bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of right and left ventricular function in the ventilatory response to exercise in chronic heart failure.
Authors: Clark A L , Swan J W , Laney R , Connelly M , Somerville J , Coats A J 
Published: June 2012

BACKGROUND
Right ventricular function may be an important determinant of exercise capacity, peak oxygen consumption (VO2), and the ventilatory response to carbon dioxide production (VE/VCO2 relation) in patients with chronic heart failure (CHF).

METHODS AND RESULTS
We studied the role of right ventricular function in CHF and also investigated the effects of absent right ventricular reserve in patients previously operated on with Fontan's procedure by measuring metabolic gas exchange during exercise in five groups of patients: (1) 10 patients who had previously undergone Fontan's procedure for congenital heart disease in whom the right ventricle is not functional; (2) 11 age-matched control subjects with dilated cardiomyopathy (DCM); (3) 15 age-matched normal subjects; (4) 42 patients with CHF; and (5) 16 age-matched control subjects. Left and right ventricular ejection fractions (LVEF and RVEF) were measured by radionuclide ventriculography in group 4. In the young subjects, the VE/VCO2 slope was lower in the control subjects than in the other two groups, being 24.4 +/- 4.3 against 33.3 +/- 6.6 in group 1 (P < .001) and 29.6 +/- 8.1 in group 2 (P < .05). The correlation between peak VO2 and VE/VCO2 was -0.80 (P = .005) in group 1 and -0.76 (P = .007) in group 2. In the older age groups, the VE/VCO2 slope was significantly greater (38.0 +/- 14.9 versus 25.4 +/- 3.7; P < .001) in the heart failure group (group 4). In neither control group was there a significant relation between peak VO2 and VE/VCO2 slope. In group 4, the relation between peak VO2 and VE/VCO2 was similar to that seen for groups 1 and 2. LVEF was 24.3 +/- 14.1%, and RVEF was 32.5 +/- 13.1%. There was no correlation between either RVEF or LVEF and peak VO2 or VE/VCO2 slope in the heart failure group.

CONCLUSIONS
The relation between excessive ventilation and reduction in peak oxygen consumption is present in patients with no functioning right ventricle. RVEF is not a determining feature of either exercise capacity or the excessive ventilatory response in CHF.
Immediate evaluation of endomyocardial biopsies for clinically suspected rejection after heart transplantation.
Authors: Winters G L , Hauptman P J , Jarcho J A , Schoen F J 
Published: June 2012

BACKGROUND
Acute rejection may be suspected in heart transplant recipients in the setting of new onset of clinical symptoms or alterations in cardiac function. Immediate diagnosis may be obtained by performing a frozen section on endomyocardial biopsy (EMB) specimens. However, little is known about the indications for, and the diagnostic reliability of, this procedure.

METHODS AND RESULTS
EMBs with frozen section (n = 98) from 65 of 214 consecutive orthotopic heart transplant recipients were reviewed and divided into early (< or = 45 days; n = 47) and late (> 45 days; n = 51) posttransplant periods. Frozen section diagnoses (means = 1.5 EMB samples) were compared with corresponding permanent section diagnoses (means = 4.4 EMB samples), and clinical indications were analyzed. Comparison of frozen and permanent section interpretation revealed concordant pathological processes-rejection (n = 31) versus no rejection (n = 37) versus ischemic injury (n = 20)-in 88 of 98 (90%) cases. Discordant pathological processes on frozen versus permanent section in 10 of 98 (10%) cases could be attributed to ischemic injury (n = 5), sampling (n = 4), and infection (n = 1). In the 92 cases with defined clinical indications, the indication and number of EMBs positive for rejection early and late after transplantation were arrhythmia: 2 of 12 early, 4 of 10 late; congestive heart failure: 1 of 2 early, 5 of 12 late; fever: 0 of 2 early, 1 of 4 late; echo abnormality: 0 of 5 early, 0 of 1 late; syncope: 1 of 5 early, 0 of 1 late; hypotension: 1 of 3 early, 1 of 2 late; noncompliance: 0 of 0 early, 4 of 5 late; more than one of the above: 3 of 7 early, 2 of 5 late; other: 1 of 7 early, 1 of 9 late; total: 9 of 43 early, 18 of 49 late.

