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Biomedical subjects

E D Bennett

Publications and source records attributed to E D Bennett.

At least 73 records · Page 4Linked to original sources

Pentoxifylline reduces pulmonary leucostasis and improves capillary patency in a rabbit peritonitis model.

This study examines the changes in pulmonary leucostasis and capillary ultrastructure in 18 rabbits divided into three groups. Those in the first group were sham operated, and those in the second and third groups underwent peritonitis induction; those in the latter group were treated with pentoxifylline (PTF). White blood cells (WBC) were counted, and tissue area, total capillary area, and capillary patency were measured from electron micrographs of lung tissue. Pulmonary WBCs were 1.2 per unit field in the sham group, 9.7 in the test group (P less than 0.001 compared with sham), and 2.5 in the PTF group (P less than 0.001 compared with sham). Capillary patency was 53 +/- 5% in the sham group, 12 +/- 4% (P less than 0.001 compared with sham) in the test group, and 24 +/- 2% (P less than 0.001 compared with sham) in the PTF group. Pentoxifylline treatment attenuates pulmonary leucostasis, pulmonary capillary occlusion, and endothelial and epithelial damage associated with peritonitis in rabbits. This study shows that PTF warrants investigation into its potential protective effects on the lungs in clinical sepsis.

Animals↗

MRI appearances of the CNS manifestations of Mycoplasma pneumoniae: a report of two cases.

Two patients are reported with Mycoplasma pneumoniae-related cervical myelitis. Magnetic resonance imaging in each case demonstrated clinically silent lesions suggesting more extensive neurological involvement. This supports the concept of widespread immunologically mediated disease occurring as a remote effect of initial M. pneumoniae respiratory infection. Differences from the MRI appearances of a patient with mycoplasma-related Guillian-Barré syndrome imply that more than one antigenic determinant is involved.

Adolescent↗

Atrial natriuretic peptide inhibits osmolality-induced arginine vasopressin release in man.

1. Eight normal volunteers were infused with 5% saline (5 g of NaCl/100 ml) at a rate of 0.06 ml min-1 kg-1 for 120 min to increase plasma osmolality and plasma arginine vasopressin. Human atrial natriuretic peptide (alpha-hANP; 100 micrograms) or placebo was given in random order in a double-blind cross-over design for the last 20 min of the saline infusion. 2. Compared with the placebo infusion, atrial natriuretic peptide (ANP) produced a 43% greater sodium excretion and a 34% greater urinary volume in the subsequent hour. 3. Mean plasma immunoreactive ANP did not increase in response to changes in osmolality and rose to a peak of 118 pg/ml during the alpha-hANP infusion. alpha-hANP produced significant suppression of mean plasma arginine vasopressin over the 60 min after the infusions. 4. We conclude that ANP is not released in response to increased osmolality in vivo, and that it inhibits osmolality-induced arginine vasopressin release in man.

Adult↗

Domperidone, a DA2-specific dopamine antagonist, has no effect on the renal or haemodynamic response to atrial natriuretic peptide in man.

1. Animal experiments have suggested that the renal effects of atrial natriuretic peptide (ANP) are dependent on dopaminergic activation, predominantly of the DA1-receptor. In man, there is evidence of dependence on the DA2-receptor for the natriuresis produced by central blood volume expansion. 2. Six normal volunteers underwent infusions of alpha-human ANP preceded by domperidone (a DA2-antagonist) or placebo. Eight volunteers underwent a 3 h period of 10 degrees head-down tilt also preceded by domperidone or placebo. 3. Both the ANP infusion and head-down tilt produced a significant diuresis and natriuresis, neither of which was antagonized by the presence of domperidone. 4. The ANP infusion significantly reduced diastolic blood pressure and produced significant increases in the Doppler-measured aortic blood velocity variables of peak velocity and maximal acceleration. Domperidone had an independent effect of increasing blood pressure but did not appear to have a specific interaction with the haemodynamic effects of ANP. 5. Head-down tilt reduced mean arterial pressure and heart rate and increased maximal acceleration. Again, an independent effect of domperidone was seen on blood pressure. Heart rate and maximal acceleration showed similar changes in the presence of domperidone. 6. Domperidone does not antagonize the renal or haemodynamic effects of ANP and if dopaminergic activation is necessary for the renal action of ANP it is unlikely to be mediated by the DA2-receptor.

Atrial Natriuretic Factor↗

The dobutamine stress test as an alternative to exercise testing after acute myocardial infarction.

