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Biomedical subjects

A T Cheung

Publications and source records attributed to A T Cheung.

At least 37 records · Page 2Linked to original sources
PubMed1999

Oxygen delivery during retrograde cerebral perfusion in humans.

UNLABELLED: Retrograde cerebral perfusion (RCP) potentially delivers metabolic substrate to the brain during surgery using hypothermic circulatory arrest (HCA). Serial measurements of O2 extraction ratio (OER), PCO2, and pH from the RCP inflow and outflow were used to determine the time course for O2 delivery in 28 adults undergoing aortic reconstruction using HCA with RCP. HCA was instituted after systemic cooling on cardiopulmonary bypass for 3 min after the electroencephalogram became isoelectric. RCP with oxygenated blood at 10 degrees C was administered at an internal jugular venous pressure of 20-25 mm Hg. Serial analyses of blood oxygen, carbon dioxide, pH, and hemoglobin concentration were made in samples from the RCP inflow (superior vena cava) and outflow (innominate and left carotid arteries) at different times after institution of RCP. Nineteen patients had no strokes, five patients had preoperative strokes, and four patients had intraoperative strokes. In the group of patients without strokes, HCA with RCP was initiated at a mean nasopharyngeal temperature of 14.3 degrees C with mean RCP flow rate of 220 mL/min, which lasted 19-70 min. OER increased over time to a maximal detected value of 0.66 and increased to 0.5 of its maximal detected value 15 min after initiation of HCA. The RCP inflow-outflow gradient for PCO2 (slope 0.73 mm Hg/min; P < 0.001) and pH (slope 0.007 U/min; P < 0.001) changed linearly over time after initiation of HCA. In the group of patients with preoperative or intraoperative strokes, the OER and the RCP inflow-outflow gradient for PCO2 changed significantly more slowly over time after HCA compared with the group of patients without strokes. During RCP, continued CO2 production and increased O2 extraction over time across the cerebral vascular bed suggest the presence of viable, but possibly ischemic tissue. Reduced cerebral metabolism in infarcted brain regions may explain the decreased rate of O2 extraction during RCP in patients with strokes. IMPLICATIONS: Examining the time course of oxygen extraction, carbon dioxide production, and pH changes from the retrograde cerebral perfusate provided a means to assess metabolic activity during hypothermic circulatory arrest.

Adult↗
PubMed1999

In vivo blood flow abnormalities in the transgenic knockout sickle cell mouse.

The accepted importance of circulatory impairment to sickle cell anemia remains to be verified by in vivo experimentation. Intravital microscopy studies of blood flow in patients are limited to circulations that can be viewed noninvasively and are restricted from deliberate perturbations of the circulation. Further knowledge of sickle blood flow abnormalities has awaited an animal model of human sickle cell disease. We compared blood flow in the mucosal-intestinal microvessels of normal mice with that in transgenic knockout sickle cell mice that have erythrocytes containing only human hemoglobin S and that exhibit a degree of hemolytic anemia and pathological complications similar to the human disease. In sickle cell mice, in addition to seeing blood flow abnormalities such as sludging in all microvessels, we detected decreased blood flow velocity in venules of all diameters. Flow responses to hyperoxia in both normal and sickle cell mice were dramatic, but opposite: Hyperoxia promptly slowed or halted flow in normal mice but markedly enhanced flow in sickle cell mice. Intravital microscopic studies of this murine model provide important insights into sickle cell blood flow abnormalities and suggest that this model can be used to evaluate the causes of abnormal flow and new approaches to therapy of sickle cell disease.

Anemia, Sickle Cell↗
PubMed1999

Nicardipine intravenous bolus dosing for acutely decreasing arterial blood pressure during general anesthesia for cardiac operations: pharmacokinetics, pharmacodynamics, and associated effects on left ventricular function.

UNLABELLED: The objective of this study was to evaluate the efficacy of nicardipine, a dihydropyridine calcium channel antagonist, administered as an IV bolus dose to acutely decrease arterial pressure in anesthetized cardiac surgical patients. We performed a double-blind, randomized, self-controlled, dose-ranging study in 40 adult cardiac surgical patients to determine the pharmacokinetics and pharmacodynamics of nicardipine 0.25 mg, 0.50 mg, 1.00 mg, and 2.00 mg administered as an IV bolus. Transesophageal echocardiography was used to assess left ventricular preload, afterload, and global systolic function. Plasma nicardipine concentration was measured using high-performance liquid chromatography. Nicardipine selectively decreased arterial pressure in a dose-dependent manner with a maximum response within 100 s and recovery to half the maximum response within 3-7 min without associated changes in heart rate. The decreases in arterial pressure were associated with only small decreases in left ventricular end-systolic wall stress and small increases in global left ventricular systolic function without changes in left ventricular end-diastolic cavity area or cardiac output. The time course for nicardipine bolus was consistent with a two-compartment pharmacokinetic model with rapid redistribution from a small central compartment. IMPLICATIONS: Nicardipine was effective for selectively decreasing arterial blood pressure acutely, but had no effects on ventricular preload or cardiac output. The absence of dose-dependent changes in cardiac output, left ventricular systolic performance, and left ventricular afterload despite significant decreases in arterial pressure suggested that nicardipine had a small negative inotropic action.

