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PubMed1990

Synthetic low and high fat diets for the study of atherosclerosis in the mouse.

Diets currently used to produce atherosclerotic lesions in mice are often undefined and cause accumulation of fat in the liver and gallstone formation. Therefore, synthetic low and high fat diets of known composition were formulated in this study. A synthetic diet containing 50% sucrose, 15% cocoa butter, 1% cholesterol, and 0.5% sodium cholate was found to produce a depression in high density lipoprotein cholesterol (HDL-C) and an elevation of very low density lipoprotein (VLDL) and low density lipoprotein cholesterol (LDL-C) in the atherosclerosis-susceptible strain, C57BL/6J. This diet was able to consistently produce aortic lesions and led to a decrease in liver damage and gallstone formation. The synthetic low fat diet did not produce HDL-C levels as high as those found in mice fed chow, but resulted in similar VLDL/LDL-C levels. Lipoprotein and apolipoprotein parameters were compared in C57BL/6J and the atherosclerosis-resistant strain, C3H/HeJ, consuming the synthetic low fat or high fat diets. As reported earlier, when consuming a high fat diet C57BL/6J mice have significantly lower HDL-C and apoA-I levels than C3H/HeJ mice. Further analysis shows that the molar ratio of plasma HDL-C to apoA-I is significantly lower in C57BL/6J mice, suggesting that HDL in the susceptible strain has a lower cholesterol-carrying capacity. This conclusion is consistent with the observation that the HDL particle size is smaller for C57BL/6J mice than for C3H/HeJ. Both strains increased their apoE levels when fed the synthetic high fat diet, but C3H/HeJ mice had higher levels of apoE on both diets. The major response to consumption of the high fat diet for both strains was an increase in apoB-48 from 5 micrograms/ml on a low fat diet to 54 and 109 micrograms/ml for C57BL/6J and C3H/HeJ, respectively. ApoB-100 showed minimal response to the high fat diet. The defined high fat diet can be used to study atherosclerosis in the mouse since it produces aortic lesions but reduces or eliminates other pathological changes such as gallstone formation and liver damage.

Animals↗
PubMed1975

Alterations in graft--ersus-host reactivity and peripheral leukocytes in mice after erythropoietin treatment.

Treatment of mice on four consecutive days with either erythropoietin (EP) or rabbit antimouse thymocyte serum (ATS) resulted in a significant reduction in antigenic reactivity of spleen cells as measured by the Simonsen assay. In normal animals, treatment with either EP or ATS resulted in lymphopenia and in most instances a neutrophilia and a variable monocytopenia. Similar alterations in these cell types were recorded for polycythemic mice subsequent to treatment with either EP or ATS. These data plus histologic analyses support the idea that there is an inverse relationship between the cells committed to differentiate along the lymphoid cell line and the cells committed to differentiate along myeloid cell lines. Further, the data are consistent with the "carrying capacity" concept regarding the stem cell microenvironment and support the monophyletic theory.

Animals↗
PubMed1989

Effects of aluminum on the liver following high-dose enteral administration to rats.

Parenteral administration of aluminum (Al) to animals can result in hepatobiliary dysfunction, including elevated total serum bile acid concentration, reduced bile flow, and reduction of mixed function oxidase activities. Despite substantial hepatic Al accumulation, biliary Al excretion is negligible. We studied the effects of enteral administration of pharmacologic doses of Al to rats in order to see if by this route Al also produced hepatobiliary dysfunction or if biliary Al excretion was enhanced following enteral administration, protecting the liver from the effects of Al. Six rats were given 100 mg/kg/day of Al for 14 days as Al citrate by duodenal cannula. Pair-fed littermate controls were given sodium citrate. Serum Al and urinary Al/creatinine were significantly higher in Al-fed rats than in controls. Liver Al was significantly increased in the Al-fed group, but very low when compared to liver Al concentration with intravenous Al administration. Biliary Al was only 2 +/- 1% of urinary Al in the experimental group. Serum bile acid concentration and bile flow were not different between groups. We conclude that Al given in pharmacologic doses is absorbed but does not accumulate in the liver. We hypothesize that a slow rate of Al absorption may not overwhelm plasma transferrin carrying capacity or renal Al excretory capacity.

Aluminum↗
PubMed1989

The efficacy of blood cardioplegia is not due to oxygen delivery.

