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Biomedical subjects

B Silke

Publications and source records attributed to B Silke.

At least 19 recordsLinked to original sources
PubMed2006

Adrenoceptor blockade alters plasma gelatinase activity in patients with heart failure and MMP-9 promoter activity in a human cell line (ECV304).

This study assessed the effects of short-term adrenoceptor blockade on plasma matrix metalloproteinase (MMP) activity in patients with heart failure, and the ability of adrenoceptor stimulation to modulate matrix metalloproteinase-9 (MMP-9) promoter activity in vitro. Patients with heart failure received standard therapy or standard therapy plus carvedilol. Plasma MMP activity was determined by zymography and tissue inhibitor (TIMP-1) expression was measured by immunoblotting. MMP-9 promoter activity was assessed in transfected ECV304 cells following exposure to isoprenaline or phenylephrine in the absence or presence of either propranolol or prazosin. In patients with heart failure, carvedilol attenuated the increase in proMMP-9 activity observed at 4 and 12 weeks in non-beta-blocker-treated patients (44.0 +/- 4.9 AU versus 60.8 +/- 6.7 AU; P < 0.05). Although TIMP-1 expression was unaltered, the MMP-9:TIMP-1 ratio was lower in those receiving carvedilol at 4 and 12 weeks (0.54 +/- 0.07 versus 1.04 +/- 0.17; P < 0.05). Isoprenaline transiently increased MMP-9 promoter activity after 4 h exposure (80.6 +/- 14.8-fold; P < 0.001) before returning to baseline. The response to isoprenaline was prevented by propranolol (P < 0.01). Phenylephrine caused a biphasic increase in MMP-9 promoter activity, with the greatest increase occurring at 24 h (23 +/- 3.7-fold) compared to baseline. This response was unaffected by co-incubation with prazosin. In conclusion, treatment with a mixed alpha1/beta-adrenoceptor antagonist attenuates MMP activity and tips the degradative balance to a less degradative phenotype in heart failure patients. Furthermore, adrenoceptor stimulation increases MMP-9 promoter activity, which is inhibited by beta- but not alpha-adrenoceptor blockade. Therefore, mixed adrenoceptor blockade may reduce remodeling in heart failure as a direct consequence of a beta-adrenoceptor-mediated reduction in MMP-9 transcription.

Adrenergic alpha-Antagonists↗
PubMed2006

Emergency department census of patients awaiting admission following reorganisation of an admissions process.

OBJECTIVES: To determine the impact of reorganisation of an acute admissions process on numbers of people in the emergency department (ED) awaiting admission to a hospital bed in a major teaching hospital. METHODS: We studied all emergency medical patients admitted to St James' Hospital, Dublin, between 1 January 2002 and 31 December 2004. In 2002, patients were admitted to a variety of wards from the ED when a hospital bed became available. In 2003, two centrally located wards were reconfigured to function as an acute medical admissions unit (AMAU) (bed capacity 59), and all emergency patients were admitted directly to this unit from the ED (average 15 admissions per day). The maximum permitted length of stay on the AMAU was 5 days. We recorded the number of patients in the ED, who were awaiting the availability of a hospital bed, at 0700 and 1700 on the days of recording during the 36 month study period. RESULTS: The impact of the AMAU reduced overall hospital length of stay from 7 days in 2002 to 5 days in 2003 and 2004 (p<0.0001). The median number of patients waiting in the ED for a hospital bed reduced from 14 in 2002 to 9 in 2003 and 8 in 2004 (p<0.0001). While age and sex of patients did not differ over the years, the factors that independently contributed to the number of patients awaiting admission were the day of the week, the month of the year, and and the extent of the comorbidity index on the previous day's intake (p<0.0001). CONCLUSIONS: This study found that reorganisation of a system for acute medical admissions can significantly impact on the number of patients awaiting admission to a hospital bed, and allow an ED to operate efficiently and at a level of risk acceptable to patients.

Adult↗
PubMed2005

Impact of an acute medical admission unit on length of hospital stay, and emergency department 'wait times'.

