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Biomedical subjects

M I Noble

Publications and source records attributed to M I Noble.

At least 55 records · Page 3Linked to original sources
PubMed1994

Lack of importance in humans of the slow component of the response of force to an increase in cardiac muscle length.

1. An increase in length in isolated animal muscles causes an immediate increase in contractile force, which is followed by a slower further progressive increase: the slow component. However, the pressure-volume concept, used in characterizing left ventricular function, is dependent on a constant relationship between pressure and volume. 2. We therefore examined the possible occurrence of the slow inotropic component of the response to cardiac muscle stretch in man at cardiac catheterization. 3. Human subjects undergoing left heart catheterization for clinical indications were studied. The development of the slow component was studied by measurement of rate of rise in left ventricular developed pressure and the time course after an increase in end-diastolic volume. 4. No evidence for any slow component was elicited. 5. It is concluded that the slow component of force (or pressure) increase after an increase in cardiac muscle length (or volume) does not have a role in the human heart in situ.

Adult↗
PubMed1994

Emerging patterns of heart disease in HIV infected homosexual subjects with and without opportunistic infections; a prospective colour flow Doppler echocardiographic study.

We studied 124 homosexual men aged 36.7 +/- 7.6 years (range 23-57) using Doppler echocardiography. One hundred and one patients (Group A) had had acquired immunodeficiency syndrome for 1.6 +/- 1.0 years and 23 patients (Group B) had had HIV infection without opportunistic infections for 3.2 +/- 2.3 years. Doppler echocardiography was normal in 31% of Group A patients and in 61% of Group B. Pericardial effusion was found in 44 Group A patients (44%) and two Group B patients (9%). In Group A, left ventricular dilatation and/or dysfunction were found in 20 patients (20%), aortic root dilatation and regurgitation in eight patients (8%) and an intracardiac echogenic mass in seven patients (7%); in Group B one patient (4%) had an intracardiac mass. Forty-four (44%) Group A patients had cardiac presentations, and of these 22 had cardiomegaly with clinical signs of heart failure; 10 patients had tachyarrhythmias compared to only two in Group B. Although the CD4 lymphocyte count (%) was significantly lower in Group A than in Group B (5.4 +/- 6.1 vs 13.3 +/- 7.3, P < 0.001), the presence of pericardial effusion, left ventricular dysfunction, right-sided cardiac enlargement or the duration of HIV infection, did not relate to the CD4 level in either group. Although often not diagnosed clinically, cardiac involvement in patients with AIDS is a clinical reality, with pericardial effusion, cardiomyopathy and left ventricular dysfunction appearing to have a high prevalence in male homosexual patients with AIDS. These clinical and echocardiographic findings are associated with clinically apparent intercurrent opportunistic infections, rather than the HIV virus per se, or the severity of infection as reflected by the CD4 count.

AIDS-Related Opportunistic Infections↗
PubMed1994

Serum lipids and thyrotropin in women with coronary artery disease.

Abnormalities of thyroid function are associated with changes in lipid concentrations and in the incidence of ischaemic heart disease. Whether lipid concentration and thyroid function are related when thyroid function is normal in ischaemic heart disease is uncertain. This study was undertaken to investigate the relationship between thyroid function, serum lipids and ischaemic heart disease in euthyroid women. Forty-six euthyroid patients were studied. Patients with diseases known to affect lipid levels or receiving drugs known to alter lipid or thyroid metabolism were excluded. Twenty-three had ischaemic heart disease (IHD) and were matched with 23 controls. Correlations were found between thyrotropin (TSH) and cholesterol (P = 0.05) low density lipoprotein (LDL) (P = 0.09) and triglyceride (P = 0.009) in the IHD group but not between any serum lipids and TSH in the control group. Analysis of covariance showed a statistically significant difference between groups of the association between cholesterol and TSH (P < 0.05 (slope) P < 0.001 (means)), LDL and TSH (P < 0.005 (means)) and between triglyceride and TSH (P < 0.05 (means)). This study suggests that TSH within the normal range is having a statistically significant effect on lipid levels in women with ischaemic heart disease.

Cholesterol↗
PubMed1994

Enoximone in chronic stable angina: a double-blind placebo-controlled cross-over trial.

