The quality of RBCs stored in CPD/ADSOL.
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Adenine↗
Biomedical subjects
C R Valeri
Publications and source records attributed to C R Valeri.
Survival and function of baboon RBCs released from clotted blood and washed before autologous transfusion.
BACKGROUND: One alternative to an allogeneic transfusion is the salvaging of the patient's own shed blood. In this study, baboon blood was allowed to clot and the RBCs that were released from the clotted blood lysed with and without urokinase were washed before autologous transfusion. STUDY DESIGN AND METHODS: Forty-four studies were done in 13 baboons (Papio cynocephalus or Papio anubis) over a 3-year period. In 24 studies, a 50-mL volume of blood was collected without an anticoagulant and stored at 22 degrees C for as long as 72 hours before washing and autologous transfusion. In 20 other studies, a 50-mL volume of blood was collected without an anticoagulant and allowed to clot for 30 to 60 minutes. Urokinase, ranging from 2,500 to 10,000 units per mL, was added, and the blood was stored at 22 degrees C for 24 hours before washing and autologous transfusion. RESULTS: RBCs that were stored at 22 degrees C without urokinase for 24 hours exhibited an in vitro recovery value of 45 percent, a (51)Cr 24-hour posttransfusion survival of 86 percent, and an index of therapeutic effectiveness of 39 percent. The (51)Cr T(50) value was normal at 14 days, and RBC oxygen-transport function was slightly reduced. RBCs that were stored at 22 degrees C for 24 hours with 10,000 units per mL of urokinase exhibited an in vitro recovery value of 89 percent, a (51)Cr 24-hour posttransfusion survival value of 86 percent, and an index of therapeutic effectiveness of 76 percent. The (51)Cr T(50) value was normal at 14 days, and the RBC oxygen-transport function was only slightly reduced. CONCLUSION: Autologous baboon RBCs isolated from clotted blood treated or not treated with urokinase and washed before transfusion have excellent survival and normal or only slightly reduced oxygen-transport function.
Animals↗
Effects of hemoglobin-based oxygen-carrying solutions in anesthetized rats with acute ischemic renal failure.
The effects of three hemoglobin solutions were compared with those of iso-oncotic human serum albumin in rats with ischemic renal failure and sham-operated controls. Unmodified and alpha-alpha cross-linked hemoglobins both increase mean arterial pressure and systemic vascular resistance and reduce cardiac output substantially and to a comparable extent. In contrast, omicron-raffinose cross-linked hemoglobin has no deleterious effect on any of these parameters. In sham-operated rats unmodified hemoglobin reduces the glomerular filtration rate (GFR) by approximately 30%, whereas neither of the two cross-linked hemoglobins has any adverse effect on GFR in this group. None of the three hemoglobin solutions exacerbated the degree to which GFR was reduced by ischemia-reperfusion injury. Also, the degree of tubular necrosis induced by ischemia-reperfusion injury was also comparable in all groups. We conclude the following: (1) omicron-raffinose cross-linking, but not alpha-alpha cross-linking, ameliorates the effects of unmodified hemoglobin on vascular resistance and cardiac output; (2) both forms of cross-linking reduce the nephrotoxicity exhibited by unmodified hemoglobin in sham-operated rats; and (3) none of the hemoglobin solutions exacerbate renal injury induced by ischemia-reperfusion.
Acute Kidney Injury↗
Posttransfusion survival (24-hour) and hemolysis of previously frozen, deglycerolized RBCs after storage at 4 degrees C for up to 14 days in sodium chloride alone or sodium chloride supplemented with additive solutions.
