bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of serum cholesterol and other coronary risk factors on vasomotion of angiographically normal coronary arteries.
Authors: Seiler C , Hess O M , Buechi M , Suter T M , Krayenbuehl H P 
Published: June 2012

BACKGROUND
It has been shown that there is impairment of the vasodilatory response to acetylcholine in patients with hypercholesterolemia and angiographically normal coronary arteries. Moreover, in patients with angiographically smooth coronary arteries, the number of coronary risk factors is associated with a loss of endothelium-dependent vasodilation. The purpose of the present analysis was to evaluate in patients with and without coronary artery disease coronary vasomotor response to dynamic exercise in angiographically normal and stenosed coronary arteries and to relate the response to serum cholesterol levels as well as to other coronary risk factors.

METHODS AND RESULTS
Luminal area change during exercise (delta-ex, percent change compared with rest = 100%) was determined by biplane quantitative coronary arteriography in three groups: Group 1 consisted of 14 patients with normal total serum cholesterol of < 200 mg/100 mL; mean, 173 mg/100 mL (mean age, 51 years). Group 2 comprised 23 patients with a slightly elevated cholesterol of 200 to 250 mg/100 mL; mean, 223 mg/100 mL (mean age, 53 years). Group 3 had 24 patients with markedly elevated cholesterol of > 250 mg/100 mL; mean, 288 mg/100 mL (mean age, 54 years). Serum cholesterol levels and categorical risk factors such as positive family history, history of hypertension, smoking, obesity, and diabetes were related to exercise-induced vasomotor response. The three groups did not differ with regard to clinical characteristics, exercise work load, and hemodynamic data measured during exercise. However, delta-ex in normal vessels was significantly different between all three groups (ANOVA, P < .01): +31% (group 1), +18% (group 2), and +4% (group 3). Delta-ex in stenotic vessels did not differ between the groups: -5% (group 1), -13% (group 2), and -12% (group 3). Delta-ex of the nonstenosed vessel correlated significantly and inversely with total cholesterol, with low-density lipoprotein cholesterol, with the ratio of total to high-density lipoprotein cholesterol, and with the number of coronary risk factors present in a patient. High total cholesterol and a history of hypertension were independent risk factors for impaired coronary vasomotion.

CONCLUSIONS
In patients with and without coronary artery disease, hypercholesterolemia and a history of hypertension independently impair exercise-induced coronary vasodilation in angiographically normal coronary arteries. In the stenotic vessel, vasomotion during exercise does not appear to be influenced by the actual serum cholesterol. The precise mechanism by which the impaired vasomotion of the angiographically normal coronary arteries is mediated is unknown, but a direct negative effect of hypercholesterolemia on endothelial function or early undetected atherosclerosis appears to be the most likely explanation.
Antineutrophil and myocardial protecting actions of a novel nitric oxide donor after acute myocardial ischemia and reperfusion of dogs.
Authors: Lefer D J , Nakanishi K , Johnston W E , Vinten-Johansen J 
Published: June 2012

BACKGROUND
It has recently been demonstrated that myocardial ischemia and reperfusion results in a marked decrease in the release of nitric oxide (NO) by the coronary endothelium. NO may possess cardioprotective properties, possibly related to inhibition of neutrophil-related activities. We tested the hypothesis that a cysteine-containing nitric oxide donor compound, SPM-5185, would reduce infarct size and inhibit neutrophil-related activities (adherence to coronary vascular endothelium, accumulation).

METHODS AND RESULTS
The effects of intracoronary infusion of SPM-5185 were investigated in a 5.5-hour model of myocardial ischemia (1 hour) and reperfusion (4.5 hours) (MI-R) in anesthetized, open-chest dogs. SPM-5185 (500 nmol/L) or saline vehicle was infused for 4.5 hours into the left anterior descending coronary artery (LAD) at the time of reperfusion after 1 hour of LAD occlusion. MI-R in dogs receiving saline vehicle resulted in severe myocardial injury characterized by dyskinesis, a profound elevation of plasma creatine kinase, marked myocardial necrosis, and high cardiac myeloperoxidase (MPO) activity in the ischemic and necrotic zones. In contrast, treatment with SPM-5185 resulted in a modest restoration of regional function, a reduction of myocardial necrosis expressed as a percentage of the area at risk (12.5 +/- 3.2% versus 41.7 +/- 5.4%, P < .001), and significant reductions of MPO activity in the ischemic zone (0.8 +/- 0.1 versus 2.5 +/- 0.7 U/100 mg tissue, P < .05) and the necrotic zone (1.6 +/- 0.2 versus 3.3 +/- 0.6 U/100 mg tissue, P < .05). In additional studies, SPM-5185 (500 nmol/L) significantly (P < .001) attenuated the adherence of LTB4-stimulated canine neutrophils to autologous segments of coronary artery and attenuated the neutrophil-induced contraction of isolated coronary arterial rings.

