bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circadian variations in ischemic threshold and their relation to the occurrence of ischemic episodes.
Authors: Benhorin J , Banai S , Moriel M , Gavish A , Keren A , Stern S , Tzivoni D 
Published: June 2012

BACKGROUND
The occurrence of ischemic episodes during daily activity has been reported to exhibit a bimodal circadian distribution, yet its relation to the ischemic threshold (heart rate at 1-mm ST segment depression) has not been explored.

METHODS AND RESULTS
To determine whether the ischemic threshold during daily activity exhibits a circadian pattern that might relate to the frequency of occurrence of ischemic episodes, we studied the time of occurrence and the heart rate at onset of ischemia in 1,371 ischemic episodes recorded in 41 patients with stable coronary disease, positive exercise testing, and repeated ischemic episodes during ambulatory ECG monitoring (AEM). All patients had 7 days of AEM; 23 were off any anti-ischemic therapy, while 18 were on low dose of beta-blockers. The occurrence of ischemic episodes exhibited the typical bimodal circadian distribution with a prominent peak between 7:00 and 11:00 AM and a second less prominent peak between 6:00 and 9:00 PM. The threshold of myocardial ischemia exhibited a different single-peaked circadian distribution; it was lowest between 1:00 and 3:00 AM and highest between 10 AM and 1 PM. Time series analyses indicated a strong hour-by-hour trend of each of the two circadian distributions, whereas the two series cross-correlated maximally at a lag of zero hours (p < 0.01), indicating a complex interplay between myocardial oxygen demand and supply in determining the occurrence of ischemic episodes during daily activity. The morning increase in the frequency of ischemic episodes could not be attributed to a reduced threshold but rather to an increase in demand. The low threshold at night-time might probably indicate that the mechanism of ischemia during these hours is reduced coronary flow due to increased coronary tone. Secondary analyses for several predefined patients' subsets gave similar results. Patients who received low-dose beta-blockers maintained the bimodal circadian distribution of the occurrence of ischemic episodes, whereas the ischemic threshold exhibited a constant pattern with no circadian changes.

CONCLUSIONS
Our results demonstrate that myocardial oxygen demand is a major determinant of daily ischemia, yet changes in the ischemic threshold that probably reflect dynamic changes in coronary tone play also an important role. The relative contribution of increased demand and decreased threshold to the genesis of ischemic episodes during daily activity can be assessed by AEM and may help to optimize medical therapy.
A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989.
Authors: Munger T M , Packer D L , Hammill S C , Feldman B J , Bailey K R , Ballard D J , Holmes D R , Gersh B J 
Published: June 2012

BACKGROUND
Virtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population.

METHODS AND RESULTS
We identified 113 residents of Olmsted County, Minnesota, during the period 1953-1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of 22% of the cohort. Approximately 50% of the population was asymptomatic at diagnosis, with 30% subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis.

CONCLUSIONS
The incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those < 40 years old, should return for medical follow-up should symptoms develop.
Adenosine alters glucose use during ischemia and reperfusion in isolated rat hearts.
Authors: Finegan B A , Lopaschuk G D , Coulson C S , Clanachan A S 
Published: June 2012

BACKGROUND
Adenosine possesses marked cardioprotective properties, but the mechanisms for this beneficial effect are unclear. The objective of this study was to determine the effect of adenosine given before ischemia or at reperfusion on mechanical function, glucose oxidation, glycolysis, and metabolite levels in isolated, paced (280 beats per minute) working rat hearts.

