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Biomedical subjects

A J Man in't Veld

Publications and source records attributed to A J Man in't Veld.

At least 19 recordsLinked to original sources
PubMed1999

Inter-observer variability in the angiographic assessment of renal artery stenosis. DRASTIC study group. Dutch Renal Artery Stenosis Intervention Cooperative.

OBJECTIVE: To assess inter-observer agreement in the interpretation of renal angiograms. DESIGN: Comparison of the assessment of renal angiograms by three experienced radiologists, who evaluated the number of renal arteries and the presence, location, aspect and severity of a renal artery stenosis. SETTING: General hospital and university hospital serving urban and rural populations. PATIENTS: Patients with difficult-to-treat hypertension referred for diagnostic work-up; 312 angiograms with the intra-arterial digital subtraction technique were obtained from 289 consecutive patients. MAIN OUTCOME MEASURES: Inter-observer agreement was tested for the following parameters: number of arteries per kidney, presence of stenosis, location of stenosis (truncal, ostial), aspect of stenosis (concentric, eccentric, post-stenotic dilatation), severity of stenosis (reduction of lumen diameter in categories of 30%, 40%, etc. to 100%), and overall quality of the angiographic images. Kappa (kappa) values and weighted kappa between the three pairs of radiologists were used as estimates of inter-observer agreement RESULTS: Agreement about the number of renal arteries was reasonable (kappa = 0.50-0.72), as was agreement about the presence of stenosis (kappa = 0.68-0.86). Agreement about stenosis location and aspect was poor (kappa = 0.26-0.47 and kappa = 0.15-0.26, respectively). There was general agreement about the severity of stenosis (weighted kappa = 0.65-0.70), but it was not possible to distinguish between 50 and 60% stenosis or between 60 and 70% stenosis (kappa < 0.40). No correlation was found between agreement on severity of stenosis and the quality of the images. CONCLUSIONS: It is not realistic to make statements about what degree of renal artery stenosis is clinically significant, as long as the intra-arterial angiogram with digital subtraction remains the gold standard. It is likewise risky to rely too strongly on stenosis morphology as visualized by renal angiography in choosing between balloon angioplasty and stent deployment.

Adult↗
PubMed1998

Influence of age on neurohormonal activation and prognosis in patients with chronic heart failure.

AIMS: Heart failure is a major medical problem in the elderly. Neurohormonal activation plays a role in the pathophysiology of heart failure, but is also affected by ageing. The present study was carried out to examine the influence of age on neurohormonal activation and prognosis in patients with chronic heart failure. METHODS AND RESULTS: We studied 372 patients with moderate to severe chronic heart failure (New York Heart Association [NYHA] functional class III-IV), who were treated with angiotensin converting enzyme (ACE) inhibitors (95%), diuretics (99%), and digoxin (59%). Their mean age was 68 +/- 8 years (range 38-80), left ventricular ejection fraction 0.23 +/- 0.08, and 77% were males. The relationship between age and plasma neurohormones (norepineprine, epinephrine, dopamine, renin, aldosterone, atrial natriuretic peptide, N-terminal atrial natriuretic peptide, and endothelin), and age and prognosis was examined. Only atrial natriuretic peptide and N-terminal atrial natriuretic peptide showed an independent, positive correlation with age (P < 0.0001). On univariate analysis, norepinephrine also increased, while renin and aldosterone decreased (all P < 0.05). As regards mortality (25%), there was no linear increase with ageing for the group as a whole during follow-up, but patients in the highest age quartile (> 74 years) had a significantly higher mortality (risk ratio 1.9) than younger patients (P < 0.05). CONCLUSIONS: Although several plasma neurohormones are affected by ageing on univariate analysis, only atrial natriuretic peptide and N-terminal atrial natriuretic peptide show a highly significant increase with ageing on multivariate analysis. There is no linear increase in mortality with ageing, but in the truly elderly heart failure patients (> 74 years), age alone was an independent predictor for mortality.

Adult↗
PubMed1998

Forearm vasorelaxation in hypertensive renal transplant patients: the impact of withdrawal of cyclosporine.

