Adrenal abnormalities in paraquat poisoning: an indication for corticosteroid therapy?
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Adrenal Cortex↗
Biomedical subjects
B Silke
Publications and source records attributed to B Silke.
Mechanical effects of ET-1 in cardiomyocytes isolated from normal and heart-failed rabbits.
Endothelin (ET-1) is found at elevated concentrations in the plasma of patients with heart failure and in animal models of cardiomyopathy. The peptide is a potent positive inotropic agent, the effects of which are mediated by increases in cytosolic Ca2+ in cardiomyocytes. The object of this study was to investigate at the cellular level, the actions of ET-1 on contractile function and on Ca2+ currents in heart-failed ventricular myocardium. Male New Zealand White rabbits (8 wks) were treated with twice weekly injections of epirubicin (4 mg/kg/wk, n = 7) or with saline (n = 7) for 6 wks, followed by a washout period of 2 wks. Ventricular cardiomyocytes were isolated from rabbit hearts using Langendorff perfusion with collagenase; contractile function was examined using a video microscopy method, and L-type Ca2+ currents were recorded using a whole-cell patch-clamp technique. ET-1 produced a concentration-dependent increase in contractile response (% increase from basal value) to a maximum at 1 nM ET-1 of 69 +/- 11% (mean +/- S.D.) in control cardiomyocytes and 33 +/- 6% in heart-failed cells. However, there was no significant change in the EC50 obtained with ET-1 for healthy (0.31 +/- 0.1 nM) and for failed cardiomyocytes (0.24 +/- 0.1 nM). The effects of ET-1 on L-type Ca2+ channels were similar with a peak amplitude at 1 nM ET-1 of -3.26 +/- 0.8 nA in control cardiomyocytes and -3.32 +/- 0.9 nA in heart-failed cells. The attenuation of the contractile response to ET-1 in heart-failed cells may reflect a desensitization of ET receptors as a consequence of elevated circulating levels of ET and was not reflected by alteration of transmembrane Ca2+ conductance. It is probable, therefore, that multiple signalling pathways are involved in the actions of ET on ventricular myocardium.
Animals↗
Attitudes to peer review as a competence assurance structure--results of a survey of Irish physicians.
BACKGROUND: The Medical Council in Ireland is currently implementing Competence Assurance Structures (CAS). Peer review has been proposed as a tool to measure physician competence. AIMS: To assess the attitudes of physicians working in the Irish healthcare system to a peer review programme of competence assurance prior to its implementation. METHODS: A postal survey was sent to all physicians in the Irish Medical Directory in November 2003. Nine questions were asked to gauge attitudes to peer review as a CA tool. The returned questionnaires were collated and data extracted based on responses. RESULTS: The response rate was 67%. The majority of respondents (92%) felt peer review would inform competence assurance in Ireland. Most physicians who were surveyed felt an on-site assessment (88%) every 5 years (87%) was the preferred method. Over 30% responded that there should be a financial incentive for completing a review, and 70% would pay to be assessed. The UK model of competence assurance was the model most physicians preferred for the Irish setting (42%). CONCLUSION: The majority of physicians practising in Ireland would favour a peer review system of competence assurance. The financial implications, and structure, of such a system would need to be explored prior to implementation.
Attitude of Health Personnel↗
Inhaled nitric oxide in combination with volume resuscitation refines a porcine model of endotoxic shock.
BACKGROUND: Existing porcine models of endotoxic shock poorly represent the human situation. AIMS: To assess whether the cardiovascular profile of a porcine model could be improved by refining the protocol. METHODS: In 30 pigs, right and left heart pressures and cardiac output were measured. Lipopolysaccharide (LPS) was administered as a bolus (n=12), as a 30 minute infusion (n=6) or as a 30 minute infusion along with inhaled NO and volume resuscitation (n=6) and six sham-treated pigs received normal saline. Haemodynamic values were measured over three hours. RESULTS: LPS increased pulmonary vascular resistance (PVR) (13.3 +/- 1.4 to 37.0 +/- 3.9kPa/l per sec, p<0.05) and reduced cardiac output (6.0 +/- 0.6 to 4.8 +/- 0.41/min). Mortality was 50% within 30 minutes. Inhaled NO and volume resuscitation controlled pulmonary vascular resistance (PVR) and preserved CO. Systemic vascular resistance (SVR) declined in the first hour (118.4 +/- 11.8 to 65.8 +/- 8.2kPa/l per sec, p<0.05) and remained low. CONCLUSIONS: Porcine models of endotoxaemia based on LPS administration are a poor model of human septic shock, but can be improved by regulating PVR and supporting CO which may contribute to future studies of septic shock
Administration, Inhalation↗
Pharmacokinetic and pharmacodynamic studies with prazosin in chronic heart failure.
