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Biomedical subjects

P A Drinker

Publications and source records attributed to P A Drinker.

At least 19 recordsLinked to original sources

Bioreactor based on suspended particles of immobilized enzyme.

A bioreactor for blood detoxification was developed in which oscillation-induced secondary flows suspend particles of immobilized enzyme in a reactor operating at clinically useful flowrates. Torsional oscillation of the reactor about its axis created a pair of counterrotating toroidal vortices which were readily observed in flow-visualization studies. Oscillation frequencies were selected to provide spatially uniform particle dispersion, as assessed visually. As a model system, blood deheparinization by reactors containing heparinase immobilized to agarose particles was investigated. Identical deheparinization profiles were observed in the continuous-flow reactor and in independent batch studies, done in well mixed test tubes of blood, demonstrating that the oscillating reactor design minimizes external mass transfer limitations. Identical heparin neutralization profiles and rates were also observed in the first and the second of consecutive heparin neutralization studies (0-2 h and 2-4 h, respectively) demonstrating an effective half-life of the immobilized enzyme in the oscillating reactor of at least 4 h. No significant decrease in red or white blood cell count, platelet count, or hematocrit, and clinically acceptable levels of plasma hemoglobin and activated complement were observed with 2 h (20 passes) of in vitro recirculation of human blood through the reactor. High, stable efficacy, operational stability, and excellent biocompatibility are attributed to secondary flow induced liquid-particle mixing within the oscillating reactor.

Biocompatible Materials↗

Forceful pulsatile local infusion of enzyme accelerates thrombolysis: in vivo evaluation of a new delivery system.

Forceful local pulsatile infusion of fibrinolytic enzyme disrupts thrombi, increases clot surface area, and thereby hastens enzyme action compared with conventional constant infusion methods, which are time consuming and therefore expensive. Prolonged thrombolytic therapy is associated with increased patient morbidity. A prototype for a clinically applicable pulsatile jet infusion system for accelerating thrombolysis was designed. The system is adaptable to standard angiographic catheters and techniques. The core of the system is a reciprocating syringe pump that delivers small volumes of thrombolytic enzyme in short, rapid, frequent pulses at high exit-jet velocity through any side-hole catheter (the smallest used was a 3-F catheter). Comparison of this system with a constant infusion system was made in vivo in a 48-hour-old thrombus model in rabbit inferior vena cava (IVC). One hour of lysis by streptokinase was conducted with each of the methods. In the first experiment, the IVC thrombi were left intact before chemical lysis. Pulsatile infusion lysed 61% of the thrombus by weight in an hour, whereas constant infusion lysed only 15% (P less than .001). In the second experiment, IVC thrombi were subjected initially to standardized mechanical perturbation by a guide wire before chemical lysis. In the latter experiment, pulsatile infusion lysed 54% of the thrombus by weight, and constant infusion lysed only 26% (P less than .005). The difference in percentage of lysis by weight between pulsatile infusion groups in the two experiments (61% vs 54%) was not significant (P greater than .1). The same was true of the difference between the two constant infusion groups (26% vs 15%, P greater than .05). The effect of initial perturbation of the thrombus by a guide wire appears to be less important than the thrombus disruption and accelerated thrombolysis caused by the pulsatile delivery system. No angiographic or macroscopically visible damage was seen in any IVC. Accelerated thrombolysis may reduce the expense, duration, and morbidity associated with conventional constant infusion methods.

Animals↗

Tidal volume and frequency dependence of carbon dioxide elimination by high-frequency ventilation.

Six patients with chronic respiratory failure received mechanical ventilation with tidal volumes less than or equal to the dead-space volume, at frequencies of 30 to 900 breaths per minute. The rate of elimination of carbon dioxide from the ventilator system during a brief trial of high-frequency ventilation accurately predicted the long-term effectiveness of a given combination of frequency and tidal volume. Below frequencies of about 200 breaths per minute, the volume of carbon dioxide eliminated from these patients was most strongly related to the product of frequency and tidal volume; at higher frequencies, carbon dioxide elimination was determined by the tidal volume and was independent of frequency. These results suggest that although the effectiveness of high-frequency ventilation is primarily a function of the product of tidal volume and frequency, above a critical frequency the mechanical characteristics of the lung reduce gas transport by limiting the volume transmitted to the periphery of the lung.

Adolescent↗

Shear-induced augmentation of oxygen transfer in blood.

