Search PubMed⌕ Search

Biomedical subjects

K M Fox

Publications and source records attributed to K M Fox.

At least 127 records · Page 7Linked to original sources

Pulmonary artery pressure changes during exercise and daily activities in chronic heart failure.

Long-term continuous pulmonary artery pressure monitoring was used to investigate pressure changes during different types of exercise and normal daily activities in patients with chronic heart failure. Nine men (mean age 55 years) with treated chronic heart failure underwent continuous pulmonary artery pressure measurement with use of a micromanometer-tipped catheter with in vivo calibration and frequency-modulated recording. The mean (+/- SD) maximal systolic pulmonary artery pressure (in mm Hg) was 59.4 +/- 26.1 on treadmill exercise, 54.9 +/- 30.6 on bicycle exercise, 52.5 +/- 26.1 walking up and down stairs and 43.5 +/- 23.9 walking on a flat surface. The mean maximal diastolic pressure (in mm Hg) was 27.8 +/- 14.6 on treadmill exercise, 25.5 +/- 14.9 on bicycle exercise, 24.9 +/- 14.8 walking up and down stairs and 20.4 +/- 12.5 walking on a flat surface. The increase in pulmonary artery pressure did not correlate with the severity of the limiting symptoms except during walking on a flat surface. All patients had marked postural changes in pressure, with the systolic pressure difference from lying to standing ranging from 8 to 25 mm Hg and the diastolic pressure difference ranging from 3 to 13 mm Hg. Eating meals caused an increase in pressure in three patients, but less than that when lying flat. There was an increase in pressure during urination in four patients equal to that when walking on a flat surface. None of these activities was associated with symptoms. Neither symptoms nor pulmonary artery pressure during maximal exercise is the same as during daily activities. This may restrict the value of maximal exercise tests in assessing patients with chronic heart failure.

Activities of Daily Living↗

Synthesis of 3-arylecgonine analogues as inhibitors of cocaine binding and dopamine uptake.

3-Arylecgonine analogues were synthesized and characterized by 1H and 13C NMR, IR, and MS. The compounds were synthesized as racemates from cycloheptatriene-7-carboxylic acid or enantiomerically from (-)-cocaine. These analogues were tested for their ability to inhibit [3H]cocaine binding to bovine striatal tissue and to inhibit [3H]dopamine uptake into striatal synaptosomes. Methyl (1RS-2-exo-3-exo)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-ca rboxylate was the most potent analogue. IC50 values for inhibition of cocaine binding and dopamine uptake were 20 and 100 nM, respectively. The racemates and the 1R isomers were equally potent inhibitors of binding and uptake. Methyl (1RS-2-endo-3-exo)-3-(2,4-dinitrophenyl)-8-methyl-8-azabicyclo[3.2 .1]octane- 2-carboxylate was the least potent. IC50 for inhibition of both binding and uptake was 40 microM.

Animals↗

Circadian variation of heart rate is affected by environment: a study of continuous electrocardiographic monitoring in members of a symphony orchestra.

Twenty four hour ambulatory ST segment monitoring was performed on 48 members (43 players and five members of the management/technical team) of the British Broadcasting Corporation (BBC) symphony orchestra without a history of cardiac disease. This period included final rehearsals and live performances (for audience and radio) of music by Richard Strauss and Mozart at the Royal Festival Hall (n = 36) and Rachmaninov and Tchaikovsky at the Barbican Arts Centre (n = 21). During the period of monitoring one person (2%) had transient ST segment changes. Mean heart rates were significantly higher during the live performances than during the rehearsals. Mean heart rates during the live performance of Rachmaninov and Tchaikovsky were significantly higher than during Strauss and Mozart in those (n = 6) who were monitored on both occasions. Mean heart rates in the management and technical team were higher than those of the players. The recognised circadian pattern of heart rate, with a peak in the morning waking hours, was altered similarly during both concert days, with a primary peak occurring in the evening hours and a lesser peak in the morning for both musicians and management/technical staff. This study showed that environmental factors are of primary importance in defining the circadian pattern of heart rate. This has important implications when identifying peak periods of cardiovascular stress and tailoring drug treatment for patients with angina pectoris.

Adult↗

Circadian variation of the total ischemic burden and influence by beta-blocking agents.

We investigated 150 unselected patients with proven coronary artery disease. All patients were off all routine antianginal treatments and there were 598 ischemic episodes, of which 75% were silent. It was found that episodes of ischemia, both silent and painful, occurred predominantly during the daytime hours from 0730 to 1930 h. This pattern is similar to that described by others. There was a significant excess of episodes of ischemia in the morning hours (0730-1330 h), with a secondary peak occurring in the evening hours. We further investigated a subgroup of 41 patients who were monitored for 1,581 h while being treated with atenolol. These patients were investigated in a double-blind fashion, and during the off treatment phase the circadian pattern of ischemic episodes was similar to that described for the group as a whole. However, on treatment with atenolol, there was a significant reduction in the frequency and total duration of ischemic episodes throughout the day. Atenolol significantly altered the circadian distribution of ischemic episodes with elimination of the morning peak; there was some preservation of the evening peak although this was smaller than that described when the patients were off therapy. The circadian distribution of ischemic episodes and the observed changes with beta-blocking treatment resemble the reported circadian variation of acute myocardial infarction and sudden death. Although these studies do not in any way prove that myocardial ischemic episodes and their alteration by treatment are related to the development of acute myocardial infarction and death, the relationship between ischemic episodes and the end points of coronary disease require further investigation.

