bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity. Workshop III. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health.
Authors: St Jeor S T , Brownell K D , Atkinson R L , Bouchard C , Dwyer J , Foreyt J P , Heber D , Kris-Etherton P , Stern J S , Willett W
Published: June 2012

The workshop provided the opportunity to discuss issues and develop and integrate ideas. The following recommendations for public policies, education programs, and high-priority research initiatives were developed: Recommendations for Public Policies: Focus on prevention by requiring school programs to emphasize appropriate diet, physical activity, and general health guidance to promote cardiovascular health and prevent disease through federal funding. Provide better access to exercise (city planning, work-site interventions). Influence food availability and accessibility. Influence reimbursement policies for effective early intervention and prevention strategies for obesity. Reevaluate policies for use of drugs in the treatment of obesity. Recommendations for Education Programs: Sponsor scientific workshop to: Define the most appropriate weight standards for prevention and treatment. Identify who should lose weight and why, when, and how. Promote the fact that obesity is an important health risk factor, even at moderate levels, and that excess visceral fat is particularly hazardous. Target health care professionals, consumers, and the media for education about: Nature of obesity as a heterogeneous syndrome. Recommendations for diet, exercise, behavioral interventions, drugs, and surgery. Recognition of special needs of populations of different ethnicity, gender, age, etc. State-of-the-art treatment and treatment programs. High-Priority Research Initiatives: Build better bridges between basic research and treatment/prevention practices. Acknowledge that obesity is a heterogeneous syndrome that may best be characterized as different obesities. Research on defining subtypes. Implications for etiology and treatment. Better characterization of genotypes and phenotypes. Study the effects of weight loss, weight gain,and weight cycling on medical and psychosocial outcomes and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)
Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group.
Authors: Newman A B , Siscovick D S , Manolio T A , Polak J , Fried L P , Borhani N O , Wolfson S K
Published: June 2012

BACKGROUND

Peripheral arterial disease measured noninvasively by the ankle-arm index (AAI) is common in older adults, largely asymptomatic, and associated with clinically manifest cardiovascular disease (CVD). The criteria for an abnormal AAI have varied in previous studies. To determine whether there is an inverse dose-response relation between the AAI and clinical CVD, subclinical disease, and risk factors, we examined the relation of the AAI to cardiovascular risk factors, other noninvasive measures of subclinical atherosclerosis using carotid ultrasound, echocardiography and electrocardiography, and clinical CVD.

METHODS AND RESULTS

The AAI was measured in 5084 participants > or = 65 years old at the baseline examination of the Cardiovascular Health Study. All subjects had detailed assessment of prevalent CVD, measures of cardiovascular risk factors, and noninvasive measures of disease. Participants were stratified by baseline clinical CVD status and AAI (< 0.8, > or = 0.8 to < 0.9, > or = 0.9 to < 1.0, > or = 1.0 to < 1.5). Analyses tested for a dose-response relation of the AAI with clinical CVD, risk factors, and subclinical disease. The cumulative frequency of a low AAI was 7.4% of participants < 0.8, 12.4% < 0.9, and 23.6% < 1.0. participants with an AAI < 0.8 were more than twice as likely as those with an AAI of 1.0 to 1.5 to have a history of myocardial infarction, angina, congestive heart failure, stroke, or transient ischemic attack (all P < .01). In participants free of clinical CVD at baseline, the AAI was inversely related to history of hypertension, history of diabetes, and smoking, as well as systolic blood pressure, serum creatinine, fasting glucose, fasting insulin, measures of pulmonary function, and fibrinogen level (all P < .01). Risk factor associations with the AAI were similar in men and women free of CVD except for serum total and low-density lipoprotein cholesterol, which were inversely associated with AAI level only in women. Risk factors associated with an AAI of < 1.0 in multivariate analysis included smoking (odds ratio [OR], 2.55), history of diabetes (OR, 3.84), increasing age (OR, 1.54), and nonwhite race (OR, 2.36). In the 3372 participants free of clinical CVD, other noninvasive measures of subclinical CVD, including carotid stenosis by duplex scanning, segmental wall motion abnormalities by echocardiogram, and major ECG abnormalities were inversely related to the AAI (all P < .01).

