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Biomedical subjects

A H Foster

Publications and source records attributed to A H Foster.

At least 19 recordsLinked to original sources
PubMed1999

Increased p53 protein expression in human failing myocardium.

BACKGROUND: The p53 gene is a tumor-suppressor gene which involves apoptosis and cell-cycle arrest under certain stress stimulate. However, the status of the p53 gene expression in human myocardium in congestive heart failure (CHF) remains unclear. Therefore, the current study was designed to investigate the expression of the p53 protein in human myocardium in normal subjects and in patients with severe CHF. METHODS: Human ventricular cardiac tissue was obtained from 7 normal subjects and 7 end-stage CHF patients during cardiac transplantation. The expression of p53 protein was determined by immunohistochemical staining. The cardiac apoptosis was determined by TUNEL staining. RESULTS: The p53 protein was minimally stained in normal human ventricular cardiomyocytes. In contrast, the staining density and positive stained nuclear (%) of p53 was significantly increased in ventricular cardiomyocytes of patients with severe CHF. Apoptosis in CHF human myocardium also markedly increased. CONCLUSIONS: The significantly increased expression of p53 in CHF human cardiomyocytes suggests that p53 may play an important pathophysiological role in the process of CHF through mechanisms involving myocardial apoptosis.

Adult↗
PubMed1998

A comparison of pectoral and abdominal transvenous defibrillator implantation: analysis of costs and outcomes.

Traditionally cardioverter-defibrillator implantation was performed by surgeons under general anesthesia. However, with advances in lead and pulse generator technology, the surgical implantation technique has been simplified and routine pectoral pulse generator placement without general anesthesia is now possible. To assess the economic benefit of pectoral implantation, we analyzed 43 consecutive initial transvenous defibrillator implantations. The patients were grouped according to whether the implant was abdominal by a surgeon in the operating room (n = 23) or pectoral by an electrophysiologist in a laboratory (n = 20). The duration of hospitalization was significantly longer in the operating room than in the laboratory group (8.1 +/- 3.4 vs 5.8 +/- 2.4 days, p = 0.01), which was due primarily to the postoperative stay which averaged 1.9 days longer. Total costs were $40,274 +/- 6,861 for the operating room cohort and $32,546 +/- 3,634 for the lab group (p < 0.001). This reduction was due to a 32% lowering of professional costs and an 18% lowering of facility costs. We conclude that pectoral defibrillator implantation is cost effective and results in significant reductions of hospital stay.

Abdominal Muscles↗
PubMed1997

Lead system optimization for transvenous defibrillation.

Lead systems that include an active pectoral shell reduce defibrillation thresholds and permit transvenous defibrillation in nearly all patients. A further improvement in defibrillation efficacy is desirable to allow for smaller pulse generators with a reduced maximum output. Accordingly, the purpose of this study was to compare defibrillation thresholds with multiple transvenous lead systems including those with an active pectoral shell to determine which system would optimize defibrillation energy requirements. This prospective study was performed on 21 consecutive patients. Each subject was evaluated with 3 lead configurations with the order of testing randomized. The configurations were a dual coil transvenous lead (lead), the distal right ventricular coil and pectoral pulse generator shell (unipolar), and all 3 components (triad). The right ventricular coil was the cathode for the first phase of the biphasic defibrillation waveform. Delivered energy at defibrillation threshold was 11.2 +/- 3.4 J for the lead configuration, 10.1 +/- 5.2 J for the unipolar configuration, and 7.8 +/- 3.6 J for the triad configuration (p <0.01). Leading edge voltage (p <0.01) and shock impedance (p <0.001) were also decreased for the triad configuration compared with the lead or unipolar configurations, whereas peak current was minimized with the unipolar configuration (p <0.01). We conclude that the combination of a dual coil, transvenous lead and an active pectoral shell reduces defibrillation energy requirements compared with either the lead alone or unipolar configuration. Moreover, the defibrillation thresholds were < or =15 J in all patients using the triad lead system.

Defibrillators, Implantable↗
PubMed1997

Effect of waveform tilt on defibrillation thresholds in humans.