Enoximone, a phosphodiesterase inhibitor (PDEI), has both positive inotropic and vasodilatory properties. We examined the effect of a single oral dose of enoximone as compared with placebo on myocardial ischaemia and global left ventricular (LV) function using both exercise ECG and Doppler measurements of aortic blood flow, respectively. Twenty patients (16 men, 4 women) with a mean age of 59 years and stable angina were studied. Total exercise duration was significantly longer after enoximone as compared with placebo treatment, with a mean difference of 22.8 s (p = 0.003). Times (mean +/- SD) to onset of angina and development of significant ST-segment decrease were similar after placebo (454 +/- 101 and 352 +/- 155 s, respectively) or enoximone (500 +/- 155 and 413 +/- 192 s, respectively), although both showed trends in favour of enoximone. As compared with placebo, significantly higher heart rate (HR) was measured for enoximone both at rest (75 +/- 18 vs. 90 +/- 22 beats/min, p < 0.01) and on recovery from exercise (81 +/- 18 vs. 89 +/- 19 beats/min, p < 0.05). Enoximone had no significant effect on systolic or diastolic blood pressure (SBP, DBP) or rate-pressure product (RPP) generated at rest or during exercise. Changes in both acceleration and velocity of aortic blood flow during exercise were similar after administration of enoximone or placebo. We showed that a single oral dose of enoximone is well tolerated in patients with ischaemic heart disease, improving both exercise capacity and favourably influencing ST-segment changes with no increase in adverse events or significant haemodynamic disturbances.

Administration, Oral↗
PubMed1994

Influences of stimulation frequency and temperature on interval-force relationships in guinea-pig papillary muscles.

Relationships between contractile force and the preceding and pre-preceding stimulation intervals were studied in papillary muscles by interposing variable test intervals during steady-state pacing. The strength of test contractions increased exponentially to a maximum as the preceding (test) interval was lengthened. Contractility decreased as an exponential function of pre-preceding interval. At 37 degrees C, the half times for these processes were unaffected by increasing the steady-state frequency from 1 to 3 Hz. At 27 degrees C, the force increase with preceding interval was accelerated and the decay with pre-preceding interval was retarded as the stimulation frequency was increased from 0.33 to 2 Hz. The time-courses of force increase and decay were similar to each other during stimulation at an optimum frequency characteristic for the temperature. Cooling from 37 to 27 degrees C prolonged the half times for force increase and decay by factors of 4.5 and 3 respectively. The slope of the linear relationship between the force of the contraction pre-preceded by the test interval and the immediately subsequent contraction (recirculation fraction) was also halved. These results suggest that high stimulation frequency and low temperature uncouples cellular processes underlying the interval dependence of cardiac contractility. The temperature sensitivities are consistent with these processes being enzymatic. The reduced recirculation fraction provides a mechanism for the lowered threshold frequency for sustained mechanical alternans at 27 degrees C.

Action Potentials↗
PubMed1994

Exercise electrocardiography and aortic Doppler velocimetry in asymptomatic identical twins discordant for type 1 (insulin dependent) diabetes.

OBJECTIVE: To determine the influence of insulin dependent diabetes on the prevalence of myocardial ischaemia and on global left ventricular systolic performance. DESIGN: Stress treadmill electrocardiograms and simultaneous Doppler measurement of aortic maximum acceleration were obtained during exercise on symptom free subjects. The electrocardiograms were scored blindly according to the Minnesota code. PARTICIPANTS: 39 identical twin pairs (22 male) discordant for insulin dependent diabetes and 39 non-diabetic controls of similar age and sex were examined. The twins and controls had a mean age of 37 (range 25-69) with a mean (SD) duration of diabetes in the diabetic twin of 17 (7) years. Those selected were normotensive and had no renal impairment. RESULTS: Systolic blood pressure was significantly higher in the diabetic twins than in their non-diabetic cotwins both at rest (p < 0.05) and at peak exercise (p < 0.01). Electrocardiographic evidence of ischaemia was not correlated within twin pairs and was found in similar numbers of diabetic twins, their non-diabetic cotwins, and control subjects. Abnormal electrocardiograms were found in a similar number of diabetic twins (23%), non-diabetic cotwins (18%), and controls (15%). There was a significant correlation in Doppler measurements of global left ventricular systolic function within the identical twins; no significant difference was found for these Doppler measurements in the diabetic twins, non-diabetic cotwins, or controls. CONCLUSION: Exercise characteristics and cardiac function seem to be subject to shared genetic or shared environmental influences or both, whereas electrocardiographic features of ischaemia seem to be environmentally determined. In a selected cohort of diabetic identical twins without evidence of nephropathy there was no evidence that diabetes influenced the prevalence of myocardial ischaemia or global left ventricular systolic function.

Adult↗
PubMed1994

Risk factors for cardiovascular disease in IDDM. A study of identical twins.

