摘要:

BackgroundBanding of the pulmonary artery to induce left ventricular (LV) hypertrophy followed by arterial switch operation (ASO) within 2 weeks has been performed when a primary ASO was considered high risk because of inadequate LV hypertrophy.Methods and ResultsPotential adverse myocardial effects of the two-stage procedure were examined by comparing outcome in 18 patients after a rapid two-stage ASO with 33 patients after a primary ASO. Regional wall motion was assessed. Echocardiographic and noninvasive pressure data were combined to obtain LV dimension, wall thickness, mass, fractional shortening, rate-corrected mean velocity of shortening, and endsystolic wall stress. Afterload-adjusted velocity of shortening was obtained as a load-independent index of contractility. In the two-stage ASO group, the magnitude and rate of hypertrophy after pulmonary artery banding were measured serially. No wall motion abnormalities were seen in either group. Systolic dysfunction due to higher afterload and lower contractility was observed in the two-stage ASO group. Contractility below the limits of normal was seen in 25% of two-stage ASO compared with 3% of primary ASO; however, symptomatic or progressive LV dysfunction was not observed. There was a significant inverse relation between the peak rate of hypertrophy immediately after banding and contractility at late exam. Lower ejection fraction before and early after pulmonary artery banding correlated with depressed contractility on late examination.ConclusionsMyocardial contractility is lower after the twostage ASO than after a primary repair. Severe or progressive dysfunction was not seen. A very high peak rate of hypertrophy and severe LV dysfunction after banding predict a greater reduction in late contractility.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundBanding of the pulmonary artery (PAB) in preparation for arterial switch operation (ASO) in patients with transposition of the great arteries (TGA) represents a unique model of acute left ventricular pressure overload in humans.Methods and ResultsTo establish the rate, magnitude, and determinants of left ventricular hypertrophy and the acute effect on ventricular function, serial bidimensional echocardiographic evaluations were performed on 26 patients with TGA after PAB. Mass, volume, and ejection fraction of the left ventricle were measured. Cardiac catheterization data before PAB and again before ASO were reviewed. The mean interval between the PAB and ASO was 9±4 days. The left ventricular to right ventricular pressure ratio before PAB was 0.5 and increased to 1.0 before ASO. The mean percentage increase in left ventricular mass from PAB to ASO was 96%, 95% of which was achieved in the first 7 days. The average rate of left ventricular hypertrophy for the entire period was 0.06 g/h and was 0.19 g/h during the interval from PAB to attainment of maximum left ventricular mass. The most rapid rate of hypertrophy was seen by day 2, with an exponential fall in the growth rate thereafter approaching zero by day 7. Ejection fraction was significantly reduced at 12 hours after PAB, but mean values returned to pre-PAB levels by 3.5 days after banding. The absolute rate of left ventricular hypertrophy correlated directly with body surface area but not to other hemodynamic variables.ConclusionsDoubling of left ventricular mass can be achieved in 1 week after PAB. Function falls acutely due to afterload excess and/or depressed contractility but recovers rapidly as compensatory hypertrophy occurs.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundFor patients with acute dilated cardiomyopathy, definition of prognosis and of clinical features predictive of outcome is particularly important due to the availability of cardiac transplantation and other innovative treatment strategies.Methods and ResultsWe reviewed our experience with 24 children under 2 years of age with dilated congestive cardiomyopathy to determine outcome and potential predictive variables. Clinical, serological, ECG, echocardiographic, hemodynamic, and histological findings were analyzed. Idiopathic cardiomyopathy or myocarditis constituted 29% of the patients presenting with congestive heart failure without structural heart disease. Among these patients, 45% recovered completely, 25% survived with persistent left ventricular dysfunction, and 30% died. All except one of the deaths occurred during the first 2 months after presentation. Poorer outcome and higher mortality were associated with a more severely depressed left ventricular ejection fraction and/or a more spherical left ventricular shape at presentation. Histological evidence of myocardial