Twenty-seven canine hearts instrumented with ultrasonic dimension crystals underwent simultaneous determination of stroke work and myocardial oxygen consumption during incremental volume loading on right heart bypass before and 30 minutes after 2 hours of cardioplegic arrest at 10 degrees C. Three cardioplegic solutions were used: Hematocrit values were 17.0% (group I), 8.2% (group II), and 0% (group III). In all groups the slope of the linear stroke work versus end-diastolic volume relationship, a measure of contractility, was unchanged after ischemic arrest. However, the myocardial oxygen consumption for basal metabolism was increased an average of 25.5% after arrest with plasma (group III). Since the plasma concentration in all three groups was identical, and the oxygen available to the hearts during ischemia was the same in groups II and III, the efficacy of blood-based cardioplegic solutions cannot be attributed to a plasma component or to the greater oxygen-carrying capacity of the red blood cell. Future studies should attempt to identify the salutory entity of the red cell responsible for preservation of myocardial oxygen consumption efficiency.

Animals↗
PubMed1989

Synthetic erythrocytes.

Synthetic erythrocytes (SEs) are made by incorporation of stroma-free hemoglobin (SFH) or lipid-heme into liposomes. They form spontaneously at the interface between the phospholipid material and aqueous solution. SEs are spheroid vesicles with diameters between 0.01 and 4 microns, capable of carrying and delivering oxygen in a manner similar to red blood cells (RBCs). Oxygen-dissociation curve is virtually identical to that of RBCs, with P50 = 28 torr, and adjustable by the addition of 2,3-DPG or inositol hexaphosphate. Liposome/heme containing lipid-heme, a synthetic O2-carrying substance, is capable of carrying as much O2 as RBCs. Liposome-encapsulated SFHs have smaller O2-carrying capacity, but can be made to equal that of RBCs. Viscosity of SE suspensions is somewhat higher than blood's viscosity, but has otherwise similar rheologic properties. A large number of in vivo experiments with laboratory animals prove the ability of SEs to maintain life after virtually complete removal of blood. Cardiorespiratory functions remain near-normal, blood chemistry exhibits reversible mild changes, and vital organs do not show significant abnormalities. Blood coagulation is not affected. Hemoglobin does not appear in urine and plasma, indicating mechanical stability in circulation and absence of diffusion through the membrane. SEs do not cause significant acute toxicity. The absence of blood groups makes them a universal blood donor. However, massive doses suppress the reticuloendothelial system (RES). The animals undergoing total exchange transfusions may die of septic shock, apparently caused by nonsterile infusate in combination with strong suppression of the RES. Longevity of SEs in circulation is proportional to the dose. At doses corresponding to more than 90% exchange transfusions, half-life is longer than 24 h. Since all materials used in preparation of SEs are naturally occurring in blood, SEs are easily metabolized and eliminated without allergic reactions. The absence of membrane proteins and chemical stability of SFH and phospholipids promises long shelf-life. SE suspensions are difficult to sterilize, particularly against the viruses that may be present in SFH. However, the use of sterile procedures during manufacturing, and extraction of hemoglobin from animals bred under strict infection control may eliminate that problem.

Animals↗
PubMed1989

Advances in the treatment of oxygenation disturbances.

The treatment of oxygen transport parameters centers on improving any aspect of oxygen delivery that is threatened. The most important improvements center on improving cardiac output and oxygen carrying capacity, primarily through improving hemoglobin levels, and to a smaller extent, PaO2/SaO2 values. This article reviewed the highlights for improving the key components of oxygen transport while providing examples to aid clinical application.

Adult↗
PubMed1989

Influence of haematocrit in the cerebral circulation.

Cerebral blood flow is inversely related to in vitro whole blood viscosity, the major determinant of which is haematocrit. Haemodilution increases cerebral blood flow in polycythaemic patients and in subjects with high normal haematocrit. There is now increasing evidence that this relationship reflects a homeostatic and physiological regulation of oxygen-carrying capacity. A high normal haematocrit proves to be a weak risk factor for stroke whilst stroke risk is clearly related to the target haematocrit in patients treated for polycythaemia rubra vera. Whilst venesection remains accepted prophylactic treatment against stroke and other vaso-occlusive events in the latter case, no large scale trial has formally assessed the role of haematocrit reduction in patients with early manifestations of cerebrovascular disease like transient ischaemic attacks or in the early stages of multi-infarct dementia. There are theoretical reasons why a high haematocrit might have adverse effects on the cerebral circulation in the presence of vessel occlusion. Thus, flow and therefore oxygen delivery would become constrained by high viscosity (haematocrit) in the maximally dilated ischaemic vascular bed, and secondary thrombosis would be encouraged by low flow rates, and increased cell-cell interaction. These arguments have led to two large multicentre clinical trials of haemodilution in acute stroke victims. Neither has revealed any clinical benefit in the treated group. The reasons for the failure of the trials are discussed. It is envisaged that haemodilution, as well as retaining a clinical role in the prevention of stroke in patients with polycythaemia, may be used as an adjunct to other therapy for the immediate sequelae of cerebral ischaemia.