BACKGROUND: Previously frozen human RBCs currently are glycerolized and deglycerolized by the use of open systems that limit storage of the deglycerolized RBCs at 4 degrees C to only 24 hours. STUDY DESIGN AND METHODS: Healthy male volunteers who met AABB requirements for blood donors (n = 38) were studied. A volume of 450 mL of blood was collected into CPDA-1. The RBC concentrates were stored at 4 degrees C for 3 to 6 days before being frozen with 40-percent (wt/vol) glycerol and stored at -80 degrees C. The RBCs were deglycerolized, resuspended in 0.9-percent sodium chloride and 0.2-percent glucose (SG) solution or SG solution supplemented with AS-1, AS-3, or AS-5, and stored in the resuspension medium at 4 degrees C for 14 days. RESULTS: The mean +/- SD freeze-thaw-wash process recovery was 90.0 +/- 4.0 percent for all 38 units. The mean 24-hour posttransfusion survival value was 79 percent for deglycerolized RBC stored at 4 degrees C for 7 days in SG alone, SG plus AS-3, or SG plus AS-5. Deglycerolized RBC that were stored at 4 C for 14 days in SG supplemented with AS-1, AS-3, or AS-5 had a mean 24-hour posttransfusion survival of 74 percent. After 7 days of storage of deglycerolized RBCs in SG alone, the mean hemolysis was 3. 7 percent. After 14 days of storage of deglycerolized RBCs in SG supplemented with AS-1, AS-3, or AS-5, the mean hemolysis was 2.5 percent. CONCLUSIONS: The levels of hemolysis did not correlate with the 24-hour posttransfusion survival values.
Adenine↗
The survival, function, and hemolysis of human RBCs stored at 4 degrees C in additive solution (AS-1, AS-3, or AS-5) for 42 days and then biochemically modified, frozen, thawed, washed, and stored at 4 degrees C in sodium chloride and glucose solution for 24 hours.
BACKGROUND: A study was done to assess the quality of RBCs stored at 4 degrees C in AS-1, AS-3, or AS-5 for 42 days before biochemical modification and freezing. STUDY DESIGN AND METHODS: RBCs were stored at 4 degrees C for 42 days in AS-1, AS-3, or AS-5 and then biochemically modified with pyruvate, inosine, phosphate, and adenine solution (Rejuvesol), frozen with 40-percent (wt/vol) glycerol, and stored at -80 degrees C for at least 2 months. The RBCs were deglycerolized by the use of a cell washer (Haemonetics 115), and stored for 24 hours at 4 degrees C in a 0.9-percent sodium chloride and 0.2-percent glucose solution before the autologous transfusion. RESULTS: The mean freeze-thaw-wash recovery process produced RBC recovery values of 85 percent, with the mean 24-hour posttransfusion survival at 75 percent, and the mean index of therapeutic effectiveness at 64 percent for the RBCs stored at 4 degrees C in AS-1, AS-3, or AS-5 for 42 days before biochemical modification and freezing. All the units exhibited normal or slightly higher than normal 2,3 DPG levels after deglycerolization and postwash storage at 4 degrees C for 24 hours. CONCLUSION: RBCs stored in AS-1, AS-3, or AS-5 at 4 degrees C for 42 days and then biochemically modified with pyruvate, inosine, phosphate, and adenine and glycerolized, frozen, washed, and stored at 4 degrees C for 24 hours before autologous transfusion had acceptable in vitro and in vivo measurements.
Adenine↗
Intravascular circulation and distribution of human 51Cr-DBBF stroma-free hemoglobin, 51Cr-plasma, 51Cr-saline, 59FE-plasma, and 125I-albumin in the mouse.
Male B6C3HF1 mice were infused with human 51Cr-labeled DBBF (bis 3,5-dibromosalicyl fumarate) crosslinked stroma-free hemoglobin (SFH). In the first hour following SFH infusion, 11.2% of the infused radioactivity was found in the skin, 11.4% in muscle, 9.1% in the skeleton, and 5% in the liver. Twenty-four hours after infusion, 15.4% of the radioactivity was found in the skin, 10.3%, in the muscle, 16.6% in the skeleton, and 6.7% in the liver. The circulation and distribution of 51Cr-labeled DBBF-SFH were compared with levels of 51Cr labeled plasma, 51Cr in saline, 59Fe labeled plasma, and 125I albumin. The radioactivity in the blood was similar for 51Cr-DBBF-SFH, 51Cr-plasma, and 59Fe-plasma. During the 24-hour post-infusion period, extravascular distribution of the 51Cr-saline, 51Cr-plasma, and 125I albumin within the organs was similar to that of 51Cr-DBBF-SFH, with the highest levels being in skin, muscle, skeleton and liver, and no increase in the levels in the lung or spleen. The distribution of 59Fe compared to that of 51Cr-DBBF, 51Cr-plasma, 51Cr-saline, and 125I albumin can be explained by the fact that 59Fe is utilized in the production of new red blood cells.
