[Physiopathology and biochemistry in the acute respiratory distress syndrome--animal experiment studies].
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Biomedical subjects
Publications and source records attributed to M Meyer.
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The determination of pulmonary capillary blood flow (Q), diffusing capacity (D) and tissue volume (Vtis) from rebreathing equilibration kinetics is studied on mathematical models. The validity of a continuously ventilated two-compartment model (model II) is analyzed with reference to a cyclically ventilated model (model III) and compared to a one-compartment model (model I). Use of model II leads to slight overestimation of Q and D, and to underestimation of Vtis whereas model I yields considerable underestimation of D, Q and Vtis. The following procedures are recommended: (1) Rebreathing data should be analyzed on the basis of model II. (2) Q and D should be calculated from the rate constant of fast (k1) and slow (k2) exponential component and extrapolated zero-time intercept of K2, based on end-expired gas fractions, of the gas under study (e.g. C2H2, CO). (3) Addition of an insoluble inert gas (e.g. He) is required only for Vtis. (4) Soluble inert gases with blood-gas partition coefficient (lambda) less than 1 (e.g. C2H2, CHC1F2) applied at low concentration should be used for determination of Q and Vtis. (5) A high rebreathing ventilation is recommended.
We have reinvestigated the problem of blood-gas equilibration of CO2 in lungs during hypercapnia. Six dogs with chronic tracheostomy and exteriorized carotid artery were subjected in acute experiments to hypercapnic inspired mixtures [CO2 fraction of expired gas (FICO2) = 0.06; 0.08; 0.10]. Expired CO2 partial pressure (PCO2) was continuously measured with a respiratory mass spectrometer and compared with arterial PCO2 determined in blood samples that were collected during apparent steady-state conditions. Particular care was taken in using continuously recorded temperature in the right heart for correction of blood PCO2 measured by CO2 electrodes. In no animal was there a significant difference between arterial and alveolar PCO2. On the average, this difference was -0.1 Torr at FICO2 = 0.06; 0.0 Torr at FICO2 = 0.08, and -0.2 Torr at FICO2 = 0.10. The results are in agreement with the conventional view that PCO2 in pulmonary capillary blood approaches PCO2 in alveolar gas.
Treatment of human blood platelets with the thiol-oxidizing agent, diamide, causes rapid oxidation of glutathione and alterations in aggregation and release reaction. Moreover, cross-linking of proteins was observed. Three high molecular weight bands of 200 - 240 X 10(3) daltons and a band of 66 X 10(3) daltons were involved in this process. After reduction with dithiotreitol the normal pattern was received. In contrast to the erythrocyte, the cross-linking of platelet proteins was not accompanied by a reorientation of phosphatidylethanolamine in the membrane. Also a considerably smaller effect of diamide on platelet protein sulfhydryl group content was measured.
A patient with Glanzmann's thrombasthenia has been analysed by high resolution two-dimensional polyacrylamide gel electrophoresis and crossed immunoelectrophoresis. Although clot retraction is subnormal, glycoproteins IIb and IIIa are completely absent and platelet fibrinogen is strongly reduced indicating an unusual subtype of type II thrombasthenia. No changes in the pI of glycoproteins have been observed. Heterogeneity in Glanzmann's thrombasthenia is discussed.
An acute pancreatitis was observed in 2 children belonging to two unrelated families in which a total of 8 kindreds also had pancreatitis. Evolution was so severe that it demanded parenteral feeding and partial pancreatectomy with Wirsung-intestinal shunting. The authors stress: the rarity of this condition (which has a dominant autosomal transmission), the lack of specificity, the severity in which pseudocysts predominate, the further occurrence of both diabetes and external pancreatic deficiency and finally, the risk of pancreatic carcinoma.