CONCLUSIONS

There was an inverse dose-response relation of the AAI with CVD risk factors and subclinical and clinical CVD among older adults. The lower the AAI, the greater the increase in CVD risk; however, even those with modest, asymptomatic reductions in the AAI (0.8 to 1.0) appear to be at increased risk of CVD.
Late potentials and ventricular enlargement after myocardial infarction. A new role for high-resolution electrocardiography?
Authors: Zaman A G , Morris J L , Smyllie J H , Cowan J C
Published: June 2012

BACKGROUND

Arrhythmias are common in patients who have developed ventricular enlargement after myocardial infarction.

METHODS AND RESULTS

A prospective study was undertaken to assess the relation between ventricular dilatation and the development of late potentials after myocardial infarction. Echocardiograms and signal-averaged ECGs were recorded on days 1,3,7, and 42 in 52 patients with a first anterior myocardial infarction. Twenty-nine percent of patients were late potential-positive on their initial signal-averaged ECG recorded on the day of admission. The incidence of late potentials rose during the next week to a peak of 42% at day 7, declining to 13% by day 42. The presence of late potentials on the day of admission was associated with an increase in end-diastolic volume index of 16.1 +/- 6.0 mL/m2 (mean +/- SEM), compared with a decreased of 4.7 +/- 2.7 mL/m2 among late potential-negative patients (P < .006). Qualitatively similar results were evident for late potentials on day 3 and day 7. By contrast, there was no association between late potentials on day 42 and ventricular dilatation. Marked dynamic changes in late potentials were evident during the first week. Patients with persistent late potentials (n = 9) on all three recordings in the first week showed a marked increase in end-diastolic volume index of 21.3 +/- 8.1 mL/m2 (P < .005 in comparison with patients who were persistently negative [n = 20]). Patients demonstrating dynamic positivity (n = 15) not present on all three recordings in the first week showed no significant increase in end-diastolic volume index.

CONCLUSION

It is concluded that late potentials during the first week after infarction are associated with subsequent ventricular dilatation. These early-phase late potentials may be a manifestation of cell slippage. They arise before gross topographical enlargement and may serve as a predictor of ventricular dilatation.
Determination of the most appropriate velocity threshold for applying hemispheric flow convergence equations to calculate flow rate: selected according to the transorifice pressure gradient. Digital computer analysis of the Doppler color flow convergence region.
Authors: Deng Y B , Shiota T , Shandas R , Zhang J , Sahn D J
Published: June 2012

BACKGROUND

While flow convergence methods have been promising for calculating volume flows from color Doppler images, it appears that the velocity threshold used and the transorifice pressure gradient dramatically influence the accuracy of application of the simple hemispheric flow convergence equation for calculation of flow rate. The present in vitro study was performed to determine whether the value of velocity threshold at which the shape of proximal isovelocity surface best fits given shape assumptions with different orifice sizes and flow rates is predictable as a function independent of orifice size from clinically measurable peak velocity or transorifice pressure gradient information.

METHODS AND RESULTS

In an in vitro model built to facilitate ultrasound imaging, steady flow was driven through circular discrete orifices with diameters of 3.8, 5.5, and 10 mm. Flow rates ranged from 2.88 to 8.28 L/min with corresponding driving pressure gradients from 14 to 263 mm Hg. At each flow rate, Doppler color-encoded M-mode images through the center of the flow convergence region were obtained and transferred into the microcomputer (Macintosh IIci) in their original digital format. Then, the continuous wave Doppler traces of maximal velocity through the orifice were derived for the calculation of driving pressure gradient. Direct numerical spatial velocity measurements were obtained from the digital color encoded M-mode velocities with computer software. For each flow rate, we could calculate flow volume from any number of velocity distance combinations with a number of assumptions and use the results to assess expected flow convergence shape based on a priori knowledge of the progression from oblate hemispheroid to hemisphere to prolate hemispheroid changes observed previously. Our results showed that for a given ratio of calculated flow rate to actual flow rate (0.7 and 1), the velocity threshold that could be used for the calculation of flow rate with a hemispheric flow convergence equation correlated well with the pressure gradient for a given orifice size, and the differences in velocity threshold that could be used this way among different orifice sizes once they were adjusted for the covariate pressure gradients were not statistically significant (P = .79 for ratio = 0.7, and P = .81 for ratio = 1).

