[On tyramine resistant adrenergic mechanisms in the rabbit cardial].
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Biomedical subjects
Publications and source records attributed to E Wolner.
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Continuous-wave Doppler echocardiography of aortic flow velocity has a variety of clinical and research applications. Recently, continuous-wave Doppler echocardiography has been added to transesophageal echocardiographic systems. However, alignment of the Doppler beam with aortic flow is not possible with standard single and biplane views. A modified transesophageal echocardiographic view; the transgastric five-chamber (TG5C) view, allows for measurement of aortic flow velocity but its feasibility and accuracy in an unselected consecutive population have not yet been described. The feasibility of obtaining the TG5C view and measuring aortic flow velocity was assessed in 58 consecutive transesophageal echocardiographic investigations. The TG5C view was obtained in 97% and adequate Doppler flow velocity signals were obtained in 91% of patients. The accuracy of measurements was assessed in 24 patients in whom flow signals from both the TG5C and standard transthoracic views could be obtained. The correlation between TG5C and transthoracic views was excellent, with r values of 0.968 and 0.952 for peak aortic flow velocity and mean aortic flow velocity, respectively. Accurate aortic flow velocity measurements can be obtained in most patients during transesophageal echocardiography with the TG5C view. This view has great utility in a variety of situations in which adequate transthoracic imaging is not possible, especially the operating room and intensive care unit.
In 5 total artificial heart (TAH)-bridge-to-transplant (BTT) patients production and secretion of atrial natriuretic factor (ANF)1 was studied before, during, and after TAH implantation. Bridging periods lasted between 9 and 28 days. Atrial biopsies were taken during implantation, and after TAH explantation for histologic and histochemical investigations to evaluate differences in morphology and ANF-content of the specific atrial granules. Plasma concentrations of ANF (pANF), aldosterone (PAC) and renin (PRC) were measured daily, as were hemodynamic parameters. In the preoperative state, pANF was always markedly elevated, while during TAH bridging, pANF remained moderately elevated with fluctuations. A positive correlation between pANF levels and right atrial pressure (RAP) was seen in all patients (p less than 0.05). Slight correlation was also observed between pANF and left atrial pressure (LAP), but no correlation was seen between pANF and systemic blood pressure, and no consistent pattern was seen in the plasma concentrations of either renin or aldosterone. After heart transplantation (HTX), which was performed in 3 patients, pANF levels were significantly higher than during TAH, and continued to show a positive correlation with RAP. From our data, we conclude that ANF production sites and secretory mechanisms remain intact during TAH-bridging, although upon implantation of a TAH, the remaining atria are deprived of all coronary blood supply and most autonomic innervation.
In centrifugal pumps, there always exists an area of stagnation between the rear of the rotor and the rear housing wall that promotes thrombus formation around the axle. Some current devices overcome the problem by using holes in the rotor plane, leading to increased hydrodynamic losses and shear stress. In this study, a simple apparatus was developed to overcome this problem. Guiding vanes were fixed to the rear housing wall. These vanes decrease the tangential velocity of the fluid and thus the centrifugal force, leading to an increased secondary flow toward the axle. The effect of such vanes was studied in videographic and ultrasound studies. An increase of washout and mixing between the flow layers could be demonstrated (stay time < 200 msec versus several seconds without vanes). In the first animal experiment using nonoptimized vanes, there was no thrombus at the back plane or the seal, and only a small thrombus at the transition between axle and rotor. Hemolysis was slightly elevated (3.2 mg/dl versus 2.5 mg/dl in control experiments). In conclusion, it is highly likely that this simple system will improve the flow characteristics in centrifugal pumps.
The gyro pump was developed as an intermediate-term assist pump (C1E3) as well as a long-term centrifugal ventricular assist device (VAD). The antithrombogenic design concept of this pump was confirmed throughout three 1 month ex vivo studies. The normalized index of hemolysis (NIH) of this gyro C1E3 model was lower than that of the BP-80. In the next step, a miniaturized centrifugal blood pump (The Gyro permanently implantable model PI-601) has been developed for use as a permanently implantable device after design optimization. A special motor design of the magnet circuit was utilized in this system in collaboration with the University of Vienna. The priming volume of this pump is 20 ml. The overall size of the pump actuator package is 53 mm in height, 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. This pump can provide 5 L/min against 120 mm Hg total pressure head at 2,000 rpm. The NIH value of this pump was comparable to that of the BP-80. The gyro PI-601 model is suitable for a VAD. The expected life from the endurance study is approximately 8 years. The evolution from C1E3 to the PI-601 converts this pump to a totally implantable centrifugal pump. Recent technologic advances in continuous flow devices are likely to realize a miniaturized and economical totally implantable VAD.