Albumins↗
An experiment with glycerol-frozen red blood cells stored at -80 degrees C for up to 37 years.
BACKGROUND AND OBJECTIVES: Red cells frozen using 40% W/V glycerol are currently FDA approved for frozen storage at -80 degrees C for up to 10 years. MATERIALS AND METHODS: Red cells frozen with 40% W/V glycerol and stored at -80 degrees C for up to 37 years were thawed, deglycerolized, and stored at 4 degrees C for 24 h. RESULTS: Red cells frozen for up to 37 years had mean freeze-thaw-wash recovery values of 75%, less than 1% hemolysis, and normal ATP, 2,3-DPG and P50 levels, and 60% of normal RBC K(+) levels. CONCLUSIONS: Red cells frozen with 40% W/V glycerol can be stored at -80 degrees C for up to 37 years with acceptable in vitro results.
2,3-Diphosphoglycerate↗
Photochemical decontamination of red blood cell concentrates with the silicon phthalocyanine PC 4 and red light.
Various approaches are being developed for virus inactivation of red blood cell concentrates (RBCC) in order to increase the safety of the blood supply. We have been studying the silicon phthalocyanine Pc 4 for this purpose, a photosensitizer activated with red light. Pc 4 targets the envelope of pathogenic viruses such as HIV. To protect RBC during the process two main approaches are used: (i) inclusion of quenchers of reactive oxygen species produced during the treatment. Tocopherol succinate was found to be most effective for this purpose; (ii) formulation of Pc 4, a lipophilic compound, in liposomes that reduce its binding to RBC but not to viruses. As a light source we used a light emitting diode array emitting at 670-680 nm. An efficient mixing device ensures homogenous light exposure during treatment of intact RBCC. Treatment of 50 ml RBCC with 5 microM Pc 4 and 18 J/cm(2) light results in the inactivation of > or = 5.5 log(10) HIV, > or = 6.3 log(10), VSV and > or = 5 log(10) of PRV and BVDV. The relative sensitivities of these viruses based on the slope of virus kill versus light dose are 1.0, 1.25, 1.5 and 1.9 for HIV, VSV, PRV and BVDV, respectively. To achieve the same level of virus inactivation in 350 ml RBCC, the light dose needed is 40 J/cm(2). HIV actively replicating in CEM cells is as sensitive as cell-free and HIV in latently infected cells is 3-4 times more sensitive. Parasites that can be transmitted by blood transfusion (P. falciparum and T. cruzi) are even more sensitive than viruses. Following treatment, RBCC can be stored for 28 days at 4 degrees C with haemolysis below 1%. Previous studies under less favourable conditions showed that baboon RBC circulated with an acceptable 24 hr recovery and half-life. Genetic toxicological studies of Pc 4 with or without light exposure (mutagenicity in bacteria, mammalian cells in vitro and clastogenicity in vivo) were negative. We conclude that a process using Pc 4 and red light can potentially reduce the risk of transmitting pathogens in RBCC.
Animals↗
Transfusion medicine.
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Blood Transfusion↗
Comparison of the effects of transfusions of cryopreserved and liquid-preserved platelets on hemostasis and blood loss after cardiopulmonary bypass.
