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Biomedical subjects

K L Dorrington

Publications and source records attributed to K L Dorrington.

At least 19 recordsLinked to original sources

Left ventricular regional function and relaxation: effects of inotropic stimulation.

The effects of increasing doses of two inotropes, isoproterenol and calcium chloride (CaCl2), on left ventricular regional myocardial function and isovolumic relaxation were studied in six anesthetized sheep. After baseline data, CaCl2 was given as intravenous boluses to yield doses of 10 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg, and 160 mg/kg. After a second series of baseline data were obtained, constant infusions of isoproterenol were begun with doses of 0.025 micrograms/kg/min, 0.05 micrograms/kg/min, 0.1 micrograms/kg/min, 0.2 micrograms/kg/min, and 0.4 micrograms/kg/min. During each stage of the protocol with both inotropes, data were recorded during acute constriction of the descending thoracic aorta. Left ventricular relaxation was assessed by analysis of peak negative left ventricular (LV) dP/dt and the time constant of isovolumic left ventricular relaxation (Trelax). Regional myocardial function showed little change in either apical or basal segments until high doses of the inotropes. Peak negative LV dP/dt significantly changed from baseline (775 +/- 60 mmHg/s) with 0.2 micrograms/kg/min (1780 +/- 400 mmHg/s, P < 0.05 v baseline) and 0.4 micrograms/kg/min (2,220 +/- 380 mmHg/s, P < 0.05 v baseline) of isoproterenol, and was unchanged by CaCl2. Trelax was significantly decreased by all doses of isoproterenol, whereas only one dose of CaCl2 decreased Trelax. Trelax was increased with afterloading and this effect was altered by isoproterenol. It is concluded that isoproterenol hastens, whereas CaCl2 does not alter, left ventricular relaxation. This may reflect beta-adrenergic modulation of calcium fluxes during isovolumic relaxation.

Animals

Femoral arteriovenous extracorporeal carbon dioxide elimination using low blood flow.

BACKGROUND AND METHODS: Conventional extracorporeal CO2 removal systems require blood flow rates of 1 to 2.5 L/min in the extracorporeal circuit. We hypothesized that standard hemofiltration equipment can be combined with a high-performance extracorporeal lung to achieve high rates of CO2 removal at lower blood flow rates. To test this hypothesis, we performed experiments on nine sheep to examine the extent to which CO2 elimination can be achieved at blood flow rates less than 600 mL/min using a 5-m2 hollow fiber membrane lung with countercurrent gas flow, combined with a hemofiltration blood pump, and connected to femoral arterial and venous hemodialysis catheters. RESULTS: CO2 eliminations of 130 to 180 mL/min at standard temperature and pressure were achieved with blood flow rates in the range 470 to 600 mL/min. With a pumpless artery-to-vein shunt, up to 90 mL/min of CO2 at standard temperature and pressure was eliminated. However, in this mode, the resistance of the access catheters and tubing was the main factor limiting CO2 elimination. CONCLUSIONS: Standard hemofiltration equipment may be combined with a hollow fiber membrane lung to remove the equivalent of a high proportion of the basal metabolic CO2 production of an adult human at low blood flow rates. Use of this technology would bring extracorporeal CO2 removal within the budget and capability of more ICUs.

Animals

Effect of potassium on ventilation in the rhesus monkey.

Increasing the concentration of arterial plasma K+ to 6-8 mM increased ventilation in two sedated analgesic-treated rhesus monkeys who had their end-tidal CO2 held constant during euoxia (arterial oxygen pressure, Pa,O2, ca 100 Torr) and hypoxia (Pa,O2, ca 40 Torr). During euoxia and hypoxia, hyperkalaemia increased ventilation up to 40 and 250%, respectively. This effect was reduced in euoxia and virtually abolished in hypoxia following an abrupt switch to 100% oxygen. Thus the ventilatory response of this primate to hyperkalaemia is at least as sensitive as that of the cat and if hypoxia is added the two stimuli generate a powerful drive to breathing.

Animals

Effect of a single inflation of the lungs on oxygenation during total extracorporeal carbon dioxide removal in experimental respiratory distress syndrome.