OBJECTIVE: To determine whether cyclosporine A-induced hypertension in renal transplant recipients is accompanied by impairment of endothelium-dependent vasodilatation, which has been suggested by in-vitro and in-vivo animal experiments. DESIGN AND METHODS: In-vivo endothelium-dependent and endothelium-independent vasodilatation, and plasma concentrations of vasoactive hormones in 16 renal transplant patients were determined while they were being treated with cyclosporine A, and 16 weeks later, after their treatment had been changed to azathioprine therapy. The vasodilator response of the forearm vascular bed was measured by strain gauge venous occlusion plethysmography during intra-arterial infusion of acetylcholine (endothelium-dependent vasodilatation) and nitroprusside (endothelium-independent vasodilatation). Postischemic reactive flow was measured after 10 min of arterial occlusion. In addition, plasma concentrations of norepinephrine, and the prostanoids prostaglandin E2 and thromboxane B2, and also concentration of cyclosporine A in blood, were measured. Glomerular filtration rate and renal blood flow were estimated 1 day before the plethysmography study during each treatment period. RESULTS: Upon changing from cyclosporine A to azathioprine treatment, mean arterial pressure fell significantly by 12+/-3% (P< 0.05). Glomerular filtration rate and renal blood flow increased by 13+/-5 and 19+/-8%, respectively (both P< 0.05), while renal vascular resistance fell by 48+/-11% (P< 0.01). Both baseline forearm blood flow and baseline forearm resistance did not change after conversion (5.7+/-0.7 versus 4.9+/-0.6 ml/100 ml/min, and 27.3+/-4.2 versus 26.2+/-3.2 arbitrary units). The absolute and relative forearm blood flow responses, and forearm vascular resistance responses to infusions of acetylcholine and nitroprusside were similar during treatments with cyclosporine A and azathioprine. Peak postischaemic forearm blood flow was 42+/-12% higher during cyclosporine A treatment than it was during azathioprine treatment (P< 0.05), but the minimal postischaemic forearm vascular resistance did not differ for these treatments. Plasma prostaglandin E2 and thromboxane B2 levels decreased by 34+/-7 and 45+/-8%, respectively, after changing treatment, but norepinephrine levels did not change. CONCLUSIONS: Our data indicate that cyclosporine A-induced hypertension in renal transplant recipients is not accompanied by an increase in forearm vascular resistance. In addition, changing from cyclosporine A to azathioprine treatment did not cause changes in endothelial vasodilator functioning, although mean arterial pressure decreased significantly. Our results do not support the hypothesis that attenuation of endothelial vasodilator functioning contributes to the development of cyclosporine A-induced hypertension.

Adult↗
PubMed1998

Noninvasive indices of autonomic regulation after alprazolam and lorazepam: effects on sympathovagal balance.

Skin conductance level (SCL) and spectral analysis of variations in heart rate (HR) and blood pressure (BP), in relation to plasma catecholamine concentrations, were used to evaluate autonomic nervous system activity during situations of supine rest within a period of 4 h after oral administration of 1 mg alprazolam and 2 mg lorazepam. Twelve healthy men received in a double-blind, randomized crossover design, either 1 mg alprazolam, or 2 mg lorazepam, or a placebo on different days. ECG, BP, respiration, and SCL were monitored continuously during each session. For HR, systolic and diastolic BP (SBP, DBP) time series, power spectra were calculated per 5 min for three 15-min periods at 30 min, 1 h and 45 min, and 3 h after dosing. Spectral power was assessed for three frequency bands: low (0.02-0.06 Hz), mid (0.07-0.14 Hz), and high (0.15-0.50 Hz). Per time segment, the gain in the mid-frequency band between the systolic BP values and the RR interval times was computed as index of baroreflex sensitivity (BRS). Blood samples for assay of plasma catecholamines were obtained after each 15-min period. Alprazolam reduced DBP during the whole recording period; the effect was accompanied by an initial increase of mid-frequency band fluctuations of BP at 30 min, which subsequently decreased at 1 h 45 min and 3 h after dose administration, in comparison with placebo (suggesting an initial reflectory increase, followed by an attenuation of sympathetic tone). The BP effects were accompanied by a reduction of plasma noradrenaline concentrations. HR showed a time-dependent decrease after alprazolam and an increase in high-frequency band fluctuations of HR and BRS (suggesting a time-dependent increase in cardiac vagal tone). SCL was decreased after alprazolam administration. Lorazepam did not show a time-dependent reduction of HR and had no effect on BP, but increased low-frequency band power of HR and DBP and mildly reduced SCL. Alprazolam and lorazepam had no effect on respiratory frequency. Noninvasive indices of autonomic regulation revealed several small, but significant, time-dependent effects of 1 mg alprazolam on sympathetic and parasympathetic processes, whereas for 2 mg lorazepam, these effects were less clear. The reduction in noninvasive indices of sympathetic tone after alprazolam administration corresponded with the attenuation of plasma noradrenaline concentrations by alprazolam.

