"Is there a need for blood substitutes in the new millennium and what should we expect in the way of safety and efficacy?".
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Blood Substitutes↗
Biomedical subjects
M Feola
Publications and source records attributed to M Feola.
Comparison of thrombolytic therapy and primary coronary angioplasty with liberal stenting for inferior myocardial infarction with precordial ST-segment depression: immediate and long-term results of a randomized study.
OBJECTIVES: The aim of the study was to compare randomly assigned primary angioplasty and accelerated recombinant tissue plasminogen activator (rt-PA), in patients with "high-risk" inferior acute myocardial infarction (ST-segment elevation in the inferior leads and ST-segment depression in the precordial leads). BACKGROUND: The ST-segment depression in the precordial leads is a marker of severe prognosis in patients with inferior myocardial infarction. The comparative outcome of treatment with primary angioplasty or lysis with accelerated rt-PA has not been investigated. METHODS: One hundred and ten patients within 6 h of symptoms were randomized to either treatment. To assess the in-hospital and 1-year outcome of both treatments the following results were compared: death or nonfatal infarction, recurrence of angina, left ventricular ejection fraction (LVEF), and the need for repeat target vessel revascularization (TVR). RESULTS: In patients treated with angioplasty (55) and rt-PA (55) the rate of in-hospital mortality and reinfarction was 3.6% versus 9.1% (p=0.4). Recurrence of angina was 1.8% versus 20% (p=0.002), new TVR was used in 3.6% versus 29.1% (p=0.0003), and the LVEF (%) at discharge was 55.2+/-9.5 versus 48.2+/-9.9 (p=0.0001). There were no hemorrhagic strokes, no emergency coronary artery bypass graft (CABG) and identical (5.5%) need for blood transfusions. At 1 year, the incidence of death, reinfarction or repeat TVR was 11% in the percutaneous transluminal coronary angioplasty (PTCA) group versus 52.7% in the rt-PA group (log-rank 22.38, p < 0.0001). CONCLUSIONS: Primary angioplasty is superior to accelerated rt-PA in terms of both myocardial preservation and reduction of in-hospital complications in patients with inferior myocardial infarction and precordial ST-segment depression. Primary angioplasty also yields a better long-term event-free survival.
Adult↗
Ambulatory 24-hour blood pressure monitoring: correlation between blood pressure variability and left ventricular hypertrophy in untreated hypertensive patients.
BACKGROUND: Left ventricular hypertrophy (LVH) appears to be poorly correlated with clinical measurements of blood pressure: a better correlation may be observed with data from 24 h ambulatory blood pressure monitoring (ABPM). The aim of this study was to compare the results of non-invasive ABPM in a population of patients with essential hypertension who had never been treated, subdividing them based on the presence or absence of LVH in the transthoracic echocardiogram (LVMI, left ventricular mass index > 135 g/m2 in males and > 110 g/m2 in females). METHODS: Eighty hypertensive patients with mild or moderate hypertension underwent routine blood tests, a 24 h ABPM and a transthoracic echocardiogram. Based on the ABPMs, we analyzed average 24 h systolic and diastolic blood pressure (BP), average daytime (6 a.m.-10 p.m.) and nighttime (10 p.m.-6 a.m.) systolic and diastolic BP, average morning (6-12 a.m.) BP and the number of dipper or non-dipper patients. The echocardiographic study included the calculation of left ventricular mass using Devereux's formula according to the Penn convention, analysis of the patterns of left ventricular geometry and a study of left ventricular diastolic function. RESULTS: Thirty-five (43.7%) patients had LVH at the echocardiographic study. In 52 subjects, the clinical history showed at least one BP measurement > 140/90 mmHg in the year prior to our observation. The average age was 48 +/- 11, without any significant correlation to LVMI (r = 0.13). The magnitude of the S-wave in V1 and the R-wave in V5 and the magnitude of the tallest R-wave and S-wave in the electrocardiogram analysis had a significant correlation with LVMI (r = 0.23 and r = 0.26, respectively). The echocardiogram revealed a normal left ventricular geometry in 43.8% of hypertensive patients, concentric remodeling in 13.8%, concentric hypertrophy in 16.2% and eccentric hypertrophy in 26.2%. The isovolumic relaxation time (IVRT) and A-wave were significantly correlated with LVMI (r = 0.49 and r = 0.33, respectively). LVMI had a significant correlation with systolic BP at ABPM (24 h systolic BP r = 0.34; daytime systolic BP r = 0.35; nighttime systolic BP r = 0.28; 6-12 systolic BP r = 0.29) but not with diastolic BP. Dipper patients represented 76.3% of the population, without any difference in LVMI between dippers and non-dippers (p = 0.09). Dipper patients had a higher prevalence of normal left ventricles as compared with non-dippers (p < 0.0001). White-coat hypertension was observed in 7.5% of hypertensive patients. CONCLUSIONS: The prevalence of LVH in our population was high (43.7%) and some parameters related to diastolic left ventricular function (IVRT, A-wave) were correlated with LVMI. Systolic ambulatory BP was significantly correlated with LVMI, while diastolic BP was not.