CONCLUSIONS
SPM-5185 reduces myocardial necrosis and neutrophil accumulation in an acute model of canine myocardial ischemia and reperfusion. This reduction in myocardial cell injury may be partially related to the inhibitory actions of this novel NO donor on neutrophil adherence to the coronary endothelium.
Optical recordings of the effect of electrical stimulation on action potential repolarization and the induction of reentry in two-dimensional perfused rabbit epicardium.
Authors: Knisley S B , Hill B C 
Published: June 2012

BACKGROUND
Prolonged membrane depolarization induced by an electric shock in the heart may produce propagation block leading to repetitive beats. We studied prolonged depolarization and its role in repetitive beats in a thin epicardial layer of endocardially prefrozen arterially perfused rabbit heart.

METHODS AND RESULTS
A laser scanner recorded optical action potentials at 63 sites within a 1-cm2 area on the left ventricle of hearts stained with potentiometric fluorescent dye. Pacing (S1) produced propagation across the myofibers; then, a 3-millisecond shock (S2) given in the S1 refractory period produced an electric field that decreased in strength with distance along the fibers. The S2 strengths at the center of the scanned region (C) were 2.1 +/- 0.2 or 5.6 +/- 0.3 V/cm (mean +/- SD, n = 4). Repetitive beats occurred in 50% of hearts when C was 2.1 V/cm and in 100% of hearts when C was 5.6 V/cm. With each occurrence of repetitive beats, prolonged depolarization of the shocked action potential occurred within 1 mm of the S2 electrode when C was 2.1 V/cm and within 3 mm when C was 5.6 V/cm. Transient block immediately after S2 occurred between tissue with prolonged depolarization (S2 strength, 6 to 9 V/cm) and tissue without prolonged depolarization (S2 strength, 1 to 3 V/cm). Propagation in the scanned region after S2 occurred first on the side of the block distal to the S2 electrode, propagated from the most recovered to the least recovered tissue, and then turned toward the S2 electrode. When C was 5.6 V/cm, reentry by retrograde propagation near the S2 electrode produced repetitive beats. The center of the reentrant circuit exhibited further transient block and small depolarizations associated with the circulating activation.

CONCLUSIONS
Prolonged depolarization occurs where the S2 strength is more than 6 V/cm, block occurs between regions of prolonged depolarization and no prolonged depolarization, and reentry occurs around the block. Shock-induced prolonged depolarization can be proarrhythmic and may account for electrically induced arrhythmias.
Ventricular arrhythmias in trials of thrombolytic therapy for acute myocardial infarction. A meta-analysis.
Authors: Solomon S D , Ridker P M , Antman E M 
Published: June 2012

BACKGROUND
Although thrombolytic therapy reduces long-term mortality in acute myocardial infarction, many clinicians remain concerned about an increased risk of ventricular arrhythmias associated with the use of these agents.

METHODS AND RESULTS
To determine whether thrombolytic therapy increases the risk of ventricular tachyarrhythmias and whether an increase in arrhythmias could be responsible for the increased mortality seen in the first 24 hours after lytic therapy, we performed a meta-analysis of 15 randomized trials of thrombolysis in acute myocardial infarction in which the odds of developing in-hospital ventricular fibrillation (VF) and ventricular tachycardia (VT) in patients receiving thrombolysis was compared with that of patients receiving placebo. For trials that reported the incidence of VF during the first 6 hours after thrombolysis, the summary odds ratio for developing VF in the thrombolytic group was 0.98 (95% confidence interval [CI], 0.6 to 1.6; P = .94). For trials that reported the incidence of VF during the first hospital day, the summary odds ratio for developing VF was 1.00 (95% CI, 0.85 to 1.2; P = .95). The summary odds ratio for the development of VF at any time during hospitalization in the thrombolytic group was 0.83 (95% CI, 0.76 to 0.90; P < .0001). In trials that reported the incidence of VT any time during hospitalization, the summary odds ratio for the development of VT in the thrombolytic group was 1.34 (95% CI, 1.15 to 1.55; P < .0001).

