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Biomedical subjects

M L Entman

Publications and source records attributed to M L Entman.

At least 163 records · Page 9Linked to original sources
PubMed1979

Spontaneous calcium release from sarcoplasmic reticulum. A re-examination.

A recent study by Blayney and co-workers (Blayney, L., Thomas, H., Muir, J. and Henderson, A. (1977) Biochim. Biophys. Acta 470, 128--133) purported to demonstrate that apparent spontaneous calcium release in sarcoplasmic reticulum is an artifact of the uptake of murexide dye. This report demonstrates that spontaneous calcium release (1) takes place despite equilibration of murexide sarcoplasmic reticulum to a stable baseline; (2) may be reversed by addition of ATP or oxalate after release has begun. The identical phenomenon can be demonstrated utilizing the indicator arsenazo III or Millipore filtration methods. The results suggest that equilibration of the murexide with sarcoplasmic reticulum vesicles must occur prior to ATP addition in order to achieve a stable baseline but that spontaneous calcium release is not an artifact.

Adenosine Triphosphate↗
PubMed1979

Microtubules in mammalian heart muscle.

Sections of adult mammalian cardiac muscles fixed at room temperature reveal numerous microtubules (24--28 nm in diameter) both near the nucleus and in the extra-myofibrillar space. Microtubules encircle the nucleus, are associated with the myofibrils in a helical arrangement, and form a network that runs transversely at the level of the I band and axially between the myofibrils. Microtubules are more numerous in muscle cells than previously recognized and may perform more than cytoskeletal function.

Animals↗
PubMed1979

Cardiac lymph flow in conscious dogs.

The cardiac lymphatic duct was cannulated in dogs and the exteriorized cannula allowed chronic collection of lymph during the awake state for as long as 3 wk. The surgical methodology and inherent difficulties in the technique are describ:d. Cardiac lymph flow ranged from 0.45--5.6 ml/h in the control state in 14 dogs. An occluding device and flow probe were placed on the circumflex coronary artery (CFX); ultrasonic segment length crystals were placed in the left ventricular free wall in 4 dogs. Occlusion of the CFX in these conscious dogs caused lymph flow to fall as great as 46% below control during the 1st half-hour. Reperfusion of the occluded vessel caused an increase in lymph flow as great as 67% above control. The effect on cardiac lymph flow was demonstrated for a few select drugs that have known effects on the cardiovascular system. Cardiac lymph flow was altered from control as follows: isoproterenol, 42 +/- 11% increase; RO 2-2985, 118 +/- 8% increase; verapamil, 101 +/- 10% increase; propranolol caused no significant change. The conscious dog with cardiac lymph vessel cannulated should provide a model to further study the complexities of cardiac metabolism and physiology without interference of anesthesia and surgical stress.

Animals↗
PubMed1979

Permanent changes of ventricular contractility and compliance in chronic volume overload.

Left ventricular volume overload (LVVO) has been created in 18 dogs by anastomosing a Dacron conduit between the infrarenal abdominal aorta and inferior vena cava. The dogs previously were instrumented so that in the awake state LV pressure, systemic arterial pressure, LV dP/dt, myocardial segment length and excursion, and coronary and renal artery velocities could be monitored. The animals were stressed with separate infusions of alpha-adrenergic and beta-adrenergic agonists. Both at rest and with stress, over a 12-wk period, preejection, ejection, and contractility indices decreased. Left ventricular compliance decreased as exemplified by the increased ratio of end-diastolic pressure to end-diastolic length. The shunt was ablated in 7 dogs, and monitoring in conjuction with alpha- and beta-adrenergic stress foan additional 12 wk demonstrated an initial improvement in the previous indices. However, the amelioration plateaued and values similar to the control state were not attained. This suggests that potentially permanent alterations in ventricular function and compliance have occurred.

Adrenergic alpha-Agonists↗
PubMed1979

Biochemical and morphological correlates of acute experimental myocardial ischemia in the dog. IV. Energy mechanisms during very early ischemia.

Tissue energy metabolism was examined in posterior (ischemic) and anterior ("control") regions of canine ventricles after 5 and 10 minutes of left circumflex coronary artery occlusion. When compared to identical regions of normal hearts, the following changes were found: (1) decreases in glycogen and phosphorylase activity in the anterior and posterior regions, (2) depressed state 3 rates of oxygen consumption of isolated mitochondria in both anterior and posterior regions, (3) shifts in optimum substrate concentrations for palmityl-CoA (+ carnitine) oxidation by mitochondria in the anterior and posterior regions, and (4) decreases in the apparent zero order and first order rates of mitochondrial palmitylcarnitine production. These changes correlated with a marked decrease in developed tension in the posterior regions. Depression in tension development in the posterior regions of the heart still was present after 30--60 minutes of reperfusion following a 10-minute period of occlusion. Glycogen content in the reperfused areas was significantly decreased after 60 minutes of reperfusion when compared to normal areas and to control hearts perfused for 70 minutes. After reperfusion, mitochondrial function appeared to return toward "normal." However, the slow restoration of contraction of the ischemic area suggests that cellular mechanisms operative in vivo to restore pump function still might be abnormal.