Adult↗
[Primary angioplasty in acute inferior myocardial infarct with anterior ST-segment depression: the long-term follow-up].
BACKGROUND: Concomitant anterior ST-segment depression is a marker of severe prognosis in inferior myocardial infarction. PATIENTS AND METHODS: Prospective observational study in patients with inferior acute myocardial infarction and ST-segment depression > or = 4 mm in the anterior leads, who were treated with primary angioplasty. Angiography was performed at hospital discharge and at six months, and a clinical follow-up was obtained at one year after the infarction. RESULTS: Sixty-three patients were included in the study. Pre-hospital and in-hospital delay were 147 +/- 70 minutes (20-355) and 54 +/- 11 minutes (18-80), respectively. Angioplasty was successful in all patients and 48 stents were implanted in 36 patients (57%). Angiography was performed at hospital discharge in 55 patients (87%) and showed a TIMI grade 3 coronary flow in the infarct-related artery in all cases. The left ventricular ejection fraction was 0.55 +/- 0.09 (0.4-0.8). One patient (1.6%) died before discharge, two (3.2%) had ischemic complications (one had non-fatal reinfarction, another had recurrent angina at rest), and three (4.9%) had local vascular complications. At the six-month follow-up, none of the patients had died. One had suffered reinfarction (1.6%) and another had been readmitted for recurrence of angina at rest (1.6%); none had symptoms of stable angina. The ejection fraction was 0.56 +/- 0.12 and eight patients (14%) showed angiographic restenosis. At twelve months, two patients had died (1.6%) and five (8%) had required readmission to hospital. CONCLUSIONS: Primary angioplasty yielded favorable results in this group of patients. Our data confirm the efficacy of primary angioplasty for the treatment of acute myocardial infarction, with a low rate of clinical (3.2%) and angiographic (14%) restenosis at six months, and a high rate (87%) of event-free survival at one year follow-up.
Adult↗
Protective effect of selenium on hemoglobin mediated lipid peroxidation in vivo.
The toxicity of hemoglobin (Hb) solutions is related, at least in part, to the generation of oxygen free radicals with consequent induction of lipid peroxidation. The present study was designed to examine whether selenium (Se) may prevent the oxidative damage observed after Hb administration. Three groups of rats were compared; (I) the negative control group receiving autotransfusion; (II) the positive control group with replacement of 40% total blood volume (TBV) with modified bovine Hb solution; and (III) the experimental group which received dietary supplemented selenium (Na2SeO3) in daily doses of 5 micrograms.kg body wt-1 in drinking water, 4 days before and 3 days after administration of Hb solution in the same volume as in group II. Three days after Hb injection, all animals were sacrificed. Oxidative stress was determined by measuring conjugated dienes (CD) and thiobarbituric acid reactants (MDA) in homogenates of the perfused liver, heart, lungs, kidney, brain and plasma. Additionally, the 45k x g supernatants of the organs homogenates and plasma were assayed for the antioxidant enzymes activity: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and the intracellular level of reduced glutathione (GSH). Also, a measurement of nonprotein bound intracellular free iron (Fe) and tissue Se concentrations was performed. Simultaneously, injury dysfunction of vital organs was assessed by the measurement of plasma LDH, SGPT, creatinine, blood PaO2 and by histopathological studies. Results indicate that the exchange transfusion with Hb solution introduced significant increases in CD and MDA formation, particularly in the liver and heart tissues, and in plasma. While the values of the SOD and CAT in the liver and heart tissue were generally altered, the SOD/CAT ratio was also increased. After the Hb injection, activity of GSH-Px remained unchanged and was associated with significant depletion of GSH. The plasma levels of SGPT and LDH were increased, but the creatinine and PaO2 was similar to that of the control and corresponded with histopathological findings. The liver and heart intracellular free Fe was found to be higher than that of control. Treatment with Se was very effective in the prevention of oxidative damage introduced by Hb. Full protection from MDA formation was noted in liver tissue (p < 0.001). Also, plasma levels of MDA, SGPT and LDH were significantly decreased and appeared similar to that of the control group (I). Treatment with Se increased liver (p < 0.05) and plasma (p < 0.1) level of GSH-Px.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Cytokines and PAF release from human monocytes and macrophages: effect of hemoglobin and contaminants.
