Calcium metabolism and the diastolic rigidity status of the myocardium in patients with ischemic heart disease under the influence of calcium antagonist treatment]

The calcium (Ca2+) metabolism disorder in IHD patients which manifests itself in an increase of blood serum content of ionized Ca2+ and its accumulation in red blood cells and in cardiomyocytes is accompanied by myocardial functional disturbances as an increase in myocardial stiffness. The increase both of ionized Ca2+ content in blood plasma and left ventricular rigidity are prerequisites for the antianginal effect of corinfar. Normalization of Ca2+ content in blood plasma by corinfar can serve as a criterion of therapy efficiency of IHD patients.     

Effects of altitude and exercise on pulmonary capillary integrity: evidence for subclinical high-altitude pulmonary edema.

Strenuous exercise may be a significant contributing factor for development of high-altitude pulmonary edema, particularly at low or moderate altitudes. Thus we investigated the effects of heavy cycle ergometer exercise (90% maximal effort) under hypoxic conditions in which the combined effects of a marked increase in pulmonary blood flow and nonuniform hypoxic pulmonary vasoconstriction could add significantly to augment the mechanical stress on the pulmonary microcirculation. We postulated that intense exercise at altitude would result in an augmented permeability edema. We recruited eight endurance athletes and examined their bronchoalveolar lavage fluid (BALF) for red blood cells (RBCs), protein, inflammatory cells, and soluble mediators at 2 and 26 h after intense exercise under normoxic and hypoxic conditions. After heavy exercise, under all conditions, the athletes developed a permeability edema with high BALF RBC and protein concentrations in the absence of inflammation. We found that exercise at altitude (3,810 m) caused significantly greater leakage of RBCs [9.2 (SD 3.1)x10(4) cells/ml] into the alveolar space than that seen with normoxic exercise [5.4 (SD 1.2)x10(4) cells/ml]. At altitude, the 26-h postexercise BALF revealed significantly higher RBC and protein concentrations, suggesting an ongoing capillary leak. Interestingly, the BALF profiles following exercise at altitude are similar to that of early high-altitude pulmonary edema. These findings suggest that pulmonary capillary disruption occurs with intense exercise in healthy humans and that hypoxia augments the mechanical stresses on the pulmonary microcirculation.     

Mechanism and time periods of the development of hyaline membranes in acute respiratory failure of traumatic origin

The model of chest trauma accompanied by acute respiratory failure was studied on 78 guinea-pigs. Histological and electron microscopic methods have revealed a typical pattern of shock lung: combination of diffuse bilateral microfocal distelectases and microcirculation disturbances, i.e. pulmonary venular spasm accompanied by sludge, disseminated intravascular coagulation, focal hemorrhages and interstitial edema. In 5 out of 13 cases 72 hours later hyaline membranes were observed as conglomerations of eosinophilic masses of plate form, distinct from intraalveolar edema. At the ultrastructural level hyaline membranes could be identified as stripes of granular or fibrillar accumulations containing cellular organella debris, ajacent to alveolar walls.     

Nitric oxide scavenging by hemoglobin regulates hypoxic pulmonary vasoconstriction

Although the importance of red blood cells in augmenting hypoxic pulmonary vasoconstriction has been recognized for decades, only recently has it become clear that this occurs primarily because of the inactivation of nitric oxide (NO) by hemoglobin. This interaction between red blood cells, NO, and the pulmonary circulation is critical in understanding the effects of anemia and polycythemia on pulmonary blood flow distribution, gas exchange, and global O2 delivery and in understanding the development of hemoglobin-based oxygen carriers. This review will discuss the proposed mechanisms for initiation of hypoxic pulmonary vasoconstriction and regulation of hypoxic pulmonary vasoconstriction by red blood cells with an emphasis on hemoglobin-NO interactions. In addition, the review will discuss how biologic (S-nitrosation) or pharmacologic (cross-linking) modification of hemoglobin may affect pulmonary circulatory-hemoglobin interactions.     