CONCLUSIONS
The likelihood of developing VF in the early hours after thrombolysis for acute myocardial infarction is similar in patients receiving thrombolytics or placebo. However, throughout the hospital course, the risk of VF is greater in patients receiving placebo, whereas the risk of VT is higher in patients receiving thrombolysis.
Ischemic preconditioning is associated with a delay in ischemia-induced reduction of beta-adrenergic signal transduction in rabbit hearts.
Authors: Iwase T , Murakami T , Tomita T , Miki S , Nagai K , Sasayama S 
Published: June 2012

BACKGROUND
It has been reported that the A1-adenosine receptor mediates the cardioprotective effect of ischemic preconditioning. This receptor couples inhibitory guanine nucleotide-binding protein (Gi) and inhibits adenylate cyclase activity. However, the role of adenylate cyclase in preconditioning is unknown.

METHODS AND RESULTS
We compared the effects of ischemia on the sarcolemmal beta-adrenergic receptor density (Bmax), the stimulatory guanine nucleotide-binding protein (Gs) activity as determined by reconstitution with S49 lymphoma cyc- membranes, and baseline and maximally stimulated adenylate cyclase activities (ACAs) in control and preconditioned rabbit hearts. The control population (n = 28) received 0, 10, 20, and 60 minutes of coronary occlusion (n = 6 to 8 per stage), and preconditioned rabbits (n = 24) received two cycles of alternating 5-minute occlusion and reperfusion before sustained ischemia (n = 6 per stage). In control hearts, occlusion induced rapid and progressive reductions in the Bmax, Gs, and ACAs after 10 to 60 minutes of ischemia. Preconditioning did not affect the reduction in Bmax, but it preserved reductions in Gs activity and ACAs after 10 to 20 but not 60 minutes of sustained ischemia. In another study, 18 rabbits were treated with pertussis toxin 48 hours before surgery to block Gi. During treatment, no significant difference was observed in the ischemia-induced reduction in ACAs in the ischemic region between control (n = 8) and preconditioned (n = 10) animals after 20 minutes of ischemia.

CONCLUSIONS
Preconditioning delays ischemia-induced reductions in beta-adrenergic signal transduction. Inhibition of ACA is not the target effect of the A1-adenosine receptor-Gi pathway responsible for the cardioprotective role of preconditioning.
Inhibition of endothelium-derived relaxing factor enhances myocardial stunning in conscious dogs.
Authors: Hasebe N , Shen Y T , Vatner S F 
Published: June 2012

BACKGROUND
Impaired endothelial-dependent vascular responses after coronary artery occlusion (CAO) and reperfusion (CAR) have been investigated extensively. However, it is not known whether impaired endogenous endothelium-derived relaxing factor production affects postischemic myocardial dysfunction, ie, myocardial stunning.

METHODS AND RESULTS
Eight dogs were instrumented with an intracoronary catheter and an hydraulic occluder on the left circumflex coronary artery. The effects of a 10-minute CAO randomized with and without intracoronary administration of NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor, were compared in the same conscious dogs. Postischemic regional contractile dysfunction in subendocardial and subepicardial as well as transmural wall thickening was measured with ultrasonic dimension crystals, and myocardial blood flow was measured with radioactive microspheres. Intracoronary infusion of L-NA did not affect systemic hemodynamics, and transmural myocardial blood flow was reduced slightly (-8%), but significantly, only in the left circumflex territory. The recovery of wall thickening was significantly delayed in the presence of L-NA compared with the absence of L-NA, eg, at 30-minute CAR, not only in the subendocardium (-76 +/- 9% versus -49 +/- 9%) but also in the subepicardium (-52 +/- 8% versus -29 +/- 7%). During CAO, blood flow was decreased identically in both conditions, and during CAR, the differences in blood flow were minor (7%).

