bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential importance of tissue angiotensin-converting enzyme inhibition in preventing neointima formation.
Authors: Rakugi H , Wang D S , Dzau V J , Pratt R E 
Published: June 2012

BACKGROUND
Angiotensin II (Ang II) induces vascular smooth muscle cell migration and growth in vitro and induces DNA synthesis in vascular smooth muscle in vivo. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists inhibit neointimal hyperplasia in many experimental models of restenosis. However, recent clinical trials (MERCATOR and MARCATOR) reported that treatment with low (antihypertensive) doses of an ACE inhibitor (cilazapril) failed to prevent restenosis. Because ACE activity is induced in the neointima after injury, we hypothesize that the inhibition of neointimal development may be dependent on the suppression of tissue ACE activity, which in turn is dependent on the dose of the ACE inhibitor.

METHODS AND RESULTS
To test this hypothesis, we treated rats with increasing doses of an ACE inhibitor, quinapril, before injury of the carotid artery. Blood pressure, serum and tissue ACE activity, and neointimal area were measured. The results demonstrated a dose-dependent inhibition by quinapril of serum and tissue ACE activities and neointima formation. However, the IC50s for blood pressure reduction and serum ACE inhibition were significantly lower than that observed for the suppression of neointima formation. The degree of neointimal formation showed a better correlation with residual tissue ACE than with serum ACE or blood pressure.

CONCLUSIONS
These results demonstrate a dissociation of the ability of an ACE inhibitor to decrease blood pressure and inhibit circulating ACE activity from its ability to inhibit tissue ACE activity. These results suggest that the need for a higher dose of an ACE inhibitor for the inhibition of neointima formation may be due to the relative difficulty in inhibiting tissue ACE activity.
Resolution of pace mapping stimulus site separation using body surface potentials.
Authors: Green L S , Lux R L , Ershler P R , Freedman R A , Marcus F I , Gear K 
Published: June 2012

BACKGROUND
Several studies have related 12-lead ECG waveform during ventricular tachycardia to ECG waveform during ventricular pacing to identify ablation sites for therapy of ventricular tachycardia. QRS isopotential maps and QRS isointegral maps derived from body surface isopotential maps have also been correlated with left ventricular pacing sites with the same objective. The comparison process used is subjective and only semiquantitative. Improved accuracy of catheter placement may improve success rates of ablation therapy.

METHODS AND RESULTS
This animal study was performed to determine the spatial resolution with which left ventricular pacing sites could be distinguished by body surface isopotential mapping. Potentials were recorded from 64 evenly spaced thoracic leads. Hexapolar or octapolar pacing catheters with 2-mm interelectrode spacing were placed percutaneously in the left ventricle in each of six dogs, and bipolar endocardial pacing was performed using each pair of adjacent electrodes. QRS isopotential maps of each pacing site for each catheter placement were cross-correlated by computer. Difference maps for each pair of pacing sites were calculated lead by lead and time instant by time instant, and root-mean-square voltage differences were calculated. Results indicated that correlation coefficients and root-mean-square error of voltage differences monotonically decrease and increase, respectively, with stimulus site separation. Both measures were significantly different (P < .05) for separations of 4 mm or more.

CONCLUSIONS
A method of quantitative comparison of body surface potential maps can be used in normal hearts to localize ventricular pacing sites within a 4-mm range. The method may have utility in determining potential ablation sites for therapy of ventricular tachycardia or preexcitation syndromes.
Exercise-induced enhancement of immune function in the rat.
Authors: Kaufman J C , Harris T J , Higgins J , Maisel A S 
Published: June 2012

BACKGROUND
There have been many anecdotal reports that regular, moderate exercise confers some protective immunity against infection. There has been little scientific evidence to support this. It is also unclear whether training alters lymphocyte trafficking from the spleen to the periphery after a bout of exhaustive exercise.