Respiratory distress syndrome (RDS) was modelled in rabbits using pulmonary lavage to remove surfactant. The stability of the resulting pressure-volume hysteresis of the lungs in vivo was studied with the aid of whole-body plethysmography during apnoeic oxygenation made possible by total extracorporeal carbon dioxide removal. Systemic oxygen delivery was measured as a function of the constant airway pressure during apnoea. In 6 subjects a single brief inflation of the lungs to 3.5 kPa resulted in a doubling of both expired lung volume (volume above functional residual capacity) and arterial oxygen partial pressure at an airway pressure of 0.65 kPa. These rises were well maintained for 40 min following the inflation. In a further 6 subjects with RDS single inflations permitted optimum systemic oxygen transport to occur at the low airway pressure of 0.3 kPa, similar to the optimum airway pressure in 6 healthy control subjects. Where pressure-volume hysteresis is present in RDS it can be exploited during apnoeic oxygenation, and probably during high frequency ventilation, to improve oxygenation by the use of infrequent single inflations of the lungs.

Animals

Effects of dopamine and domperidone on ventilation during isocapnic hypoxia in humans.

In order to investigate the role of dopamine in the ventilatory response to sustained, isocapnic hypoxia six subjects were studied three times in each of three pharmacological conditions: (1) in the absence of any drug administration, (2) during i.v. infusion of dopamine (3 micrograms.kg-1.min-1), and (3) after pretreatment with domperidone. Otherwise the experimental protocol was identical on each day and consisted of holding the subjects' end-tidal PO2 at 100 Torr for 10 min, then 50 Torr for 20 min and finally at 100 Torr again for 5 min. End-tidal PCO2 was held constant 2-3 Torr above normal throughout the experiment. Domperidone increased, and dopamine decreased the magnitudes of both the fast on- and off-responses, but neither drug affected the magnitude of the hypoxic ventilatory decline (HVD). The results of this study suggests: (1) that a peripheral dopaminergic mechanism is not involved in the genesis of HVD, and (2) the peripheral chemoreflex may be modulated peripherally to produce HVD.

Adult

A randomized comparison of total extracorporeal CO2 removal with conventional mechanical ventilation in experimental hyaline membrane disease.

Apnoeic oxygenation (AO) combined with extracorporeal CO2 removal (ECCO2R), using venovenous perfusion across a membrane area of 0.1 m2 has been shown to be feasible in six healthy anaesthetized rabbits. In a further twelve rabbits, ECCO2R has been randomly compared with conventional mechanical ventilation (CMV) following saline lavage to induce respiratory failure. Blood gases were maintained for up to 6 h within the same range (PaO2 = 8-20 kPa, PaCO2 = 4-6 kPa) in two groups of six by varying airway pressures and the oxygen fraction delivered either to the membrane lung (ECCO2R group) or to the ventilator (CMV group). The influence of single hourly sustained inflations (SI) on oxygenation was studied. ECCO2R subjects remained stable and survived. CMV subjects deteriorated and had 80% mortality. Hyaline membranes were absent from ECCO2R subjects and present in all CMV subjects. The response to SI suggests that a lung volume recruitment is maintained during AO for up to 1 h but is ineffective during CMV.

Animals

Haemolysis during in vitro CO2 removal from human blood using a membrane lung.

Haemolysis of human blood has been examined in vitro as a function of pH in the range 7.2-8.0. The hydrogen ion concentration of freshly donated blood from 11 donors was manipulated in 42 experiments, entirely by altering the carbon dioxide fraction of air with which the blood was equilibrated using a membrane lung. In contrast to the known alkalaemic haemolysis which occurs in canine blood, we observed no correlation between plasma haemoglobin concentrations and blood pH. We conclude that alkalaemic haemolysis is unlikely to complicate the clinical application of extracorporeal carbon dioxide removal in the management of acute respiratory failure.

Acid-Base Equilibrium

Peak airway pressure during high frequency jet ventilation: theory and measurement.

A mathematical model has been developed to predict the peak airway pressure attainable during jet ventilation. The theory assumes inviscid and incompressible flow and agrees closely with experimental results using bench models of simple jet systems and systems using a tracheal tube designed for jet ventilation. The results of a previous published study also show good agreement with the predicted results.

High-Frequency Jet Ventilation

Rebreathing during spontaneous and controlled ventilation with T-piece breathing systems: a general solution.

A general solution is presented to the problem of finding the degree of rebreathing generated by T-piece breathing systems. The solution is applicable to any ventilatory waveform, dead space volume and tidal volume and is identical for spontaneous and controlled ventilation for any given ventilatory waveform. The method is graphical and its use and understanding require no mathematical skills. However, if an analytical form of the ventilatory waveform is known, the method is easily extended by use of calculus to obtain a precise analytical solution.