CONCLUSIONS
Frozen section on EMB specimens accurately reflected the permanent section diagnosis in 90% of cases. No specific clinical indication predicted EMB rejection positivity with high sensitivity in either the early or late posttransplant periods.
Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload.
Authors: Ito H , Hiroe M , Hirata Y , Fujisaki H , Adachi S , Akimoto H , Ohta Y , Marumo F 
Published: June 2012

BACKGROUND
We have recently shown that angiotensin II-induced hypertrophy of cultured rat cardiomyocytes was partially blocked by an endothelin (ET) receptor antagonist (BQ123) selective for the ETA subtype, suggesting the possible involvement of endogenous ET-1 in the mechanism of cardiac hypertrophy in vitro. In the present study, we studied the in vivo blockade effects of BQ123 on cardiac hypertrophy provoked by left ventricular overload with aortic banding in adult rats.

METHODS AND RESULTS
Forty rats were divided into four groups: (1) sham-operated rats without BQ123 administration, (2) rats with aortic banding without BQ123 administration, (3) sham-operated rats with BQ123 administration, and (4) rats with aortic banding with BQ123 administration. BQ123 (250 micrograms/h) was administered continuously by an osmotic pump starting 24 hours before operation. BQ123 blocked increases in the ratio of left ventricular weight to body weight and in the diameter of cardiomyocytes provoked by aortic banding at 1 week, but those blockade actions were no longer observed at 2 weeks. Skeletal alpha-actin and atrial natriuretic peptide (ANP) mRNA in the left ventricle, transcriptional markers for cardiac hypertrophy, significantly increased in the rats with aortic banding at 1 week and 2 weeks. In the rats with BQ123 administration, despite the hemodynamic overload, skeletal alpha-actin and ANP mRNA in the left ventricle remained at the control levels at 1 week; however, those blockade actions were abolished at 2 weeks. Plasma ET-1 levels increased after aortic banding, peaking at 24 hours, then returned to the basal level at 4 days. Prepro-ET-1 mRNA levels in the left ventricle also increased 24 hours after aortic banding, then declined to the basal level at 4 days.

CONCLUSIONS
These data suggest that endogenous ET-1 synthesized in the cardiovascular system plays a role in the mechanism of cardiac hypertrophy during the early phase of pressure overload in vivo.
17 beta-estradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine.
Authors: Keaney J F , Shwaery G T , Xu A , Nicolosi R J , Loscalzo J , Foxall T L , Vita J A 
Published: June 2012

BACKGROUND
Cardiovascular events are less prevalent in premenopausal women and women receiving estrogen replacement than in postmenopausal women or men. Endothelium-derived relaxing factor (EDRF) is an important local modulator of vascular tone, and abnormal endothelial function is related, in part, to the oxidative modification of low-density lipoprotein (LDL). Estrogens possess substantial antioxidant activity and inhibit LDL modification in vitro.

METHODS AND RESULTS
We investigated the effects of 17 beta-estradiol (E2) on endothelial vasomotor function in cholesterol-fed miniature swine. Animals underwent ovariectomy or a sham procedure and received E2 or placebo via implant yielding three groups: sham, ovariectomy (E2 placebo), and implant (E2 implant). After 16 weeks, coronary arteries were harvested and endothelial function was examined in vitro. Vessels from the sham and implant groups demonstrated preserved endothelium-dependent relaxation to bradykinin, substance P, and A23187. Vessels from the ovariectomy group exhibited impaired relaxation to bradykinin and substance P (P < .05 versus sham and implant groups) but not to A23187. Plasma E2 levels were strongly correlated with the response to bradykinin (R = .82, P < .001), substance P (R = .64, P < .01), and A23187 (R = .65, P < .01). Compared with the ovariectomy group, LDL derived from the sham and implant groups was markedly resistant to ex vivo oxidation (P < .05), and this effect correlated with preserved endothelium-dependent relaxation to bradykinin (R = .62, P < .03) and substance P (R = .61, P < .03).

CONCLUSIONS
Thus, E2 preserves endothelial function in cholesterol-fed swine in association with protection of LDL against oxidative modification. These data suggest that E2 may, in part, favorably affect vascular function and coronary artery disease by virtue of its antioxidant properties.
Metoprolol does not attenuate atherosclerosis in lipid-fed rabbits exposed to environmental tobacco smoke.
Authors: Sun Y P , Zhu B Q , Sievers R E , Glantz S A , Parmley W W 
Published: June 2012

BACKGROUND
We previously demonstrated that exposure to environmental tobacco smoke (ETS) increases the development of atherosclerosis in lipid-fed rabbits. Clinical studies have suggested a protective effect of beta-blockers in smokers. Accordingly, we evaluated the effects of metoprolol in this animal model to see whether this beta-blocker would block the atherogenic effects of ETS.

