bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of the transient outward potassium current in canine X-linked muscular dystrophy.
Authors: Pacioretty L M , Cooper B J , Gilmour R F 
Published: June 2012

BACKGROUND
The xmd dog develops a cardiomyopathy similar to that seen in Duchenne muscular dystrophy patients. In both the canine and human diseases, ECG abnormalities may precede the development of overt cardiac pathological lesions. The purpose of this study was to determine whether specific cellular electrical abnormalities occur in dystrophic ventricular tissue.

METHODS AND RESULTS
Action potentials were recorded in epicardial tissue strips obtained from normal and xmd dogs. Phase 1 amplitude was increased from 86.8 +/- 2.7 mV in normal dogs to 94.3 +/- 1.8 mV in xmd dogs (mean +/- SEM; P < .05). The 4-aminopyridine-sensitive transient outward potassium current (Ito), as recorded in isolated epicardial myocytes using the whole-cell patch-clamp technique, was reduced in xmd dogs compared with age-matched normal dogs. Cell capacitance also was reduced significantly in xmd compared with normal cells, as was the current density (3.6 +/- 0.3 versus 5.4 +/- 0.8 pA/pF, respectively). No differences were observed in the time constants of current decay or in the kinetics of recovery from inactivation between groups. The slope factor (k) of steady-state inactivation was significantly greater in xmd compared with normal cells (7.2 +/- 0.9 versus 5.4 +/- 0.5, respectively), whereas the V1/2 of inactivation did not differ (-38.2 +/- 2.4 versus -36.8 +/- 1.6 mV, respectively).

CONCLUSIONS
These data indicate that the magnitude of Ito is reduced in dystrophic epicardial myocytes, resulting in an increase in phase 1 amplitude. The reduction of Ito may alter the balance of inward and outward currents in dystrophic myocardium and thereby contribute to the development of cardiac pathology.
Dobutamine echocardiography for determining the extent of myocardial salvage after reperfusion. An experimental evaluation.
Authors: Sklenar J , Ismail S , Villanueva F S , Goodman N C , Glasheen W P , Kaul S 
Published: June 2012

BACKGROUND
Although dobutamine echocardiography is being increasingly used to determine the presence of viable myocardium in patients who have undergone successful reperfusion therapy, the physiological basis for such a use has not been clearly defined. Because postischemic myocardium has contractile reserve, we hypothesized that the absolute degree of wall thickening induced by dobutamine during reflow would be directly related to the amount of myocardium that has escaped necrosis.

METHODS AND RESULTS
Three groups of 12 dogs each were studied at baseline and during 2 to 6 hours of coronary artery occlusion and 15 minutes of reperfusion. In group 1 dogs, which did not receive dobutamine during any of these stages, percent wall thickening at these stages was 32 +/- 6%, -2 +/- 6%, and 5 +/- 6%, respectively, and there was no relation between infarct size and percent wall thickening during reflow (r = .20, P = .51). In group 2 dogs, which received 15 micrograms/kg per minute of dobutamine at all stages, wall thickening at these stages was 40 +/- 8%, 0 +/- 8%, and 19 +/- 10%, respectively, and a good inverse correlation was noted between infarct size and percent wall thickening during reflow (r = -.81, P = .001). In group 3 dogs, in which wall thickening during reflow was measured both before and during infusion of 15 micrograms/kg per minute of dobutamine, it was 5 +/- 8% and 18 +/- 14%, respectively, at these stages. Although the correlation between infarct size and percent wall thickening was poor in the absence of dobutamine (r = .36, P = .26), an excellent inverse correlation was noted between the two in the presence of dobutamine (r = -.93, P < .001). A fair inverse correlation was also noted between infarct size and the absolute change in wall thickening induced by dobutamine (r = -.72, P < .01). Maximal wall thickening was noted at a dobutamine dose of 15 micrograms/kg per minute, and lower doses did not elicit thickening in the presence of larger infarcts despite the presence of viable myocardium.

CONCLUSIONS
When myocardial necrosis coexists with post-ischemic myocardial dysfunction and no residual coronary stenosis, the absolute degree of wall thickening during dobutamine can be used to determine the extent of myocardium that has escaped necrosis. The dose of dobutamine needed to elicit maximal thickening of the postischemic myocardium is related to the amount of myocardial necrosis.
Global alteration in perfusion response to increasing oxygen consumption in patients with single-vessel coronary artery disease.
Authors: Sambuceti G , Marzullo P , Giorgetti A , Neglia D , Marzilli M , Salvadori P , L'Abbate A , Parodi O 
Published: June 2012

BACKGROUND
Recent evidence suggests that, in coronary artery disease (CAD), myocardial blood flow (MBF) regulation is abnormal in regions supplied by apparently normal coronary arteries. However, the relation between this alteration and MBF response to increasing metabolic demand has not been fully elucidated.