CONCLUSIONS
Inhibition of NO synthesis enhanced myocardial stunning transmurally in conscious dogs, potentially independent of its effects on blood flow.
Effects of intracoronary acetylcholine and atropine on basal and dobutamine-stimulated left ventricular contractility.
Authors: Landzberg J S , Parker J D , Gauthier D F , Colucci W S 
Published: June 2012

BACKGROUND
The role of cholinergic pathways in modulating left ventricular contractile function in humans is not known. This study evaluated the effect of a cholinergic agonist (acetylcholine) and antagonist (atropine) on basal and beta-adrenergically stimulated left ventricular contractile function in normal subjects and subjects with denervated hearts after cardiac transplantation.

METHODS AND RESULTS
Six subjects with normal left ventricular function and seven subjects who were 1 to 3 years after cardiac transplantation were studied. Acetylcholine, atropine, and the beta-adrenergic agonist dobutamine were infused via the left main coronary artery, and changes in left ventricular contractile function were assessed by measurement of peak +dP/dt. Intracoronary dobutamine increased +dP/dt by 70 +/- 15% and 66 +/- 20% in the normal subjects and transplant recipients, respectively. Intracoronary acetylcholine and atropine alone each had no effect on left ventricular +dP/dt in either normal subjects or transplant recipients. The concurrent infusion of acetylcholine with dobutamine reduced the response to dobutamine by 66 +/- 10% and 79 +/- 9% in normal subjects and transplant recipients, respectively. The concurrent infusion of atropine with dobutamine potentiated the response to dobutamine by 25 +/- 7% in normal subjects but had no effect in transplant recipients.

CONCLUSIONS
Stimulation and inhibition of cholinergic receptors in the human heart can modulate the positive inotropic response to beta-adrenergic stimulation.
Rise in chronic defibrillation thresholds in nonthoracotomy implantable defibrillator.
Authors: Venditti F J , Martin D T , Vassolas G , Bowen S 
Published: June 2012

BACKGROUND
To establish the chronic stability of defibrillation thresholds (DFTs) in a transvenous cardioverter/defibrillator (TCD) system, we studied 37 consecutive patients with TCD systems implanted for > 6 months.

METHODS AND RESULTS
DFT was measured by a step-down method at implant and 2 and 6 months later. The mean ejection fraction was 34.5 +/- 14.3%. Coronary artery disease with previous myocardial infarction was present in 31 patients. The mean DFT rose from 13.3 +/- 4.3 J at implant to 16.5 +/- 4.7 J at 2 months (P < .001) and 17.6 +/- 5.4 J at 6 months (P < .0001). ANOVA revealed a statistically significant rise in DFT over time (P < .0005). At 2 months, 25 patients had a rise in DFT, and 14 had a rise > or = 5 J. The observed rise at 2 months persisted in 19 patients. A chronic rise, defined as > or = 5 J rise at 6 months, occurred in 17 patients. Univariate analysis of clinical as well as implant variables revealed no predictors of a rise in DFT in this group.

CONCLUSIONS
We conclude that there is a significant rise in DFT at 2 and 6 months in this TCD system. Although the chronic threshold remained well within the available energy range of the pulse generator, this observation has important implications for implantation guidelines, programming, and future pulse generator development for TCD patients.
Esmolol tilt testing with esmolol withdrawal for the evaluation of syncope in the young.
Authors: Ovadia M , Thoele D 
Published: June 2012

BACKGROUND
Head-upright tilt (HUT) testing is valuable in evaluating syncope. Isoproterenol is used to increase sensitivity. However, isoproterenol is contraindicated or dangerous in undiagnosed heart disease and produces false-positives. We introduced esmolol withdrawal during esmolol HUT, hypothesizing that (1) acute withdrawal of the ultrashort-acting beta-blocker induces beta-adrenergic effects by unmasking endogenous catecholamines and may provoke syncope with fewer risks, and (2) response to esmolol/esmolol withdrawal may predict effective therapy.

METHODS AND RESULTS
Thirty-six patients with unexplained recurrent syncope/presyncope (7 to 35 years old, known heart disease or arrhythmia in 14) underwent 2 to 4 HUT tests (60 degrees, 49 minutes): (1) baseline, (2) esmolol (500 micrograms/kg plus 50 micrograms.kg-1.min-1), (3) esmolol withdrawal (HUT continued after esmolol stopped), and (4) isoproterenol if tests 1 through 3 were negative and isoproterenol was not contraindicated. A positive test reproduced symptoms with hypotension or bradycardia, requiring recumbency for recovery. Twenty-five had positive tests, and 11 had negative tests. In 5, only the baseline test was positive; in 15, esmolol/esmolol withdrawal tests were also positive, with 3 in whom esmolol withdrawal was positive although negative at baseline. Two isoproterenol tilts were positive. Esmolol withdrawal and isoproterenol tilts had the highest initial heart rate and similar maximal heart rate increment. Only isoproterenol caused hypertension. One isoproterenol test was false-positive, with hypertension-induced arterial baroreflex. Treatment was beta-blockers (8), Na/fludrocortisone (9), both (6), and DDD pacemakers (2). Esmolol/esmolol withdrawal accurately predicted therapeutic response in 15; isoproterenol predicted therapeutic response in none.