METHODS AND RESULTS
Thirty-two New Zealand White male rabbits on a 0.3% cholesterol diet were randomly divided into four groups: ETS-metoprolol (ETS-M), ETS-control (ETS-C), and non-ETS with metoprolol (NETS-M) and without metoprolol (NETS-C). The two metoprolol-treated groups received metoprolol at a dose of 0.4 mg.kg-1.h-1 administered subcutaneously by an osmotic pump. Rabbits in the ETS groups were exposed to sidestream smoke from four Marlboro cigarettes per 15 minutes, 6 hours a day, for 10 weeks. Average air carbon monoxide (CO), nicotine, and total particulates (TP) in the exposure chambers were 67.2 +/- 3.1 (SEM) ppm, 1133.7 +/- 78.4 micrograms/m3, and 37.7 +/- 3.0 mg/m3, respectively. Plasma nicotine was significantly higher in ETS-exposed rabbits than in nonexposed rabbits (7.1 +/- 1.9 versus 0.5 +/- 0.1 ng/mL, P < .01). Blood carbon monoxide hemoglobin (COHb) in the ETS-M group was significantly higher than that in the NETS-M group (4.0 +/- 0.2% versus 1.3 +/- 0.1%, P < .0001). The lipid lesions in the aorta and pulmonary artery were 57.2 +/- 7.6% and 33.1 +/- 6.4% (ETS-M), 62.8 +/- 8.4% and 58.4 +/- 6.1% (ETS-C), 38.7 +/- 9.4% and 24.8 +/- 7.7% (NETS-M), and 49.8 +/- 8.7% and 32.7 +/- 7.1% (NETS-C). There were significant differences in lipid deposits of the arteries between the controls and the ETS-exposed rabbits (37 +/- 1% versus 53 +/- 1%, P = .004) and between the controls and metoprolol-treated rabbits (51 +/- 1% versus 38 +/- 1%, P = .027). The benefit of metoprolol was independent of ETS exposure (ETS x metoprolol interaction, P = .595).

CONCLUSIONS
Exposure to ETS significantly accelerated and metoprolol decreased the development of atherosclerosis in lipid-fed rabbits, but there was no interaction between the effects of ETS exposure and metoprolol. Metoprolol did not protect against the effects of ETS on atherosclerosis, suggesting that the beta-adrenergic system is not the mechanism of ETS-induced atherosclerosis.
Biphasic effects of repeated alcohol intake on 24-hour blood pressure in hypertensive patients.
Authors: Abe H , Kawano Y , Kojima S , Ashida T , Kuramochi M , Matsuoka H , Omae T 
Published: June 2012

BACKGROUND
The association between alcohol and blood pressure (BP) may be related to the temporal sequencing of alcohol use and BP measurement. We investigated the effects of single and repeated intakes of alcohol on 24-hour BP.

METHODS AND RESULTS
Fourteen male habitual drinkers with essential hypertension were placed sequentially on a 4-day control phase: a nonalcoholic drink with the same calories as alcohol was given at dinner (5 PM to 6 PM) and a 7-day drinking phase: alcohol (ethanol, 1 mL/kg) was given at dinner under standardized conditions. Ambulatory BP measurements were performed on day 3 of the control phase and on days 1 and 7 of the alcohol phase. The average 24-hour systolic and diastolic BPs on day 1 were significantly lower than those in the control phase and on day 7. Between 6 PM and midnight, both systolic and diastolic BPs on days 1 and 7 (121 +/- 2/73 +/- 1 and 126 +/- 4/75 +/- 2 mm Hg, respectively) were significantly lower than those in the control phase (139 +/- 4/83 +/- 2 mm Hg). Between midnight and 8 AM (6 to 14 hours after the last drink), both systolic and diastolic BPs on day 7 (138 +/- 4/83 +/- 2 mm Hg) were significantly higher than those in the control phase (131 +/- 4/79 +/- 2 mm Hg) and day 1 (129 +/- 3/77 +/- 1 mm Hg). Between 8 AM and 3 PM, BPs showed no difference among the three phases.

CONCLUSIONS
A single intake of alcohol has a depressor effect on BP that lasts for several hours after drinking, while repeated intakes for 7 days have both depressor and pressor effects according to the differences in time intervals after the last drink. This study suggests that the chronic effects of alcohol on BP might be overestimated when based on casual BP measurements alone.
Effects of radiofrequency catheter ablation on regional myocardial blood flow. Possible mechanism for late electrophysiological outcome.
Authors: Nath S , Whayne J G , Kaul S , Goodman N C , Jayaweera A R , Haines D E 
Published: June 2012

BACKGROUND
We postulated that the late electrophysiological effects of radiofrequency (RF) ablation may be related to microvascular injury extending beyond the region of acute coagulation necrosis.