INTRODUCTION: Despite the common use of the implantable cardioverter defibrillator to treat patients with life-threatening ventricular arrhythmias, the mechanism of defibrillation and the optimal waveform for implanted devices are poorly understood. All of the currently available pulse generators deliver exponentially declining pulses that are either automatically or manually truncated to achieve tilts of about 50% to 65%. Although this value was chosen based on experimental animal data, several theoretical models have been developed to describe defibrillation, which raise into question this choice of waveform shape. Accordingly, the present study was designed to test the effect of waveform tilt on defibrillation efficacy in humans. METHODS AND RESULTS: Twenty-three patients undergoing cardioverter defibrillator implantation were studied. Monophasic defibrillation thresholds (DFTs) were measured using a single reversal protocol at 35%, 50%, 65%, and 80% tilts by altering the pulse width of the shock. Mean defibrillation impedance was 41 +/- 6 omega. The DFT, measured by either leading-edge voltage or stored energy, was insensitive to altering the waveform tilt from 50% to 80%, only increasing when the tilt was reduced to 35%. A tilt of 65% yielded the lowest DFT voltage in only 8 of 23 patients. Significantly lower DFTs (> or = 40 V) were obtained using other tilts in seven patients. When the relationship between average current and pulse width was fit with a Weiss-Lapicque model, the data yielded a mean chronaxie of 4.6 +/- 3.0 msec and a rheobase of 4.2 +/- 1.7 A, but considerable patient variability was observed. CONCLUSION: On average, DFTs in humans are insensitive to altering monophasic waveform tilts between 50% and 80%. There is, however, considerable patient variability, raising into question the premise that a single defibrillator waveform tilt is best for all patients.

Aged↗
PubMed1996

Effects of an active pectoral-pulse generator shell on defibrillation efficacy with a transvenous lead system.

Transvenous lead systems have become routine for defibrillator implantation. A reduction of pulse generator size has made pectoral placement possible and enabled the pulse generator shell to become an active part of the defibrillation pathway. To directly assess the effect of the addition of an active generator on defibrillation thresholds to a transvenous lead system, we prospectively measured paired, randomized defibrillation thresholds (DFTs) in 21 patients undergoing defibrillator implantation. A dual coil lead (Endotak C, Cardiac Pacemakers, Inc., Guidant Corp., St. Paul, Minnesota) was used with the distal coil as the cathode for all shocks. The DFT was 8.4 +/- 3.2 J with the active shell, compared with 13.1 +/- 6.9 J with the lead alone (p < 0.01). This reduction was greatest in those patients with higher thresholds with the lead-alone configuration and resulted in DFT < or = 15 J with the active shell configuration in all patients. Shock impedance was reduced from 49 +/- 5 to 42 +/- 4 ohms (p < .001), but peak current at defibrillation threshold was unaffected by the addition of the active pectoral shell. We conclude that the addition of an active pectoral shell to a 2-coil transvenous lead system resulted in a marked reduction of defibrillation energy requirements. The uniformly low DFT ( < or = 15 J) observed suggests that an active pulse generator with a 25 J maximum output could be implanted in most patients while maintaining an adequate defibrillation safety margin.

Aged↗
PubMed1996

Nitric oxide mediates fluid accumulation during cardiopulmonary bypass.

Fluid accumulation during cardiopulmonary bypass may be related to the production of endogenous vasoactive substances. We investigated the role of nitric oxide in mediating fluid accumulation during cardiopulmonary bypass. Normothermic cardiopulmonary bypass was carried out for 3 hours in male Sprague-Dawley rats with constant, nonpulsatile flow and hemodilution. Fluid accumulation (rate of change of external reservoir volume) was measured under three experimental conditions: saline solution control (n = 8), L-arginine infusion (n = 6), and N-nitro-L-arginine methyl ester infusion (n = 6). At the end of the experiments, body weight and organ wet/dry ratios were examined. Percentage weight gain was 77% greater in the N-nitro-L-arginine methyl ester group and 23% less in the L-arginine group compared with control values. Fluid accumulation was increased with N-nitro-L-arginine methyl ester after 30 minutes (p < 0.01) and reduced with L-arginine after 120 minutes (p < 0.01) compared with control animals. Water content was significantly decreased in the heart, lung, skin, muscle and peritoneum in rats receiving L-arginine. These data suggest that endogenous nitric oxide plays an important role in minimizing fluid accumulation during cardiopulmonary bypass.

Animals↗
PubMed1995

Acute hemodynamic effects of atrio-biventricular pacing in humans.