The correlation between the plasma concentration of prazosin and the effects on supine and standing systemic blood pressure and heart rate was examined at 1/2, 1, 2, 4, and 8 hr after single oral doses of 0.5, 1, 2, and 4 mg in 8 patients with severe refractory heart failure due to coronary heart disease. Despite wide between-patient and within-patient variation in the plasma concentration, the grouped results showed a significant linear relationship between dose, peak concentration, and area under the time-concentration curve. Time of maximum plasma concentration (2 hr) and half-life in plasma (5.6 hr) were similar after all four doses. Compared to the reported pharmacokinetic profile of the drug in normal subjects, the plasma clearance of the drug in these patients in heart failure was substantially reduced. In the recumbent posture there were reductions in systolic and diastolic blood pressure without consistent changes in heart rate after all doses of prazosin. A clear dose-response effect of the drug on both variables only became apparent during standing, when there was a significant correlation between dose, the postural fall in systolic and diastolic blood pressure, and the increase in heart rate. Three of the 8 patients were unable to tolerate more than 1 mg prazosin due to postural hypotension.
Adult↗
Haemodynamic dose-response effects of intravenous oxprenolol in coronary heart disease.
The haemodynamic dose-response effects of intravenous oxprenolol over the range of 2--64 mg were measured in 28 patients with coronary heart disease. At rest there were statistically significant dose-response trends, linear or quadratic, between the cumulative doses of oxprenolol and reductions in systolic pressure, heart rate, and cardiac output and increases in stroke volume and pulmonary wedge pressure. The magnitude of the changes was uninfluenced by the degree of left ventricular functional disability as judged by the level of the pulmonary wedge pressure. During dynamic exercise the haemodynamic changes induced by oxprenolol were significantly greater in patients with more marked left ventricular disability than in those less severely affected. These observations define the immediate effects of intravenous oxprenolol over a relatively wide dose range and confirm its relative haemodynamic safety in patients with stable coronary heart disease.
Adult↗
Influence of nicardipine on the blood pressure at rest and on the pressor responses to cold, isometric exertion, and dynamic exercise in hypertensive patients.
The dose-response effects of a new slow-calcium-channel blocker, nicardipine, on the resting blood pressure and on the pressor responses induced by skin cold, isometric exertion, and dynamic exercise were examined in a single-blind placebo-controlled study in six male patients with stable uncomplicated essential hypertension. Nicardipine was administered orally in doses of 5 mg, 10 mg, 20 mg, and 20 mg each given three times daily consecutively for 1 week. At the end of each dose period the effects on blood pressure and heart rate at rest and during the three pressor stimuli were measured. There was a significant dose-related reduction in the resting diastolic blood pressure without change in pulse pressure, accompanied by an increase in heart rate. No postural effects on blood pressure were observed. There was a small reduction in the pressor response to hand cold, which was statistically significant at the higher doses. There was no attenuation of the increases in pressure and heart rate induced by handgrip contraction or submaximal treadmill walking at any dose of nicardipine. These results are compatible with direct relaxing effect of the drug on the smooth muscle of the arteriolar resistance vessels without substantial impairment of the sympathetic influences responsible for postural control of the systemic blood pressure or those involved in the pressor responses to the three stimuli tested.
Adult↗
alpha- and beta-blockade with labetalol in acute myocardial infarction.
On the hypothesis that the addition of alpha-blockade would mitigate the haemodynamic disadvantages of beta-blockade alone in the early stages of uncomplicated acute myocardial infarction, 15 patients were studied during the intravenous infusion of labetalol (0.5 mg/kg/h). The mean systemic arterial pressure was reduced by an average of 15 mm Hg. In the nine patients haemodynamically evaluated, the cardiac output (thermal dilution) was reduced without change in the heart rate or left heart filling pressure (pulmonary artery occluded pressure); left ventricular stroke work was significantly decreased. The reduction in these major determinants of myocardial oxygen consumption suggests that the combination of alpha- and beta-blockade may be haemodynamically advantageous in normotensive patients in the early stages of uncomplicated acute myocardial infarction.
