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Biomedical subjects

J A Watts

Publications and source records attributed to J A Watts.

50 records · Page 3Linked to original sources
PubMed1990

Shifts in calcium in ischemic and reperfused rat hearts: a cytochemical and morphometric study of the effects of diltiazem.

Effects of diltiazem upon mitochondrial ultrastructure and distribution of calcium were studied following ischemia (27 minutes) and reperfusion (30 minutes). Hearts receiving no drug recovered low contractile function, while mitochondria nearly doubled in cross-sectional area (0.98 vs 0.56 micron 2) and were structurally damaged (1.88 vs 0.17 score). Mitochondria contained fine calcium deposits (0.029-micron diam) in mildly damaged cells, larger deposits in moderately damaged cells, and a large deposit (0.17-0.29-micron diam) in severely injured cells. Glycocalyx Ca2+ stain, observed in nonischemic hearts, was reduced in moderately and severely damaged cells. Increased mitochondrial Ca2+ may be associated with loss of glycocalyx Ca2+. Diltiazem (7.5 microns), added before ischemia, improved recovery of contractile function and prevented mitochondrial swelling, structural grade change, and increase in mitochondrial Ca2+. Reduction in mitochondrial Ca2+ stain by diltiazem was associated with the maintenance of normal glycocalyx Ca2+.

Animals↗
PubMed1987

A low concentration of nisoldipine reduces ischemic heart injury: enhanced reflow and recovery of contractile function without energy preservation during ischemia.

Isolated working rat hearts which received no drug treatment had reduced ATP and creatine phosphate levels and increased lactate content during 20 min of ischemia. When subjected to 33 min of ischemia and 30 min of reperfusion, these hearts recovered low values of cardiac output (9.8 ml/min), heart rate, maximum developed pressure, pressure-rate product (72.9, 32.6, 27.5% of control, respectively), had low levels of tissue ATP, and reduced coronary flow upon reperfusion. Addition of nisoldipine (1 nM) 10 min before ischemia caused no decrease in cardiac output or heart rate, slightly decreased maximum developed pressure and pressure-rate product (93% of control), and did not reduce the degradation of ATP and creatine phosphate or the accumulation of lactate during 20 min of ischemia. When nisoldipine was included 10 min before ischemia, during ischemia (33 min) and reperfusion (30 min), however, the recovery of cardiac function and tissue ATP levels was significantly increased. This protective effect occurred when drug treated ischemic hearts were reperfused with control buffer, indicating residual effects. The beneficial effects of nisoldipine were not due to changes in afterload or preload (isolated perfused heart), collateral flow (zero flow model), energy preservation during ischemia (little contractile depression, ATP not enhanced during ischemia), or reduced lactate accumulation during ischemia. The beneficial effects were associated with increased coronary flow (31% higher than no drug) during reperfusion, indicating a reduction in the no-reflow phenomenon.

Adenosine Triphosphate↗
PubMed1986

Protection of ischemic hearts by Ca2+ antagonists.

Treatment of isolated, working rat hearts with equiactive conditions of buffer containing low Ca2+ (LC), verapamil (Ver), diltiazem (Dil) or nifedipine (Nif) prior to global ischemia (33 min, 37 degrees C) resulted in an equal enhancement in recovery of contractile function, and high energy phosphate (HEP) stores in reperfused hearts. Treatment only during reperfusion did not enhance recovery or HEP stores. Pretreatment with doses which did not depress preischemic contractile function did not afford protection to globally ischemic hearts. In contrast with Dil (2.5 uM), pretreatment with an equiactive concentration of bepridil (Bep) (20 uM) did not preserve contractile function, HEP, or mitochondrial function and did not reduce Ca2+ overload. The Ca2+ was concentrated in mitochondria of hearts receiving no drug or Bep pretreatment (oxalate-pyroantimonate stain). Increasing concentrations of Ver or Dil given before ischemia resulted in a progressive increase in recovery of contractile function which was proportional to depression of preischemic function. The increase in HEP in these hearts was not proportional to drug concentration, preischemic or postischemic function. Pretreatment with Dil reduced lactate production in both normal and K+-arrested ischemic hearts. Energy preservation is only part of the protective mechanisms of Ca2+ antagonists. The Ca2+ antagonists also reduce Ca2+ overload from reperfusion, and may alter Ca2+ compartmentation during ischemia.

Animals↗
PubMed1986

Comparison of the protective effects of verapamil, diltiazem, nifedipine, and buffer containing low calcium upon global myocardial ischemic injury.

