Recommendations for pacing.
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Cardiac Pacing, Artificial↗
Biomedical subjects
R Sutton
Publications and source records attributed to R Sutton.
A guide to temporary pacing.
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Bradycardia↗
CATS and biochemistry at Wolverhampton Polytechnic.
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Biochemistry↗
Haemodynamic and neurohumoral response in heart failure produced by rapid ventricular pacing.
OBJECTIVE: The aim was to determine the exact sequence of hormone changes during the progression of fluid retention in a canine model of "congestive cardiac failure" induced by rapid right ventricular pacing, and during recovery when pacing is stopped. METHODS: Rapid ventricular pacing at a rate of 250 pulses.min-1 was used in six mongrel dogs with implanted right ventricular pacemakers. Right heart haemodynamics were measured by means of Swan Ganz catheterisation, allowing flow measurement by thermodilution and pressure measurement by external manometry. Plasma renin activity, arginine vasopressin, and atrial natriuretic factor were assayed on venous blood samples by radioimmunoassay. Noradrenaline was assayed by high pressure liquid chromatography. RESULTS: The onset of rapid pacing was accompanied by a fall in cardiac output and a rise in pulmonary arterial, pulmonary capillary wedge, and right atrial pressures. Noradrenaline and atrial natriuretic factor rose. Plasma renin activity showed an initial fall followed by a rise, and arginine vasopressin was unchanged in the first 8 h. When rapid pacing was continued for a further 35 d, clinical signs of fluid retention appeared by day 28, by which time cardiac output had fallen, and central pressures risen further. Atrial natriuretic factor peaked at around 14 d whereas plasma renin activity, arginine vasopressin, and noradrenaline tended to reach a plateau at about d 20 and then to show further increases as clinical signs of fluid retention appeared; this was most marked with plasma renin activity. Cessation of pacing at d 35 caused a rapid reversal (increase) of cardiac output but a more gradual reversal (decrease) of right heart pressures over 5 d; only wedge pressure returned to base line. Arginine vasopressin and plasma renin activity fell rapidly to around 40% of the final pacing levels and reached basal values after 8 h and 48 h respectively. Noradrenaline fell after 8 h and reached basal levels in 5 d. Atrial natriuretic factor fell quickly by 60% after 8 h but remained above basal levels for 5 d. At the end of pacing, body weight fell rapidly in conjunction with a large diuresis. CONCLUSIONS: These findings are compatible with a major role of one or more of renin, vasopressin, and noradrenaline in the pathophysiology of the fluid retention of heart failure; the manifestations are not counteracted by the rise in atrial natriuretic factor.
Animals↗
Development of a rate adaptive pacemaker based on the maximum rate-of-rise of right ventricular pressure (RV dP/dtmax).
The maximum rate of rise of right ventricular pressure (RV dP/dtmax) may change in response to physiological stress and thereby provide an appropriate parameter upon which to base rate adaptive pacing. Initial feasibility testing was carried out in six patients using externally closed loop rate adaptive pacing with a pressure sensing lead (Model 6220) and an investigational VVI pulse generator (Medtronic, Model 2451). During exercise, maximum positive RV dP/dtmax increased from 223 +/- 55 to 405 +/- 181 mmHg.sec.1 (P less than 0.05). Based on these results, rate adaptive pulse generators using maximum positive RV dP/dt were implanted in 12 patients (Medtronic, Model 2503). Exercise treadmill testing in the VVI mode resulted in heart rates ranging from 69 +/- 6 beats/min at rest to 79 +/- 14 beats/min (n = 12; P greater than 0.05). In contrast, VVIR mode pacing rates ranged from 71 +/- 11 beats/min to 115 +/- 24 beats/min (n = 17; P less than 0.05). Holter recording showed heart rates ranging from 51 +/- 6 to 110 +/- 22 beats/min during activities of normal daily living (n = 9; P less than 0.05). Passive postural tilt resulted in rates of 69 +/- 8 beats/min in the supine position increasing to 74 +/- 14 beats/min with 60 degrees upright tilt (n = 16; P greater than 0.05). With up to 5-year follow-up data, there have been no late failures of pacing but one lead showed insulation failure with over- and undersensing after 4.5 years. A number of deficiencies were identified in the prototypes leading to modifications of a subsequent generation of rate responsive pacemaker based on RV dP/dtmax. These initial data demonstrate that rate adaptive pacing based on RV dP/dtmax responds in a physiological manner. This rate responsive system is of particular interest as it is based on a beat-to-beat parameter of cardiac mechanical function.