Acetylcholine↗
PubMed1998

Symptomatic BPH and hypertension: does comorbidity affect quality of life?

Most alpha 1-adrenoceptor antagonists are non-subtype selective and act on smooth muscle in the prostate, as well as in the vascular system and, as such, have effects on blood pressure as well as relieving LUTS (lower urinary tract symptoms) in symptomatic benign prostatic hyperplasia (BPH). As many elderly patients with LUTS also take concomitant antihypertensive therapy, it has been suggested by some that these patients should be treated with an alpha 1-adrenoceptor antagonist that targets both symptomatic BPH and hypertension simultaneously. However, an alternative school of thought believes that hypertension, as a malignant disease, should be treated optimally first, before the LUTS are controlled. Many different classes of antihypertensive drugs have been developed and evidence, with regard to reduction of cardiovascular morbidity and mortality, supports the use of diuretics and beta-blockers in this indication. However, from this point of view, few data support the use of alpha 1-adrenoceptor antagonists in antihypertensive therapy, and studies indicate that elderly patients in particular are prone to orthostatic hypotension and its effects when treated with alpha 1-adrenoceptor antagonists. This, together with the fact that hypertension is such a potentially morbid disease, suggests that alpha 1-adrenoceptor antagonists should not be used as a first line treatment for the treatment of hypertension. Rather, patients with comorbidity should be treated optimally for both diseases, being treated initially for hypertension with the optimal agent available and then with an alpha 1-adrenoceptor antagonist that is not haemodynamically active to target their LUTS. Tamsulosin, a selective alpha 1A-adrenoceptor antagonist, has no clinically significant effect on blood pressure compared with placebo, thus posing less risk for the patient, especially with regard to symptomatic orthostatic hypotension.

Adrenergic alpha-Antagonists↗
PubMed1997

Losartan, an angiotensin-II receptor antagonist, reduces hematocrits in kidney transplant recipients with posttransplant erythrocytosis.

BACKGROUND: Posttransplant erythrocytosis (PTE) occurs in 10-15% of patients with a well-functioning kidney transplant and is associated with increased morbidity. Although the mechanism of PTE is unknown, PTE responds to inhibitors of ACE (ACE-i) in most cases. ACE converts angiotensin I to angiotensin II and is a metabolizer of a number of other peptides. METHODS: Because ACE-i frequently show side effects we wanted to elucidate the pathway by which ACE-i mediate their effect in PTE. Therefore, we treated eight patients (five with newly diagnosed PTE, two with PTE unresponsive to ACE-i, and one with PTE responsive to ACE-i, which had to be withdrawn due to side effects) with 50 mg of the type 1 angiotensin II receptor antagonist losartan for at least 14 weeks. RESULTS: Hematocrit values in the two patients who were unresponsive to ACE-i did not change significantly. In contrast, hematocrits decreased in all the other six patients from 0.53+/-0.02 to 0.44+/-0.02 after 14 weeks of treatment with losartan (mean +/- SE; P<0.005, paired t test). Graft function, cyclosporine concentration, and leukocyte and platelet count remained stable. The serum potassium level rose in one patient from 6.0 to 6.8 mmol/L but remained stable in all other patients. CONCLUSIONS: We conclude that blockade of the type 1 angiotensin II receptor is safe and effective in treating PTE.

Angiotensin Receptor Antagonists↗
PubMed1997

Plasma semicarbazide-sensitive amine oxidase is elevated in patients with congestive heart failure.