Acyl Coenzyme A↗
PubMed1979

Role of cyclic AMP in myocardial cell function.

A series of agents which stimulate the formation of cyclic AMP are well-known positive inotropic agents in the heart. This fact has suggested that cyclic AMP may indeed mediate the positive inotropic effects. The elucidation of precise in vivo mechanisms utilizing in vitro and isolated techniques is always difficult; in the myocardial cell, a very complicated and multicompartmented cell, all such in vivo-in vitro correlation must be viewed with caution. In this review, the authors has attempted to list possible cellular sites of inotropic intervention based on current concepts of excitation contraction coupling (which also are speculative). Recent evidence from in vitro experiments have suggested several sites which are apparently affected by cyclic AMP-mediated events and which are thought to be intimately related to the control of myocardial contraction. It is suggested that the myocardium be viewed as a multicompartmented system with several effector sites for cyclic AMP-mediated events, all of which have individual controls; this type of thesis would be necessary to explain the volume of experimental data which fails to show simple correlation between myocardial cyclic AMP levels and cardiac contractility. The difficulties in designing experiments to further elucidate these mechanisms and the possibility of "linked enzyme systems" are also discussed.

Adenylyl Cyclases↗
PubMed1979

Myocardial depression after elective ischemic arrest. Subcellular biochemistry and prevention.

The hemodynamic and cardiac biochemical effects of global ischemic arrest during cardiopulmonary bypass (CPB) were studied in 54 animals and compared to seven animals without ischemic arrest. Ischemic arrest alone reduced the first derivative of left ventricular force of contraction (LV dF/dt) to 52 percent of control 10 minutes after resuming function and to 64 percent after 1 hour of reperfusion. Cardiac output was depressed to 52 percent of control after 10 minutes of reperfusion, and to 74 percent of control after 60 minutes of reperfusion. In six animals, moderate hypothermia (26 degrees C.) resulted in no protection of cardiac function from ischemic arrest, whereas profound hypothermia to 18 degrees C. resulted in values of LV dF/dt and cardiac output nearly equivalent to the CPB control group (no arrest). A continuous infusion of a hyperkalemic hypothermic solution slightly improved the degree of protection over hypothermia alone. The sarcoplasmic reticulum (SR) isolated from hearts which had undergone 60 minutes of ischemic arrest bound significantly less calcium when the isolation was done after 10 minutes of reperfusion as well as when it was done after 60 minutes of reperfusion. The time to spontaneous release of calcium from the SR also was significantly longer. Moderate hypothermia did not result in improved SR function, whereas deep hypothermia induced by local cooling or by hypothermic potassium infusion retained SR function at normal levels. Oxidative phosphorylation of mitochondria isolated after 60 minutes of reperfusion was also depressed. The mitochondrial respiration rate after normothermic ischemic arrest was 155 natoms of oxygen per minutes versus 237 natoms for the hypothermic hyperkalemic group. Respiratory control index was 5.5 for the normothermic group versus 9.4 for the hypothermic group. It is concluded that hypothermia, whether effected by surface cooling or by hypothermic potassium infusion, allowed full recovery of hemodynamic and biochemical functions within 1 hour of reperfusion.

Animals↗
PubMed1978

Rapid purification of canine cardiac sarcoplasmic reticulum Ca2+-ATPase.

A pure, enzymatically active Ca2+-dependent adenosine triphosphatase (Ca2+-ATPase) has been isolated from canine ventricular sarcoplasmic reticulum. In contrast to that derived from skeletal muscle, the Ca2+-ATPase from cardiac sarcoplasmic reticulum was more active when solubilization and subsequent purification took place in the presence of its substrates, Ca2+ and ATP. Cholate- or deoxycholate-solubilized Ca2+-ATPase is recovered following rapid glycerol dilution and centrifugation. The Ca2+-ATPase is stable and possesses hydrolytic capacities up to 4 mumol/mg/min. Sodium dodecyl sulfate-polyacrylamide gels reveal the presence of one protein in the range of 95,000 to 100,000 daltons. This method also yields purified Ca2+-ATPase from fast skeletal muscle of similar activities to those reported by other laboratories.

Animals↗
PubMed1978

Cholinergic stimulation of skeletal muscle alanine and glutamine formation and release. Evidence for mediation by a nicotinic cholinergic receptor and guanosine 3':5'-monophosphate.