Activities of Daily Living↗
Pacemaker syndrome: an iatrogenic condition.
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Bradycardia↗
Relative expression of surface IgM, IgD and the Ig-associating alpha(mb-1) and beta(B-29) polypeptide chains.
Membrane immunoglobulins are associated with a transmembrane disulphide-linked heterodimer composed of an alpha-chain (mb-1) and a beta-chain (B-29). The relative surface expression of all of the polypeptide chains comprising the Ig-alpha beta complex has been investigated using surface labelling coprecipitation analysis and two-colour flow cytometric analysis. The main conclusions are that mb-1 and B-29 are B-cell surface markers on immature and mature B cells, and that all components of the surface Ig-alpha beta complex are expressed in stoichiometrically equivalent amounts. Thus the complex was quantitatively precipitated from digitonin lysates of 125I-surface-labelled cells with anti-B-29, anti-mb-1 or anti-Ig. Secondly, by two-colour FACS analysis there was a proportionality between the relative amounts of cell surface mb-1 or B-29 and surface IgM or IgD, but not other B-cell markers (class II, B220, FcR gamma, FcR epsilon). Finally there was an insignificant number of B cells expressing membrane Ig without alpha- and beta-chains, and vice versa. Thus there appears to be a closely controlled relative synthesis and surface expression of all components of the B-cell receptor complex.
Animals↗
myc protooncogenes of wool and hair growth.
The growth of hard keratin fibers such as wool and hair is dependent on the proliferation of cells in the follicle bulb. If the cells leaving the bulb could be induced to undergo an extra division, then fiber growth should increase. The cellular division within the follicle is complex and probably involves one or more growth factors, which act by altering the expression of transcription factors and other nuclear proteins. We propose that the expression of the myc protooncogenes is a central part of this mechanism. In support of this hypothesis we have detected the mRNAs for TGF-beta 1, basic FGF, TGF-alpha, and c-myc in plucked wool follicles using PCR amplification. We have also shown that the TGF-beta 1, TGF-beta 2, TGF-beta 3, EGF, TGF-alpha, basic FGF, N-myc, and c-myc genes are expressed in mouse skin, and we looked for changes during the hair cycle. The PCR data suggest that in whole skin the levels of mRNA for TGF-beta 1, TGF-beta 2, TGF-alpha, and c-myc do not change. In Quackenbush mice the levels for N-myc, TGF-beta 3, and basic FGF mRNA appear to be lower at the end of the hair cycle. We have confirmed in CBA/C57 black mice that lower levels of N-myc mRNA are detected when hair growth ceases in catagen and telogen. To test our hypothesis further and to assess its practical application, we are making transgenic mice in which the N-myc gene is overexpressed in the hair follicle by way of a wool keratin promoter. The transgene consists of 3.3 kb of 5' sequence from an ovine type 1 IF gene, the murine N-myc genomic coding sequence, and an SV40 polyadenylation signal. The native keratin type 1 IF gene is expressed exclusively in the wool follicle, as shown by in situ hybridization. However, in mice the injection of the transgene has resulted in high embryonic mortality and some embryos with large body size and head malformations. Since these mice were not transgenic, this is likely to be an effect of transient expression of the transgene during embryogenesis. The two transgenic mice produced so far have a normal phenotype.
Aging↗
Ultrasound of the common bile duct in patients undergoing cholecystectomy.
One hundred patients undergoing cholecystectomy underwent ultrasonography of the biliary tree on the day prior to surgery. At operation a per-operative cholangiogram was performed unless stones were palpable in the duct. Pre-operative biliary ultrasonography accurately identified dilatation of the common bile duct (sensitivity 96%, specificity 95%) but was less accurate at detecting common duct stones (sensitivity 36%, specificity 98%). Thirty three percent of patients with dilated ducts on ultrasound did not have stones in the duct, while 20% of patients with common duct stones had normal sized ducts. We conclude that ultrasonography alone cannot reliably select patients who require exploration of the common bile duct, or select patients for operative cholangiography. Although pre-operative demonstration of common bile duct dilation is an absolute indication for operative cholangiography, by itself it does not indicate the need for exploration.
Adult↗
Factors influencing the ocular pulse--the heart rate.