A totally implantable centrifugal artificial heart has been developed using a miniaturized pivot bearing supported centrifugal pump (Gyro PI pump). The authors report current progress in its development. The Gyro PI-601 has a priming volume of 20 ml, weighs 100 g, has a height of 60 mm, and has a diameter of 65 mm. This pump can provide 8 L/min against 150 mmHg at 2,250 rpm. It is driven by an miniaturized DC brushless motor with the coils fixed in a plastic mold that is waterproof and made of titanium (weight, 204 g; height, 18 mm; diameter, 65 mm). In this centrifugal artificial heart, two Gyro PI pumps are implanted independently to replace cardiac function without resecting the native heart. Its anatomic and surgical feasibility were confirmed experimentally. The Gyro PI-601 was implanted as a right or left ventricular assist device in the preperitoneal space of five calves. All five tests proceeded without any thromboembolic symptoms. One of five tests was extended more than 1 month to confirm the long-term feasibility of the Gyro PI-601 pump system. Based on the satisfactory results of the in vivo tests, the material conversion of the Gyro PI from polycarbonate to titanium alloy (Ti-6A1-4V) was undertaken to improve its biocompatibility for long-term implantation.
A totally implantable centrifugal artificial heart has been developed. The plastic prototype, Gyro PI 601, passed 2 day hemodynamic tests as a functional total artificial heart, 2 week screening tests for antithrombogenicity, and 1 month system feasibility. Based on these results, a metallic prototype, Gyro PI 702, was subjected to in vivo left ventricular assist device (LVAD) studies. The pump system employed the Gyro PI 702, which has the same inner dimensions and the same characteristics as the Gyro PI 601, including an eccentric inlet port, a double pivot bearing system, and a magnet coupling system. The PI 702 is driven with the Vienna DC brushless motor actuator. For the in vivo LVAD study, the pump actuator package was implanted in the preperitoneal space in two calves, from the left ventricular apex to the descending aorta. Case 1 achieved greater than 9 month survival without any complications, at an average flow rate of 6.6 L/min with 10.2 W input power. Case 2 was killed early due to the excessive growth of the calf, which caused functional obstruction of the inlet port. There was no blood clot inside the pump. During these periods, neither case exhibited any physiologic abnormalities. The PI 702 pump gives excellent results as a long-term implantable LVAD.
Currently, at least two permanent implantable left ventricular assist devices (LVADs) are used clinically. Unfortunately, there is no small implantable right ventricular assist device (RVAD) available, even though at least 25-30% of this patient population has right ventricular failure. If a small implantable RVAD were available, biventricular assist could support patients with right ventricular failure. A small atraumatic and antithrombogenic RVAD is being developed to meet this clinical need. This small centrifugal blood pump, the Gyro PI pump, is 6.5 cm in diameter and 4.6 cm in height and has three unique characteristics to prevent thrombus formation: (1) the double pivot bearing and magnetic coupling system enable this pump to be completely sealless; (2) the secondary vanes at the bottom of the impeller accelerate the blood flow and prevent blood stagnation; and (3) the eccentric inlet port enables the top female bearing to be embedded into the top housing and decrease blood cell trauma. The inflow conduit consists of a wire reinforced tube and a hat-shaped tip that is biolized with gelatin to create a thrombus resistant material. This conduit is directly implanted into the right ventricle, and the outflow conduit is anastomosed to the PA. The pump can be implanted inside the abdominal wall or in the thoracic cavity. Biocompatibility of this pump was proved in two calves by thrombus free implantation as an LVAD for 284 days and 200 days. Two RVAD implantations were conducted, aiming for 1-month system feasibility studies. During the month, the RVADs operated satisfactorily without any thromboembolic incident. No blood clots or abnormal findings were seen inside the pump, nor were there abnormal findings in the explanted lungs except for small areas of atelectasis. The pump flow was 3.02 +/- 0.38 L/min in calf 1 and 3.75 +/- 1.18 L/min in calf 2. The power requirement was 7.28 +/- 0.43W for calf 1 and 14.52 +/- 3.93W for calf 2. The PaO2 was 72.0 +/- 3.60 mm Hg (calf 1) and 72.0 +/- 7.63 mm Hg (calf 2); PaCO2 was 38.3 +/- 2.17 mm Hg (calf 1) and 34.1 +/- 1.95 mm Hg (calf 2); and SaO2 was 94.1 +/- 1.37% (calf1) and 95.0 +/- 1.95% (calf 2). Gas exchange via the lungs was maintained. These studies indicate that the Gyro PI pump is suitable as a single implantable RVAD, and is a feasible RVAD as a part of a BiVAD system in terms of pump performance and thrombus resistance.
We investigated the immunohistochemical expression of bcl-2 in 55 non small cell lung cancer patients in order to understand if the altered expression of this gene is involved in the development of this kind of neoplasm. Our results showed bcl-2 immunopositivity to be a frequent event in non small cell lung cancer (54.5%) with a higher expression in squamous carcinomas compared to adenocarcinomas (p = .04). In addition, we found a positive correlation between bcl-2 expression levels and nodal status (p < .003). We suggest that bcl-2 immunostaining could be considered as marker of loco-regional invasivity.