Adrenergic beta-Antagonists↗

Therapeutic rationale for the management of silent ischemia.

Prognostic data on the importance of silent ischemia is lacking. Preliminary reports suggest that ambulatory electrocardiographic monitoring provides additional information not contained in the exercise test, but it is still unclear whether silent ischemia is a marker of subsequent events or is responsible for their development. Recent investigations also suggest that intermittent episodes of ischemia may cause myocardial necrosis. Drugs that are effective in the treatment of angina are also effective in the treatment of silent ischemia, but their value in terms of long-term morbidity and mortality is unclear. Recently, the circadian distribution of silent ischemia has been reported in 150 patients off therapy, in 33 receiving nifedipine, and in 41 receiving atenolol. Most ischemic episodes off therapy occurred between 7:30 AM and 7:30 PM with a peak in the morning and a lesser peak in the evening. Nifedipine did not alter the circadian pattern of ischemic episodes; atenolol abolished the morning peak, the peak incidence of ischemia then occurring in the evening. This circadian distribution of ischemic episodes and the observed changes with treatment resemble the reported circadian variations of acute myocardial infarction and sudden death. Large multicenter studies are now being performed to determine the effects of treatment on silent ischemia and how this treatment may influence outcome. Until such studies have been completed, it is not possible to clearly define the indication for drug therapy in the management of silent ischemia.

Circadian Rhythm↗

A nuclear magnetic resonance (NMR) method for the determination of the cis/trans isomeric content of chlorprothixene.

Proton NMR spectroscopy was applied to the assignment of the isomeric identity of commercially available chlorprothixene. Nuclear Overhauser effect studies confirmed that the clinically useful isomer is the cis (Z) configuration. An NMR method for determining the isomeric content of chlorprothixene was developed based on integration of the ratio of areas of signal strength of the cis-N-methyl in comparison to the trans-N-methyl resonances.

Chlorprothixene↗

Unpredictable zero drift in intravascular micromanometer tipped catheters during long term pulmonary artery pressure recording: implications for catheter design.

Zero drift may be a cause of imprecision when micromanometer tipped catheters are used for intravascular pressure measurement over long periods of time. Drift of only a few mm Hg may represent a significant error when accurate recording of low vascular pressures is required. To overcome this problem a micromanometer tipped catheter has been modified so that it can be calibrated easily while it is in the circulation. Laboratory testing has demonstrated that when zero drift occurs this intravascular "reference calibration" is a valid linear function of true zero (r = 0.999). As the sensitivity of the catheter is unaffected by zero drift, it is possible to measure pressure accurately by compensating for this zero drift. During dynamic testing of two catheters, there was a mean net drift over 24 h of -0.54 mm Hg. Clinical evaluation of the catheter was undertaken in the human pulmonary circulation in eight patients (two for 48 h, five for 24 h and one for 8 h). In contrast to the laboratory findings, over the first 4 h after catheterisation there was a phase of rapid zero drift: the net drift was -1.9 (SD 3.3) mm Hg with a range of drift of 5.5 (7.4) mm Hg. Subsequently there was gradual drift: the net drift between 4 and 24 h was -0.44 (2.1) mm Hg with a range of drift of 2.8(1.0) mm Hg; and the net drift between 24 and 48 h was 3.7(2.1) mm Hg with a range of drift of 4.1(1.9) mm Hg. During long term intravascular pressure measurement with micromanometer tipped catheters, zero drift may occur unpredictably and should be quantified.

Ambulatory Care↗

Diurnal variation of pulmonary artery pressure in chronic heart failure.

Variation in pulmonary artery pressure has important consequences for the interpretation of isolated pressure measurements in patients with chronic heart failure. To investigate the nature of diurnal variation in pulmonary artery pressure in chronic heart failure, eight angina-free men (aged 50-72 years) with treated chronic heart failure caused by ischaemic heart disease underwent continuous ambulatory pulmonary artery pressure recording by a transducer tipped catheter. The mean (1 SD) daytime pulmonary artery pressure was 29.6 (5.0) mm Hg systolic and 13.7 (5.6) mm Hg diastolic. The mean change in pressure from day to night was +5.1 (3.2) mm Hg systolic and +3.8 (1.7) mm Hg diastolic; and the mean change from standing to lying +9.3 (2.3) mm Hg systolic and +6.4 (2.1) mm Hg diastolic. In six of the eight patients there was considerable rise in pulmonary artery pressure at night, but in the two patients with the most severe symptoms there was no nocturnal rise. In patients with chronic heart failure, nocturnal pulmonary artery pressure is not determined by postural change alone. But interpretation of isolated pulmonary artery pressure measurements must take the posture of the patient into account.

