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Biomedical subjects

K W Butler

Publications and source records attributed to K W Butler.

At least 19 recordsLinked to original sources
PubMed1995

Contractile dysfunction caused by normothermic ischaemia and KCL arrest in the isolated pig heart: a 31P NMR study.

The aims of this study were to assess (1) whether contractile dysfunction caused by ischaemia under hyperkalaemic conditions ("cardioplegic ischaemia") is associated with impaired energy production or abnormalities in regulation of contractility and (2) whether hyperkalaemia itself contributes to contractile dysfunction. We used 31P and 23Na NMR spectroscopy in conjunction with measurements of mechanical function and oxygen consumption in Langendorff perfused pig hearts to evaluate the mechanism of contractile failure caused by (1) total global cardioplegic (17 mM [K+]) ischaemia (36 degrees C, 50 min KCl arrest, 45 min ischaemia, 20 min reflow with high KCl) and (2) KCl arrest alone (115 min) without flow cessation. KCl arrest plus ischaemia and subsequent reperfusion (Group I) resulted in decreases in ATP (mean +/- S.D.; 61 +/- 13% of initial, n = 5; P < 0.01) and pressure-rate product (PRP) (31 +/- 9%, n = 17; P = 0.0001) while phosphocreatine (PCr), Pi, total creatine (Cr) and intracellular Na+ levels were unaffected. KCl arrest itself (Group II, n = 6) did not affect PCr, ATP or total Cr levels but decreased the PRP to 59 +/- 12% (P < 0.001). Oxygen consumption rates (Vo2) were reduced in both groups to similar levels (67 +/- 18, P < 0.01 and 77 +/- 13%, P < 0.02, respectively). The efficiency of energy conversion to mechanical work (PRP/delta VO2) decreased to 51 +/- 15 (P < 0.001) and 67 +/- 13% (P < 0.012) of initial levels, respectively. To assess metabolic and contractile reserves of post-ischaemic (n = 7) and KCl-treated (n = 3) hearts, the effects of isoproterenol (Iso) and increased Ca2+ were compared with those in normal beating hearts (Group III, n = 3). In all groups treatment with Iso (0.1 micron) greatly increased PRP (to 526 +/- 116, 203 +/- 16 and 198 +/- 8% of the level prior to stimulation (baseline), P < 0.01, respectively) and Vo2 (162 +/- 9, 153 +/-16 and 128 +/-10% of baseline, P < 0.05, Respectively). Increasing [Ca2+] from 1 to 1.66 mM produced less stimulation than Iso: PRP increased to 195 +/- 23, 156 +/- 13 and 163 +/- 22% (P < 0.05) and Vo2 increased to 138 +/- 22 (P < 0.05), 115 +/- 4 and 120 +/- 10% of baseline in Groups I, II and III, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1995

Protective effect of amiloride during hypothermic hyperkalemic preservation: a 31P NMR study in isolated pig hearts.

To assess the possible role of Na+/H+ exchange in ischemia-reflow damage during cold preservation, pig hearts retrogradely perfused with Krebs-Henseleit (KH) bicarbonate buffer were arrested by increasing [K+] (to 17 mM), cooled (10 degrees C) and subjected to no flow ischemia for 15 h in the absence (C, n = 5) and in the presence of 0.5 mM amiloride (A, n = 5). A was added 7 min prior to ischemia and removed after 3 min reflow. 31P nuclear magnetic resonance (NMR) spectra were continuously acquired and functional indices were assessed prior to and after ischemia. Before reflow, the levels of phosphocreatine (PCr), ATP, inorganic phosphate (Pi)+phosphomonoesters (PME) and cytosolic pH in C and A did not differ: C, 12 +/- 7, 56 +/- 13, 427 +/- 75% of initial and 5.90 +/- 0.20; A, 15 +/- 4, 82 +/- 21, 371 +/- 60% and 5.90 +/- 0.19, respectively; no contracture occurred. Upon reflow with hyperkalemic buffer PCr recovery in A-treated hearts was greater than in C (73 +/- 21 v 49 +/- 13%, P < 0.05) and parallel increases in left ventricular end diastolic (LVEDP) and perfusion pressure took place in both groups, however these parameters remained lower in A-treated hearts. Upon switching to KH buffer the oxygen uptake rate (VO2) was higher in A than in C (79 +/- 18 v 59 +/- 6%, P < 0.05) whereas the differences in the pressure-rate product (PRP, 51 +/- 21 in A v 38 +/- 11% in C) and LVEDP (16 +/- 11 in A v 24 +/- 7 mmHg in C) did not reach statistically significant levels. Adjusting LVEDP in both groups to the same levels (19 +/- 6 v 21 +/- 9 mmHg in C) by changing balloon volume resulted in significant difference in PRP (61 +/- 19% v 42 +/- 6% in C, P < 0.02). The coronary resistance measured in beating hearts remained lower in A than in C (34.5 +/- 3.0 v 57 +/- 11 mmHg/(ml/min g), P = 0.04). To estimate contractile and metabolic reserves post-ischemic heart were challenged by increasing [Ca2+] in the perfusate from 1.0 to 1.6 mM. PRP and VO2 increased; PRP reached 71 +/- 32 (A) and 54 +/- 10% (C) and VO2 remained higher in A: 90 +/- 16 (A) v 62 +/- 4% (C) (P = 0.01) of preischemic levels. We suggest that Na+/H+ exchange may contribute to ischemia-reflow damage during cold preservation of isolated pig hearts.

Adenosine Diphosphate↗
PubMed1995

A 31P-nuclear magnetic resonance study of intermittent warm blood cardioplegia.

This study was designed to assess the effects of intermittent warm blood cardioplegia on myocardial energy metabolites, intracellular pH, and contractile function. The isolated blood-perfused pig hearts were divided into three groups. After 30 minutes of control perfusion, the hearts in group 1 (n = 10) received 90 minutes of continuous warm (37 degrees C) blood cardioplegia; the hearts in group 2 (n = 9) received six 5-minute periods of warm blood cardioplegia, interrupted by six 10-minute episodes of ischemia (37 degrees C). The hearts were then reperfused for 30 minutes. The hearts in group 3 underwent 150 minutes of control perfusion without cardioplegia or ischemic episodes. Phosphorus 31-nuclear magnetic resonance spectra showed that a 10-minute interruption of warm blood cardioplegia decreased phosphocreatine levels and intracellular pH by approximately 47% (p < 0.01) and 0.12 unit (p < 0.05), respectively, and increased inorganic phosphate levels by approximately 87%, whereas resumption of cardioplegia for 5 minutes resulted in almost 100% recovery of phosphocreatine and inorganic phosphate levels and intracellular pH. More important, subsequent interruptions did not result in any cumulative changes in phosphocreatine level, inorganic phosphate level, or intracellular pH beyond those changes observed after the initial cardioplegic interruption. Moreover, during reperfusion there were no significant differences in adenosine triphosphate and phosphocreatine levels among the three groups of hearts. Furthermore, hearts from groups 1 and 2 showed comparable recovery of contractile function. These results indicate that six 10-minute interruptions and six 5-minute restorations of warm blood cardioplegia caused only mild and reversible changes in myocardial energy metabolites and intracellular pH and these changes were not cumulative. This study suggests that antegrade intermittent warm blood cardioplegia may provide as much myocardial protection as does antegrade continuous warm blood cardioplegia in the normal heart.

Adenosine Triphosphate↗
PubMed1991

The effect of high buffer cardioplegia and secondary cardioplegia on cardiac preservation and postischemic functional recovery: a 31P NMR and functional study in Langendorff perfused pig hearts.

High buffer cardioplegia may provide protection against ischemic damage by reducing the extent of intracellular acidosis. Secondary cardioplegia may improve postischemic recovery by restoration of high energy phosphates, ionic gradients, and intracellular pH. To test these hypotheses, pig hearts were arrested with high buffer (150 mM MOPS) cardioplegia or modified St. Thomas' solution II and then kept ischemic at 12 degrees C for 8 h. High energy phosphates and intracellular pH were followed during the period of ischemia, using 31P nuclear magnetic resonance spectroscopy, and functional recovery was followed during reperfusion. The hearts arrested by high buffer cardioplegia showed significantly higher intracellular pH than hearts preserved with St. Thomas' solution, but there were no significant differences in high energy phosphates. There were no significant differences in functional recovery. We found, however, that secondary cardioplegia abolished ventricular fibrillation, and resulted in improved functional recovery after 8 h of ischemic preservation compared with the hearts reperfused with Krebs-Henseleit solution alone. Our results suggest that despite attenuating the decreases in intracellular pH, high buffer cardioplegia does not improve recovery following 8 h of preservation at 12 degrees C. Secondary cardioplegia reduces the incidence of ventricular fibrillation and improves postischemic functional recovery of the myocardium.

Adenosine Triphosphate↗
PubMed1990

In vivo hepatic energy metabolism during the progression of alcoholic liver disease: a noninvasive 31P nuclear magnetic resonance study in rats.

We investigated serially in vivo the ratios of phosphorylated metabolites and the intracellular pH in the livers of rats fed ethanol chronically to evaluate the relation between changes in energy metabolism and the progression of alcoholic liver disease with 31P nuclear magnetic resonance spectroscopy. 31P nuclear magnetic resonance spectra of the liver were acquired noninvasively from rats pair-fed a nutritionally adequate liquid diet containing ethanol or an isocaloric amount of dextrose with an implanted intragastric cannula for up to 24 wk. A high blood alcohol level was constantly maintained. The spectra were obtained using a surface coil combined with a ferrite screen to eliminate nuclear magnetic resonance signals derived from the superficial muscles. Contaminating 31P nuclear magnetic resonance signals arising from abdominal tissues other than the liver were eliminated from the spectra by digital subtraction. Throughout the study the inorganic phosphate/beta-ATP peak area ratio observed in alcohol-fed rats was found to be consistently elevated in comparison with the control rats (at 3 to 5 wk alcohol-fed rats = 1.20 +/- 0.10, control rats = 0.78 +/- 0.04, p less than 0.05.; at 22 to 24 wk alcohol-fed rats = 1.23 +/- 0.10, control rats = 0.81 +/- 0.06, p less than 0.05.; mean +/- S.E.). The phosphomonoesters/beta-ATP ratio tended to be higher in alcohol-fed rats when compared with control rats. The intracellular pH measured by the chemical shift of the inorganic phosphate peak showed no significant differences between alcohol-fed rats and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

Palmitic and erucic acid metabolism in isolated perfused hearts from weanling pigs.

Hearts from 4 week-old weanling pigs were capable of continuous work output when perfused with Krebs-Henseleit buffer containing 11 mM glucose. Perfused hearts metabolized either glucose or fatty acids, but optimum work output was achieved by a combination of glucose plus physiological concentrations (0.1 mM) of either palmitate or erucate. Higher concentrations of free fatty acids increased their rate of oxidation but also resulted in a large accumulation of neutral lipids in the myocardium, as well as a tendency to increased acetylation and acylation of coenzyme A and carnitine. When hearts were perfused with 1 mM fatty acids, the work output declined below control values. Erucic acid is known to be poorly oxidized by isolated rat heart mitochondria and, to a lesser degree, by perfused rat hearts. In addition, it has been reported that erucic acid acts as an uncoupler of oxidative phosphorylation. In isolated perfused pig hearts used in the present study, erucic acid oxidation rates were as high as palmitate oxidation rates. When energy coupling was measured by 31P-NMR, the steady-state levels of ATP and phosphocreatine during erucic acid perfusion did not change noticeably from those during glucose perfusion. It was concluded that the severe decrease in oxidation rates and ATP production resulting from the exposure of isolated pig and heart mitochondria to erucic acid are not replicated in the intact pig heart.

Acetylation↗
PubMed1989

31P NMR studies of the metabolic status of pig hearts preserved for transplantation.

31P NMR spectroscopy has been used to evaluate the metabolic status of cardioplegically arrested pig hearts. Hearts were stored with Plegisol for up to 12 hours at either 5 degrees C or 12 degrees C. Results indicated that the ATP content of hearts could be maintained (greater than 70% of initial values) for up to 5 hours in the ischemic storage state. The ATP loss was greater at 12 degrees C. PCr was lost exponentially under the same conditions. Functional testing by reperfusing the stored hearts in vitro indicated a good correlation between the ATP content and survivability of the preparations. Twenty-four hour preservation of pig hearts using slow perfusion with a modified cardioplegic solution (Wicomb) allowed for preservation of both PCr and ATP, in all cases, reperfusion of hearts revealed a loss of NMR- visible ATP and PCr.

Adenosine Triphosphate↗
PubMed1988

The use of immobilized ferrite to enhance the depth selectivity of in vivo surface coil NMR spectroscopy.

Ferrite particles immobilized on a flexible support and arranged in a specific pattern will produce localized gradients in the homogeneous B0 magnetic field. The screening gradients are strong enough to cause inhomogeneous broadening of the NMR signals arising from the region of a specimen which is adjacent to the ferrite particles. This technique allows improvement of the depth selectivity in non-invasive surface coil NMR spectroscopy while optimizing both the signal-to-noise ratio and the data acquisition time of in vivo NMR experiments. The ferrite screen method also facilitates the routine application of high resolution NMR pulse sequences to in vivo experiments. The technique is readily implemented without special hardware or software and displays a great versatility in the size, shape and depth of the screening effect.

Animals↗
PubMed1986

Effects of antimalarial drugs on oxygen consumption by erythrocytes infected with Plasmodium berghei: an ESR study.

