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Biomedical subjects

W J Kolff

Publications and source records attributed to W J Kolff.

At least 37 records · Page 2Linked to original sources

Loss of anticoagulant effect of heparin during circulation of human blood in vitro.

Device-induced thrombogenesis was studied in an in vitro model using human blood circulated through an artificial ventricle. A new constant pressure filtration technique was used to detect circulating microemboli, the activated partial thromboplastin time (APTT) test was used to monitor the blood for the presence of anticoagulant activity of heparin, and hemolysis was quantified by measuring the plasma free hemoglobin level. Circulation of blood through a 20-ml stroke volume pneumatically driven ventricle for 6-9 h resulted in a significant reduction of APTT, indicating the loss of the anticoagulant effect of heparin. Microemboli concentration was minimal until the APTT decreased below 125 s, at which time the microemboli concentration increased rapidly. This was presumed to be due to the formation of thrombi following a decrease in heparin activity. A significant increase in hemolysis was also noted when blood was pumped. None of these changes was noted in the nonpumped control blood. Spontaneous loss of heparin activity in blood circulated by a pneumatically driven pump may have clinical implications and may help understanding of the problems associated with device-induced thrombogenesis.

Adult↗

Development of a new inflow valve for a 20cc semisoft ventricle: preliminary results.

We remodeled and tested our semisoft 20cc ventricle and made a new bileaflet flap inflow valve. Housings, bases, outflow valve, and a newly designed diaphragm were all made by vacuum forming and put together by radiofrequency welding or glue. In vitro, the ventricle produced a cardiac output of 2.5 to 3.0 L/min and showed reliable durability results. Hematological testing showed no important thrombogenicity of the new valve. Cardiac output was higher than expected for the volume of the ventricle, perhaps because of stretching or flow through. Animal experiments with the left ventricular assist device (LVAD) version was done at Ohio State University. Earlier in Utah, we did 20 cc total artificial heart (TAH) implantations and LVAD experiments in lambs and recently in calves with the 60cc TAH version. A soft ventricle is easy to implant and low in production costs.

Animals↗

The return of elastomer valves.

This paper concerns the heart valves to be used mainly in artificial hearts. Most of our tricusp semilunar valves are made of polyurethane. These valves have functioned in artificial hearts for up to 62 days, and have been implanted in sheep for 1 year without evidence of thromboembolism. Our valves have a wide opening, using redundant leaflets that are "bistable." Accelerated testing by air jet provides 1,000 closures per second. Regurgitation is measured in an apparatus with the help of a competent valve. All polyurethanes change with age, but Silastic does not.

Animals↗

In vitro comparison of velocity profiles and turbulent shear distal to polyurethane trileaflet and pericardial prosthetic valves.

A comparative study of flow dynamics past biomer trileaflet valves and a pericardial bioprosthetic valve under steady and physiological pulsatile flow conditions in vitro is reported in this paper. The velocity profiles and the turbulent shear stresses distal to the valves were measured using laser Doppler anemometry. The authors' results showed that the velocity profiles distal to the trileaflet valves were similar to that measured distal to the pericardial valve. Higher magnitudes of absolute turbulent shear stresses were measured distal to the synthetic valves in comparison to the pericardial valves. However, when the stresses were nondimensionalized with respect to the orifice diameter at the inlet aspect, the stresses were comparable for all of the three valves. With design modifications to increase the orifice diameter at the inlet aspect of the polyurethane valves, the turbulent stresses distal to the valves can be minimized. Such in vitro studies on the flow dynamics past the polyurethane valves can provide information towards design changes to improve the performance characteristics of these valves. Polyurethane valves with flow characteristics comparable to the pericardial valves can be manufactured relatively inexpensively compared to mechanical or tissue valve prosthesis. Hence, the synthetic valves may be a viable alternative for short-term use in total artificial heart devices as a bridge to transplant.

Bioprosthesis↗

Development of the Philadelphia Heart System.