Aged↗
PubMed1998

Extraction and quantification of nicardipine in human plasma.

A novel simple method of extraction, separation, identification and quantification of nicardipine in human plasma samples was completely studied. The human plasma samples were initially purified by solid-phase extraction (SPE) using a C18 cartridge. The extracted samples were separated and nicardipine present in the samples was quantified by high-performance liquid chromatography (HPLC) on a reversed-phase C18 column employing a mobile phase consisting of 60% (v/v) acetonitrile in 0.02 M NaH2PO4 with pH of 6.3 and a variable wavelength UV detector set at 254 nm. The recovery of nicardipine from plasma samples using selective SPE was 91+/-6.0% and had less interfering compounds in the HPLC analysis compared to the use of liquid-liquid (L/L) extraction. In the HPLC analysis, examining the effect of pH values of the mobile phase on the capacity factor (k') of nicardipine revealed a method for selecting a critical k' value of nicardipine to eliminate interfering peaks near the peak specific to the analyte. This method for quantification of nicardipine in human plasma samples was suitable for studying the pharmacokinetic profile of nicardipine administered as an intravenous bolus to cardiac surgical patients.

Antihypertensive Agents↗
PubMed1998

Regulation of new blood vessel growth into ischemic skeletal muscle.

PURPOSE: In a rabbit model, transposition of a muscle pedicle flap to an ischemic hind limb has been shown to result in the development of new blood vessels that connect the arterial circulation of the flap to the circulation of the limb. The hypothesis that exogenous recombinant basic fibroblast growth factor (bFGF) would enhance the development of this new blood supply was examined and the regulation of bFGF in this process was investigated. METHODS: The right common iliac artery was ligated in 12 male New Zealand white rabbits. An abdominal wall muscle flap based on the left inferior epigastric artery was transposed to the right thigh. bFGF in phosphate-buffered saline (PBS) at 3 ng/h (n = 6), or PBS alone (n = 6), was infused for 7 days via mini-osmotic pumps with an infusion catheter positioned at the flap-muscle interface. The flap-muscle interface was immunostained with anti-alpha-actin antibody to determine blood vessel density (number of vessels/mm) and with anti-bFGF antibody to evaluate bFGF distribution. RNA was isolated from these sections, and polymerase chain reaction (PCR) was used to examine endogenous bFGF messenger RNA (mRNA) expression. RESULTS: Blood vessel density was significantly increased in animals receiving exogenous bFGF (22. 0 +/- 10.6 vessels/mm vs. 10.7 +/- 8.8 vessels/mm, P =.009). In the controls, neovessels were arranged in clusters with endogenous bFGF concentrated around these clusters. In bFGF-treated animals, vessels were diffusely scattered throughout the flap-limb interface, corresponding to the distribution pattern of infused bFGF. There was no difference in bFGF mRNA expression between the control and the bFGF-treated groups. CONCLUSION: Exogenous bFGF infusion significantly augmented new blood vessel development at the flap-limb interface. Endogenous bFGF was up-regulated around the newly developed microvessels in control animals, and vessel growth correlated with the diffuse distribution of exogenous bFGF, implicating bFGF as an important factor in angiogenesis. Exogenous bFGF did not affect bFGF mRNA expression, suggesting that the regulation of bFGF is not under autocrine control.

Animals↗
PubMed1998

Neurophysiologic effects of retrograde cerebral perfusion used for aortic reconstruction.