Cerebrovascular Circulation↗
PubMedDate not supplied

[Stress fractures].

In spite of the fact that the first description of stress fracture appeared 130 years ago, its origins still remain unknown. There are numerous potential factors causing fractures in some circumstances. It is sure that this is the result of disharmony of overstrain (bending force or compression force) of groups of muscles on the one hand and skeletal carrying capacity, i. e. one skeletal segment on the other hand. In differential diagnosis, particular attention is to be paid to some localizations, firstly to tibia and femur, since sometimes they are similar to osteomyelitis, osteoid-osteoma or osteogenic sarcoma. It may be supposed that the number of cases constantly grows, corresponding to higher number of participants of various sports and of different age, to be determined by the application of new diagnostic methods, revealing the development of the process far earlier than x-ray (scintiphotography, thermography, ultrasonography and CT). The majority of cases are successfully treated and cured by conservative methods, frequently only by resting, while only rarely there are cases with shift of segments and indicated surgical treatment. A lot of cases are asymptomatic. In the period from 1981 to 1986, we clinically registered 113 cases of stress fractures with soldiers, 105 of them of metatarsus bones, 4 of tibia, 3 of fibular malleolus and 1 of cuboid bone.

Fractures, Stress↗
PubMed1988

Nonimmunologic hydrops fetalis resulting from intrauterine human parvovirus B-19 infection: report of two cases.

Two cases of nonimmunologic hydrops fetalis associated with intrauterine human parvovirus B-19 infection are reported. In these cases, hydrops fetalis was diagnosed with ultrasound at 21 and 22 weeks' gestation after 10 or more days of maternal flu-like symptoms. The outcome was stillbirth in one case and neonatal death in the other. In both cases, intrauterine infection by human parvovirus B-19 was confirmed based on two findings: maternal serum positive for human parvovirus B-19 immunoglobulin M (IgM) antibody, and human parvovirus B-19 DNA detected in the fetal organs using Southern blotting and hybridization with a 32P-labeled probe. Laboratory tests on cord blood demonstrated a red blood cell count of 163 x 10(4)/microL, and nucleated red cells numbering 1267 per 50 white cells in the live-birth case. Histologic examinations of fetal tissues demonstrated leukoerythroblastic reaction in the liver and spleen, granular hemosiderin deposition in hepatocytes and Kupffer cells, and bilirubin deposition in the intercellular space in the liver. This evidence indicates that, in some fetuses with intrauterine human parvovirus B-19 infection, hydropic changes may be induced by the sudden decrease in oxygen-carrying capacity of the blood due to severe anemia caused by the infection.

Adult↗
PubMed1988

The pathophysiology and clinical relevance of platelet heterogeneity.

Recent studies on platelet heterogeneity support the hypothesis that platelet production is regulated to maintain a constant functional platelet mass. In concept this form of regulation is analogous to the manner by which RBC production is controlled to maintain the oxygen-carrying capacity of blood. The platelet mass appears to correlate more closely with platelet function than the platelet count alone, since several factors in addition to the platelet count have been shown to influence the platelets' hemostatic function. These factors include platelet size, density, age, and previous hemostatic interactions. Application of these concepts to clinical problems has provided important insights into platelet physiology and reactivity. Failure to account for differences in platelet heterogeneity among individuals may introduce significant errors in the interpretation of data from laboratory and clinical investigations. However, despite advances, a number of practical issues remain to be resolved before measurements of platelet heterogeneity become accepted as routine clinical tests and are used in the diagnosis of pathologic states.

Animals↗
PubMed1987

Hematologic aspects of toxicology.

Exposure to a number of toxins may result in a variety of hematologic abnormalities. Derangements of the synthesis of cellular elements, a shortened red cell half life, abnormalities of coagulation, and interference in oxygen-carrying capacity are some of the pathologic effects. Pharmacologic agents, heavy metals, and animal and insect venoms are among the toxins implicated in the production of hematologic abnormalities. This article focuses on some of these issues.