A new pneumatic artificial heart system has been developed. The design criteria have been to produce an integrated series of blood pumps and drive systems that would reduce blood trauma and reactivity, while incorporating industrial, mass-production techniques. The system attempts to reproduce the natural heart's pressure and flow waveforms and allows the prosthetic valves to be installed in a manner consistent with their design. The system's ventricles are constructed entirely of polyurethane by a combination of vacuum-forming and solution-casting techniques. The atrial cuffs and arterial grafts are permanently attached to the pumps and do not incorporate a quick connect system. The prosthetic valves are sewn into the inflow and outflow tracts using their clinical sewing rings. Besides eliminating the crevices normally found in quick connect systems, this method mounts the valves in an extremely compliant housing to increase shock absorption. The drive system produces a systolic air flow with a variable pressure rise (dP/dt) to reduce mitral valve closing velocity. This system has been implanted into 25 calves to date, of which 17 were chronic experiments. In 14 animals, St. Jude bileaflet valves were used and these animals had a mean survival of 39 days. Six of these animals survived over 30 days, with the longest being 129 days. All of the animals showed the characteristic postoperative drop in red blood cell count and hematocrit that returned to near preoperative values in about 3 weeks. The plasma free hemoglobin values generally remained below 5 mg/dl. The necropsies performed on several of the earlier animals revealed renal infarcts. However, in two of the later experiments, no kidney damage was found. The blood contacting surfaces of the atrial cuffs from the animals surviving over 100 days were covered with a fibroproliferative pseudoneointimal growth that extended from the sewing rings to the natural atrial tissue. Grossly, this appears to be the same type of tissue response seen when only a valve is implanted in a natural calf heart.

Animals↗

Hemodynamic and energetic assessment of calves implanted with a left ventricular assist device (LVAD).

Hemodynamic and ventricular energetic parameters were measured in calves implanted with the air driven Utah Ventricular Assist Device (UVAD). Uptake site was varied to determine the effect of control mode and vacuum augmentation of filing. Uptake was drawn solely from the left atrium or combined with a left ventricular apical vent. LVAD outflow returned to the descending, thoracic aorta. Control modes examined included asynchronous pumping as well as 1:1 and 1:2 synchronous diastolic counterpulsation. The 85cc LVAD, vacuum formed from PELLETHANE, was implanted acutely in four animals and chronically in six (7, 49 and 116 days paracorporeally, 1, 28 and 32 days intrathoracically). Instantaneous blood pressures, intramyocardial pressure, aortic outflow, oxygen consumption, LVAD output and drive parameters were recorded. LVAD output was independent of control mode when the natural heart rate was greater than or equal to 80 beats per minute. Intrathoracically positioned LVADs pumped a mean flow of approximately equal to 5 liters/min without vacuum augmentation of filling. Paracorporeally positioned LVADs pumped approximately equal to 3 liters/min mean flow without vacuum augmentation and up to approximately equal to 6 liters/min with 38 mm Hg of vacuum augmentation of filling. Instantaneous ascending aortic pressure and flow showed distinct beat-to-beat variation depending on LVAD control mode. Lower average ventricular afterload was observed when pumping the LVAD asynchronously or 1:2 synchronously. In one acute preparation, left ventricular myocardial oxygen consumption was reduced from the unassisted average control level by 37% for the asynchronous and 1:1 synchronous control modes with left atrial uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Predilution hemofiltration for the removal of protein bound antigens.

In cancer, tumor antigen (Ag) and the antigen-antibody immune complexes (IC) have been implicated with the inhibition of macrophage or lymphocyte function, interleukin generation and induction of suppressor cells and immunosuppressants. Plasma exchange depletes both Ag and antibodies (Ab) from the circulation. However, the Abs might be cytotoxic to cancer cells. Hence, a better treatment would be to remove the Ag without depleting the Abs. Such a procedure involves dissociation of Ag from Ab either by a change in pH of the plasma or by a hemodilution of the blood followed by removal of both the free and the dissociated Ag by ultrafiltration. The present work presents a theoretical analysis of the predilution hemofiltration system designed to remove the antigens which are weakly bound to proteins. A single pool model for the patient was assumed. The variables which effect the clearance of Ag are the protein binding constant (K), the extent of dilution of blood, the initial ratio between Ag and Ab concentrations. A computer simulation of the derived mass balance equations shows that the clearance of total Ag from the plasma pool decreases with (i) increase in the value of K, but it can be off set by increasing the extent of hemodilution, and (ii) decrease in initial Ag/Ab ratio, but this effect can be minimized by increasing the hemodilution fluid flow rate.

Antigens, Neoplasm↗

Comparative hematological data from animals implanted with a total artificial heart containing different valves.

A review of animals receiving a TAH with 4 mechanical valves suggests that the least damage to the blood cell components is associated with the BS valve when compared with the MH valve at similar heart rates. Clinical anemia in varying stages was observed in most animals in this study. However, most calves compensated for the increased rate of hemolysis and none required blood transfusions. The BS valve would appear to combine minimal turbulence and mechanical crushing in a physiological setting.

Animals↗