METHODS AND RESULTS
MBF was assessed at baseline, during atrial pacing tachycardia, and after dipyridamole (0.56 mg/kg IV over 4 minutes) in 9 normal subjects and in 24 patients with ischemia on effort, no myocardial infarction, and isolated left anterior descending (n = 19) or left circumflex (n = 5) coronary artery stenosis (> or = 50% diameter narrowing). Perfusion of both poststenotic (S) and normally supplied (N) areas was measured off therapy by positron emission tomography and [13N]ammonia. Normal subjects and CAD patients showed similar rate-pressure products at baseline, during pacing, and after dipyridamole. In CAD patients, MBF was lower in S than in N territories at rest (0.68 +/- 0.14 versus 0.74 +/- 0.18 mL.min-1.g-1, respectively, P < .05), during pacing (0.92 +/- 0.29 versus 1.16 +/- 0.40 mL.min-1.g-1, respectively, P < .01), and after dipyridamole (1.18 +/- 0.34 versus 1.77 +/- 0.71 mL.min-1.g-1, respectively, P < .01). However, normal subjects showed significantly higher values of MBF both at rest (0.92 +/- 0.13 mL.min-1.g-1, P < .05 versus both S and N areas), during pacing tachycardia (1.95 +/- 0.64 mL.min-1.g-1, P < .01 versus both S and N areas), and after dipyridamole (3.59 +/- 0.71 mL.min-1.g-1, P < .01 versus both S and N areas). The percent change in flow was strictly correlated with the corresponding change in rate-pressure product in normal subjects (r = .85, P < .01) but not in either S (r = .04, P = NS) or N regions (r = .08, P = NS) of CAD patients.

CONCLUSIONS
Besides epicardial stenosis, further factors may affect flow response to increasing metabolic demand and coronary reserve in patients with CAD.
Left ventricular function at 3 months after successful thrombolysis. Impact of reocclusion without reinfarction on ejection fraction, regional function, and remodeling.
Authors: Meijer A , Verheugt F W , van Eenige M J , Werter C J 
Published: June 2012

BACKGROUND
After successful thrombolysis for acute myocardial infarction, reocclusion is observed in about 30% of patients after 3 months and usually occurs without reinfarction. We studied the impact of reocclusion without reinfarction on global and regional left ventricular function and on remodeling during that period.

METHODS AND RESULTS
The patients for this analysis constituted a subset of those enrolled in the APRICOT-trial, which was designed to study the efficacy of antithrombotics on the prevention of reocclusion. Patients were selected who had a left anterior descending- or right coronary artery-related myocardial infarction, had an angiographically patent infarct-related vessel when studied < 48 hours after intravenous thrombolysis, and underwent repeat cardiac catheterization at 3 months. Paired contrast ventriculograms of quality sufficient to analyze regional wall motion, global ejection fraction, and ventricular volumes were analyzed in 129 patients. Enzymatic infarct size and baseline left ventricular function as well as other baseline characteristics were similar in patients with (n = 34) and without (n = 95) reocclusion. Ejection fraction improved in anterior infarction without reocclusion from 47 +/- 10% to 54 +/- 13% (P = .0001) but not with reocclusion (baseline, 48 +/- 13%; 3 months, 48 +/- 16%). No improvement was seen in inferior infarction with or without reocclusion. Persistent patency allowed preservation of end-systolic volume index (ESVI) at 3 months (37 +/- 14 mL/m2) to baseline level (38 +/- 13 mL/m2), with a better chance for improvement of > 10 mL/m2 without reocclusion in those with baseline values > 40 mL/m2. After reocclusion, in contrast, ESVI increased from 37 +/- 14 to 43 +/- 20 mL/m2 (P = .08). Comparable mean changes of ESVI in response to persistent patency or reocclusion were seen in anterior versus inferior infarction. Recovery of infarct zone contractility was impaired by reocclusion, both in terms of abnormality of segment shortening and expressed in the number of segments showing abnormal wall motion. In anterior but not in inferior infarction, infarct zone contractility was better with good collaterals to the reoccluded artery compared with poor collaterals.

