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Biomedical subjects

V Chen

Publications and source records attributed to V Chen.

At least 109 records · Page 6Linked to original sources

Dissociation of adenosine from metabolic regulation of coronary flow in the lamb.

The objective of these studies was to evaluate the contribution of an adenosine mechanism to metabolic regulation of coronary flow. Cardiac O2 metabolism (MVO2) was altered by changing cardiac output while aortic pressure and heart rate were held constant (paced). Ganglionic (tetraethylammonium chloride) and beta blockade (propranolol) were employed. Relationships of coronary flow to MVO2 were determined in control and alloxan diabetic animals. The latter have previously been shown to have reduced sensitivity to adenosine [Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H252-H258, 1982]. In each group, responses were measured before and after adenosine receptor blockade with aminophylline (10 mg/kg). Responses to infused adenosine were also compared. A linear relationship between adenosine infusion rate and flow was found in all conditions. Aminophylline caused a 70% reduction in adenosine sensitivity in controls. In the diabetics, adenosine sensitivity was much reduced and was identical with blocked controls. A close correlation between left ventricular work and MVO2 was found in both groups. Coronary flow increased linearly with MVO2, and the slopes before and after aminophylline were identical. Myocardial O2 extraction remained unchanged. The same relationships were found in the diabetics, and responses did not differ from controls. Thus, in two conditions of sharply reduced sensitivity to exogeneous adenosine, coronary flow (and resistance) were as equally well matched to MVO2 as in controls. These data suggest that mechanisms other than, or in addition to, adenosine provide the close link between MVO2 and coronary flow with changing cardiac work loads.

Adenosine↗

Successful treatment of experimental neonatal respiratory failure using extracorporeal membrane lung assist.

A total of 44 preterm fetal lambs at great risk of developing respiratory failure were delivered by Cesarean section, and were then managed on conventional mechanical pulmonary ventilation. Fifteen animals initially fared well, and 14 of these were long term survivors. Twenty-nine other lambs showed a progressive deterioration in arterial blood gases within 30 minutes of delivery, of which 10 lambs were continued on mechanical pulmonary ventilation (20% survival), while the remaining 19 lambs were placed on an extracorporeal membrane lung respiratory assist (79% survival). Extracorporeal membrane lung bypass rapidly corrected arterial blood gas values, and permitted the use of high levels of CPAP instead of the continuation of mechanical pulmonary ventilation at high peak airway pressures. Improvement in lung function was gradual, and predictable. Early institution of extracorporeal respiratory assist using a membrane artificial lung rapidly corrected arterial blood gas values and significantly improved on neonate survival.

Animals↗

Effects of insulin on glucose metabolism in isolated heart myocytes from adult rats.

The study examined the effect of insulin on glucose metabolism in freshly isolated calcium-tolerant heart myocytes from adult rats. The uptake of 2-deoxyglucose demonstrated an initial lag in response to insulin and the maximal insulin effect was not attained until after 3 min preincubation with the hormone. A dose-response study of 14CO2 production from [14C]glucose revealed that the maximum insulin stimulation of glucose utilization occurred with 5 mU/ml. Both the uptake and the oxidation of glucose proceeded at a linear rate in the absence and presence of insulin. However, insulin exerted a greater effect on the uptake (42-54%) than on the oxidation (17-22%) of exogenous glucose. Incorporation of glucose into glycogen was markedly increased by insulin and resulted in the myocyte glycogen concentration returning to in vivo levels. In the absence of insulin, glucose incorporation plateaued within 10 min of incubation and the glycogen concentration was not altered. Our findings also indicate that at equilibrium, insulin-treated cells exhibited a higher glycogen turnover rate. It thus appears that insulin exerts a differential effect on the different pathways in glucose metabolism in the isolated cardiac cells. This may be related in part to their quiescent state and lower energy demand.

Animals↗

Myocardial injury following endogenous catecholamine release in rabbits.

Catecholamines (CAT) given in large doses produce cardiomyopathic changes in several animal species. This study was designed to determine if endogenous release can also induce cardiac injury. Rabbits were infused with doses of tyramine (TYR), ranging from 200 to 500 micrograms/min/kg, i.v. for 90 min. Arterial pressure and heart rate were measured, as were total CAT concentrations, blood gases, pH and glucose. Two days later the animals were killed and cardiac injury assessed using a histological scoring system. All data were compared with controls given saline. Initial CAT averaged 452 pg/ml, rose to 2890 pg/ml after starting TYR, 500 micrograms/min/kg, and remained elevated for the duration of infusion. Circulating CAT levels were a function of TYR dose, and bore a linear relationship to the histological score (P less than 0.001). Development of lesions was unaltered by beta 1 blockade with practolol, but sharply reduced by alpha blockade with phentolamine (P less than 0.01). Pretreatment with insulin also reduced lesion formation, but diabetic (alloxan) rabbits showed no greater CAT injury. It is concluded that endogenous release of CAT induces myocardial injury in the rabbit in a dose-dependent manner. This is unrelated to myocardial O2 demand, and microvascular pathology was absent. Activation of alpha adrenergic pathways is likely the dominant or exclusive mechanism.