Monocytes [M] were isolated from venous blood of healthy volunteers and activated macrophage-leukocytes (Mø-L] were obtained from peritoneal fluid of patients with mild endometriosis. The M were incubated with pyrogen free CELLGRO culture medium [Control], and with 0.2 mM of [A] unmodified bovine hemoglobin (UHb), [B] Hb crosslinked to form polymers with M.W. < 400 kDa (LMWHb), [C] Hb crosslinked to form large polymers (< 1,020 kDa) (HMWHb), and Mø-L additionally with [D] UHb contaminated with endotoxin (Hb+E) (2.5 EU/mL), and [E] UHb contaminated with phospholipids (Hb+PLs). The Mø-L medium of incubation was tested for TNF alpha, IL-1 alpha, IL-6, GM-CSF and PAF after 6 and 24 hours, but M for TNF alpha and GM-CSF at 12, 24 and 36 hours. Mø-L were found more responsive than M colonies. The strongest reaction of Mø-L was to Hb+E, which produced levels of cytokines and PAF higher than Controls (p < 0.001). Hb+PLs induced smaller increases of TNF and IL-6, and a decrease in the levels of IL-1 and GM-CSF. However, the release of PAF was much greater with this Hb than with Hb+E. UHb caused an increase in TNF, as compared to control (p < 0.01). LMWHb generated a similar increase in TNF, but also a decrease in IL-1. Both polymerized Hb forms inhibited expression of GM-CSF. HMWHb induced high levels of TNF, IL-1 and PAF. UHb, LMWHb and HMWHb significantly increase levels of TNF in M cultures after 36 hours of incubation.
Animals↗
Reaction of human endothelial cells to bovine hemoglobin solutions and tumor necrosis factor.
Human umbilical vein endothelial cells (HUVEC) were incubated for 24 hours with 0.1 mM or 0.3 mM of: [A] unmodified (U) Hb-FeIIO2; [B] UHb-FeIII; [C] UHb-FeIV-OH; [D] polymerized low molecular weight Hb (< 400 kDa); [E] polymerized high molecular weight Hb (< 1,020 kDa); [F] polymerized low molecular weight Hb + Endotoxin (2.5 EU/mL); [G] rTNF alpha 100 pg/mL; [H] rTNF alpha 400 pg/mL; [I] rTNF alpha 800 pg/mL. The medium of the incubation was tested for LDH (index of cell injury), and for cytokines GM-CSF and IL-1 alpha released by the cells. The data suggests that oxidation status of the iron in the Hb molecule and concentration of Hb play an important role in causing EC injury. The highest toxicity was observed when EC were incubated with 0.1 mM of UHb-FeIV-OH (ferryl-Hb) and no toxicity with 0.3 mM of Hb-FeIII (ferric-Hb). The direct stimulation of EC by Hb for the production of IL-1 was limited, related only to high molecular weight Hb polymers or to Hb+E, however GM-CSF expression was increased by almost all Hb forms. TNF induced dose-related injury (R2 = 0.986), and dose-related release of IL-1 (R2 = 0.977). A different EC reaction was observed on the release of GM-CSF. Intermediate levels of TNF (400 pg/mL) increased the expression of this cytokine, while high levels (800 pg/mL) blocked its release.
Animals↗
[Analysis of right electrocardiographic leads in 195 normal subjects].
