Search

Piezoresistance describes the change of electrical resistance in a material undergoing deformation. Heterogeneous materials having different resistivities of dispersed and continuous matrix phases, such as blood (comprised of red and white blood cells and platelets suspended in plasma), can exhibit the piezoresistance effect. For an initially isotropic material, two independent intrinsic material coefficients, λ1 and λ2, would uniquely describe the piezoresistance phenomenon. Materials undergoing deformation affect a material's resistivity in two ways: (a) by introducing anisotropy in the material, which is characterized by λ1 and (b) by changing the volume density of the inclusions, which is associated with (1/3 λ1+λ2). In this paper, the piezoresistance effect in bovine blood samples is studied under oscillatory shear flow with a planar sensor rosette. The first piezoresistance coefficient, λ1, was measured at various frequencies and shear rates in the blood flow and compared with cos δ (equal to G'/G*, where G' and G* are the storage and complex moduli, respectively), which reflects the degree of elasticity. The coefficient λ1 was found to have a trend similar to that of cos δ under all conditions tested. Thus λ1 might potentially be used to characterize the viscoelastic properties of blood and the deformability of red blood cells, thus clarifying pathophysiology and facilitating diagnosis., (© 2011 – IOS Press and the authors. All rights reserved)

Background: We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia., Methods: We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1x10(11), 2.2x10(11), or 4.4x10(11) platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria)., Results: In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25x10(11)) than in the medium-dose group (11.25x10(11)) or the high-dose group (19.63x10(11)) (P=0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001)., Conclusions: Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1x10(11) and 4.4x10(11) platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.), (2010 Massachusetts Medical Society)

The mechanism by which hyperoxia decreases blood flow is still not understood. Hyperoxemia-induced vasoconstriction is known to occur in many organs, including brain and retina, skeletal muscle, and myocardium. Whether this also occurs in skin is unknown. This study was conducted in healthy volunteers exposed intermittently to 100% oxygen (F(I)O(2) 1.0). Perfusion of forearm skin was measured by laser Doppler imaging (LDI). In series 1, it was measured in 7 subjects before, during, and after 15 min of oxygen breathing. In series 2, flow was measured, also during air and O(2) breathing, after perfusion was raised by (a) sympathetic blockade (induced by a topically applied local anesthetic) (n=9) and by (b) current-induced vasodilation (n=8). In normal unperturbed skin, there was no significant change with hyperoxia. When basal perfusion was raised by topical anesthesia or by current, there was also no change in mean perfusion overall with hyperoxia. However, areas with the highest perfusion (upper decile) showed a significant perfusion decrement with hyperoxia (-30% and -20%, respectively; p<0.001). Vasoconstriction with hyperoxia has been demonstrated in human skin. The fact that it is observed only when flow is increased above basal levels and then only in high-flow vessels suggests that cutaneous blood flow control is primarily regulated by variables other than oxygen.

The rationale for immunosuppressive therapy of thrombotic thrombocytopenic purpura (TTP) was established by observations that TTP may be caused by autoantibodies to ADAMTS13. Patients with high-titer autoantibodies to ADAMTS13 may have a higher mortality, and survivors may require prolonged plasma exchange therapy in spite of adjunctive glucocorticoid treatment. More intensive immunosuppressive therapy with rituximab may provide benefit for many of these patients. The Transfusion Medicine/Hemostasis Clinical Trials Network is developing a randomized, clinical trial to test the hypothesis that addition of rituximab to standard treatment of TTP with plasma exchange and glucocorticoids will decrease initial treatment failure rates as well as subsequent relapses over the following 3 years. To provide the background data for this clinical trial, a systematic review of all published reports on rituximab treatment of immune-mediated disorders was performed. Twelve articles have reported 27 patients treated with rituximab for TTP, with benefit described in 25 (93%) of the patients. Additional reports have described rituximab treatment of 37 other immune-mediated disorders, with clinical response in most patients. These observations from small uncontrolled case series provide the background and rationale for a randomized clinical trial to establish the role of rituximab in the management of patients with TTP.

Pulse oximetry is a widely used, noninvasive instrument for monitoring oxygen saturation. Its use, however, is limited in the setting of dyshemoglobinemias. We report a case of hemoglobin Rothschild in an Asian patient diagnosed as a result of routine pulse oximetry. This case reiterates the limitations of pulse oximetry in patients with dyshemoglobinemias, while introducing its use as a case-finding tool for such conditions., (Copyright 2003 Wiley-Liss Inc.)