Standard postoperative dual-chamber pacing uses ventricular leads placed on the right ventricle that produce dysynchronous ventricular activation and contraction. The hypothesis that simultaneous stimulation of both ventricles by atrio-biventricular pacing improves hemodynamic performance compared with that observed with standard atrio-monoventricular pacing was tested in 18 patients 12 to 36 hours after elective coronary artery revascularization. Temporary epicardial pacing electrodes were placed on the right atrium and into anterior paraseptal sites on the right and left ventricle. Simultaneous biventricular activation was documented by fusion morphology of surface electrocardiograms and by isochronal epicardial activation mapping during biventricular pacing. Hemodynamic data were acquired after 10 minutes of pacing at a fixed overdrive rate during atrial pacing and during dual-chamber pacing using unipolar right ventricular, unipolar left ventricular, and bipolar biventricular (left ventricular cathode) leads. Atrio-biventricular pacing increased cardiac index and decreased systemic vascular resistance compared with atrial pacing and with atrio-right ventricular and atrio-left ventricular dual-chamber pacing (p < 0.05). These data support the use of atrio-biventricular pacing employing paraseptal electrodes to optimize hemodynamic performance.

Adult↗
PubMed1995

Technique for implantation of cardioverter defibrillators in the subpectoral position.

The downsized cardioverter defibrillators in early clinical trials in the United States are smaller and lighter than approved cardioverter defibrillators, but they remain relatively bulky. Prepectoral implantation of these devices may increase the risk of erosion, particularly in those patients with cardiac cachexia. This report describes a versatile technique for submuscular pectoral cardioverter defibrillator implantation using a lateral approach to the subpectoral space that has been used in 6 patients. Alternative surgical approaches for pectoral cardioverter defibrillator implantation and potential problems with these techniques are discussed.

Adult↗
PubMed1995

Spurious discharges due to late insulation break in endocardial sensing leads for cardioverter defibrillators.

Despite their similarity to permanent pacemaker leads, endocardial sensing leads for cardioverter defibrillators have a relatively high failure rate. We describe four patients with endocardial rate sensing leads who developed inappropriate discharges 10-30 months after implantation due to small breaks in the lead insulation. This problem may become increasingly common as the number of cardioverter defibrillator implants with transvenous leads continues to grow and should be considered in the differential diagnosis of late sensing failure or inappropriate device discharges.

Aged↗
PubMed1992

Implantation of cardioverter defibrillators in the post-sternotomy patient.

In an attempt to minimize the hazards of redo sternotomy or thoracotomy in patients who have undergone previous cardiac procedures, a technique has been developed for cardioverter defibrillator implantation that involves dissection through a left subcostal incision and placement of extrapericardial defibrillation patches. This approach was used in 22 consecutive patients who required an implantable cardioverter defibrillator 4 to 156 months after previous median sternotomy. Defibrillation threshold energy was less than or equal to 20 J in every patient. Ninety-one percent of patients were extubated during the first 24 hours and were transferred out of the intensive care unit by the second postoperative day. One patient died of an acute myocardial infarction 3 days postoperatively (1/22, 4.5%). It was necessary to replace one lead for mechanical failure of an adapter, one patch required repositioning, and 1 patient needed drainage of a persistent pleural effusion (3/22, 13.6%). No further complications occurred during 3 to 27 months of follow-up. Advantages of the subcostal approach included prompt extubation, a single incision, and minimal morbidity. This approach is safe and effective, and is the method of choice for implantation of a cardioverter defibrillator in patients who have undergone prior sternotomy.

Adult↗
PubMed1991

Effect of desipramine on norepinephrine metabolism in humans: interaction with aging.

To determine whether differences in neuronal reuptake contribute to age-related changes of sympathetic nervous system activity, we compared norepinephrine (NE) release and metabolism during [3H]NE infusion and decay in six young (age 19-26 yr) and seven older (age 61-73 yr) healthy nonobese subjects. Subjects were studied on a control day and on a separate day after desipramine (DMI; 125 mg orally), a neuronal reuptake blocker. Compartmental analysis of plasma NE specific activity was used to determine several NE kinetic parameters. Plasma NE levels and NE spillover rates were higher in the elderly. Although plasma NE was unaffected by DMI in both age groups, both the metabolic clearance rate of NE from plasma and the rate of NE spillover into plasma fell in young and older groups during DMI. Furthermore, DMI dramatically lowered the mass of NE in the extravascular compartment and the rate of NE entry into the extravascular compartment. Thus neuronal uptake blockade has major effects on NE release as well as NE metabolism in humans. However, age-related differences in NE kinetics cannot be explained by differences in neuronal uptake.