BACKGROUND: While many UK hospitals have introduced an acute medical admissions unit (AMAU) to facilitate an efficient emergency admission process and reduce length of hospital stay (LOS), there is a lack of such data in the Republic of Ireland. AIM: To determine the impact of an AMAU on emergency department (ED) wait times for a hospital bed, consultant practice, and LOS. DESIGN: Retrospective analysis of data recorded in the hospital in-patient enquiry (HIPE) system. METHODS: We studied all emergency medical patients admitted to St James' Hospital Dublin between 1 January 2002 and 31 December 2003. In 2002, patients were admitted directly to a variety of wards, many of which were not affiliated with a medical specialty, under the care of a named consultant physician. In 2003, two centrally located wards were re-configured to function as an AMAU, and all emergency patients were admitted to this unit. RESULTS: For all physician teams, median LOS shortened significantly from 2002 to 2003 (6 vs. 5 days, p<0.0001). Overall, patients seen by general physicians had a shorter LOS (5 days) than that of those seen by sub-specialists (6 days) (p<0.0001). The number of patients waiting in the ED for a hospital bed was reduced by 30% from 2002 to 2003 (p<0.001). Extrapolated cost savings for the hospital with the introduction of the AMAU were estimated at approximately 4039 bed-days and 1 714 152. DISCUSSION: Introduction of the AMAU speeded access to acute medical service and reduced costs.

Adult↗
PubMed2005

Do consultants differ? Inferences drawn from hospital in-patient enquiry (HIPE) discharge coding at an Irish teaching hospital.

OBJECTIVE: To find out if there was a difference between hospital consultants, all trained in acute general medicine, in length of stay (LOS), re-admission rates, resource utilisation, and diagnostic coding, among patients admitted as emergencies to St James' Hospital (SJH) Dublin. METHODS: A retrospective analysis was performed of data on discharges from hospital, recorded in the hospital in-patient enquiry (HIPE) system, relating to 9204 episodes among 6968 emergency medical patients admitted to SJH between 1 January 2002 and 31 October 2003. For comparative analysis, four physician groups were defined consisting of gastroenterology (GI, n = 4), respiratory (n = 3), general internal medicine (GIM, n = 2), or specialty (n = 5). RESULTS: GIM consultants had the shortest LOS (median 5 days); GIM and respiratory consultants were less likely to have long stay patients (> 30 days, p<0.0001). Patients re-admitted under the same consultant had a longer LOS than those re-admitted under a different consultant (p<0.0001). Endoscopy and GI radiology investigations were used most by GI consultants, computed tomography of the thorax by respiratory, ECHO by respiratory and specialty, and computed tomography of brain by GIM and specialty consultants. GI diagnostic codings were more frequent with GI consultants (p<0.0001), respiratory diagnoses and malignancy with respiratory (p<0.0001 for both), diabetes and hypertension with specialty (p = 0.0017), and heart failure more with GIM consultants (p = 0.001). CONCLUSIONS: This study found that the HIPE database was very powerful in predicting differences between hospital consultants in LOS, re-admission rates, resource utilisation, and disease coding. It would be of interest to examine the extent to which protocols and guidelines could reduce such variations.

Consultants↗
PubMed2004

Patient and disease profile of emergency medical readmissions to an Irish teaching hospital.

OBJECTIVE: To determine whether there was a relationship between coded diseases at the time of hospital discharge, a pattern of ordering investigations, and hospital readmission in a major teaching hospital. DESIGN: Systematic review of data relating to emergency medical patients admitted to St James' Hospital Dublin between 1 January and 31 December 2002. DATA SOURCES AND METHODS: Data on discharges from hospital recorded in the Hospital In-Patient Enquiry (HIPE) system. The value of HIPE data in describing the relationship between the pattern of resource utilisation, diagnostic related groups, and hospital readmission has not previously been examined. RESULTS: Of 5038 episodes recorded among 4050 patients admitted, the number of readmissions was up to 15. Age and male gender were factors associated with readmission, and readmitted patients remained in hospital for longer. No particular test request predicted readmission, but computed tomography of the brain was associated with a reduced readmission rate. Discharge diagnostic related group coding at first discharge predicted readmission-codes related to heart failure, respiratory system, alcohol, malignancy, and anaemia. CONCLUSIONS: It was found that clinical coding using the HIPE database strongly predicted hospital readmission. It may be argued that early hospital readmission reflects unsatisfactory patient care, alternatively that many readmissions are not preventable, representing either new events in elderly patients with chronic illnesses and frequent co-morbidity or related to social factors. The utility of specific interventions, in patients at high risk for hospital readmission, could be explored.

Adult↗
PubMed2004

Resource utilisation, length of hospital stay, and pattern of investigation during acute medical hospital admission.

