Apolipoprotein epsilon 4 and coronary artery disease.
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Apolipoprotein E4↗
Biomedical subjects
R G Murray
Publications and source records attributed to R G Murray.
Serum cortisol levels predict infarct size and patient mortality.
We have investigated prospectively the serum cortisol response to acute myocardial infarction in 70 consecutive patients admitted to a coronary care unit and we have shown that the levels are significantly raised early in the course of the illness and prior to elevation of the cardiac specific enzyme fraction, creatine kinase MB. The magnitude of the cortisol response is related to the size of the ensuing infarction (rs = 0.54) as calculated from the total creatine kinase MB release (P < 0.001) and very high levels (> 2000 mumol/l) are predictive of mortality (P < 0.05). Serum cortisol levels may have a role in the early identification of myocardial infarction and in predicting those patients with a poor prognosis.
Anistreplase↗
Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure.
Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Agonists↗
Comparison of the haemodynamic effects of dopexamine and dobutamine in patients with severe congestive heart failure.
Dopexamine hydrochloride is a novel compound with properties of DA1-dopaminergic and beta 2-adrenergic receptor agonism and neuronal noradrenaline uptake inhibition. It has been shown to produce beneficial renal and haemodynamic effects in patients with severe heart failure. We compared the haemodynamic effects of dopexamine (0.5 to 6 micrograms/kg/min) with those of dobutamine (5 to 25 micrograms/kg/min) in 9 patients with severe congestive heart failure. The two drugs were similar in their effects at peak infusion rates: heart rate increased (dopexamine 87 +/- 17 to 100 +/- 14; dobutamine 91 +/- 18 to 103 +/- 17 min-1), cardiac index increased (dopexamine 1.7 +/- 0.5 to 2.8 +/- 1.1; dobutamine 1.8 +/- 0.5 to 3.0 +/- 1.1 l.min-1.m-2) and systemic vascular resistance decreased (dopexamine 1553 +/- 221 to 1117 +/- 432; dobutamine 1721 +/- 347 to 1280 +/- 433 dyne.s.cm-5). Neither drug affected pulmonary artery wedge pressure (dopexamine 24 +/- 6 to 22 +/- 6; dobutamine 25 +/- 9 to 24 +/- 10 mm Hg). Dopexamine had significantly lower peak effects on left ventricular stroke work index (dopexamine 20 +/- 9, dobutamine 27 +/- 15 g.m.m-2, P less than 0.05) and cardiac power output (dopexamine 0.71 +/- 0.36, dobutamine 0.93 +/- 0.46 W, P less than 0.05). These haemodynamic effects, due largely to vasodilatation but with some contributory positive inotropy, indicate that dopexamine will be useful in the acute treatment of congestive heart failure.
Dobutamine↗
DNA polymorphisms in new isolates of 'Deinococcus radiopugnans'.
Nineteen new Deinococcus isolates from soil, 18 of which were from samples immediately adjacent to a lake in Nottingham, UK, were characterized by conventional criteria, and found to be identical to each other and to conform most closely to the species D. radiopugnans. However, we detected three different restriction enzyme activities in three different isolates. Because of this suggestion of heterogeneity, we examined the isolates for restriction fragment length polymorphisms (RFLPs). RFLP analysis of the 19 original isolates, using three different probes, distinguished 17 divergent groups. This extraordinary diversity cannot be attributed to geographical differences, nor to the method of isolation, which employed UV-radiation selection.
Blotting, Southern↗
A correlation of phylogenetic diversity in the Proteobacteria with the influences of ecological forces.
The Proteobacteria are physiologically and morphologically diverse, although they form a coherent set of four main lineages on phylogenetic analysis of ribosomal RNA. A rational and consistent taxonomic arrangement bringing today's phenotypic and phylogenetic conclusions about them into register is not yet possible. It is also difficult to understand the selective forces involved in their evolution that fostered such diversity. This latter problem is addressed in this essay and is based on the assumption that bacterial evolution could only have occurred in ecological consortia whose products of metabolism modified the environment, provided nutrition, and have a basis for selection of new capabilities.
Bacteria↗
The correlation of cardiac power output to exercise capacity in chronic heart failure.
Cardiac haemodynamics are deranged in chronic heart failure but fail to predict the exercise capacity of the patient. Cardiac power output is a descriptor of cardiac function derived from preload, blood pressure and cardiac output. Forty-one patients with moderately severe and severe chronic heart failure were exercised on a cycle ergometer to determine the relationship between traditional haemodynamics and cardiac power output and exercise capacity. Resting cardiac power output was no more predictive of exercise capacity than resting stroke-work index or resting cardiac index (r = 0.53, 0.61 and 0.51 respectively). Maximum cardiac power output and the ability to increase cardiac power output, however, were correlated with exercise capacity (r = 0.79 and 0.80). It is concluded that resting cardiac power output does not predict subsequent exercise capacity but that maximum cardiac power output and the ability to increase cardiac power output on stimulation are good descriptors of functional cardiac reserve.