CONCLUSIONS
After successful thrombolysis for acute myocardial infarction, reocclusion without reinfarction withholds salvaged myocardium from regaining contractility. This has deleterious consequences for regional and global left ventricular function and for remodeling. To further optimize prognosis in patients after thrombolysis, future research should focus on the prevention of reocclusion and should evaluate revascularization therapy in patients with reocclusion.
Sex differences in the management and long-term outcome of acute myocardial infarction. A statewide study. MIDAS Study Group. Myocardial Infarction Data Acquisition System.
Authors: Kostis J B , Wilson A C , O'Dowd K , Gregory P , Chelton S , Cosgrove N M , Chirala A , Cui T 
Published: June 2012

BACKGROUND
We wished to evaluate whether differences in the rate of invasive cardiac procedures between men and women with acute myocardial infarction are associated with different short- and long-term mortality.

METHODS AND RESULTS
The database (Myocardial Infarction Data Acquisition System, MIDAS) included all discharges for the years 1986 and 1987 with the diagnosis of acute myocardial infarction in New Jersey, based on the New Jersey hospital discharge data system (MIDS/UB-82). Accuracy of the data was evaluated by auditing 726 randomly selected charts. The variables examined included age, sex, race, comorbidity (anemia, chronic liver disease, cancer, chronic obstructive pulmonary disease, diabetes, hypertension, prior myocardial infarction), complications (left ventricular dysfunction, arrhythmias, conduction defects), insurance status, performance of cardiac catheterization, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery, and survival up to 3 years. Women were older, had longer hospital stay, and were more likely than men to have anemia, diabetes, hypertension, left ventricular dysfunction, and Medicare or Medicaid insurance coverage. They were less likely than men to be admitted to a hospital equipped to perform invasive procedures or to have chronic obstructive pulmonary disease, chronic liver disease, prior myocardial infarction, or arrhythmias. After adjustment for these differences, women were less likely than men to have cardiac catheterization. Cardiac catheterization was associated with lower mortality. Women up to age 70 had higher 3-year death rates than men after adjustment for age, race, comorbidity, complications, and insurance type. This difference between men and women was somewhat diminished after the performance of cardiac catheterization and revascularization was taken into account. Unadjusted mortality was high in this study group.

CONCLUSIONS
Women with acute myocardial infarction are less likely to have invasive cardiac procedures and have higher 3-year adjusted death rate up to age 70 than men.
Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty.
Authors: Tcheng J E , Ellis S G , George B S , Kereiakes D J , Kleiman N S , Talley J D , Wang A L , Weisman H F , Califf R M , Topol E J 
Published: June 2012

BACKGROUND
Thrombosis has been implicated as central to the clinical complications of coronary angioplasty (PTCA). Chimeric monoclonal 7E3 Fab (c7E3 Fab) is the first of a new class of antiplatelet drugs directed at the platelet glycoprotein IIb/IIIa integrin. This study was performed to determine the pharmacodynamics of c7E3 Fab administration during PTCA and to gain an initial clinical experience with this novel agent.

METHODS AND RESULTS
The study was a multicenter, open-label, dose-escalation study conducted in two stages. Enrollment included 56 patients scheduled for elective PTCA who were estimated to be at moderate to high risk of sustaining ischemic complications. All patients were given aspirin and heparin. The study drug was given at least 10 minutes before PTCA. In stage 1, increasing bolus doses of c7E3 Fab were given to 15 patients; a bolus dose of 0.25 mg/kg was found to result in blockade of > 80% of the receptors and reduce platelet aggregation to < 20% compared with baseline, establishing this dose as that necessary to sufficiently suppress platelet activity. In stage 2, additional c7E3 Fab was administered by continuous infusion to 32 patients for progressively longer periods of time (up to 24 hours) to confirm that platelet inhibition could be maintained with prolonged drug infusion. Also, 9 patients otherwise meeting entry criteria were given placebo. There were no thrombotic events among patients receiving c7E3 Fab. Overall procedural and clinical success and complication rates as well as rates of bleeding were statistically similar among groups. However, minor bleeding was more frequent with administration of the active drug.