OBJECTIVES: To describe the patient demographic characteristics and organisational factors that influence length of stay (LOS) among emergency medical admissions. Also, to describe differences in investigation practice among consultant physicians and to examine the impact of these on LOS. DESIGN: Prospective observational study. SETTING: General medicine department of a teaching hospital in Belfast, UK. PARTICIPANTS: Data were recorded for patients who were admitted as emergencies and reviewed on the post-take ward rounds (PTWR) attended by the investigation coordinator. OUTCOME MEASURES: Non-laboratory investigations requested, LOS, and diagnosis on discharge. RESULTS: Of 830 episodes evaluated, the median LOS was 7 days (interquartile range 3-12 days); this was significantly longer for admissions on Fridays (p = 0.0011) and for patients managed on medical wards (p<0.0001). There was a positive correlation between patient age and LOS (r = 0.32, p<0.0001). Chest radiographs (p = 0.002) and echocardiography (p = 0.015) were associated with a prolonged LOS; no investigations were associated with a shortened LOS. Diagnoses of congestive heart failure, respiratory disease, and cancer were associated with a longer LOS; a diagnosis of angina was associated with a shorter LOS. Considerable variation in investigation ordering, but no difference in LOS, was observed between consultants. High use of a given medical test did not correlate with high use of other tests. CONCLUSION: A systematic means of dealing with the NHS resource crisis should include an improved organisational strategy as well as social care provision. A more unified approach to investigation practice should also have a sparing effect on resources.

Acute Disease↗
PubMed2004

Length of hospital stay, diagnoses and pattern of investigation following emergency admission to an Irish teaching hospital.

Data on discharges from acute public hospitals in Ireland is recorded in the hospital in-patient enquiry (HIPE) system; its value in describing the casemix and pattern of resource utilization following emergency medical admissions has not been examined. We wished to determine whether there was a relationship between coded diseases at the time of discharge, patterns of investigation, and length of hospital stay (LOS) in a major teaching hospital. Data relating to emergency medical patients admitted to St James' Hospital Dublin between 1st January and 31st December 2002 was recorded. Of 5038 episodes evaluated, the median LOS was 6 days (IQR 3-13); this was significantly shorter when the patient was admitted under a general medical service (p<0.0001). There was also a positive correlation between patient age and LOS (r = 0.32; p<0.0001). No test request was associated with a shortened LOS. Prolonged LOS was associated with oesophago-gastro-duodenoscopy, echocardiography, computerised tomography, magnetic resonance imaging, and abdominal ultrasonography testing. Furthermore, prolonged LOS was associated with the following disease related groups (DRG) at discharge; codes related to heart failure, respiratory system, malignancy, stroke, diabetes, psychiatry, and anaemia. We found that clinical coding using the HIPE database strongly predicted hospital LOS for acute general medical admissions. Spare bed capacity is essential if an acute hospital is to operate efficiently and at a level of risk acceptable to patients. Therefore, determining major influences on hospital LOS is valuable, to develop potential strategies to optimise efficient utilization of acute bed capacity.

Adult↗
PubMed2003

Central and peripheral haemodynamic effects of L-NAME infusion in healthy volunteers.

AIMS: To evaluate the effects of the intravenous administration of the nitric oxide synthesis inhibitor N(g)nitro-L-arginine methyl ester (L-NAME) in healthy volunteers. METHODS: L-NAME (0.25, 0.5 and 0.75 mg/kg over 8 min) was infused in 13 healthy male volunteers. Finally, subjects were infused with either L- or D-arginine. RESULTS: L-NAME resulted in dose-dependent falls in heart rate 60 bpm (55-64 bpm) to 49 bpm (46-52 bpm) (P<0.01) and increased mean arterial pressure 77.0 mmHg (73.2-80.8 mmHg) to 90.0 mmHg (87.1-92.8 mmHg) (P<0.01). The cardiac output was significantly reduced after each L-NAME infusion, and systemic vascular resistance increased linearly over the dosage range. Cardiac stroke volume was significantly reduced only following 0.75 mg/kg/min L-NAME: from 100 ml (91.3-108.7 ml) to 83 ml (74.7-91.4 ml); P<0.01. Forearm blood flow was unchanged at any dosage. L-arginine but not D-arginine infusion reversed the haemodynamic effects of L-NAME. CONCLUSIONS: Contrasting with the profound dose-dependent effects of L-NAME had significant effects on central haemodynamics but no discernible effects on peripheral blood flow.

Dose-Response Relationship, Drug↗
PubMed2002

Early vascular abnormalities and de novo nitrate tolerance in diabetes mellitus.