OBJECTIVE: The results of neurophysiologic monitoring using somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) were analyzed to determine if retrograde cerebral perfusion (RCP) supported central nervous system electrical function during surgery that required temporary interruption of antegrade cerebral perfusion (IACP). DESIGN: A prospective, observational study. SETTING: A university hospital. PARTICIPANTS: Fifteen adult patients who underwent aortic reconstruction using RCP and three patients who underwent thoracic aortic operations using hypothermic circulatory arrest without RCP. INTERVENTIONS: SSEPs and EEG were monitored continuously throughout the operation. Regression analysis was performed to determine the factors that affected the rate of decrease in SSEP amplitudes during IACP and the time required for SSEP and EEG activity to recover after antegrade cerebral perfusion (ACP) was restored. MEASUREMENTS AND MAIN RESULTS: The amplitude of SSEPs that were elicited decreased over time after IACP. The mean +/- standard deviation (SD) time required for the brachial plexus (Erb's point), cervicomedullary junction (N13), and brainstem (N18) SSEPs to decrease to 0.5 of their original amplitude after IACP were 30 +/- 2, 19 +/- 2, and 16 +/- 2 minutes, respectively. The rate of decrease in the N18 SSEP amplitude after IACP correlated positively to the fraction of no-flow time (p = 0.01). CONCLUSION: RCP attenuated the rate of decay in SSEP amplitudes during IACP. This suggested that RCP had a measurable physiologic effect on central nervous system function and may increase the time that ACP can be safely interrupted.

Adult↗
PubMed1998

Relationships between cerebral blood flow velocities and arterial pressures during intra-aortic counterpulsation.

OBJECTIVE: To determine the effects of intra-aortic counterpulsation (IABP) on cerebral blood flow velocity. DESIGN: Prospective self-controlled study. SETTING: University hospital surgical intensive care unit. PARTICIPANTS: Nineteen cardiac surgical patients requiring perioperative IABP assistance. INTERVENTIONS: Simultaneous recording of transcranial Doppler middle cerebral artery blood flow velocity and arterial pressure in response to changes in the magnitude of augmentation and trigger ratio. MEASUREMENTS AND MAIN RESULTS: Instantaneous cerebral blood flow velocities correlated with arterial pressures during IABP (r = 0.650) at different magnitudes of augmentation and trigger ratios. The increase in arterial pressure during balloon inflation was associated with an increase in cerebral blood flow velocity, and the decrease in arterial pressure in response to balloon deflation was associated with a decrease in cerebral blood flow velocity that was dependent on the magnitude of augmentation. Different magnitudes of augmentation or trigger ratios had no effect on peak systolic cerebral blood flow velocity, mean cerebral blood flow velocity, mean arterial pressure, or the mean velocity-to-pressure ratio. Instantaneous cerebral blood flow velocity to arterial pressure ratios were lowest in response to balloon deflation at the time of pre-ejection. CONCLUSIONS: IABP modified the phasic profile of cerebral blood flow to reflect the arterial pressure waveform without affecting mean cerebral blood flow velocity. Peak systolic cerebral blood flow velocity was maintained in augmented beats despite the decreased systolic arterial pressure associated with afterload reduction. The acute decrease in cerebral blood flow velocity at pre-ejection was balanced by increased cerebral blood flow velocity during balloon inflation in diastole.

Adult↗
PubMed1998

An in vivo model for elucidation of the mechanism of tumor necrosis factor-alpha (TNF-alpha)-induced insulin resistance: evidence for differential regulation of insulin signaling by TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce insulin resistance in cultured cells as well as in animal models. The aim of this study was to map the in vivo mechanism whereby TNF-alpha contributes to the pathogenesis of impaired insulin signaling, using obese and lean Zucker rats in which TNF-alpha activity was inhibited through adenovirus-mediated gene transfer. We employed a replication-incompetent adenovirus-5 (Ad5) vector to endogenously express a TNF inhibitor (TNFi) gene, which encodes a chimeric protein consisting of the extracellular domain of the human 55-kDa TNF receptor joined to a mouse IgG heavy chain. Control animals consisted of rats infected with the same titer of adenovirus carrying the lac-z complementary DNA, encoding for beta-galactosidase. There was a significant reduction in plasma insulin and free fatty acid levels in TNFi obese rats 2 days following Ad5 administration. The peripheral insulin sensitivity index was 50% greater, whereas hepatic glucose output was completely suppressed during hyperinsulinemic glucose clamps in TNFi obese animals, with no differences observed between the two lean groups. The improvement in peripheral and hepatic sensitivity to insulin seen in the obese animals was independent of insulin receptor (IR) number and insulin binding affinity for IR. However, TNF-alpha neutralization led to a 2.5-fold increase in tyrosine phosphorylation of IR in skeletal muscle, whereas this was unchanged in liver. There was also a 4-fold increase in particulate protein tyrosine phosphatase activity of skeletal muscle in TNFi obese animals vs. beta-galactosidase controls, whereas protein tyrosine phosphatase activity in liver was unchanged. These results suggest that TNF-alpha is a mediator of insulin resistance in obesity and may modulate IR signaling in skeletal muscle and liver through different pathways. TNF-alpha may affect insulin action in the liver either at sites distal to the IR or indirectly, possibly because of increased provision of gluconeogenic substrates or altered counterregulation. In addition, the Ad5-mediated gene delivery system employed here provides an in vivo model that is efficient and economical for exploring mechanisms involved in TNF-alpha-induced insulin resistance in various genetic models of obesity-linked diabetes.

