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Human pulmonary vascular responses to hypoxia and hypercapnia.
The ability of alveolar gas composition to influence pulmonary vascular tone has been appreciated for over 50 years. In particular, it has been proposed that both O2 and CO2 could play a role in the matching of perfusion to ventilation within the lung, improving the overall efficiency of gas exchange. A wide variety of experimental approaches has been used to investigate pulmonary vascular effects of the respiratory gases in a range of mammalian species. In this article, we review experiments performed in healthy humans, identify particular difficulties in the interpretation of such experiments, and discuss possible approaches to future study.
Inhibition of nitric oxide synthesis augments pulmonary oedema in isolated perfused rabbit lung.
The role of nitric oxide (NO) in precipitating pulmonary oedema in acute lung injury remains unclear. We have investigated the mechanism of involvement of NO in the maintenance of liquid balance in the isolated rabbit lung. Thirty pairs of lungs were perfused with colloid for up to 6 h, during which pulmonary vascular resistance (PVR) and capillary pressure (PCP) were measured frequently, and time to gain 5 g in weight (t5) was recorded. Four protocols with different perfusate additives were studied: (i) none (control, n = 11); (ii) 10 mmol NG-nitro-L-arginine methyl ester (L-NAME) (n = 6); (iii) 10 mmol L-NAME with 100 mumol lodoxamide, an inhibitor of mast cell degranulation (n = 7); (iv) 10 mmol L-NAME with 10 mumol 8-bromo-3',5'-cyclic guanosine monophosphate (8Br-cGMP), an analogue of cGMP that may reduce vascular permeability by relaxing contractile elements in endothelial cells (n = 6). Neither PVR nor PCP differed between protocols. L-NAME markedly reduced t5 from 248 (27) min (mean (SEM)) in protocol (i) to 144 (5) min in protocol (ii) (P < 0.05). Both lodoxamide (t5 = 178 (7) min) and 8Br-cGMP (t5 = 204 (10) min) substantially corrected the effect of L-NAME (P < 0.005). Results suggest that maintenance of a low permeability by NO may involve mast cell stabilization and endothelial cell relaxation.
Effect of lung inflation on active and passive liquid clearance from in vivo rabbit lung.
Active sodium transport contributes to liquid clearance from the alveoli. We hypothesized that the magnitude of active transport of alveolar liquid depends on the extent to which the alveolar epithelium is stretched and, consequently, on the degree of alveolar inflation. In a study on 38 adult rabbits, the left lung was filled in vivo with a solution of glucose (10 mmol/l) made isosmotic with plasma, using sodium chloride, and held at a constant airway pressure of 3, 6, or 9 cmH2O for 6 h. Alveolar liquid clearance was measured directly as a flow into a left main bronchial catheter. Control animals were compared with animals in which active epithelial sodium transport was inhibited by adding amiloride and phloridzin (both 1 mmol/l) to the instillate. At low inflation, active sodium transport reversed a secretion of liquid into the alveoli; at high inflation, active sodium transport made little or no contribution to transepithelial flow. Hydraulic conductance of the left lung was 1.57 microliters.min-1.cmH2O-1.kg body wt-1. The experiments suggest that pulmonary inflation renders active liquid clearance ineffective.
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.
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.
Asystole with convulsion following a subanesthetic dose of propofol plus fentanyl.
A case is presented in which asystole and convulsions occurred after an attempted induction of anaesthesia with propofol and fentanyl. The case suggests that a history of syncope may be associated with unusual susceptibility to the bradycardic effects of propofol.
Cardiac sympathetic nerve stimulation enhances cardiovascular performance during hyperkalaemia in the anaesthetized pig.
A rapid increase in arterial plasma potassium concentration to values seen during intense exercise depresses cardiac function at rest. Increasing the cardiac concentration of noradrenaline by right-sided sympathetic stimulation in eleven anaesthetized pigs significantly augmented cardiovascular performance during hyperkalaemia, while electrical pacing of the right atrium at equivalent rates to sympathetic stimulation afforded no protection against the deleterious effects of hyperkalaemia. We conclude that the inotropic effect of sympathetic activation may be important in sustaining cardiac function during exercise-induced hyperkalaemia.
Intense slow hypoxic pulmonary vasoconstriction in gas-filled and liquid-filled lungs: an in vivo study in the rabbit.
To examine the hypothesis that hypoxic pulmonary vasoconstriction may have a slower time course and greater intensity than is currently recognized, experiments were conducted in twelve anaesthetized rabbits subjected to unilateral lung hypoxia for 6 h. Endobronchial cannulation was used to maintain apnoea of one lung at constant airway pressure whilst inflating the lung with nitrogen or liquid. The second lung was ventilated with oxygen to maintain normocapnia and oxygen transfer. A pulmonary ventilated with oxygen to maintain normocapnia and oxygen transfer. A pulmonary artery catheter was introduced non-invasively. Pulmonary shunt was derived from mixed venous and arterial blood gas parameters. Pulmonary artery pressure was monitored continuously and cardiac output was estimated from oxygen uptake measurements before and after 6 h unilateral hypoxia. The experiments show that a rapid phase of hypoxic pulmonary vasoconstriction is followed by a slow phase which develops over hours. The slow phase is associated with a massive blood flow diversion from the hypoxic lung, such that pulmonary shunt after 6 h unilateral hypoxia is indistinguishable from baseline shunt during bilateral ventilation with oxygen. The response is reversible, but with a similarly slow time course. Results from nitrogen and liquid filling of the lung are similar. These findings are consistent with early experiments by Dirken and Heemstra in 1948 (Quart F Exp Physiol 34, 193-211), and challenge the prevailing notion that hypoxic pulmonary vasoconstriction is always a rapid and relatively weak physiological response to hypoxia.
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.
Active transport in the alveolar epithelium of the adult lung: vestigial or vital?
Active secretion by mammalian fetal pulmonary alveolar epithelium is well recognized, as is the role of the adult epithelium in the secretion of surfactant. Recent studies have demonstrated active absorption by adult epithelium involving two sodium-dependent pathways. This finding has focused attention on how poorly we understand both the disposition of alveolar liquid and the physiological role of surfactant. In this paper we review the evidence that the adult mammalian alveolar epithelium absorbs solutes by active transport, and we assess the physiological importance of the resulting liquid movements.
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.