OBJECTIVE: The aim of the study was to compare the clinical effects and hemostatic efficiency of transfusions of platelets preserved in the frozen state for as long as 2 years with transfusions of platelets preserved in the conventional manner for as long as 5 days in patients undergoing cardiopulmonary bypass. METHODS: Seventy-three patients were prospectively randomly assigned to receive transfusions of cryopreserved or liquid-preserved platelets. Nonsurgical blood loss was measured during and after the operation. Bleeding time, hematologic variables, and the bleeding time site shed blood were assayed before cardiopulmonary bypass and at 30 minutes and 2, 4, and 24 hours after transfusion. In vitro platelet function tests were conducted on platelets obtained from healthy volunteers. RESULTS: No adverse sequelae of the transfusions were observed. Blood loss and the need for postoperative blood product transfusions were lower in the group receiving cryopreserved platelets. Lower posttransfusion platelet increments and a tendency toward decreased platelet survival were observed in patients receiving cryopreserved platelets. Hematocrit and plasma fibrinogen were significantly higher in this group, and the duration of intubation was shorter. In vitro, cryopreserved platelets demonstrated less aggregation, lower pH, and decreased response to hypotonic stress but generated more procoagulant activity and thromboxane. CONCLUSIONS: (1) Cryopreserved platelet transfusions are superior to liquid-preserved platelets in reducing blood loss and the need for blood product transfusions after cardiopulmonary bypass. (2) The reduction in blood loss in the patients receiving cryopreserved platelet transfusions after cardiopulmonary bypass probably reflects improved in vivo hemostatic function of cryopreserved platelets. (3) Some in vitro measures of platelet quality (aggregation, pH, hypotonic stress) may not reflect in vivo quality of platelet transfusions after cardiopulmonary bypass, whereas other in vitro measures (platelet procoagulant activity and thromboxane) do.
Aged↗
The effects of aspirin and hypothermia on platelet function in vivo.
Patients undergoing hypothermic cardiopulmonary bypass are often receiving aspirin therapy. Hypothermia, aspirin and cardiopulmonary bypass can each induce a platelet function defect, but it is not known if the effects of aspirin and hypothermia are additive in this regard. To address this question in humans in vivo, the forearm skin temperature of healthy volunteers was equilibrated and maintained at either normothermia (32 degrees C) or hypothermia (28 degrees C or 22 degrees C) before and 16 h after the ingestion of 650 mg aspirin. A standardized template bleeding time was performed on the forearm and the shed blood emerging from the wound was assayed for platelet surface P-selectin expression by whole blood flow cytometry (reflecting alpha granule secretion) and thromboxane B2 (the stable metabolite of thromboxane A2) by radioimmunoassay. Hypothermia resulted in marked prolongation of the bleeding time. Aspirin resulted in prolongation of the bleeding time under normothermic conditions, but only minimally augmented the hypothermia-induced prolongation of the bleeding time. Platelet surface P-selectin up-regulation in shed blood was abolished by hypothermia. Aspirin had no effect on maximal platelet surface P-selectin expression under normothermic or hypothermic conditions. Both hypothermia and aspirin resulted in markedly reduced shed blood thromboxane B2. Although aspirin slightly augmented the hypothermia-induced reduction in shed blood thromboxane B2, the concentration of thromboxane generated in shed blood under hypothermic conditions in the absence of aspirin had no effect on platelet surface P-selectin or platelet aggregation in whole blood. In conclusion, as determined by three independent parameters of the shed blood emerging from a standardized bleeding time wound (bleeding time, platelet surface P-selectin, and thromboxane B2), aspirin did not significantly augment hypothermia-induced platelet dysfunction in vivo.
Aspirin↗
Effect of 24-hour whole-blood storage on plasma clotting factors.