Animals↗
PubMed1996

Detection of stroke during cardiac operations with somatosensory evoked responses.

OBJECTIVES: The objectives of this study were to determine if monitoring of intraoperative somatosensory evoked potentials could be used to detect stroke during cardiac operations and to establish indicators of cerebral ischemia based on changes in these potentials. METHODS: Twenty-five patients undergoing cardiac operations underwent preoperative and postoperative neurologic examinations as well as intraoperative recording of somatosensory evoked potentials. Detailed analysis of the waveforms of these potentials was performed. RESULTS: Two of the 25 patients had intraoperative strokes. These patients and only these patients had changes in their somatosensory evoked potentials during the operation suggesting cerebral ischemia. The unilateral disappearance of the cortical somatosensory evoked potential waves correlated significantly with the clinical outcome of stroke (p < 0.004). Ischemic changes were detected in real time and were related to the removal of the aortic crossclamp in one patient and to the initiation of cardiopulmonary bypass in the other. CONCLUSIONS: Somatosensory evoked potentials can detect intraoperative stroke during cardiac operations. Acute, unilateral decreases in amplitude of the cortical potential are more useful than changes in latency in detecting intraoperative stroke.

Adult↗
PubMed1996

New blood vessels can be induced to invade ischemic skeletal muscle.

PURPOSE: Despite intense investigation of angiogenesis, little effort has been made to exploit this phenomenon in ischemic tissue. The few studies on this topic have focused primarily on the development of collateral arteries in existing arterial beds. A previous study showed that a perfused muscle flap transposed to an ischemic limb formed vascular connections, which were demonstrated with angiography, between the arteries of the flap and the limb vasculature. Microsphere studies suggested that these vascular connections increased the resting perfusion of the ischemic limb. This study is designed to confirm histologically that such connections develop and to quantitate the number and dimensions of these new vessels. METHODS: Through a midline laparotomy, the right common iliac artery was ligated and divided in 18 male New Zealand white rabbits. An abdominal-wall muscle flap based on the left inferior epigastric artery was transposed to the right thigh. On the seventh day, contrast dye was injected into the flap artery of eight rabbits and an arteriogram was obtained. The tissue of the remaining rabbits was perfusion-fixed at 3 days (n = 2), 7 days (n = 4), and 14 days (n = 4). Thin sections of the flap-thigh muscle interface were stained with hematoxylin and eosin and for alpha-actin and proliferating cell nuclear antigen and were examined microscopically. RESULTS: An arteriogram confirmed vascular connections between the flap and the native limb circulation in seven of the eight rabbits. Histologic evaluation of the flap-thigh muscle interface showed no new vessels on the third day. On the seventh day, 6.8 +/- 4.8 new vessels (positive alpha-actin staining, red blood cells in lumen) were seen per 40 x field; the vessels averaged 10.2 +/- 5.2 microns in diameter. On the fourteenth day, there were 7.3 +/- 3.8 vessels per 40 x field (p = 0.46), but the vessel diameter increased to 20.7 +/- 10.6 microns (p = 0.013). Proliferating cell nuclear antigen staining confirmed that these were proliferating vessels. CONCLUSION: Within seven days, new vessels that were more mature than capillaries (stained for alpha-actin, a smooth muscle cell protein) formed between the flap and the thigh muscle. These new connecting vessels continue to enlarge in diameter between 7 and 14 days, but the stimulus to form new vessels appeared to decline or disappear before the fourteenth day. Attempts to sustain this phenomenon with angiogenic factors are underway.

Angiography↗
PubMed1996

Beat-to-beat augmentation of left ventricular function by intraaortic counterpulsation.