inflammation was a favorable prognostic indicator, whereas histological evidence of endocardial fibroelastosis was associated with a poor outcome. During the recovery phase, diastolic volume fell rapidly. Ventricular mass was elevated from the earliest observations and fell more slowly, with persistent elevation of the mass-to-volume ratio up to 2 years. Function and contractility improved over the first several months in most patients who recovered, although in occasional patients continued improvement was seen for as long as 2 years after presentation.ConclusionsHistological and echocardiographic features can be used to identify patients at particularly high risk for death. To have any impact on outcome, decisions about cardiac transplantation must be reached rapidly, since almost all deaths occurred within the first 2 months after presentation. Recovery of function is often rapid, but continued improvement may be seen for as long as 2 years.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundIn animal models of atherosclerosis, augmentation of circulating high-density lipoprotein (HDL) cholesterol exerts a protective effect against development of fatty streaks and promotes plaque regression.Methods and ResultsTo investigate the potential of gene transfer to increase HDL cholesterol, a fusion gene encoding human apolipoprotein A-I (apo A-I) under the control of the human cytomegalovirus (CMV) immediate-early promoter was packaged into a recombinant adenovirus (AdCMV apo A-I). BALB/c mice infected with AdCMV apo A-I by intravenous injection accumulate immunoreactive apo A-I in serum; levels 5 days after infection averaged 168 mg/dL. A 35% increase in HDL cholesterol and a 47% increase in total cholesterol were observed in mice infected with AdCMV apo A-I compared with control viruses. Analysis of size-fractionated lipoproteins revealed that human apo A-I is incorporated into murine HDL particles. Expression of human apo A-I declined to <10% of maximum after 12 days and mRNA encoding apo A-I, prevalent 5 days after infection, was undetectable in the livers of infected mice after 12 days.ConclusionsWe conclude that adenovirus-mediated transfer of a gene encoding apo A-I produces transient elevations of circulating HDL cholesterol of a magnitude correlated with important physiological effects. These observations suggest the potential for gene-based therapeutic strategies to reduce cardiovascular risk.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundDuring senescence, the plasma angiotensin II concentration is decreased, but the regulation of intracardiac angiotensin II synthesis has never been investigated. The purpose of this work was to determine the cardiac content of both angiotensinogen (ANG) and angiotensin-converting enzyme (ACE) mRNAs in 24-month-old Wistar rats.Methods and ResultsTotal cardiac RNAs and known amounts of ANG and ACE mRNA transcripts, used as standards, were hybridized on slot blots with specific cDNA probes. The quantities of ANG and ACE mRNA were evaluated from the regression lines obtained with fragments of ANG and ACE mRNA in vitro transcripts. With aging, while the overall plasma renin-angiotensin system (RAS) activity decreased, in the left ventricle (LV) the amounts of ANG and ACE mRNAs were increased by fivefold (P<.01) and 2.5-fold (P<.01), respectively, compared with young adult controls. By contrast, in the right ventricle (RV) the same mRNA levels remained unchanged. In parallel, we also found an enhanced expression of the atrial natriuretic factor (ANF) in the LV but not in the RV.ConclusionsDuring senescence, the depressed circulating RAS activity is in contrast to the increase of both ANG and ACE mRNA levels in the LV. Such an upregulation in both gene activities is more likely to be related to the age-associated changes in arterial compliance rather than to hormonal changes, since (1) this regulation is found only in the LV and (2) the same pattern of regulation is also observed for the ANF mRNA level.