OBJECTIVE: Semicarbazide-sensitive amine oxidase (SSAO) is present in various mammalian tissues, especially in vascular smooth muscle cells, but also in plasma. The enzyme has been suggested to play a role in vascular endothelial damage through conversion of amines into cytotoxic aldehydes, ammonia and hydrogen peroxide. Endothelial dysfunction is present in diabetes mellitus (DM) and congestive heart failure (CHF). Elevated plasma SSAO activities have been reported in patients with DM, but no data on patients with CHF are as yet available. METHODS AND RESULTS: Plasma SSAO was measured in 271 patients with CHF and compared to values in 77 controls. SSAO was found to be elevated in patients with CHF compared to controls (589 +/- 252 vs. 455 +/- 114 mU/l; P < 0.0001). Plasma SSAO was higher in NYHA class III/IV than in class III (662 +/- 288 vs. 555 +/- 226 mU/l; P = 0.004) and also higher in patients with concomitant DM than in those without (706 +/- 248 vs. 557 +/- 245 mU/l; P < 0.0001). Plasma SSAO correlated with plasma atrial natriuretic peptide (r = 0.42; P < 0.0001), with plasma norepinephrine (r = 0.27; P < 0.0001) and with left ventricular ejection fraction (r = -0.13; P = 0.0162). Multiple regression analysis showed atrial natriuretic peptide, norepinephrine, DM and cardiothoracic ratio to be the main determinants of plasma SSAO. CONCLUSION: The finding of elevated plasma SSAO in CHF, increasing with severity of the disease and with the concomitant presence of DM, supports the suggestion that SSAO may be involved in the pathogenesis of vascular endothelial damage. Plasma SSAO may be a useful parameter in assessing severity of CHF and in prognostic evaluation. Pharmacologic manipulation of SSAO activity might be an interesting new concept for prevention of vascular endothelial damage in various vascular disease entities.

Amine Oxidase (Copper-Containing)↗
PubMed1997

Conversion from cyclosporine A to azathioprine treatment improves LDL oxidation in kidney transplant recipients.

The use of the immuno-suppressant cyclosporine A (CsA) after transplantation has been associated with less favorable plasma lipid profiles, which may contribute to the high incidence of cardiovascular morbidity and mortality in transplant recipients. Recent studies have suggested that oxidative modification of LDL plays an important role in the initiation and progression of atherosclerosis. It has also been demonstrated that CsA may facilitate lipid peroxidation in vitro and in vivo. Therefore, we determined several parameters of LDL oxidizability in renal transplant recipients who were switched from CsA to azathioprine (AZA)-based immunosuppressive treatment. The susceptibility of LDL to in vitro oxidation, LDL particle size, plasma titers of IgG and IgM antibodies against oxidized LDL and plasma LDL subclass patterns in 19 renal transplant recipients were determined during CsA treatment and 16 weeks after these patients were converted to AZA treatment. In addition, mean arterial pressure was recorded, and glomerular filtration rate and renal blood flow were estimated from the clearance of radiolabeled thalamate and hippurate. After conversion, the plasma concentrations of total cholesterol, LDL cholesterol and triglyceride decreased, while plasma HDL cholesterol did not change. During CsA therapy plasma LDL was significantly more susceptible to in vitro oxidation than during AZA, as reflected by a longer lag phase during in vitro oxidation (98.9 +/- 24.3 vs. 114.7 +/- 17.3 min, P = 0.031). In addition, the LDL size increased (236.5 +/- 7.3 vs. 240.7 +/- 6.8 nm, P = 0.00001), and the titers of IgM- and IgG-autoantibodies against oxidized LDL decreased significantly after patients were converted from CsA to AZA. The more atherogenic LDL subclass pattern B was present in 13 out of 19 patients during CsA. In five patients, pattern B changed into pattern A after conversion. The subclass B pattern was maintained in eight patients and subclass A pattern in six patients. In all patients the lag time of in vitro LDL oxidation increased, although the biggest changes were found in those patients in whom the LDL subclass changed from pattern B to pattern A. Mean arterial pressure decreased and renal function improved significantly after conversion. No correlation between parameters of lipid peroxidation and changes in blood pressure or renal function upon conversion, underlying renal disease, time since transplantation, or antihypertensive treatment was found. Our study demonstrates that treatment with CsA increases the susceptibility of LDL to in vitro oxidation, and also enhances the oxidation of LDL in vivo. In addition, conversion to AZA results in a more favorable lipid profile, which in combination with a lower arterial pressure and better renal function may decrease the risk for atherosclerosis. These factors may account for the cardiovascular complications during CsA treatment after organ transplantation, and also when CsA is used for other diseases.

