillation and stroke in 507 paced patients with sick sinus syndrome, adjusting for differences in baseline clinical variables with multivariate analysis.

METHODS AND RESULTS
From 1980 to 1989, we implanted 376 dual-chamber, 19 atrial, and 112 ventricular pacemakers to treat patients with sick sinus syndrome. After a maximum follow-up of 134 months (mean: 59 +/- 38 months for chronic atrial fibrillation, 65 +/- 37 months for stroke), actuarial incidence of chronic atrial fibrillation was 7% at 1 year, 16% at 5 years, and 28% at 10 years. Independent predictors for this event, from Cox's proportional hazards model, were history of paroxysmal atrial fibrillation (P < .001; hazard ratio [HR] = 16.84), use of antiarrhythmic drugs before pacemaker implant (P < .001; HR = 2.25), ventricular pacing mode (P = .003; HR = 1.98), age (P = .005; HR = 1.03), and valvular heart disease (P = .008; HR = 2.05). For patients with preimplant history of paroxysmal atrial fibrillation, independent predictors were prolonged episodes of paroxysmal atrial fibrillation (P < .001; HR = 2.56), long history of paroxysmal atrial fibrillation (P = .004; HR = 2.05), ventricular pacing mode (P = .025; HR = 1.69), use of antiarrhythmic drugs before pacemaker implant (P = .024; HR = 1.71), and age (P = .04; HR = 1.02). Actuarial incidence of stroke was 3% at 1 year, 5% at 5 years, and 13% at 10 years. Independent predictors for stroke were history of cerebrovascular disease (P < .001; HR = 5.22), ventricular pacing mode (P = .008; HR = 2.61), and history of paroxysmal atrial fibrillation (P = .037; HR = 2.81).

CONCLUSIONS
Development of chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome are strongly determined by clinical variables and secondarily by the pacing modality. Ventricular pacing mode predicts chronic atrial fibrillation in patients with preimplant paroxysmal atrial fibrillation but not in those without it.
Application of color Doppler flow mapping to calculate effective regurgitant orifice area. An in vitro study and initial clinical observations.
Authors: Vandervoort P M , Rivera J M , Mele D , Palacios I F , Dinsmore R E , Weyman A E , Levine R A , Thomas J D 
Published: June 2012

BACKGROUND
Analogous to stenotic valve area in the assessment of valvular stenosis, regurgitant orifice area (ROA) represents a fundamental parameter to assess valvular insufficiency. However, this parameter has not been routinely available up to now. In this study, we introduce the concept and provide the methodology to calculate regurgitant orifice area noninvasively, based on the analysis of the proximal flow convergence zone.

METHODS AND RESULTS
In an in vitro study, we showed the feasibility and the accuracy of calculating effective ROA by the proximal flow convergence method throughout a range of driving pressures. The calculated and true ROA showed an excellent correlation with r = .992, delta ROA = -1.4 +/- 2.9 mm2. We then applied this concept clinically in 77 patients with mitral regurgitation and showed a very good correlation between effective ROA calculated by the proximal flow convergence method and calculated by the Doppler echocardiographic method: r = .95, delta ROA = -0.2 +/- 3.9 mm2. The ROA also correlated very well with Doppler echocardiographic-derived regurgitant stroke volume (r = .93) and regurgitant fraction (r = .82). In a subgroup of 20 patients who underwent invasive evaluation, the calculated effective ROA also correlated well with the angiographic grade of mitral regurgitation (rho = .81).

CONCLUSIONS
We conclude that effective ROA represents unique information on the severity of a regurgitant lesion and can easily be calculated by the proximal flow convergence method. This new parameter should enhance our understanding and improve the serial assessment of valvular regurgitation.
Downregulation of c-myc expression by antisense oligonucleotides inhibits proliferation of human smooth muscle cells.
Authors: Shi Y , Hutchinson H G , Hall D J , Zalewski A 
Published: June 2012

BACKGROUND
Proliferation of smooth muscle cells (SMCs) plays an important role in vascular pathobiology, being involved in the development of coronary restenosis and atherosclerosis. The activation of nuclear proto-oncogenes appears to be a final common pathway onto which various mitogenic signals coverage. Accordingly, we attempted to determine whether the activation of the c-myc nuclear proto-oncogene is essential for human SMC proliferation and explored the possibility of inhibiting their growth using antisense oligonucleotides directed against c-myc messenger RNA (mRNA).

METHODS AND RESULTS
Proliferation of human SMCs was associated with an increase in c-myc mRNA expression after growth stimulation. Using 15-mer phosphorothioate oligonucleotides (oligomers), we tested their growth-inhibitory effect in SMCs in vitro. Antisense oligomers directed against the translation initiation region of the human c-myc gene exhibited a significant antiproliferative effect, whereas sense and mismatched oligomers did not inhibit the growth. The growth-inhibitory effect of c-myc antisense oligomers was dose dependent and preventable by an excess of sense oligomers. Furthermore, growth inhibition of SMCs treated with c-myc antisense oligomers was associated with a marked decrease in the c-myc mRNA level. Phosphorothioate oligomers remained stable in medium containing 20% serum and were detectable in SMCs as early as 1 hour after cell exposure. Intact oligomers rapidly accumulated intracellularly and persisted within human SMCs for at least 16 hours.

CONCLUSIONS
c-myc antisense oligomers reduced c-myc expression and produced a significant growth inhibition of human SMCs, indicating an important role of c-myc gene activation in the process of SMC proliferation. Furthermore, extracellular stability and rapid cellular uptake provide the basis for future studies assessing the therapeutic role of the c-myc antisense approach in reducing SMC proliferation in the process of vascular restenosis.
Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction.
Authors: Marber M S , Latchman D S , Walker J M , Yellon D M 
Published: June 2012

BACKGROUND
To test the hypothesis that the heat shock response is associated with myocardial salvage, the heat stress protein (HSP) content of cardiac tissue was increased by either ischemic or thermal stress.