O(2) transport and O(2) diffusion interact in providing O(2) to tissue, but the extent to which diffusion may be critical in the heart is unclear. If O(2) diffusion limits mitochondrial oxygenation, a change in blood O(2) affinity at constant total O(2) transport should alter cardiac O(2) consumption (VO(2)) and function. To test this hypothesis, we perfused isolated isovolumically working rabbit hearts with erythrocytes at physiological blood-gas values and P(50) (PO(2) required to half-saturate hemoglobin) values at pH of 7.4 of 17 +/- 1 Torr (2,3-bisphosphoglycerate depletion) and 33 +/- 5 Torr (inositol hexaphosphate incorporation). When perfused at 40 and 20% of normal coronary flow, mean VO(2) decreased from the control value by 37 and 46% (P < 0.001), and function, expressed as cardiac work, decreased by 38 and 52%, respectively (P < 0.001). Perfusion at higher P(50) during low-flow ischemia improved VO(2) by 20% (P < 0.001) and function by 36% (P < 0.02). There was also modest improvement at basal flow (P < 0.02 and P < 0.002, respectively). The improvement in VO(2) and function due to the P(50) increase demonstrates the importance of O(2) diffusion in this cardiac ischemia model.

We did a retrospective analysis on the safety and efficacy of sequential infusion fludarabine and cytosine arabinoside (ara-C) in treating refractory, recurrent or poor prognosis acute leukemia in adult patients. Forty-five adult patients with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) received a total of 68 courses of sequential continuous infusion of fludarabine for 2 days (total dose 71.5 mg/m(2) ) followed by 3 days of ara-C (total dose 7590 mg/m(2) ). Thirty-nine patients had refractory or recurrent disease, and six had other adverse prognostic features. Thirty-six patients had AML, seven had ALL, and two had CML in blastic phase. Complete remission was seen in 20 patients (44%), and partial remission in 5 patients (11%), giving a total response rate of 56%, similar for both AML and ALL. Duration of response to prior therapy did not affect the response rate. All 3 patients with Philadelphia chromosome positive ALL obtained complete remission. Median remission duration was 4.7 months (range 0.6-36.6), and median overall survival was 5.0 months (0.7-40+). Median overall survival was 10.1 months in responders. Pulmonary toxicity was seen in 8 patients, of whom 2 died from adult respiratory distress syndrome. No cardiac toxicity was observed, but 3 patients had transient cerebellar toxicity. Profound myelosuppression was seen in all patients. We conclude that the sequential infusion of fludarabine and ara-C is an effective non-cardiotoxic regimen for adults with refractory, recurrent or poor prognosis acute leukemia, may be particularly useful for resistant Philadelphia chromosome positive ALL, and may warrant further investigation in this subset. Pulmonary rather than neurological toxicity may be a unique side effect of the regimen.

Objective: To present a case of cold agglutinin disease/cryoglobulinemia secondary to a monoclonal anti-Pr2 IgM lambda antibody, and review the literature on the occurrence of this antibody in cold-induced disease and the clinical disease associated with it., Methods: Cryoantibody characteristics were evaluated by cold precipitation. The antigen specificity of the monoclonal IgM lambda antibody was evaluated using techniques of selective red blood cell absorption., Results: In our patient, we were able to identify an antibody with both cryoglobulinemic and cold agglutinin (cryoagglutinin) properties. This antibody was found to be monoclonal IgM lambda with specificity to the Pr2 antigen on red blood cells., Conclusions: Monoclonal IgM lambda anti-Pr is a rarely found cold agglutinin antibody. In this report we describe the clinical course of a patient who had this antibody, which not only agglutinated red cells in the cold but also had cryoglobulin properties. The clinical illness of this man was characterized by severe acrocyanosis and digital necrosis with eventual organ necrosis and death. We also review the literature on cold induced disease due to monoclonal anti-Pr IgM lambda antibody. Our patient was found to be unique among the reports reviewed. Our case is the first to report both cold agglutinin and cryoglobulinemic properties with the evaluation of the thermal amplitudes of these activities of the antibody. Also, unlike the lymphoproliferative malignancy observed in the cold agglutinin-associated disease in the other reports, our patient's disease was associated with a monoclonal B-cell expansion on the spectrum between benign monoclonal gammopathy and a low grade lymphoproliferative disorder.