Adolescent↗
PubMed1997

Systemic, pulmonary and coronary haemodynamic actions of the novel dopamine receptor agonist in awake pigs at rest and during treadmill exercise Z1046.

1. In view of the potential therapeutic application of specific dopamine receptor agonists in the treatment of hypertension and left ventricular dysfunction, we investigated the cardiovascular actions of the novel mixed D1/D2 dopamine receptor agonist Z1046 in awake pigs at rest and during treadmill exercise. 2. Thirteen swine were chronically instrumented under sterile conditions for measurement of systemic, pulmonary, and coronary haemodynamics. Regional blood flows were determined with the radioactive microsphere technique. 3. Z1046 (1, 10, 100 micrograms kg-1, i.v.) produced dose-dependent reductions in central aortic blood pressure (up to 27 +/- 3%, P < or = 0.05) in awake resting pigs which was accompanied by only minimal reflex activation of the sympathetic nervous system. The hypotensive response was principally the result of peripheral vasodilatation (system vascular resistance decreased up to 35 +/- 4%, P < or = 0.05), which was located in the cerebral, coronary, renal, mesenteric, adrenal, splenic and skeletal muscular vascular beds (vascular resistance decreased up to 30-40% after the highest dose in these beds). Only in the cerebral and mesenteric bed was the vasodilatation sufficiently large to overcome the decrease in blood pressure and result in an increased blood flow; the vasodilatation in the coronary bed was most likely due to autoregulation as neither coronary blood flow nor myocardial oxygen demand were changed significantly by Z1046. The systemic vasodilatation that was caused by the highest i.v. dose (100 micrograms kg-1) was accompanied by transient and minor increases in heart rate (15 +/- 5%, P < or = 0.05) and cardiac output (15 +/- 5%, P < or = 0.05) whereas after 10 micrograms kg-1, i.v., a slight decrease in cardiac output also contributed to the hypotension. Z1046 had no effect on pulmonary vascular resistance. 4. The systemic vasodilator responses to Z1046 (100 micrograms kg 1, i.v.) were sustained during treadmill exercise (2-4 km h-1 which produced heart rates of up to 233 +/- 10 beats min-1), but with increasing treadmill speed attenuation of the exercise-induced increase in heart rate (-11 +/- 3%, P < or = 0.05) and hence cardiac output (-10 +/- 3%, P < or = 0.05) (as stroke volume was not altered by Z1046) contributed significantly to a lower aortic blood pressure (-20 +/- 3%, P < or = 0.05) Z1046 had no effect on pulmonary vascular resistance during exercise. 5. Oral administration of Z1046 (0.5, 1.5 mg kg-1) produced a fall in central aortic blood pressure (up to 15 +/- 3%, P < or = 0.05), which developed gradually during the first 90 min and lasted up to 4 h after administration, again with negligible changes in heart rate and LVdP/dtmax. 6. Neither non-selective alpha- and beta-adrenoceptor blockade, nor selective alpha 2-adrenoceptor blockade altered the vasodilator actions of Z1046, but non-selective alpha- and beta-adrenoceptor blockade abolished the cardiac responses to dopamine receptor stimulation, suggesting that its cardiac actions were principally caused by D2-receptor-mediated inhibition of catecholamine release, whereas the vasodilator response was probably the result of vascular D1-receptor stimulation. 7. In conclusion, the novel dopamine receptor agonist Z1046 is an effective blood pressure lowering agent that elicits minimal reflex activation of the sympathetic nervous system in awake resting pigs Systemic vasodilatation was not affected by combined alpha- and beta-adrenoceptor blockade, which is consistent with a predominantly D1 receptor-dependent vasodilator mechanism. The hypotensive effect is maintained during treadmill exercise during which systemic vasodilatation and a lower cardiac output both contribute to the blood pressure lowering actions of Z1046. The cardiovascular profile of this orally active compound warrants further investigation of this class of drugs in experimental and clinical hypertension.

Administration, Oral↗
PubMed1997

Clinical overview of irbesartan: expanding the therapeutic window in hypertension.