METHODS AND RESULTS
Hearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate, and 500 microU.mL-1 insulin at an 11.5 mm Hg left atrial preload and 80 mm Hg aortic afterload. Adenosine (100 microM) pretreatment or adenosine (100 microM) at reperfusion markedly increased the recovery of mechanical function (from 44% to 81% and 96%, respectively) after 60 minutes of low-flow ischemia (coronary flow, 0.5 mL.min-1). Glucose oxidation (mumol.min-1 x g dry wt-1) was inhibited during ischemia (from 0.44 +/- 0.04 to 0.12 +/- 0.01), and this was not altered by adenosine (100 microM). During reperfusion, glucose oxidation recovered (to 0.38 +/- 0.02) and adenosine (100 microM), given at reperfusion, further increased glucose oxidation (to 0.52 +/- 0.06). The rate of glycolysis (mumol.min-1 x g dry wt-1), which was unaffected by ischemia per se, was inhibited by adenosine pretreatment (from 4.7 +/- 0.3 to 2.6 +/- 0.3). During reperfusion, glycolysis was also inhibited by adenosine relative to control (3.9 +/- 0.8) either when present during ischemia (2.6 +/- 0.6) or during reperfusion (1.4 +/- 0.4). These effects of adenosine on glucose metabolism reduced the calculated rate of H+ production attributable to glucose metabolism during the ischemic and reperfusion periods. Tissue lactate levels (mumol.g dry wt-1), which increased during ischemia (from 9.3 +/- 1.1 to 87.4 +/- 10.3) and then declined during reperfusion (to 26.2 +/- 3.7), were depressed further by adenosine pretreatment (to 19.7 +/- 4.1) and by adenosine at reperfusion (to 13.6 +/- 2.1). ATP levels (mumol.g dry wt-1), which were depressed by ischemia (from 18.1 +/- 1.1 to 10.6 +/- 1.3) and tended to be further depressed during reperfusion (to 7.1 +/- 0.7), were increased by adenosine pretreatment (to 14.1 +/- 1.2) and by adenosine at reperfusion (to 15.6 +/- 2.4).

CONCLUSIONS
The effects of adenosine on glucose metabolism that would tend to decrease cellular acidosis and hence, Ca2+ overload, may explain the beneficial effects of adenosine on mechanical function observed in these hearts during reperfusion after ischemia.
Heat-shock response and limitation of tissue necrosis during occlusion/reperfusion in rabbit hearts.
Authors: Currie R W , Tanguay R M , Kingma J G 
Published: June 2012

BACKGROUND
Induction of stress proteins, such as heat-shock protein 71 (HSP71), is associated with cardioprotection in isolated ischemic myocardium. We tested this hypothesis in rabbits pretreated with whole-body hyperthermia and then subjected to 30 or 45 minutes of regional coronary occlusion (CO) followed by 3 hours reperfusion (Rep).

METHODS AND RESULTS
Control rabbits did not undergo whole-body hyperthermia; heat-shocked (HS) rabbits were subjected to whole-body hyperthermia at 42 degrees C for 15 minutes. Rabbits were allowed to recover from whole-body hyperthermia for 24 or 40 hours and were then subjected to CO/Rep. Heart rate and arterial blood pressure were recorded during the experiments. Area of necrosis (tetrazolium staining) was normalized to anatomic risk zone size (microsphere autoradiography). In rabbits treated with whole-body hyperthermia and 24 hours of recovery, infarct size was significantly reduced in HS rabbits compared with control rabbits (41.2 +/- 7.8% versus 23.2 +/- 6.6%; p < or = 0.05; mean +/- SD) after 30 minutes of CO and 3 hours of Rep. Risk zone size was similar for the two experimental groups. In rabbits treated with whole-body hyperthermia and 40 hours of recovery, infarct size was similar for control and HS animals with either 30 or 45 minutes of CO (p = NS) and 3 hours of Rep. Risk zone size and area of necrosis were similar for these experimental groups. Biopsies from ischemic and nonischemic myocardium were obtained from rabbits at 24 and 40 hours after heat shock and control rabbits to verify expression of HSP71; expression was determined by Western blot analysis.

CONCLUSIONS
Our findings demonstrate a considerable increase in expression of HSP71 in myocardium from hyperthermia-treated rabbits. Infarct size was significantly reduced after 30 minutes of CO and 3 hours of Rep in hearts at 24 but not 40 hours after heat shock compared with control hearts. We conclude that heat shock-induced cardioprotection is transient and delays the onset of irreversible myocardial injury caused by ischemia.
Prognostic significance of progression of coronary atherosclerosis.
Authors: Waters D , Craven T E , Lespérance J 
Published: June 2012

BACKGROUND
Angiographic progression of coronary atherosclerosis is frequently observed in clinical practice and is used as an end point in clinical trials; however, its prognostic significance is unclear.