CONCLUSIONS

Our present study provides an orifice size-independent quantitative method that can be used to select the most suitable velocity threshold for applying a simple hemispheric flow convergence equation based on clinically predictable pressure gradients ranging from 40 to 200 mm Hg, and it offers a correction factor that can be applied to the hemispheric flow convergence equation when the pressure gradient is less than 40 mm Hg.
Sustained activation of vascular cells and leukocytes in the rabbit aorta after balloon injury.
Authors: Tanaka H , Sukhova G K , Swanson S J , Clinton S K , Ganz P , Cybulsky M I , Libby P
Published: June 2012

BACKGROUND

To improve understanding of the cellular basis of the arterial response to injury, we tested whether balloon withdrawal can induce certain inflammatory functions of vascular cells and leukocytes and whether such "activation" persists even after the acute phase of injury.

METHODS AND RESULTS

We examined the expression of several inducible cell surface molecules in the rabbit aorta at 2, 5, 10, and 30 days after balloon injury. Longitudinal sections encompassing parts of the uninjured, border, and injured zones were examined for expression of vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), class II major histocompatibility (MHC) antigens, and markers for smooth muscle cells (SMCs), macrophages, endothelial cells, and T-lymphocytes. Endothelial cell healing involved true endothelial regeneration as well as migration, as shown by nuclear incorporation of bromodeoxyuridine. Luminal endothelial cells at the leading edge of repopulation at each time point expressed VCAM-1. As healing progressed, VCAM-1 expression decreased in the regenerated endothelial cells. The neointimal endothelium also expressed high levels of ICAM-1 that persisted longer than the elevation of VCAM-1. SMCs in the neointima also showed increased levels of ICAM-1. Some neointimal endothelial cells, SMCs, and macrophages also expressed high levels of class II MHC antigens during 30 days after injury.

CONCLUSIONS

Local inflammatory activation of endothelial cells, SMCs, and leukocytes occurs in a predictable sequence and persists up to 30 days after balloon injury to the rabbit aorta. Our findings suggest that ongoing local signals persisting after the original balloon injury may contribute to later phases of intimal thickening.
Response of human coronary arteries to serotonin after injury by coronary angioplasty.
Authors: Mc Fadden E P , Bauters C , Lablanche J M , Quandalle P , Leroy F , Bertrand M E
Published: June 2012

BACKGROUND

Atherosclerotic stenoses that have exaggerated vasomotor responses are especially prone to restenosis after coronary angioplasty. Experimental studies show that vasomotor responses in normal vessels are altered by acute mechanical injury, an alteration that in part reflects changes in the functional characteristics of endothelium that has regenerated after injury.

METHODS AND RESULTS

We examined, by quantitative coronary arteriography, the response of dilated and control coronary segments to intracoronary infusions of graded doses of serotonin, an endothelium-dependent vasoactive agent, and to intracoronary injection of isosorbide dinitrate, an endothelium-independent smooth muscle dilator in 15 patients who had undergone a single percutaneous transluminal coronary angioplasty procedure and who had no clinical features of variant angina. Dose-dependent constriction to serotonin occurred at all measured sites. The mean +/- SEM diameter reductions, expressed as percent reduction in baseline diameter that was observed at proximal (18.1 +/- 2.9, 18.8 +/- 2.2) and distal (30.9 +/- 4.4, 35.4 +/- 5.3) control sites in the dilated and nondilated vessels, respectively, at the highest dose, were similar. The degree of constriction in distal segments was significantly (P < .01) greater than that in proximal segments. Total or subtotal occlusion occurred at the angioplasty site in 4 patients at the highest infused dose (10(-4) mol/L). The mean percent reduction in baseline diameter at previously dilated sites (53.8 +/- 5.9) at this dose was significantly (P < .05) greater than that observed at the adjacent proximal control sites and similar to that observed at distal control sites. All segments dilated significantly after intracoronary injection of isosorbide dinitrate.

CONCLUSIONS

In dilated and nondilated vessels, serotonin caused significantly more marked constriction in distal than in proximal vessel segments. In dilated vessels, the vessel segments that had been subjected to angioplasty had a constrictor response to serotonin that was more marked than at adjacent proximal control sites and equivalent to that in the distal vessel segments. This enhanced constrictor response could be related to changes in endothelial cell function after regeneration or to hyperreactivity of smooth muscle cells at the angioplasty site.
Differences between men and women in hospital mortality associated with coronary artery bypass graft surgery. The Northern New England Cardiovascular Disease Study Group.
Authors: O'Connor G T , Morton J R , Diehl M J , Olmstead E M , Coffin L H , Levy D G , Maloney C T , Plume S K , Nugent W , Malenka D J
Published: June 2012

BACKGROUND

A prospective study of patients undergoing coronary artery bypass graft surgery (CABG) was conducted to examine differences in hospital mortality by sex. Outcome data on 3055 CABG patients undergoing operation between 1987 and 1989 were examined for differences in patient, disease, and treatment factors.