BACKGROUND: The clinical management of hypertension has traditionally been hampered by a limited therapeutic window, which has resulted in the maintenance of patients on doses of antihypertensive agents that often produce clinically significant side effects and suboptimal blood pressure control. To expand this window, a therapeutic agent must provide optimal, dose-related blood pressure control with placebo-like tolerability. IRBESARTAN: Irbesartan, a new angiotensin II receptor antagonist, has been shown to provide significant blood pressure reductions compared with placebo and equal or better reductions compared with major antihypertensive agents of other classes. These effects have been demonstrated in an extensive clinical trials program, comprising 1691 irbesartan-treated patients and 539 placebo-treated patients. Active-drug-controlled trials with beta-blockers, angiotensin converting enzyme inhibitors, calcium antagonists and diuretics have further confirmed the excellent results with irbesartan. Moreover, irbesartan demonstrates a clear dose-related therapeutic response with no dose-related effects on adverse event rates. CONCLUSIONS: The clear advantages of irbesartan over antihypertensive agents of other classes have the potential to expand the therapeutic window in the treatment of hypertension, thus improving the chances that a majority of patients will attain long-term blood pressure control with freedom from side effects.

Angiotensin Receptor Antagonists↗
PubMed1995

Evaluation of importance of central effects of atenolol and metoprolol measured by heart rate variability during mental performance tasks, physical exercise, and daily life in stable postinfarct patients.

BACKGROUND: Physical exercise and mental work cause alterations in cardiac autonomic control. beta-Blockers protect the heart against stress, and this effect may be in part centrally mediated. In this context, the lipophilicity of the drug would be clinically relevant. METHODS AND RESULTS: Thirty postinfarct patients were randomized to receive 100 mg atenolol or 200 mg metoprolol CR in a double-blind, crossover manner, each for a 6-week period. Heart rate (HR) variability was used to study autonomic effects during mental and physical stress and to study circadian variations. Mean 24-hour HR decreased from 77 +/- 7 to 60 +/- 6 beats per minute after atenolol and to 62 +/- 6 beats per minute after metoprolol (P = .046). At baseline, mental performance tasks did not affect HR, but decreased HR variability (SDNN index from 51 +/- 26 to 30 +/- 13 milliseconds [ms], P < .001; high-frequency power from 130 +/- 143 to 110 +/- 125 ms2, P = .046; and low-frequency power from 538 +/- 447 to 290 +/- 275 ms2, P < .001). Both beta-blockers decreased HR during mental performance tasks (P < .001) and increased SDNN index and high-frequency power. Before treatment, bicycle exercise decreased HR variability; root-mean-square of successive difference decreased from 21 +/- 8 to 15 +/- 10 ms (P = .004). beta-Blockade could not prevent this decrease. No differences between atenolol and metoprolol were observed for absolute high- and low-frequency power or after adjustment for HR. Vagal blockade with methylatropine during chronic beta-blocker treatment nearly abolished all components of spectral power. HR was found to be the parameter most strongly affected by beta-blockade but not by an influence on vagal tone. No differences were found between atenolol and metoprolol. CONCLUSIONS: In stable postinfarct patients, chronic treatment with metoprolol and atenolol attenuates the reduction in HR variability induced by mental performance tasks, but the effects during exercise are limited. beta-Blockers do not appear to increase vagal tone in this stable patient group. The point of action in these patients is mainly a reduction in HR, probably due to a reduction in stress-induced sympathetic activation. Clinically significant differences between atenolol and metoprolol were absent, indicating that the degree of lipophilicity does not distinguish among the beta-blockers what their salutary effects are on HR variability during the specific challenges used.

Activities of Daily Living↗
PubMed1995

Dose-dependent separation of dopaminergic and adrenergic effects of epinine in healthy volunteers.