CONCLUSIONS
Esmolol withdrawal tilt testing is preferable to isoproterenol for provocative testing of syncope in the young, and it appears to be safer. Esmolol withdrawal testing has clinical utility before invasive testing as a first-line investigation for syncope in patients with or without heart disease.
An evaluation of ribonuclease protection assays for the detection of beta-cardiac myosin heavy chain gene mutations.
Authors: MacRae C A , Watkins H C , Jarcho J A , Thierfelder L , McKenna W J , Seidman J G , Seidman C E 
Published: June 2012

BACKGROUND
Ribonuclease (RNase) protection has been used to identify beta-cardiac myosin heavy chain (MHC) gene mutations that cause familial hypertrophic cardiomyopathy (FHC). Since more than 10 different mutations within this gene have been demonstrated to cause FHC in unrelated individuals, the genetic diagnosis of this condition will involve screening the beta-MHC gene. The accuracy with which RNase protection identifies such mutations is critical to defining the utility of this methodology in detecting mutations that cause FHC.

METHODS AND RESULTS
Twelve unrelated individuals with FHC were selected for further study because their beta-MHC genes had been screened for mutations by use of RNase protection, and no mutation was found. We performed linkage analysis of the families of these 12 probands using polymorphic short tandem repeats within the beta-MHC gene to determine whether FHC was genetically linked to the MHC locus on chromosome 14. FHC was not genetically linked to the MHC locus in 11 families whose beta-cardiac MHC gene did not contain mutations detectable by RNase protection.

CONCLUSIONS
We conclude that RNase protection is a sensitive method for screening for mutations within the beta-cardiac MHC gene. Further, mutations in the noncoding regions of the beta-MHC gene and mutations in the alpha-cardiac MHC gene are not a common cause of FHC. Negative RNase protection assays of affected individuals suggest that their FHC is due to mutations at other loci.
Interaction between plasma potassium and epinephrine in coronary thrombosis in dogs.
Authors: Lin H , Young D B 
Published: June 2012

BACKGROUND
Both plasma potassium ([K]) and epinephrine concentrations have been known to increase during exercise and decrease rapidly shortly after exercise; in addition, it is also known that exercise can promote coronary thrombosis in human and animal subjects. Many studies have shown that epinephrine has a stimulatory effect on coronary thrombosis; however, little information is available concerning the effect of raising plasma [K] on coronary thrombosis. The present study was designed to investigate the effect of raising plasma [K] and its interaction with epinephrine infusion on coronary thrombosis.

METHODS AND RESULTS
A canine model of coronary thrombosis was used, and the frequency of cyclic blood flow reductions (CFRs) resulting from thrombus formation in the circumflex artery was analyzed in the study. By acutely raising plasma [K] to approximately 6.0 mEq/L, the frequency of CFRs was reduced from 8.0 +/- 0.6 to 3.7 +/- 1.0 in 40 minutes (P < .01). Epinephrine infusion (0.5 microgram.kg-1 x min-1) stimulated the frequency of CFRs from 7.1 +/- 0.5 to 11.5 +/- 0.7 in 40 minutes (P < .01). However, if plasma [K] was raised to approximately 6.0 mEq/L while the epinephrine infusion was continued, the frequency fell from 11.5 +/- 0.7 to 7.7 +/- 1.1 in 40 minutes (P < .01).

CONCLUSIONS
The present study demonstrated that acutely raising plasma [K] inhibited coronary thrombosis in dogs and also blocked the potentiating effect of epinephrine on coronary thrombosis. These findings may suggest that raising plasma [K] exerts a protective effect against coronary thrombosis and that a rapid decrease in plasma [K], such as that occurring shortly after exercise, facilitates coronary artery thrombosis when the artery has a preexisting pathological condition.