Adult↗
The effects of the partial beta 1-agonist xamoterol on heart rate and ventricular arrhythmias in patients with mild to moderate heart failure.
A major concern with the use of oral inotropes in chronic heart failure is their propensity to exacerbate cardiac arrhythmias. In a double-blind randomized placebo-controlled crossover study of xamoterol, a novel beta 1-partial agonist, 24 h ambulatory electrocardiograms were obtained in 26 patients prior to and at the end of 13-week treatment periods. During treatment with xamoterol there was no significant change in mean hourly number of ventricular extrasystoles compared with baseline and placebo (30 +/- 17 vs 56 +/- 42 and 18 +/- 7, respectively), or in the number of patients showing complex forms (multiform VEs, pairs, ventricular tachycardia) (20/26 vs 19/26 and 19/26, respectively), or ventricular tachycardia alone (5/26 vs 4/26 and 6/26, respectively). Xamoterol therapy also stabilized heart rate variability over the 24 h period.
Adrenergic beta-Agonists↗
Structural and chemical characterization of the S layer of a Pseudomonas-like bacterium.
Sections and freeze-fractured preparations showed an S layer on the surface of Pseudomonas-like strain EU2. Polyacrylamide gel electrophoresis of cell envelopes extracted with 1% sodium dodecyl sulfate (SDS) at room temperature showed three proteins (45K, 55K, and 110K). The 55K protein was identified as the S-layer protein. Incubation in 1.5 M guanidine hydrochloride removed the S layer from cell envelopes and dissociated the structure into subunits. The soluble 55K protein reassembled into planar sheets upon removal of the guanidine hydrochloride by dialysis. Electron microscopy and image processing indicated that these sheets had p4 symmetry in projection with a lattice constant of 13.2 +/- 0.1 nm (corresponding to 9.3 nm between adjacent fourfold axes). In some instances these reassemblies appeared to form small three-dimensional crystals which gave particularly clear views of the structure in projection because of the superimposition of information from a number of layers. A model is proposed with molecules having rounded lobes connected by a narrower linker region and joining at the lobes to form the fourfold axes of the array. The pattern superficially resembles those of other bacterial S layers, such as those of Aeromonas salmonicida, Aeromonas hydrophila, and Azotobacter vinelandii. Extraction of cell envelopes with 1% SDS at 50 degrees C released the 110K protein from the envelopes and removed an amorphous backing layer from the S layer. The 45K protein displayed heat-modifiable migration in SDS-polyacrylamide gel electrophoresis and was insoluble in SDS at 50 degrees C or in high concentrations of guanidine hydrochloride, suggesting that it was associated with the peptidoglycan.
Bacteria↗
Isolation and in vitro assembly of the components of the outer S layer of Lampropedia hyalina.
The outermost component of the S layer of Lampropedia hyalina, the punctate layer, is assembled onto an inner perforate layer. The punctate layer is composed of long, tapered cylindrical units centered on p6 symmetry axes and connected by six fine linking arms, joining at the axis of threefold symmetry to create a hexagonal layer with a lattice constant of 25.6 +/- 0.5 nm (J. A. Chapman, R. G. E. Murray, and M. R. J. Salton, Proc. R. Soc. London Ser. B 158:498-513, 1963; R. G. E. Murray, Can. J. Microbiol. 9:593-600, 1963). Extraction of cell envelopes with 100 mM Tris buffer (pH 8) containing 2% deoxycholate resulted in the release of several proteins, but left the S layers intact. The punctate layer was then extracted with 3 M guanidine hydrochloride or 6 M urea, leaving the perforate layer intact. This treatment led to the release of three polypeptides with molecular weights of 60,000, 66,000, and 240,000 (60K, 66K, and 240K polypeptides). These three polypeptides reassembled on the perforate layer as a template to form the S-layer complex or self-assembled to form the punctate layer alone after dialysis of the extract against 50 mM HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) buffer (pH 7.5) containing 10 mM CaCl2. The self-assemblies were composed of a 240K polypeptide and a 60K polypeptide. The 240K and 60K polypeptides were separated by column chromatography and examined by electron microscopy. The 240K polypeptide appeared in negative stain as a long, flexible structure and assembled into loose arrays with sixfold symmetry with obvious Y-shaped linking elements, while fractions containing both the 60K and 240K polypeptides showed assemblies closely resembling the punctuate layer. Immunoelectron microscopy was used to confirm the presence of both the 60K and 240K polypeptides as components of the punctuate layer.