AIM: The aim of the present study was to analyse age-related differences in the morphology of QRS complex and ST-T segment of right-sided chest ECG leads (V3R-V6R) in normal subjects. METHODS: One hundred ninety-five subjects evaluated for competitive sport training were divided into 2 groups according to age: group A (18-35 years) 77 subjects; group B (36-65 years) 118 subjects. All subjects underwent a complete clinical examination, conventional 12-lead ECG with right-sided chest leads, spirometric tests, a maximal stress-test (Bruce protocol), and a cardiac ultrasound study. None had signs or symptoms of cardiopulmonary disease nor of thoracic abnormalities, and all had normal standard ECGs. RESULTS: An rS morphology in V3R-V4R was observed in 92%-84% and 92%-81% of subjects in groups A and B, respectively (p = NS). The QS morphology in V6R was observed in 15% of subjects in group A and in 11% in group B (p = NS). Negative T-waves in V6R were more often observed in group A than B (94% vs 85%, p < 0.03). Isoelectric T-waves in V3R were found in 10% of subjects in group A and 21% in group B (p < 0.04). The amplitude of R-wave was always higher in group A (p < 0.01). An upsloping ST-T segment (0.5-1 mm) was observed only in V3R-V4R, with a prevalence of 23% in group A and 13% in group B in V3R (p < 0.05). CONCLUSIONS: No significant differences were observed between the 2 groups as to QRS complex of the right-sided ECG leads. A QS morphology may be observed even in normal subjects. The polarity of T-wave is quite variable, but in V6R it is most often negative among young people. Elevation of ST-T segment may be observed only in V3R and V4R, and more often in young subjects in the former lead.
Adolescent↗
[Diagnostic and prognostic elements of echography in parapneumonic pleural effusion].
A retrospective study was made with the purpose of testing Ultrasound usefulness in differential diagnosis between empyematous and non empyematous evolution of parapneumonic effusions. A total of 64 patients with pneumonia and pleural effusion assisted between February 1st, 1982 and June 30th, 1989 had an Ultrasound transparietal study at the beginning and after 3 and/or 7 days of admission, with a real time equipment and a 3.5 Mhz linear transducer; they ranged between 12 and 90 years old, 27 were females and 37 males. Of these, 51 were cured by medical treatment, and 13 needed surgical drainage because of empyema evolution. The very high significant statistic signs of good prognosis in Ultrasound study were: free effusion (Table 2, p < 0.0002), maximal width less than 30 mm in sitting position (Table 1, p < 0.0001), unblurred peripleural images (Table 3, p < 0.002), and maximal homolateral diaphragmatic movement percentage more than 39% of the total (Table 4, p < 0.004); in the evolution, decrease of the maximal width effusion and slow improvement of diaphragmatic movement. Patients not included in the previous setting (31.2% of the total) were in the risk group (Fig. 1) and had loculated effusion, and/or maximal width of 30 mm or more, and/or blurred peripleural images, and/or homolateral maximal diaphragmatic movement percentage lower than 25% of the total. Less than half of this risk group was cured only with medical treatment; and they had an ultrasound evolution similar to the others cured in the same manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Clinical trial of a hemoglobin based blood substitute in patients with sickle cell anemia.
A hemoglobin based "blood substitute" developed at Texas Tech University and produced in Italy was used in nine children with sickle cell anemia admitted to the Centre de l'Anemie S. S. of Kinshasa, Zaire. Five of the children presented an "aplastic crisis," for example, a sudden decrease in hemoglobin concentration associated with absence of reticulocytes in the peripheral blood, and four were admitted with unremitting severe pain because of a "vaso-occlusive crisis." The blood substitute contained 10 per cent hemoglobin and was infused in a volume corresponding to 25 per cent of blood volume (calculated for each child as equal to 7 per cent of body weight in kilograms). No adverse reaction was noted. To the contrary, all patients presented beneficial effects. In the patients with aplastic crisis, the hemoglobin solution stimulated the bone marrow to a significant erythropoietic effect, whereby the number of reticulocytes in the peripheral blood increased from zero to 47 +/- 7 per cent. In the patients with vaso-occlusive crises, pain was quickly relieved.
Adolescent↗
Quality control of hemoglobin solutions. I. The purity of hemoglobin before modification.
It is not yet clear whether the toxicity of hemoglobin solutions is due to hemoglobin per se, contaminants, or both. To elucidate the problem, it is first necessary to prepare "pure hemoglobin," i.e., hemoglobin completely free of (a) bacterial endotoxins, (b) phospholipids of the red cell membrane, and (c) other proteins and/or peptides. The methods found most sensitive in the determination of such purity are here presented. Consensus on the adoption of these methods and on the meaning of the term "purity" would help to achieve (a) a better understanding of the toxicity problem, (b) a more meaningful exchange of information among investigators and (c) the ultimate development of nontoxic solutions.
Chromatography, High Pressure Liquid↗
In vitro and in vivo studies of heparinized-collageno-elastic tubes.