METHODS AND RESULTS

Odds ratios (OR), risk differences, and 95% confidence intervals (CI95%) were calculated. Mortality rates for women (7.1%) and men (3.3%) differed, the OR (women versus men) being 2.23 (CI95%, 1.58 to 3.15). Women were older, more often diabetic, and had more urgent or emergent surgery; adjustment yielded an OR (women versus men) of 1.75 (CI95%, 1.17 to 2.63). Body surface area (BSA) was associated with risk of death in both sexes (P = .007) and positively associated with coronary artery luminal diameters. After adjustment for BSA, sex was no longer significantly associated with mortality (OR [women versus men] of 1.18; CI95%, 0.72 to 1.95). Internal mammary artery (IMA) grafting was performed less frequently among women than men (64.8% versus 78.4%, P < .001). Smaller BSA and absence of IMA grafting were each associated with increased risk of death (RD) from heart failure. Risk of death from heart failure (RD [women minus men] = 2.05; CI95%, 0.89 to 3.22) and hemorrhage (RD [women minus men] = 0.63; CI95%, 0.13 to 1.13) was greater among women; these accounted for 71.1% of the sex-specific difference in mortality rates.

CONCLUSIONS

Excess risk of hospital mortality among women having CABG was largely the consequence of death from heart failure and, to a lesser extent, from hemorrhage. Smaller BSA (probably because of its association with coronary artery luminal diameter) and the absence of IMA grafting were each associated with increased risk of death from heart failure.
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.
Relation between left ventricular oxygen consumption and pressure-volume area in conscious dogs.
Authors: Nozawa T , Cheng C P , Noda T , Little W C
Published: June 2012

BACKGROUND

The relation between left ventricular (LV) oxygen consumption (MVO2) and pressure-volume area (PVA) developed in isolated hearts provides a powerful method to understand cardiac energetics. We investigated application of this relation to the intact circulation, determining its response to steady-state and transient load alterations and enhanced contractility in conscious animals.

METHODS AND RESULTS

Eight dogs were instrumented to measure LV pressure (micromanometer), LV volume (three sonomicrometers), and left circumflex and anterior descending coronary artery flows (ultrasonic flowmeter). Data were acquired after recovery from the surgery with the animals awake and unsedated. After administration of hexamethonium and atropine, steady-state loading conditions were changed with phenylephrine or nitroprusside in four to five steps before and during the infusion of dobutamine (6 to 10 micrograms.-1kg.-1min). MVO2 and PVA obtained under steady-state conditions were linearly correlated both before and during dobutamine. The MVO2-PVA relation obtained on a beat-to-beat basis during transient caval occlusion was less linear and not coincident with the steady-state relation. Dobutamine shifted the steady-state MVO2-PVA relation upward in all hearts, increasing the MVO2 axis intercept of the MVO2-PVA relation (P < .01). This intercept correlated with ventricular contractility assessed by the slope (Ees) of the LV end-systolic pressure-volume relation determined by caval occlusion (r = .76, P < .05). The slope of the MVO2-PVA relation increased with dobutamine in seven of eight animals, with the inverse of the slope (representing contractile efficiency) being 31 +/- 6% during control and 24 +/- 6% after dobutamine (P = .06).

CONCLUSIONS

MVO2 and PVA are linearly related during steady-state alterations in loading conditions in conscious dogs but not on a beat-by-beat basis during transient caval occlusion. Increase in contractility by dobutamine produces an upward shift of the MVO2-PVA relation.
Blood pressure and endocrine responses to changes in dietary sodium intake in cardiac transplant recipients. Implications for the control of sodium balance.
Authors: Singer D R , Markandu N D , Buckley M G , Miller M A , Sagnella G A , Lachno D R , Cappuccio F P , Murday A , Yacoub M H , MacGregor G A
Published: June 2012

BACKGROUND

The role of cardiac extrinsic innervation in the regulation of sodium balance and blood pressure is controversial.