METHODS AND RESULTS
Eighteen RF lesions created in the left anterior descending coronary artery (LAD) perfusion bed of seven open chest anesthetized dogs were studied. The ablation electrode and surrounding myocardium were imaged using high-resolution two-dimensional echocardiography at x 4 magnification. After 60 seconds of RF delivery, sonicated albumin microbubbles (mean size, 4.3 microns) were injected into the LAD to measure regional myocardial perfusion, and time-intensity plots were generated from simultaneously acquired two-dimensional echocardiography images. The regions with persistent contrast effect on two-dimensional echocardiography were larger than the pathological lesions (mean cross-sectional area, 48.3 +/- 6.3 versus 19.3 +/- 4.7 mm2, respectively; P < .0001). The mean contrast transit rate in the area corresponding to the pathological lesion was 25 +/- 12% of that in the normal myocardium, but it was also reduced beyond the lesion, being 48 +/- 27% and 82 +/- 28% of normal, respectively, in the 3-mm and 3- to 6-mm circumferential rims surrounding the pathological lesion (P < .05). Electron microscopy performed in two additional dogs with similar lesions demonstrated the presence of ultrastructural damage to the microvascular endothelium well beyond the pathological lesion edge.

CONCLUSIONS
RF catheter ablation not only results in a marked reduction in blood flow within the acute pathological lesion but also causes reduced flow beyond the borders of the acute lesion because of microvascular endothelial cell injury. The progression or resolution of tissue injury within the region beyond the border of the pathological lesion may explain the late electrophysiological effects of RF ablation.
Role of vascular endothelium in exercise-induced dilation of large epicardial coronary arteries in conscious dogs.
Authors: Berdeaux A , Ghaleh B , Dubois-Randé J L , Vigué B , Drieu La Rochelle C , Hittinger L , Giudicelli J F 
Published: June 2012

BACKGROUND
The role of vascular endothelium in the control of epicardial coronary artery vasomotion during treadmill exercise remains unclear. Therefore, we examined the consequences of in vivo balloon endothelial denudation on external coronary diameter of the left circumflex artery during exercise in conscious dogs.

METHODS AND RESULTS
Seven dogs instrumented for the measurement of arterial blood pressure, external coronary artery diameter, and coronary blood flow were studied during exercise before and up to 21 days after balloon endothelial denudation of the proximal left circumflex artery. Endothelial denudation was confirmed by abolition of the epicardial coronary artery dilation induced by acetylcholine (0.3 microgram/kg IV) and reactive hyperemia. Epicardial coronary vasodilation was observed in the control state during treadmill exercise (+5.2 +/- 1.0%). In contrast, a marked vasoconstriction was observed 3 (-4.6 +/- 0.6%) and up to 6 days after endothelial denudation. Complete epicardial coronary artery dilation in response to acetylcholine and exercise was restored 9 days after endothelial denudation. In addition, epicardial coronary artery vasomotor responses to acetylcholine and treadmill exercise were closely correlated (r = .82, P < .001). Reactive dilation was not completely restored 21 days after endothelial denudation, but reactive hyperemia and exercise vasomotor responses during the 21 days follow-up were correlated (r = .70, P < .001). Vasodilation induced by nitroglycerin (1 microgram/kg IV) was reduced by 25% (P < .01) 3 days after endothelial denudation and returned to its corresponding control level 3 days later. Prazosin (50 micrograms/kg IV) significantly attenuated the exercise-induced coronary artery constriction after endothelial denudation (+1.5 +/- 1.4% versus -4.6 +/- 1.0%).

CONCLUSIONS
These data demonstrate that endothelium is essential for the mediation of epicardial coronary dilation during exercise and may protect these vessels against the vasoconstrictor effect of endogenous catecholamines.
The relative importance of arterial remodeling compared with intimal hyperplasia in lumen renarrowing after balloon angioplasty. A study in the normal rabbit and the hypercholesterolemic Yucatan micropig.
Authors: Post M J , Borst C , Kuntz R E 
Published: June 2012

BACKGROUND
Although arterial renarrowing after angioplasty has been attributed largely to intimal hyperplasia, there has been no systematic effort to correlate the actual hyperplastic tissue mass with angiographic lumen reduction. Using balloon angioplasty in various animal restenosis models, we quantitatively assessed the separate contributions of intimal hyperplasia and arterial remodeling to angiographic late lumen loss.