This study was designed to compare the effects of the Ca2+ slow channel blocking agents verapamil (2 X 10(-6) M), diltiazem (7.5 X 10(-7) M), and buffer containing reduced Ca2+ content (0.95 mM) on myocardial ischemic injury. These treatments were equiactive, reducing cardiac function to 20% of the control value, and fully reversible in nonischemic, isolated, working rat hearts. Hearts which were reperfused (30 min) following 27 min of global ischemia recovered 17% of control cardiac function and had a markedly reduced ATP and creatine phosphate content and ATP/ADP ratio compared to nonischemic hearts. When verapamil, diltiazem, nifedipine, or low Ca2+ treatments were given before and during ischemia, equal improvement in cardiac function was observed upon reperfusion, and tissue ATP levels, creatine phosphate levels, and ATP/ADP ratio were significantly higher than in hearts which did not receive the treatments or which received the drug vehicle. Large increases in recovery of contractile function were observed with a partial preservation of ATP reserves. These treatments, which were equiactive in nonischemic hearts, provided equivalent preservation of cardiac function, ATP, and creatine phosphate in the reperfused ischemic hearts. When the ischemic period was increased to 33 min and the effective concentrations reduced to depress cardiac function to 40% of the control value (4.5 X 10(-7) M verapamil, 2.5 X 10(-6) M diltiazem, 3 X 10(-7) M Nifedipine, 1.25 mM Ca2+), equal improvement in cardiac function was again observed. Thus, major differences among these Ca2+ slow channel blockers or low Ca2+ treatment were not detected in this experimental system.

Adenosine Diphosphate↗
PubMed1985

Protection by verapamil of globally ischemic rat hearts: energy preservation, a partial explanation.

The relationship between energy preservation and the recovery of heart function was studied in globally ischemic hearts which were treated with verapamil. Isolated working rat hearts reperfused after 27 min of ischemia recovered 17.9 +/- 5.11% of pre-ischemic contractile function and had markedly reduced tissue ATP, total adenine nucleotide, and creatine phosphate levels. The ATP/ADP ratio was also decreased in these hearts. When verapamil (2 X 10(-6) M) was present before and during ischemia, but not during reperfusion, the recovery of cardiac function following reperfusion was improved (82.4 +/- 12.1%). When hearts were treated with 0.0, 7.5 X 10(-8) M, 5 X 10(-7) M, or 2 X 10(-6) M verapamil, the recovery of cardiac function was proportional to the concentration of verapamil present and showed a linear relationship with the depression of cardiac function prior to ischemia. The ATP, total adenine nucleotide and creatine phosphate levels were significantly higher in those hearts which were treated with verapamil, but the increase was not proportional to the recovery of cardiac function. It is possible that a critical pool of ATP may correlate with the recovery of verapamil treated hearts, but a large degree of mechanical recovery occurred with significant loss of high energy phosphate stores. Thus, while high energy compounds were preserved, there was not a good correlation between recovery of cardiac function and the preservation of total tissue energy reserves. A portion of the protection afforded by verapamil to globally ischemic hearts may be due to energy preservation, but additional mechanisms may also be involved in the enhanced recovery of contractile function.

Adenosine Diphosphate↗
PubMed1984

Dimethyl sulfoxide: inhibition of acetylcholinesterase in the mammalian heart.

The heart rate of the isolated, perfused, working rat heart was significantly and equally depressed by 1 X 10(-6)M acetylcholine (ACh) and by 6 X 10(-5)M 4-ketoamyltrimethylammonium (4K), a cholinomimetic agonist. Dimethyl sulfoxide (DMSO) (10 microliter/ml, 140 mM) strongly potentiated the effect of ACh but did not alter the effect of 4K. DMSO (10 microliter/ml, 140 mM) strongly potentiated the effect of ACh but did not alter the effect of 4K. DMSO (10 microliter/ml, 140 mM final concentration) alone had no significant effect upon heart rate when added to the perfusate in incremental additions of 1 microliter X (ml perfusate)-1 X min-1 over a 10-min period. The specific activity of atrial homogenate cholinesterase was 48.8 +/- 3.46 nmoles X min-1 X (mg protein)-1 (mean +/- S.E.M.), 38.2 +/- 1.60 for butyrylcholinesterase, and 11.2 +/- 0.86 for acetylcholinesterase (AChE). True AChE activity (measured in the presence of a maximally effective concentration of tetraisopropylpyrophosphoramide) had a Vmax of 13.4 +/- 0.17 nmoles X min-1 X mg protein)-1 and an apparent Km value of 1 X 10(-4)M acetylthiocholine. At this Km substrate concentration, DMSO inhibited atrial AChE activity (I50 = 9 microliter/ml). At the concentration tested, DMSO inhibited atrial AChE and potentiated ACh effects.

Acetylcholine↗
PubMed1984

Capnocytophaga ochracea infection: two cases and a review of the published work.

Bacteria of the genus Capnocytophaga are recently recognised pathogens which may cause oral disease and subsequent septicaemia in the immunocompromised host. We present two cases of infection caused by Capnocytophaga ochracea; a soft tissue infection in an immunologically normal patient and an episode of septicaemia in a child with leukaemia. The microbiology, pathogenicity, and antimicrobial susceptibility of the genus capnocytophaga are reviewed.

Bacterial Infections↗
PubMed1983

Competitive inhibition by dimethylsulfoxide of molluscan and vertebrate acetylcholinesterase.