METHODS AND RESULTS
To determine the effect of moderate training on in vivo antibody production, using rats as an animal model, we gradually trained 18 rats using a swimming protocol for a 4-week period after injection and booster with Keyhole limpet hemocyanin antigen. There were 9 age-matched controls. At the conclusion of training, both groups underwent a short-term exhaustive swim. The trained group showed marked enhancement of IgM and IgG production. After short-term exercise, both groups had acute lymphocytosis, mainly T(suppressor)/cytolytic and natural killer cells with decreases in T(helper) (trained), B cells, and the Th-to-Ts ratio. The changes in the splenocyte subsets were the opposite of the changes in the peripheral blood. With respect to function, after exhaustive exercise, there was a slight increase in mitogenesis and interleukin-2 receptor expression to concanavalin A (untrained more than trained) compared with controls.

CONCLUSIONS
Regular, moderate training enhances antibody production to specific de novo antigen both early and late. In addition, short-term exercise leads to selective release of immune cells from the spleen and results in slightly enhanced function of splenocytes. Direct stimulation by the sympathetic nervous system and catecholamines is the proposed mechanism for the changes seen after short-term exercise and possibly antibody production during training.
Heart rate variability as a prognostic tool in cardiology. A contribution to the problem from a theoretical point of view.
Authors: Moser M , Lehofer M , Sedminek A , Lux M , Zapotoczky H G , Kenner T , Noordergraaf A 
Published: June 2012

BACKGROUND
Recent clinical studies have proposed standard deviation of heart rate as a diagnostic tool for the outcome of cardiac infarction. Mathematical analysis of heart rate variability shows that heart rate is influenced by different frequency components derived from different parts of the autonomous nervous system. In the experimental part of this study, we investigated the possibility of calculating a variable describing the parasympathetic branch of the autonomous nervous system exclusively.

METHODS AND RESULTS
In 60 healthy volunteers, heart rate was measured to 1 millisecond during two different conditions: 5 minutes of rest, and 5 minutes of intermittent handgrip dynamometry; the latter is known to increase sympathetic arousal selectively. Heart rate was found to be lower at rest (65.9 +/- 9.7 beats per minute) than during dynamometry (72.8 +/- 10.4 beats per minute, P < .001). Respiratory sinus arrhythmia (RSA) calculated from the mean absolute differences between successive heart beats showed no significant change (3.01 +/- 1.62 beats per minute at rest versus 2.97 +/- 1.30 beats per minute during dynamometry). In contrast, standard deviation increased from 5.19 +/- 1.98 to 9.22 +/- 3.56 beats per minute (P < .001).

CONCLUSIONS
It can be concluded from these data as well as from other plots presented in this article that RSA is a measure of the parasympathetic vagal tone, whereas standard deviation is increased by both sympathetic and parasympathetic arousal. Clinical evidence and data from physiological experiments are presented to show that a selective measure of vagal tone like RSA may offer advantages over standard deviation as a prognostic tool in cardiology.
Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study.
Authors: Tsuji H , Venditti F J , Manders E S , Evans J C , Larson M G , Feldman C L , Levy D 
Published: June 2012

BACKGROUND
The prognostic implications of alterations in heart rate variability have not been studied in a large community-based population.

METHODS AND RESULTS
The first 2 hours of ambulatory ECG recordings obtained on original subjects of the Framingham Heart Study attending the 18th biennial examination were reprocessed to assess heart rate variability. Subjects with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1 hour of recording time, processed time < 50% of recorded time, and those taking antiarrhythmic medications were excluded. The associations between heart rate variability measures and all-cause mortality during 4 years of follow-up were assessed. There were 736 eligible subjects with a mean age (+/- SD) of 72 +/- 6 years. The following five frequency domain measures and three time domain measures were obtained: very-low-frequency power (0.01 to 0.04 Hz), low-frequency power (0.04 to 0.15 Hz), high-frequency power (0.15 to 0.40 Hz), total power (0.01 to 0.40 Hz), the ratio of low-frequency to high-frequency power, the standard deviation of total normal RR intervals, the percentage of differences between adjacent normal RR intervals that are > 50 milliseconds, and the square root of the mean of the squared differences between adjacent normal RR intervals. During follow-up, 74 subjects died. In separate proportional hazards regression analyses that adjusted for relevant risk factors, very-low-frequency power (P < .0001), low-frequency power (P < .0001), high-frequency power (P = .0014), total power (P < .0001), and the standard deviation of total normal RR intervals (P = .0019) were significantly associated with all-cause mortality. When all eight heart rate variability measures were assessed in a stepwise analysis that included other risk factors, low-frequency power entered the model first (P < .0001); thereafter, none of the other measures of heart rate variability significantly contributed to the prediction of all-cause mortality. A 1 SD decrement in low-frequency power (natural log transformed) was associated with 1.70 times greater hazard for all-cause mortality (95% confidence interval of 1.37 to 2.09).