METHODS AND RESULTS
Data used for this study were obtained from experiments of conventional and thermal (37 degrees C or 55 degrees to 90 degrees C) balloon angioplasty-treated femoral and iliac arteries in normal rabbits and conventional balloon angioplasty-treated iliac arteries in Yucatan micropigs fed either a normal or an atherogenic diet. Quantitative angiography was performed immediately before and after intervention and at 3 or 8 weeks thereafter, and late loss in lumen diameter was taken as the difference between arterial diameter immediately after treatment and at 3 or 8 weeks of follow-up. Intimal hyperplasia was quantified histologically as the area of tissue mass within the internal elastic lamina. We observed a consistent discrepancy between the actual late loss seen with angiography and the diameter reduction that could be explained by histological intimal thickness alone in both animal models. This discrepancy ranged from 86 +/- 3% of the late loss in the 8 weeks/37 degrees C group to 77 +/- 22% in the conventional group for rabbits and 52 +/- 23% in an atherogenic diet group (n = 10) to 89 +/- 11% in a normal diet group (n = 6) for pigs. This discrepancy appeared to be due predominantly to reduction of the area circumscribed by the internal elastic membrane, a process that is tentatively designated as arterial remodeling. In both the rabbit femoral artery and in the Yucatan iliac artery, remodeling, not intimal hyperplasia, correlated with angiographic late loss.

CONCLUSIONS
In both the normal rabbit and the normal and atherosclerotic pig, restenosis after angioplasty results from both intimal hyperplasia and arterial remodeling. The exact etiology of arterial renarrowing after angioplasty has important implications on the design of antirestenosis drugs and new coronary devices.
Probucol promotes endogenous antioxidants and provides protection against adriamycin-induced cardiomyopathy in rats.
Authors: Siveski-Iliskovic N , Kaul N , Singal P K 
Published: June 2012

BACKGROUND
The potential usefulness of adriamycin (ADR) is restricted because of its cardiotoxic side effects. Since free radicals and lipid peroxidation are suggested to be involved in ADR cardiomyopathy, we examined the beneficial effects of probucol, a lipid-lowering drug with strong antioxidant properties.

METHODS AND RESULTS
ADR was administered to rats in six equal intraperitoneal injections over a period of 2 weeks (cumulative dose of 15 mg/kg). After a 3-week posttreatment period, cardiomyopathy and congestive heart failure were characterized by ascites, congested liver, depressed cardiac function, elevated left ventricular end-diastolic pressure, and myocardial cell damage. Myocardial glutathione peroxidase (GSHPx) activity was decreased, and lipid peroxidation was increased. Probucol (cumulative dose, 60 mg/kg IP) was administered in six equal injections over a 2-week period on days alternating with ADR treatment. Probucol significantly attenuated the myocardial effects of ADR, improved left ventricular function, and lowered mortality as well as the amount of ascites. Treatment with probucol was also accompanied by an increase in myocardial GSHPx and superoxide dismutase activities, with a concomitant decrease in lipid peroxidation.

CONCLUSIONS
These data provide evidence that ADR cardiomyopathy is associated with an antioxidant deficit. Improved cardiac function resulting from treatment with probucol may be related to the maintenance of the antioxidant status of the heart. The study suggests potential usefulness of antioxidant (probucol) therapy in ADR cardiomyopathy.
Iron stores are not associated with acute myocardial infarction.
Authors: Baer D M , Tekawa I S , Hurley L B 
Published: June 2012

BACKGROUND
This study evaluated the relation between body iron stores and coronary artery disease. It has been suggested that total body iron stores are an independent risk factor for acute myocardial infarction (AMI).

METHODS AND RESULTS
Our study population consisted of 46,932 members of a prepaid health plan who were > or = 30 years old and who received a standard health check between 1969 and 1971. Blood collected during this examination was analyzed for serum iron and total iron-binding capacity. Transferrin saturation (TS), calculated as (serum iron/total iron-binding capacity) x 100, was categorized as low (< or = 10%), normal (11% to 61%), or elevated (> or = 62%). Hospital stays for AMI were identified from the health plan's computerized discharge records for its Northern California Region through December 31, 1991. Mean follow-up time was 14.1 years. During the follow-up period, 969 men and 871 women had an AMI-related hospital stay. Analysis of AMI-related hospital stays was performed overall and by sex. Age-adjusted incidence rates were obtained for each TS level, and proportional hazards regression models were used to assess the significance of TS as a risk factor for AMI, controlling for other known coronary disease risk factors. Our results did not show iron deficiency as defined by low TS to be protective against AMI. Subjects with increased iron stores indicated by TS > or = 62% had a relative risk for AMI of 1.3, which was not statistically significant.

CONCLUSIONS
Our observations do not support the hypothesis that coronary artery disease risk is related to iron stores.