Effect of increased blood O2 affinity on cardiac output and its distribution was studied in conscious sedated rats by the microsphere-reference sample method. After a preliminary measurement of cardiac output and its distribution, rats were exchange transfused with normal blood or low-P50 (PO2 at which hemoglobin is half-saturated with O2) blood; other groups were made anemic with and without a simultaneous reduction in P50. Reduction in P50 from 38 to 17 Torr did not change cardiac output, pulse, or blood pressure but caused, after allowance for changes in controls, a 102% increase in coronary blood flow and an 88% increase in cerebral blood flow. Anemia (hematocrit = 22%) produced similar changes in coronary and cerebral flow. When anemia was combined with a 12-Torr reduction in P50, coronary and cerebral flow increased by 297 and 209%, respectively. These increases in coronary and cerebral flow were not attributable to increased cardiac work or hypercapnia. It is concluded that a left shift of the O2 dissociation curve induces increased blood flow to brain and heart, probably in compensation for decreased tissue O2 pressure.

The effect of an acute left shift in the oxygen dissociation curve (ODC) was examined in several animal models. When combined with hemorrhagic shock, a left shift of the ODC produced diminished shock tolerance with evidence of increased sympathetic outflow and increased mortality. Perfusion of the isolated canine brain with low P50 blood produced major electroencephalographic abnormalities and a sharp decrease in cerebral oxygen consumption. Exchange transfusion of normal rats with low P50 blood resulted in a major increase in coronary and cerebral flow. The data suggest that an acute left shift of the ODC is capable of disturbing oxygen delivery significantly, particularly to the brain and probably to the heart. Normal animals appear to compensate for an acute increase in oxygen affinity by increasing blood flow to these organs. When oxygen affinity is increased in combination with a fixed rate of blood flow, hypoxia results.

We have studied the effect of increased blood O2 affinity on O2 delivery to the isolated canine brain. After surgical isolation, the brain, enclosed in the calvarium, was perfused alternately from two pump-oxygenators with normal blood (P 50 [7.4] = 30 +/- 2 torr [S.D.]) and with blood whose P50 was reduced to 18 +/- 2 torr by carbamylation. [Hb], acid-base balance, blood gases, and flow rate were carefully matched in the two circuits. Although blood [Hb] was reduced to approximately 10 gm/dl, other perfusion variables such as CBF (65 +/- 6 ml/min/100 gm) and arterial blood oxygen saturation (96% to 99%) were normal for the dog. Under these conditions cerebral VO2 (Fick) averaged 3.87 +/- 0.73 ml/min/100 mg (S.D.) with control blood and 2.94 +/- 0.69 with low P50 blood (mean delta = 24%, n = 14, p less than 0.001), and PVO2 averaged 31 +/- 2 and 21 +/- 2 torr, respectively (p less than 0.001). The fall in VO2 during low P50 perfusion was associated with a decrease in [A-V]O2 difference and a rise in CVO2 of 1.2 ml/dl, which suggests that O2 extraction at PVO2 approximately 20 torr is curtailed. The EEG, previously shown to correlate with VO2 in this model, invariably deteriorated after 30 to 60 sec of low P50 perfusion and improved in 30 to 60 sec after reperfusion with normal blood. CBV increased by 0.9 ml/100 gm during low P50 perfusion, implying capillary recruitment. In a parallel series of experiments, four brains were alternately perfused with normal blood (pH 7.41, PCO2 38 torr, P50 [7.4] = 30 torr) and alkalotic blood (pH 7.98, PCO2 39 torr, P50 [7.98] = 17.3 torr). With flow rates equal for both normal and experimental blood, PVO2 averaged 31 +/- 4 (S.D.) and 21 +/- 3 torr (p less than 0.001), respectively, and VO2 averaged 4.33 +/- 0.52 ml/min/100 gm and 3.18 +/- 0.52 (p less than 0.001). With pH at 7.4 and 7.8, VO2 averaged 4.42 +/- 0.77 ml/min/100 gm and 3.66 +/- 0.99, respectively (p less than 0.01). The data indicate that a reduced P50 limits O2 diffusion to brain at a normal but fixed blood flow rate despite capillary recruitment.

Effect of anemia on tolerance of hemorrhagic shock in rats was studied to examine opposing effects of altered oxygen capacity and viscosity on oxygen delivery at reduced blood flow. Hematocrit was first reduced by exchange transfusion. Hypotension (BP = 30 Torr) was induced and maintained at this level by controlled hemorrhage; it was terminated when reinfusion of shed blood became necessary to sustain this blood pressure. The period of compensation (time at 30 Torr until reinfusion) in control rats (Hct = 42.5 +/- 2.7%) was 59.23 min; in anemic rats (Hct = 23.3 +/- 2.2%) it was 53 +/- 15 min (SD, P = 0.086). Bleeding rate during shock, mortality, VO2, acid-base balance, and mortality were not influenced by anemia, except for slightly higher lactate in late shock in anemia. The lack of influence of anemia (cf. other perturbations of oxygen transport) was apparently due to a 59-88% increase in cardiac ouput during shock in anemia, which maintained VO2.

