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Biomedical subjects

M L Entman

Publications and source records attributed to M L Entman.

At least 145 records · Page 8Linked to original sources
PubMed1983

Comparison of hepatic extraction of insulin and glucagon in conscious and anesthetized dogs.

Previous studies in anesthetized dogs demonstrated that basal hepatic extraction of insulin and glucagon are approximately 50 and 10-20%, respectively. Because of the stress of anesthesia and surgery, these values may not be relevant to normal physiology. In this study, hepatic extraction of insulin and glucagon were compared in conscious and anesthetized dogs. The conscious dogs had chronically implanted catheters in the portal and hepatic vein and the carotid artery and Doppler flow probes on the portal vein and hepatic artery. The mean basal portal vein insulin (42 +/- 10 and 44 +/- 7 microU/ml, respectively) and glucagon (247 +/- 37 and 219 +/- 20 pg/ml, respectively) concentrations were similar in conscious and anesthetized animals. The mean basal portal vein, but not hepatic artery, plasma flow was significantly increased in conscious dogs (462 +/- 62 vs. 294 +/- 35 ml/min, respectively). Despite the increased portal vein plasma flow in conscious animals, the basal hepatic extractions of insulin (42 +/- 6 vs. 39 +/- 6%, respectively) and glucagon (12 +/- 7 vs. 7 +/- 7%, respectively) were similar in both types of animals. Arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion, which increased the amount of insulin and glucagon presented to the liver in conscious and anesthetized dogs, significantly decreased the hepatic extraction of insulin. Hepatic extraction of glucagon did not change in either group of animals. In contrast, infusion of insulin (1.0 mU/kg X min) and glucagon (4 ng/kg X min) into the portal system did not alter hepatic extraction of insulin even though the amounts of insulin and glucagon presented to that organ were similar to those obtained with arginine and CCK-PZ. The basal arterial glucose level was significantly lower in the conscious dogs but the basal hepatic glucose output was similar in the two groups. The glucose response to the infusion of arginine and CCK-PZ and exogenous hormones was significantly greater in the anesthetized animals.

Anesthesia, General↗
PubMed1982

Evidence for membrane microheterogeneity in the sarcoplasmic reticulum of fast twitch skeletal muscle.

Sarcoplasmic reticulum (SR) from rabbit back muscles can be readily subfractionated into two morphologically and compositionally different vesicular populations, SRH (heavy) and SRL (light) derived from terminal cisternae and longitudinal SR, respectively. Polyacrylamide gels indicate that SRH contains most of the calsequestrin. Quantitation of freeze-fractured isolated preparations reveals that, while differences in vesicular dimensions are seen in SRH and SRL, the intramembrane particle (Ca2+ ATPase) density is identical. Phospholipid headgroup composition is the same in SRH and SRL, but fatty acyl moieties show significant differences in the ratio of saturated to unsaturated phospholipids in the two fractions. The vesicular dimensions of the purified Ca2+-ATPases, SRHP and SRLP, from the two fractions are identical, but the freeze-fracture particle density is higher in the SRLP fraction. The phospholipid composition remains similar after purification, but the differences in phospholipid fatty acyl composition of the preparations are maintained. SRH and SRHP contain almost twice as much of the unsaturated species as compared to SRL and SRLP. Differences in intramembrane particle density in purified fractions, thermotropic segregation of particles in freeze-fractured purified fractions, as well as differences in turnover of the acyl phosphate, appear to reflect the differences in fatty acyl chain composition of the two SR fractions and provide evidence of microheterogeneity in lipid-protein environment of the SR.

Animals↗
PubMed1982

Studies on the mechanism of an antibiotic ionophore, R02-2985 (X537A) in the conscious chronically instrumented dog: involvement of the prostaglandin synthetic pathway.

Conscious dogs were pretreated with a large dose of indomethacin in order to test the hypothesis that prostaglandin synthesis may be involved in the mechanism of action of the inophore R02-2985. The increase in renal blood flow and decrease in renal vascular resistance usually produced by R02-2985 were inhibited by indomethacin. In fact, the calculated renal resistance doubled. In contrast to the effects on renal circulation, indomethacin did not affect coronary blood flow increases which occur independent of contractility changes produced by this ionophore. Effects associated with facilitated release of catecholamines, ie, increases in heart rate, central aortic pressure, and dP/dt were prolonged in comparison to the control study published earlier where these parameters returned to control levels within 2.5 h, thus suggesting that prostaglandin synthesis may somehow potentiate the effects of R02-2985 on the release of catecholamines in vivo.

Animals↗
PubMed1981

Evidence for a calcium-sensitive factor which alters the alkaline pH sensitivity of sarcoplasmic reticulum calcium transport.

