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Anthony T W Cheung

Publications and source records attributed to Anthony T W Cheung.

6 recordsLinked to original sources
PubMed2004

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo.

Microvascular occlusion in sickle cell disease can be initiated by adhesion of sickle red blood cells (RBCs) to the endothelium. Our objective in this study was to verify the relevance in vivo of our discovery that sickle RBCs adhere abnormally to endothelial P-selectin in vitro. We used computer-assisted intravital microscopy to characterize RBC flow velocity (V(RBC)) in mice. We found faster V(RBC) of sickle RBCs in P-selectin knock-out and control mice than in sickle cell mice, which have increased endothelial cell P-selectin expression. Agonist peptide for murine protease-activated receptor-1 (PAR-1), which selectively activates mouse endothelial cells but not platelets, was used to assess the effects of endothelial cell P-selectin on microvascular flow. Suffusion of venules with this agonist stopped flow promptly in normal and sickle mice but not in P-selectin knock-out mice or in control mice pretreated with anti-P-selectin monoclonal antibody or unfractionated heparin (UFH). Agonist-induced slowing of flow was reversed rapidly by suffusion with UFH, provided flow had not already stopped. We conclude that endothelial cell P-selectin contributes to the microcirculatory abnormalities in sickle cell disease and that blocking P-selectin may be useful for preventing painful vasoocclusion in sickle cell disease.

Anemia, Sickle Cell↗
PubMed2004

Blood substitute resuscitation as a treatment modality for moderate hypovolemia.

Blood substitute resuscitation as a treatment modality for moderate hypovolemia (approximately 40% blood loss) in a canine model has been evaluated using Oxyglobin (Biopure Hemoglobin Glutamer-200/ Bovine; a hemoglobin-based oxygen-carrier) and Hespan (6% hetastarch; a nonoxygen-carrier) as resuscitants. Autologous (shed) blood served as control. Nine dogs were studied--after splenectomy, each dog was hemorrhaged (32-36 mL/kg; MAP = approximately 50 mmHg) and randomly assigned to the three resuscitation groups. Microvascular, systemic function and oxygenation characteristics were monitored and/or measured simultaneously in prehemorrhagic (baseline), posthemorrhagic and postresuscitation phases for correlation-real-time microvascular changes in the bulbar conjunctiva were noninvasively measured via computer-assisted intravital microscopy and systemic function and oxygenation changes were monitored and/or measured via instrumentation and devices incorporated into our bioengineering station in an operating room setting. Blood chemistry was also studied for relevant measurements. Prehemorrhagic microvascular characteristics were similar in all animals (venular diameter = 41 +/- 12 microm, A:V ratio = approximately 1:2, red-cell velocity = 0.5 +/- 0.3 mm/s). All animals also showed similar prehemorrhagic systemic function and oxygenation measurements comparable to a previous study and were consistent with normal measurements in dogs. At the completion of hemorrhaging to achieve moderate hypovolemia (approximately 40% blood loss with MAP at approximately 50 mmHg), all nine animals showed similar significant (P < 0.01) posthemorrhagic microvascular changes, including approximately 17% decrease in diameter (34 +/- 7 microm), A:V ratio = variable, and approximately 80% increase in velocity (0.9 +/- 0.5 mm/s). All animals also showed similar significant (P < 0.01) posthemorrhagic systemic function and oxygenation changes, with decreases in Hct, aHb(total), MPAP, MAP, SAP, DAP, CO, SVI, CaO2, and CvO2 and increases in HR and lactic acidosis. Shed blood (control) resuscitation restored posthemorrhagic microvascular changes close to prehemorrhagic values (diameter = 39 +/- 6 microm, A:V ratio = approximately 1:2, velocity = 0.6 +/- 0.4 mm/s). Oxyglobin and Hespan restored microvascular changes in similar manner close to prehemorrhagic values (Oxyglobin: diameter = 38 +/- 3 microm, A:V ratio = approximately 1:2, velocity = 0.6 +/- 0.4 mm/s; Hespan: diameter = 38 +/- 7 microm, A:V ratio = 1:2, velocity = 0.5 +/- 0.4 mm/s). After resuscitation, shed blood (control) restored all systemic function and oxygenation changes close to prehemorrhagic values. However, both Oxyglobin and Hespan resuscitation restored systemic function changes, but not oxygenation changes, to prehemorrhagic values. This was an interesting finding because of the different oxygen-carrying capability of Oxyglobin (oxygen-carrying) and Hespan (nonoxygen-carrying). The result suggests that either volume replenishment alone (and not oxygen-carrying capability) is needed to treat moderate hypovolemia or oxygenation measurements obtained by standard methods (oximetry, blood chemistry) may not reflect tissue oxygenation levels.