Three weeks after myocardial infarction in 50 patients the effect of the infusion of a graded dose of dobutamine was compared with that of symptom limited treadmill exercise testing. The following variables were measured: blood pressure, heart rate, ST segment changes, Doppler aortic blood flow, and cross sectional echocardiographic dimensions. The heart rate and double product increased more during exercise than during dobutamine infusion, while maximum acceleration in the ascending aorta increased more during dobutamine infusion than during exercise. Significant ST depression was recorded in 22 patients during exercise and in 24 during dobutamine infusion; the concordance between the two tests was 88%. In all cases in which ST segment depression occurred in both tests the site of ST depression was the same. Dobutamine stress testing is an alternative to exercise testing in patients after myocardial infarction.

Adult↗

High gain signal averaged electrocardiogram combined with 24 hour monitoring in patients early after myocardial infarction for bedside prediction of arrhythmic events.

The value of the high gain, signal averaged electrocardiogram combined with 24 hour electrocardiographic monitoring in the prediction of arrhythmic events was assessed in 159 patients in the first week after myocardial infarction. Eleven patients (7%) suffered arrhythmic events during a mean (SD) of 12 (6) months of follow up (range 2-22, median 13 months). The combination of high gain, signal averaged electrocardiography and 24 hour electrocardiographic monitoring was more accurate than either technique alone or than clinical information collected during admission in predicting these events. The combination identified a high risk group of 13 (8%) patients, with an arrhythmic event rate of 62% and a low risk group with an event rate of 2%. The combination of high gain, signal averaged electrocardiography and 24 hour electrocardiographic monitoring in the first week after myocardial infarction provides a rapid, cheap, and non-invasive bedside method for the prediction of arrhythmias.

Adult↗

A phospholipase inhibitor modifies the pulmonary damage associated with peritonitis in rabbits.

Peritonitis has been produced in rabbits by the spreading of 5 ml of caecal contents throughout the peritoneal cavity. After sacrifice at 5 h, electron microscopy revealed a increase of 600% in PMN and 1200% in lymphocytes in the pulmonary capillaries of the test animals when compared to the sham operated group. The pulmonary capillaries in the test group showed a 27% reduction in their luminal area, which was associated with a 73% reduction in their patency due to occlusion by WBC and cell debris. In addition there was endothelial and epithelial disruption with basement membrane exposure. The PMN were degranulated and adherent to the pulmonary endothelium. Pretreatment with the phospholipase inhibitor, mepacrine, significantly attenuated these responses, so that there was only an increase of 200% in PMN and 450% in lymphocytes in the lungs with no evidence of degranulation or adhesion to the pulmonary endothelium. Furthermore there was no change in capillary luminal area when compared to the sham operated group. In addition there was only slight damage to the endothelium and epithelium with no exposure of the basement membrane. Peripheral WBC in both the test and mepacrine groups showed a similar 62% and 75% reduction after 5 h when compared to baseline values. The sham group did not show this change. These results suggest that phospholipase inhibition plays an important role in attenuating the pulmonary response to faecal peritonitis and may be of potential benefit in treating clinical septicaemia.

Animals↗

Endogenous vasopressin affects postural control of blood pressure in man.

1. Six healthy volunteers received intravenous infusions of isotonic (0.9% NaCl) and hypertonic (3% NaCl) saline on separate days. There were no significant changes in blood pressure or forearm blood flow, despite an increase in plasma arginine vasopressin (AVP) during hypertonic saline. 2. Immediately and 10 min after passive tilting to 50 degrees, mean forearm blood flow fell by 17.1 and 14.3% compared with the values in the supine position during isotonic saline and by 40.3 and 43.3% during hypertonic saline. Forearm vascular resistance rose by 23.6 and 17.8% with isotonic saline and by 80.2 and 88.2% with hypertonic saline for the two readings in the tilted compared with the supine position. 3. Tilting was associated with a 14.9 and 12.1% rise in diastolic blood pressure immediately and 10 min after assuming this position during hypertonic saline, and a rise of 6.4% in mean arterial pressure. 4. The results from this study are similar to those obtained previously, when small amounts of AVP were infused. They provide further evidence that AVP may have a physiological role in the postural regulation of blood pressure.

Adult↗

Determination of the optimal dose of glyceryl trinitrate in the treatment of stable angina.

There has been recent controversy over the efficacy of transdermal glyceryl trinitrate (GTN) preparations in the treatment of angina and their effects on exercise tolerance. To determine the dose of GTN that produces significant anti-anginal effects, symptom limited exercise testing has been undertaken in seven patients with stable angina. Doses of 10, 20, 40 and 80 micrograms min-1 of GTN or placebo were infused during treadmill exercise until symptom limiting chest pain or greater than or equal to 3 mm ST segment depression occurred. Compared with placebo, total exercise time increased by 47% at 20 micrograms min-1 (P less than 0.05) with no further change at the higher doses. Duration of exercise before the onset of significant ST segment depression increased by 51% at 20 micrograms min-1 (P less than 0.05) with no further increase at the higher doses. These changes were accompanied by a 21% increase in double product (heart rate X systolic blood pressure) at 20 micrograms min-1 (P less than 0.05) reflecting a higher heart rate achieved as a result of the increased duration of exercise. These results suggest that 20 micrograms min-1 may be the optimal dose of GTN to achieve significant antianginal effects as demonstrated by the improved exercise tolerance and reduction of myocardial ischaemia. This implies that the dose of GTN delivered by transdermal preparations may be below the therapeutic level.