BACKGROUND: The current requirements for the preparation of fresh-frozen plasma within 8 hours of whole-blood collection were designed to maintain clotting factor activities. These requirements, however, limit the production of fresh-frozen plasma in a large blood center. There are few data on the effect of the extension of CPD whole-blood storage to 24 hours on clotting factor activity. STUDY DESIGN AND METHODS: A 500-mL unit of whole blood was collected from 10 volunteer donors. At 1 hour after collection, a plasma sample was separated by centrifugation, and each unit was equally divided into 2 half-units, with 1 half-unit stored at 4 degrees C (range, 1-6 degrees C) and 1 half-unit stored at 22 degrees C (range, 20-24 degrees C) for 8 hours after collection. Each half-unit was then placed at 4 degrees C for further storage for 16 hours. At 8 and 24 hours after collection, plasma samples were separated from each half-unit. All plasma samples were frozen at -18 degrees C. Factors V, VII, VIII, and X; fibrinogen; antithrombin III; protein C; and protein S were measured. RESULTS: No significant changes were noted in factors V, VII, and X; fibrinogen; antithrombin III; protein C; and protein S over the 24-hour storage period. Factor VIII in both half-units was significantly reduced, by 13 percent, from the baseline sample as compared to the level in the 8-hour storage sample (p<0.05). Factor VIII was further reduced by 15 to 20 percent after the 24-hour storage period (p<0.05). CONCLUSION: The coagulation factor activity for all factors measured, with the exception of factor VIII, showed no significant change over the 24-hour storage period. Factor VIII was significantly decreased by 13 percent in 8-hour storage and by an additional 15 to 20 percent in 24-hour storage. For clinical situations not requiring the replacement of factor VIII only, 24-hour frozen plasma has properties comparable to those of fresh-frozen plasma.
Analysis of Variance↗
Platelet surface p-selectin, platelet-granulocyte heterotypic aggregates, and plasma-soluble p-selectin during plateletpheresis.
BACKGROUND: Plateletpheresis components have been shown to contain p-selectin-positive platelets after collection and storage. P-selectin mediates binding of activated platelets to granulocytes and monocytes. This study was undertaken to assess platelet activation, granulocyte activation, platelet-granulocyte heterotypic aggregate formation, and the plasma-soluble p-selectin level during plateletpheresis performed on a particular instrument (MCS+, Haemonetics). STUDY DESIGN AND METHODS: Flow cytometry was used to assay platelet surface p-selectin, granulocyte iC3b receptor, and platelet-granulocyte aggregates in the platelet component, residual blood in the disposable polycarbonate bowl of the MCS+, and in the donor blood with and without the addition of in vitro agonists before, during, and after plateletpheresis. The plasma-soluble p-selectin levels in the platelet component, disposable bowl, and donor venous blood were measured by an enzyme-linked immunosorbent assay. RESULTS: Levels of p-selectin-positive platelets, activated granulocytes, and platelet-granulocyte aggregates were greater in the disposable bowl than in the preapheresis donor blood. Levels of p-selectin-positive platelets, activated granulocytes, and platelet-granulocyte aggregates in the postapheresis donor blood were similar to those in the preapheresis donor blood. The platelet components contained no activated granulocytes or detectable platelet-granulocyte heterotypic aggregates, and only about 10-percent activated platelets. The plasma-soluble p-selectin level in the platelet component was significantly greater than that in the preapheresis donor blood, the residual blood in the disposable bowl, or the postapheresis donor blood. CONCLUSIONS: Measurements of platelet surface p-selectin, platelet-granulocyte heterotypic aggregates, and plasma-soluble p-selectin can be used to detect platelet activation during plateletpheresis.
Antibodies, Heterophile↗
Fresh, liquid-preserved, and cryopreserved platelets: adhesive surface receptors and membrane procoagulant activity.
BACKGROUND: A study in humans showed that the transfusion of previously frozen human platelets after cardiopulmonary bypass, despite decreased survival, resulted in better hemostatic function than that of liquid-preserved platelets stored at 22 degrees C for 3 to 4 days. STUDY DESIGN AND METHODS: In this study, fresh, 3- to 4-day-old liquid-preserved, and cryopreserved human platelets were studied by the use of monoclonal antibodies directed against p-selectin, glycoprotein (GP)Ib, activated GPIIb/IIIa, and coagulation factor V in a three-color flow cytometric method. RESULTS: The fresh and liquid-preserved platelets had normal surface levels of GPIb, while the cryopreserved platelets were composed of distinct subpopulations of GPIb-normal and GPIb-reduced platelets. On the basis of the binding of factor V, both subpopulations of cryopreserved platelets exhibited greater surface binding of factor V than did fresh and liquid-preserved platelets. Activated GPIIb/IIIa was elevated on GPIb-normal platelets, but not on GPIb-reduced platelets. Baboon platelets frozen by a procedure identical to that used to freeze human platelets also had GPIb-normal and GPIb-reduced subpopulations after the freezing-thawing-washing procedure. Autologous cryopreserved baboon platelets labeled with biotin-X-N-hydroxysuccinimide showed a rapid removal of GPIb-reduced platelets during the 5-minute postinfusion period, whereas GPIb-normal platelets had an in vivo recovery of 48 percent and a lifespan of slightly less than 6 days. CONCLUSIONS: Improved in vivo function of cryopreserved platelets may be related to the rapid hemostatic effect of the GPIb-reduced subpopulation secondary to increased binding of factor V and expression of p-selectin.