The use of canine erythrocytes suspended in artificial plasma to maintain the isolated brain was investigated in 18 preparations. Two plasmas were studied: One (AP1) contained electrolytes, amino acids, and albumin; the other (AP2) was similar to CSF and contained a mixture of 37 organic nutrients plus electrolytes and albumin. The CMRO2, CMRglu, and cerebral vascular resistance (CVR) were measured during 2 h of perfusion, and tissue high-energy phosphates were measured at the end of perfusion. The AP1 and AP2 groups were compared with control preparations perfused with canine red blood cells suspended in buffy coat-poor canine plasma. Both CMRO2 and ATP decreased to 60% of the control value; CVR increased to 187% of the control value in both groups following 2 h of perfusion. After 2 h of perfusion, the calculated value of intracellular pH (pHi)--based on creatine kinase equilibrium--remained normal (6.96) for the control brains, but decreased to 6.49 and 6.63, respectively, for the AP1- and AP2-perfused brains. Thus, there appears to be an eventual disruption of normal oxidative metabolism resulting in energy failure, possibly caused by the absence of an essential nutrient from the artificial plasma. For studies of intermediary metabolism in isolated normothermic brain, diluted whole blood appears to be the perfusate of choice.

Effects of acute and maintained isovolemic anemia on oxygen transport was studied during rest and exercise in normal males. Following 34% reduction in hemoglobin concentration (Hb), supine and standing Q rose acutely by 56% and 20%, respectively, but returned nearly to the control value by 10-14 days, producing a decrease in PVO2. Redistribution of blood flow appeared to compensate significantly for the decrease in systemic oxygen transport. 2,3-Diphosphoglycerate rose by 18%, in vivo PO2 at half-saturation of hemoglobin (P50) rose by approximately 2 mm over 7-9 days and probably afforded some compensation. The relationship between VO2 and external work intensity was independent of Hb. During exercise, Q/VO2 and VE/VO2 were increased in acute anemia, but PVO2, for a given VO2, decreased below control levels. After 10-14 days the relative increase in VE with exercise persisted; the increase in Q was less pronounced; and PVO2 was further decreased. With both acute and extablished anemia maximal exercise capacity and maximal VO2 (VO2 max) decreased in proportion to the Hb reduction.

Recently we have found that stimulation of NaCl transport in high-resistance MDCK cells enhances their prostaglandin formation. In the present study, we investigated the mechanisms by which prostaglandin formation could be linked to the ion transport in these cells. We found that stimulation of transport caused a transient stimulation of prostaglandin formation lasting 5-10 min. The rise in prostaglandin formation was paralleled by a rise of free intracellular arachidonic acid. Analysis of membrane lipids revealed that the rise of free arachidonic acid was paralleled by a loss of arachidonic acid from polyphosphoinositides. We failed to obtain indications for the stimulation of calcium-dependent phospholipase A2. However, we did obtain evidence that the incorporation of arachidonic acid into phospholipids was diminished during stimulation of ion transport, indicating a decreased rate of reesterification. Despite the fact that there was no significant fall in total cellular ATP on stimulation of ion transport, we found a high and transient rise of lactate production of the cells on stimulation of the ion transport indicating an alteration of the ADP/ATP ratio. Moreover, prostaglandin formation and lactate formation were linearly correlated in this situation. When glucose utilization was inhibited by mannoheptulose, the rise in lactate formation was abolished, whereas that of PG formation was unaltered, indicating that lactate formation and prostaglandin formation were not causally linked on stimulation of ion transport. Our results suggest that an increase in the rate of sodium chloride transport by MDCK cells stimulates formation by an inhibition of reesterification of free arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of increased blood-oxygen affinity on tolerance of hemorrhagic shock was studied in pentobarbital-anesthetized rats. Rats were first exchanged transfused with blood whose P50 had been reduced by various methods by 4-21 Torr. Hypotension (BP = 30 Torr) was induced and maintained at this level by controlled hemorrhage; it was terminated when reinfusion of shed blood became necessary to sustain this blood pressure. Initial rate of bleeding during shock was inversely proportional to P50, varying from 0.52 ml.min-1.kg-1 in controls to 1.5 ml.min-1.kg-1 in the group with the lowest P50, a reaction probably indicating increased sympathetic output in the latter group. Duration of shock tolerance varied from 50 +/- 16 min in controls to 28 +/- 11 min (SD, P less than 0.001) in the group with the lowest P50. Central venous SO2 (SCVO2) and PO2 (PCVO2) were significantly higher and lower, respectively, in low-P50 animals than in controls, probably because of limited oxygen extraction due to increased blood oxygen affinity. VO2 and cardiac output were significantly lower, and mortality was significantly greater, in low-P50 animals. The data suggest that a left shift of the oxygen dissociation curve limits oxygen delivery during hemorrhagic shock.

