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Biomedical subjects

C W White

Publications and source records attributed to C W White.

At least 91 records · Page 5Linked to original sources
PubMed1989

Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts.

Hearts isolated from rats pretreated 24 hr before with endotoxin had increased myocardial catalase activity, but the same superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities, as hearts from untreated rats. Hearts isolated from rats pretreated with endotoxin 24 hr before also had increased myocardial function (decreased injury) after ischemia and reperfusion (Langendorff apparatus, 37 degrees C), as assessed by measurement of ventricular developed pressure, contractility (+dP/dt), and relaxation rate (-dP/dt), compared to control hearts. In contrast, hearts isolated from rats pretreated with endotoxin 1 hr before isolation or hearts perfused with endotoxin did not have increased catalase activity or decreased injury following ischemia and reperfusion. Aminotriazole pretreatment prevented increases in myocardial catalase activity and myocardial function after ischemia-reperfusion in hearts from endotoxin-pretreated rats. The results suggest that endotoxin pretreatment decreases cardiac ischemia-reperfusion injury and that increases in endogenous myocardial catalase activity contribute to protection.

Amitrole↗
PubMed1989

Cytokines increase rat lung antioxidant enzymes during exposure to hyperoxia.

Pretreatment with the combination of tumor necrosis factor/cachectin (TNF/C) and interleukin 1 (IL-1) increased glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD) activities in lungs of rats continuously exposed to hyperoxia for 72 h, a time when all untreated rats had already died. Pretreatment with TNF/C and IL-1 also increased, albeit slightly, lung G6PDH and GR activities of rats exposed to hyperoxia for 4 or 16 h. By comparison, no differences occurred in lung antioxidant enzyme activities of TNF/C and IL-1- or saline-pretreated rats exposed to hyperoxia for 36 or 52 h; the latter is a time just before untreated rats began to succumb during exposure to hyperoxia. The results raise the possibility that TNF/C and IL-1 treatment can increase lung antioxidant enzyme activities and that increased lung antioxidant enzymes may contribute to the increased survival of TNF/C and IL-1-pretreated rats in hyperoxia for greater than 72 h.

Animals↗
PubMed1989

Polyethylene glycol-attached antioxidant enzymes decrease pulmonary oxygen toxicity in rats.

When exposed continuously to hyperoxia (100% O2, 760 Torr barometric pressure), rats pretreated with polyethylene glycol (PEG)-attached superoxide dismutase and catalase (PEG-SOD + PEG-CAT) lived longer (79.1 + 7.6 h) than rats pretreated with saline (60.7 +/- 2.1 h) or PEG-inactivated-SOD + PEG-inactivated-CAT (62.3 +/- 1.6 h). Rats pretreated with PEG-SOD + PEG-CAT also had less hyperoxia-induced acute oxidative edematous lung injury, as assessed by increases in lung oxidized glutathione (GSSG) contents, pleural effusions, and lung lavage albumin concentrations than saline-pretreated rats. Rats pretreated with the long-lived conjugates PEG-inactivated-SOD + PEG-inactivated-CAT or PEG-albumin also had decreased acute oxidative edematous lung injury compared with rats pretreated with PEG, SOD + CAT + PEG, SOD + CAT, or saline. In vitro studies suggested that PEG itself may have contributed to protection by scavenging hydroxyl radical (.OH) but not superoxide (O2-.) or H2O2. Compared with more effective endogenous (via preexposure to hypoxia) or exogenous (via liposomes) means for increasing lung antioxidant enzymes, PEG enzymes are less protective against lung injury from continuous hyperoxia.

Animals↗
PubMed1989

Blood sulfhydryl level increases during hyperoxia: a marker of oxidant lung injury.