Heparin was covalently coupled to collageno-elastic grafts (CET) derived from lamb carotid arteries, by using the crosslinking agent 1-ethyl-3 (3-dimethyl-aminopropyl) carbodiimide (EDC). The collagenous grafts were pretreated with various aminating agents in order to enhance the number of available binding sites on the collagen surface. By varying the EDC/heparin weight ratio, the pH of the immobilization media, and the pretreatment agent, a global search pattern maximized heparin loading at 3.90 +/- 0.36 USP heparin/cm2 collagenous graft surface when the EDC/heparin ratio was 2:1 at a pH of 1.5 with 1 M hydroxylamine sulfate as the pretreatment agent. Heparinized CETs were superior to nonheparinized CETs by exhibiting both enhanced antiplatelet activity in using an in vitro differential recirculation reactor with chromium-51 tagged platelets and enhanced patency when interposed in canine carotid arteries. Both antiplatelet activity and patency duration for heparinized CETs were independent of heparin loading.
Animals↗
Management of hepatic hydrothorax with a peritoneovenous (Denver) shunt.
One patient with alcoholic cirrhosis and a massive hydrothorax resistant to medical management and thoracocentesis was treated with a Denver peritoneovenous shunt. This patient's progress has been followed for 14 months and the pleural effusion has not recurred.
Female↗
Biocompatibility of hemoglobin solutions. II. The inflammatory reaction of human monocytes and mouse peritoneal macrophages.
This study explored the inflammatory mechanism of toxicity of hemoglobin solutions (Hb-S). Human monocytes and mouse activated peritoneal macrophages were incubated with seven different solutions. The first four consisted of non-cross-linked bovine Hb. Of these, Hb-SI was incompletely purified of stromal phospholipids, Hb-SII was contaminated with environmental bacterial endotoxins, Hb-SIII was pure hemoglobin, and Hb-SIV was pure Hb with the addition of superoxide dismutase (SOD), catalase (CAT), and mannitol (M). The other three solutions were made of pure bovine Hb cross-linked with different agents: Hb-SV, reacted with glutaraldehyde; Hb-SVI reacted with bis-3,5-dibromosalicyl fumarate (DBSF); and Hb-SVII reacted with a ring-opened dialdehyde derivative of 5'(pyro)-phosphate of adenosine (ATP) (o-ATP). The reaction of monocytes and macrophages was studied in terms of (a) O2-derived radicals, as determined by the measurement of H2O2 and lipid peroxides; (b) complement factor C3a desArg; (c) 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin); and (d) TxB2 (stable metabolite of thromboxane) released into the culture supernatants. The most significant reactions were obtained with the solutions contaminated with stromal phospholipids or bacterial endotoxins. Pure Hb was less reactive. Further reduction in proinflammatory activity was achieved by the addition of oxygen radical-scavengers (SOD, CAT, and M), or by the cross-linking of Hb with DBSF or o-ATP.
6-Ketoprostaglandin F1 alpha↗
Generation of free oxygen radicals and the toxicity of hemoglobin solutions.
The observed toxicity of hemoglobin solutions (HbS) might depend, at least in part, on the tendency of Hb to autoxidation with generation of oxygen free-radicals. Aims of this study were: (1) to quantitate plasma elevations of H2O2 and lipid peroxides after replacement of 1/3 of calculated blood volume in various groups of rabbits with different Hb solutions; (2) to correlate these elevations with parameters of brain, heart, lung, liver and kidney injury or dysfunction; and (3) investigate the protective effect of mannitol as a radical scavenger. One Hb solution contaminated with stromal phospholipids raised H2O2 from 31.2 +/- 1.9 to 166 +/- 20 mumol/ml, lipid peroxides from 1.62 +/- 0.5 to 7.29 +/- 0.3 nmol/ml, CK-BB (brain isoenzyme) from 250 +/- 25 to 470 +/- 50 IU/L, CK-MB (myocardial isoenzyme) from 2.98 +/- 0.03 to 10.73 +/- 1.3 IU/L and SGPT from 38.1 +/- 5 to 167 +/- 45 IU/L, and reduced PaO2 from 87 +/- 10 to 57.5 +/- 2.5 mm Hg and creatinine clearance from 1.5 +/- 0.3 to 0.13 +/- 0.03 mg/min/Kg. These changes were progressively less severe with pure unmodified Hb, pure Hb crosslinked with "o-ATP", and pure crosslinked Hb + mannitol (4 mg/ml). These observations indicate a significant role for oxygen-derived radicals in the toxicity of Hb solutions.
Alanine Transaminase↗
Nephrotoxicity of hemoglobin solutions.