Anticholinesterase-like effects of dimethylsulfoxide (DMSO) were demonstrated on a variety of invertebrate muscles. The excitatory effects of acetylcholine (ACh) on the isolated preparations of the Geukensia demissa heart and anterior byssus retractor muscle (ABRM), and of the Busycon contrarium radula protractor muscle, were potentiated by DMSO (1-5 microliters/ml; 1 microliter/ml = 14 mM). The negative chronotropic effects of ACh, but not of 4-ketoamyltrimethylammonium, were potentiated by DMSO (1-5 microliters/ml) on the isolated heart of the oyster Crassostrea virginica. These four muscles have acetylcholinesterase enzymes of high activity. In contrast, Mercenaria mercenaria hearts have weak cholinesterase activity, and the effects of ACh on this isolated myocardium were not potentiated by DMSO (2-20 microliters/ml). DMSO (0.1-15 microliters/ml) was a competitive inhibitor of both a crude preparation of oyster heart acetylcholinesterase (AChE) (the Km increased 24-fold with DMSO at 15 microliters/ml; the I50 was 1.3 microliters/ml DMSO when [ACh] = Km) and a purified Electrophorus AChE (the Km increased 4.5-fold when DMSO was 10 microliters/ml; the I50 was 10 microliters/ml DMSO near [ACh] = Km). The same doses of DMSO were needed to potentiate the pharmacological effects of ACh on the oyster heart, as to inhibit the AChE of this tissue.

Acetylcholinesterase↗
PubMed1981

Adenine nucleotide transport during cardiac ischemia.

The suggestion that long-chain acyl coenzyme A (CoA) derivatives may inhibit mitochondrial adenine nucleotide transport in heart cells during ischemia has been reevaluated. The effectiveness of media palmitoyl-CoA as an inhibitor is a function of mitochondrial protein and media adenine nucleotide concentrations. Extrapolation to the protein and adenine nucleotide levels of the cardiac cell suggest that physiological concentrations of cytosolic long-chain acyl-CoA would not inhibit adenosine 5'-triphosphate (ATP) transport. Palmitoyl-CoA was varied in the mitochondrial matrix by incubating the isolated mitochondria with and without palmitoyl carnitine. Intramitochondrial nucleotides were depleted by incubating the isolated mitochondria for various periods of time with arsenite and phosphate. Even at low substrate (matrix ATP) concentrations, no palmitoyl-CoA inhibition of ATP transport could be demonstrated. Further experiments showed that endogenous nucleotide levels are significantly depleted in mitochondria isolated from hearts made ischemic for 30-90 min. Since mitochondrial adenine nucleotide transport occurs by an exchange mechanism, this depletion of the internal pool of nucleotides from ischemic heart mitochondria may result in an irreversible diminution of ATP transport.

Acyl Coenzyme A↗
PubMed1980

Effects of Ca2+ antagonism on energy metabolism: Ca2+ and heart function after ischemia.

Isolated rat hearts reperfused after 25 min of ischemia have 23% of control mechanical function, 65% of control nucleotides, 52% of control ATP, and 75% of control creatine phosphate, whereas cellular calcium is increased 2.3-fold. Initiating reperfusion with verapamil or low Ca2+-containing buffer did not alter these tissue parameters or improve function over hearts reperfused with control buffer only. Also, when verapamil was present before and during ischemia, improvement in cardiac function resulted, and the adenine nucleotides, tissue ATP, and creatine phosphate concentrations were increased while cellular Ca2+ was reduced compared with the other reperfused ischemic hearts. Verapamil apparently improves recovery of function by decreasing energy demand during ischemia rather than by blocking Ca2+ influx during reprefusion. The respiration of isolated mitochondria and homogenates from reperfused ischemic hearts and homogenates of ischemic hearts was decreased by 20-30%, possibly due to sarcolemmal damage, although the respiration of isolated cells from ischemic hearts was normal. Cells isolated from ischemic hearts may represent a selected population lacking sarcolemmal damage.

Adenine Nucleotides↗
PubMed1978

Acetylcholinesterase: a useful marker for the isolation of sarcolemma from the bivalve (Modiolus demissus demissus) myocardium.

The presence of cholinesterase activity in M. demissus hearts was demonstrated by light- and electron-microscopic histochemistry and by enzymic assay. The enzyme proved to be acetylcholinesterase (AChE) since acetylthiocholine was the preferred substrate, and eserine or BW284C5I inhibited the enzyme activity, while isoOMPA was without effect. The AChE was localized and uniformly distributed along the cell surface membranes of the cardiac muscle cells. A fraction 8-fold enriched in AChE was isolated from pooled ventricles by a combination of differential and sucrose density gradient centrifugation. This sarcolemmal fraction contained little mitochondrial contamination as determined by electron microscopy and by succinate cytochrome c reductase activity. In addition, this fraction stained uniformly for AChE, indicating that it was free of other membrane types (for example sarcoplasmic reticulum which did not stain for AChE). Therefore, this fraction contained purified cell surface membrane free of contamination by other membranous organelles.

Animals↗
PubMed1972

5-Hydroxyindole-secreting rectal carcinoid tumour.

A patient with a 5-hydroxyindole-secreting rectal carcinoid tumour is described, the second on record. There was no clinical evidence of carcinoid syndrome. Prostaglandin-like substances were isolated from hepatic metastases.

Adult↗