Adrenergic alpha-Antagonists↗
Arteriolar or venous dilatation in left ventricular failure following acute myocardial infarction: a haemodynamic trial of hydralazine and isosorbide dinitrate.
We undertook a randomised between-group comparison of the haemodynamic effects of arteriolar dilatation and venodilatation in 20 males, following acute myocardial infarction, with persisting left ventricular failure after pretreatment with intravenous frusemide. All had radiographic pulmonary oedema and a pulmonary artery occluded pressure (PAOP) exceeding 15 mm Hg. The average cardiothoracic ratio was 52% (range 48-65%). Following control haemodynamic measurements, 10 patients received intravenous hydralazine (0.15 mg/kg) and 10 received intravenous isosorbide dinitrate infusion (50-200 micrograms/kg/h). Subsequent measurements were made at 30, 60, and 90 min. Isosorbide dinitrate reduced the PAOP by 3 mm Hg (p less than 0.01) and the mean systemic arterial pressure by 9 mm Hg (p less than 0.05) without significant change in the heart rate, cardiac output, or systemic vascular resistance. In contrast, hydralazine reduced the PAOP and systemic arterial pressure by a similar amount, but this was accompanied by a reduction in the systemic vascular resistance (p less than 0.01) and an increase in the cardiac output (p less than 0.01), heart rate (p less than 0.01), and stroke volume (p less than 0.01). This randomised study defines the contrasting haemodynamic results of arteriolar dilatation and venodilation in patients with resistant left ventricular failure following acute myocardial infarction. The different pharmacodynamic effects of these two methods of circulatory manipulation suggest that they are not mutually exclusive and together may offer therapeutic advantages.
Aged↗
A randomised study of the haemodynamic changes induced by venodilatation and arteriolar dilatation singly and together in left ventricular failure complicating acute myocardial infarction.
A randomised between-group study of the immediate haemodynamic effects of venodilatation by intravenous isosorbide dinitrate infusion (50-200 micrograms/kg/h) and arteriolar dilatation by intravenous hydralazine bolus (0.15 mg/kg) given either in random sequence (Groups 1 and 2; n = 12) or simultaneously (Group 3; n = 6) was undertaken in 18 men with radiographic and haemodynamic evidence (left ventricular [LV] filling pressure greater than 20 mm Hg) of LV failure 6-19 h following acute myocardial infarction. Control measurements (1 h) preceded either two consecutive 90-min treatment periods (Groups 1 and 2) or a single 90-min period (Group 3). Given independently, both drugs reduced systemic arterial pressure and vascular resistance, whereas only isosorbide dinitrate reduced LV filling pressure and only hydralazine increased cardiac output and stroke volume. Isosorbide dinitrate/hydralazine in combination significantly reduced LV filling pressure, systolic and diastolic arterial pressure, and total systemic vascular resistance. Cardiac output, stroke volume, and heart rate were increased. In conclusion, combined arteriolar dilatation and venodilatation appears to be of greater haemodynamic benefit than either alone, if the fall in mean systemic pressure does not compromise peripheral perfusion.
Adult↗
Alpha-beta blockade, left ventricular filling pressure and cardiac preload.
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Adrenergic alpha-Antagonists↗
Cardioselective beta-blockade with atenolol and acebutolol following acute myocardial infarction: a multiple-dose haemodynamic comparison.
In patients with acute myocardial infarction the haemodynamic relevance of the ancillary pharmacological properties of cardioselectivity and of intrinsic sympathomimetic activity (ISA) possessed by beta-blocking drugs is unclear. The dose-response effects of atenolol and acebutolol, two cardioselective compounds, the latter also possessing a degree of ISA, were therefore compared in a single-blind, dose-response, crossover study in patients within 18 h of suffering an uncomplicated acute myocardial infarction. The logarithmic cumulative dosage schedule achieved plasma concentrations in the clinical therapeutic ranges for both atenolol (0.05 +/- 0.04-0.19 +/- 0.03 micrograms/ml) and acebutolol (0.22 +/- 0.14-0.8 +/- 0.29 micrograms/ml). Incremental doses of intravenous atenolol (cumulative, 1-8 mg) resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Pulmonary artery occluded pressure (p less than 0.05) and systemic vascular resistance (p less than 0.01) increased. Incremental doses of intravenous acebutolol (cumulative, 10-80 mg) also resulted in significant decreases in systolic blood pressure, heart rate, cardiac output, stroke volume, and stroke work index (p less than 0.01 for each). Systemic vascular resistance increased (p less than 0.01); there was no consistent change in the pulmonary artery occluded pressure. Within the limits of the experimental protocol, the additional property of ISA possessed by acebutolol resulted in no statistically significant haemodynamic differences from atenolol. This may reflect either an insufficient degree of ISA possessed by acebutolol to confirm the original hypothesis, or its haemodynamic irrelevance in the presence of the increased sympathetic tone that is frequently present following acute myocardial infarction.