OBJECTIVE: The haemodynamic consequence of altered mechanical wall properties in diabetes can impair the compliance characteristics or pulsatile function of arteries before changes in calibre or peripheral resistance become evident. We studied the sensitivity of pulsatile and steady-state haemodynamic variables in identifying vascular abnormalities and assessing arterial responsiveness to glyceryl trinitrate (GTN) in patients with diabetes, free from clinical complications of the disease. METHODS: Radial artery pressure waveforms were recorded in 22 patients with diabetes and 22 age- and sex-matched control subjects, using a calibrated tonometer device. A computer-based assessment of the diastolic pressure decay was used to quantify changes in arterial waveform morphology in terms of pulsatile (arterial compliance) and steady-state (peripheral resistance) haemodynamics. Pressure pulse waveforms were recorded before and 3, 6 and 9 min after the administration of 300 micro g of GTN. RESULTS: Of the pulsatile and steady-state impedance parameters, only small artery compliance was significantly different in patients, 4.7 ml/mmHg (95% CI 3.8-5.8), compared with control subjects 7.1 ml/mmHg (95% CI 5.4-8.7); (p < 0.05). In response to GTN small artery compliance increased, and systemic vascular resistance decreased significantly in control subjects; (p < 0.05) but remained unchanged in patients with diabetes. CONCLUSIONS: Arterial waveform analysis proved more sensitive in detecting early vascular abnormalities and tracking the haemodynamic effects of GTN in patients with diabetes than changes in total peripheral resistance. The diminished responsiveness of the arterial vasculature to organic nitrates may have therapeutic implications for the treatment of cardiovascular disease in diabetes mellitus.

Adult↗
PubMed2002

The potential cardiotoxicity of antipsychotic drugs as assessed by heart rate variability.

Most antipsychotic drugs have cardiac effects as a consequence of their pharmacological actions. Recently, thioridazine has been subjected to a restricted indications notice and sertindole had its license withdrawn because of concerns about their potential cardiotoxicity. In the development of new atypical agents, heart-rate corrected QT effects are evaluated but it is unclear how predictive these are of clinically significant cardiotoxicity or sudden death. Heart rate variability (HRV) is a potential index of cardiotoxicity which has been found to be decreased following antidepressants and clozapine. We studied acute HRV changes following antipsychotic agents. Sixteen healthy male volunteers received risperidone (4 mg), olanzapine (10 mg), thioridazine (50 mg) or placebo in a randomized cross-over design. Subjective effects and psychomotor function were assayed at 2 h and both linear (summary statistics) and non-linear (scatterplot) measures of HRV were evaluated by continuous electrocardiogram recording over 10 h. Differential effects of single doses of the three antipsychotic drugs on HRV were found, and these were independent of their sedative effects. Olanzapine increased, and thioridazine decreased HRV, while risperidone had no effect. HRV is sensitive to the acute effects of antipsychotics. It may prove to be a reliable index of their potential for cardiotoxicity. Further studies in both healthy volunteers and patients on antipsychotic medication will be valuable.

Adult↗
PubMed2001

Breath isoprene in patients with heart failure.

BACKGROUND: Chronic heart failure (CHF) is characterised by increased vascular resistance. This increased after load on the left ventricle contributes to the vicious cycle that leads to progression of myocardial failure, multiple organ failure and death. There is evidence for increased oxidative stress in heart failure, which will influence the myocardium but also peripheral vasculature endothelium. AIMS: The aim of the present study was to examine the production of isoprene, reputed to reflect oxidative stress, in patients with CHF compared to control subjects. METHODS: Twelve patients with CHF and thirty-one healthy control subjects free from heart disease were studied. Breath was collected via a two-way non-re-breathing valve into a 60-l gas collection bag. A sample of ambient air was collected at the same time. A measured aliquot of patient breath and ambient air (approx. 1.5 l) was adsorbed onto a gas adsorption tube packed with poropak-Q. Isoprene was measured using GC/MS and the production rate calculated. All samples of breath were collected at 10.00 h after subjects had been sitting at rest for 15 min. RESULTS: Breath isoprene production in subjects with CHF was significantly reduced compared to controls 83(23) vs. 168(20) pmol min(-1) kg(-1). CONCLUSION: Breath isoprene does not directly reflect oxidative stress in CHF.

Adult↗
PubMed2001

Myocardial expression of the endothelin system in endotoxin-treated rats.