Bax, bcl-2 and their homologues regulate a distal step in an evolutionary very well conserved pathway of apoptotic cell death. It plays a crucial role in the balance between proliferation rate and cell viability. Thus in the last years the attention of the scientific community towards these proteins has remarkably increased, in particular in the oncologic field. We developed an immunohistochemical assay allowing us to evaluate the bax expression in formalin fixed and paraffin embedded lung cancer tissues to investigate bax expression in a cohort of 55 patients affected by non-small cell lung cancer. We detected high expression of bax in 72.7% of our patients. When we statistically analyzed our data we did not find any correlation between bax expression and any clinicopathologic parameters (sex, age, TNM status, tumor grade, histological type). In conclusion, our study shows the frequent overexpression of bax, and this highlights the "apoptotic tendency" of cells during the neoplastic proliferation. But, the role of bax in non-small cell lung cancer pathogenesis still remains unclear and further studies of large numbers of patients, including different stage groups, are needed to better define the involvement of this protein in the complex mechanism of lung carcinogenesis.
Twenty patients undergoing orthotopic heart transplantation were randomized preoperatively to receive either the serine proteinase inhibitor aprotinin in a low dose (560 mg; n = 10) or a placebo (control group, n = 10) at the time of transplantation. Blood loss 24 and 48 hours after transplantation was significantly lower in the group treated with aprotinin (i.e., 510 ml vs 820 ml, p less than 0.01, and 690 ml vs 1000 ml, p less than 0.03, respectively. Accordingly, the aprotinin group required significantly less transfused blood in the first 48 postoperative hours 0 to 250 ml versus 0 to 1000 ml (p less than 0.04). Seventy percent of the patients treated with aprotinin underwent transplantation without the need of nonautologous blood, compared with only 30% in the control group.
The scarcity of donor organs remains the main restricting factor for heart, heart-lung, and lung transplantation. Recently new techniques for separate harvesting of the heart and the lungs from one donor for two recipients have been developed. These techniques enable the optimal use of available grafts. Another approach to this problem is combined heart-lung transplantation for patients with end-stage lung disease but still adequate heart performance, and the subsequent transplantation of the recipient's heart into a second patient with end-stage heart disease. The main advantages of this procedure are its technical simplicity compared with double lung transplantation; the preservation of aortobronchial collaterals, resulting in improved blood supply to the trachea; and the possibility of transplanting a conditioned right heart well adapted to chronically elevated pulmonary pressure. We recently have performed this procedure with good clinical results and suggest it as the method of choice whenever two well-matched recipients are available.
Long-standing release of locally cytotoxic aldehyde concentrations is responsible for lack of spontaneous endothelialization and increased calcification of glutaraldehyde fixed bovine pericardium. Postfixation treatment with amino acids made in vitro endothelialization of bioprosthetic heart valves possible. Such treated pericardium calcified significantly less (13 +/- 4 micrograms/mg dry weight) than did conventionally processed pericardium (114 +/- 25 micrograms/mg) after 63 days of subcutaneous implantation in rats. To test the ability for spontaneous in vivo endothelialization, 5 sheep had 6 mm grafts made from postfixation treated pericardium (PTP) implanted into the carotid artery, compared to PTFE grafts on the contralateral side, which spontaneously endothelialize in animal models. In a pregnant animal, both grafts occluded. All remaining pericardial grafts remained patent, but one additional PTFE graft occluded and another one was stenosed. The area covered with red thrombus was significantly smaller in the PTP grafts (3.05 +/- 3.9%) than in the PTFE grafts 42 +/- 14% (p = 0.0036); TEM and SEM showed endothelial cells growing directly on the PTP, but only on myofibroblasts in PTFE grafts. Postfixation treatment of glutaraldehyde fixed pericardium aids spontaneous endothelialization and decreases tissue calcification.
The Duromedics Edwards (DE) bileaflet valve prosthesis was withdrawn from the market after 12 leaflet escapes had been reported in 20,000 implants. Effort is necessary to identify the failure mode to improve valve design or production, but the rate of other valve related complications will tell if it is worthwhile reintroducing this prosthesis. Five-hundred and sixty-four DE valves have been implanted in 508 patients between September 1983 and May 1988. Two-hundred and sixty-eight had aortic valve replacement (AVR), 183 mitral valve replacement (MVR) and 56 double valve replacement (DVR); the perioperative mortality was 6.9%. Follow-up has been 98.7% complete for a total of 1064 patient years and a mean follow-up of 26 months (range 3 to 54 months). Late mortality was 3.7%/yr and actuarial survival was 85 +/- 3% without and 78 +/- 3% including operative mortality after 54 months. Event free actuarial rates (linearized rates in parenthesis) were 93 +/- 2% (1.5%/yr) for thromboembolism, 91.7 +/- 1.9% (2.3%/yr) for anticoagulant related hemorrhage, 89 +/- 4.8% (2.3%/yr) for valve failure, 93 +/- 2% (1.8%/yr) for valve related mortality, 72 +/- 4.8% (6.3%/yr) for all valve related morbidity and mortality and 83 +/- 4.4% (3%/yr) for treatment failure. Two leaflet escapes occurred in the study group (0.18%/yr), both patients survived reoperation. The concept of reducing thrombus formation by a specially designed irrigating hinge mechanism was proven by a low rate of thromboembolism in our clinical follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)