bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperinsulinemia, sex, and risk of atherosclerotic cardiovascular disease.
Authors: Modan M , Or J , Karasik A , Drory Y , Fuchs Z , Lusky A , Chetrit A , Halkin H 
Published: June 2012

BACKGROUND
The possibility that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease (CVD) was first suggested 20 years ago. During the last decade, this possibility has received support from three large prospective studies.

METHODS AND RESULTS
In the present study, the association between CVD, glucose intolerance, obesity, and hypertension (the GOH conditions) and hyperinsulinemia was examined cross-sectionally in a representative sample (n = 1,263) of the adult Jewish population aged 40-70 years in Israel. Previously known diabetics were excluded. CVD comprising clinical or ECG evidence of ischemic heart disease, as well as clinical evidence of cerebrovascular or peripheral vascular disease, was identified in 97 men and 39 women. A significant (p less than 0.01) hyperinsulinemia-sex interaction was found for CVD rate, with the adjusted risk ratios (followed by 95% confidence limits), relative to the rate in 298 normoinsulinemic women, being 1.15 (0.68-1.95) in 328 normoinsulinemic men, 0.85 (0.48-1.49) in 277 hyperinsulinemic women, and 2.27 (1.33-3.08) in 360 hyperinsulinemic men. Age-adjusted CVD rates in men versus women were: a) similar and low among all normoinsulinemic normotensives and hyperinsulinemics free of any of the GOH conditions (all rates less than or equal to 6.5%); b) similar and high among normoinsulinemic hypertensives (13.4% versus 10.4%); c) significantly higher in men among hyperinsulinemic normotensives with glucose intolerance and/or obesity (15.2% versus 3.3%; p = 0.02) and all hyperinsulinemic hypertensives (21.5% versus 12.8%; p = 0.04). These trends remained significant after adjusting for age, ethnic group, and blood lipids.

CONCLUSIONS
Therefore, hyperinsulinemia was associated with excess CVD risk in men but not in women, and all excess CVD risk in men was confined to hyperinsulinemic individuals in the presence of glucose intolerance, obesity, or hypertension.
Localization of breakthrough site of canine monomorphic ventricular tachycardia by pacemapping. A vectorial approach.
Authors: Lin J L , Wilber D J , Du D , Pearlman J , Ruskin J N , Garan H 
Published: June 2012

BACKGROUND
The precision and limitations of ventricular pacemapping as a method to localize the site of earliest breakthrough of ventricular tachycardia (VT) were investigated in a canine model of experimental myocardial infarction.

METHODS AND RESULTS
Forty-one episodes of VT induced in 10 animals were mapped using a standard grid of 64 endocardial and epicardial bipolar electrodes to determine the site of earliest endocardial or epicardial breakthrough of activation during VT. Each of these 64 recording sites was also used for ventricular pacing during sinus rhythm at cycle lengths comparable to those of the VTs. Orthogonal X, Y, and Z Frank electrocardiographic (ECG) leads were recorded during all episodes of VT and ventricular pacing from all sites after the chest was closed in all animals. Surface ECG waveforms corresponding to each VT and each ventricular pacing were compared pairwise by measuring the Euclidean metric difference between the VT and ventricular pacing vectors with the orthogonal ECG leads as their X, Y, and Z components. The pacing site that generated the vector most similar to VT vector (smallest vectorial difference) was defined as the predicted breakthrough site. This predicted site of breakthrough was identical to the actual site of breakthrough determined by activation sequence mapping during VT for only nine VTs (22%). However, for an additional 27 VTs (66%), the observed and predicted breakthrough locations were at adjacent (1 cm or less apart) recording sites. For five VTs (12%), the two sites were remote, the distance between them exceeding 1 cm.

CONCLUSIONS
In this model, locating the breakthrough site by pacemapping is exact in only a small minority of VTs. However, when orthogonal surface ECG leads are used for comparison, pacemapping can predict the site of earliest breakthrough during VT with a 1-cm resolution in the majority of VTs.
Effect of altered activation sequence on epicardial QRST area and refractory period in dogs.
Authors: Hanashima K , Kubota I , Ozawa T , Shibata T , Yamaki M , Ikeda K , Yasui S 
Published: June 2012

BACKGROUND
We investigated the effects of activation sequence on cardiac surface QRST areas and refractory periods in experiments on dogs.