Animals↗

Value of the 14C-D-xylose breath test in patients with intestinal bacterial overgrowth.

18 control subjects and 18 patients, with a variety of gastrointestinal conditions were investigated using a 10-muCi 14C-D-xylose breath test. The latter also underwent quantitative bacterial studies of fluid obtained by intestinal intubation. In 14 patients a smaller dose of 3 muCi 14C-D-xylose was compared to the standard dose and there was a good correlation between the two doses. The peak value of the 14C-D-xylose test provided the best discrimination between patients with and without bacterial overgrowth. The 14C-glycocholic acid test performed in 15 patients, although as sensitive, was less discriminating. The 14C-D-xylose breath test is reliable and more specific in confirming the diagnosis of small intestinal bacterial overgrowth without having to resort to direct bacterial studies.

Breath Tests↗

Dietary determinants of gastric cancer in south Louisiana inhabitants.

In south Louisiana, 391 recently diagnosed gastric cancer patients and an equal number of controls were interviewed. Questions asked covered residential and occupational histories, environmental exposures, tobacco use, diet, alcohol consumption, and pertinent demographic characteristics. Elevated relative risks were found for use of tobacco and alcohol products. Diet was found to be the main determinant of gastric cancer risk in south Louisiana. Both dietary patterns and dietary risk factors differed for blacks and whites, although fruits as a group and dietary vitamin C were found to exert strong protective effects for both blacks and whites. Consumption of smoked foods and homemade or home-cured meats increased risk of gastric cancer for blacks but not for whites. The findings are discussed in the light of the prevailing etiologic hypotheses.

Adult↗

Esophageal cancer in Uruguay: a case-control study.

Esophageal cancer has constituted a major public health problem in Uruguay, with age-adjusted death rates of 14.5 X 10(5) for males and of 3.8 X 10(5) for females. A case-control study was undertaken to ascertain the possible association of the local custom of drinking infusions of Ilex paraguariensis ("maté") with cancer of the esophagus, after controlling for well-known risk factors, such as alcohol and tobacco consumption. Two hundred twenty-six patients with esophageal cancer and 469 controls (control:case = 2.1) were interviewed at the time of admission or consultation at the Oncology Institute of Montevideo from 1979 through 1984. Males showed elevated risks of esophageal cancer associated with heavy tobacco [relative risk (RR) = 10.8] and alcohol (RR = 10.3) exposures. Among females, the independent effects of tobacco and alcohol were nonsignificant. Maté consumption had an independent effect in both males and females, with odds ratios of 6.5 and 34.6, respectively, for heavy users. Moreover, a well-defined dose response was evident in both sexes.

Adult↗

Regulation of substrate oxidation in isolated myocardial cells by beta-hydroxybutyrate.

The role of ketone bodies in myocardial substrate oxidation was examined using freshly isolated Ca2+-tolerant heart myocytes, beta-hydroxybutyrate (beta OHB) inhibited lactate oxidation by the myocytes by 30-60%, and the inhibition was concentration dependent. Palmitate oxidation was also markedly decreased, whereas octanoate oxidation was only minimally affected by the presence of beta OHB. Lactate, octanoate, or palmitate had little, if any, effect on beta OHB oxidation. beta OHB oxidation was reduced by 22-28% in myocytes isolated from chronically diabetic rats, whereas the oxidation of palmitate remained similar to the controls. However, beta OHB still inhibited palmitate oxidation to the same extent as in the control cells. Our data support the role of beta OHB as a physiologic regulator of myocardial substrate metabolism.

3-Hydroxybutyric Acid↗

Effect of experimental dysthyroidism on the enzymatic character of the diaphragm.

This study examined the effects of long-term experimental dysthyroidism on the enzymatic character of the costal diaphragm and selected respiratory parameters. Costal diaphragms from thyroidectomized (TX), euthyroid (EU), and hyperthyroid (HT) male albino rats were used. HT was induced by subcutaneous injections of triiodothyronine on alternate days for 6 wk. Minute ventilation was greater for the HT (70%) compared with the TX rats. The enzymatic potentials of glycolysis (28%), tricarboxylic acid cycle (30%), and fatty acid oxidation (16%) were significantly increased in the HT diaphragms, whereas the potentials were lower by a similar relative extent in the TX diaphragms. The proportion of alkali-labile fibers were greater in the TX and lower in the HT diaphragm. The shifts in heart and muscle lactate dehydrogenase isoenzyme activities were consistent with the fiber type changes. These findings show that dysthyroidism modifies the overall enzymatic capacity of the diaphragm (i.e., glycolysis, tricarboxylic acid cycle, and fatty acid oxidation) along with the proportion of alkali-labile to alkali-stable fiber types. These enzymatic changes are similar to those resulting from exercise training, tracheal banding, streptozotocin diabetes, and emphysema.

Animals↗

Respiratory distress syndrome in immature lambs. Prevention through antenatal accelerated conditioning of the lung.

We tested the effectiveness of constant distending pressure applied to immature lungs in preventing respiratory distress syndrome. Fetal lambs of 131 to 134 days gestation were delivered by cesarean section, but the umbilical circulation was kept intact for CO2 removal through the natural in situ placenta. The lungs were inflated to a pressure of 35 cm H2O (Group I, 11 animals) or 25 cm H2O (Group II, 14 animals), after which the airway pressure was maintained at 15 cm H2O through apneic oxygenation until total static compliance exceeded 0.5 ml (cm H2O)- 1kg -1. After a mean of 1.1 and 5.7 h, respectively, the animals were delivered and were given mechanical ventilation for 24 h. Twenty-four animals reached this aimed-for compliance and survived the period of mechanical ventilation in excellent health. A control group of fetal lambs was delivered immediately and treated with mechanical ventilation. Three of 10 control animals developed severe respiratory distress syndrome and died; 1 additional animal survived but with central nervous system involvement from severe hypoxia. We conclude that pulmonary inflation to 35 cm H2O pressure, followed by a constant distending pressure of 15 cm H2O, held until compliance reaches 0.5 ml (cm H2O)- 1kg -1, is an important element in the prevention of respiratory distress syndrome.

Animals↗

The effects of acute and chronic diabetes on myocardial metabolism in rats.

This study examined how the duration of experimentally induced diabetes affects myocardial metabolism. Both acutely (2-day) and chronically (30-day and 90-day) streptozocin (STZ)-diabetic rats exhibited hyperglycemia and hyperketonemia, while hyperlipemia was evident only in the chronically diabetic rats. The activity of succinate dehydrogenase was lower, whereas that of 3-hydroxyacyl-CoA-dehydrogenase was higher in the hearts of chronically diabetic rats. Although myocardial concentrations of glucose-6-phosphate, glycogen, and triacylglycerols were elevated in diabetes, the patterns of alterations differed between acute and chronic diabetes. The fructose-1,6-diphosphate/fructose-6-phosphate ratio declined progressively after STZ administration, which was not accompanied by a reciprocal increase in citrate levels, although citrate concentrations were elevated. Impaired glucose oxidation was more severe in the freshly isolated heart cells from 30-day than from 2-day diabetic rats. For a given substrate concentration, the oxidation rates of palmitate and 3-hydroxybutyrate were markedly reduced in myocytes from 30-day diabetic rats. However, they were similar to or even higher than the rates found in their control counterparts under conditions that reflected the respective in vivo concentrations of the substrates. Incubating isolated myocytes from 2-day diabetic rats in the presence of insulin only partially restored the impaired glucose oxidation. Insulin administered to the animals 4 h before the experiments restored the impaired glucose oxidation by the cells. Insulin in vitro or single injection in vivo had little or no effect on glucose oxidation in isolated myocytes from 30-day diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Exogenous substrate utilization by isolated myocytes from chronically diabetic rats.

The effect of chronic streptozotocin-induced diabetes on the utilization of exogenous substrates by freshly isolated, Ca2+-tolerant nonbeating myocytes was investigated. The rates of glucose (5 or 25 mM) and lactate (1 mM) oxidation were significantly reduced in myocytes of diabetic rats, whereas palmitate (0.4 or 1 mM) oxidation was similar to the controls. Glucose oxidation in diabetic (but not in control) and palmitate oxidation in control (but not in diabetic) myocytes were increased by raising the respective substrate concentrations in the medium to levels found in vivo in diabetic rats. Inhibition of glucose and lactate oxidation in the presence of competing substrates were generally similar between control and diabetic myocytes. However, the inhibitory effect of glucose on lactate oxidation was greater in control cells. The rate of palmitate oxidation was diminished by glucose in the controls, but this was not observed in the diabetic myocytes. Oxygen consumption by the myocytes of diabetic rats was below that of control cells when lactate or palmitate was present in the medium. ATP and phosphocreatine contents were similar in the myocytes of diabetic and control rats. All the observed changes in myocytes prepared from diabetic rats were reversed by in vivo insulin treatment.

Adenosine Triphosphate↗

Prevention of hyaline membrane disease in premature lambs by apneic oxygenation and extracorporeal carbon dioxide removal.

Hyaline membrane disease is found only in lungs where pulmonary ventilation has been established, i.e. after birth. We delivered eleven fetal lambs of a gestational age of 128-130 days but instead kept their lungs in total apnea and inflated to constant pressure, while removing all metabolically produced carbon dioxide with an extracorporeal membrane lung. Oxygen was provided by the membrane lung, and by apneic oxygenation through the natural lungs. Hence, arterial blood gases remained always normal, without any pulmonary ventilation. After 6-66 h the lungs had sufficiently cleared to allow normal mechanical pulmonary ventilation in 10 our of 11 lambs so treated. In a control group treated with mechanical ventilation alone, five of seven lambs died within the first 24 h of severe hyaline membrane disease.

Animals↗