Blood↗
PubMed1987

Determinants of regional myocardial oxygen supply in the left ventricle. An experimental study in the in situ working canine heart.

The main factors that regulate myocardial oxygen supply include the 1. coronary blood flow controlling the volume flow fraction of red cells, 2. the oxygen carrying capacity of capillary blood dependent on the red cell volume fraction occupying the capillaries, and 3. the density of perfused capillaries affecting the capillary diffusion capacity and the diffusion distance in the tissue. Differences exist between the inner and outer layers of the left ventricle that include differences of systolic and possibly diastolic tissue stresses and oxygen consumption. The highest values were observed in the vicinity of the left ventricular cavity. The regional differences of myocardial oxygenation were studied in anaesthetized open-chest dogs by measuring the myocardial perfusion rate, the microvascular hematocrit, the PS-product of 51Cr-EDTA, and the microvascular blood volume across the left ventricular wall in the heart working in situ. Gradients of blood flow rates were present with the highest flow in deep myocardial layers. Maximally increasing the coronary blood flow at normal perfusion pressure and metabolic load did not change the distribution of blood flow between subendocardial and subepicardial layers. Distal to a coronary stenosis, blood flow was markedly reduced and redistributed away from the subendocardial layers, indicating a relatively severe decrease of fractional red cell flow to the left ventricular myocardium. The microvascular dynamic hematocrit, i.e. the volume fraction of red cells, was evenly distributed across the left ventricular wall, but consistently reduced to 75 per cent of great vessel hematocrit. The maximal increase of coronary blood flow provoked a further reduction of microvascular hematocrit due to a decrease of the red cell volume, possibly by shunt flow of red cells through low resistance vessels of capillary size. At restricted coronary inflow, the microvascular hematocrit was decreased with a redistribution of red cells away from deep myocardial layers. Extern compression of microvessels by the tissue pressure, phase-separation between red cells and plasma at microvascular bifurcations, or decrease of the red cell fluidity may all contribute to this change. Reduction both of microvascular red cell flow fraction and the hematocrit diminishes the red cell flux within capillaries and decreases the ability of blood to deliver oxygen to the tissue, and more so in the subendocardial layers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Does excessive tissue oxygen supply contribute to the development of spontaneous arterial hypertension in rats?

Fifteen spontaneously hypertensive rats of the Okamoto strain and 14 normotensive Wistar rats were kept on low iron diet until 3 weeks old. Nine hypertensive and 10 normotensive rats fed regular diet served as controls. Hypertensive rats exhibited higher haematocrit and haemoglobin levels. Low iron diet produced a more pronounced decrease in the haemoglobin level in hypertensive than in normotensive rats, indicating increased iron turnover in the former group. Anaemia inhibited development of arterial hypertension in Okamoto strain rats whereas it did not affect blood pressure in normotensive rats. The results point to an important role of the blood oxygen carrying capacity for the development of spontaneous hypertension in rats.

Anemia↗
PubMed1986

Anesthesiology update #19. Adverse reactions to transfusion.

Adverse reactions to blood transfusion are not often recognized in the operating room. However, immediate reactions are reported to occur in 5% of patients and delayed reactions in a similar number. Many physicians tend to ignore the risks associated with transfusion and administer blood to achieve some magic end point such as a specific hematocrit or platelet count. Blood products are often administered when crystalloid solutions would suffice. Red cells are administered to increase oxygen carrying capacity and platelets and FFP to promote coagulation. Blood products must not be used as volume expanders. A positive aspect of the AIDS epidemic is increased awareness of disease transmission through transfusion. Many patients are requesting that transfusion be withheld or that they receive only autologous blood. A significant percentage of patients scheduled for elective surgery are candidates for predonation and should be encouraged to do so. Particularly suitable are patients scheduled for spine surgery and total hip replacement.

Blood Group Incompatibility↗
PubMed1986

Cardiovascular adaptation to exercise at high altitude.