Animals↗
O-raffinose cross-linking markedly reduces systemic and renal vasoconstrictor effects of unmodified human hemoglobin.
The hemodynamic effects of a 20% exchange-transfusion with different solutions of highly purified human hemoglobin A-zero (A0) were evaluated. We compared unmodified hemoglobin with hemoglobin cross-linked with O-raffinose. Unmodified hemoglobin increased systemic vascular resistance and mean arterial pressure more than the O-raffinose cross-linked hemoglobin solution (by approximately 45% and approximately 14%, respectively). Unmodified hemoglobin markedly reduced cardiac output (CO) by approximately 21%, whereas CO was unaffected by the O-raffinose cross-linked hemoglobin solution. Unmodified and O-raffinose cross-linked hemoglobin solutions increased mean arterial pressure to comparable extents ( approximately 14% and approximately 9%, respectively). Unmodified hemoglobin increased renal vascular resistance 2-fold and reduced the glomerular filtration rate by 58%. In marked contrast, the O-raffinose cross-linked hemoglobin had no deleterious effect on the glomerular filtration rate, renal blood flow, or renal vascular resistance. The extents to which unmodified and O-raffinose cross-linked hemoglobin solutions inactivated nitric oxide also were compared using three separate in vitro assays: platelet nitric oxide release, nitric oxide-stimulated platelet cGMP production, and endothelium-derived relaxing factor-mediated inhibition of platelet aggregation. Unmodified hemoglobin inactivated or oxidized nitric oxide to a greater extent than the O-raffinose cross-linked hemoglobin solutions in all three assays. In summary, O-raffinose cross-linking substantially reduced the systemic vasoconstriction and the decrease in CO induced by unmodified hemoglobin and eliminated the deleterious effects of unmodified hemoglobin on renal hemodynamics and function. We hypothesize that O-raffinose cross-linking reduces the degree of oxidation of nitric oxide and that this contributes to the reduced vasoactivity of this modified hemoglobin.
Animals↗
Does erythrocyte infusion improve 3.2-km run performance at high altitude?
The effects of autologous erythrocyte infusion on improving exercise performance at high altitude have not previously been studied. The effects of erythrocyte infusion on 3.2-km (2-mile) run performance were evaluated during 3 days (HA3) and 14 days (HA14) exposure to high altitude (4300 m) in erythrocyte-infused (ER) and control (CON) subjects that were initially matched (P>0.05; n = 8 in each group) for age, body size and aerobic fitness. After sea-level runs (SL; 50 m), unacclimated-male subjects received either 700 ml of saline and autologous erythrocytes (42% hematocrit; ER) or saline alone (CON). The 3.2-km run times (min:s) did not differ (P>0.05) between groups at SL [mean (SEM) ER, 13:14 (00:19); CON, 13:39 (00:32)] or during HA3 [ER, 19:02 (00:18); CON, 19:44 (00:43)] and HA14 [ER, 17:44 (00:27); CON, 18:45 (00:55)] but times were slower (P<0.05) when comparing HA3 or HA14 to SL. Heart rates (HR) did not differ between groups at SL [ER, 188 (3) beats x min(-1); CON, 191 (3) beats x min(-1)], or during HA3 [ER, 170 (4) beats x min(-1); CON, 178 (4) beats x min(-1)] and HA14 [ER, 162 (6) beats x min(-1); CON, 169 (5) beats x min(-1)], but HR were lower (P<0.05) when comparing HA3 or HA14 to SL. Ratings of perceived exertion (local, central, and overall ratings) did not differ between groups at SL, HA3 or HA14, but local ratings were higher (P<0.05) at HA3 and HA14 compared to SL, and overall ratings were higher for HA3 than SL. Analysis of covariance (adjusted for SL group run times) revealed (min:s) 00:14 (HA3) and 00:28 (HA14) mean improvement tendencies (P>0.05) for ER compared to CON. Thus, no significant improvements in 3.2-km run performance were associated with erythrocyte infusion, although the ER group showed a tendency to run slightly faster at high altitude.