Blood acid-soluble sulfhydryl, but not glutathione (GSH), levels increased during the development of acute edematous lung injury in rats exposed to normobaric hyperoxia for 48 h or more. A relationship between increases in blood sulfhydryl levels, lung injury, and O2 metabolite generation during exposure to hyperoxia was suggested by two observations. First, increases in blood sulfhydryl levels occurred simultaneously with increases in lung oxidized glutathione (GSSG) levels and lung GSSG-to-GSH ratios (GSSG/GSH). Second, hyperoxia-induced increases in blood sulfhydryl levels, blood hematocrits, pleural effusion volumes, lung GSSG levels, and lung GSSG/GSH were decreased by pretreating rats with dimethylthiourea (DMTU), an O2 metabolite scavenger. Our findings indicate that exposure of rats to hyperoxia increases blood acid-soluble sulfhydryl levels in vivo and that increases in blood sulfhydryl levels may provide an accessible marker of increased oxidant exposure and/or oxidant-mediated lung injury.

Animals↗
PubMed1989

The role of oxygen free radicals in postasphyxia cerebral hypoperfusion in newborn lambs.

Previous work in a neonatal lamb model has demonstrated abnormalities in cerebral blood flow (CBF) and oxygen consumption (CMRO2) after asphyxia. Immediately after resuscitation, there was a marked increase in CBF and a significant decrease in CMRO2 compared to control. During the late period after asphyxia (30 min to 4 h), both CBF and CMRO2 were significantly depressed. The same postasphyxia model (n = 16) was used to examine the hypothesis that generation of oxygen free radicals during cerebral reperfusion may be involved in the genesis of late postasphyxia hypoperfusion and depressed CMRO2. Before asphyxia, the animals were pretreated with either inactivated (n = 8) or active (n = 8) polyethylene glycol superoxide dismutase, 5000 U/kg, and polyethylene glycol catalase, 100 000 U/kg. CBF (radioactive microspheres) and arterial and venous (superior sagittal sinus) blood gases and O2 contents were measured during control, and at 5 min, 1 h, 2 h, and 4 h postasphyxia (PA). In the active enzyme group, 5 min postasphyxia CBF was significantly increased compared to control: 211.5 +/- 28.0 versus 78.6 +/- 11.4 ml.100 g-1.min-1, +/- SEM, p less than 0.005. At 1 h (82.9 +/- 17.6), 2 h (62.3 +/- 5.5), and 4 h (78.9 +/- 12.2) PA, CBF did not differ significantly from control. More importantly, CMRO2 did not differ from control at any time PA. In the inactive enzyme group, both CBF and CMRO2 were depressed at 1, 2 and 4 h PA. These findings are consistent with a conclusion that damage by oxygen free radicals during postasphyxia cerebral reperfusion is important to the genesis of late PA blood flow and O2 metabolism abnormalities. To the extent that depressions in CBF and CMRO2 result in ongoing brain injury, agents that ameliorate these abnormalities may improve neurologic outcome.

Animals↗
PubMed1989

Paralyzed left vocal cord associated with ligation of patent ductus arteriosus.

We reviewed the records of 167 neonates and older children undergoing ligation of a patent ductus arteriosus to determine the prevalence of recurrent laryngeal nerve injury and identify risk factors that might increase the likelihood of injury. Paralysis or paresis of the left vocal cord was identified by fiberoptic laryngoscopy in seven patients. All seven weighted less than 1500 gm at the time of operation and the ductus had been ligated with a metal clip. All had persistent symptoms when observed for 5 to 19 months. Injury to the left recurrent laryngeal nerve occurs infrequently but may have long-term consequences.

Child↗
PubMed1988

Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance.

Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from less than 10 min to 40 h, reduces immunogenicity, and decreases sensitivity to proteolysis. Because PEG has surface active properties and can induce cell fusion, we hypothesized that PEG conjugation could enhance cell binding and association of normally membrane-impermeable enzymes. Incubation of cultured porcine aortic endothelial cells with 125I-PEG-catalase or 125I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Endothelial cell cultures incubated with PEG-superoxide dismutase and PEG-catalase for 24 h and then extensively washed were protected from the damaging effects of reactive oxygen species derived from exogenous xanthine oxidase as judged by two criteria: decreased release of intracellular 51Cr-labeled proteins and free radical-induced changes in membrane fluidity, measured by electron paramagnetic resonance spectroscopy of endothelial membrane proteins covalently labeled with 4-maleimido-2,2,6,6-tetramethylpiperidinooxyl. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species.