METHODS AND RESULTS
Progression defined as an increase in diameter stenosis by > or = 15% of at least one coronary lesion was seen in 141 (42%) of 335 patients who underwent repeat coronary arteriography after a 2-year interval as part of clinical trial. Coronary lesions were measured quantitatively from comparable end-diastolic frames selected by a radiologist viewing each pair of films together. During a mean follow-up of 44 +/- 10 months after the second arteriogram, cardiac death occurred in 19 patients (5.7%), cardiac death or nonfatal infarction was seen in 40 cases (11.9%), and 90 patients (26.9%) underwent coronary revascularization. At least one end point event occurred in 112 of the 335 patients. Sixteen of the 19 cardiac deaths were in progressors, a relative risk of 7.3 (95% CI, 2.2-24.7; p < 0.001). The relative risk of cardiac death or nonfatal infarction for progressors was 2.3 (1.3-4.2, p = 0.009) and of any cardiac event was 1.7 (1.3-2.3, p < 0.001). A stepwise multivariable Cox regression model of time to event was used to assess the relative contribution of progression as a predictor of coronary events. Low ejection fraction (p = 0.001), progression (p = 0.001), and hypertension (p = 0.011) were retained as predictors of cardiac death. Angina and the number of diseased vessels were the strongest predictors of revascularization.

CONCLUSIONS
Coronary progression is a strong, independent predictor of future coronary events, particularly cardiac death, and its use as a surrogate end point in clinical trials is justified.
Coronary artery size and dilating capacity in ultradistance runners.
Authors: Haskell W L , Sims C , Myll J , Bortz W M , St Goar F G , Alderman E L 
Published: June 2012

BACKGROUND
Increases in coronary artery size and dilating capacity have been observed in some animals after endurance training, and at autopsy, active men appear to have enlarged epicardial coronary arteries. This cross-sectional study was designed to test the hypothesis that highly trained endurance runners have larger epicardial coronary arteries and greater dilating capacity than inactive men.

METHODS AND RESULTS
The subjects, ages 39-66 years, included 11 male volunteers who had participated in ultradistance running during the past 2 years and 11 physically inactive men who had been referred for arteriography but had no visible coronary artery disease. The internal diameter of the proximal segments of each major epicardial coronary artery was measured before and after nitroglycerin administration using a computer-based quantitative arteriographic analysis system. Measurements also included maximal oxygen uptake, plasma lipoprotein concentrations, body composition, and cardiac mass by echocardiography. Before nitroglycerin, the sum of the cross-sectional areas for the proximal right, left anterior descending, and circumflex arteries was not different for the runners and the inactive men: 22.7 +/- 4.79 versus 21.0 +/- 7.97 mm2 (p = 0.57), respectively. However, the increase in the sum of the cross-sectional area for the proximal right, left anterior descending, and circumflex arteries in response to nitroglycerin was greater for the runners (13.20 +/- 4.76 versus 6.00 +/- 3.02 mm2; p = 0.002). Left ventricular mass index (152 +/- 21 versus 116 +/- 41 g/m2; p < 0.05) but not left ventricular mass (284 +/- 40 versus 246 +/- 91 g; p = 0.22) was significantly greater for the runners. Among the runners, dilating capacity was positively correlated with aerobic capacity and negatively related to adiposity, resting heart rate, and plasma lipoprotein concentrations.

CONCLUSIONS
Highly trained, middle-aged endurance runners demonstrated a significantly greater dilating capacity of their epicardial coronary arteries in response to nitroglycerin compared with inactive men. The causes of this greater dilating capacity and its clinical significance need to be determined.
Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease.
Authors: Linnanmäki E , Leinonen M , Mattila K , Nieminen M S , Valtonen V , Saikku P 
Published: June 2012

BACKGROUND
An association of chronic Chlamydia pneumoniae infection to coronary heart disease has been suggested recently. In a recent study, we demonstrated circulating immune complexes containing chlamydial genus-specific lipopolysaccharide in patients with coronary heart disease. The objective of the present study was to investigate whether C. pneumoniae species-specific immune complexes are present in chronic coronary heart disease.