CONCLUSIONS
The novel antiplatelet agent c7E3 Fab can be administered during PTCA in combination with aspirin and heparin. Suppression of platelet activity is dose dependent and can be maintained for up to 24 hours. Further evaluation will be required to determine the extent of improvement in ischemic complication and restenosis rates and to provide additional insight into the safety profile of this potent monoclonal platelet antibody.
Diagnosis of mild hypertension by ambulatory blood pressure monitoring.
Authors: Weber M A , Neutel J M , Smith D H , Graettinger W F 
Published: June 2012

BACKGROUND
Between 20% and 30% of patients with clinically diagnosed hypertension have normal blood pressure (BP) values during automated ambulatory 24-hour BP monitoring. It has not been clear, however, whether these patients can be regarded as normotensive or whether they should be treated in the same way as confirmed hypertensive patients.

METHODS AND RESULTS
Ambulatory BP monitoring was performed in 88 normal control subjects and 171 hypertensive patients (office diastolic BP > or = 90 mm Hg on three visits; never treated or off treatment for more than 6 months). Hypertensive patients were classified as nonconfirmed or white coat (n = 58) if their 24-hour diastolic averages were < 85 mm Hg and at least 15 mm Hg lower than their office values. For comparisons, white coat patients were pair-matched with normal subjects by 24-hour diastolic averages and sex, and by similar age and weight; there were 40 such pairs. White coat patients were likewise pair-matched with confirmed hypertensive patients by identical office BPs (51 pairs). Participants were studied by individualized treadmill testing, Doppler echocardiography, and assays of resting plasma catecholamines, upright plasma renin and aldosterone, and lipid, glucose, and insulin concentrations. Because of the matching, compared with normal subjects, patients with white coat hypertension and normal subjects had identical 24-hour BP averages. The white coat patients exhibited slightly greater variability among individual readings (obtained each 15 minutes) throughout the day [P < .05]), but there were no differences in hemodynamic responses to exercise. Plasma norepinephrine (P < .05), renin and aldosterone (P < .01 for each), and insulin and low-density lipoprotein cholesterol levels (P < .01 for each) were higher in the white coat group, as were left ventricular septal wall (P < .05) and muscle mass (P = .07) echocardiographic measurements. When compared with the confirmed hypertensive patients, the white coat patients had higher renin (P < .01) but were otherwise similar. Within the white coat group, plasma norepinephrine correlated with total cholesterol and triglycerides (P < .05 for each), and aldosterone correlated with left ventricular mass (P < .01); there were no significant correlations within the normal control subject or confirmed hypertension groups.

CONCLUSIONS
Patients with white coat hypertension differ in metabolic, neuroendocrine, and cardiac findings from normal control subjects and have greater BP variability. These changes appear to be mediated by heightened activity of the sympathetic and renin-angiotensin systems. Although these characteristics could reflect an alerting reaction in the clinic due to awareness of their diagnosis, the white coat hypertensive patients also have evidence for additional, more-sustained differences from normal subjects. Thus, this condition appears to be a true variant of hypertension.
A comparison of internal mammary artery and saphenous vein grafts after coronary artery bypass surgery. No difference in 1-year occlusion rates and clinical outcome. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.
Authors: van der Meer J , Hillege H L , van Gilst W H , Brutel de la Rivière A , Dunselman P H , Fidler V , Kootstra G J , Mulder B J , Pfisterer M , Lie K I 
Published: June 2012

BACKGROUND
Superior patency rates for internal mammary artery (IMA) grafts compared with vein coronary bypass grafts have been demonstrated by retrospective studies. This difference may have been affected by selection bias of patients and coronary arteries for IMA grafting.

METHODS AND RESULTS
To estimate the difference between IMA and vein grafts, we analyzed graft patency data of 912 patients who entered a randomized clinical drug trial. In this trial, 494 patients received both IMA and vein grafts (group 1) and 418 only vein grafts (group 2). Occlusion rates of IMA grafts and IMA plus vein grafts in group 1 were compared with those of vein grafts in group 2. Multivariate analysis was used to compare occlusion rates of IMA and vein grafts while other variables related to graft patency were controlled for. In addition, 1-year clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding, and death. Occlusion rates of distal anastomoses in group 1 versus group 2 were 5.4% (IMA grafts) versus 12.7% (vein grafts) (P < .0001) and 10.4% (IMA plus vein grafts) versus 12.7% (vein grafts) (P = .14). There was no difference in adjusted risk of occlusion between IMA grafts and vein grafts (P = .089). Type and location of distal anastomosis and lumen diameter of the grafted coronary artery were shown to be predictors of occlusion. Clinical events occurred in 17.8% (group 1) and 16.0% (group 2) of patients (P = .53).