To exercise at high altitude means working in an environment with reduced atmospheric pressure. The oxygen tension of the inspired air is therefore decreased, that is, there is atmospheric hypoxia. Exercise increases oxygen requirements which must now be met in the face of this decreased oxygen driving pressure. The initial handicap is less complete oxygenation of blood within the lung. In an effort to preserve oxygen delivery, a greater volume of blood is circulated, that is, cardiac output is increased. However, this pattern of compensation is only temporary. Within days, hemoconcentration increases the oxygen-carrying capacity of the blood, and as a consequence, less cardiac output is required to maintain oxygen delivery. In fact, cardiac output decreases to levels lower than existed prior to ascent. This reduction in cardiac output results primarily from a decrease in stroke volume due to less venous return secondary to the smaller blood volume produced by hemoconcentration. The hypoxia of high altitude produces sustained stimulation of the sympathetic nervous system. Initially, this increases heart rate, but, with time, the responsiveness of the heart decreases, so the initial tachycardia may not be sustained. Other consequences of sympathetic stimulation include an increase in resting metabolic rate, a shift away from glycogen toward free fatty acids as primary energy sources, and bone marrow stimulation to increase red cell production. The parasympathetic nervous system may also be stimulated at high altitude, which may explain the reduction in maximum heart rate. Upon arrival at high altitude, aerobic working capacity is reduced. Although this may or may not be attenuated following adaptation, endurance capacity does seem to improve. Several parallels therefore emerge between adaptation to the hypoxia of high altitude and adaptation to the struggle for oxygen created by exercise training at low altitude. Sympathetic stimulation is common to both forms of hypoxic stress, and similar responses, particularly metabolic, result. Not surprisingly, then, exercise training provides an advantage to adaptation to high altitude.

Acclimatization↗
PubMed1987

The effect of cardioplegic oxygenation on the correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting postischemic heart.

To ascertain whether oxygenated cardioplegia is beneficial during surgically induced global ischemia, 27 canine hearts underwent sonomicrometric determination of cardiac mechanics and energetics during volume loading on right heart bypass before and after 2 hr of potassium cardioplegic arrest with crystalloid, oxygenated crystalloid, or blood vehicles. The slope of the linear stroke work vs end-diastolic volume relationship, an index of contractility, was preserved by each vehicle. Similarly, oxygen utilization to perform external mechanical work during reperfusion was unaffected in all groups. However, there were significant 119% and 122% increases in basal oxygen utilization after both unoxygenated and oxygenated crystalloid cardioplegia (p less than .05) that were prevented by the blood-based vehicle. These data suggest that the salutary effects of blood cardioplegia on postischemic myocardial energetics may not be solely mediated by its oxygen-carrying capacity.

Animals↗
PubMed1986

Prolonged vascular retention of a hemoglobin solution modified by cross-linking with 2-nor-2-formylpyridoxal 5'-phosphate.

The usefulness of hemoglobin solutions as plasma expanders with oxygen-carrying capacity is limited by a high oxygen affinity and a rapid clearance from the circulation. A large amount of the hemoglobin is cleared by the kidneys, because the hemoglobin can pass the glomeruli after dissociation into dimers. This dissociation can be prevented by cross-linking the beta chains with 2-nor-2-formylpyridoxal 5'-phosphate (NFPLP), a modification that also diminishes the oxygen affinity. In the present study, the vascular retention of modified hemoglobin (HbNFPLP) compared with unmodified hemoglobin (Hb) was investigated in rats and rabbits by replacing half the blood volume with a mixture of Hb and HbNFPLP (7 gm/100 ml). The amount of free hemoglobin in the circulation was determined from the plasma concentration, corrected for the decrease in plasma volume. The decrease in plasma volume was calculated from the increase in hematocrit (in the rats, 30% to 40% in 3 hours). The ratio Hb/HbNFPLP was determined by high-performance anion-exchange chromatography. The half-disappearance times for HbNFPLP and Hb were found to be 3 hours and 1 hour in rats and 7 hours and 2.5 hours in rabbits, respectively. In the rats, one third of the unmodified Hb was found in the urine 5 hours after the exchange, against only 5% of the HbNFPLP. In rats without kidneys, the ratio of Hb/HbNFPLP in the circulation remained constant. The results demonstrate that intramolecular cross-linking of hemoglobin with NFPLP prevents excretion by the kidneys, but does not influence other clearance mechanisms.

Animals↗
PubMed1979

In utero opiate dependence and sudden infant death syndrome.

Infants born to smoking, alcoholic, and drug-dependent women appear to suffer increased prenatal and postnatal growth deficiency, vascular changes, and hypoxic episodes as a result of decreased oxygen carrying capacity in the blood, depression with overdose, and withdrawal symptoms. The author reviews these associations and suggests further research to clarify their role in the sudden infant death syndrome.

Alcoholism↗