Patients with insulin-dependent diabetes mellitus (IDDM) have an excess mortality, predominantly attributable to cardiovascular disease. To determine the effect of IDDM on potential risk factors for cardiovascular mortality, we studied subjects from the British Diabetic Twin Study Group. Forty-five identical twin pairs discordant for IDDM were recruited in addition to 45 matched nondiabetic singleton control subjects. All were selected to be normotensive and to have normal albumin excretion rates. Four variables differed significantly between the diabetic twins and their nondiabetic identical co-twins: diabetic twins had higher systolic blood pressure (sBP) ([mean +/- SD] 127 +/- 17 vs. 123 +/- 18 mmHg, P < 0.05), high-density lipoprotein (HDL) cholesterol (1.36 +/- 0.31 vs. 1.25 +/- 0.29 mM, P < 0.05) and fibrinogen (3.23 +/- 0.81 vs. 2.98 +/- 0.71 mg/ml, P < 0.05) but lower factor VII (114 +/- 34 vs. 122 +/- 31%, P < 0.05). All four of these risk factors were significantly correlated (P < 0.001) within the identical twin pairs, as were the other risk factors. These significant correlations within twins for the risk factors studied reflects the impact of shared genetic and environmental influences. IDDM affects sBP, HDL cholesterol, fibrinogen, and factor VII, but only sBP and fibrinogen are affected adversely.

Adult↗
PubMed1994

Macroaggregation of platelets in plasma, as distinct from microaggregation in whole blood (and plasma), as determined using optical aggregometry and platelet counting respectively, is specifically impaired following cardiopulmonary bypass in man.

We determined changes in platelet aggregability following cardiopulmonary bypass, using optical aggregometry to assess macroaggregation in platelet-rich plasma (PRP), and platelet counting to assess microaggregation both in whole blood and PRP. Hirudin was used as the anticoagulant to maintain normocalcaemia. Microaggregation (%, median and interquartile range) in blood stirred with collagen (0.6 micrograms/ml) was only marginally impaired following bypass (91 [88, 93] at 10 min postbypass v 95 (92, 96] prebypass; n = 22), whereas macroaggregation (amplitude of response; cm) in PRP stirred with collagen (1.0 micrograms/ml) was markedly impaired (9.5 [8.0, 10.8], n = 41 v 13.4 [12.7, 14.3], n = 10; p < 0.0001). However, in PRP, despite impairment of macroaggregation (9.1 [8.5, 10.1], n = 12), microaggregation was near-maximal (93 [91, 94]), as in whole blood stirred with collagen. In contrast, in aspirin-treated patients (n = 14), both collagen-induced microaggregation in whole blood (49 [47, 52]) and macroaggregation in PRP (5.1 [3.8, 6.6]) were more markedly impaired, compared with control (both p < 0.001). Similarly, in PRP, macroaggregation with ristocetin (1.5 mg/ml) was also impaired following bypass (9.4 [7.2, 10.7], n = 38 v 12.4 [10.0, 13.4]; p < 0.0002, n = 20), but as found with collagen, despite impairment of macroaggregation (7.2 [3.5, 10.9], n = 12), microaggregation was again near-maximal (96 [93, 97]). The response to ristocetin was more markedly impared after bypass in succinylated gelatin (Gelofusine) treated patients (5.6 [2.8, 8.6], n = 17; p < 0.005 v control), whereas the response to collagen was little different (9.3 v 9.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗
PubMed1993

Effects of trimetazidine on in vivo coronary arterial platelet thrombosis.

We used Folts' model of critical coronary artery stenosis with endothelial damage, which measures platelet-rich thrombus accumulation from cyclic flow reductions (CFRs). This paper reports results applied to trimetazidine, a member of the piperazine group. Trimetazidine at a dose of 1 mg/kg completely abolished CFRs caused by accumulating thrombus in the circumflex coronary artery in 4 of 8 open-chest anesthetized beagles. More trimetazidine (up to 5 mg/kg) abolished CFRs in two more and attenuated them in the remaining two dogs. There were no systemic hemodynamic effects observed. Adrenaline was then infused to stimulate platelet activation. At a rate of 0.4 microgram/kg/min, CFRs were restored in one dog only. Adrenaline given at 1.6 micrograms/kg/min resulted in restoration or increase in the slope of CFRs in all animals. A further six nonoperated dogs were anesthetized and given trimetazidine 3 mg/kg. Routine coagulation studies were not altered. However, aspirin 5 mg/kg significantly increased bleeding time, whereas trimetazidine alone did not. These findings suggest that trimetazidine is effective in preventing intracoronary platelet aggregation in this model. Because of its demonstrated sparing of coagulation factors and its lack of effect on bleeding time, the cause is unlikely to be inhibition of the fibrinogen or thrombin receptors, or interference with arachidonic acid metabolism.