METHODS AND RESULTS
The presence of Chlamydia-specific circulating immune complexes was studied in 46 patients with chronic coronary heart disease and in control subjects. Chlamydial lipopolysaccharide-containing immune complexes were detected with the antigen-specific capture method, and they were present in 41% of patients and 15% of control subjects (p < 0.01). The presence of C. pneumoniae antibodies in circulating immune complexes was studied by testing the specificity of antibodies derived from isolated and dissociated immune complexes by microimmunofluorescence testing and immunoblotting. The C. pneumoniae indexes based on the relative amount of immune complex-derived antibodies and free antibodies were significantly higher among patients compared with control subjects (median, 1/8 versus 1/16; p < 0.001). Immune complex bound antibodies showed specificity for 98-kd and 42-kd proteins of C. pneumoniae.

CONCLUSIONS
The results suggest that the majority of the patients with chronic coronary heart disease have a chronic C. pneumoniae infection in which chlamydial components have an easy access to circulation to form immune complexes with preexisting antibodies. These findings give further evidence for the association of chronic C. pneumoniae infection with coronary heart disease.
Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation.
Authors: Cheng G C , Loree H M , Kamm R D , Fishbein M C , Lee R T 
Published: June 2012

BACKGROUND
Although rupture of an atherosclerotic plaque is considered to be the cause of most acute coronary syndromes, the mechanism of plaque rupture is controversial.

METHODS AND RESULTS
To test the hypothesis that plaque rupture occurs at sites of high circumferential stress in the diseased vessel, the distribution of stress was analyzed in 24 coronary artery lesions. Histological specimens from 12 coronary artery lesions that caused lethal myocardial infarction were compared with those from 12 stable control lesions. A finite element model was used to calculate the stress distributions at a mean intraluminal pressure of 110 mm Hg. The maximum circumferential stress in plaques that ruptured was significantly higher than maximum stress in stable specimens (4,091 +/- 1,199 versus 1,444 +/- 485 mm Hg, p < 0.0001). Twelve of 12 ruptured lesions had a total of 31 regions of stress concentration of more than 2,250 mm Hg (mean, 2.6 +/- 1.4 high stress regions per lesion); only one of 12 control lesions had a single stress concentration region of more than 2,250 mm Hg. In seven of 12 lethal lesions (58%), rupture occurred in the region of maximum circumferential stress; in 10 of the 12 lethal lesions (83%), rupture occurred in a region where computed stress was more than 2,250 mm Hg.

CONCLUSIONS
These data suggest that concentrations of circumferential tensile stress in the atherosclerotic plaque may play an important role in plaque rupture and myocardial infarction. However, plaque rupture may not always occur at the region of highest stress, suggesting that local variations in plaque material properties contribute to plaque rupture.
Suppression of protein degradation in progressive cardiac hypertrophy of chronic aortic regurgitation.
Authors: Magid N M , Borer J S , Young M S , Wallerson D C , DeMonteiro C 
Published: June 2012

BACKGROUND
The heart adapts to the volume overload of aortic regurgitation with dilation and hypertrophy. The development of left ventricular hypertrophy at the protein level is a dynamic process resulting from an imbalance between cardiac protein synthesis and degradation. The objective of the present study was to determine in vivo the relative contributions of cardiac protein synthesis and degradation to the progressive hypertrophy that occurs in response to chronic aortic regurgitation and to compare these with responses earlier in the course of this stress.

METHODS AND RESULTS
Continuous intravenous infusions of [3H]-leucine were administered 3 days and 1 month after surgical induction of aortic regurgitation and sham operation in rabbits. Total cardiac protein and myosin heavy chain fractional synthesis rates were obtained by analysis of plasma and protein hydrolysate data using [14C]-dansyl chloride assays. Left ventricular growth rates were determined from serial echocardiographic and postmortem left ventricular weight and protein concentration measurements; protein degradation rates were determined by subtraction of growth rates from synthesis rates.