Using pneumotonometry combined with a Langham ocular blood-flow system, measurements of pulsatile ocular blood flow (POBF) were performed in eight ocular normotensive patients with implanted cardiac pacemakers, with the subjects assuming both the erect and the supine postures. Sequential measurements of POBF were made at pre-set values of heart rate over the physiological range between 60 and 120 beats/min at intervals of 10 beats/min. With patients in the supine position, measurements of cardiac output and stroke volume indices were also recorded by impedance cardiography. The mean pulse amplitude of the intraocular pressure (the ocular pulse) decreased as heart rate increased, and this change was statistically significant in both postures according to repeated-measures analysis of variance (erect: f = 18.7, P less than 0.0001; supine: f = 18.8, P less than 0.0001). As measured in supine patients following an increase in heart rate, the pulse amplitude decreased in parallel with a decline in stroke volume index (f = 18.8, P less than 0.0001). Up to a level of 90 beats/min, the mean POBF increased with heart rate, but it declined above this rate in both erect and supine postures. At all heart rates, intraocular pressure was higher when subjects were supine than when they stood erect (f = 4.3, P less than 0.001). At lower heart rates of 70 and 80 beats/min, ocular pulse volume and POBF were significantly lower in supine patients than in erect subjects (70 beats/min: t = 3.89, P less than 0.01 vs; t = 3.87, P less than 0.01; 80 beats/min: t = 2.85, P less than 0.05 vs; t = 2.87, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Failure of adjuvant heparin to reduce myocardial ischemia in the early treatment of patients with unstable angina.
Although the efficacy of long-term administration of antithrombotic agents in unstable angina has been established, short-term effects on myocardial ischemia are unknown. A retrospective analysis was performed in 47 patients undergoing three-channel continuous ST segment monitoring as part of a multicenter trial using esmolol in unstable angina, in which 20 patients received a continuous heparin infusion during the initial assessment of chest pain. Concomitant medications included calcium channel blockers, beta-adrenergic blockers, nitrates, and aspirin in the majority of patients. Clinical variables between the heparin and no heparin groups were similar, except for fewer males and fewer total artery occlusions in the heparin group. No significant differences in the incidence or duration of ischemia were found in a 36 +/- 16 hour monitoring period. Forty percent of the heparin group had 35 episodes of ischemia with a mean of 11 +/- 10 minutes per episode and a total ischemic time of 48 +/- 39 minutes per patient with ischemia. Forty-four percent of the no heparin group had 47 episodes of ischemia with a mean of 13 +/- 13 minutes per episode and a total ischemic time of 58 +/- 47 minutes per patient with ischemia. Multiple linear regression analysis to adjust for intergroup differences did not alter the results. Eighty-five percent of all episodes were asymptomatic. Clinical events, such as episodes of chest pain, emergency coronary arteriography, or coronary revascularization, were also similar between groups. Thus the short-term administration of heparin did not alter the incidence or duration of ischemia in patients with unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
Properties of ATPase activity associated with peroxisomes of rat and bovine liver.
1. Peroxisomes were isolated from bovine and rat liver by use of differential and density gradient centrifugations. 2. In the final density gradient (Nycodenz) a distinct peak of ATPase activity codistributed with the peroxisome marker catalase and was well separated from the bulk of the ATPase activity and from markers for other subcellular organelles. 3. The peroxisome-associated ATPase had a pH optimum of 7.5 and was inhibited by N-ethylmaleimide, by N,N'-dicyclohexylcarbodiimide and by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, but was unaffected by up to 30 microM n-tributyltin chloride. 4. Prolonged incubation with oligomycin at high concentrations indicated that 50% of peroxisomal ATPase was resistant to this inhibitor. The oligomycin-sensitive ATPase activity required at least a four-fold higher ratio of inhibitor to protein for inhibition than mitochondrial ATPase did. It was concluded that oligomycin-sensitive and oligomycin-resistant ATPase may be associated with liver peroxisomes.
Adenosine Triphosphatases↗
Methodology of head-up tilt testing in patients with unexplained syncope.