Animals↗
PubMed2004

Effects of poloxamer 188 treatment on sickle cell vaso-occlusive crisis: computer-assisted intravital microscopy study.

Nine patients with sickle cell disease (SCD) who were hospitalized at UC Davis Medical Center for vaso-occlusive crisis (VOC) were studied as part of a randomized double-blind phase III clinical trial to investigate the real-time effects of poloxamer 188 on VOC. All patients showed significant microvascular changes from normal (steady-state) values during VOC (diminished venular diameter and red cell velocity). The patients were randomly assigned to be treated with poloxamer 188 or placebo. Poloxamer 188 (n = 4) but not placebo (n = 5) significantly reversed these microvascular changes approximately 2 hours postinitiation of loading infusion (100 mg/kg in 1 hour). Further significant improvement induced by poloxamer 188 but not placebo was observed > or = 7 hours postinfusion, resulting in a significant reversal of the microvascular changes to steady-state values.

Adolescent↗
PubMed2002

Microvascular abnormalities in sickle cell disease: a computer-assisted intravital microscopy study.

The conjunctival microcirculation of 18 homozygous sickle cell disease (SCD) patients during steady-state, painful crisis, and postcrisis conditions was recorded on high-resolution videotapes using intravital microscopy. Selected videotape sequences were subsequently coded, frame-captured, studied, and blindly analyzed using computer-assisted image analysis protocols. At steady-state (baseline), all SCD patients exhibited some of the following morphometric abnormalities: abnormal vessel diameter, comma signs, blood sludging, boxcar blood flow phenomenon, distended vessels, damaged vessels, hemosiderin deposits, vessel tortuosity, and microaneurysms. There was a decrease in vascularity (diminished presence of conjunctival vessels) in SCD patients compared with non-SCD controls, giving the bulbar conjunctiva a "blanched" avascular appearance in most but not all SCD patients during steady-state. Averaged steady-state red cell velocity in SCD patients was slower than in non-SCD controls. During painful crisis, a further decrease in vascularity (caused by flow stoppage in small vessels) and a 36.7% +/- 5.2% decrease in large vessel (mostly venular) diameter resulted. In addition, the conjunctival red cell velocities either slowed significantly (6.6% +/- 13.1%; P <.01) or were reduced to a trickle (unmeasurable) during crisis. The microvascular changes observed during crisis were transient and reverted to steady-state baseline after resolution of crisis. When combined, intravital microscopy and computer-assisted image analysis (computer-assisted intravital microscopy) represent the availability of a noninvasive tool to quantify microvascular abnormalities in vascular diseases, including sickle cell disease. The ability to identify and relocate the same conjunctival vessels for longitudinal studies uniquely underscores the applicability of this quantitative real-time technology.

Adolescent↗
PubMed2002

Microvascular abnormalities in pediatric diabetic patients.

Microvascular abnormalities are associated with and causative of the development of end-stage organ complications in adult diabetic patients. Whether the same microvascular abnormalities are present in pediatric patients is not known and has not been studied because of a lack of real-time technology, methodology to study young patients, and availability of an appropriate noninvasive site for in vivo studies. We hypothesized that microvascular abnormalities should be present in pediatric patients despite their young age and the relatively short durations of the disease. In this study, computer-assisted intravital microscopy (CAIM) was adapted to blindly quantify microvascular abnormalities in 12 pediatric type 1 diabetic mellitus (T1DM) patients (ages = 6-16 years; mean +/- SD = 11.42 +/- 3.42; duration since diagnosis = 2-14 years; mean +/- SD = 6.75 +/- 3.79) in vivo, using the microcirculation of the bulbar conjunctiva as a noninvasive site. Microvascular abnormalities, commonly found in adult patients, existed in the conjunctival microcirculation of all pediatric T1DM patients in varying degrees despite their relatively young age. A severity index (SI) was developed to reflect the cumulative severity of the microvascular abnormalities and was computed as the summation of all microvascular abnormalities found in each patient. SI for the 12 T1DM patients (mean +/- SD = 7.42 +/- 1.88; median = 8; mode = 9) differed significantly from that for the nondiabetic controls (mean +/- SD = 0.67 +/- 0.78; median = 0.5; mode = 0; P < 0.0001). In addition, SI correlated with hemoglobin A1c levels (mean +/- SD = 9.18 +/- 1.57) of T1DM patients but did not correlate with the duration of disease since diagnosis of the same patients. This observation raises the possibility that diabetic pathogenesis may precede the onset of overt disease or clinical diagnosis. This study confirms that CAIM may represent the availability of a useful real-time technology to study conjunctival microvascular abnormalities in vascular diseases in juvenile as well as adult patients.

Adolescent↗