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Biomedical subjects

J W Long

Publications and source records attributed to J W Long.

At least 19 recordsLinked to original sources

Long-term use of a left ventricular assist device for end-stage heart failure.

BACKGROUND: Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation, but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated. METHODS: We randomly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device (68 patients) or optimal medical management (61). All patients had symptoms of New York Heart Association class IV heart failure. RESULTS: Kaplan-Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at two years were 23 percent and 8 percent (P=0.09), respectively. The frequency of serious adverse events in the device group was 2.35 (95 percent confidence interval, 1.86 to 2.95) times that in the medical-therapy group, with a predominance of infection, bleeding, and malfunction of the device. The quality of life was significantly improved at one year in the device group. CONCLUSIONS: The use of a left ventricular assist device in patients with advanced heart failure resulted in a clinically meaningful survival benefit and an improved quality of life. A left ventricular assist device is an acceptable alternative therapy in selected patients who are not candidates for cardiac transplantation.

Activities of Daily Living↗

Advanced mechanical circulatory support with the HeartMate left ventricular assist device in the year 2000.

This paper describes the HeartMate left ventricular assist device (ThermoCardiosystems Inc, Woburn, MA) technology, which has been successfully introduced into the clinical arena with more than 2,400 implants as of the year 2000. The review summarizes the clinical experience, and identifies the benefits and limitations of the current state-of-the-art technology of the leading implantable circulatory support system.

Adolescent↗

Treatment of infected left ventricular assist device using antibiotic-impregnated beads.

There is no well-established therapy for treating infections of heart-assist or artificial heart devices, a serious problem with life-threatening consequences. We used a promising new approach in which antibiotic-impregnated polymethylmethacrylate beads were placed around an implanted left ventricular assist device to control an external blood pump infection in a bridge-to-transplant patient. In this case report, we describe the potential of antimicrobial-impregnated polymethylmethacrylate beads for in situ control of infections involving external surfaces of cardiovascular devices.

Combined Modality Therapy↗

Measurement of oxygen consumption and arterial-venous oxygen saturation following total artificial heart implantation.

Current algorithms for control of the total artificial heart are directed at maintaining hemodynamic homeostasis. Future control systems will also need to modify cardiac output in response to metabolic needs. This study was undertaken to evaluate oxygen metabolism monitoring as an indicator of the adequacy of organ and tissue perfusion. Following recovery from implantation of the Utah-100 pneumatic total artificial hearts, five calves (85 to 95 kg) underwent placement of fiberoptic oximetry catheters to determine mixed venous and arterial oxygen saturations. By continuously measuring oxygen consumption with a gas analyzer, oxygen utilization and delivery were determined. In the awake calves, at-rest cardiac output was varied to produce hyperperfused and hypoperfused conditions while the adequacy of tissue perfusion was assessed with continuous mixed venous oximetry and confirmed with serum lactate (Lact) levels. Inadequate tissue perfusion (Lact > 1.0 mmol/L) was evidenced by a mixed venous oxygen saturation < 40%, oxygen delivery of < 200.0 milliliters/minute/m2), and oxygen delivery to utilization ratio of < 1.8 during the hypoperfusion conditions of the experiment. By accounting for oxygen consumption, the ratio of oxygen delivery to oxygen utilization was predictive of the adequacy of tissue perfusion. These results suggest that continuous oxygen metabolism monitoring may be useful as a physiologic control modifier to maintain total artificial heart output sufficient to meet physiologic needs, while avoiding hyperperfusion, unnecessary wear and deterioration of the implanted device due to excessive heart rates.

Animals↗

Calves chronically implanted with a total artificial heart as a pharmacological model.

Pharmacological therapy for congestive heart failure includes drugs that have both inotropic and vasoactive effects, although it is sometimes difficult to differentiate between the two effects. An animal with an implanted total artificial heart (TAH) allows the investigation of the vascular effect of these drugs in the absence of the effect on the myocardium. An advantage of the TAH model is its sensitivity to changes in right and left ventricular preload and afterload. Four instrumented TAH calves were given vasoactive drugs and the response was compared to control. Epinephrine, dopamine, isoproterenol, and nitroprusside were selected because of the predictability of their responses. Epinephrine caused a significant increase in systemic vascular resistance (SVR), and dopamine caused a significant increase in Pulmonary vascular resistance (PVR) and Isoproterenol caused a significant decrease in PVR. TAH implanted calves can thus serve as a pharmacological model to study the vascular response, which may be useful in investigation of new agents with inotropic and vascular effects.