Humans

Anticoagulation by ancrod for carbon dioxide removal by extracorporeal membrane lung in the dog.

Ten dogs were subjected to defibrinogenation with an intravenous perfusion of ancrod (1 unit/kg) (Arvin, Knoll AG, Ludwigshafen, Federal Republic of Germany) over a 2 1/2 hour period. Six of them were subjected to extracorporeal elimination of carbon dioxide with a polypropylene membrane lung by means of veno-venous bypass. The remaining four dogs did not undergo extracorporeal circulation and served as control subjects. In both groups, ancrod administration itself resulted in a marked drop in alpha 2-antiplasmin (33% and 67%, respectively, of the baseline values) and in slight but significant decreases in factor II and plasminogen activities of 25% and 20%, respectively (p less than 0.05), in the group subjected to carbon dioxide removal. There were no significant changes in platelet number or factor V and antithrombin III activities. During the 6-hour bypass period, platelet count and antithrombin III and factor II and V levels decreased significantly. No bleeding was observed. Histologic examination of lung biopsy tissue showed no pathologic features. Analysis of the membrane of the artificial lungs revealed no fibrin deposits. In the control group, except for a drop in alpha 2-antiplasmin levels (54%), no significant changes in hemostatic parameters occurred during the corresponding 6 hours. We conclude that, despite the drop in coagulation factors and in alpha 2-antiplasmin activity during bypass, ancrod can be considered as a valuable alternative anticoagulant for extracorporeal carbon dioxide removal.

Ancrod

Physiological profile during venovenous perfusion in dogs using a polypropylene membrane lung with secondary flows.

Venovenous perfusion has been conducted in 12 healthy dogs to examine carbon dioxide (CO2) transfer and haemocompatibility over 9 h during total extracorporeal CO2 removal using a microporous polypropylene membrane lung with secondary flows in the blood channel. The anaesthetized animals were maintained normocapnic by including CO2 in the inspired gases. The CO2 removal was achieved using 0.631 m2 of active membrane, at a pulsatile Reynolds number of 50, and a CO2 extraction from blood of 17.8 ml (STP) dl-1. Gas exchange remained constant during the perfusions. Several aspects of our results suggest that the haemocompatibility of a system of the kind used here is at least as favourable as that of a steady flow device using a continuous silicone rubber membrane of equivalent gas transfer capability.

Animals

Minimum fresh gas flow requirements of anaesthetic breathing systems during spontaneous ventilation: a graphical approach.

A general solution is presented to the problem of finding the minimum fresh gas flow requirements, during spontaneous ventilation, of anaesthetic breathing systems in the Mapleson classification. The solution is applicable to any pattern of breathing, dead space volume and tidal volume. The method is graphical and its use and understanding require no mathematical skills. However, if an analytical form of the respiratory waveform is known, the method is easily extended by use of calculus to obtain a precise analytical solution.

Anesthesia, Inhalation

Extracorporeal oxygen and CO2 transfer of a polypropylene dimpled membrane lung with variable secondary flows: partial bypass in the dog.

In vivo gas transfer performance, during veno-venous bypass, is presented for one form of the Oxford membrane lung in which vortex mixing is induced in blood flow across a dimpled polypropylene membrane. Good agreement has been found with in vitro data presented in an earlier paper. Two experiments were extended to attain total extracorporeal CO2 removal with apnoeic diffusion oxygenation to motionless lungs. Measurements of arterial oxygen partial pressure during apnoea suggest that the time-constant for equilibration of alveolar nitrogen partial pressure with that on the gas side of the membrane lung is of the order of 100 min.

Animals

Oxygen and CO2 transfer of a polypropylene dimpled membrane lung with variable secondary flows.

Gas transfer performance is presented for one form of the Oxford membrane lung in which vortex mixing is induced in blood flow across a dimpled polypropylene membrane. Dimensional analysis has been used to define the parameters characterizing mass transfer in the device, and of three fluid mechanical parameters: Reynolds number based on peak pulsation velocity, Strouhal number, and ratio of mean to oscillatory flows, only the first has been found to affect mass transfer significantly in the ranges studied. For oxygenation, rated flows in excess of 5 l min-1 m-2 are measured. A new definition is presented for a rated flow for extracorporeal CO2 removal and values in excess of 1.2 l min-1 m-2 are obtained.

Animals

Splitting ratio.

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Gases