CONCLUSIONS
The estimation of heart rate variability by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional risk factors.
Magnetic resonance imaging of the iliofemoral arteries after balloon dilation angioplasty of aortic arch obstructions in children.
Authors: Burrows P E , Benson L N , Babyn P , MacDonald C 
Published: June 2012

BACKGROUND
We wished to determine the nature and incidence of changes in the iliofemoral arteries after balloon dilation angioplasty (BDA) for aortic arch obstruction in children and to determine the reliability of gradient magnetic resonance imaging (MRI) in their detection.

METHODS AND RESULTS
Sixty-three children, including 62 with and 1 without arch obstruction, underwent MRI of the iliofemoral vessels. Of these, 36 patients had undergone transfemoral BDA (7 after previous transfemoral diagnostic catheterization), 12 had undergone diagnostic transfemoral catheterization but not BDA, and 15 had no history of femoral arterial catheterization. The iliofemoral arteries were normal on MRI in all 15 children without catheterization. Among the 36 children who had undergone BDA, the ipsilateral iliofemoral artery was normal in 15, mildly narrowing in 7, and severely stenotic or occluded in 14 (39%), including 6 of 9 patients treated for acute femoral artery thrombosis and 8 with no history of femoral artery thrombosis. Two patients had documentation of progressive obstruction. Six patients had concordant conventional angiography. There was a significant correlation between the number of balloon catheters used for the angioplasty and severe occlusive changes. Nine of 19 patients who had undergone diagnostic transfemoral catheterization had severe obstructive changes on MRI; 8 of 9 weighed < 10 kg at catheterization.

CONCLUSIONS
Obstructive lesions of the iliofemoral arteries are common after transfemoral BDA of arch obstructions (58%) and can be reliably evaluated with gradient MRI. Catheter size and manipulation are the main contributing factors.
Physical conditioning decreases norepinephrine-induced vasoconstriction in rabbits. Possible roles of norepinephrine-evoked endothelium-derived relaxing factor.
Authors: Chen H I , Li H T , Chen C C 
Published: June 2012

BACKGROUND
Physical activity can reduce sympathetic tone and may be beneficial to human health. Whether the vascular responses to norepinephrine (NE), an adrenergic vasoconstrictor, could be altered by chronic exercise was unclear. We therefore conducted this study to investigate the effects of endurance exercise training on NE-induced vasoconstrictive response in healthy rabbits. Possible mechanisms were also studied.

METHODS AND RESULTS
Twenty-four male New Zealand White rabbits were used for this study. They were divided into two groups: control and training. The training group was trained on a treadmill with running speed of 0.88 km/h at a 0 degree grade for 10 to 60 minutes per day, for 5 days a week for a total of 8 weeks. At the end of the experiments, thoracic aortae (3 mm long) were isolated. The vascular tension was measured with a force transducer. The dose-response relation of NE-induced vasoconstriction was determined and compared for control (n = 5) and trained (n = 6) groups. To verify the possible involvement of endothelium-derived relaxing factor (EDRF) in the alteration of NE-induced vasoconstriction after exercise training, we compared the vascular responses to NE in endothelium-intact, N omega-nitro-L-arginine (L-NNA, 10(-4) mol/L)-pretreated, or denuded vessel segments (n = 4 for each experiment of each group). EDRF release in the presence or absence of NE was also evaluated by the increased tension induced by hemoglobin (10(-5) mol/L), an EDRF scavenger (n = 6 for the control group and n = 8 for the trained group). In addition, vascular responses to some specific adrenergic agonists (ie, phenylephrine, an alpha 1-agonist, and clonidine, an alpha 2-agonist) were also studied to see if a specific adrenergic receptor was involved (n = 4 for each experiment of each group). Our results indicated that (1) [NE]ED50 of the thoracic aorta was elevated by exercise training; (2) in the presence of NE, EDRF release from the thoracic aorta, assessed by addition of hemoglobin or L-NNA, was higher in the trained group than in the control group; (3) both phenylephrine (10(-8) mol/L) and clonidine (10(-6) mol/L) could evoke vasorelaxation that would be inhibited by L-NNA; and (4) in addition to causing vasoconstriction, NE could stimulate EDRF release, possibly via alpha 1- and alpha 2-receptors of endothelial cells.