Adult↗
PubMed1987

Intrinsic failure of Hancock mitral bioprostheses: 10- to 15-year experience.

Hancock porcine bioprostheses have been implanted in the mitral position at the National Institutes of Health since July, 1970. Eight models (330, 330A, 330B, 330C, 332, 340, 341, and 342) were used during a 54-month period ending December, 1974, and 100 consecutive surviving patients were evaluated for subsequent bioprosthetic valve failure and prosthesis-related complications by annual clinic examinations and serial hemodynamic studies. Actuarial patient survival was 76 +/- 4%, 51 +/- 5%, and 30 +/- 6% after 5, 10, and 15 years, respectively. Intrinsic valve failure, defined as structural degeneration of bioprosthetic tissue or stent geometry alteration or both, in the absence of prior infection, occurred in 23 patients. The linear occurrence rate of bioprosthetic valve failure was 0.2%, 5%, and 15% per patient-year, and it affected 1 patient, 14 patients, and 8 patients at sequential 5-year milestones. The actuarial freedom from valve failure was 99 +/- 1%, 75 +/- 6%, 58 +/- 8%, and 40 +/- 12% after 5, 10, 12, and 14 years, respectively. The valve durability of early Hancock bioprostheses (models 330 through 341; N = 39) was not appreciably different from that of the current model 342 valves (N = 61). However, an increased incidence of intrinsic valve failure was observed for the first polypropylene-stented valve type (model 330) compared with the currently available model 342 valve (8/16, 50%, versus 12/61, 20%; p = 0.034). The yearly occurrence rate of prosthesis-related complications remained constant, but the rate of intrinsic valve failure increased in a progressive, nonlinear fashion. The high intrinsic failure rate of the Hancock porcine bioprosthesis after 10 to 12 years has moderated our initial enthusiasm for this valve in the mitral position, and has resulted in more frequent implantations of mechanical valve substitutes at this institution.

Actuarial Analysis↗
PubMed1986

Valve replacement in narrow aortic roots: serial hemodynamics and long-term clinical outcome.

No long-term data are available that correlate clinical outcome with serial hemodynamic studies for small-diameter (17-mm or 19-mm) aortic prostheses implanted without enlargement of the annulus. After insertion of these valves without annuloplasty, 52 patients underwent resting catheterization and were followed up at the Surgery Clinic of the National Heart, Lung, and Blood Institute for 295 patient-years (mean, 5.7 years per patient). At similar flow rates, peak systolic gradients across 17-mm Björk-Shiley aortic prostheses (N = 6) tended to exceed those of the 19-mm Björk-Shiley model (N = 38); these gradients averaged 30 +/- 6 mm Hg (mean +/- standard error of the mean) and 20 +/- 2 mm Hg, respectively (p = .053). Those patients with 19-mm Hancock (N = 4) and St. Jude Medical valves (N = 4) were studied, and the lowest prosthetic gradients were found with the St. Jude Medical prosthesis (mean, 3 +/- 2 mm Hg). Aortic gradient was independent of flow for 17-mm but not for 19-mm Björk-Shiley valves. There was no difference in calculated effective orifice area with respect to valve size. Effective orifice area and prosthetic gradients were stable during intervals of 2 to 12 years in 10 patients who underwent additional catheterizations. No association was found between prosthetic gradients, flows, or calculated orifice areas and early or late functional class. Actuarial survival was 86 +/- 5% at 5 years, 83 +/- 5% at 8 years, 71 +/- 9% at 10 years, and 60 +/- 12% at 12 years of complete follow-up. It is concluded that small aortic prostheses provide acceptable palliation for long periods and that resting hemodynamic studies have a limited predictive value for long-term prognosis.

Adult↗
PubMed1983

Restoration of full mass in nerve-intact muscle grafts after delayed reinnervation.

A rat muscle freely grafted with the motor nerve intact becomes restored to full mass and contractile function, in contrast to the reduced weight of a standard free graft. By crushing the nerve to a nerve-intact graft and delaying reinnervation, full mass is still restored. One can conclude that earlier reinnervation is not the reason for the success of nerve-intact grafts, but that it is rather due to reinnervation along preserved Schwann cell channels.

Animals↗