The morphological changes in the erythrocytes and in the blood iron level of rats under the action of E. coli endotoxin]

Development of endotoxin shock in rats is accompanied by decreasing dry mass and content of dense substances in red blood cells. Endotoxin reduces circulating iron concentration as well. During endotoxin administration morphological changes of erythrocytes become stable, appearance of echinocytes promotes elevation of hemostatic potential and enhancement of blood cells aggregability.     

Spontaneous injury in isolated sheep lungs: role of perfusate leukocytes and platelets

Perfusion of isolated sheep lungs with blood causes spontaneous edema and hypertension preceded by decreases in perfusate concentrations of leukocytes (WBC) and platelets (PLT). To determine whether these decreases were caused by pulmonary sequestration, we continuously measured blood flow and collected pulmonary arterial and left atrial blood for cell concentration measurements in six lungs early in perfusion. Significant sequestration occurred in the lung, but not in the extracorporeal circuit. To determine the contribution of these cells to spontaneous injury in this model, lungs perfused in situ with a constant flow (100 ml.kg-1.min-1) of homologous leukopenic (WBC = 540 mm-3, n = 8) or thrombocytopenic blood (PLT = 10,000 mm-3, n = 6) were compared with control lungs perfused with untreated homologous blood (WBC = 5,320, PLT = 422,000, n = 8). Perfusion of control lungs caused a rapid fall in WBC and PLT followed by transient increases in pulmonary arterial pressure, lung lymph flow, and perfusate concentrations of 6-ketoprostaglandin F1 alpha and thromboxane B2. The negative value of reservoir weight (delta W) was measured as an index of fluid entry into the lung extravascular space during perfusion. delta W increased rapidly for 60 min and then more gradually to 242 g at 180 min. This was accompanied by a rise in the lymph-to-plasma oncotic pressure ratio (pi L/pi P). Relative to control, leukopenic perfusion decreased the ratio of wet weight to dry weight, the intra- plus extravascular blood weight, and the incidence of bloody lymph. Thrombocytopenic perfusion increased lung lymph flow and the rate of delta W, decreased pi L/pi P and perfusate thromboxane B2, and delayed the peak pulmonary arterial pressure. These results suggest that perfusate leukocytes sequestered in the lung and contributed to hemorrhage but were not necessary for hypertension and edema. Platelets were an important source of thromboxane but protected against edema by an unknown mechanism.     

Effect of essentiale on pulmonary edema and changes in the lipid metabolism during adrenaline administration

The experiments on white rats have confirmed that the development of lung edema following epinephrine infusion is characterized by considerable changes in phospholipid and cholesterol blood and lung metabolism. Essentiale preinjection prevented the decrease in phospholipid lung content and blood plasma cholesterol, which was accompanied by less prominent lung edema.     

Red cell distribution and the recruitment of pulmonary diffusing capacity.

The distribution of red blood cells in alveolar capillaries is typically nonuniform, as shown by intravital microscopy and in alveolar tissue fixed in situ. To determine the effects of red cell distribution on pulmonary diffusive gas transport, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of red blood cells. Red blood cells are spaced uniformly, randomly, or clustered without overlap within the capillary. Total CO diffusing capacity (DLCO) and membrane diffusing capacity (DmCO) are calculated by a finite-element method. Results show that distribution of red blood cells at a fixed hematocrit greatly affects capillary CO uptake. At any given average capillary red cell density, the uniform distribution of red blood cells yields the highest DmCO and DLCO, whereas the clustered distribution yields the lowest values. Random nonuniform distribution of red blood cells within a single capillary segment reduces diffusive CO uptake by up to 30%. Nonuniform distribution of red blood cells among separate capillary segments can reduce diffusive CO uptake by >50%. This analysis demonstrates that pulmonary microvascular recruitment for gas exchange does not depend solely on the number of patent capillaries or the hematocrit; simple redistribution of red blood cells within capillaries can potentially account for 50% of the observed physiological recruitment of DLCO from rest to exercise.     

