PubMed Health⌕ Search

Biomedical subjects

B Silke

Publications and source records attributed to B Silke.

At least 55 records · Page 3Linked to original sources
PubMed1997

Sources of inaccuracy in the use of the Hawksley random-zero sphygmomanometer.

OBJECTIVE: To identify possible causes of inaccuracy in the use of the Hawksley random-zero sphygmomanometer and methods that could reduce this. METHODS: Four Hawksley random-zero sphygmomanometers were compared with a standard sphygmomanometer under static conditions. Two methods (standard and rapid) were used to release pressure from the inflated cuff with pressures recorded by independent blinded observers. The rate at which the hand valve released pressure was analysed. The effects of varying filling times and pressures on the size of the final zero correction were investigated. RESULTS: The Hawksley devices all under-recorded pressure compared with that measured by using a standard machine. A rapid means of pressure release approximately halved this error in each case. Pressure release through the hand valve was shown to have a characteristic and prolonged exponential decay. Using low filling times and pressures reduced the observed range of zeros seen, with the production of a correlation between the size of the zero and the inflation pressure used. CONCLUSION: These findings suggest that overestimation of the final zero correction is a common and major source of error in the use of the Hawksley sphygmomanometer. A simple change in the design of the final pressure release would improve the machine's reliability in clinical usage. The machine's zero mechanism is susceptible to unintentional misuse. Such misuse could occur when the machine is used in accordance with current sphygmomanometry guidelines.

Equipment Design↗
PubMed1997

Effects of beta-adrenoceptor agonists and antagonists on heart-rate variability in normal subjects assessed using summary statistics and nonlinear procedures.

The influence of celiprolol (beta1- and beta2-adrenoceptor partial agonist), propranolol (beta1- and beta2-adrenoceptor antagonist), and atenolol (beta1-adrenoceptor antagonist) on heart-rate variability (HRV) was assessed from Holter records in 12 normal volunteers. A combination of summary statistics and nonlinear procedures was used to assess HRV and autonomic balance. Under double-blind and randomised conditions (Latin-square design), subjects received placebo, celiprolol (200 and 800 mg), propranolol (160 mg), atenolol (50 mg), and combinations of these agents. Single oral doses of medication (at weekly intervals) were administered at 22:30 h with sleeping heart rates (HRs) recorded overnight. Compared with placebo, celiprolol (200 and 800 mg) increased the sleeping HR, the HR effect of celiprolol was different from the bradycardia after propranolol, 160 mg, and atenolol, 50 mg. Dose-response effects on HR with celiprolol were evident in the presence of atenolol, unlike those with propranolol that abolished the HR increase between celiprolol, 200 mg and 800 mg. These data were consistent with beta1-selective adrenoceptor agonism with 200 mg but agonism at both the beta1- and beta2-adrenoceptor with celiprolol, 800 mg. The action of the drugs on short-term HRV indices (rMSSD and pNN50) closely followed their effects on HR. The longer-term HRV indices (global SD, SDANN) were reduced by celiprolol but increased by propranolol and atenolol. At a fixed HR, the data dispersion (SDNN5) was higher with propranolol compared with celiprolol; however, the dispersion was not merely an HR-dependent phenomenon. A novel nonlinear approach (quadrant analysis) revealed the sequencing of cardiac accelerations and decelerations after the high correlation between adjacent intervals had been removed. Celiprolol increased the frequency of consecutive cardiac accelerations; the duration between and variance of these beat-to-beat differences shortened after celiprolol but lengthened with increased variance after propranolol and atenolol. These results demonstrated reduced HRV indices and a shift toward sympathetic dominance after the beta-adrenoceptor agonist celiprolol contrasting with increased HRV indices and parasympathetic dominance after the beta-adrenoceptor antagonists propranolol and atenolol. The implications of these findings for the treatment of patients with cardiovascular disease warrant further study.

Adrenergic beta-Agonists↗
PubMed1996

Dual effects of endothelin-1 on the L-type Ca2+ current in ventricular cardiomyocytes.