METHODS AND RESULTS
Right and left ventricular pacings were performed, and the pacing site was altered every 6 minutes. After 4 minutes of a given pacing, 54 unipolar electrograms distributed over the entire cardiac surface were recorded. Next, refractory periods at electrode sites near pacing electrodes were measured. Paired right ventricular/left ventricular (RV/LV) pacing data were obtained six or seven times in each sample. Although the QRST isoarea maps during the two activation orders were qualitatively similar, it was recognized consistently from the right ventricle-left ventricle difference map that leads around the RV free wall had positive values and that leads around the LV free wall and apex had negative values. Compared with the same leads at RV and LV pacing, QRST areas were larger when pacing sites were near the leads. The local QRST areas of individual leads at which we measured local refractory period were consistently larger during drive from proximal pacing sites than during drive from distant pacing sites. Refractory periods were consistently longer during proximal pacing than during distal pacing, and there was a positive correlation between change in local QRST area and change in refractory period (r = 0.64) during altered activation sequence, whereas there was an inverse correlation between change in QRST area and change in refractory period (r = -0.91) during localized myocardial warming.

CONCLUSIONS
Both local QRST areas and local refractory periods were dependent on the activation sequence, and there was a positive correlation between QRST areas and refractory periods during various activation sequences compared with localized myocardial warming.
Effects of an increase in intracellular free [Mg2+] after myocardial stunning on sarcoplasmic reticulum Ca2+ transport.
Authors: Krause S M , Rozanski D 
Published: June 2012

BACKGROUND
Myocardial stunning has been associated with a greater than twofold increase in intracellular free [Mg2+] from 0.6 to 1.5 mM. The effect of this increase in free [Mg2+] on the function of the sarcoplasmic reticulum (SR) Ca2+ pump was assessed in SR isolated from Langendorff perfused, isovolumic rabbit hearts after 15 minutes of global ischemia.

METHODS AND RESULTS
Our results indicate that myocardial stunning results in a shift in the Ca2+ sensitivity of oxalate-supported, Ca2+ transport over the entire range of free [Ca2+] associated with the cardiac cycle. Using 0.6 mM free Mg2+ as control, maximal rates of Ca2+ transport occurred at 1 microM free Ca2+ (control, 519 +/- 32; stunned, 337 +/- 37 nmol Ca2+.min-1.mg-1). At 0.56 microM free Ca2+, SR Ca2+ transport was reduced from a control of 351 +/- 49 to 263 +/- 12 nmol Ca2+.min-1.mg-1 at 0.6 mM free [Mg2+]. Moreover, an increase in the free [Mg2+] from 0.6 to 1.5 mM results in a greater shift in the Ca2+ activation curve with no change in the level of maximal activation. Ca2+ transport at 0.56 microM free Ca2+ was shifted in the stunned SR from 263 +/- 12 to 138 +/- 29 nmol Ca2+.min-1.mg-1 at 0.6 and 1.5 mM free Mg2+, respectively.

CONCLUSIONS
These results indicate that an increase in free [Mg2+] after stunning in combination with the inherent defect in the SR Ca2+ ATPase may reduce the ability of the cell to regulate Ca2+ to a greater extent than previously observed. This impairment in Ca2+ regulatory function may contribute directly to the increase in diastolic tone and indirectly to the reduced systolic function characteristic of the stunned myocardium.
Myocardial oxygen consumption and the left ventricular pressure-volume area in normal and hypertrophic canine hearts.
Authors: Izzi G , Zile M R , Gaasch W H 
Published: June 2012

BACKGROUND
To assess and compare the energy demands of normal and hypertrophic hearts, we defined the relation between myocardial oxygen consumption (MVO2, an index of the energy consumed by contraction) and the left ventricular pressure-volume area (PVA, an index of the total mechanical energy generated by contraction) in eight normal and eight hypertrophic (aortic band model) dog hearts; MVO2 was also measured in the nonworking (empty beating) and basal (potassium arrest) states.

METHODS AND RESULTS
The hearts were studied in an isolated, blood-perfused heart apparatus. The slope of the MVO2-PVA relation (the inverse of which reflects myofibrillar efficiency) was similar in normal and hypertrophic hearts (3.89 +/- 1.91 and 4.19 +/- 1.25 ml O2/mm Hg.ml.10(5), p = NS). The MVO2 in empty beating (0.038 +/- 0.006 and 0.041 +/- 0.015 ml/beat/100 g, p = NS) and potassium-arrested (1.95 +/- 0.06 and 1.98 +/- 0.20 ml/min/100 g, p = NS) hearts was likewise similar in the two groups.