An experimental study was performed to determine the extent of shear-induced augmentation of oxygen diffusion in blood. The results were obtained using whole human blood in laminar flow through semipermeable membrane tubes. Transfer enchancement in whole blood was found to be dependent on the fluid shear rate and the hemoglobin saturation level. Very little agumentation was observed in saturated blood for shear rates up to 2500 s-1. However, with partially unsaturated blood, oxygen transfer was increased up to 250 percent at the higher shear rates. The implications for modeling oxygen transfer in blood are discussed.

Erythrocytes↗

Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study.

Nine medical centers collaborated in a prospective randomized study to evaluate prolonged extracorporeal membrane oxygenation (ECMO) as a therapy for severe acute respiratory failure (ARF). Ninety adult patients were selected by common criteria of arterial hypoxemia and treated with either conventional mechanical ventilation (48 patients) or mechanical ventilation supplemented with partial venoarterial bypass (42 patients). Four patients in each group survived. The majority of patients suffered acute bacterial or viral pneumonia (57%). All nine patients with pulmonary embolism and six patients with posttraumatic acute respiratory failure died. The majority of patients died of progressive reduction of transpulmonary gas exchange and decreased compliance due to diffuse pulmonary inflammation, necrosis, and fibrosis. We conclude that ECMO can support respiratory gas exchange but did not increase the probability of long-term survival in patients with severe ARF.

Acute Disease↗

Engineering aspects of ECMO technology.

The primary areas of extracorporeal membrane oxygenation (ECMO) technology with engineering components are: biomaterials, oxygenator design, ECMO physiology and total system design. The evolution of ECMO has been largely empirical, with many innovations introduced directly from clinical experience and observation. Major advances are needed in both materials ans oxygenator design if current hematologic hazards are to be reduced. Optimization of ECMO systems has not been attempted in any systematic way because the basic physiology is not well enough understood to define the rationales for optimum control and management strategies. Once these strategies have been developed and tested, currently available automation technology can be applied to make the ECMO system system simpler and safer for clinical use.

Engineering↗

Retrograde aortic perfusion by partial cardiopulmonary bypass: effect of mixing on measured arterial oxygen tension.

Partial venoarterial bypass with return of oxygenated blood to the femoral artery can produce mixing in the aorta of the blood from the oxygenator and left ventricular sources at flow rates of less than 50% of the total body flow. This was observed in six anesthetized sheep with normal lungs maintained on controlled ventilation on partial cardiopulmonary (venoarterial) bypass. The evidence of mixing increases with the extracorporeal flow rate, reaching the aortic arch in a majority of cases at the higher rates. Management of bypass and the interpretation of its effects depend on definite knowledge of the presence or absence of mixing. Partial bypass will raise the arterial oxygen tension (Pao-2) of the blood continuing to flow through the lungs. This effect is independent of mixing (Pao-2) and may be related either to the addition of oxygen to the blood or to an enhanced pulmonary ventilation-perfusion relationship.

Animals↗

The physician, the manufacturer, and medical devices.

Better communication between physicians and manufacturers of medical devices is becoming increasingly important due to wider usage of these devices, as well as more intense scrutiny by consumer interest groups. Physicians should therefore have more complete knowledge of techniques of new product development. A new product typically passes through at least six stages, as follows: (1) idea conception; (2) merit and feasibility study; (3) design and testing; (4) production preparation; (5) market preparation; and (6) marketing. These steps are completed over a period of several years at an ever increasing cost. We propose that interaction procedures be undertaken so as to enhance direct physician-manufacturer communications in the medical device arena. Some possible techniques of improving these communications include the direct training of physicians and manufacturers in each other's problems, the establishment of hospital engineering groups, the placement of medical consultants in industry, and the active participation in device standards-generating groups and other groups of mutual interest.

Biomedical Engineering↗

Pulmonary insufficiency induced by oleic acid in the sheep: a model for investigation of extracorporeal oxygenation.

Most previous studies of the efficiency of bypass techniques for respiratory support have been conducted in hypoxic but otherwise normal animals. However, mechanisms of improved oxygenation by partial venoarterial bypass in the presence of acute respiratory insufficiency can be better studied with an appropriate pathophysiologic model; for this purpose, acute hemorrhagic pulmonary edema was induced in sheep by injection of oleic acid into the right atrium. The model presented a 3 hour period of elevated pulmonary shunting with stable hemodynamics. This preparation is being employed to the study of the mechanisms of extracorporeal oxygenation.

Animals↗