Although circulating plasma levels of endothelin (ET)-1 are elevated in endotoxemia, little is known about the myocardial expression of the ET system in endotoxic shock. We assessed the temporal mRNA expression pattern of key components of the ET system (pre-pro ET (ppET) -1, -2, ET-converting enzyme-1, ET(A) and ET(B) receptors) by reverse transcription polymerase chain reaction in a rat model of early endotoxic shock. Lipopolysaccharide (5 mg/kg, i.p.) caused a transient increase (p < 0.05) in inducible nitric oxide synthase mRNA expression. ppET-1 mRNA expression was increased at 2 h (approximately 12-fold increase; p < 0.05) in the lipopolysaccharide compared with the saline group and ppET-2 mRNA expression was unaltered. ET-converting enzyme-1, ET(A), and ET(B) receptor mRNA expression was unaltered in the lipopolysaccharide compared with the saline group. While ppET-1 mRNA expression is selectively upregulated in ventricular myocardium of lipopolysaccharide-treated rats, an absence of alteration in ET-converting enzyme-1 mRNA expression suggests an excess capacity of ET-converting enzyme-1 to cope with the increased expression of ET-1. At the level of the receptor, endotoxic shock did not affect the expression of either ET(A) or ET(B) receptor mRNA. These data are consistent with the increased expression of myocardial ET-1 as an acute-phase response due to hemodynamic instability associated with the early stages of endotoxic shock.

Animals↗
PubMed2001

A survey of the dose of ACE inhibitors prescribed by general physicians for patients with heart failure.

AIM: To describe the pattern of angiotensin converting enzyme (ACE) inhibitor doses prescribed by general physicians for patients with chronic heart failure and to review the current evidence favouring the use of higher doses. DESIGN: A retrospective survey of the medications of 125 patients with chronic heart failure (in both inpatient and outpatient settings) was carried out between December 1999 and February 2000. RESULTS: Altogether 18.4% of patients surveyed were receiving no ACE inhibitor, the majority of these (65%) having a contraindication to such an agent. Of those patients who were prescribed an ACE inhibitor, 65% were receiving a high dose. The majority of patients who were prescribed a low dose of ACE inhibitor had no identifiable contraindication to receiving a higher dose. Of all patients with chronic heart failure studied, 25% were receiving either no ACE inhibitor or only a low dose in the absence of contraindication. CONCLUSION: Since no objectively measurable variable has been shown to share a clear relationship with the outcome benefits of ACE inhibitors, no convenient and reliable assessment exists for determining when an adequate dose has been reached for each patient. There is an abundance of evidence favouring high dose ACE inhibitors in heart failure; evidence for the role of low doses is much less clear. The fact that only half of the patients with chronic heart failure were found to be receiving a high dose of ACE inhibitor is probably testimony to inaccurate perceptions and unreliable assumptions among physicians. It is likely that a change in current prescribing patterns would benefit patients with chronic heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Nitric oxide modulation of blood vessel tone identified by arterial waveform analysis.

Traditionally, nitric oxide-mediated alteration in blood vessel tone has been inferred from changes in flow in response to physical and pharmacological interventions using plethysmographic or ultrasonic techniques. We hypothesized that alteration in pulsatile arterial function may represent a more sensitive measure to detect and monitor nitric oxide-mediated modulation of arterial smooth muscle tone. Healthy male volunteers (n = 15) had radial artery pressure pulse waveforms recorded using a calibrated tonometer device. A computer-based assessment of the diastolic pressure decay was employed to quantify changes in arterial waveform morphology in terms of altered pulsatile (arterial compliance) and steady-state (peripheral resistance) haemodynamics. N(G)-nitro-L-arginine methyl ester (L-NAME), a stereospecific inhibitor of nitric oxide synthesis, was infused intravenously in incrementally increasing doses of 0.25, 0.5 and 0.75 mg/kg for 8 min each. Subjects then received either L-arginine or D-arginine (200 mg/kg over 15 min) intravenously in a blinded fashion. On a separate day, subjects had radial artery pressure pulse waveforms recorded before and after the sublingual administration of glyceryl trinitrate, an exogenous donor of nitric oxide. Cardiac output and heart rate decreased and mean arterial blood pressure increased significantly (P < 0.01 for all) in response to the incremental intravenous infusion of L-NAME. Small artery compliance decreased, whereas systemic vascular resistance increased in response to nitric oxide synthesis inhibition (P < 0.01 for both). The intravenous infusion of L-arginine restored the pulsatile and steady-state haemodynamic parameters to pre-treatment values, whereas D-arginine had no effect. Sublingual glyceryl trinitrate decreased systemic vascular resistance by 11%, whereas large artery- and small artery-compliance increased by 25% and 44% respectively. Pressure pulse contour analysis represents a sensitive and convenient technique capable of tracking changes in the pulsatile function of arteries accompanying nitric oxide-mediated alteration in arterial smooth muscle tone.