Prolonged 60 degree head-up tilt has been shown to be valuable in the investigation of unexplained syncope, diagnosing neurally mediated bradycardia/hypotension or malignant vasovagal syndrome. To evaluate the methodology of tilt testing, the following were examined: reproducibility of results, tilt duration, angle of tilt, method of tilt support and effect of age in patients and control subjects. Seventy-one patients with recurrent unexplained syncope underwent 60 min of 60 degree tilt; 53 (75%) had an abnormal test with vasovagal syncope at 24 +/- 10 min (mean +/- SD). Tilting to 60 degrees resulted in an abnormal test in only 2 (7%) of 27 control subjects without cardiovascular symptoms (p less than 0.001); and 5 (15%) of 34 patients with syncope and documented conduction tissue disease (p less than 0.001). Of 15 youthful fainters, 3 (20%) had vasovagal reactions as did 1 (8%) of 12 asymptomatic youthful control subjects. These 12 control subjects also underwent tilting with a saddle support and 7 (67%) had vasovagal reactions. It is concluded that the duration of tilting at 60 degrees should be 45 min (mean time to syncope +2 x SD in the 53 patients with abnormal results). Twenty percent of patients with an abnormal tilt test may not demonstrate syncope with repeat tilting. Saddle tilt testing in unexplained syncope may result in a loss of specificity. Tilting at less than 60 degrees results in a loss of sensitivity. Head-up tilt may be less useful in youthful subjects with vasovagal syncope than in other subjects.
Aged↗
Transfection with SV40 gene of human pancreatic endocrine cells.
At present, only islet cell lines of animal origin have been successfully generated (e.g. RIN, HIT). A fully differentiated human beta cell line would be advantageous for diabetes research. We now report the generation of a human endocrine pancreatic cell line obtained by transfection using a plasmid containing the early region of SV40 viral DNA. Viral integration and transcription was assessed by Southern and Northern blotting. This cell line has been growing continuously for more than 2 years and maintains several of the characteristics of the parental cells from which they were generated. The presence of Neuron Specific Enolase, Protein Gene Product 9.5, cytokeratin, microvilli, cytoplasmic electrodense granules and the secretion of insulin, glucagon and somatostatin supports the neuroendocrine origin of this cell line. However, hormone production progressively decreased and finally stopped at passage 8. Flow cytometric analysis showed that HLA expression in this cell line is readily induced by IFN-gamma and modulated by TNF-alpha. The establishment of this human endocrine cell line indicates the feasibility of immortalizing human islets by transfection with viral oncogenes. To obtain a fully differentiated cell line it may be necessary to use other DNA constructs which immortalize the cells without fully transforming their phenotype.
Antigens, Viral, Tumor↗
The incidence of malignant vasovagal syndrome in patients with recurrent syncope.
We reviewed 322 patients with recurrent syncope between 1984 and 1988. Investigation included limited intracardiac electrophysiological study in all cases with programmed extra-stimulus studies in 48 cases. In 93 patients (29%), all investigations were normal, (including negative extrastimulus in 30). In the other 229 cases syncope was explained by AV-block (n = 111, 34%), sinus node disease (n = 68, 21%), carotid sinus syndrome (n = 32, 10%) and inducible sustained tachyarrhythmia (n = 18, 6%). Prolonged 60 degrees head-up tilt was performed in 71 out of 93 patients with unexplained syncope, and reproduced vasovagal syncope and presenting symptoms in 53 (75%), or 16% of the whole population reported. These patients were diagnosed as having malignant vasovagal syndrome. Positive tilts were significantly less common in a group of 27 subjects of similar age without a history of syncope (7%), and a random sample of 37 patients with atrioventricular block (n = 16), sick sinus syndrome (n = 18) and inducible tachyarrhythmia (n = 3), (19%, 11% and 0% respectively, P less than 0.01). From this retrospective review it appears, therefore, that tilt testing is a valuable provocative tool for vasovagal syncope and may reduce the number of syncopal patients that remain undiagnosed, although these early observations do not allow an exact appraisal of the sensitivity and specificity of the tilt test.
Arrhythmias, Cardiac↗
Dual chamber pacing aborts vasovagal syncope induced by head-up 60 degrees tilt.