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundAlthough angiotensin-converting enzyme (ACE) inhibitors have become a mainstay of treatment for chronic congestive heart failure (CHF), it is not known whether the cardiac remodeling effects are a secondary phenomenon, resulting from ACE inhibitors' hemodynamic actions of afterload reduction, or occur through an independent mechanism.Methods and ResultsWe used ultrasonic tissue characterization to define potentially salutary effects of treatment with ACE inhibitors on the material properties of the heart and its potential influence on cardiac remodeling at the cellular level. Ten 1-month-old, cardiomyopathic (CM) Syrian hamsters and 6 normal (NL) hamsters were treated with captopril (2 g/L water ad libitum), and 10 CM hamsters and 10 NL hamsters were maintained untreated for 3 months. Hearts were excised, and backscattered radiofrequency data were acquired from 1200 independent sites from each specimen with a highresolution 50-MHz acoustic microscope for calculation of integrated backscatter (IB). Treatment with captopril reduced left ventricular mass, calcium concentration, and IB in CM hearts without affecting myofiber size or collagen concentration. The IB from grossly normal regions of myocardium in NL hamsters, treated CM hamsters, and untreated CM hamsters was not significantly different. The IB from the microscopic regions of scar tissue in treated CM hamsters was significantly less (P=.0004) than that from scar tissue in untreated CM hamsters.ConclusionsThe reduced IB from treated scar tissue components reflects specific alterations in the material properties (elastic stiffness, density) of fibrous regions in CM hearts induced by captopril. This is the first report that defines specific cellular effects of ACE inhibitors on the material properties of isolated components of cardiac tissue in experimental cardiomyopathy. These alterations in material properties of scar tissue components represent a potential mechanism for the salutary actions of ACE inhibitors in heart failure.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundAdenosine, a physiological coronary vasodilator, has been proposed to regulate coronary circulation according to myocardial oxygen demand. In the present study, we investigated the mechanisms of adenosine formation and utilization in isolated rabbit cardiomyocytes and, in particular, the existence and the role of substrate cycling between AMP and adenosine in the regulation of its concentration.Methods and ResultsRabbit cardiomyocytes were isolated by collagenase perfusion and incubated in HEPES-buffered Krebs-Henseleit solution at 37°C, pH 7.4, in control conditions and in ATP depletion achieved by inhibiting glycolysis with 5 mmol/L iodoacetate. Under control conditions, adenosine accumulated at a rate of 4 pmol · min−1.10−6cells. The 13-fold elevation of adenosine accumulation induced by iodotubercidin (ITu), an inhibitor of adenosine kinase, proves that adenosine is normally recycled into AMP. This recycling involves 95% of the adenosine formed. In ATP depletion, adenosine accumulated at the rate of 335 pmol · min−1· 10−6cells and was no longer rephosphorylated after 20 minutes, as shown by the absence of effect of ITu after this time interval. Moreover, adenosine was deaminated, as indicated by the twofold increase of its accumulation induced by deoxycoformycin (dCF), an inhibitor of adenosine deaminase. Both in control conditions and in ATP depletion, adenosine-dialdehyde, an inhibitor ofS-adenosylhomocysteine (SAH) hydrolase, had no significant effect on adenosine formation, indicating that the transmethylation pathway is not an important source of adenosine in rabbit cardiomyocytes.ConclusionsThe results indicate that recycling of adenosine into AMP is essential for the maintenance of low, nonvasodilatory concentrations of the nucleoside under control conditions and that interruption of recycling plays an important role in elevating adenosine during ATP depletion.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThexmddog develops a cardiomyopathy similar to that seen in Duchenne muscular dystrophy patients. In both the canine and human diseases, ECG abnormalities may precede the development of overt cardiac pathological lesions. The purpose of this study was to determine whether specific cellular electrical abnormalities occur in dystrophic ventricular tissue.Methods and ResultsAction potentials were recorded in epicardial tissue strips obtained from normal and xmd dogs. Phase 1 amplitude was increased from 86.8±2.7 mV in normal dogs to 94.3± 1.8 mV inxmddogs (mean±SEM;P<.05). The 4-aminopyridine-sensitive transient outward potassium current (Ito), as recorded in isolated epicardial myocytes using the whole-cell patch-clamp technique, was reduced in xmd dogs compared with age-matched normal dogs. Cell capacitance also was reduced significantly inxmdcompared with normal cells, as was the current density (3.6±0.3 versus 5.4±0.8 pA/pF, respectively). No differences were observed in the time constants of current decay or in the kinetics of recovery from inactivation between groups. The slope factor (k) of steadystate inactivation was significantly greater inxmdcompared with normal cells (7.2±0.9 versus 5.4±0.5, respectively), whereas the V1/2of inactivation did not differ (−38.2±2.4 versus −36.8±1.6 mV, respectively).ConclusionsThese data indicate that the magnitude of Ito, is reduced in dystrophic epicardial myocytes, resulting in an increase in phase 1 amplitude. The reduction of Itomay alter the balance of inward and outward currents in dystrophic myocardium and thereby contribute to the development of cardiac pathology.