Oxalase-supported, ATP-dependent Ca2+ uptake by cardiac and skeletal muscle sarcoplasmic reticulum (SR) exhibits a pH profile with the maximal rate of Ca2+ uptake at pH 6.6-6.8 and marked inhibition (90-95%) at pH 7.4-7.6, a point at which Ca2+-dependent ATPase activity is optimal. These observations are noted when the SR is first preincubated in media containing no added Ca2+. This alkaline pH inhibition is not caused by an irreversible perturbation since the Ca2+ uptake rate is fully restored by changing the alkaline pH preincubation medium to pH 6.8. When SR is preincubated with added Ca2+, Ca2+ uptake at alkaline pH (7.4-7.6) is only inhibited by 10-30%. Ca2+ uptake at pH 6.8 is the same regardless of preincubation conditions. A depressed oxalate permeability is not a factor in the observed alkaline pH inhibition of Ca2+ uptake. At alkaline pH, the relationship between the preincubation Ca2+ concentration and the rate of Ca2+ uptake is hyperbolic; the half-maximal free Ca2+ concentration for stabilization of Ca2+ uptake is 8-15 microM with a Vmax equal to the velocity at the optimal pH. The Hill coefficient is 1.0, implying a single class of Ca2+-requiring sites for stabilization at alkaline pH. In contrast to its effect on Ca2+ uptake, the presence of Ca2+ during preincubation does not alter the pH sensitivity of Ca2+-dependent ATPase activity. Thus, the presence of Ca2+ during preincubation may stabilize a state of the CaATPase, conducive to the coupling of net Ca2+ translocation to Ca2+-dependent ATPase activity, which is ordinarily opposed by alkaline pH. The data suggest a single class of Ca2+-requiring sites which favors this coupled state.

Animals↗
PubMed1981

Myocardial protection from ischemic arrest: potassium and verapamil cardioplegia.

Prolonged normothermic myocardial ischemic arrest results in myocardial dysfunction. This study has investigated the technique of preserving myocardial function by a single bolus intracoronary infusion of combination potassium and verapamil at the onset of ischemic arrest. Sixty-one dogs underwent cardiopulmonary bypass with 60 min of ischemic arrest: 25 received no myocardial protection, 12 received a single intracoronary bolus of KCl, 12 received combination verapamil and KCl, and 12 received verapamil alone. Following the ischemic arrest, hearts protected by combination of potassium and verapamil demonstrated better survival evidenced by the ability of all 12 dogs to resume normal hemodynamic function. The hemodynamic function in the combination potassium and verapamil group also demonstrated better cardiac output, left ventricular dF/dt, and myocardial segment shortening than survivors in the other groups. Subsarcolemmal (SSL) and intermyofibrillar IMF) mitochondria were isolated from these hearts and function evaluated. NADH-linked oxygen consumption was impaired as was calcium transport in the SSL from unprotected ischemic hearts. Intermyofibrillar mitochondria were not different from control or sham. The hearts protected by verapamil and potassium demonstrated normal mitochondrial function.

Animals↗
PubMed1981

[125I]iodopindolol: a new beta adrenergic receptor probe.

When utilizing iodohydroxybenzylpindolol (IHYP) as an adrenergic receptor probe in muscle membrane systems, the data demonstrated an unacceptably high nonspecific binding component. Bearer et al. have reported that chloramine-T induced iodination of hydroxybenzylpindolol (HYP) results in the incorporation of iodine into the indole ring rather than into the phenolic moiety as noted previously by others. These results suggest that pindolol itself can also be iodinated. Therefore, the usefulness of carrier free 125I-labeled iodopindolol (IPIN) as an adrenergic receptor probe was investigated. Using between 0.01 nM and 0.1 nM [125I]IPIN in two different muscle membrane systems, we found the nonspecific binding component to be 10% or less of total binding. When [125I]IPIN was used with membranes prepared from rat skeletal muscle, we found it to interact with a single set of high affinity binding sites (KD = 0.13 +/- 0.01 nM) with the characteristics of beta adrenergic receptors and a density of 48.5 fmoles/mg protein. IPIN binding was also studied with purified dog cardiac sarcolemma. A single set of binding sites was detected having a KD of 1.64 +/- 0.5 nM; the density of these sites was 289 fmoles/mg membrane protein. [125I]IPIN may be a useful probe for the beta adrenergic receptor of tissues in which [125I]IHYP and other beta adrenergic receptor probes have a non-specific binding component which approaches that of the specific binding component.

Animals↗
PubMed1981

Microspheres in cardiac lymph: control and ischemic states.

The cardiac lymph from conscious animals was monitored for the presence or absence of radiolabelled 15 micrometer microspheres during: 1) control periods after left atrial injection of microspheres and b) after circumflex coronary artery (CFX) occlusions (10--20 min total or less than 40 mins 50% of control flow) followed by full reperfusions. Microspheres (15 mu) numbering 7--150 were present in the lymph within 2 hrs after the occlusions; and in three experiments, the presence of a small number in the lymph on the following day implied continual release overnight. No microspheres were present in 8--48 hr lymph samples prior to occlusions. This study suggests that some microspheres escape from the intravascular space of the myocardium and are channeled into the cardiac lymphatics; this is apparent even after short-term ischemic events.

Animals↗
PubMed1981

The comparative electrophysiologic and hemodynamic effects of verapamil in puppies and adult dogs.

Verapamil has been studied extensively in adult animals. However, there is limited data about the effects of this antiarrhythmic agent in young animals. We studied the electrophysiologic and hemodynamic effects of verapamil in 5 awake, chronically instrumented puppies and in 6 anesthetized, acutely instrumented puppies. We compared the responses in puppies to those in 7 awake, chronically instrumented adult dogs and in 6 anesthetized, acutely instrumented adult dogs. In the awake, chronically instrumented animals, we measured heart rate and the effective refractory period of the atrio-ventricular specialized conduction system (ERP-AVSCS). In the anesthetized, acutely instrumented preparation, we measured heart rate, ERP-AVSCS, mean right atrial and systemic arterial blood pressure, and velocity of blood flow in the aorta, carotid and femoral arteries. We infused verapamil intravenously at doses of 50, 100, 200 and 400 microgram/kg. Verapamil (400 micrograms/kg) increased the ERP-AVSCS by 64% in awake, chronically instrumented puppies; 62% in awake, chronically instrumented adult dogs; 125% in anesthetized, acutely instrumented puppies, and 120% in anesthetized, acutely instrumented adult dogs. The effect of verapamil upon heart rate and ERP-AVSCS was more pronounced in anesthetized animals than in awake animals. Mean systemic arterial blood pressure was reduced by verapamil in anesthetized, acutely instrumented puppies and adult dogs. Verapamil reduced the velocity of aortic, femoral and carotid artery blood flow in anesthetized, acutely instrumented puppies.

Aging↗
PubMed1981

The comparative hemodynamic effects of isoproterenol in chronically instrumented puppies and adult dogs.

Although isoproterenol is the sympathomimetic amine used most often to augment cardiovascular function in infants and children, little is known about the hemodynamic effects of this drug on the immature cardiovascular system. To compare the hemodynamic effect of isoproterenol in the young animal with that in the mature animal, we infused the drug into 11 puppies of 12-38 days of age, 12 puppies of 56-89 days of age and 10 adult beagle dogs. The animals were chronically instrumented and nonsedated during the study. Isoproterenol was infused in doses of 0.05, 0.125, 0.25 and 0.5 microgram/kg/min. Isoproterenol decreased systemic arterial mean blood pressure, increased heart rate and had no effect on renal blood flow in all three groups of animals. While cardiac output was increased and systemic vascular resistance decreased in the adult dogs, neither changed in puppies. Stroke volume increased slightly in adult dogs, but decreased in puppies. This refractoriness to change of cardiac output in immature dogs may be a function of elevated resting cardiac output, developmental changes of contractility or ventricular compliance or developmental changes of vascular smooth muscle responsiveness.

Aging↗
PubMed1980

Skeletal muscle protein and amino acid metabolism in hereditary mouse muscular dystrophy. Accelerated protein turnover and increased alanine and glutamine formation and release.

Interactins between skeletal muscle protein and amino acid metabolism were investigated using C57BL and 129ReJ mice with hereditary muscular dystrophy. On incubation, hind limb muscle preparations from dystrophic mice released large quantities of amino acids, particularly alanine and glutamine which were increased 70% and 40% compared to muscles from carrier or control mice. The increased alanine release did not result from altered alanine oxidation to CO2 or reincorporation into protein. Alanine and glutamine formation from added amino acids were equal with dystrophic and control muscles. Incorporation in vitro of leucine, alanine, and glutamate into proteins of dystrophic muscle was 3- to 7-fold greater than control muscle, and the incorporation in vivo of [3H]- or [14C]arginine into muscle proteins was greater in extent and earlier in time with dystrophic as compared to control muscle. Proteins were also labeled in vivo using [guanido-14C]arginine. On incubation of these muscles in vitro, a 100% greater loss of label from protein was observed with dystrophic as compared to control preparations, and the appearance of label in the media was correspondingly increased. Sodium dodecyl sulfate-gel electrophoresis of dystrophic skeletal muscle showed numerous protein bands to be reduced in density, but autoradiographic studies demonstrated that these same bands were more highly labeled in vitro by [35S]methionine in dystrophic than in control muscle. Although insulin stimulation of glucose uptake was markedly blunted in dystrophic muscle, insulin inhibited alanine and glutamine release equally from both control and dystrophic muscle. These data indicate that alanine and glutamine formation and release are increased in hereditary mouse muscular dystrophy. An accelerated degradation and an increased resynthesis of many muscle proteins were also observed in dystrophic compared to control animals. This increased proteolysis may account for the increased alanine and glutamine formation in dystrophic muscle.