Effect of lithium oxybutyrate on lipid metabolic changes in pituitrin-induced pulmonary edema

The experiments on white rats have confirmed that the development of lung edema following pituitrin infusion is characterized by considerable changes in phospholipid and cholesterol lung metabolism and cholesterol blood metabolism. Lithium hydroxybutyrate preinjection at a dose of 400 mg/kg prevented a decrease in cholesterol lung content and an increase in cholesterol blood plasma level which was accompanied by less prominent lung edema.     

Characteristics of the pulmonary transport functions for heat and dye in pulmonary edema and orthostasis

The aim of this study was to investigate whether changes in the distribution of pulmonary blood flow and disturbances of the pulmonary microcirculation can be detected by use of inflow-outflow indicator-dilution measurements. In 18 anesthetized (N2O-piritramide) mongrel dogs 221 thermal-indocyanine green dye indicator dilution kinetics were recorded in the pulmonary artery and aorta after central venous indicator injection. The lagged normal density function was used as a model for the pulmonary transport functions for heat and dye. The parameters of the lagged normal density function were computed by a non-linear least squares procedure by iterative convolution. After baseline measurements, in nine dogs, pulmonary edema was induced by central venous application of oleic acid. In nine other dogs, measurements were performed before and after postural changes. Our data show that both the microvascular injury caused by oleic acid edema and the perfusion heterogeneity caused by orthostasis can be detected by the indicator dilution technique since the both relative dispersion and skewness of the transport functions for heat and dye were significantly increased after these interventions.     

The study of cytokine content and ganglioside metabolism in experimental brain edema

A blood cytokine profile and also the brain content of lipid peroxidation (LPO) products and gangliosides were investigated in rats with experimental brain edema. The development of brain edema was accompanied by the increase in pro-inflammatory and a decrease in anti-inflammatory cytokine content. In parallel, accumulation of LPO products (conjugated dienes, hydroperoxides, and malondialdehyde) was observed. The study of ganglioside content under conditions of experimental brain edema revealed a decrease of their hydrolytic degradation product, sphingosine.     

Changes in content of glycolipids, sphingosine and cytokines in the rat brain with experimental edema

The study of the content of cerebrosides, gangliosides and their hydrolytic degradation product--sphingosine in the rat brain with experimental edema was carried out. In parallel, the cytokine profile of pro- and anti-inflammatory cytokines in the blood of rats with experimental cerebral edema was studied. The experiments indicated that a decrease of the total fraction of glycolipids and an increase of sphingosine content in the brain of rats with brain swelling were observed. The development of brain edema was accompanied by the increase in proinflammatory and decrease in anti-inflammatory cytokine content.     

Endothelial cell changes are associated with pulmonary edema and respiratory distress in mice infected with the WA1 human Babesia parasite.

A C3H/HeN mouse model was established to study the pathogenesis of the human babesial parasites, WA1 and Babesia microti. To evaluate the course of parasitemia and the associated lesions, mice were inoculated intraperitoneally with either WA1-infected, B. microti-infected, or uninfected hamster red blood cells. WA1-infected mice developed dyspnea and moderate parasitemias, after which death occurred. Babesia microti-infected mice experienced low parasitemias with no apparent morbidity or mortality. WA1-infected mice were thrombocytopenic but not anemic. Hemograms for B. microti-infected mice were similar to controls. Postmortem examination of WA1-infected mice revealed prominent lesions in the lungs, including pulmonary edema and intravascular margination of leukocytes. No pulmonary changes were detected in B. microti-infected mice. Blood gas measurements of WA1-infected mice showed reduced oxygen saturation and pH, and increased carbonic acid compared to controls, indicating hypoxia and respiratory acidosis. Ultrastructure studies of WA1-infected lungs showed hypertrophied endothelial cells containing transcellular channels associated with protein-rich intra-alveolar fluid. Endothelial cell activation was demonstrated by an upregulation of intercellular adhesion molecule-1 in the lungs of WA1-infected mice. The results suggest that recruitment of inflammatory cells to the lungs in WA1-infected mice induces endothelial cell alterations, leading to pulmonary edema and acute respiratory failure.     