Animals↗
PubMed1993

Mechanisms of excitation-contraction coupling studied using the principle of transient perturbation.

We have studied the responses to a brief interruption of a train of steady state beats, namely: (1) a single prolonged depolarisation within the train; (2) a single short interval within the train; (3) a single long interval within the train. These responses are predicted by a two compartment model of intracellular calcium handling. They are characterised by the following phenomena. (1) Prolongation of one depolarisation/action potential in the steady state train causes potentiation of the following beat. We postulate on the basis of the published evidence that this may be due to "reversed" sodium/calcium exchange during late systole leading to extra calcium entry during the prolonged depolarisation. (2) Postextrasystole potentiation is postulated to share this mechanism when a depolarisation (extrasystole) is introduced immediately after one of the steady state depolarisations (single short interval). The postextrasystolic beat is then potentiated. (3) A single short interval during the steady state train also leads to attenuation of contractile force on the beat immediately after the short interval, that is, the extrasystole. Mechanical restitution is the term applied to the recovery of this force with increasing interval. This consists of two phases. The initial rapid phase is ryanodine and caffeine insensitive, indicating possible independence of sarcoplasmic reticular function. We postulate that a "membrane compartment" of internal calcium may be responsible. The second, slower, phase of mechanical restitution is ryanodine and caffeine sensitive, indicating that it is likely to be a property of the sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Safety of intravenous dipyridamole thallium myocardial perfusion imaging: experience in 435 patients.

Dipyridamole stress 201Tl scintigraphy is widely used in the investigation of myocardial ischaemia. We report our experience of adverse effects observed during this diagnostic procedure. A prospective study was undertaken of 435 consecutive patients (mean age 59 years; 273 males) referred to two nuclear medicine departments for assessment of myocardial perfusion was undertaken. Patients were monitored prior to and following the infusion of dipyridamole. All symptomatic, haemodynamic and electrocardiographic changes were documented. No deaths occurred in this series. Adverse events were observed in 174 (40%) patients. Of these, three patients experienced 'major' adverse events (0.6%) requiring hospitalization (myocardial infarction = 1; chest pain = 1; simple partial seizure = 1). 'Moderate' adverse events occurred in 39 (8.9%) patients and required intravenous aminophylline to reverse effects (ST segment abnormalities = 26; nausea = 7 headache = 3; chest pain = 2; bronchospasm = 1; protracted vomiting = 1; diarrhoea = 1). 'Minor' adverse events were experienced by 132 (30.3%) patients and did not require aminophylline. Sixty per cent of our patients experienced no ill effects from dipyridamole given as an exercise substitute in conjunction with 201Tl imaging. The rest had symptoms which were mostly mild, although a few patients found the experience unpleasant. Only one patient experienced a life-threatening episode.

Adult↗
PubMed1993

Interaction between the effects of 5-hydroxytryptamine and adrenaline on the growth of platelet thrombi in the coronary artery of the anaesthetized dog.

1. The interaction between adrenaline and 5-hydroxytryptamine (5-HT) has been quantitated on the rate of thrombus formation, in the stenosed coronary artery with damaged endothelium of the anaesthetized dog. 2. Changes in the plasma concentration of adrenaline were produced by varying the rate of an intravenous infusion of adrenaline and in the effects of 5-HT, by intravenous injections of the selective 5-HT2 receptor antagonist, ICI 170809. 3. Increases in the plasma concentration of adrenaline, which did not cause significant changes in blood pressure and heart rate, increased the rate of thrombus formation. 4. Antagonism of the 5-HT2 receptor by ICI 170809, in the absence of an infusion of adrenaline, abolished thrombus formation (mean ED50 0.41 microgram kg-1, i.v.). 5. The effects of adrenaline were non-competitively antagonized by ICI 170809; maximum effects were obtained in the dose-range 50-200 micrograms kg-1, i.v., when the mean dose-ratio increase in adrenaline required to restore equivalent rates of thrombus formation was 39 fold. 6. These results are consistent with a synergism between adrenaline and 5-HT and emphasize the importance of both on thrombus formation.

Anesthesia↗
PubMed1993

Blood pressure versus blood flow.