BACKGROUND: Measuring the effects of intraaortic balloon counterpulsation (IABP) in single cardiac beats may permit an improved understanding of the physiologic mechanisms by which IABP improves the circulation. The objective of the study was to use trans- esophageal echocardiography in combination with hemodynamic measurements to test the hypothesis that IABP improves global left ventricular systolic function selectively in the IABP-augmented cardiac beats by acutely decreasing left ventricular afterload. METHODS: Twenty-seven studies in which the IABP-to-R wave trigger ratio was serially changed from 1:1, 1:2, 1:4, 0:1 (IABP off) and back to 1:1 were performed in 20 anesthetized cardiac surgical patients during IABP support. Left ventricular short-axis end-diastolic cross-sectional area, end-systolic area, mean end-systolic wall thickness, and ejection time were measured by transesophageal echocardiography at the midpapillary muscle level. Aortic pressure was measured simultaneously from the central lumen of the intraaortic balloon catheter. These measurements were used to calculate the fractional area change, end-systolic meridional wall stress, and heart rate-corrected velocity of circumferential fiber shortening. The echocardiographic and hemodynamic parameters of left ventricular preload, afterload, and systolic function immediately after balloon deflation (IABP-augmented cardiac beats) were compared to the parameters measured during nonaugmented cardiac beats to determine the beat-to-beat effects of IABP on left ventricular function. RESULTS: IABP-augmented cardiac beats had a decreased systolic arterial pressure and end-systolic meridional wall stress and increased diastolic blood pressure, fractional area change, and velocity of circumferential fiber shortening compared to nonaugmented cardiac beats. IABP did not cause significant beat-to-beat changes in heart rate, pulmonary artery diastolic pressure, or central venous pressure. The improvement in left ventricular systolic function associated with IABP-augmented cardiac beats correlated with the decrease in end-systolic meridional wall stress for that cardiac beat. CONCLUSIONS: Beat-to-beat echocardiographic and hemodynamic measurements performed in anesthetized cardiac surgical patients during IABP support demonstrated improved left ventricular systolic function and decreased left ventricular systolic wall stress in the cardiac beats immediately after balloon deflation. The relationship between left ventricular systolic function and left ventricular systolic wall stress during IABP support suggests that afterload reduction was an important mechanism by which IABP instantaneously improved circulatory function in anesthetized cardiac surgical patients.

Adult↗
PubMed1996

Functional immaturity in neonatal polymorphonuclear leukocytes of rhesus monkeys.

Despite major advances in the management and care of critically ill and low-birth weight human and nonhuman primate infants over the past two decades, infection remains a major source of neonatal morbidity and mortality. Although the causes of enhanced susceptibility and dissemination of neonatal infections are incompletely defined in the literature, substantial evidence from this and other laboratories has implied that functional abnormalities of neonatal polymorphonuclear leukocytes (PMNs) may be a major contributor. Increased understanding of the functional characteristics of neonatal PMNs should, therefore, provide significant insight into the pathogenesis and possible therapy of infections in neonates. Our laboratory has been actively involved in evaluating the functional competence of PMNs in neonatal human and nonhuman primates. This report describes a study in which we have confirmed and characterized the functional compromises in neonatal PMNs of rhesus monkeys, including deficiencies in chemotaxis, membrane deformability, phagocytosis, and killing.

Aging↗
PubMed1995

Plasma fluorescein binding and transcapillary fluorescein escape rate in renal failure associated with diabetes.

Microvascular damage, often resulting in renal failure, is a common complication of diabetes. Transcapillary fluorescein escape rate (TCFER) as monitored by intravital microscopy has been used as an indicator of the extent of capillary damage in diabetes and to assess improvement in microvascular function after combined kidney-pancreas transplant. However, fluorescein anion binds to plasma albumin, and albumin-ligand binding may be altered in the presence of renal disease. The purpose of this study was to compare fluorescein binding by plasma from diabetics with renal failure with plasma from healthy nondiabetics. Fluorescein binding by plasma from seven type I diabetics awaiting kidney-pancreas transplant and seven healthy adults of similar age and sex was studied using ultrafiltration and dialysis. There was no significant difference in the apparent albumin binding of fluorescein at physiologically relevant fluorescein concentrations, even though the TCFER was significantly increased in the diabetics as compared with the controls. Hippurate, a ligand that accumulates in renal failure, did alter fluorescein binding in a defatted albumin solution but not sufficiently to account for the differences in TCFERs. These data indicate that impaired albumin binding of fluorescein does not contribute significantly to the TCFER in diabetics with renal failure.

Adult↗
PubMed1994

Intracardiac thrombus: a risk of incomplete anticoagulation for cardiac operations.

Mitral valve replacement was performed urgently in a patient with hemorrhagic brain lesions. To decrease the risk of intracranial hemorrhage, cardiopulmonary bypass was performed using a heparin-coated perfusion system and a reduced dose of heparin. The detection of an acute intracardiac thrombus by transesophageal echocardiography during cardiopulmonary bypass exposed a potential hazard of techniques employing reduced systemic anticoagulation for cardiac operations.

Acute Disease↗