Acclimatization↗
Porphyrin loading of lipofuscin granules in inflamed striated muscle.
To further the understanding of oxidative effects on inflammation injury to muscle fiber structure, fluorescent imaging analysis of human striated muscle tissues from a variety of inflammatory or postinflammatory etiologies was undertaken in a search for accumulated coproporphyrin, a red autofluorescent byproduct of heme biosynthesis that would theoretically be formed under oxidative insult. Using a differential excitation method of in situ analysis, porphyrin autofluorescence was detected in intact fibers within the context of the yellow autofluorescent subsarcolemmal lipofuscin granules. Relative measurements of porphyrin concentration in the granules from different patients indicated that the acute/subacute inflammatory specimens grouped significantly higher than the more chronic inflammatory and nonpathological specimens. Myoglobin was also found to be associated with the granules. Myoglobin heme iron could potentially serve as a Fenton reagent for the intracellular generation of hydroxyl radicals, which are responsible for the oxidation of the porphyrinogens. High-performance liquid chromatography analysis of extracted dense particles revealed coproporphyrin as the sole porphyrin present. The observation of coproporphyrin within lipofuscin granules, previously unreported, suggests that lipofuscin accumulation in striated muscle may begin under conditions of acute oxidative stress, as marked by the oxidation of extramitochondrial porphyrinogens that are immediately incorporated into the granules.
Animals↗
Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease.
OBJECTIVES: We sought to examine whether patients with stable coronary artery disease (CAD) have increased platelet reactivity and an enhanced propensity to form monocyte-platelet aggregates. BACKGROUND: Platelet-dependent thrombosis and leukocyte infiltration into the vessel wall are characteristic cellular events seen in atherosclerosis. METHODS: Anticoagulated peripheral venous blood from 19 patients with stable CAD and 19 normal control subjects was incubated with or without various platelet agonists and analyzed by whole blood flow cytometry. RESULTS: Circulating degranulated platelets were increased in patients with CAD compared with control subjects (mean [+/- SEM] percent P-selectin-positive platelets: 2.1 +/- 0.2 vs. 1.5 +/- 0.2, p < 0.01) and were more reactive to stimulation with 1 micromol/liter of adenosine diphosphate (ADP) (28.7 +/- 3.9 vs. 16.1 +/- 2.2, p < 0.01), 1 micromol/liter of ADP/epinephrine (51.4 +/- 4.6 vs. 37.5 +/- 3.8, p < 0.05) or 5 micromol/liter of thrombin receptor agonist peptide (TRAP) (65.7 +/- 6.8 vs. 20.2 +/- 5.1, p < 0.01). Patients with stable CAD also had increased circulating monocyte-platelet aggregates compared with control subjects (percent platelet-positive monocytes: 15.3 +/- 3.0 vs. 6.3 +/- 0.9, p < 0.01). Furthermore, patients with stable CAD formed more monocyte-platelet aggregates than did control subjects when their whole blood was stimulated with 1 micromol/liter of ADP (50.4 +/- 4.5 vs. 28.1 +/- 5.3, p < 0.01), 1 micromol/liter of ADP/epinephrine (60.7 +/- 4.3 vs. 48.0 +/- 4.8, p < 0.05) or 5 micromol/liter of TRAP (67.6 +/- 5.7 vs. 34.3 +/- 7.0, p < 0.01). CONCLUSIONS: Patients with stable CAD have circulating activated platelets, circulating monocyte-platelet aggregates, increased platelet reactivity and an increased propensity to form monocyte-platelet aggregates.
Adenosine Diphosphate↗