Rapid but not slow spinal cord compression elicits neurogenic pulmonary edema in the rat

The development of neurogenic pulmonary edema (NPE) can be elicited by an immediate epidural balloon compression of the thoracic spinal cord. To evaluate whether a slower balloon inflation could prevent NPE development, we examined the extent of NPE in animals lesioned with a rapid (5 microl - 5 microl - 5 microl) or slow rate (3 microl - 2 microl - 2 microl - 2 microl - 2 microl - 2 microl - 2 microl) of balloon inflation. These groups were compared with the NPE model (immediate inflation to 15 microl) and with healthy controls. Slow balloon inflation prevented NPE development, whereas the pulmonary index and histology revealed a massive pulmonary edema in the group with a rapid rate of balloon inflation. Pulmonary edema was preceded by a considerable decrease in heart rate during the inflation procedure. Moreover, rapid inflation of balloon in spinal channel to either 5 microl or 10 microl did not cause NPE. Thus, a slow rate of balloon inflation in the thoracic epidural space prevents the development of neurogenic pulmonary edema, most likely due to the better adaptation of the organism to acute circulatory changes (rapid elevation of systemic blood pressure accompanied by profound heart rate reduction) during the longer balloon inflation period. It should be noted that spinal cord transection at the same level did not cause neurogenic pulmonary edema.     

Erythropoietin-driven proliferation of cells with mutations in the tumor suppressor gene TSC2

Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction, resulting from proliferation of smooth-muscle-like cells, which have mutations in the tumor suppressor genes TSC1 or TSC2. Among 277 LAM patients, severe disease was associated with hypoxia and elevated red blood cell indexes that accompanied reduced pulmonary function. Because high red cell indexes could result from hypoxemia-induced erythropoietin (EPO) production, and EPO is a smooth muscle cell mitogen, we investigated effects of EPO in human cells with genetic loss of tuberin function, and we found that EPO increased proliferation of human TSC2-/-, but not of TSC2+/-, cells. A discrete population of cells grown from explanted lungs was characterized by the presence of EPO receptor and loss of heterozygosity for TSC2, consistent with EPO involvement. In LAM cells from lung nodules, EPO was localized to the extracellular matrix, supporting evidence for activation of an EPO-driven signaling pathway. Although the high red cell mass of LAM patients could be related to advanced disease, we propose that EPO, synthesized in response to episodic hypoxia, may increase disease progression by enhancing the proliferation of LAM cells.     

SPORADIC ACUTE GLOMERULONEPHRITIS IN ADULTS

Nineteen adults who had acute glomerulonephritis were reviewed with respect to the clinical course and long-term follow-up. The age range was from 17 to 55 years. Only one patient died during the acute episode. In 11 cases, onset occurred between November and January and 15 of the patients had a known respiratory tract infection three to 30 days before the onset. The most important symptoms noted were weight gain, edema, dyspnea, oliguria and red or smoky urine. The most prominent physical signs were elevated blood pressure, edema, abnormalities in the chest and fever of over 100° F. Fifteen patients showed roentgen evidence of pulmonary vascular congestion, pleural effusion, cardiomegaly, pneumonia or a combination of these abnormalities. All the patients had proteinuria and red blood cells in the urine, and half of them had red blood cell casts. Azotemia, when present, subsided in 9.4 days. The average diastolic pressure was 105 mm. of mercury and the mean fall was 26 mm. in 23.5 days. At six months, nine of the 13 patients still being observed continued to show proteinuria or microscopic hematuria (seven showed both). A late follow-up of ten patients showed one to have significant hypertension and one to have early functional impairment and inconstant proteinuria. In these cases the average blood pressure was 140/91 mm. as compared with 119/74 mm. at the time of discharge.Sporadic glomerulonephritis in adults presents essentially the same pattern as it does in children. Urinary abnormalities may persist for months or even years, and neither the present series nor those reported by others clearly reveal the ultimate prognosis.     