METHODS AND RESULTS
Rabbits were divided into four groups. Ischemic pretreatment (n = 15) comprised four 5-minute episodes of coronary ligation separated by 10 minutes of reperfusion. The corresponding control group (n = 21) underwent surgical preparation without coronary ligation. Thermal pretreatment (n = 16) involved whole-body temperature elevation to 42 degrees C for 15 minutes; corresponding controls (n = 15) were treated with anesthetic alone. Twenty-four hours later, hearts were removed for HSP estimation or infarct size assessment after a 30-minute coronary ligation. Myocardial HSP72 content assessed by Western blotting was elevated by both ischemic and thermal pretreatments (2.5 +/- 0.2 units, n = 4, and 2.8 +/- 0.3 units, n = 4, mean +/- SEM; P = NS, respectively) compared with the corresponding control groups (1.0 +/- 0.3, n = 4, P < or = .01 and 0.3 +/- 0.1, n = 4, P < or = .01, respectively). HSP60 was preferentially elevated by ischemic pretreatment. After a 30-minute coronary occlusion and 120 minutes of reperfusion, ischemic and thermal pretreatments limited infarct size as a percentage of the volume at risk by 28.8 +/- 5.2% vs 52.0 +/- 5.2%, P < or = .01 and 32.8 +/- 3.8% vs 56.9 +/- 6.5%, P < or = .01, respectively.

CONCLUSIONS
Myocardial stress protein induced by either sublethal thermal or ischemic injury is associated with myocardial salvage. Our findings suggest that stress protein elevation, rather than the nonspecific effects of thermal or ischemic stress, may be responsible for the myocardial protection seen in this model. Our observations may have important implications regarding myocardial adaptation to brief periods of ischemia.
Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction.
Authors: Liu Y , Thornton J D , Cohen M V , Downey J M , Schaffer S W 
Published: June 2012

BACKGROUND
The vulnerability of the myocardium of a diabetic animal to an ischemic insult is controversial. To address this issue, streptozotocin-induced non-insulin-dependent diabetes (NIDD) was induced in rats, and the effects of regional myocardial ischemia were assessed by measuring infarct size.

METHODS AND RESULTS
Open-chest rats with NIDD and age-matched control rats underwent 30 or 45 minutes of regional ischemia and 2-hour reperfusion. Infarct size was measured by tetrazolium. Control rats had 32.0 +/- 3.3% infarction of the risk zone after a 30-minute coronary occlusion, whereas NIDD rats had significantly smaller infarcts (11.5 +/- 3.1% of the risk area, P < .005). When ischemic time was extended to 45 minutes, infarct size in control animals averaged 57.9 +/- 6.2%, whereas only 37.3 +/- 5.6% of ischemic myocardium was infarcted in NIDD rats (P < .05). In a subset NIDD group, rats experienced a period of ischemic preconditioning (three cycles of 5-minute ischemia/5-minute reperfusion) before 45-minute ischemia. Infarct size in these rats averaged only 6.9 +/- 3.0% (P < .01 vs nonpreconditioned NIDD rats with 45-minute coronary occlusions). Collateral flow was measured in NIDD rat hearts with radioactive microspheres. Collateral flow was < 1% of normal myocardial blood flow.

CONCLUSIONS
We conclude that NIDD protects the heart from infarction and that this protection is not related to the development of coronary collaterals. Furthermore, preconditioning can further protect the NIDD heart.
Regional differences in function within noninfarcted myocardium during left ventricular remodeling.
Authors: Kramer C M , Lima J A , Reichek N , Ferrari V A , Llaneras M R , Palmon L C , Yeh I T , Tallant B , Axel L 
Published: June 2012

BACKGROUND
The mechanisms of ventricular enlargement and dysfunction during postinfarct remodeling remain largely unknown. Although global left ventricular architectural changes after myocardial infarction are well documented, differences in function between adjacent and remote noninfarcted myocardium during left ventricular remodeling have not been investigated. These functional differences may relate to regional differences in wall stress during contraction and may contribute to chamber enlargement and global dysfunction after infarction.

METHODS AND RESULTS
Anteroapical infarcts were produced in seven sheep by ligation of the mid left anterior descending coronary artery and second diagonal branch at thoracotomy. Magnetic resonance short-axis and long-axis images tagged by spatial modulation of magnetization were obtained before and 1 week, 8 weeks, and 6 months after infarction. Left ventricular volumes, mass, ejection fraction, and lengths of infarcted and noninfarcted segments were measured. Circumferential and longitudinal shortening in the subendocardium and subepicardium, wall thickness, and histopathology were assessed in infarcted segments and regions adjacent to and remote from the infarct border. We found that a difference in circumferential and longitudinal segmental shortening between adjacent and remote noninfarcted myocardium present at 1 week persisted up to 6 months after myocardial infarction. However, partial improvement of function in adjacent regions occurred during infarct healing between 1 and 8 weeks after infarction. Left ventricular volume increased up to 6 months after infarction, out of proportion to the concomitant eccentric hypertrophy, whereas the ejection fraction fell. Left ventricular dilatation late in the remodeling process was secondary to lengthening of noninfarcted segments, which were free of significant fibrosis.

CONCLUSIONS
Left ventricular dilatation and eccentric hypertrophy during remodeling are associated with persistent differences in segmental function between adjacent and remote noninfarcted regions. These functional differences may reflect increased wall stress in adjacent noninfarcted regions and contribute to the global dilatation and dysfunction characteristic of left ventricular remodeling after infarction.