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundNitric oxide (NO), in addition to its potent vasorelaxant properties, may participate in growth regulation of cultured smooth muscle cells. It was recently demonstrated that in vivo endothelial injury induces the production of NO from L-arginine in the arterial wall.Methods and ResultsWe studied the effects of long-term administration of L-arginine, the precursor of NO, on neointimal thickening and on neoendothelium-dependent vasorelaxation 4 weeks after balloon denudation of normocholesterolemic rabbit iliac arteries. Rabbits were fed with either a standard diet or a diet supplemented with L-arginine (2.25%) in their drinking water 3 days before and during 4 weeks after balloon denudation. The effectiveness of L-arginine supplementation was confirmed by measurement of plasma arginine levels. L-Arginine had no effect on hemodynamic parameters. All animals were killed 4 weeks after balloon denudation, and a digital histomorphometric analysis of three serial nonconsecutive histological cross sections per iliac artery was performed. Intimal thickening was reduced (P<.05) from 0.43±0.08 (SE) mm2in controls (n=8) to 0.24±0.02 mm2in treated animals (n=8). Ten animals (n=5 in each group) were used for in vitro vasoreactivity assessment 4 weeks after balloon denudation. Neoendotheliumdependent acetylcholine-induced relaxation (10−8mol/L to 3.10−5mol/L) in treated animals (Emax=−24.1±5.5%) was significantly greater than in controls (Emax=−8.9±2.2%). Endothelium- independent relaxation did not differ between groups (Emax= −58.1±6.5% in L-argimine-supplemented animals versus −52.9±6.8% in controls).ConclusionsOur results demonstrate that L-arginine, a precursor of NO, reduces neointimal thickening after balloon denudation and improves neoendothelial-dependent acetylcholine- induced relaxation.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundA number of epidemiologic studies have suggested that every year environmental tobacco smoke (secondhand smoke) is responsible for tens of thousands of deaths, mostly from heart disease, in the United States. Environmental tobacco smoke is composed mainly (80% to 85%) of aged and diluted sidestream smoke. The remainder is exhaled mainstream smoke. Among the thousands of compounds that have been identified in environmental tobacco smoke are a number of carcinogens, including polynuclear aromatic hydrocarbon carcinogens, such as benzo(a)pyrene. We have demonstrated previously that a number of carcinogens, including benzo(a)pyrene, promote plaque development after injection into cockerels. There have been almost no studies showing a direct stimulatory effect of environmental tobacco smoke on plaque development. Recently we demonstrated that cockerels exposed to sidestream smoke for approximately 0.4% of their projected lifespan exhibited accelerated development of arteriosclerotic plaques.6In that study, cockerels in specially designed inhalation chambers were exposed to the steady-state sidestream smoke from 5 cigarettes for 6 h/d for 16 weeks. This level of exposure is high but environmentally plausible. Statistically significant increases in plaque size were demonstrated in the smoke-exposed cockerels.Methods and ResultsIn the present study, exposure levels were decreased by a factor of 5. Thirty cockerels were exposed to the steady-state sidestream smoke from 1 cigarette for 6 hours per day for 16 weeks. The smoke was mixed with filtered air. Ten control cockerels were exposed to filtered air only. Levels of smoke surrogates, including carbon monoxide and total suspended particulates, were measured three times a day. Again, there was a statistically significant increase in plaque size in the smoke-exposed cockerels. To place these studies within a context of environmental relevance, levels of carbon monoxide were measured independently over 1 to 3 hours in four bars where there was heavy smoking. Measured carbon monoxide levels were as high or higher in the bars than they were in the exposure chambers during the 1-cigarette sidestream-smoke study.ConclusionsExperimental exposure to secondhand smoke at levels equal to or even below those routinely encountered by people in smoke-filled environments is sufficient to promote arteriosclerotic plaque development.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID