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Biomedical subjects

C J Lockett

Publications and source records attributed to C J Lockett.

At least 19 recordsLinked to original sources
PubMed1996

Proton nuclear magnetic resonance spectroscopy of lactate production in isolated rat liver during cold preservation.

Lactate-edited 1H NMR difference spectra have been acquired from intact rat liver tissue following flushing and preservation in ice. A peak, initially at 1.26 ppm, was seen to increase in the liver tissue with preservation time. This peak was assigned to lactate, despite the fact that its chemical shift was initially shifted by approximately -0.1 ppm relative to an externally added standard. The assignment was based on the following: (a) the peak increased over a 24-h ischemic storage period; (b) it was coupled to a signal 2.78 +/- 0.02 ppm upfield; and (c) a parallel increase in lactate was noted in perchloric acid extracts of tissue from the same liver. An additional peak, assigned to alanine, was also observed during storage and was also shifted by approximately -0.1 ppm. Inclusion of dimethyl sulfoxide, which readily permeates liver tissue, demonstrated that this chemical shift alteration was a tissue-specific effect. These results demonstrate that 1H NMR spectroscopy of intact liver tissue during hypothermic ischemia is possible, though chemical shift assignments should be made with caution.

Animals↗
PubMed1995

Hypothermic perfusion preservation of liver: the role of phosphate in stimulating ATP synthesis studied by 31P NMR.

Hypothermic perfusion of rat livers was investigated by 31phosphorus nuclear magnetic resonance (31P NMR) spectroscopy using a temperature-controlled module that allowed data acquisition at various time points during a 48-h period. The livers were perfused with an oxygenated lactobionate/raffinose-based solution containing adenosine and inorganic phosphate, and changes in tissue oedema were monitored by direct on-line measurements of liver weight changes. Liver tissue ATP concentrations, determined by fluorimetric assay, were low immediately after organ removal, probably reflecting metabolic stress during the removal period, and these increased slightly during the next 3 h. This was reflected by changes in the 31P NMR spectra. However, by 24 h ATP levels had increased significantly, and these were maintained for up to 48 h, suggesting a shift in the balance between energy production and consumption. When inorganic phosphate was replaced by another anion (citrate), ATP was maintained at a constant lower level during perfusion for 48 h. Tissue weight changes were similar in both groups, suggesting that volume control was not affected by the different ATP contents of the livers. By combining the temperature-controlled module with a separate perfusion circuit, NMR spectroscopy can provide a sensitive method for following energy metabolism in the same organ over long periods during hypothermic perfusion.

Adenosine Triphosphate↗
PubMed1995

Resuscitation of cardiac energy metabolism in the rabbit heart by brief hypothermic reperfusion after preservation studied by 31P NMR spectroscopy.

Rabbit hearts were subjected to 24-h cold ischaemic storage (at 0 degree-2 degrees C in melting ice) after initial flushing with either St Thomas' cardioplegic solution (STS) or modified lactobionate/raffinose solution (LR), and the status of phosphorylated energy metabolites was measured by 31phosphorus nuclear magnetic resonance (P NMR) spectroscopy. In both groups signals for ATP and phosphocreatine (PCr) were still detectable by 31P NMR after 24 h, and there was significantly more ATP in the LR group (P < 0.01). The hearts were then subjected to coronary reperfusion via an aortic cannula using the same storage solution (either STS or LR) at 6 degrees-8 degrees C, which was oxygenated. In both groups PCr recovered within 30 min of cold reperfusion, and by 60 min PCr was significantly higher in the LR group (P < 0.001). Also, levels of ATP were maintained at higher values during cold reperfusion i the LR group. These studies suggest two important points: (1) the general supply of phosphorylated high-energy intermediates of hearts during cold ischaemic storage is better preserved using LR, and (2) brief cold reperfusion may be used to restore energy metabolism in hearts before re-implantation.

Adenosine Triphosphate↗
PubMed1992

The effect of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart.

This investigation was conducted to determine the influence of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart and myocardial electrolyte levels. Ventricular fibrillation threshold was measured using the Langendorff perfusion apparatus. Heart rate was measured by a universal digital counter and the cardiac flow by collecting the outflow of the heating chamber below the heart into a graduated measuring cylinder. Magnesium and zinc were measured by atomic absorption spectrophotometry and potassium by flame photometry. Two groups of rats were studied; those in the experimental group were given 0.2 ml of hexane and the control group 0.2 ml olive oil subcutaneously for 90 days. Their hearts were removed under anaesthesia. Half of the experimental and control hearts were mounted on the Langendorff perfusion apparatus and the heart rate, coronary flow and ventricular fibrillation threshold were measured. The hearts of the other half were used to measure myocardial electrolyte levels. In the experimental group the ventricular fibrillation threshold decreased (4.72 (S.D. +/- 1.87) vs 9.48 (S.D. +/- 2.98); P less than 0.001). There was no change in the coronary flow and heart rate in between the groups. The mean myocardial potassium levels (2586 (S.D. +/- 162) vs 2968 (S.D. +/- 218) micrograms/g; P less than 0.001), magnesium levels (164 (S.D. +/- 28) vs 208 (S.D. +/- 18) micrograms/g; P less than 0.001) and zinc levels (19.6 (S.D. +/- 4) vs 33.8 (S.D. +/- 6.8) micrograms/g; P less than 0.001) were significantly lower in the hexane-treated group compared to controls. Hexane, a constituent of glue and benzine, is cardiotoxic; marked derangement in myocardial electrolytes and a reduced ventricular fibrillation threshold, indicating an increased myocardial vulnerability to arrhythmias, was noted in the experimental animals.

Animals↗
PubMed1992

Influence of ethyl alcohol when given alone or in combination with potassium and/or magnesium supplements on ventricular fibrillation threshold levels in laboratory rats.

Five groups of rats were studied in an investigation to determine whether changes in the ventricular fibrillation threshold (VFT) occur when ethyl alcohol (EtOH) is given alone or in combination with K+ and/or Mg2+ supplements; the first group (n = 20) served as controls, the second (n = 18) was given only EtOH, the third (n = 18) EtOH+KCl, the fourth (n = 16) EtOH+MgCl2, and the fifth (n = 18) EtOH+MgCl2 + KCl for a 9 month period. Two rats from each group were killed on each day. One rat heart was perfused using the Langendorff apparatus and the other used for tissue electrolyte analyses. A significant fall in the mean VFT (9.7 +/- SD 1.9 mA vs 4.5 +/- 1.6 mA; P less than 0.0001) was noted in the rats given EtOH solution as drinking water for 9 months, and a significant increase in the VFT levels was seen in the Mg(2+)-supplemented group (9.7 +/- 1.9 mA vs 18.9 +/- 4.1 mA; P less than 0.0001) and in the K+ + Mg2+ supplemented group (9.7 +/- 1.9 mA vs 15.8 +/- 1.3 mA; P less than 0.0001) compared to controls. In addition, an increase in the heart rate was observed in the group supplemented with Mg2+ (213 +/- 8 beats/min vs 231 +/- 10 beats/min; P less than 0.0001) as well as in the group supplemented with K+ + Mg2+ (213 +/- 8 beats/min vs 222 +/- 10 beats/min; P less than 0.002) compared to controls. There was no significant change in the coronary blood flow (CF) in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of clopamide, a thiazide diuretic, on copper and zinc levels in hypertensive patients.

Thiazide diuretics, which are often prescribed to treat mild to moderate hypertension, commonly cause an increase in urinary zinc (Zn) excretion. Metabolic interrelationships between Zn and copper (Cu) are known to exist; consequently, Zn might influence Cu levels. This study aims to determine whether or not Cu and Zn levels in hypertensive patients were influenced by treatment with clopamide, a thiazide diuretic. Eight male patients, aged 36-59 and with an average supine diastolic pressure of 95-115 mm Hg, were treated with single daily doses of clopamide 5 mg as monotherapy for 16 weeks. Plasma, erythrocyte (RBC), and mononuclear leukocyte (WBC) levels of Cu and Zn were determined immediately before therapy (week 0) and again at weeks 8 and 16. There was a significant fall in Cu in mononuclear WBCs from 13.25 (SEM = 0.86) to 1.9 fg/cell (SEM = 0.56) (p less than 0.001) and an increase in Zn from 33.87 (SEM = 3.7) to 70.8 fg/cell (SEM = 11.7) (p less than 0.001), with no change in either cell count or measurable cell volume. Plasma Cu levels increased significantly (p less than 0.001), but the Zn levels decreased only slightly (p less than 0.03). Changes in RBC Cu levels during the treatment period were not significantly altered (p less than 0.1). Zn levels in RBCs were significantly (p less than 0.04) lower. It is concluded that treatment with clopamide may induce some changes in Cu and Zn levels in normal hypertensives, particularly in WBCs. Further investigation is needed to determine the extent of this influence.

Adult↗
PubMed1991

Changes in myocardial electrolytes and ventricular fibrillation threshold induced by alcohol feeding in laboratory rats.

Three groups of rats were studied in an investigation to determine the influence of alcohol on myocardial electrolytes and the ventricular fibrillation threshold (VFT) levels. Drinking water was provided ad libitum; the control group received water while the other 2 groups drank a water-ethanol solution, constituted in a ratio of 75: 25, for periods of 3 and 9 months, respectively. Two rats from each of the experimental groups, together with a control rat were killed on each experimental day. One heart was studied on the Langendorff preparation and the other used for tissue electrolyte analysis. The mean myocardial Mg2+ levels (233 +/- 28 micrograms/g vs 148 +/- 23 micrograms/g and 233 +/- 28 micrograms/g vs 107 +/- 15 micrograms/g; p less than 0.0001), K+ levels (3260 +/- 437 micrograms/g vs 1779 +/- 312 micrograms/g and 3260 +/- 437 micrograms/g vs 1195 +/- 205 micrograms/g; p less than 0.0001) and Zn2+ levels (32.7 +/- 6.8 micrograms/g vs 14.0 +/- 4 micrograms/g and 32.7 +/- 6.8 micrograms/g vs 4.2 +/- 3.4 micrograms/g; p less than 0.0001) were significantly lower in alcohol fed rats than the controls. In addition, a significant fall in the mean VFT levels (10.1 +/- 1.94 mA vs 6.27 +/- 2.17 mA, p less than 0.001) was noted in rats given water: alcohol solution for 9 months. This study reveals that chronic exposure to alcohol induces a deficiency of myocardial Mg2+, K+ and Zn2+, and an increase in myocardial irritability in laboratory rats.