The effects of endothelin-1 on the L-type Ca2+ current were studied in rabbit ventricular cardiomyocytes, using both the 'perforated' and the conventional 'ruptured' whole-cell patch-clamp techniques. Endothelin-1 exerts a dual effect on ventricular cardiomyocytes using experimental conditions which minimize intracellular dialysis; endothelin-1 produced both an increase (10(-9) M) and a decrease (10(-8) M) in the L-type Ca2+ current using the perforated patch-clamp technique. However, using the ruptured patch-clamp technique, endothelin-1 produced a similar decrease in L-type Ca2+ current at 10(-8) M, but no effect was observed at a concentration of 10(-9) M. These effects suggest multiplicity in the receptor-effector coupling mechanism.

Animals↗
PubMed1996

Hemodynamic effects of intravenous elgodipine in coronary artery disease during rest and exercise, and basic pharmacokinetic parameters.

Using an echo-Doppler method (Quantascope), the hemodynamic profile of the calcium channel antagonist elgodipine (64 micrograms/kg, i.v.) was investigated in 22 patients with angina pectoris at rest and during exercise. A placebo control was used. At rest, elgodipine significantly decreased systemic vascular resistance as well as systolic and diastolic blood pressure, while increasing cardiac output and stroke volume. During supine bicycle exercise the constant workload, elgodipine significantly increased cardiac output and stroke volume, and decrease the rate-pressure-product (double product); the exercise systolic blood pressure was decreased without change in the diastolic component. Elgodipine significantly reduced the incidence and severity (self-rated pain score) of exercise-induced anginal systems. Heart rate was not affected by elgodipine, either at rest or during exercise. In particular, no negative inotropy could be inferred from the echo-Doppler data. In the elgodipine plasma concentration profile (HPLC), three phases of elimination with half-life times of less than 1 hour, between 3 and 7 hours, and between 10 and 24 hours may be distinguished, indicating a "shallow" and a "deep" compartment. The hemodynamic data indicate an intermediate pharmacodynamic profile of elgodipine, lying between that of other dihydropyridines and that od compounds such as verapamil or diltiazem.

Adult↗
PubMed1996

Endothelin-1 mediated inhibition of the acetylcholine-activated potassium current from rabbit isolated atrial cardiomyocytes.

1. Endothelin-1 is a 21 amino acid peptide with potent inotropic and chronotropic actions in the heart. Relatively little is known about the underlying electrophysiological effects of the peptide. In this study, the effects of endothelin-1 (ET-1) on the acetylcholine-activated potassium current (IK(ACh) were investigated in the absence and presence of the receptor-selective antagonists, PD155080 (ETA receptor-selective) and RES-701 (ETB receptor-selective) in rabbit atrial cardiomyocytes. 2. Cells were obtained from New Zealand White rabbits (2.5-3 kg) by enzymatic dissociation with collagenase. Potassium currents were recorded, in the presence of nifedipine (5 microM), by use of the whole cell ruptured patch-clamp technique. Following stabilization, control recordings were made with standard pulse protocols, and drugs were applied by a gravity fed microperfusion system. 3. Endothelin-1 (10 nM) alone did not affect the "steady state' potassium current. Acetylcholine (1 microM) increased (P < 0.05) the potassium current to-1321 +/- 290 pA, from a control value of -955 +/- 191 pA, at a step potential of -100 mV. Acetylcholine also increased the holding current at -40 mV from +80 +/- 9 pA to +242 +/- 38 pA, and this effect was abolished (P < 0.05) in the presence of endothelin-1 (+44 +/- 13 pA). The responses to acetylcholine were attributed to activation of the atrial muscarinic-activated potassium current (IK(ACh)) as they were blocked by atropine (10 microM). Endothelin-1 (10 nM) in the presence of acetylcholine did not affect the "steady state' potassium current (-882 +/- 88 pA compared to a control value of -870 +/- 98 pA, at -100 mV). 4. The ETA receptor-selective antagonist, PD155080 (1 microM), prevented (P < 0.05) the ET-1 induced inhibition of IK(ACh) at all potentials. PD155080, in the presence of endothelin-1 and acetylcholine, increased the inward component of the "steady state' potassium current to -1030 +/- 210 pA from a control value of -804 +/- 224 pA at a step potential of -100 mV. Also the outward component was increased at a potential of -20 mV from +90 +/- 17 pA to +241 +/- 47 pA. 5. Unlike PD155080, the ETB receptor-selective antagonist, RES-701 (1 microM), only prevented (P < 0.05) the inhibitory effect of endothelin-1 on the inward component of the IK(ACh); at -100 mV, RES-701, in the presence of endothelin-1 and acetylcholine, increased the "steady state' potassium current to -913 +/- 137 pA from -733 +/- 116 pA. Furthermore, RES-701, in contrast to PD155080, failed to sustain this inhibitory effect as, in the presence of endothelin-1 and acetylcholine, the "steady state' potassium current returned to a value of -768 +/- 96 pA, at a step potential of -100 mV. 6. In conclusion, endothelin-1 clearly inhibits the effects of acetylcholine on IK(ACh) in rabbit atrial cardiomyocytes. This effect is primarily mediated by an ETA receptor-subtype, but is transiently and partially mediated by a RES-701-sensitive ETB receptor subtype. Inhibition of the IK(ACh) may account for the positive chronotropic properties of endothelin-1.