METHODS AND RESULTS

We performed a double-blind study of endocrine and blood pressure responses to 5 days of low- (LS, 10 mmol/d) and 5 days of high- (350 mmol/d) sodium intake in 12 cardiac transplant recipients, 12 matched healthy subjects, and 12 matched subjects with untreated essential hypertension. In transplant recipients on low sodium, supine blood pressure was 137/94 +/- 8/4 (mean +/- SEM) mm Hg and plasma atrial natriuretic peptide (ANP) was 59.3 +/- 6.3 pg/mL; on high sodium, blood pressure was 148/97 +/- 5/3 mmHg (P < .05 for systolic pressure versus LS), and ANP was 94.3 +/- 10.6 pg/mL (P < .01 versus LS), respectively. Plasma ANP for those on each diet was significantly higher in the cardiac transplant recipients than in healthy or hypertensive controls; relative changes in plasma ANP in changing from low- to high-sodium diet were similar in each group. Urinary sodium excretion by the fifth day of each diet was similar in each group. Suppression of plasma renin activity and aldosterone by high-sodium diet was blunted in cardiac transplant recipients compared with healthy subjects (respectively, plasma renin activity: 1.41 +/- 0.30 versus 0.68 +/- 0.21 ng.mL-1 x h-1, P < .05; aldosterone: 391 +/- 35 versus 166 +/- 21 pmol/L, P < .05).

CONCLUSIONS

These results suggest that extensive denervation of the heart does not result in major abnormalities in regulation of large changes in sodium intake and that intact cardiac innervation is not required for plasma ANP responses to altered sodium intake. Blood pressure after cardiac transplantation is sensitive to reduced sodium intake.
Kinetic properties of 99mTc-Q12 in canine myocardium.
Authors: Gerson M C , Millard R W , Roszell N J , McGoron A J , Gabel M , Washburn L C , Biniakiewicz D , Blankenship D , Mallin W H , Elder R C
Published: June 2012

BACKGROUND

99mTc-Q12 is a new Tc(III) perfusion imaging agent that permits prompt myocardial visualization in humans. We postulated that 99mTc-Q12 myocardial activity is related to actual myocardial blood flow during conditions of myocardial ischemia and pharmacological coronary artery vasodilation and that 99mTc-Q12 shows little or no myocardial redistribution as long as 4 hours after intravenous injection.

METHODS AND RESULTS

In seven anesthetized, open chest dogs, the left circumflex coronary artery was occluded, and dipyridamole (0.32 or 0.56 mg/kg) was infused into the right atrium, followed by 10 mCi of 99mTc-Q12. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized, and a total of 315 myocardial samples were assayed in a well counter for 99mTc activity. One week later, radiolabeled microsphere activity was determined, and myocardial blood flow was calculated. 99mTc activity (y) was related to myocardial blood flow (x) from 0 to 2 mL.g-1 x min-1 by the relation y = 0.64x + 0.35 (r = .88, P = .0001). In 14 additional anesthetized, open chest dogs, an occluder was placed around the left circumflex coronary artery, and an ischemic level of circumflex blood flow was maintained constant over 4 hours as measured by an ultrasonic flowmeter. Dipyridamole (0.56 mg/kg) was infused intravenously beginning 15 minutes after coronary occlusion and then followed by 10 mCi of 99mTc-Q12. Gamma camera images, hemodynamics, microsphere blood flow, and endocardial biopsies (latter in six dogs) were performed at 30, 60, 120, and 240 minutes after 99mTc-Q12 injection. Myocardial blood flow in the distribution of the left anterior descending artery decreased by 29.6% from 30 to 240 minutes (P < .05), whereas left circumflex blood flow increased by 40.4% from 30 to 120 minutes (P < .05) as the dipyridamole hemodynamic effects dissipated. Nevertheless, the ratio of myocardial perfusion defect zone counts to normal myocardial zone counts remained constant over 4 hours, as did the technetium counts from the needle biopsy endocardial samples.

CONCLUSIONS

Over a limited range of myocardial blood flows from 0 to approximately 2 mL.g-1 x min-1, 99mTc-Q12 myocardial activity is related to actual myocardial flow at the time of tracer injection. 99mTc-Q12 shows no evidence of myocardial redistribution.