Cell Fractionation↗
Non Q wave infarction: exercise test characteristics, coronary anatomy, and prognosis.
The exercise test characteristics, coronary anatomy, and prognosis of patients discharged after non Q wave myocardial infarction were compared with those in whom Q wave infarction occurred. Of the 339 patients studied, all of whom were less than or equal to 70 years, 87 (26%) had had a non Q wave infarction. There were no significant differences in the exercise test characteristics between the two groups, and in those 149 patients in whom angiography was performed triple vessel disease was present in 36/114 (32%) of the Q wave group and 9/35 (26%) of the non Q wave group. The infarct related artery was more often patent in the non Q wave group (27/35 (77%] than in the Q wave group (53/114 (46%]. The one year mortality and the reinfarction and angina rates were similar in the two groups and the exercise test remained a good discriminator for predicting patients at risk of future cardiac events in both groups. In view of the similar outcome and severity of coronary disease in those aged less than or equal to 70 with non Q wave infarcts, the distinction between Q and non Q wave infarction need not influence management decisions in patients after myocardial infarction.
Adult↗
Sustained improvement in left ventricular function after successful coronary angioplasty.
The short and long term effects of successful percutaneous transluminal coronary angioplasty on left ventricular function, at rest and on exercise were investigated in 49 patients. Thirty-four had had no previous infarction (group 1) and 15 had (group 2). Technetium-99m gated blood pool images were obtained at rest and during exercise before, six weeks after, and a mean of fifteen months after successful angioplasty. Before angioplasty the mean (SD) ejection fraction fell significantly on exercise in both groups from 58 (10)% to 53 (13)% in group 1 and from 48 (10)% to 40 (16)% in group 2. This change was paralleled by a worsening wall motion score (from 0.6 (0.4) to 1.6 (1.2) in group 1 and from 2.3 (1.9) to 3.3 (2.4) in group 2). Six weeks after the procedure there was little change in resting ejection fraction but it increased significantly on exercise (to 62 (11)% in group 1 and to 53 (13)% in group 2). There was a concomitant significant improvement in the exercise wall motion score (to 0.4 (0.6) in group 1 and to 1.8 (1.1) in group 2). This improvement in exercise ejection fraction and wall motion was maintained at later follow up with no significant deterioration in either variable and a clearly sustained improvement in ejection fraction (60 (10)% in group 1 and 51 (10)% in group 2) and wall motion score (0.2 (0.2) in group 1 and 1.3 (0.8) in group 2) compared with values before angioplasty. The initial improvement in left ventricular function on exercise after successful angioplasty was maintained for at least 9-24 months both in patients with previous myocardial infarction and in those without.
Angioplasty, Balloon, Coronary↗
The structure and associations of the double S layer on the cell wall of Aquaspirillum sinuosum.
Aquaspirillum sinuosum cell walls bear two paracrystalline, proteinaceous surface layers (S layers). Each shows a different symmetry: the inner layer is closely apposed to the outer membrane and is a tetragonal array (90 degrees axes; 5-nm units; repeat frequency 8 nm); the outer layer is a hexagonal array on the external surface (14-nm units; repeat frequency 18 nm) and, although the units have a six-pointed stellate form, the linkage between units is not resolved. The outer layer consists of a major 130-kDa protein and a 180-kDa minor component; these co-extract, co-assemble, and are inseparable by hydroxylapatite chromatography or by recrystallization. The solubilizing effects of reagents suggest stabilization by hydrogen bonding and Ca2+. The two outer layer proteins are serologically related and show partial identity by peptide mapping. Periodic acid--Schiff staining of the 180-kDa band suggests that this may be a glycosylated form of the 130-kDa component. The inner layer components form a doublet of 75- and 80-kDa polypeptides with extreme resistance to extraction. Close apposition to the outer membrane, resistance to chaotropes, aqueous insolubility, and behaviour in charge-shift electrophoresis suggest hydrophobic interaction between subunits and an integral association with the outer membrane.
Antigens, Bacterial↗
[Study of survival using anistreplase (Eminase)].
Thrombolytic therapy has been one of the most important advances in the field of cardiovascular medicine. Several agents are available and research is continuing to develop new effective thrombolytics with a rapid onset of action. The efficacy of thrombolytic therapy can be evaluated by a number of criteria such as the reperfusion time, the incidence of coronary recanalisation, left ventricular function, and survival. Survival is certainly the parameter of choice for assessing any thrombolytic protocol. The aim of this paper is therefore to review the results of survival studies with Eminase, one of the new thrombolytic agents used in the treatment of acute myocardial infarction.