CONCLUSIONS
In comparison with sham-operated control rabbits, protein fractional synthesis rates were increased at 3 days but not at 1 month after induction of aortic regurgitation Progressive cardiac hypertrophy occurring at 1 month was caused by a decrease in protein fractional degradation rates. An increase in protein synthesis contributes only to the early phase of hypertrophy caused by acute aortic regurgitation, whereas progressive eccentric hypertrophy in chronic volume overload is due to suppression of protein degradation.
Intraluminal vapor bubble induced by excimer laser pulse causes microsecond arterial dilation and invagination leading to extensive wall damage in the rabbit.
Authors: van Leeuwen T G , Meertens J H , Velema E , Post M J , Borst C 
Published: June 2012

BACKGROUND
Previous in vitro studies demonstrated that during excimer laser ablation of aortic tissue in saline, a fast-expanding and imploding vapor bubble is formed. The present in vivo study was designed to demonstrate the formation of a fast-expanding intraluminal bubble in flowing blood and to assess any damage to the adjacent arterial wall.

METHODS AND RESULTS
Excimer laser pulses (one to 10, at 55 mJ/mm2 per pulse) were delivered coaxially in the femoral and iliac arteries of nine normal rabbits. Time-resolved flash photography of dissected arteries in situ demonstrated a 50% diameter increase within 75 microseconds after the laser pulse and a subsequent invagination (150-500 microseconds) that corresponded with the temporal course of the bubble expansion (up to 3.2 mm in diameter) and implosion observed in a hemoglobin solution. One day after laser light delivery, light microscopy (47 arterial segments) showed abrasion of the internal elastic lamina, medial necrosis, and extensive dissection planes filled with red blood cells. The degree (up to 100% medial necrosis) and extent of damage (up to 1.9 mm in length) increased with the number of delivered laser pulses.

CONCLUSIONS
In blood, each excimer laser pulse generated a fast-expanding and imploding vapor bubble. In vivo, the intraluminal vapor bubble produced microsecond dilation and invagination of the adjacent arterial segment, which induced dissections and extensive wall damage far beyond the penetration depth of 308-nm laser light (< 100 microns). This unique pattern of extensive wall damage observed in the rabbit might explain the mechanism of dissection observed in humans and might have an impact on the acute and chronic outcome after excimer laser coronary angioplasty.
Changes in diastolic function during development and correction of chronic LV volume overload produced by mitral regurgitation.
Authors: Zile M R , Tomita M , Ishihara K , Nakano K , Lindroth J , Spinale F , Swindle M , Carabello B A 
Published: June 2012

BACKGROUND
Mitral regurgitation (MR) causes an augmentation in left ventricular (LV) diastolic function, increasing early diastolic filling rate and decreasing LV stiffness. Whether these changes in diastolic function persist, return to normal, or become abnormal after mitral valve replacement (MVR) is unknown.

METHODS AND RESULTS
Simultaneous LV echocardiography and catheterization studies were performed in six dogs in the baseline state (baseline), 3 months after creation of MR (chronic MR), and 3 months after MVR. Chronic MR caused LV dilation (end-diastolic dimension increased from 4.5 +/- 0.1 cm in baseline to 5.8 +/- 0.1 cm in chronic MR, p < 0.05) and eccentric LV hypertrophy (LV-to-body weight ratio increased from 3.6 +/- 0.2 g/kg in baseline to 4.9 +/- 0.4 g/kg in chronic MR, p < 0.05). Chronic MR caused an increase in LV early diastolic filling rate (peak rate of increase in minor-axis dimension increased from 11 +/- 1 cm/sec in baseline to 18 +/- 1 cm/sec in chronic MR, p < 0.05), did not change the time constant of myocardial relaxation (tau was 31 +/- 4 msec in baseline and 30 +/- 2 msec in chronic MR), and caused a decrease in the modulus of regional chamber stiffness from 7.7 +/- 1.2 in baseline to 2.4 +/- 0.03 in chronic MR, p < 0.05. MVR caused the resolution of LV dilation (end-diastolic dimension returned to normal [4.8 +/- 0.2 cm]), but three months after MVR, regression of LV hypertrophy was incomplete (LV-to-body weight ratio remained elevated [4.4 +/- 0.5 g/kg]). After MVR, LV early diastolic filling rate (8 +/- 1 cm/sec), the relaxation time constant (31 +/- 2 msec), chamber stiffness (7.1 +/- 1.8), myocardial stiffness (11.2 +/- 3.1), and LV end-diastolic pressure (8 +/- 1 mm Hg) returned to normal.

CONCLUSIONS
The enhanced diastolic function seen in chronic MR returned to normal after correction of the chronic volume overload by MVR.