Fifteen patients with internuclear ophthalmoplegia (INO) were examined by simultaneous electro-oculography of each eye. In 11 patients the INO was bilateral and in 4 patients unilateral. In 6 of the bilateral cases, the INO was asymmetric. A classic presentation of the INO was shown by only 2 patients. The rest had additional disorders of eye mobility (INO plus). The high percentage of additional affections, which were not often clinically apparent, consisted of slowing of abduction (45%), impairment of vertical movements (80%) and convergence (30%), and dysmetric overshoot of the abducing eye (65%). Impairment of vertical movements were combined in 3 patients with unilateral INO. Isolated downward vertical gaze paresis was found in 4 patients. Thus an investigation by quantitative methods demonstrates the very rare occurrence of isolated lesions of the medial longitudinal fascicle (MLF). Affections of the MLF mostly are combined with lesions of the surrounding reticular formation and therefore with additional optomotoric defects.
Thermally isolated dog gastrocnemii were stimulated to exhaustion by rhythmic isotonic tetani of 0.2s duration (30 min-1) in complete occlusion of blood flow. Total enthalpy change, H = heat + work, work output, w, (kJ . kg-1) and average mechanical efficiency over the working period, n = w/H, were determined from deep muscle temperature increase and amount of shortening, and lactate produced, La, (mol . kg-1) from washout curves, respectively. Under these conditions H is the sum of the enthalpies due to a) alactic sources (Hal), i.e., net approximately P depletion and muscle O2 stores utilization, and b) formation: H = Hal + "delta HLa" . La. Thus, as "delta HLa", the molar enthalpy of La formation, amounts to 76 kJ . mol-1, Hal could be calculated. It was observed that: i) n ranged from 0.2-0.5 and was higher the lower H, this inverse relationship being essentially due to the dependence of n on Hal as described by: Hal = Ho . 10-kn + a (where Ho = 9.3, k = 3.7 and a = 0.15), and ii) the shortening speed of the first few tetani (vi, mm . s-1), was directly related to Hal as described by: vi = 63.3 + 30.7 Hal. Hal is essentially proportional to the approximately P content of resting muscle. These findings suggest therefore that the efficiency of contraction and the shortening speed are both affected by the approximately P concentration, the efficiency increasing, and the speed decreasing with decreasing approximately P.
The effect of positive end-expiratory pressure on a value resulting in maximum static effective compliance was studied in 13 artificially ventilated patients suffering from adult respiratory distress syndrome. Applying positive end-expiratory pressure in this manner resulted in improvement of oxygen delivery and left ventricular stroke work. In the patients with high venous admixture under zero end-expiratory pressure cardiac output increased but in those with moderate pre-existing venous admixture cardiac output decreased. We conclude that the response to positive end-expiratory pressure depends on the importance of the venous admixture. Artificial ventilation with positive end-expiratory pressure on a level resulting in maximum static effective compliance is indicated in cases with high venous admixture.
Vitamin D3 deficient (D-) mice show a depressed inflammatory response and both inflammatory peritoneal macrophages and bone marrow polymorphonuclear leukocytes of D- mice exhibit a decreased spontaneous migration under agarose. The impaired phagocytic response of peritoneal macrophages from D- mice can be corrected by incubation with 1,25-dihydroxyvitamin D3 and is not affected by interaction with other vitamin D3 metabolites. Transfer of mice from the D- to the D+ state results in correction of both the inflammatory and the phagocytic response. Intactness of phagocyte function is thus directly dependent on vitamin D3 metabolism.
A computer-assisted method is described which allows the non-invasive measurement of excitability and conduction velocity during the relative refractory period of alpha motor fibres in peripheral nerves. The method is based on a collision technique combined with a correlation analysis of the compound muscle potential. Using this procedure, the recovery in excitability and conduction velocity succeeding the absolute refractory period was measured in 13 normal subjects. In all subjects a period of subnormal conduction followed by a period of supernormal conduction was observed. The first fibres recovered at a mean of 0.75 +/- 0.07 msec; the last fibres recovered 1.3 +/- 0.3 msec. The period of subnormal conduction for a 100 mm conditioned conduction path length had a mean of 1.87 msec. When the period of subnormal conduction was plotted as a function of the conditioned nerve section, a linear section was observed. Stimulus intensity influenced the recovery in excitability but not the subnormal period. Temperature was found to affect both the excitability and subnormal period.