Acetylcholine↗
PubMed1995

Differential effects of phosphodiesterase inhibitors on accumulation of cyclic AMP in isolated ventricular cardiomyocytes.

The intracellular actions of phosphodiesterase (PDE) inhibitors on the accumulation of cyclic nucleotides were studied in isolated ventricular cardiomyocytes from adult Sprague-Dawley rats. Elevated levels of cyclic AMP, due to the effects of selective PDE inhibitors, were detected only when the levels of cyclic nucleotide were enhanced with forskolin (10 microM). The time course for the elevation of cyclic AMP levels was similar for all the PDE inhibitors tested, following the pattern of an initial rise in the first 2-4 min, proceeded by a steady state at 67 +/- 6% of the maximum stimulation. HN-10200 (2-[3-methoxy-5-methylsulfinyl-2-thienyl]-1H-imidazo-[4,5-c]- pyridine hydrochloride), a new imidazopyridine derivative, had a similar concentration-dependent profile to the structurally related compound, sulmazole (AR-L 115 BS, 2-[2-methoxy-4-methylsulfinyl)phenyl]-1H- imidazo-[4,5-b]-pyridine). Both the non-selective inhibitor, 3-isobutyl-1-methylxanthine (IBMX), and the selective PDE IV inhibitor, Ro 20-1724 (4-[(3-butoxy-4-methoxyphenyl)methyl]-2- imidazolidinone), potentiated the forskolin-stimulated levels of cyclic AMP with a much greater efficacy than sulmazole or HN-10200. The concentrations of forskolin required by IBMX, sulmazole and HN-10200 (10(-3) M) to increase levels of cyclic AMP by 4 pmol/mg protein were 3.2 x 10(-6) M, 1.32 x 10(-5) M and 1.46 x 10(-5) M, respectively. Enoximone failed to cause an increase in the levels of cyclic AMP, even when stimulated with maximal concentrations of forskolin. Furthermore, in the presence of forskolin, enoximone attenuated the response of Ro 20-1724 and IBMX in a concentration-dependent manner. Enoximone, similarly to HN-10200, sulmazole, Ro 20-1724 and IBMX did not produce any significant effect on levels of cyclic GMP under elevated conditions in the presence of sodium nitroprusside. The combined action of Ro 20-1724, with either HN-10200, sulmazole, or IBMX (10(-4) M), on intracellular levels of cyclic AMP, was not greater than the response to Ro 20-1724 alone. These data demonstrate the differential actions of PDE III and PDE IV inhibitors in rat ventricular cardiomyocytes. It is suggested that enoximone has a high selectivity for the PDE III isoenzyme so that hydrolysis of cyclic AMP by the PDE IV isoenzyme is not inhibited, in accordance with the lack of increase in cyclic AMP by enoximone in rat cardiomyocytes. HN-10200 and sulmazole, producing small increases in intracellular levels of cyclic AMP, are less selective PDE III inhibitors than enoximone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Felodipine in addition to beta-adrenergic blockade for angina pectoris. a multicentre, randomized, placebo-controlled trial.