Acebutolol↗
Haemodynamic advantages of a combined inotropic/venodilator regimen over inotropic monotherapy in acute heart failure.
The haemodynamic influence of positive inotropic therapy with dobutamine, both alone and when combined with isosorbide dinitrate, was evaluated in 10 consecutive patients admitted to Coronary Care with acute left ventricular failure (pulmonary artery occluded pressure greater than 20 mm Hg) complicating myocardial infarction. Dobutamine increased systemic arterial blood pressure and heart rate without reduction in the left heart filling pressure; cardiac index (+0.9 L/min/m2; p less than 0.01) was substantially increased. Thus, consequent on these effects, dobutamine could increase myocardial oxygen requirements. The addition of intravenous isosorbide dinitrate reduced systemic arterial pressure and left heart filling pressure; the augmented cardiac index following therapy with dobutamine alone was maintained. Combined dobutamine/nitrate therapy, therefore, appeared haemodynamically superior to dobutamine monotherapy, in that it improved cardiac stroke volume at a normalised left ventricular filling pressure. These data suggest that combined dobutamine/nitrate therapy may prove useful as an adjunct to the treatment of normotensive heart failure complicating acute myocardial infarction.
Adult↗
Haemodynamic dose-response effects of intravenous amrinone in left ventricular failure complicating acute myocardial infarction.
The haemodynamic dose-response effects of intravenous amrinone were measured in 16 male patients, aged 40-65 years, with radiographic and haemodynamic evidence of left ventricular failure 4-18 h after acute myocardial infarction. After a l-h control period to confirm stable haemodynamic baseline variables, patients were randomised to either low-dose (200-400-800 micrograms/kg/h) or high-dose (800-1600-3200 micrograms/kg/h) intravenous amrinone. Each of the three infusions was given consecutively over 30 min (total infusion time 90 min) in each group, and haemodynamic measurements were made at the end of each infusion step. No arrhythmias or other untoward side effects, including haematological changes, were observed during the infusions. In both groups, intravenous amrinone reduced the pulmonary artery-occluded pressure (PAOP) (p less than 0.01), increased the cardiac output (p less than 0.05), and reduced the systemic vascular resistance (p less than 0.05). The reductions in PAOP and systemic arterial diastolic pressure and the increase in heart rate were directly dose-related, but the changes in cardiac output and systemic vascular resistance were not. These results suggest that peripheral vasodilation, particularly of venous capacitance vessels, as well as positive inotropic stimulation, may play a role in the haemodynamic changes induced by intravenous amrinone in acute ischaemic left ventricular failure.
Adult↗
Systemic lupus erythematosus: renal involvement and prognosis.
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Adolescent↗
Haemodynamic effects of selective alpha 1-blockade (trimazosin) in essential hypertension.
As a preliminary to a larger clinical trial, the haemodynamic effects of the selective alpha 1-adrenoceptor antagonist trimazosin were studied at rest and during bicycle exercise in the upright position in 14 patients with uncomplicated, stable essential hypertension. Rest and exercise studies before the drug was given revealed no evidence of left ventricular pumping deficiency. A single intravenous bolus of trimazosin (2 mg/kg) resulted in a plasma concentration of 13.1 +/- 1.0 mg/ml 30 min after injection. This plasma concentration of trimazosin was associated with a reduction in the systemic vascular resistance (p less than 0.01); in the absence of any increase in the cardiac output, this resulted in a fall in the systemic blood pressure (p less than 0.01) at rest. Heart rate and left heart filling pressure were unchanged. During 4 min of upright dynamic exercise after drug, the increment in systemic blood pressure was similar to that in the control study; i.e., the absolute level of pressure was reduced (p less than 0.01). The increases in heart rate, cardiac output, and left heart filling pressure during exercise were also unchanged after drug compared with those measured in the control study. The left heart filling pressure and cardiac output were slower to increase at the onset of exercise after trimazosin, which may imply a degree of venodilatation. There were no hypotensive symptoms or large falls in blood pressure after trimazosin at rest, but following 4 min of submaximal upright bicycle exercise, three of the 14 patients developed postural hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