Pulmonary microvascular response to LTB4: effects of perfusate composition

We examined the effects of leukotriene B4 (LTB4) on pulmonary hemodynamics and vascular permeability using isolated perfused guinea pig lungs and cultured monolayers of pulmonary arterial endothelial cells. In lungs perfused with Ringer solution, containing 0.5 g/100 ml albumin (R-alb), LTB4 (4 micrograms) transiently increased pulmonary arterial pressure (Ppa) and capillary pressure (Pcap). Pulmonary edema developed within 70 min after LTB4 injection despite a normal Pcap. The LTB4 metabolite, 20-COOH-LTB4 (4 micrograms), did not induce hemodynamic and lung weight changes. In lungs perfused with autologous blood hematocrit = 12 +/- 1%; protein concentration = 1.5 +/- 0.2 g/100 ml), the increases in Ppa and Pcap were greater, and both pressures remained elevated. The lung weight did not increase in blood-perfused lungs. In lungs perfused with R-alb (1.5 g/100 ml albumin) to match the blood perfusate protein concentration, LTB4 induced similar hemodynamic changes as R-alb (0.5 g/100 ml) perfusate, but the additional albumin prevented the pulmonary edema. LTB4 (10(-11)-10(-6) M) with or without the addition of neutrophils to the monolayer did not increase endothelial 125I-albumin permeability. Therefore LTB4 induces pulmonary edema when the perfusate contains a low albumin concentration, but increasing the albumin concentration or adding blood cells prevents the edema. The edema is not due to increased endothelial permeability to protein and is independent of hemodynamic alterations. Protection at higher protein-concentration may be the result of LTB4 binding to albumin.     

Pulmonary circulation in experimental pulmonary edema during diverse artificial respiration regimes

In acute experiments on cats with closed chest by ultrasonic method the authors studied the blood flow in low-lobar pulmonary artery and the vein, the blood pressure in pulmonary artery, lung vessels resistance in experimental pulmonary edema caused by intravenous infusion of mixture fatty acids at artificial ventilation of increased frequencies or volumes, at was shown, that artificial ventilation of increased frequencies in pulmonary edema reduces the pressure increase in pulmonary artery, lung vessels resistance and increases the blood flow in pulmonary artery and vein. Artificial ventilation of increased volumes produces more intense pressure increase in pulmonary artery and lung vessels resistance than in initial ventilation but the blood flow was slightly changed. The authors assume that artificial ventilation of increased frequencies or volumes in pulmonary edema due to pulmonary circulation change reduces the pulmonary edema intensity at the beginning.     

Seizure-associated pulmonary edema and cerebral oxygenation in the rat

Cerebral partial pressure of O2 (PO2), relative changes in the ratio of reduced/oxidized cytochrome aa3, blood flow, and the arteriovenous difference in O2 content were measured during seizures with and without pulmonary edema. Seizures were induced with bicuculline (0.2-1.2 mg/kg iv) in rats anesthetized with 70% N2O and paralyzed with curare. Briefer seizures were accompanied by increased cerebral PO2 and increased oxidation of cytochrome aa3. Lung water content and arterial O2 partial pressure (PaO2) remained normal. Longer duration seizures were also accompanied initially by increases in cerebral oxygenation. Within minutes, however, PaO2 fell from a mean of 118 to 51 mmHg, and lung water content increased from 76.2 to 83.6%. Cerebral PO2 fell but most often rose back to or above control levels, while cytochrome aa3 became markedly reduced. Simultaneously, cerebral blood flow increased more than 300% above preseizure values and O2 delivery increased more than O2 consumption. The reductive shift of cytochrome aa3 was greater than that produced by lowering PaO2 to equivalent values in seizure-free rats. The reductive shift of cytochrome aa3, despite increased O2 delivery, may be indicative of derangements in cerebral O2 diffusion or energy metabolism.     

The action of humidified gas on the pulmonary lining layer. Ultrastructural observations after administration of pure oxygen and of various mixtures of oxygen and carbon dioxide.

The study concerns the action of dehumidified or humidified gas on the pulmonary lining layer. The results of our research suggest that water vapor used in artificial ventilation may be an important determining factor of the respiratory problems reported by clinicians in man. Important modifications of the lining layer of the alveolar epithelium occur, accompanied by more important alterations, including those of the content of the alveolus, all of which contribute to the pulmonary edema observed.