Animals↗

Right-left ventricular output balance in the totally implantable artificial heart.

Pneumatically powered artificial hearts readily accommodated the higher net stroke volumes by the right ventricle than from the left ventricle. We published that this discrepancy was approximately 8% of the left ventricular cardiac output. A variety of methods have been used to achieve balance between the right and left atrial pressures. Relatively large volume-displacement chambers (VDC) present potential problems, but do provide balance. The VDC in volumetrically coupled right-left stroke volumes was eliminated by using a small-diameter interatrial shunt (IAS). Preliminary studies demonstrated excellent balance in contracted and expanded blood volume (preload) and by hypotension and hypertension created with vasoactive drugs (afterload). At a mean aortic pressure of 120 mmHg, heart rate of 120 BPM, cardiac output of 8 L/minute and right atrial pressure of 13 mmHg, the peak IAS flow was 3.2 ml/beat in a right to left direction and 8.0 ml/beat in a left to right direction. The net left to right flow was 4.8 ml/beat. Over a wide range of preload (2 to 20 mmHg) and afterload (45 to 180 mmHg), the left atrial pressure was routinely 5 mm Hg more than the right atrial pressure. Elimination of the VDC reduces the number of components, volume, and weight of the totally implantable artificial heart. The IAS offers a simple solution to a very complex problem and provides a device that is simpler to implant and is possible to explant.

Animals↗

Reliability of continuous-wave Doppler probes.

Small-diameter, thin-walled latex tubes, through which a blood-simulating agent (0.1% suspension of simethicone in 0.9% sodium chloride) flowed at controlled rates, were embedded at varying depths in a tissue-mimicking matrix of powered graphite suspended in 4% agar. A continuous-wave (CW) Doppler probe was mounted at a 45-degree angle to the flow and passed transversely over the tube by a motorized drive mechanism at a rate of 0.42 mm/sec. Flow rates through the tubes were monitored with electromagnetic flow probes. The maximum depth from which quantitatively reliable signals could be obtained was 1.2 cm for 10 MHz probes and 3.3 cm for 5 MHz probes. Qualitative detection of flow was possible to a depth of 3.1 cm for 10 MHz probes and 7.0 cm for 5 MHz probes. The distances from the tube center for obtaining quantitatively reliable signals were limited to +/- 0.9 mm with a 10 MHz probe and +/- 1.8 mm with a 5 MHz probe. Qualitatively useful signals could be detected +/- 2.9 mm from the beam center by the 10 MHz probes and +/- 4.4 mm by the 5 MHz probes indicating a need for cautious interpretation as an interfering signal might be generated by any vessel within that range. Twenty percent of the randomly tested CW probes were considered unsuitable for use in quantitating blood flow, which underscores the importance of probe characterization before use.

Blood Flow Velocity↗

A high-affinity, calmodulin-sensitive (Ca2+ + Mg2+)-ATPase and associated calcium-transport pump in the Ehrlich ascites tumor cell plasma membrane.

A unique cytoplast preparation from Ehrlich ascites tumor cells (G. V. Henius, P. C. Laris, and J. D. Woodburn (1979) Exp. Cell. Res. 121, 337-345), highly enriched in plasma membranes, was employed to characterize the high-affinity plasma membrane calcium-extrusion pump and its associated adenosine triphosphatase (ATPase). An ATP-dependent calcium-transport system which had a high affinity for free calcium (K0.5 = 0.040 +/- 0.005 microM) was identified. Two different calcium-stimulated ATPase activities were detected. One had a low (K0.5 = 136 +/- 10 microM) and the other a high (K0.5 = 0.103 +/- 0.077 microM) affinity for free calcium. The high-affinity enzyme appeared to represent the ubiquitous high-affinity plasma membrane (Ca2+ + Mg2+)-ATPase (calcium-stimulated, magnesium-dependent ATPase) seen in normal cells. Both calcium transport and the (Ca2+ + Mg2+)-ATPase were significantly stimulated by the calcium-dependent regulatory protein calmodulin, especially when endogenous activator was removed by treatment with the calcium chelator ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid. Other similarities between calcium transport and the (Ca2+ + Mg2+)-ATPase included an insensitivity to ouabain (0.5 mM), lack of activation by potassium (20 mM), and a requirement for magnesium. These similar properties suggested that the (Ca2+ + Mg2+)-ATPase represents the enzymatic basis of the high-affinity calcium pump. The calcium pump/enzyme system was inhibited by orthovanadate at comparatively high concentrations (calcium transport: K0.5 congruent to 100 microM; (Ca2+ + Mg2+)-ATPase: K0.5 greater than 100 microM). Upon Hill analysis, the tumor cell (Ca2+ + Mg2+)-ATPase failed to exhibit cooperative activation by calcium which is characteristic of the analogous enzyme in the plasma membrane of normal cells.