Animals↗
PubMed1988

Sensitivity and specificity of assessing coronary bypass graft patency with ultrafast computed tomography: results of a multicenter study.

Because a significant number of all patients seen by cardiologists have had coronary bypass surgery, a relatively noninvasive method of assessing coronary bypass graft patency would be very helpful. Ultrafast computed tomography, by virtue of its rapid data acquisition time and reasonable spatial resolution, may be useful in this regard. To determine the sensitivity, specificity and predictive accuracy of this imaging modality as compared with cardiac catheterization, a multicenter study was undertaken. There were two parts to the study. Part I involved the evaluation of 179 grafts in 74 patients studied in the five participating centers between March 1985 and August 1986. Twenty-nine percent of these graft studies were found to be technically inadequate and were excluded before patency determinations began. The remaining group of 127 bypass grafts in 62 patients had studies adequate for interpretation. Fifty-one grafts were to the left anterior descending coronary artery or a diagonal branch, 37 to branches of the left circumflex artery and 28 to the right coronary artery or a posterior descending vessel; in addition, there were 11 internal mammary artery bypass grafts primarily into the left anterior descending or diagonal artery distribution. The sensitivity of detecting angiographically open grafts was 93.4%, the specificity of detecting angiographically closed grafts 88.9% and the predictive accuracy was 92.1%. A subsequent study (Part 2) was performed 9 months later to assess the ability to carry out technically adequate examinations. Of the 138 consecutive graft examinations (50 patients) included in this part of the study, 94.2% of the examinations were found to be technically adequate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Videodensitometric analysis of coronary stenoses. In vivo geometric and physiologic validation in humans.

Assessment of the severity of coronary stenoses on arteriograms conventionally is based on subjective estimates of percent luminal diameter narrowing. However, in studies in patients with multivessel coronary artery disease, we have found a poor correlation between percent stenosis and the physiologic significance of an individual coronary obstruction. The purpose of this study was to determine whether computerized videodensitometry would allow estimation of coronary luminal area and therefore prediction of the physiologic significance of individual coronary stenoses in humans. Videodensitometry was used to define the minimal luminal area of 15 left anterior descending, 15 circumflex, and 15 right coronary artery segments in 43 patients. Computer-assisted quantitative coronary arteriography (method of Brown et al) was used to determine the minimal luminal cross-sectional area of these same segments. In each arterial segment, coronary vasodilator reserve was assessed using intraoperative (n = 18 segments) or intracoronary (n = 27 segments) Doppler measurements of coronary vasodilator reserve. Videodensitometric estimates of coronary luminal area correlated well with minimal luminal area defined using the independent geometric technique of quantitative coronary arteriography (r = 0.82, y = 0.97 X + 0.71, SEE = 1.83 mm2, n = 45) and with lesion physiologic significance as defined by studies of the peak-to-resting velocity ratio (r = 0.71, 0.92, and 0.74 for the left anterior descending, circumflex, and right coronary arteries, respectively). Thus, videodensitometry is a promising method that may supplement geometric approaches to quantitative analysis of coronary arteriograms in humans.

Absorptiometry, Photon↗
PubMed1988

Pulmonary inflation reflex: its lack of physiological significance in coronary circulation of humans.

In awake dogs, voluntary deep inspiration results in a marked, reflex-mediated increase in coronary blood flow. To study this reflex in humans, we subselectively measured coronary blood flow velocity (CBFV) with a 3-F coronary Doppler catheter in 12 subjects with angiographically normal coronary arteries. In each subject, intracoronary papaverine increased CBFV to 4.8 +/- 0.2 X resting CBFV and reduced coronary resistance to 0.20 +/- 0.01 X resting coronary resistance, demonstrating normal vasodilator reserve in the vessel under study. Valsalva maneuver reduced CBFV to 0.67 +/- 0.09 X resting CBFV and increased coronary resistance to 1.37 +/- 0.20 X resting coronary resistance (P less than 0.05 vs. control). Maximum voluntary inspiration, however, did not significantly change CBFV (peak response 1.03 +/- 0.05 X resting CBFV) or coronary resistance (0.96 +/- 0.04 X resting). To determine whether augmentation of resting alpha-adrenergic tone would potentiate the reflex, eight patients performed a sustained 33% maximal handgrip for 2 min. Maximal deep inspiration during handgrip failed to result in any significant change in CBFV or coronary resistance. These studies demonstrate that the canine pulmonary inflation reflex has little or no physiological significance in the coronary circulation of conscious humans. Additionally, these data suggest that the magnitude of reflex control of the coronary circulation may vary considerably between dogs and humans.