Angina Pectoris↗

Accurate detection of triple vessel disease in patients with exercise induced ST segment depression after infarction.

The severity of coronary artery disease is an important determinant of prognosis after acute myocardial infarction. The ability of a symptom limited exercise test to predict the presence of triple vessel disease was assessed in 221 patients three weeks after infarction. Coronary angiography was performed in patients with exercise induced ST segment depression. The presence of ST segment depression alone was poorly indicative of triple vessel disease; however, some specific features of ST segment changes on exercise were of predictive value. Downsloping ST segment configuration alone or horizontal ST segment depression associated with an early onset and a late recovery time after exercise correctly identified 30 (90%) of 33 patients with triple vessel disease whereas it incorrectly identified only 6 (15%) of 39 patients with single and double vessel disease. An abnormal blood pressure response was also predictive. In patients with ST segment depression after infarction triple vessel disease can be detected accurately by a combination of the electrocardiographic and haemodynamic variables attained on exercise.

Adrenergic beta-Antagonists↗

Application of the medical anti-shock trouser (MAST) increases cardiac output and tissue perfusion in simulated, mild hypovolaemia.

We have studied the haemodynamic effects of the application of the medical anti-shock trouser (MAST) in 10 healthy subjects in the semi-upright position in order to simulate mild hypovolaemia. Left ventricular end diastolic dimension (EDD) was measured by M-mode echocardiography and cardiac output (CO) by the Doppler ultrasound technique. Forearm blood flow (FBF) was measured by plethysmography and blood pressure (BP) by the standard cuff technique. Systematic increases in MAST pressure of up to 80 mm Hg were applied. EDD increased to a maximum of 9.3% (p less than or equal to 0.01) which was associated with a maximum increase in CO of 31.7% (p less than or equal to 0.05). FBF increased by a maximum of 54.2% (p less than or equal to 0.001) whilst BP increased by a maximum of 12% (p less than or equal to 0.001). These results demonstrate that the application of the MAST is an effective means of transferring blood to the central circulation by compression of the capacitance vessels resulting in significant increases in cardiac output and tissue perfusion. At high pressures there was evidence of compression of resistance vessels, which may be useful in reducing blood loss. The ease and rapidity with which his suit can be applied suggests that it may be useful in the short term treatment of hypovolaemia.

Adult↗

Haemodynamic effects of vasopressin in man are related to posture.

Ten healthy volunteers received intravenous infusions of arginine vasopressin (AVP) at 0.1 m-unit min-1 kg-1 and 5% D-glucose on separate days. AVP caused a small fall in forearm blood flow and small rises in mean arterial pressure and systemic vascular resistance. Cardiac output was unaffected. When subjects were tilted to 50 degrees the fall in forearm blood flow was much greater, mean fall being 44.8% with AVP compared with 18.2% with D-glucose. Cardiac output also fell significantly more with AVP, and diastolic pressure, mean arterial pressure and systemic vascular resistance rose significantly more on tilting during AVP infusion than with D-glucose. Six of the same volunteers were given sequential infusions of 'low dose' (0.0125 m-unit min-1 kg-1) and 'high dose' (0.3 m-unit min-1 kg-1) AVP on a third occasion. Tilting still produced a mean fall in forearm blood flow of 41.2% during low dose infusion, despite a mean plasma AVP level of only 1.9 pg/ml, which is well within the physiological range. When the AVP concentration was increased 24-fold to the high dose, forearm blood flow fell only a further 8.8%. The low dose infusion was also associated with a marked fall in cardiac output on tilting and a rise in systemic vascular resistance. We conclude that AVP has profound haemodynamic effects in man at physiological concentrations. Although these effects are modest in the supine position, they become marked on tilting, suggesting a possible role for AVP in the postural control of blood pressure.

Adult↗

Decelerating inspiratory flow waveform improves lung mechanics and gas exchange in patients on intermittent positive-pressure ventilation.

The effects of two inspiratory flow waveforms (WFs), decelerating and constant have been studied in 14 patients undergoing intermittent positive-pressure ventilation (IPPV). With tidal volume (VT), inspiratory time, inspiratory-expiratory (I/E) ratio and frequency being kept constant, the decelerating waveform produced statistically significant reduction of peak pressure, total respiratory resistance, work of inspiration, ratio of dead space to tidal volume (VD/VT) and alveolar-arterial gradient for oxygen (A-a)PO2. There was significant increase in total static and kinetic compliances and PaO2, with no significant changes in PaCO2, in cardiac output (CO) and in other haemodynamic measurements.