The additional efficacy, duration of action and tolerability of felodipine were evaluated in patients with stable angina pectoris and a positive stress test who were already receiving therapy with a beta-adrenergic blocker. One hundred and twenty-eight patients were randomized to double-blind treatment with 5-10 mg felodipine once daily or matching placebo, and were evaluated by serial exercise testing during 12 weeks of treatment. Felodipine at 4 h significantly increased exercise duration assessed after 4 weeks of treatment (increase 34 +/- 65 s vs 18 +/- 71 s in placebo-treated patients; 95% confidence interval 1.01-1.11; P = 0.01), and after 12 weeks of treatment (increase 39 +/- 103 s vs 3 +/- 72 s; 95% confidence interval 1.01-1.16; P = 0.02). The time until onset of exercise-induced anginal pain and time until 1 mm ST depression assessed after 4 weeks of treatment also increased significantly with felodipine compared to placebo. No statistically significant changes in exercise test parameters evaluated 24 h after medication were observed. The addition of felodipine once daily demonstrated a sustained improvement in exercise duration in patients symptomatic despite treatment with a beta-blocker evaluated 4 h after drug intake. At 24 h post dose, no statistically significant effect was observed. Felodipine is well tolerated with a low incidence of side-effects and no adverse effect on quality of life.

Adrenergic beta-Antagonists↗
PubMed1995

Actions of the novel vasodilator, flosequinan, in isolated ventricular cardiomyocytes.

Although the potent vasodilating effect of flosequinan is well characterised, the positive inotropic action reported is more varied and less well understood. We examined the contractile and electrophysiologic effects of flosequinan and its metabolite, BTS 53554, in cardiomyocytes from either adult male Sprague-Dawley rats (200-250 g) or New-Zealand White rabbits (2-2.5 kg) and compared the effects with those of sulmazole and enoximone [selective phosphodiesterase (PDE) III inhibitors], Ro 20-1724 and rolipram (selective PDE IV inhibitors) and 3-isobutyl-1-methylxanthine (IBMX, nonselective PDE inhibitor). Flosequinan and BTS 53554 had positive contractile effects (p < 0.05) in both rat and rabbit ventricular cardiomyocytes only at the maximum concentration (10(-3) M). Differences were noted between species, however. Flosequinan 10(-3) M had a greater contractile effect than BTS 53554 (10(-3) M) in rabbit cardiomyocytes, but not in rat cardiomyocytes. We studied the interaction of flosequinan or the metabolite with other PDE inhibitors in rat cardiomyocytes. Contractile amplitudes were not significantly different with equimolar concentrations (3 x 10(-4) M) of Ro 20-1724, flosequinan, or BTS 53554 alone (15 +/- 6, 18 +/- 4, and 32 +/- 10%, respectively, greater than the mean basal dL value of 7.38 +/- 0.12%, mean +/- SE error). However, the combinations of Ro 20-1724 with flosequinan and Ro 20-1724 with BTS 53554 produced synergistic responses: 71 +/- 10 and 72 +/- 14%, respectively, greater than the mean basal dL value (p < 0.05). In contrast, the combinations of either flosequinan or BTS 53554 with IBMX or sulmazole produced no further increase in contractile amplitude. Neither flosequinan nor BTS 53554 produced any detectable increase in cyclic AMP, whereas significant increases were noted with Ro 20-1724, IBMX, and sulmazole (p < 0.05) in rat cardiomyocytes. Flosequinan increased beating frequency in rat isolated right auricles concentration dependently and was significant over the concentration range of 10(-5)-3 x 10(-4) M; flosequinan 3 x 10(-4) M maximally increased the mean frequency of beating by 35% of the predrug value (255 +/- 15 beats/min). Flosequinan had no effect on resting membrane potential, amplitude, or maximum upstroke velocity in rat isolated left ventricular (LV) papillary muscle, but at the maximum concentration (10(-3) M), flosequinan decreased action potential duration (APD) at 10, 50, and 75% of repolarization (p < 0.05). BTS 53554 produced no changes in AP characteristics over the concentration range of 10(-5)-10(-3) M.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1995

A placebo controlled comparison of the effects of metoprolol and celiprolol on echo-Doppler measurements of cardiovascular function in normal volunteers.