The oxygen delivery system consists of multiple components balanced to provide optimal oxygen supply to all tissues and arranged such that an abnormality in one component is compensated by adjustments in others. Analysis of pertinent data indicates that leftward shifts of the oxygen dissociation curve (ODC) in normal animals and persons elicit adaptive changes in other components which sustain normal oxygen supply. By contrast, several recent studied indicate that leftward ODC shifts, when occurring in combination with other abnormalities of oxygen delivery, produce or aggravate hypoxia. These data suggest that the brain and heart are the organs particularly at risk. It is concluded that leftward ODC shifts, due to massive transfusion of stored blood and to hyperventilation of unconscious patients, are most likely to be hazardous in the presence of poor perfusion, coronary artery disease, or cerebrovascular disease.

The Bohr effect was measured in normal whole blood and in blood with low DPG concentration as a function of oxygen saturation. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of isotonic NaOH or HC1 at constant PCO2 (fixed acid Bohr effect). At nornal DPG concentration CO2 Bohr effect was -0.52 at 50% blood oxygen saturation, increasing in magnitude at lower saturation and decreasing in magnitude at higher saturation. In DPG depleted blood with base excess (BE) similar to 0 meq/1, there was similar dependence of CO2 Bohr effect on oxygen saturation. At BE similar to -10 meq/1, influence of saturation was comparable, but the magnitude of the Bohr effect was markedly increased at all saturations. Fixed acid Bohr effect at normal DPG concentration was -0.45 at saturations of 50-90% but decreased at lower saturations. In DPG-depleted blood fixed acid Bohr effect averaged about -0.33 with minimal variation with saturation. Influence of DPG on oxygen affinity was greater at intermediate saturations and less at saturations below 20% and above 80%. Effect of CO2, independent of pH, was many fold greater at lower oxygen saturations than at higher saturations. These results support the suggestion that the alpha chain of hemoglobin is the site of the initial oxygenation reaction. Physiologically they indicate that the relative contribution of CO2 and fixed acid, as well as the level of oxygen saturation and DPG concentration, may be important in determining PO2 of capillary blood and resulting oxygen delivery.

The oxygen dissociation curve (ODC) and Bohr effect of human blood were measured over a wide range of acid-base conditions and blood-O2 saturations at normal and low 2,3-diphosphoglycerate (DPG) concentrations. The fixed-acid Bohr factor (H+ titration) was relatively constant as a function of O2 saturation. At normal DPG levels, the H+ Bohr factor was not dependent on PCO2 except for a modest increase (in absolute magnitude) at very low PCO2 (7 Torr). For low DPG blood, the H+ Bohr factor decreased markedly with increasing PCO2 such that at PCO2 101 Torr, delta log PO2/delta pH varied between 0 and -0.13. The CO2 Bohr factor (CO2 titration) was strongly dependent on O2 saturation, being greatest at low O2 saturation. For normal DPG blood, this factor did not differ significantly at base excess (BE) +0.1 and +19.5 mmol/l, but decreased slightly at BE -20.3 mmol/l. For low DPG blood this factor showed a modest decrease with BE from -0.5 to +19.5 mmol/l but increased appreciably at BE -18.6 mmol/l. The data indicate that the Bohr factor may vary from unmeasurable levels to -0.93 under physiological and pathophysiological conditions. Results allow calculation of the shape and position of the ODC under the diverse conditions which may attend gas exchange.

Temperature-dependent change in hemoglobin-oxygen affinity was measured as a function of hemoglobin-oxygen saturation. In addition, the CO2 Bohr factor and fixed acid Bohr factor were measured as a function of saturation of temperatures of 23, 30, 37, and 44 degrees C. Measurements were made on normal blood and blood with reduced 2,3-diphosphoglycerate (DPG). The influence of temperature is greatest at low saturation and is enhanced slightly by DPG depletion. The CO2 Bohr factor is increased at high temperatures; this is primarily due to increased carbamino formation with rising temperature, especially at lower oxygen saturation. The effect of DPG on oxygen affinity is reduced at a high temperature and elevated at low temperature. These diverse effects of temperature on hemoglobin-ligand interaction require consideration in assessing oxygen delivery when temperature is increased or decreased.