CONCLUSIONS
Our data suggest that exercise training may decrease NE-induced vasoconstrictive response and may increase NE-stimulated EDRF release.
Unexpected interaction between beta-adrenergic blockade and heart rate variability before and after myocardial infarction. A longitudinal study in dogs at high and low risk for sudden death.
Authors: Adamson P B , Huang M H , Vanoli E , Foreman R D , Schwartz P J , Hull S S 
Published: June 2012

BACKGROUND
Heart rate (HR) variability is a marker of tonic cardiac autonomic activity and contributes in assessing risk for sudden death after myocardial infarction. Recent clinical observations have indicated that attenuation of HR variability, which occurs after myocardial infarction, may be transient. This study addresses the issue of whether autonomic control of heart rate recovers at different rates after myocardial infarction in subjects at high and low risk for ventricular fibrillation (VF).

METHODS AND RESULTS
Thirty dogs, 22 with myocardial infarction and 8 sham-prepared animals, completed the study. Changes and recovery in cardiac autonomic activity after myocardial infarction were examined by measuring HR variability before and at defined intervals during the first 30 days after infarction. Each HR variability measurement was made before and after beta-blockade in dogs at high (n = 10) and low (n = 12) risk for VF. Arrhythmia risk was determined on the basis of development of VF during exercise and transient myocardial ischemia 30 days after infarction. No sham-prepared animals developed VF. Preinfarction measurements of HR variability were not different between the groups before beta-blockade, but HR variability increased much more in response to beta-blockade in animals destined to be resistant compared with susceptible animals (289 +/- 26 to 369 +/- 35 msec, delta 27.7%, versus 270 +/- 36 to 283 +/- 34 milliseconds, delta 4.8%, respectively, P < .01). Immediately after infarction, HR variability was significantly attenuated in all dogs, but in the resistant dogs it recovered to pre-myocardial infarction levels within 10 days. After the infarction, beta-blockade did not increase HR variability in either group of animals. Postoperative increases in HR variability from beta-blockade were preserved in the sham group. Susceptible animals were characterized by a persistent attenuation of HR variability throughout the 30 days.

CONCLUSIONS
The depression in HR variability produced by myocardial infarction has a clearly different temporal recovery pattern between low- and high-risk animals. After myocardial infarction, beta-adrenergic blockade does not alter HR variability, thus preserving its predictive value. Before myocardial infarction, however, beta-blockade increases HR variability only in the animals destined to be at low risk for lethal arrhythmias after the infarction. The recovery pattern of HR variability after myocardial infarction may contribute to the early recognition of individuals at high risk for sudden death.
Stress echocardiography in the detection of myocardial ischemia. Head-to-head comparison of exercise, dobutamine, and dipyridamole tests.
Authors: Beleslin B D , Ostojic M , Stepanovic J , Djordjevic-Dikic A , Stojkovic S , Nedeljkovic M , Stankovic G , Petrasinovic Z , Gojkovic L , Vasiljevic-Pokrajcic Z 
Published: June 2012

BACKGROUND
Exercise and pharmacological stress echocardiography have emerged as convenient alternatives to myocardial scintigraphy. The objective of this study was to compare in the same patients the diagnostic values of exercise, dobutamine, and dipyridamole stress echocardiography tests for detection of myocardial ischemia.