Animals↗
PubMed1988

Photochemistry in the isolated Photosystem II reaction-centre core complex.

The photochemistry of the isolated Photosystem II reaction-centre core from pea and the green alga Scenedesmus was examined by e.s.r. Two types of triplet spectrum were observed in addition to the spin-polarized reaction-centre triplet previously identified. The additional triplet formed on continuous illumination at 4.2 K was attributed to a monomeric phaeophytin molecule. The second triplet, which was stable in the dark at 4.2 K following illumination, was assigned to the radical pair Donor+I-. This provides evidence that an electron donor to chlorophyll P680 is present on the polypeptide D1-polypeptide D2-cytochrome b-559 core complex.

Chlorophyll↗
PubMed1983

Zinc, angiotensin I-converting enzyme and hypertension.

Angiotensin-converting enzyme, or kininase II, is a zinc metallo-enzyme; the cation forms part of its active site. The enzyme transforms angiotensin I into angiotensin II and hydrolyses bradykinin into inactive peptides. Antihypertensive diuretics may decrease the activity of the angiotensin-converting enzyme by increasing urinary zinc excretion. Captopril inhibits the angiotensin-converting enzyme, but also affects electrolyte excretion and should be reassessed as a possible first-choice antihypertensive agent in the treatment of essential hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics.

Diuretics which principally act in the first portion of the distal convoluted tubule, such as the thiazides and chlorthalidone, significantly increase the urinary excretion of zinc. The potassium-retaining diuretic amiloride reduced urinary zinc excretion significantly. The hyperzincuria provoked by common distal tubular diuretics can cause zinc deficiency, especially when other aetiological factors such as alcoholism, renal insufficiency and pregnancy are also present. Zinc deficiency may be expressed clinically by hypogeusia, hyposmia, sexual impotence or delayed healing; the latter might be an important factor in cases of myocardial infarction.

Adult↗
PubMed1983

Biochemistry of zinc.

Zinc forms part of the active site and/or stabilizes the conformation of several enzymes. The protein metallothionein constitutes a zinc deposit from which the metal is transferred to enzymes. Zinc participates in the synthesis of nucleic acids and hence in the synthesis of proteins, principally through multi-enzyme pir 1-3 and DNA-dependent RNA polymerase, which are metallo-enzymes of zinc. Zinc is therefore necessary for normal growth, development, healing and ossification.

Alcohol Oxidoreductases↗
PubMed1983

Magnesium and deaths ascribed to ischaemic heart disease in South Africa. A preliminary report.

The incidence of death from ischaemic heart disease (IHD) and acute cardiac arrhythmias is increased in some regions where magnesium levels are reduced in soil and water. Magnesium levels in the drinking water of twelve South African magisterial districts have been evaluated together with corrected statistics for deaths apparently due to IHD in White males from the same districts. A significant negative correlation was found between the incidence of deaths ascribed to IHD and the magnesium content of drinking water. Future, prospective, multivariate studies are required to elucidate whether magnesium scarcity in a geological environment is a major coronary risk factor.

Coronary Disease↗
PubMed1983

Zinc metabolism under physiological conditions.

Zinc is the sixth commonest cation in the human body. The daily dietary requirement for adults is 15 mg, and foods of animal origin are the richest dietary source. Zinc absorption (10-25% of the ingested amount) occurs in the small intestine. Plasma zinc is transported mainly by protein and also by amino acids. Zinc is widely distributed throughout the body, and is mainly excreted in faeces but also in urine and sweat.

Adult↗
PubMed1982

Diuretics and zinc.

Distal tubule diuretics (DTDs), including chlorothiazide, hydrochlorothiazide, bendroflumethiazide, chlorthalidone and xipamide, have been found to increase urinary zinc output through a poorly understood mechanism which could involve both direct and hormone-mediated processes. Significant zinc depletion may occur during long-term administration of DTDs, principally in conditions associated with diminished total body zinc levels such as hepatic cirrhosis, diabetes mellitus, gastro-intestinal disorders and several renal diseases. Attention to the early symptoms of zinc deficiency such as hypogeusia, hyposmia, abnormal dark adaptation and impotence and the monitoring of serum zinc levels are advisable during long-term treatment with common DTDs.

Adult↗