Adult↗
PubMed1988

Hypoxia increases glutathione redox cycle and protects rat lungs against oxidants.

Preexposure to hypoxia increased survival and lung reduced glutathione-to-oxidized glutathione ratios (GSH/GSSG) and decreased pleural effusions in rats subsequently exposed to continuous hyperoxia. In addition, lungs from hypoxia-preexposed rats developed less acute edematous injury (decreased lung weight gains and lung lavage albumin concentrations) than lungs from normoxia-preexposed rats when isolated and perfused with hydrogen peroxide (H2O2) generated by xanthine oxidase (XO) or glucose oxidase (GO). In contrast, when perfused with elastase or exposed to a hydrostatic left atrial pressure challenge, lungs isolated from hypoxia-preexposed rats developed the same acute edematous injury as lungs from normoxia-preexposed rats. The mechanism by which hypoxia preexposure conferred protection against H2O2 appeared to depend on hexose monophosphate shunt (HMPS)-dependent increases in lung glutathione redox cycle activity. First, before perfusion with GO, lungs from hypoxia-preexposed rats had increased glutathione peroxidase and glucose 6-phosphate dehydrogenase (but not catalase or glutathione reductase) activities compared with lungs from normoxia-preexposed rats. Second, after perfusion with GO, lungs from hypoxia-preexposed rats had increased H2O2 reducing equivalents, as reflected by increased GSH/GSSG and NADPH/NADPH+, compared with lungs from normoxia-preexposed rats. Third, pretreatment of rats with an HMPS inhibitor, (6-aminonicotinamide) or a glutathione reductase inhibitor, [1,3-bis(2-chloroethyl)-1-nitrosourea] prevented hypoxia-conferred protection against H2O2-mediated acute edematous injury in isolated lungs. These findings suggest that increased detoxification of H2O2 by glutathione redox cycle and HMPS-dependent mechanisms contributes to tolerance to hyperoxia and resistance to H2O2 of lungs from hypoxia-preexposed rats.

6-Aminonicotinamide↗
PubMed1988

The effect of coronary angioplasty on coronary flow reserve.

To determine the effects of coronary angioplasty on coronary flow reserve (CFR), we studied 32 patients before and immediately after single-vessel coronary angioplasty and 31 patients evaluated late after angioplasty (7.5 +/- 1.2 months, mean +/- SEM). The geometry (percent area stenosis and minimal cross-sectional area) of each lesion was determined by quantitative coronary angiography (Brown/Dodge method) and the integrated optical density was measured by videodensitometry. CFR was measured with a No. 3F coronary Doppler catheter placed immediately proximal to the lesion and a maximally vasodilating dose of intracoronary papaverine. The translesional pressure gradient was obtained in all lesions before and immediately after angioplasty and in 18 of 31 vessels late after angioplasty. CFR immediately after angioplasty returned to normal levels (greater than 3.5 peak/resting velocity ratio) in 14 of 31 patients and was improved, although not normalized, in the remaining 17 patients. CFR immediately after dilation was not significantly correlated with any of the angiographic variables of arterial stenosis nor the resting pressure gradient. Moreover, the pressure gradient and absolute distal coronary pressure at peak hyperemia were not significantly different in vessels with normal and those with abnormal flow reserve immediately after dilation, suggesting that the residual stenosis did not significantly limit hyperemia. Late after angioplasty, however, a significant relationship emerged between CFR and all four indexes of residual arterial stenosis (percent area stenosis r = .70, p less than .01; minimum arterial cross-sectional area r = .70, p less than .01; integrated optical density r = .60, p less than .01; and translesional pressure gradient r = .77, p less than .01). Furthermore, in the absence of restenosis, CFR eventually normalized in all patients. These findings demonstrate that in one-half of patients there is a transient reduction in coronary flow reserve immediately after angioplasty. In the absence of restenosis, coronary flow reserve later normalizes. Consequently, measurements of coronary flow reserve immediately after angioplasty may not reflect the eventual success of the procedure in removing physiologic obstruction to coronary blood flow.