The mechanism of cholinergic stimulation of alanine and glutamine formation and release from skeletal muscle was studied using rat epitrochlaris preparations. The increased alanine and glutamine release produced by carbamylcholine (10(-6) M) was reproduced by tetramethylammonium (10(-6) M) but not by pilocarpine (10(-6) M) and was blocked by hexamethonium (10(-4) M) but not by atropine (10(-7) M). This increased alanine and glutamine release was not associated with altered muscle cAMP levels. However, carbamylcholine (10(-6) M) and tetramethylammonium (10(-6) M) did not increase levels of cGMP, 134% and 101%, respectively, and these increments in cGMP were blocked by hexamethonium but not by atropine. Carbamylcholine produced a concentration-dependent increase in cGMP levels. Methylisobutylxanthine and theophylline augmented the increased amino acid release and increased cGMP levels produced by carbamylcholine. Neither xanthine derivative alone altered alanine and glutamine release or cyclic nucleotide levels. Added cGMP increased amino acid release and the uptake of [U-14C]alanine and alpha-amino[14C]isobutyric acid. Carbamylcholine did not alter muscle phosphorylase a activity, glycogen levels, or basal adenylate cyclase activity. These data indicate that cholinergic stimulation of muscle alanine and glutamine formation and release involves a nicotinic cholinergic receptor and may be mediated by increased levels of cGMP, which in turn may result from a cholinergic stimulation of muscle guanylyl cyclase.

1-Methyl-3-isobutylxanthine↗
PubMed1978

Morphological and biochemical correlates of skeletal muscle contractility in the cat. II. Physiological and biochemical studies.

Isometric twitch characteristics and biochemical parameters of isolated myosin and sarcoplasmic reticulum have been compared in three cat hind limb muscles. The fast twitch caudofemoralis and the slow twitch soleus are almost pure muscles as judged from histochemical studies. Isolated myosin from the caudofemoralis is not only 2- to 3-fold higher in its ATPase activities than that of the soleus, but also in non-dissociated forms has greater electrophoretic mobility than the soleus myosin. Purified myosins from fast muscles as well as soleus exhibited three light chains upon electrophoresis. However, the intact non-solubilized myosins differed in electrophoretic mobilities. The sarcoplasmic reticulum fraction isolated from caudfemoralis exhibits faster rates of Ca++ binding and uptake than soleus, and when fit to a two component model, the caudofemoralis SR exhibits a higher amount of a fast binding site than does soleus SR, features reflected in differences in the relaxation time of the two muscles. In contrast, the fast twitch tibialis anterior has been shown to be a gradient of fiber types and its isometric twitch may be separated by selective nerve stimulation, into a fast and a slow twitch component. Our findings that myosin fractions, as well as sarcoplasmic reticulum fractions isolated from these two components differ with respect to their biochemical characteristics add support to the possibility of a dual function in this muscle.

Adenosine Triphosphatases↗
PubMed1977

The cardiac sarcoplasmic reticulum-glycogenolytic complex. A possible effector site for cyclic AMP.

Cardiac sarcoplasmic reticulum-glycogenolytic complex, isolated as a single peak on sucrose density gradient, may function as a "compartmented" effector site for cyclic AMP resulting in modulation of both glycogenolysis and calcium transport. The conversion of phosphorylase b to a is stimulated by ATP and inhibited by protein kinase inhibitor. Cyclic AMP alone stimulated neither phosphorylase b to a conversion nor calcium uptake. An inhibitor of adenylate cyclase depressed both calcium uptake and phosphorylase activation and both functions were subsequently stimulated by micromolar concentrations of cyclic AMP. Endogenous phosphorylation of sarcoplasmic reticulum was also inhibited by adenylate cyclase inhibitor and the inhibition was reversed by cyclic AMP. These results suggest that the sarcoplasmic reticulum of cardiac muscle is an internal effector site for cyclic AMP which may regulate both calcium and metabolism. It appears that cyclic AMP formation in vitro is not the rate-controlling step in the activation sequence.

Adenylyl Cyclase Inhibitors↗
PubMed1977

Cyclic AMP modulation of calcium accumulation by sarcoplasmic reticulum from fast skeletal muscle.

The role of cyclic 3',5'-AMP in modulating sarcoplasmic reticulum from fast skeletal muscle was studied. The rate of Ca2+ uptake was stimulated in the presence of protein kinase plus 1 micron cyclic AMP. The stimulation was absent when denatured protein kinase was used. When an adenylate cyclase inhibitor was added, the uptake rates fell to 55% of control. This decrease in rate was partially overcome by 1 micron cyclic AMP. A modulating role for cyclic AMP in fast skeletal muscle is proposed.

Adenosine Triphosphatases↗
PubMed1977

Physiological, biochemical, and morphological characteristics of myocardial anoxia: the use of a semi-perfusion canine preparation.

Regional myocardial anoxia was produced in dogs by perfusion of the left circumflex artery (LCA) with deoxygenated blood. Isolated sarcoplasmic reticulum fragments (cardiac relaxing system) showed decreased Ca2+ binding and uptake. The ability of isolated mitochondria to utilise long-chain fatty acids was markedly reduced. This model has revealed inherent biochemical differences between ischaemia and anoxia.

Animals↗