1. This study used a continuous-wave echo-Doppler method (Exerdrop) to investigate the effects of beta-adrenoceptor antagonism and partial agonism on cardiovascular responses at rest and during dynamic exercise. 2. A double-blind, randomised, placebo controlled comparison of metoprolol (50 mg) and celiprolol (200 mg) was undertaken in nine normal volunteers; single oral doses of medication were administered at weekly intervals. Rest and exercise (supine bicycle) haemodynamics were assessed at 0, 2, 4, 6 and 8 h following dosing. 3. Before dosing and after placebo, the aortic flow velocity, acceleration and velocity integral increased progressively during exercise, as did heart rate, blood pressure and cardiac output. 4. Following metoprolol 50 mg, heart rate was significantly reduced without change in systolic or diastolic blood pressure. Echo-Doppler peak acceleration and velocity decreased at rest. On exercise, heart rate and systolic blood pressure fell significantly; the increase in acceleration was significantly blunted compared with placebo (a decrease of 15.2% at rest and 22.9% at 75 watts; P < 0.01 vs placebo). Peak velocity fell significantly by 75 watts exercise. 5. Celiprolol 200 mg at rest significantly increased systolic blood pressure, peak acceleration and velocity. On exercise celiprolol, in contrast to metoprolol, did not reduce peak acceleration or peak velocity; however exercise heart rate and systolic blood pressure were significantly reduced. The difference between celiprolol and metoprolol in respect of peak acceleration persisted over the 8 h of the study. 6. These differences between metoprolol and celiprolol are compatible with the partial agonism of celiprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Evaluation of non-invasive blood pressure measurement by the Finapres method at rest and during dynamic exercise in subjects with cardiovascular insufficiency.

The accuracy and precision of the Finapres in recording rest and exercise blood pressure compared with the intra-arterial (aortic and branchial) and random-zero sphygmomanometer methods was assessed in 84 ischaemic patients in three different studies. Firstly, comparison at rest with the aortic intra-arterial pressure in 50 ischaemic patients demonstrated that the Finapres systolic (136.5 +/- 21.1 vs. 129.3 +/- 19.0 mmHg; p < 0.001) and mean (92.4 +/- 13.4 vs. 90.7 +/- 11.4 mmHg; p < 0.001) arterial pressures were higher and diastolic pressures lower (70.4 +/- 11.5 vs. 71.5 +/- 9.8 mmHg; p < 0.001). The reproducibility of the Finapres and invasive method was similar for systolic (4.6% vs. 4.0%), diastolic (2.8% vs. 2.7%) and mean (3.3% vs. 3.0%) blood pressures. Second, in seven subjects studied twice at rest and during 4 min supine bicycle exercise, the exercise increase in blood pressure was greater on the Finapres compared with the brachial intra-arterial pressure (systolic +10.2 +/- 6.3 vs. +3.6 +/- 9.8 mmHg; diastolic +9.6 +/- 11.1 vs. +0.2 +/- 2.1 mmHg; p = 0.02 for each); however, at steady-state the peak/trough differences in pressure between the methods were similar. Thirdly, compared under rest conditions, to random zero sphygmomanometer (RZO), the Finapres systolic pressure was higher (6.8 +/- 3.5 mmHg) and diastolic pressure lower (-6.0 +/- 1.9 mmHg). During upright bicycle exercise, the difference between the Finapres and RZO in systolic blood pressure increased at each level of exercise (+14.3 +/- 4.2, +17.9 +/- 4.0 and +22.2 +/- 4.1 mmHg respectively at each exercise stage: p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Assessment of ability of levcromakalim and sodium nitroprusside to reverse the cardiovascular effects of nitric oxide synthase inhibition in the anaesthetised pig.