Oxygen consumption in mouse erythrocytes infected with Plasmodium berghei has been followed by electron spin resonance (ESR) spectroscopy of nitroxide radical spin probes. The parasitized red cell suspension is mixed with the spin probe CTPO (3-carbamoyl-2,2,5,5-tetramethyl-3-pyrrolin-1-yloxy) in a closed chamber. Oxygen consumption is monitored by the increasing resolution of the superhyperfine splittings of the spin label. The antimalarial drugs quinacrine, primaquine, and quinine are shown to decrease the rate of oxygen consumption of the parasitized erythrocyte suspensions. The spin-label method offers advantages over conventional polarographic and spectrophotometric assays for highly parasitized cell populations where cells are fragile and contain oxidized hemoglobin as well as hemoglobin-derived pigments.

Animals↗
PubMed1985

31P nuclear magnetic resonance studies of crayfish (Orconectes virilis). The use of inversion spin transfer to monitor enzyme kinetics in vivo.

31P nuclear-magnetic resonance (NMR) has been used to observed in vivo the steady-state levels of phosphorus-containing metabolites in the crayfish Orconectes virilis and the intracellular pH of the abdominal muscle was determined. Measurement of spin-lattice relaxation times and spin transfer experiments have enabled calculation of unidirectional rate constants and activation energies for the arginine kinase reaction in vivo.

Adenosine Triphosphate↗
PubMed1984

31P-NMR studies of the freeze-tolerant larvae of the gall fly, Eurosta solidaginis.

31P NMR was applied to an examination of the freeze-tolerant larvae of the gall fly, Eurosta solidaginis. Resonances from sugar phosphates, inorganic phosphate, adenylates and arginine phosphate were identified. Two peaks of Pi were identified corresponding to intracellular and extracellular Pi. Anoxia produced an expected decrease in peak intensities of ATP and arginine phosphate while the peak of intracellular Pi was enhanced and shifted to indicate intracellular acidification during anoxia. Spectra of whole larvae were monitored over a temperature range from -30 degrees to +25 degrees C. No abrupt alterations in the spectra were seen at the point of extracellular freezing which occurs at about -8 degrees C but temperature had dramatic effects upon the peak intensities of ATP and arginine phosphate. A reversible increase/decrease in peak intensities, relative to Pi, was observed as temperature was raised/lowered. At 15 degrees and -20 degrees C, the beta peak of ATP was 64% and 2% of the peak intensity of Pi while that of arginine phosphate was 78% and 11%, respectively. This temperature effect was not an artifact of instrumentation (as model solutions containing Pi, ATP and arginine phosphate did not show this effect) or a result of changes in the total amounts of these compounds in the cell with temperature. Rather it is apparent that these molecules become restricted in their rotational movement as temperature is lowered perhaps via binding to subcellular components. Changes in the amounts of freely soluble ATP and arginine phosphate with temperature could have important implications for metabolism and its control. Analysis of the effect of temperature on the chemical shift of Pi was also used to determine pH in the intracellular and extracellular compartments. Temperature change had no effect on extracellular (hemolymph) pH which remained constant at 6.1-6.3. Intracellular pH varied with temperature, however, from pH 6.8 at 15 degrees C to pH 7.3 at -12 degrees C with a change, delta pH/delta 0, of -0.0185 degrees C consistent with alphastat regulation.

Adenosine Triphosphate↗
PubMed1984

Plasmodium berghei: electron spin resonance and lipid analysis of infected mouse erythrocyte membranes.

Red blood cells from mice infected with Plasmodium berghei and from uninfected mice were labeled with stable, free radical derivatives of stearic acid. Electron spin resonance spectra of these samples showed that the degree of molecular order in these membranes decreased, and the rate of motion of the probe increased, with increasing levels of parasitemia. Parasitemia increased the ratio of unsaturated to saturated 18-carbon fatty acids, and decreased the percentage of arachidonic acid and of cholesterol. The effects of parasitemia on the membrane properties correlated with decreases in cholesterol/fatty acid ratios.

Animals↗
PubMed1984

Use of 13C nuclear magnetic resonance spectroscopy for the evaluation of hepatic drug-metabolizing enzyme activity in perfused mouse livers.

Experiments were performed to determine whether the activity of hepatic drug-metabolizing enzymes could be estimated in intact livers by 13C NMR spectroscopy. 13C-labelled aminopyrine was administered to isolated perfused mouse livers and the rate of decline in the NMR signal arising from the drug was used to estimate the half-life of aminopyrine. The technique was sufficiently sensitive to discriminate between the enzyme activities in normal livers and in livers whose enzyme activity was enhanced by treatment with sodium phenobarbitone. It was also demonstrated that demethylation of aminopyrine was not impaired in perfused livers from mice infected with Plasmodium berghei.