Adult↗

Validation of a Doppler technique for beat-to-beat measurement of cardiac output.

We have measured aortic flow in the ascending aorta in man with a Bach-Simpson BVM 202 blood velocity meter, and aortic root diameter by M-mode echocardiography, and thus derived beat-to-beat cardiac output (Q). We tested the technique in 21 patients (53 comparisons) with various cardiovascular problems against a thermodilution method, and in four normal subjects at rest and two levels of exercise (50 and 100 W) against a nitrous oxide rebreathing method. We obtained excellent overall correlation in a range of 0.5-10 litres/min (r = 0.98, n = 77, sy,x = 0.48 litre/min), the formula for the least squares regression being: (Q Doppler) = 0.95 (Q Thermodilution/N2O) + 0.11 litre/min. The Doppler signal is sufficiently noise-free to obtain maximum acceleration of flow from the first derivative of velocity.

Adult↗

A possible explanation for the absence of anti-anginal properties of transdermal nitroglycerin units: an echocardiographic study.

The failure of clinical trials to demonstrate any anti-anginal properties of the transdermal nitroglycerin units has resulted in the re-evaluation of one such product, Transiderm-Nitro. Haemodynamic assessment following the application of 10, 20 and 40 cm2 units has been made in eight healthy volunteers over a 6 h period. Measurements of heart rate, blood pressure, stroke volume and left ventricular dimension (by 'M' mode echocardiography) were made 2 h after the application of the units. End diastolic dimension fell by 5.2% and stress by 12.6% implying a reduction in myocardial oxygen consumption. However this was offset by an increase in double product of 10.7% and in circumferential fibre shortening of 23.4%. These results imply that the doses used produce venodilatation leading to a reduction in myocardial oxygen consumption. However this is counterbalanced by the reflex induced increase in heart rate and inotropic state. It suggests therefore that much larger doses are required to produce significant anti-anginal effects.

Administration, Topical↗

The haemodynamic responses to incremental doses of intravenous nitroglycerin in left ventricular failure.

The effects of incremental dose infusions of nitroglycerin, 10-160 micrograms/min, on pulmonary capillary wedge pressure and other haemodynamic variables have been studied in patients with left ventricular failure. Intravenous (IV) nitroglycerin caused a dose-related improvement in myocardial performance, with significant reductions in the raised pulmonary capillary wedge pressure and systemic vascular resistance. At the lowest dose of infusion only the venodilator action of nitroglycerin was apparent. From 40-160 micrograms/min the associated arteriolar dilatation was associated with a consistent improvement in myocardial performance.

Aged↗

A haemodynamic and pharmacokinetic study to assess a new transdermal nitroglycerin preparation in normal subjects.

A continual application of a transdermal Nitroglycerin ( Nitrodur ) has been haemodynamically and pharmacokinetically assessed in a group of 10 normal healthy volunteers over a 24 h period. There were significant decreases in left ventricular end systolic dimension and end diastolic dimension over this period, demonstrating a continuous haemodynamic effect. A dose related response was not demonstrated, although low plasma nitroglycerin levels produced significant haemodynamic changes. The persistent decrease in left ventricular wall stress implies a reduction in myocardial oxygen consumption. Thus Nitrodur may play an important role in the long term prophylaxis of angina.

Adult↗

Ascending aortic blood velocity and acceleration using Doppler ultrasound in the assessment of left ventricular function.

We have used a 2.2 MHz continuous-wave Doppler blood velocity meter (Bach-Simpson BVM 202) to measure ascending aortic blood velocity and acceleration, and have obtained from the velocity signal a noninvasive measure of stroke volume and cardiac output by combining the Doppler technique with M-mode echocardiography. In two separate studies we have systematically altered the loading conditions of the heart with lower body pressure; and the inotropic state of the heart with dobutamine (5 micrograms . kg-1 . min-1), and documented the changes in mean velocity (MV), maximum acceleration (MA), stroke volume (SV), cardiac output (CO) and left ventricular end-diastolic dimension (EDD) (M-mode echocardiography). Application of lower body pressure to subjects in a 30 degrees head-up tilt position caused a systematic increase in preload, as shown by a 9% increase in EDD, which raised SV by a maximum of 33% (p less than or equal to 0.001) and CO by 32% (p less than or equal to 0.01), thus showing a classical Starling response; whilst there was relatively little increase in MA. Conversely, infusion of dobutamine, an inotropic agent, caused a 29.2% increase in MA (p less than or equal to 0.01) with minimal increase in SV. Thus, the ability to measure ascending aortic blood velocity allows noninvasive monitoring of changes in both inotropic state and Starling function, with considerable ease and rapidity.

Adolescent↗