Adult↗
PubMed2001

Individuals with cystic fibrosis do not display impaired endothelial function or evidence of oxidative damage in endothelial cells exposed to serum.

Heightened systemic oxidative stress is increasingly recognized as a feature of cystic fibrosis (CF). The consequences of long-term exposure to free radical attack include a predisposition to diseases such as cancer and atherosclerosis. An increased incidence of malignancy among adult patients with CF has been reported, but the absence of atherosclerotic disease is well described. The aim of the present study was to assess endothelial function in vivo and relate this to the potential of serum from patients with CF to induce oxidative-mediated damage in cultured human endothelial cells. A group of 11 CF patients was matched with a group of healthy volunteers with regard to age and sex. Endothelial function was assessed as endothelium-dependent and -independent vasodilation by measuring forearm blood flow in response to infused acetylcholine and sodium nitroprusside respectively. Confluent monolayers of cultured human endothelial cells were exposed to serum from CF patients and control subjects. Following exposure, cell death was assessed by lactate dehydrogenase release, and the degree of lipid peroxidation in the membrane was assessed by measuring the content of lipid hydroperoxides, malondialdehyde and 4-hydroxynonenal. Endothelial monolayers exposed to serum from CF patients released significantly less lactate dehydrogenase following exposure than those exposed to serum from healthy controls (1.8% and 3.0% respectively; mean difference -1.2%; 95% confidence intervals -1.9% to -0.1%; P<0.05) and contained significantly less 4-hydroxynonenal (0.75 and 3.41 micromol/g of protein respectively; mean difference -2.66 micromol/g; 95% confidence intervals -5.10 to -0.22 micromol/g; P<0.05). There was no significant difference between patients and controls in the extent of serum-induced membrane peroxidation, as assessed by malondialdehyde or lipid hydroperoxides, or in endothelial function, as assessed by forearm blood flow. In conclusion, despite evidence for heightened systemic oxidative stress in CF, patients displayed no impairment of endothelial function, and their serum caused significantly less damage to human endothelial cells than that from matched controls.

Adolescent↗
PubMed2001

Spironolactone prescribing in heart failure: comparison between general medical patients and those attending a specialist left ventricular dysfunction clinic.

We compared the rate of prescription of low-dose spironolactone among patients with heart failure in a general medical inpatient setting and in a specialist left ventricular (LV) dysfunction clinic. 38% of general medical patients and 72% of patients attending the specialist clinic had been prescribed spironolactone. When contraindications were considered, 54% of patients in the general medical group and 77% of patients in the specialist clinic group were appropriately treated in respect of spironolactone prescribing. Patients attending a specialist LV dysfunction clinic are therefore more likely to be treated with low dose spironolactone, an accepted appropriate treatment for heart failure, than those admitted to general medical and acute geriatric units. Improvement in care for patients with CHF may be achieved either by increasing the use of specialist clinics or by better dissemination of evolving evidence.

Diuretics↗
PubMed2000

Positive effect of bumetanide on contractile activity of ventricular cardiomyocytes.

Although the beneficial effects of loop-diuretics in relieving congestive heart failure and essential hypertension are well established, there has been limited investigation into the direct cardiac effect of these drugs. The aim of the present study was to investigate mechanical and electrophysiological effects of three loop-diuretics, namely, frusemide, bumetanide and torasemide, in ventricular cardiomyocytes isolated from rabbit myocardium. Contractile performance was assessed using a video edge detection method and effects on L-type Ca(2+) currents were determined using a 'perforated' patch-clamp technique. Unlike frusemide and torasemide, bumetanide produced concentration-dependent (3x10(-8) to 10(-5) M) increases in cell shortening and velocity of cell shortening. Neither frusemide, bumetanide nor torasemide exerted any action on peak Ca(2+) current amplitudes. In summary, the present investigation provides evidence for a direct contractile effect of the loop diuretic, bumetanide, in contrast to absence of effects by frusemide and torasemide, in ventricular cardiomyocytes isolated from rabbit myocardium.

Animals↗