Gradual tapering of benzodiazepines is better tolerated.
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Biomedical subjects
Publications and source records attributed to W S Pierce.
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An implantable, electrically powered pump that will provide tether-free circulatory support is being developed. The blood pump consists of a seamless polyurethane sac within a polysulfone case. Björk-Shiley Monostrut valves provide unidirectional flow. The blood sac is compressed by a pusher plate with a stroke of 1.9 cm and actuated by a brushless direct-current electric motor and motion translator. The current unit is completely sealed, and inductive coupling techniques provide the electrical energy. The system has an implantable electronic control system as well as a battery that provides 30 minutes of operation when the external coil is disconnected. During normal operation, however, the pump is powered by a portable battery pack or by house current. The unit can pump 8.5 L/min at physiologic pressures. Twenty-six animals have had circulatory support for a period of more than 1 week. The average period of pumping was 62 days; the longest was nearly 8 months. Experiments were terminated in 18 animals because of pump-related problems and in 8 because of biologically related problems. Studies to date are very encouraging and suggest that, with further refinement, a reliable 2-year assist pump that will have important clinical application can be developed.
The two main ingredients of blood clots formed on artificial surface are platelets and fibrinogen. In this study, we measured platelet and fibrinogen survival in calves implanted with total artificial heart (TAH) and left ventricular assist device (LVAD), and correlate these data with autopsy findings. Platelet survival with autologous 111In-labeled platelets was performed on nine calves implanted with TAH and five with LVAD. Fibrinogen survival with 131I-labeled homologous fibrinogen was performed on six calves with TAH and three with LVAD. Platelet survival was significantly shortened in both groups of animals: 5.89 +/- 0.52 days, control 6.46 +/- 0.31 days, p = 0.0013; fibrinogen survival was normal: 8.79 +/- 1.20 days, control 8.64 +/- 1.16 days. At autopsy two calves with TAH had multiorgan thromboembolism. Two other animals with TAH and four with LVAD had focal renal infarcts. Most animals had minor clot formation within the prosthetic device. Major septic complications occurred in four calves with TAH and one with LVAD. Continuous platelet activation by artificial surface probably explains the shortened platelet survival and thromboembolic complications.
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The two most serious complications associated with long-term use of a total artificial heart (TAH) are thromboembolism and infection. In this article, we review our experience in one patient implanted with a pneumatic TAH for 396 days, and in 24 calves implanted with the same type of device for 70 to 353 (median 150) days. During his survival with the TAH, our patient suffered several thromboembolic episodes despite adequate anti-coagulation with warfarin. Autopsy showed widespread thrombotic lesions, mostly in the brain. Throughout his survival, the patient had markedly elevated plasma beta-thromboglobulin and fibrinopeptide A levels, indicating sustained activation of platelets and the coagulation system secondary to blood contact with the artificial surface. Long-term use of TAH in calves causes significant mechanical hemolytic anemia and a small reduction in the total leukocyte and neutrophil counts. The platelet count normalized to preimplantation levels by 25 to 35 weeks. At autopsy, thrombotic lesions and organ infarction were noted in 13 calves, and major septic complications were documented in 10 animals. Although impressive gains in the clinical and experimental use of TAH were achieved during the last 15 years, thromboembolism and infection remain challenging problems.
An artificial heart should be controlled in a noninvasive fashion; the presence of the control system should pose no risk to the patient. Ideally, much of the control function would be attained passively, by designing the pumps and energy converter so that they naturally respond in an appropriate manner to changes in the circulation. We present methods of controlling both left-right output balance and providing response to changing demands for blood flow for a class of total artificial hearts with implanted energy converters. Our balance control actively maintains left-right balance, but does so in concert with the natural response of the pumps to changes in filling pressures. Cardiac output (CO) can be made to be sensitive to right atrial pressure, but peripheral resistance is our usual cue. Alternative means of determining the correct cardiac output are discussed.
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Data submitted voluntarily to the combined registry since its inception in 1985 to December 31, 1990, on the use of ventricular assist devices for postcardiotomy cardiogenic shock in 965 patients were analyzed. Approximately 45% of patients were weaned from temporary circulatory assistance and 24.6% reached hospital discharge regardless of the original operation. In 90% of patients who were discharged from the hospital, circulatory support was able to be discontinued by 1 week. Rates of weaning and discharge were statistically different and favored those patients requiring univentricular support only. Results were equal whether nonpulsatile centrifugal or pulsatile pneumatic devices were used for support. Although complications were frequent and multiple during assist pumping, patient variables including age greater than 70 years rather than direct complications caused by circulatory support were likely to affect overall outcome. In patients achieving hospital discharge, 2-year actuarial survival was 82% with 86% of patients being in New York Heart Association functional class I or II. In rare instances of device dependency in 43 patients (4.5%) with no contraindications to transplantation, 32 (74.4%) underwent bridge to cardiac transplant and 20 (62.5%) were discharged. This multi-institutional experience would continue to support the use of ventricular assist devices in postcardiotomy cardiogenic shock.