Aminopyrine↗
PubMed1983

Studies on the thermotropic behavior of aqueous phosphatidylethanolamines.

The thermal response of aqueous dispersions of a series of synthetic saturated phosphatidylethanolamines was studied by differential scanning calorimetry and by infrared spectroscopy. Dispersions which had not been previously heated above tm, the temperature of the gel to liquid crystalline transition, showed transitions at a higher temperature, tm+h, having a considerably greater enthalpy change. It is demonstrated that the higher temperature transition is due to the simultaneous hydration and acyl chain melting of these saturated phosphatidylethanolamines. This transition has not been observed in the corresponding phosphatidylcholines.

Calorimetry, Differential Scanning↗
PubMed1982

A 2H-NMR study of Acholeplasma laidlawii membranes highly enriched in myristic acid.

Myristic acid specifically deuterated at several positions along the acyl chain was biosynthetically incorporated into the membrane lipids of Acholeplasma laidlawii B to the level of greater than or equal to 90%. 2H-NMR was used to study the molecular order and lipid phase composition of the membranes as a function of temperature. Isolated membranes and intact cells give rise to similar 2H spectra. Below 25 degrees C the spectra exhibit a broad gel phase component which at 0 degrees C reaches the rigid limit value expected for an immobilized methylene group. Spectral moments were used to determine the relative amounts of gel and liquid crystalline phase lipids throughout the gel-liquid crystal phase transition. The results indicate that at the growth temperature (37 or 30 degrees C) the A. laidlawii B membrane lipids are approximately 85-90% in the gel state, and that protein has little effect on lipid order of the liquid crystalline lipid, but leads to an increase in the linewidth by approx. 20%.

Acholeplasma laidlawii↗
PubMed1982

Effects of cholesterol on the orientational order of unsaturated lipids in the membranes of acholeplasma laidlawii. A 2H-NMR study.

We have investigated by 2H-NMR the effects of the incorporation of cholesterol on the orientational order of unsaturated lipid acyl chains in the membranes of acholeplasma laidlawii B. This is the only 2H-NMR study to date of the influence of cholesterol in a biological membrane using specifically labelled fatty acids. We observed the characteristic condensing effect of cholesterol on the lipid acyl chain order in the liquid crystalline phase. In terms of the percentage increase in the quadrupolar splittings, the presence of cholesterol has its greatest effect on the methyl end of the labelled oleoyl chains, with a maximum at the C-14 segment. In absolute terms, the perturbation is greatest in the carboxyl end of the chains. The temperature dependence of the 2H spectra for the cholesterol-containing membranes is very similar to that for the cholesterol-free membranes. The broad phase transition of the membrane lipids, which is characteristic for the samples lacking cholesterol, is apparently little affected by the presence of up to 27 mol% cholesterol. In addition, the temperature of onset of the phase transition is not significantly depressed by the presence of cholesterol.

Acholeplasma laidlawii↗
PubMed1980

Orientational order of unsaturated lipids in the membranes of Acholeplasma laidlawii as observed by 2H-NMR.

Oleic acid specifically deuterated at fifteen different positions along the chain, including the double bond, was biosynthetically incorporated into the membrane lipids of the microorganism Acholeplasma laidlawii B. A detailed study of the dynamic conformation of these chains was carried out using deuterium nuclear magnetic resonance. The deuterium spectra fourteen different samples were recorded as a function of temperature over the range 0-41 degrees C. Spectra were obtained down to -52 degrees C for the sample enriched with oleic acid deuterated at the C-12' position. Above 20 degrees C, where the lipids are in the liquid crystal phase, a single quadrupolar powder pattern was observed for each C2H2 segment, except for the C-2' position which gave rise to a three-component spectrum characteristic for this position in both model and biological membranes. Simulation of this spectrum indicates that there are two conformations of the lipid molecule in the region of the C-2' segment of the sn-2 chain. The orientationa fluctuations of the fatty acid chain segments in the A. laidlawii membranes are described by the deuterium order parameters, and a striking similarity is shown to exist between the oleate chain conformation of the A. laidlawii membrane and a phospholipid model membrane. Remarkable similarities are also demonstrated in the A. laidlawii membrane enriched in palmitic and oleic fatty acids when the order parameter profiles are plotted at the same reduced temperature. Below 15 degrees C a second component, due to gel phase lipid, starts to appear in the spectra. This broad gel phase component grows at the expense of the liquid crystal phase component as the temperature is reduced. The spectra indicate that the center of the phase transition is at about -12 degrees C, in good agreement with DSC studies.

Acholeplasma laidlawii↗