OBJECTIVE: The aim was to test the ability of levcromakalim, a potassium channel opener, and sodium nitroprusside, a nitric oxide donor, to reverse the systemic and pulmonary vasoconstrictor actions of NG-nitro-L-arginine methyl ester (L-NAME), and thus to restore cardiac output in anaesthetised pigs. METHODS: In separate groups of pigs administration of a bolus of L-NAME (10 mg.kg-1) was followed either by no further agent (control group; n = 8) or by increasing bolus doses of levcromakalim (10, 20, and 40 micrograms.kg-1; n = 8) or by increasing infused doses of sodium nitroprusside (1, 2, and 4 micrograms.kg-1.min-1 for 15 min at each dose). The same doses of levcromakalim and sodium nitroprusside were also given to pigs (n = 6 in each group) which had been pretreated with saline rather than L-NAME. The changes in systemic and pulmonary haemodynamic indices and cardiac output as a result of each intervention were measured at each stage and compared between and within drug groups. RESULTS: In each group, the bolus of L-NAME caused increases in systemic vascular resistance, mean arterial pressure, pulmonary vascular resistance, and mean pulmonary artery pressure, and a reduction in cardiac output. These effects were significantly different from pretreatment values at 15 min, and were maintained for at least 60 min when no further agent was given. The subsequent administration of levcromakalim caused significant reductions in systemic vascular resistance and mean arterial pressure, the effects being greater than in animals that had been pretreated with saline rather than L-NAME. Pulmonary vascular resistance and mean pulmonary artery pressure were also reduced, but to a lesser degree. Cardiac output was partially but significantly restored. The subsequent administration of sodium nitroprusside caused significant reductions in systemic vascular resistance, mean arterial pressure, pulmonary vascular resistance, and mean pulmonary artery pressure. These effects were significantly greater than those in animals that had been pretreated with saline rather than L-NAME. Cardiac output was weakly, though significantly restored. CONCLUSIONS: Increased systemic vascular resistance following a bolus of L-NAME (10 mg.kg-1) is reversed by subsequent administration of levcromakalim (10-40 micrograms.kg-1) or sodium nitroprusside (1-4 micrograms.kg-1.min-1) associated with partial restoration of cardiac output. The degree to which cardiac output is restored by these two agents is limited by a concomitant reduction in preload.

Amino Acid Oxidoreductases↗
PubMed1994

Comparison of the ability of nicardipine, theophylline and zaprinast to restore cardiovascular haemodynamics following inhibition of nitric oxide synthesis.

1. The use of pharmacological inhibitors of nitric oxide (NO) synthesis to treat patients with septic shock is limited by the observation that they cause a fall in cardiac output in some subjects. The aim of this work was to investigate this fall and to test whether it was reversible by subsequent administration of nicardipine, theophylline or the cyclic GMP-selective phosphodiesterase inhibitor, zaprinast (M&B 22948). 2. In pentobarbitone-anaesthetized pigs, haemodynamic indices were measured before and after intravenous administration of NG-nitro-L-arginine methyl ester (L-NAME) in a dose-response protocol (0.2-20 mg kg-1; n = 6) and as a single bolus of 10 mg kg-1 either alone or followed by increasing doses of nicardipine, theophylline or zaprinast (n = 8 in each group). 3. L-NAME caused a dose-dependent rise in systemic vascular resistance and mean systemic arterial pressure and a dose-dependent fall in cardiac output. A single bolus of L-NAME (10 mg kg-1) produced these effects within 15 min. 4. Subsequent administration of nicardipine (0.05-0.2 mg kg-1) caused complete reversal of systemic vasoconstriction and hypertension and in doing so completely restored cardiac output. Theophylline (7.5-10 mg kg-1) partially reversed the rise in systemic vascular resistance and partially restored cardiac output but the effect was small compared to that of nicardipine. Zaprinast (1-5 mg kg-1) had no significant effect on any of these variables. 5. These results suggest that reduced cardiac output following inhibition of NO synthesis is an effect of increased afterload on the heart and is reversible by nicardipine and to a lesser extent by theophylline.These findings may have potential value for those using NO synthase inhibitors to treat patients with septic shock.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

Haemodynamic impact of diuretic therapy in chronic heart failure.