Nephrotoxicity is a problem of hemoglobin solutions (HbS) that still awaits full elucidation and correction. Therefore, a study was conducted using five HbS with different characteristics to replace 1/3 of blood volume in five groups of rabbits. All HbS contained bovine Hb, 6.5 g/dl, dissolved into a balanced electrolyte solution. HbS-I was Hb incompletely purified of stromal phospholipids and environmental bacterial endotoxins, and uncrosslinked; HbS-II was pure Hb non crosslinked; HbS-III was completely purified and crosslinked; HbS-IV was like HbS-III, but with pH 8.4; and HbS-V was like HbS-III, with the addition of mannitol. The effects of blood replacement with these solutions were studied on: (a) PAH clearance (expression of renal plasma flow); (b) endogenous creatinine clearance (expression of glomerular filtration); (c) fractional excretion of sodium and (d) urine/plasma osmolarity (expressions of tubular function). Histological changes were assessed after 24 hours. Significant alterations were observed in decrescent order following the administration of HbS-I, -II and -III, while HbS-IV and -V were well tolerated. These results suggest that the nephrotoxicity of Hb solutions can be prevented by the following steps: (1) complete purification of Hb; (2) complete crosslinking; and (3) protection of the kidney by alkalinization of the urine and/or the addition of mannitol.
Animals↗
Toxic factors in the red blood cell membrane.
The toxic effects of hemolysed RBCs have been studied for more than 100 years, but the specific factors involved have not been identified. This study focused on phosphatidylethanolamine (PE) and phosphatidylserine (PS), two aminophospholipids that normally reside on the cytoplasmic side of the red cell membrane. An in vitro experiment with murine peritoneal exudate macrophages showed that PE and PS: a) stimulated the production of H2O2, complement factor C3a, prostacyclin, and thromboxane at a dose of 5 micrograms/ml; b) produced cell injury, evidenced by release of lipid peroxides, LDH, and by morphologic changes on phase-contrast and electron microscopy at a dose of 50 micrograms/ml; and c) caused cell death in 50-66% of cells at a dose of 100 micrograms/ml. An in vivo experiment showed that PE and PS injected intravenously into various groups of rabbits: a) caused only transient hypotension at a dose of 0.05 mg/kg body weight; b) caused significant hypotension, cardiac arrhythmias, bronchospasm, activation of intravascular coagulation, complement, platelets, and leukocytes with release of histamine, serotonin, and thromboxane at a dose of 0.10 mg/kg; and c) caused cardiac arrest and death at a dose of 0.30 mg/kg. In contrast, the phospholipids of the outer cell membrane (phosphatidylcholine and phosphatidylinositol) caused minimal toxicity in vitro and none in vivo.
Animals↗
Biocompatibility of hemoglobin solutions. I. Reactions of vascular endothelial cells to pure and impure hemoglobins.
Hemoglobin (Hb) solutions can cause vasoconstriction and activation of intravascular coagulation. Because the endothelium plays a major role in the regulation of vascular tone and hemostasis, a study was conducted of human umbilical vein endothelial cells (EC) incubated with various Hbs. Cell injury was evaluated by electron microscopy and the release of lactic dehydrogenase, H2O2, and procoagulant "tissue factor." Cell reaction was assessed by the measurement of 6-keto-prostaglandin F (PGF)1 alpha (metabolite of prostacyclin) and thromboxane B2 (metabolite of thromboxane A2). Incubation with unmodified bovine hemoglobin for 24 h caused no cell injury and a reaction characterized by 48.4 +/- 8.2% increase in 6-keto-PGF1 alpha production, accompanied by 40.2 +/- 9.4% reduction in thromboxane (Tx)B2 (compared with a control group of EC incubated with saline solution). Incubation with a nonpure Hb solution (Hb plus red blood cell membrane aminophospholipids; a-PLs) caused cell injury with significant release of tissue factor, plus a reaction characterized by 97.5 +/- 12.5% increase in TxB2 production accompanied by 25.3 +/- 3% reduction in 6-keto-PGF1 alpha. A second nonpure Hb [Hb plus bacterial environmental endotoxin (E)] caused cell injury, the release of tissue factor, and increased production of both prostaglandins, with greater release of TxB2 (197 +/- 17%) than of 6-keto-PGF1 alpha (112 +/- 8.3%). These data indicate that the endothelium reacts differently to pure and nonpure hemoglobins. The biocompatibility of Hb solutions, with regard to vasoconstriction and activation of intravascular coagulation, depends on the absence of stromal a-PLs and bacterial E.
Animals↗