Aged↗

The variable effects of angiotensin converting enzyme inhibition on myocardial ischaemia in chronic stable angina.

The effect of angiotensin converting enzyme inhibition on myocardial ischaemia was studied in 12 normotensive patients with chronic stable angina and exercise induced ST segment depression. The study was randomised, double blind, placebo controlled, and crossover with treatment periods of two weeks. Enalapril was used to inhibit angiotensin converting enzyme. Assessment was by angina diaries and maximum symptom limited treadmill exercise tests. The results for the whole group showed a significant reduction in systolic blood pressure at rest and at peak exercise. Mean total exercise duration was 466 s (95% confidence interval 406 to 525) when the patients were taking placebo and 509 s (436 to 583) when they were taking enalapril. Four patients prolonged their total exercise time (mean 450 to mean 591 s) by more than 20%. Two patients, however, developed ischaemia earlier on exercise and reduced their total exercise duration (mean 490 to mean 390 s). Although angiotensin converting enzyme inhibition tended to reduce myocardial ischaemia in the group as a whole, some patients improved while others deteriorated. Thus the effects of enalapril are variable and this may have important implications when enalapril is used to treat heart failure in patients with underlying severe ischaemic heart disease.

Aged↗

Smoking, catecholamines, and the ischemic myocardium.

Catecholamine stimulation increases the heart rate and the force of cardiac contraction. Cardiac output then increases, with a decrease occurring in total peripheral resistance due to smooth muscle dilation in the vascular beds of the muscle and heart, though there is constriction of the skin and viscera; this leads to a net decrease in total peripheral resistance. Consequently, systolic pressure rises and diastolic pressure falls. The net effect is to increase myocardial oxygen demand. Smoking stimulates catecholamine secretion and may therefore be expected to have detrimental effects in patients with angina. In a double-blind study of ten patients with stable angina pectoris treated with nifedipine, propranolol, and atenolol, smoking was found to have direct and adverse effects on the heart and to interfere with the efficacy of all three antianginal drugs, but with that of nifedipine the most. Differences between the two beta blockers may be related, at least in part, to the known different metabolic pathways of these drugs.

Angina Pectoris↗

Digital and palmar dermatoglyphics in dementia of the Alzheimer type.

Digital and palmar dermatoglyphics were examined in 29 men and 27 women with dementia of the Alzheimer type (DAT) and 112 age-, sex-, and racial group-matched controls. Female patients had significantly (p less than 0.05) more accessory triradii and complete Sydney creases than controls; no dermatoglyphic differences were detected in the males. Separating the patients by age of onset prior to or after age 65 years did not help differentiate patients from controls by dermatoglyphic profile. This study failed to confirm either the previously reported dermatoglyphic differences between DAT patients and controls or the reported similarity of the dermatoglyphic pattern of DAT to that of Down syndrome patients.

Adult↗

Effects of intracoronary isosorbide dinitrate during acute myocardial ischaemia: a study during angioplasty.

The effects of isosorbide dinitrate on acute myocardial ischaemia were studied in 19 patients during coronary angioplasty. The duration of balloon inflation to the onset of ST segment depression was increased by the administration of intracoronary isosorbide dinitrate from (mean +/- SEM) 13 +/- 2 to 20 +/- 2 s (48%) (P less than 0.01) and the duration to 1 mm ST segment depression increased form 23 +/- 2 to 29 +/- 3 s (28%) (P less than 0.01). Systolic blood pressure fell from 118 +/- 3 to 111 +/- 4 mmHg but there was no change in intracoronary distal occlusion pressure. Thus during coronary occlusion isosorbide dinitrate prolongs the time to the onset of myocardial ischaemia.

Acute Disease↗

Perforation thresholds and safety factors in in vivo coronary laser angioplasty.

Laser angioplasty can cause early (acute perforation) or late (stenosis or aneurysm) complications. To find how much intravascular laser energy can be delivered via a 100 microns core optical fibre passed down a balloon angioplasty catheter without causing angiographic abnormalities up to 10 days later, argon laser energy was delivered percutaneously under radiographic screening to the coronary circulation of 12 normal closed chest dogs. With the balloon inflated, sequential laser pulses were delivered to the same site. Angiograms were recorded before, immediately, and again at one week, after laser delivery. There were two laser-induced perforations (both fatal). Mechanical perforation with the 100 microns fibre occurred four times, but there were no haemodynamic sequelae. To find the acute perforation threshold of similar sized arteries to energy delivered via the bare 100 microns core fibre, the tip of which was held in contact with the luminal surface, 32 argon laser pulses were delivered transluminally in vivo to separate sites in normal rabbit iliac and canine coronary arteries. The acute perforation threshold with energy delivered via the angioplasty catheter lay between 6 and 10 J and that without the balloon angioplasty catheter lay between 3 and 4 J. After delivery of up to 6 J via a balloon angioplasty catheter, there were no angiographic abnormalities at one week. Fibre optic transluminal delivery of laser energy may improve the primary success rate of, and perhaps widen the indications for, coronary angioplasty.

Angioplasty, Balloon↗