An immediate improvement in haemodynamic variables and cardiac performance is achieved in chronic heart failure following diuretic therapy, primarily due to reductions in plasma and extracellular fluid volumes. Humoral markers of these alterations are increased plasma renin, angiotensin and aldosterone levels; these increase maximally over the first week of treatment but attenuate during sustained therapy. There are reciprocal alterations in plasma alpha-atrial natriuretic peptide levels. These findings suggest that the initial volume contraction is maintained, though somewhat attenuated, during chronic therapy. The neurohumoral consequences of diuretic therapy are of particular interest in heart failure, as they may contribute to diuretic resistance. Activation of the renin-angiotensin system favours the proximal tubular reabsorption of sodium and water, which may result in dilutional hyponatraemia. Diuretics have both direct vascular and non-vascular (volume-dependent) haemodynamic actions. Together these substantially reduce the left heart filling pressure (-29%) with a consequent fall in cardiac output (-10%). Systemic vascular resistance initially increases but subsequently normalizes, allowing cardiac output to return towards control values. Haemodynamic tolerance to diuretics does not usually occur during sustained oral therapy; additionally, echocardiographic contractility indices and exercise capacity may increase. The vasodilator activity of the diuretics is due to prostaglandin release; the initial pressor action is due to activation of the renin-angiotensin system. Direct pulmonary vasodilatation with improved pulmonary compliance remains an interesting possibility. Over the longer term, substantial reductions in left heart filling pressure during exercise occur at unaltered cardiac output. The impact of diuretic therapy on the underlying myocardial disease process is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Diuretics↗
PubMed1993

Central hemodynamic effects of diuretic therapy in chronic heart failure.

In chronic heart failure diuretic drugs improve central hemodynamic variables and cardiac pumping secondary to altered plasma and extracellular volumes; humoral markers of these changes include increased plasma renin and aldosterone levels. The latter increases are maximal over the first week but decline with chronic therapy. The plasma alpha-ANP levels show a reciprocal effect; these data are compatible with a rapid contraction of the plasma volume which is sustained during chronic therapy. The acute hemodynamic actions of diuretic agents reflect both immediate and direct vascular actions and also effects secondary to diuresis (volume redistribution). At rest substantial reductions in pulmonary "wedge" pressure (-29%), with a consequent fall in cardiac output (-10%), are described. Total systemic vascular resistance initially increases but "reverse autoregulation" over subsequent weeks returns this elevation gradually towards control values. Tolerance to these initial hemodynamic effects does not occur with maintained therapy; moreover, echocardiographic markers of contractility and exercise capacity may increase. The early venodilator effects of diuretic drugs can be attributed to prostaglandin release and the initial pressor actions to activation of the renin angiotensin system; these vascular actions may have limited relevance to long-term beneficial effects on hemodynamics. Direct pulmonary vasodilation and improved pulmonary compliance remain an interesting finding. Although most patients are both symptomatically and hemodynamically improved at rest, the actions during exercise are more varied. Some individuals with severely impaired left ventricular function show little hemodynamic improvement, whereas those with milder dysfunction usually benefit; in the main this is probably related to the latter being on a steeper cardiac function curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Bumetanide↗
PubMed1993

Time and frequency domain assessment of heart rate variability: a theoretical and clinical appreciation.

Non-invasive techniques for assessing heart rate variability can be used either diagnostically, as in identification of autonomic neuropathy associated with diabetes mellitus or tissue rejection following cardiac transplantation, or as a prognostic indicator in coronary artery disease. The methodology is based upon calculation of successive R-R intervals from an electrocardiogram, which can then be plotted as a frequency histogram (time domain analysis), undergo power spectral analysis to yield information in the frequency domain or be applied to chaos theory. In this review, several parameters are discussed which can be derived to quantify heart rate variability in the time and frequency domains; the latter providing information on autonomic balance. In the frequency domain up to three peaks may be observed, with the peak below 0.15 Hz being mediated by sympathetic and parasympathetic activity and peaks above 0.15 Hz being of vagal origin. The effects of different physiological and pathophysiological conditions on various indices of heart rate variability, and the use of heart rate variability analysis as a pharmacological method to assess the impact of drug therapy on sympathovagal balance are discussed.

Animals↗