CONCLUSIONS
The observed difference in 1-year occlusion rates between IMA and vein grafts can be explained by a maldistribution of graft characteristics by selection of coronary arteries for IMA grafting rather than being ascribed to graft material. One-year clinical outcome is not improved by IMA grafting.
Survival after myocardial infarction in the rat. Role of tissue angiotensin-converting enzyme inhibition.
Authors: Wollert K C , Studer R , von Bülow B , Drexler H 
Published: June 2012

BACKGROUND
Chronic treatment with high doses of angiotensin-converting enzyme (ACE) inhibitors prolongs survival after myocardial infarction. Since the plasma renin-angiotensin system (RAS) is not consistently activated in the chronic phase after myocardial infarction, the beneficial effects of ACE inhibition have been attributed, in part, to inhibition of an activated tissue RAS. However, a relation between tissue ACE inhibition and long-term efficacy (ie, concerning left ventricular [LV] hypertrophy and survival) has not been established. The present study was designed to evaluate the impact of low-dose ACE inhibition (predominant inhibition of plasma ACE) and high-dose ACE inhibition associated with substantial tissue ACE inhibition) on reversal of LV hypertrophy and 1-year mortality after myocardial infarction in the rat.

METHODS AND RESULTS
Infarcted rats were randomized to placebo, low-dose lisinopril, or high-dose lisinopril (each, n = 80) and compared with sham-operated animals (n = 40). In a separate group of animals, tissue ACE activity was determined after 6 weeks of therapy, demonstrating that both regimens were effective with regard to both plasma and pulmonary ACE inhibition; however, only high-dose lisinopril inhibited renal ACE. Neither dose affected LV ACE activity and ACE mRNA levels as determined by competitive polymerase chain reaction, whereas LV ANF mRNA levels were significantly reduced by high-dose lisinopril. High-dose lisinopril reduced arterial blood pressure and normalized right ventricular and LV weight and resulted in a substantial reduction of 1-year mortality, whereas the low dose did not (1 year mortality: placebo, 56.3%; low dose, 53.3%; high dose, 22.9%, P < .0001 versus low dose and versus placebo).

CONCLUSIONS
Hemodynamically effective ACE inhibition is required for reduction of LV hypertrophy and long-term mortality after myocardial infarction in the rat. Sustained inhibition of renal ACE during long-term therapy may contribute to the beneficial effect of high-dose lisinopril. Low-dose lisinopril, although exerting sustained inhibition of the plasma ACE, does not improve survival after myocardial infarction.
DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy.
Authors: Iwai N , Ohmichi N , Nakamura Y , Kinoshita M 
Published: June 2012

BACKGROUND
The cardiac renin-angiotensin system has been suggested to be involved in the development of left ventricular hypertrophy. In humans, a strong correlation has been found between plasma angiotensin I-converting enzyme (ACE) activity and the insertion/deletion (I/D) polymorphism of the ACE gene, which has been reported to be associated with myocardial infarction, ischemic and idiopathic dilated cardiomyopathy, sudden death in hypertrophic cardiomyopathy, and restenosis after percutaneous transluminal coronary angioplasty. In the present study, we examined the possibility that the genotype of the ACE gene might influence the development of left ventricular hypertrophy.

METHODS AND RESULTS
The study population consisted of 268 subjects randomly selected from our outpatient clinic. In 142 subjects, left ventricular mass (LVM) was determined by echocardiogram. The genotype of the ACE gene was determined by the polymerase chain reaction. ANCOVA revealed that the genotype of the ACE gene had no effect on blood pressure. The percentage of the explained variance of LVM with variables including diastolic blood pressure (DBP, P = .0001), body mass index (BMI, P = .0001), sex (P = .0009), and the genotype of the ACE gene (P = .0017) was 34.61%. Significant differences in the effects of the genotype of the ACE gene on LVM were observed between the II and DD (P = .0004) and between the ID and DD (P = .0077) genotypes. The percentage of the explained variance of the LVM/ht ratio with variables including sex (P = .134), age (P = .3655), the genotype of the ACE gene (P = .0014), BMI (P = .0001), and DBP (P = .0001) was 31.25%. Significant differences in the effects of the genotype of the ACE gene on LVM/ht were observed between the II and DD genotypes (P = .0003) and between the ID and DD genotypes (P = .0091).

CONCLUSIONS
In addition to BMI and DBP, the genotype of the ACE gene was a significant predictor of LVM and LVM/ht in our study population.