Aged↗
Percutaneous transluminal coronary angioplasty in patients with reduced left ventricular ejection fraction: effects on myocardial perfusion and left ventricular response to exercise.
Many patients with coronary artery disease treated by percutaneous transluminal coronary angioplasty (PTCA) have a history of previous myocardial injury resulting in a reduced left ventricular ejection fraction (EF). The effects of successful PTCA on myocardial perfusion and left ventricular function in these patients were compared to treatment in patients with normal left ventricular EF. There were 21 patients with a normal EF (mean EF 59 +/- 2%) (Group I) and 15 patients with reduced EF (mean EF 43 +/- 1%) (Group II). Before PTCA a similar degree of reversible myocardial ischemia was present on thallium scintigraphy. At peak exercise left ventricular EF in the Group I patients decreased by 4 +/- 1% compared to 8 +/- 1% in Group II. At one month following successful PTCA there was resolution of reversible myocardial ischemia in both groups. No changes in EF at rest were observed. At the same level of exercise as before PTCA the mean EF was 5 +/- 1% higher than the pretreatment value in Group I and 10 +/- 1% higher in Group II. Thus in this study reversible myocardial ischemia was associated with severe compromise in the left ventricular response to exercise which was substantially improved by PTCA.
Angioplasty, Balloon↗
Central haemodynamic changes during lower body positive pressure in patients with congestive cardiac failure.
Fifteen patients with moderately severe and severe chronic congestive heart failure were studied to determine the central haemodynamic results of short term increases in lower body positive pressure. Central haemodynamic variables were determined by Swan-Ganz thermodilution catheterisation and arterial cannulation. Graded increases in lower body positive pressure were applied to supine patients using Medical Anti-Shock Trousers (MAST). Increasing lower body positive pressure by 25 mm Hg and 55 mm Hg caused increases in mean right atrial pressure (6.0 to 13.2 to 17.9 mm Hg; p less than 0.001 and p less than 0.0001 respectively) and mean pulmonary artery pressure (26.8 to 35.5 to 41.3 mm Hg; p less than 0.05 and p less than 0.01 respectively). No significant changes were seen in left heart filling pressures or in pulmonary vascular resistance. Furthermore, there were no significant increases in indices of cardiac work (cardiac index, left ventricular stroke work index, right ventricular stroke work index or cardiac power output) despite the increased right heart filling pressures. These results show that in patients with longstanding severe congestive heart failure, short term increases in cardiac return may increase right heart pressures but do not appear to cause either beneficial or detrimental changes in left heart haemodynamic indices.
Coronary Disease↗
The acute effects of intravenous xamoterol ('Corwin', I.C.I. 118, 587) on resting and exercise haemodynamics in patients with mild to moderate heart failure.
The known properties of xamoterol, a partial beta 1-agonist, provide a basis to pharmacologically modulate cardiac responses to variations in sympathetic tone. Haemodynamic variables were assessed at rest and on exercise before and after intravenous xamoterol (0.2 mg kg-1), in 30 patients with mild to moderate cardiac failure. Xamoterol produced significant improvements in resting cardiac index (2.51 +/- 0.15 to 2.80 +/- 0.14 l min-1 m-2; P less than 0.001), stroke volume (62 +/- 4 to 75 +/- 5 mljbeat-1; P less than 0.001) and stroke work index (42.4 +/- 3.6 to 47.7 +/- 3.9 gm beat-1 m-2; P less than 0.01). This occurred despite a significant reduction in heart rate (78 +/- 3 to 74 +/- 2 beats min-1; P less than 0.05). There were also significant reductions in systemic vascular resistance (1990 +/- 141 to 1669 +/- 112 dynes s-1 cm-5; P less than 0.01) and double product (1146 +/- 46 to 1051 +/- 41 mmHg min-1 x 10(-1); P less than 0.05), with no significant changes in systolic blood pressure, pulmonary wedge pressure or ejection fraction. Xamoterol significantly attenuated the heart rate response to exercise (112 +/- 4 to 97 +/- 3 beats min-1; P less than 0.001), with no impairment in the expected exercise induced increase in cardiac index. This was due to the significant increase in stroke volume from 81 +/- 6 to 95 +/- 7 ml beat-1 (P less than 0.001). There were no significant changes in resting or exercise noradrenaline levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Agonists↗
Detrimental haemodynamic effects of cyclizine in heart failure.
The haemodynamic effects of intravenous cyclizine, an antiemetic that is widely given with opioids in left ventricular failure and myocardial infarction, were studied in 11 patients with severe heart failure. Cyclizine significantly increased systemic and pulmonary arterial pressures, and right and left ventricular filling pressures, and negated the venodilatory effects of diamorphine. The use of cyclizine in patients with heart failure should, therefore, be avoided.
Adult↗