The efficacy of cerebral revascularization by a superficial temporal-middle cerebral artery anastomosis done 4 and 24 hours following combined occlusion of the middle cerebral and internal carotid arteries (MCA/ICA) was tested in 15 dogs. An untreated and a sham-operated group of 8 and 5 dogs, respectively, controlled possible intercurrent variables. Regional cerebral blood flow (rCBF) was measured by the hydrogen clearance method. Values of normal and preocclusion blood flow under basal conditions and following inhalation of 5% CO2 were similar to values reported by other researchers. Combined MCA/ICA occlusion produced a significant drop in rCBF in the ipsilateral hemisphere (p less than 0.01). The rCBF returned to normal following revascularization in 4 and 24 hours, and after the sham procedure. The rCBF response to inhalation of 5% CO2 was normal in the revascularized group, but was reversed (p less than 0.01) in the sham group. The reversal of flow in the sham group suggested that loss of cerebral autoregulation and steal of blood flow in the infarcted area occurred.
Pulmonary diffusing capacity for CO (DCO) was measured in human subjects at various CO concentrations using a rebreathing procedure. Two stable CO isotopes, 12C18O and 13C18O, were used. These isotopes could be simultaneously and continuously recorded by a respiratory mass spectrometer. For 13C18O the initial concentration in the rebreathing bag was constant at 0.00016, whereas it was varied for 12C18O from 0 to 0.00224. DCO was calculated for both isotopes. In five normal subjects, both D12C18O and D13C18O were independent of the rebreathing CO concentration, with mean values of 31.0 and 30.2 ml . min-1 . Torr-1, respectively. These results, which are at variance with those of Mendoza et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 43: 880-884, 1977), are compatible with the assumption that diffusion is the sole mechanism of alveolocapillary CO transport; in particular, there is no evidence for facilitated transport.
Pulmonary diffusion capacity (D) for O2 and CO was determined from alveolar-mixed venous equilibration kinetics of 16O2, 18O2, and C18O measured during rebreathing by mass spectrometry. During the rebreathing maneuver (15 s) the ventilation was extremely high (about 100 1 X min-1) and PO2 and PCO2 in lung gas were close to their mixed venous values (aveolar hypoxia and hypercapnia). The following mean values (+/- SD) were found in six healthy males (20-33 yr) sitting on a bicycle ergometer (in ml X min-1 X Torr-1): 1) without work load, D18O2 = 54 +/- 10, Dc18O = 47 +/- 11; 2) with the highest work load tested (150 W, O2 uptake 2.1 l X min-1), D18O2 = 62 +/- 12, Dc18O = 54 +/- 8. The ratio D16O2/D18O2 averaged 1.07. The ratio D18O2/Dc18O, averaging 1.2 at rest and at all exercise levels, was close to the estimated O2/CO ratio of Krogh's diffusion constants for tissue and, therefore, was in agreement with the diffusion limitation model. An analysis of the various factors affecting the DO2/DCO ratio does not allow to reliably assess the role of diffusion in red blood cells and reaction with hemoglobin in limiting alveolar-capillary O2 transfer.
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Disturbed water balance at the alveolo-capillary membrane resulting in decreased pulmonary compliance is one of the functional characteristics in the Adult Respiratory Distress Syndrome (ARDS). In artificially ventilated LEWE Mini Pigs repeated pulmonary lavage was performed. The aim was to produce a state like ARDS by affecting the lung alveolar surfactant system which is included into the sum of factors which are responsible for the normal water balance of the alveolo-capillary membrane. This condition was supposed to be maximized if the lung compliance reached its lowest value after pulmonary lavage. Regarding this the pathophysiologic changes in this ARDS model were characterized by increased airway resistance and dead space ventilation as well as decreased arterial oxygenation. Severe ventilation perfusion abnormality was represented hemodynamically by the increased pulmonary vascular resistance and the decreased pulmonary non-shunt blood flow. The morphological (macroscopic, light-and electronmicroscopic) changes indicate strongly that in this type of ARDS model all functional compartments of the alveolocapillary membrane are severely affected. Decreased colloid osmotic pressure of blood plasma samples underlines the severity of changes in the water balance at the alveolo-capillary membrane in this type of lung injury.