METHODS AND RESULTS
We performed exercise (maximal treadmill Bruce protocol), dobutamine (up to 40 micrograms/kg per minute) and dipyridamole (up to 0.84 mg/kg over 10 minutes) stress echocardiography tests, in random sequence and on separate days, in 136 consecutive patients. All patients underwent coronary angiography. Significant coronary artery disease was defined by quantitative coronary angiography as a lesion with a diameter stenosis > or = 50%. A stress echocardiogram was considered positive when new or worsening of preexisting wall motion abnormality was observed. Most of the patients (94%) were receiving the same antianginal medication for each stress test; 59 patients were receiving concomitant beta-blocker therapy. The prevalence of coronary artery disease was 87.5%, with 108 patients having one-vessel coronary artery disease. Peak heart rate and systolic blood pressure were higher with exercise than with dobutamine or dipyridamole (P < .01). Sensitivity of exercise, dobutamine, and dipyridamole stress echocardiography was 88%, 82%, and 74% (dipyridamole versus exercise, P < .01), respectively. Specificity was 82%, 77%, and 94%, respectively. The overall accuracy was 87%, 82%, and 77% (dipyridamole versus exercise, P < .01), respectively. The accuracy of dipyridamole was higher (P = .02) in the group of patients not receiving beta-blockers (84%) than in the patients receiving beta-blocker therapy (66%), whereas the accuracy of exercise and dobutamine were only slightly higher in the patients not receiving beta-blockers. Significant side effects occurred in 3%, 11%, and 1% of patients during exercise, dobutamine, and dipyridamole tests, respectively.

CONCLUSIONS
Despite the different hemodynamic effects, exercise, dobutamine, and dipyridamole echocardiography have high overall diagnostic values. In this group of patients with a predominance of one-vessel coronary artery disease, the overall diagnostic accuracy of stress echocardiography tests was higher for exercise than for dobutamine or dipyridamole. Concomitant beta-blocker therapy significantly decreased the accuracy of the dipyridamole stress echocardiography test. Pharmacological stress testing (dipyridamole without beta-blockers) can therefore be used as an efficient option for detection of myocardial ischemia in patients who are unable or poorly motivated to exercise adequately.
Conjoint high triglycerides and low HDL cholesterol across generations. Analysis of proband hypertriglyceridemia and lipid/lipoprotein disorders in first-degree family members.
Authors: Sprecher D L , Hein M J , Laskarzewski P M 
Published: June 2012

BACKGROUND
To discern whether hypertriglyceridemia (hyper-TG, TG > 95th percentile) and hypoalphalipoporteinemia (hypoalpha, high-density lipoprotein [HDL-C] < or = 10th percentile) are jointly transmitted in families, we studied 385 probands with marked elevations in TG or cholesterol levels (TG or cholesterol > 99th percentile in a previous visit) and their 2072-first-degree relatives in the Lipid Research Clinics' Family Study. Repeat TG measurement, with exclusion criterion of TG < or = 95th percentile, resulted in 162 probands with hyper-TG.

METHODS AND RESULTS
When the proband demonstrated the conjoint trait (CT; ie, TG > 95th percentile, HDL-C < or = 10th percentile, n = 82), an average of 10.6% of first-degree relatives conjointly expressed hyper-TG and hypoalpha in contrast to only 4.1% of first-degree relatives of a proband who expressed high TG levels with normal HDL-C levels (TG > 95th percentile, HDL-C > 10th percentile, n = 80). Hyper-TG was expressed in 24.2% of first-degree relatives of probands with CT. However, hyper-TG was expressed in only 14.4% of first-degree degree relatives of probands with hyper-TG alone. CT probands and their family members tended to have more reported cardiac events and symptoms (P = .02 and .09, respectively) than those subjects associated with hyper-TG alone.

CONCLUSIONS
The differences in HDL-C-TG abnormalities between families related to hyper-TG probands with or without hypoalpha indicate that bottom decile HDL-C is not simply secondary to hyper-TG. A familial interaction is suggested between HDL-C and TG levels consistent with the transmission of hyper-TG and hypoalpha among first-degree relatives. Among subjects and their families with hyper-TG, those who in addition have low HDL-C demonstrate a tendency for more coronary artery disease than do those with normal HDL-C levels.