Ca(2+)-ATPases keep cytoplasmic [Ca(2+)] low by pumping Ca(2+) into intracellular compartments or out of the cell. The transport properties of Ca(2+)-pumping ATPases from carrot (Daucus carota cv Danvers) tissue culture cells were studied. ATP-dependent Ca(2+) transport in vesicles that comigrated with an endoplasmic reticulum marker, was stimulated three- to fourfold by calmodulin. Cyclopiazonic acid (a specific inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase) partially inhibited oxalate-stimulated Ca(2+) transport activity; however, it had no effect on calmodulin-stimulated Ca(2+) uptake driven by ATP or GTP. The results would suggest the presence of two types of Ca(2+)-ATPases, an endoplasmic reticulum- and a plasma membrane-type. Interestingly, incubation of membranes with [gamma(32)P]ATP resulted in the formation of a single acyl [(32)P]phosphoprotein of 120 kilodaltons. Formation of this phosphoprotein was dependent on Ca(2+), but independent of Mg(2+). Its enhancement by La(3+) is characteristic of a phosphorylated enzyme intermediate of a plasma membrane-type Ca-ATPase. Calmodulin stimulated Ca(2+) transport was decreased by W-7 (a calmodulin antagonist), ML-7 (myosin light chain kinase inhibitor) or thyroxine. Acidic phospholipids, like phosphatidylserine, stimulated Ca(2+) transport, similar to their effect on the erythrocyte plasma membrane Ca(2+)-ATPase. These results would indicate that the calmodulin-stimulated Ca(2+) transport originated in large part from a plasma membrane-type Ca(2+) pump of 120 kilodaltons. The possibility of calmodulin-stimulated Ca(2+)-ATPases on endomembranes, such as the endoplasmic reticulum and secretory vesicles, as well as the plasma membrane is suggested.
Advances in microelectronics, high-strength magnets, and control system design now make replacement of the heart using an implantable, electrically powered pump feasible. The device described herein is a compact, dual pusher plate unit with valved polyurethane sac-type ventricles positioned at either end. The power unit consists of a small, brushless direct current motor and a motion translator. A microprocessor control system is used to regulate heart beat rate and provide left-right output balance. Bench studies lasting for as long as 1 year have been performed. Heart replacement with the electric heart has been performed in 18 calves since 1984. The longest survivor lived for more than 7 months. Among the causes of termination were component failure, thromboembolic complications, and bleeding. No major problem has been identified that precludes prolonged use of the electric heart. In the future the patient with end-stage heart disease will have an electric artificial heart as one therapeutic option.
We investigated vascular effects of dopamine and dobutamine infusions in awake calves implanted with the Penn State total artificial heart (TAH). This preparation uniquely permits independent servo-control of cardiac output (CO) and arterial blood pressure (BP). Thirty-two studies (22 with dopamine and 10 with dobutamine) were performed in four juvenile calves from 1 to 4 months after TAH implantation. Studies were performed in one of two TAH operating conditions: (a) constant aortic flow, in which the CO is fixed and aortic BP varies with systemic vascular resistance (SVR), or (b) constant pressure, in which the CO varies to maintain a constant BP when SVR changes. During both constant flow and constant pressure studies, dopamine caused a dose-dependent increase and dobutamine caused a dose-dependent decrease in SVR. There was no difference in the SVR response between constant flow or constant pressure conditions at any dose of dopamine or dobutamine (p greater than 0.05). The infusion doses of dopamine required to raise the SVR 20 and 50% during constant flow studies were 7.2 and 12.4 micrograms.kg-1.min-1, respectively. In constant pressure studies, these doses were 7.7 and 13.5 micrograms.kg-1.min-1. The infusion dose of dobutamine resulting in a 20% reduction in SVR was 27.2 micrograms.kg-1.min-1 in constant flow studies 26.2 micrograms.kg-1.min-1 in constant pressure studies. These data suggest that baroreflex and other indirect mechanisms are less important than direct vascular drug effects in this system.(ABSTRACT TRUNCATED AT 250 WORDS)
Permanent circulatory support systems are required for patients in whom myocardial damage is irreversible and cardiac transplantation is not possible. Two systems are described which provide long term circulatory support: the left ventricular assist system and the total artificial heart. These systems are based on the design of a pusher plate actuated blood pump, driven by a small brushless dc electric motor and rollerscrew driver. An implantable motor controller maintains suitable physiologic flow rates for both systems and controls left-right balance in the total artificial heart. Other parts of the system include an intra-thoracic compliance chamber, transcutaneous energy and data transmission system, and internal and external batteries.
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Pneumatic total artificial heats, although demonstrating utility as temporary mechanical circulatory support devices, have not demonstrated a great deal of promise as permanent cardiac replacements. The increasing number of patients who would be candidates for total heart replacement suggests a large role for a permanent implantable total artificial heart. To that end, the Pennsylvania State University is developing an electric motor-driven total artificial heart; the results with implants in calves are encouraging. In this device, a roller-screw mechanism is used to translate the rotation of a brushless direct-current motor into rectilinear motion of a pusher-plate assembly, which in turn empties the blood sacs. The total artificial heart of the future will function under automatic control without percutaneous leads, and this should provide the patient with a nearly normal life-style. Although further experimental efforts are necessary to prepare the device for clinical trials, the technology to provide a safe and reliable electric blood-pump system is at hand.
In an effort to determine whether the population of patients undergoing isolated coronary artery bypass grafting and the outcome of these operations have changed, we analyzed the records of two patient populations from our institution. Interventional cardiology techniques (angioplasty, thrombolysis) were not used at our institution before 1982. The records of 736 patients (group 1) who underwent isolated coronary artery bypass grafting from January 1975 to July 1981 were reviewed and compared with a group of 603 patients (group 2) who underwent operation from July 1985 to December 1987. The techniques of operation and myocardial preservation were virtually identical during the two periods. During the group 2 analysis period, 343 angioplasty procedures were performed. The patients in group 2 were significantly older, had increased preoperative New York Heart Association classification, had sustained more previous myocardial infarctions, and had more associated morbid medical conditions. There was a threefold increase in patients seen for reoperative revascularization procedures and a fourfold increase in emergency operations. Overall mortality, although not significantly different, did increase slightly from 2.69% in group 1 to 3.83% in group 2. Mortality after elective procedures remained essentially unchanged (2.05% for group 1 and 1.90% for group 2).
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