CONCLUSIONS
Basal and nonworking energy demands and working efficiencies of hypertrophic hearts are equivalent to those of normal hearts.
Muscle carnitine deficiency in patients with severe peripheral vascular disease.
Authors: Brevetti G , Angelini C , Rosa M , Carrozzo R , Perna S , Corsi M , Matarazzo A , Marcialis A 
Published: June 2012

BACKGROUND
This study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease.

METHODS AND RESULTS
Nine biopsy specimens of ischemic muscles were obtained from five patients undergoing reconstructive vascular surgery. Biopsies from 35 normal subjects served as controls. Ischemic muscles showed a significant reduction in total carnitine from the control value of 20.9 +/- 5.2 to 11.6 +/- 6.2 nmol/mg noncollagen protein (p less than 0.01). A significantly lower free carnitine and acylcarnitine content contributed to this reduction. Similarly, carnitine acetyltransferase activity was reduced in the ischemic muscles from the control value of 102.1 +/- 41.2 to 52.9 +/- 22.1 nmol/min/mg noncollagen protein (p less than 0.01). On the contrary, carnitine palmitoyltransferase activity did not show any change (0.29 +/- 0.05 nmol/min/mg noncollagen protein in the ischemic muscles and 0.28 +/- 0.07 nmol/min/mg noncollagen protein in controls). Carnitine, acylcarnitines, and enzyme activities were also measured in the ischemic muscles in four additional patients 2 days after intravenous administration of L-propionylcarnitine (1.5 g as a single bolus followed by an infusion of 1 mg/kg/min for 30 minutes). Treatment restored normal levels of carnitine and its esters in the ischemic muscles but did not affect enzyme activities.

CONCLUSIONS
Demonstration of carnitine deficiency in severe peripheral vascular disease substantiates previous findings showing the efficacy of carnitine supplementation to ischemic muscles. Furthermore, the feasibility of restoring carnitine homeostasis with L-propionylcarnitine provides the basis for clinical trials aimed at assessing the efficacy of this carnitine ester in the treatment of peripheral vascular disease.
QT interval prolongation predicts cardiovascular mortality in an apparently healthy population.
Authors: Schouten E G , Dekker J M , Meppelink P , Kok F J , Vandenbroucke J P , Pool J 
Published: June 2012

BACKGROUND
In myocardial infarction patients, heart rate-adjusted QT interval (QTc), an electrocardiographic indicator of sympathetic balance, is prognostic for survival.

METHODS AND RESULTS
In a 28-year follow-up, the association between QTc and all-cause, cardiovascular, and ischemic heart disease mortality was studied in a population of 3,091 apparently healthy Dutch civil servants and their spouses, aged 40-65 years, who participated in a medical examination during 1953-1954. Moderate (QTc, 420-440 msec) and extensive (QTc, more than 440 msec) QTc prolongations significantly predict all-cause mortality during the first 15 years among men (adjusted respective relative risks [RRs], 1.5 and 1.7) and among women (RRs, 1.7 and 1.6). In men, cardiovascular (RRs, 1.6 and 1.8) and ischemic heart disease mortality (RRs, 1.8 and 2.1) mainly account for this association. In women, the association cannot be attributed specifically to cardiovascular and ischemic heart disease mortality. RRs for a subpopulation without any sign of heart disease at baseline are similar. The same is observed for QTc prolongation after light exercise, although in this situation most associations are not statistically significant, probably because of smaller numbers in the QTc prolongation categories.

CONCLUSIONS
Our results suggest that QTc contributes independently to cardiovascular risk. If autonomic imbalance is an important mechanism, it might be speculated that changes in life-style (e.g., with regard to physical exercise and smoking) may have a preventive impact.
Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A2-receptor blockade. A randomized, double-blind, placebo-controlled trial. Coronary Artery Restenosis Prevention on Repeated Thromboxane-Antagonism Study (CARPORT).
Authors: Serruys P W , Rutsch W , Heyndrickx G R , Danchin N , Mast E G , Wijns W , Rensing B J , Vos J , Stibbe J 
Published: June 2012

BACKGROUND
GR32191B is a novel thromboxane A2-receptor antagonist with potent antiagregational and antivasoconstrictive properties. We have conducted a randomized, double-blind placebo-controlled trial to study its usefulness in restenosis prevention.