Animals↗

Ca2+ release from energetically coupled tumor mitochondria.

A Na+/Ca2+ exchange activity for Ca2+ efflux has been identified in isolated Ehrlich ascites tumor mitochondria. Further, under conditions favoring cycling of Ca2+ across the mitochondrial inner membrane, extramitochondrial [Ca2+] also was shown to be Na+-dependent. The Na+/Ca2+ exchange showed sigmoidal kinetics with a mean (+/-SD) [Na+] required for half maximal stimulation of Ca2+ efflux of 8.4 +/- 3.8 mM and a Hill coefficient of 1.6. Na+/Ca2+ exchange was very sensitive to inhibition by the Ca2+ antagonist diltiazem (56% inhibition at 7.5 nmoles X mg protein-1) whereas a number of other compounds, including verapamil, nupercaine, and trifluoperazine were less effective in inhibiting Ca2+ efflux. These data demonstrate for the first time the presence of a pathway in tumor mitochondria for unidirectional Ca2+ efflux induced by Na+, and provide a mechanism for regulation of tumor intra- and extramitochondrial [Ca2+]. Results of the present study support the need for further study of intracellular Na+ and its role in regulation of Ca2+ homeostasis in tumor cells.

Animals↗

Ca2+-dependent depolarization of energized mitochondrial membrane potential by chlortetracycline (aureomycin).

The addition of chlortetracycline (CTC) to succinate-energized rat liver mitochondria resulted in depolarization of the membrane potential and decreased respiratory control. CTC inhibited both processes at concentrations that were half maximally effective at approximately 13 and 16 microM, respectively. These inhibitory effects were prevented by either the Ca2+ chelator, ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, or the inhibitor of mitochondrial Ca2+ influx, ruthenium red. These findings are consistent with the formation of a membrane associated calcium-CTC complex and suggest that CTC can alter mitochondrial energy metabolism during transmembrane Ca2+ cycling.

Adenosine Diphosphate↗

Paradoxical effect of hyperoncotic albumin in acutely burned children.

Hyperoncotic albumin proved ineffective as a plasma volume expander in the resuscitation of four acutely burned children. Hypovolemia and pulmonary edema were apparently intensified by an obligatory fluid shift following tissue extravasation of protein. We conclude that, when used, hyperoncotic albumin should be suspended in a sufficient volume of saline to produce a solution isotonic and iso-oncotic relative to plasma.

Acute Kidney Injury↗

Computerized 3-dimensional analysis of mitochondrial structure.

A computer program has been written to calculate surface area and volume of subcellular organelles. Sophisticated and extremely accurate point sampling routines and volume computational techniques have been developed. This program has been used to study mitochondrial 3-dimensional structure when stereological estimates have proven inadequate.

Animals↗

Bateman UPF prosthesis in fractures of the femoral neck.

The Bateman universal proximal femoral (UPF) endoprosthesis has been used in 225 patients for treatment of acute fractures of the femoral neck. In 156 patients with an average follow-up of 29 months and an average age of 79 years, there were no demonstrable advantages over the Moore prosthesis.

Aged↗

Prognosis for life in patients with diabetes: relation to severity of retinopathy.

In a group of 709 individuals with diabetes diagnosed prior to age 50 and followed for five to thirteen years a strong inverse relationship was demonstrated between the severity of the retinopathy at the initial visit and survival. Survival in patients with no retinopathy or with microaneurysms only was little different from that of the general population (five-year rate .99, SE .01). The five-year survival rate for patients with more severe nonproliferative retinopathy, characterized by the presence of hemorrhages and/or exudates, but without new vessels or vitreous hemorrhage (B2), was .81 (SE .04), and that for patients with proliferative retinopathy (PDR) was .56 (SE .03). After adjustment for age at diagnosis of diabetes, duration of diabetes and sex, the differences in survival between these three groups were highly statistically significant. Impairment of visual acuity was also shown to be inversely related to survival. The five-year survival rate for patients with visual acuity of 20/200 or worse in each eye was .42 (SE .05). In patients with B2 retinopathy there was a weak but statistically significant trend towards decreasing survival with increasing duration of diabetes. In patients with PDR survival decreased with increasing duration up to 20 years, but then improved for patients with 20 years or more of diabetes.

Adolescent↗