Actins↗
PubMed1980

The sarcoplasmic reticulum-glycogenolytic complex in mammalian fast twitch skeletal muscle. Proposed in vitro counterpart of the contraction-activated glycogenolytic pool.

Evidence is presented that the sarcoplasmic reticulum (SR)-glycogenolytic complex isolated from fast twitch skeletal muscle is a highly specific, functionally defined compartment for phosphorylase regulation. The addition of ATP alone results in prompt phosphorylase activation which demonstrates calcium dependence similar to the calcium-magnesium ATPase that catalyzes SR calcium transport suggesting that these two calcium-requiring -ystems might interact within the complex. Lowering extravesicular calcium concentration by transport of calcium into the SR lumen resulted in inactivation of phosphorylase a. This effect could be prevented by the addition of the calcium ionophore X537A which inhibits SR calcium sequestration or a calcium EGTA buffer which maintains free calcium. It was mimicked by EGTA addition. Since exogenous phosphorylase b and phosphorylase a were not activated or inactivated, respectively, by the endogenous activating enzymes or phosphatase in the SR-glycogenolytic complex, these regulatory enzymes may be compartmented. In addition, endogenous phosphorylase could be uncoupled from its activating enzymes by amylase treatment. These results suggest that the SR-glycogenolytic complex in fast twitch skeletal muscle is a compartmented system for phosphorylase activation controlled by SR calcium flux, a feature in contrast to the cardiac complex (Entman, M.L., Kaniike, K., Goldstein, M.A., Nelson, T.E., Bornet, E.P., Futch, T.W., and Schwartz, A. (1976) J. Biol. Chem. 251, 3140-3146). We suggest that the complex is the in vitro counterpart of the well documented rapid burst of glycogenolysis which ensures with the onset of contraction.

Adenosine Triphosphate↗
PubMed1980

Calcium uptake by two preparations of mitochondria from heart.

Ca/+ transport and respiratory characteristics of two preparations of cardiac mitochondria (Palmer, J.W., Tandler, B. and Hoppel, C.L. (1977) J. Biol. Chem. 252, 8731-8739) isolated using polytron homogenization (subsarcolemmal mitochondria) and limited Nagarse exposure (intermyofibrillar mitochondria) are described. The Nagarse procedure yields mitochondria with 50% higher rates of oxidative phosphorylation than the polytron-prepared mitochondria in both rat and dog. Rat hear intermyofibrillar mitochondria contain 50% more cytochrome aa3 than the polytron preparation, whereas in the dog, cytochrome aa3 content is not significantly different. Cytochrome oxidase activities and cytochrome c, c1 and b contents were comparable in both populations of rat and dog heart mitochondria. The V of succinate-supported Ca2+ accumulation for Nagarse-prepared mitochondria from rat heart was 1.8-fold higher than the polytron-prepared mitochondria. In dog heart, the Nagarse preparation showed a 3.0-fold higher V for Ca2+ uptake compared to the polytron preparation. A lower apparent affinity for Ca2+ was demonstrated in the intermyofibrillar mitochondria for both species (Km is 2-2.5-fold higher). The Hill coefficient was 1 both mitochondrial types. Subsarcolemmal mitochondria from both species were treated with Nagarse to determine the role of this treatment on the observed differences. Nagarse did not alter any kinetic parameter of Ca2+ uptake. The properties of these mitochondria with reference to their presumed intracellular location may pertain to the role of mitochondria as an intracellular Ca2+ buffering mechanism in contractile tissue.

Absorption↗
PubMed1980

Mitochondrial water in myocardial ischemia: investigation with nuclear magnetic resonance.

Nuclear magnetic resonance studies of mitochondria isolated from ischemic hearts after coronary vessel occlusion indicated a decrease in water proton relaxation times. This change coincided with a decrease in the hydration of the samples. It is suggested that in ischemia, changes in macromolecular hydration may be one of the first mechanisms to alter function in the mitochondria, which are vital to the energy-transducing process in heart muscle.

Animals↗