METHODS AND RESULTS
Patients received either GR32191B (80 mg orally before angioplasty and 80 mg/day orally for 6 months) or 250 mg i.v. aspirin before angioplasty and placebo for 6 months. Coronary angiograms before angioplasty, after angioplasty, and at 6-month follow-up were quantitatively analyzed. Angioplasty was attempted in 697 patients. For efficacy analysis, quantitative angiography at follow-up was available in 522 compliant patients (261 in each group). Baseline clinical and angiographic parameters did not differ between the two treatment groups. The mean difference in coronary diameter between postangioplasty and follow-up angiogram (primary end point) was -0.31 +/- 0.54 mm in the control group and -0.31 +/- 0.55 mm in the GR32191B group. Clinical events during 6-month follow-up, analyzed on intention-to-treat basis, were ranked according to the highest category on a scale ranging from death (control, six; GR32191B, four) to nonfatal infarction (control, 22; GR32191B, 18), bypass grafting (control, 19; GR32191B, 22) and repeat angioplasty (control, 52; GR32191B, 48). No significant difference in ranking was detected. Six months after angioplasty, 75% of patients in the GR32191B group and 72% of patients in the control group were symptom free.

CONCLUSIONS
Long-term thromboxane A2-receptor blockade with GR32191B does not prevent restenosis and does not favorably influence the clinical course after angioplasty.
Mitral regurgitation following mitral balloon valvotomy. Differing mechanisms for severe versus mild-to-moderate lesions.
Authors: Essop M R , Wisenbaugh T , Skoularigis J , Middlemost S , Sareli P 
Published: June 2012

BACKGROUND
This study was designed to evaluate the incidence and mechanisms of mitral regurgitation following mitral balloon valvotomy (MBV) in 40 consecutive patients with symptomatic tight pliable mitral stenosis.

METHODS AND RESULTS
Transthoracic echocardiography with color flow mapping was performed before and 24 hours after the procedure. Patients who developed significant mitral regurgitation following MBV also underwent transesophageal echocardiography. The relation between increased mitral regurgitation and both valvular morphology and procedure-related factors was examined. Gorlin mitral valve area increased from 0.81 +/- 0.3 to 1.95 +/- 0.7 cm2 (p less than 0.001). No patient had more than 2+ mitral regurgitation by angiography and color Doppler prior to MBV. There was a moderate correlation between Doppler and angiographic increase in mitral regurgitation (r = 0.73, p less than 0.0001). By Doppler criteria 33 patients had no (n = 6) or mild (n = 27) increase in mitral regurgitation (group 1), and seven developed significant new mitral regurgitation (group 2). Baseline clinical, echocardiographic, and procedure-related data for the two groups were similar. Multiple regression analysis did not select any individual valve characteristic (valvular thickening, mobility, calcification, and subvalvular disease), total echocardiographic score, balloon diameter, or ratio of balloon to mitral annular diameter as disruption with a torn anterior or posterior mitral leaflet in six and a ruptured papillary muscle in one. Two of these patients have required mitral valve replacement (6 and 9 months following the procedure), whereas the remainder are significantly symptomatic. By contrast, mitral regurgitation in group 1 either occurred at the site of commissural split (n = 20) or was associated with prolapse of the anterior mitral leaflet (n = 6).

CONCLUSIONS
Thus, severe new mitral regurgitation following MBV is due to noncommissural tearing of the mitral leaflet and confers an adverse long-term prognosis. A mild increase in mitral regurgitation following MBV is frequent and occurs at the site of commissural split or is associated with prolapse of the anterior leaflet. Furthermore, in this study, an increase in mitral regurgitation could not be predicted from any valvular or procedure-related factor.
Induction of myocardial hypertrophy after coronary ligation in rats decreases ventricular dilatation and improves systolic function.
Authors: Litwin S E , Raya T E , Anderson P G , Litwin C M , Bressler R , Goldman S 
Published: June 2012

BACKGROUND
Previous studies have shown that hypertrophy of surviving myocytes after myocardial infarction (MI) is limited. Progressive ventricular dilatation after MI may occur when compensatory hypertrophy cannot restore left ventricular (LV) wall stress to normal.

METHODS AND RESULTS
To test whether induction of additional myocyte hypertrophy might prevent pathological LV remodeling after large MI, we administered 2-tetradecylglycidic acid (TDGA) 20 mg/kg/day to sham-operated (n = 12) and MI (n = 10) rats for 10 days, beginning the third day after infarction. We have previously shown that chronic inhibition of long-chain fatty acid oxidation with TDGA in rats results in myocardial hypertrophy without any apparent impairment of LV systolic function. When compared with untreated MI rats (n = 9), we found that TDGA-treated MI rats had increases in LV weight/body wt, myocyte cross-sectional area, and peak developed LV pressure during abrupt aortic occlusion. MI rats treated with TDGA had lower LV end-diastolic pressures and smaller end-diastolic volumes, whereas stroke volume was maintained. The ex vivo passive LV pressure-volume relation was shifted toward the pressure axis compared with untreated infarct rats. In sham-operated rats, TDGA caused increases in LV weight/body wt, myocyte size, peak developed LV pressure, cardiac index, and stroke volume index, and a shift of the passive LV pressure-volume relation toward the pressure axis.