Angiography↗
PubMed1988

Coronary vasodilator reserve after human orthotopic cardiac transplantation.

Cardiac transplantation is frequently associated with accelerated coronary atherosclerosis and immune-mediated microvascular injury. To determine if orthotopic cardiac transplantation impairs the capacity of the coronary vasculature to vasodilate and conduct hyperemic blood flow, maximal coronary vasodilator reserve was measured in 25 cardiac allograft recipients with no evidence of rejection 6-57 months after transplantation and in 20 normal subjects. Left ventricular wall thickness was assessed echocardiographically, and epicardial coronary anatomy was evaluated by quantitative coronary angiography. Coronary vasodilator reserve (CVDR) was measured in all patients with a coronary Doppler catheter and a maximally vasodilating dose of intracoronary papaverine. CVDR measured in the transplant recipients with normal coronary arteries, left ventricular function, and wall thickness (5.0 +/- 0.3 [mean +/- SEM] peak/resting velocity; range, 3.8-7.3; n = 16) was not different from that of normal subjects (4.8 +/- 0.2; range, 3.7-8.3). CVDR in the five cardiac allograft recipients with diffuse coronary atherosclerosis producing 30 +/- 5% narrowing (range, 25-38%) of epicardial vessel diameter also was normal (5.1 +/- 0.3; range, 4.3-6.2; n = 5). The CVDR was reduced, however, in two of the four cardiac allograft recipients with left ventricular hypertrophy. In the only transplant recipient in whom a regional wall motion abnormality was present, CVDR was abnormal in the vascular distribution of the hypokinetic wall segment (1.8) but was normal in the artery that supplied normally functioning myocardium (4.0). These findings demonstrate that in the absence of allograft rejection, acquired left ventricular hypertrophy, and regional wall motion abnormalities, coronary vasodilator reserve is normal after orthotopic human cardiac transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1988

Sulfonylureas inhibit metabolic flux through rat liver pyruvate carboxylase reaction.

The effect of oral hypoglycemic sulfonylureas, tolbutamide and glyburide, on metabolic flux through the pyruvate carboxylase reaction was evaluated in liver mitochondria isolated from 24-hr fasted rats. Both these sulfonylureas inhibited the metabolic flux through the pyruvate carboxylase reaction in a concentration dependent manner. Half-maximal inhibition was achieved at tolbutamide and glyburide concentrations of 0.85 mM and 63.3 microM, respectively. Neither sulfonylurea altered the activity of pyruvate carboxylase or the Km of the enzyme for ATP and pyruvate. However, glyburide and tolbutamide decreased mitochondrial ATP content and elevated mitochondrial ADP and AMP levels. The decrease in mitochondrial ATP was greater with 400 microM glyburide compared with 2.0 mM tolbutamide. Glyburide also decreased mitochondrial acetyl-coenzyme A/CoASH ratio. Additionally, glyburide and tolbutamide stimulated pyruvate (5 mM) supported mitochondrial respiration in the absence of ADP. These data indicate that these sulfonylureas inhibit the metabolic flux through the pyruvate carboxylase reaction by decreasing mitochondrial ATP/ADP and acetyl-coenzyme A/CoASH ratios. Decreased mitochondrial nucleotide content and increased mitochondrial respiration caused by sulfonylureas suggest that these compounds may uncouple oxidative phosphorylation.

Acetyl Coenzyme A↗