To determine if pacing might prevent syncope in cardioinhibitory 'Malignant Vasovagal Syndrome' (also known as 'Neurally-Mediated Bradycardia/Hypotension'), a study of dual chamber pacing during head-up 60 degrees tilt was undertaken. Paired invasive tilts were performed in 10 patients who had a history of recurrent syncope, normal routine investigations including electrophysiological study and prior tilt-induced vasovagal syncope. Vasovagal reactions of identical severity were produced by prolonged 60 degrees head-up tilt on consecutive days in seven out of 10 patients. On day 2, without pacing, seven patients had tilt-induced vasovagal reactions and six became syncopal during the reaction. On day 3, with temporary DVI pacing with rate hysteresis, seven patients had tilt-induced vasovagal reactions and 1 patient was syncopal. Syncope was aborted in the other five patients. DVI pacing significantly improved cardiac index (CI) (one +/- 0.2 to 1.6 +/- 0.3 L/min/m2, P less than 0.01) and mean arterial blood pressure (MABP) (30 +/- 11 to 48 +/- 12 mmHg, P less than 0.01) during vasovagal reactions on day 3 compared with day 2. The mean period of time that patients could tolerate in the tilted position after the onset of the tilt-induced vasovagal reaction was significantly prolonged by pacing from 0.9 +/- 1.2 to 3.2 +/- 1.6 min (P less than 0.01). Dual chamber pacing may abort syncope in 85% of patients with cardioinhibitory malignant vasovagal syndrome. Pacing may prolong consciousness sufficiently during a vasovagal reaction to allow injury to be avoided.
Adult↗
Natural history of sinus node chronotropy in paced patients.
The natural history of chronotropic incompetence is not clear. To assess this, we evaluated corrected sinus node recovery time (cSNRT) and sinus node chronotropy at rest and during exercise in two groups of syncopal patients with sinus node disease. Group A comprised patients with resting bradycardia but normal cSNRT and group B had resting bradycardia and prolonged cSNRT (greater than 1000 ms). An additional two groups (C and D) were studied. Group C comprised patients with complete AV (CAVB) and no evidence of sinus node disease and group D were asymptomatic controls of similar age. At diagnosis, patients with symptomatic bradycardia but normal cSNRT and no evidence of carotid sinus syndrome (group A) had resting bradycardia and impaired peak heart rate (PHR-I) on exercise compared to controls (P less than 0.001 and P less than 0.05, respectively), but no reduction in exercise duration. At follow-up group A patients demonstrated an increase in resting rate that was significantly slower than the controls (P less than 0.01). Peak heart rate (PHR-II) also remained significantly slower (P less than 0.05). There was no difference in exercise duration between groups A and D at follow-up. Group B was further subdivided according to follow-up findings of preservation of atrial activity in seven patients (group B-1) and junctional rhythm without any atrial activity in four patients (group B-2). Retrospective analysis showed no significant difference in resting heart rate at initial examination but group B-2 showed a significantly lower peak heart rate on exercise compared with B-1 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Voltage-activated calcium and potassium currents in human pancreatic beta-cells.
1. The whole-cell configuration of the patch clamp technique was used to study inward and delayed outward currents in beta-cells isolated from human pancreatic islets. 2. The delayed outward current activated at about -20 mV and increased linearly with further depolarization. The instantaneous current-voltage (I-V) relation, measured by tail current analysis, reversed at -70 mV. This is close to the K+ equilibrium potential and suggests the outward current is carried primarily by potassium ions. In support of this idea, outward currents were abolished when internal K+ was replaced by the impermeant cation N-methyl-D-glucamine (NMG). 3. The voltage dependence of K+ current activation could be fitted by a sigmoidal function with a mid-point at +1 mV. K+ currents showed voltage-dependent inactivation which was half-maximal at -25 mV. 4. Inward currents were studied after outward currents were suppressed by replacing internal potassium with NMG. In 5 mM [Ca2+]o, the inward current activated between -50 and -40 mV, had a peak amplitude at -10 mV and reversed at potentials positive to +60 mV. The voltage dependence of inward current activation was sigmoidal with half-maximal activation at -10 mV in 5 mM [Ca2+]o and at -22 mV in 5 mM [Ba2+]o. 5. Inward currents were unaffected by tetrodotoxin (TTX), but could be blocked by cadmium ions. Barium was also capable of carrying inward current. This pharmacology is consistent with inward currents flowing through Ca2+ channels. 6. The inactivation of the inward current was dependent on calcium entry. In two-pulse experiments, the voltage dependence of inactivation was U-shaped, and resembled that of the calcium current. Barium currents showed little inactivation. 7. In two-pulse experiments the degree of inward current inactivation during the test pulse was related to the amount of calcium entry during the first pulse. Calcium entering at more positive potentials was less effective at producing inactivation. 8. Calcium and barium currents also showed a slow, voltage-dependent inactivation when the holding potential was changed between -100 and -40 mV. This inactivation developed with a time course of seconds. 9. The Ca2+ and K+ currents described here are similar to those reported for rodent beta-cells and indicate the rodent beta-cell provides a good model for that of man.
Action Potentials↗