The pressure-volume diagram of the left ventricle is fundamental to understanding the mechanics of contraction and its modification by disease, drugs and anaesthetics. For monitoring patients perioperatively, we advocate variables derived from the pressure-volume diagram: cardiac output to monitor circulatory failure, pulmonary capillary wedge pressure to monitor the acute state of left ventricular filling and echocardiography to determine the chronicity and severity of chronic heart failure. Use of the pressure-volume diagram shows that whenever arterial pressure is raised by the use of vasoconstrictor agents, the flow of blood to the tissues is impaired. In patients in whom the heart is damage or failing, this adverse effect of raising arterial pressure causes further deterioration of circulatory failure and flow. In view of the prime need of the body tissues for blood flow, together with oxygen and substrates, it is advocated that vasoconstricting agents should not be used to maintain arterial pressure in the perioperative period. Plasma expansion and control of posture are preferred methods for maintaining the circulation. If circulatory failure continues in the presence of a high filling pressure of the left ventricle (wedge pressure), drugs combining positively inotropic and vasodilator properties are advocated.

Anesthesia, General↗
PubMed1993

Do the cardiac nerves optimise efficiency?

The cardiac nerves were removed by surgical dissection in anaesthetised dogs. At least 3 weeks were then allowed to elapse to permit degeneration of post-ganglionic sympathetic nerve fibres and myocardial catecholamines. We then established that: 1) Myocardial oxygen consumption was increased for a given work output, indicating metabolic inefficiency; 2) glucose oxidation was inhibited; 3) uncoupled oxygen consumption of isolated myocardial tissue was increased, and 4) sodium-potassium ATPase activity was enhanced. These results are compatible with the hypothesis that the cardiac nerves optimise efficiency. There is some evidence from cardiac transplantation studies in man that a similar effect of innervation on efficiency is present. However, examination of this concept as a postulated result of evolutionary pressure led us to reject such a hypothesis (at least in man) because such a mechanism should be irrelevant to the factors determining survival at the time of human evolution. However, the hypothesis may be tenable for the situation at some earlier evolutionary era. This could be determined, in theory, by a comparative study between species of the effect of cardiac innervation upon efficiency.

Animals↗
PubMed1993

Obliterative bronchiolitis with atypical features: CT scan and necropsy findings.

We describe the natural history of cryptogenic bronchiolitis obliterans in a patient followed for 24 yrs with serial pulmonary function tests and radiology. Severe, progressive airway obstruction developed, with overinflation but preservation of KCO. There was progressive hypoxaemia, which worsened on exertion; hypercapnoea was modest until late in the illness. Neither bronchodilators nor steroids were effective. The chest radiograph remained normal; CT showed irregular areas of low attenuation peripherally throughout the lungs, with Hounsfield numbers typical of emphysema, but no bullae. Postmortem studies included histology and quantitative studies of a corrosion cast of one lung. They showed marked airway narrowing at all levels, with pruning of peripheral branches, mucus plugging, and some emphysema. The case illustrates that cryptogenic bronchiolitis obliterans may be chronic and difficult to distinguish clinically or by investigation from other forms of chronic obstructive airways disease, particularly emphysema.

Adult↗
PubMed1992

Erythrocyte sodium-lithium countertransport and blood pressure in identical twin pairs discordant for insulin dependent diabetes.

OBJECTIVE: To investigate whether insulin dependent diabetes is responsible for the abnormal behaviour of the carrier in sodium-lithium countertransport and whether the diabetic state is associated with rise in blood pressure. DESIGN: Case-control study. SETTING: London teaching hospital. SUBJECTS: 44 twin pairs discordant for insulin dependent diabetes living in United Kingdom and 44 healthy control subjects matched for age, sex, and body mass index. None of the twin pairs or the controls had evidence of microalbuminuria. MAIN OUTCOME MEASURES: Sodium-lithium countertransport activity in erythrocytes and arterial blood pressure. RESULTS: The mean (95% confidence interval) sodium-lithium countertransport activity (mmol Li per litre of red blood cells per h) of the diabetic twins (0.291 (0.244 to 0.338)) was similar to that of their non-diabetic cotwins (0.247 (0.204 to 0.290)); both values were significantly higher than that of the controls (0.187 (0.157 to 0.216); p < 0.05). In addition, systolic blood pressure was higher in those twins with diabetes (127 (122 to 133) mm Hg) than in the non-diabetic cotwins (122 (117 to 127) mm Hg; p < 0.01). There were no significant differences in mean diastolic blood pressure between any of the groups studied. CONCLUSIONS: The raised erythrocyte sodium-lithium countertransport activity in the diabetic twins compared with the controls seems to be inherited rather than a consequence of overt diabetes. The higher systolic blood pressure in diabetic twins than non-diabetic cotwins indicates that insulin dependent diabetes does exert a small influence on systolic blood pressure.

Adult↗