CONCLUSIONS
Induction of myocardial hypertrophy with an inhibitor of long-chain fatty acid oxidation retarded the process of LV dilatation and produced beneficial effects on systolic function after large myocardial infarction. These data support the hypothesis that inadequate hypertrophy of residual myocardium after infarction may contribute to LV dilatation and the development of congestive heart failure.
Correlates of sodium-lithium countertransport. Findings from the Gubbio Epidemiological Study. The Gubbio Collaborative Study Group.
Authors: Trevisan M , Laurenzi M 
Published: June 2012

BACKGROUND
Numerous reports have presented evidence for a positive association between the maximal velocity of the sodium-lithium countertransport (Na-Li CT) in erythrocytes and hypertension. The nature of this association remains to be clarified.

METHODS AND RESULTS
This report presents correlates of Na-Li CT in a population sample of 3,591 people aged 5-74 years. Males had higher mean age-specific levels of Na-Li CT than females except for the 5-14-year age stratum. In adults aged 25-74, for both men (n = 1,044) and women (n = 1,192), body mass index, plasma uric acid and glucose, alcohol consumption, and red blood cell mean corpuscular volume were positively related to countertransport in multivariate analyses; plasma high-density lipoprotein (HDL) cholesterol and plasma potassium were inversely related. Plasma non-HDL cholesterol was independently and directly related to Na-Li CT in women, and plasma sodium was inversely associated with Na-Li CT in men. These relations prevailed for men when persons with hypertension were excluded from the analyses and prevailed in part for women. When stepwise regression analyses were done for all men and women combined (n = 2,236), sex ceased to be significantly related to countertransport with plasma uric acid and alcohol intake in the model. In adults of either sex, no independent association was detected between Na-Li CT and age, heart rate, or the ratios of sodium to potassium or of sodium to creatinine in overnight untimed urine.

CONCLUSIONS
In both sexes, Na-Li CT is significantly and independently associated with a number of metabolic variables (plasma uric acid, plasma glucose, body mass index, plasma potassium, and life-style habits [e.g., alcohol intake]). Further research is needed to elucidate the meaning of the significant associations between Na-Li CT and the foregoing variables (all of them also related to blood pressure).
Short-term vasodilator effect of captopril in patients with severe mitral regurgitation is parasympathetically mediated.
Authors: Wisenbaugh T , Essop R , Sareli P 
Published: June 2012

BACKGROUND
Few data exist regarding the effects of angiotensin converting enzyme inhibitors in patients with regurgitant valvular lesions. We postulated an immediate improvement in cardiac performance with captopril in mitral regurgitation, which, in a hemodynamically compensated group of patients, might be mediated through parasympathetic vasodilation rather than through blockade of angiotension converting enzyme.

METHODS AND RESULTS
Hemodynamics were examined before and 90 minutes after oral captopril (25-50 mg) in 18 patients (mean age, 31 years) with chronic, severe mitral regurgitation in New York Heart Association functional class II and III. One group of patients was given captopril alone (group 1, n = 9) and a second group was given captopril plus atropine 0.04 mg/kg i.v. (group 2, n = 9). Captopril alone (group 1) produced decreases in heart rate (90-81 beats/min, p less than 0.001), mean arterial pressure (90-73 mm Hg, p less than 0.001), systemic resistance (28-23 Wood units, p = 0.068), and pulmonary wedge pressure (19-14 mm Hg, p less than 0.001). There was no improvement in either arteriovenous oxygen difference or thermodilution cardiac output; in fact, the latter slightly declined (3.45-3.35 l/min, p = 0.002). Pretreatment with atropine (group 2) diminished the effects of captopril on heart rate (107-103 beats/min, p = 0.065 for atropine effect by two-way ANOVA), mean arterial pressure (88-82 mm Hg, p = 0.01 for atropine effect), and systemic resistance (26-27 Wood units, p = 0.04 for atropine effect).

CONCLUSIONS
In patients with chronic, severe mitral regurgitation, captopril reduced systemic arterial and left ventricular filling pressures but did not immediately augment cardiac output as expected. Furthermore, the modest systemic vasodilator effect of captopril was parasympathetically mediated.