Epinine (N-methyl-dopamine, the active metabolite of ibopamine), is a full agonist at dopamine (DA)-receptors and alpha- and beta-adrenoceptors. To study whether in vivo DA-receptors mediated effects can be separated from alpha- and beta-adrenoceptor effects we compared in 10 male volunteers the effects of i.v. epinine (0.5; 1; 2; 4 micrograms/kg/min for 15 min each) on DA-receptor (changes in serum prolactin)- and alpha- and beta-adrenoceptor (changes in systolic [Psyst] and diastolic blood pressure [Pdiast] and heart rate)-mediated effects with those of dopamine before and after propranolol (5 mg i.v. 45 min pre-infusion), bisoprolol (15 mg p.o. 2 h pre-infusion) and domperidone (10 mg p.o. 1 h pre-infusion). At the 0.5 and 1 microgram doses of dopamine and epinine did not effect Psyst, Pdiast and heart rate but significantly decreased prolactin levels. At the higher dose both dopamine and epinine significantly increased Psyst and heart rate, while only epinine significantly increased Pdiast. In addition, both dopamine and epinine significantly increased diuresis and natriuresis; in contrast, only dopamine, but not epinine dose-dependently increased plasma noradrenaline levels. Domperidone did not affect dopamine- and epinine-evoked blood pressure- and heart rate-changes, but antagonized their prolactin-effects (at least at the lower doses). Bisoprolol and propranolol significantly reduced dopamine-induced Psyst- and heart rate-increases to about the same extent. Propranolol enhanced epinine-induced Psyst- and Pdiast-increases while bisoprolol reduced epinine-evoked Psyst-increase but not Pdiast-increase. Epinine-induced heart rate-increase was abolished by bisoprolol and was converted into heart rate-decrease by propranolol. We concluded that in 0.5 and 1 microgram doses (plasma levels of 20-80 nmol/l)epinine acts only at DA-receptors. Thus, ibopamine in therapeutically recommended doses (3 x 100 mg/day with peak plasma epinine-levels of 50-80 nmol/l) very likely activates only DA-receptors. In higher doses, however, epinine-like dopamine-activates alpha- and beta-adrenoceptors whereby epinine has a stronger alpha-adrenoceptor agonistic activity than dopamine. Moreover, part of the dopamine-effects are indirect via release of endogenous noradrenaline whereas epinine-effects do not appear to include an indirect component.

Adult↗
PubMed1994

Heart rate variability in left ventricular dysfunction and heart failure: effects and implications of drug treatment.

OBJECTIVE: To review the importance of heart rate variability analysis in left ventricular dysfunction and heart failure and to assess the effects of drug treatment. In patients with left ventricular dysfunction or heart failure, a low heart rate variability is a strong predictor of a low probability of survival. Because drug treatment in these patients has rapidly changed over the past two decades, the effect of these drugs on heart rate variability needs special attention. DESIGN: A study of published reports to give an overview of heart rate variability in patients with left ventricular dysfunction or heart failure and how it is affected by drug treatment. RESULTS: Analysis of heart rate variability provides an easily obtained early marker for progression of disease. It seems to be more closely related to the degree of neurohumoral activation than to haemodynamic variables. Cardiovascular drugs may either stimulate or inhibit the degree of neurohumoral activation, and the effects of pharmacological intervention can be closely monitored with this method. CONCLUSIONS: The analysis of heart rate variability, including spectral analysis, is a novel non-invasive way to obtain potentially useful clinical information in patients with reduced left ventricular function. The effects of drug treatment on heart rate variability are in general consistent with their long-term effects in left ventricular dysfunction and heart failure.

Heart Failure↗
PubMed1994

Diurnal variation of blood pressure in patients with catecholamine-producing tumors.

To investigate the role of plasma catecholamines in diurnal blood pressure variation, invasive 24-h ambulatory blood pressure recordings (Oxford technique) were performed on 10 untreated patients; all had increased plasma concentrations of norepinephrine (mean 27.3; range 2.50 to 134.6 nmol/L) or epinephrine (mean 13.5; range 0.13 to 96.6 nmol/L) either attributable to a pheochromocytoma (n = 7) or a paraganglioma (n = 3). The nocturnal change in blood pressure was calculated as the percentage difference of blood pressure between night (midnight to 6 AM) and day (8 AM to 10 PM). The group average nocturnal change in blood pressure was 12.4%, ranging from a 32.0% decrease to a 2.8% increase, whereas the average nocturnal fall in heart rate was 18.6%, ranging from 2.2% to 33.4%. Although the nocturnal change in blood pressure was not significantly correlated with plasma values of norepinephrine (r = 0.60) or total catecholamines (r = 0.54), no nocturnal decrease in blood pressure occurred in the two patients with a plasma norepinephrine level of > 55 nmol/L. Recordings of three patients, all with a pheochromocytoma showed several paroxysms of blood pressure elevations, which lasted 18 to 47 min and had an amplitude of 32 to 94 mm Hg. In two cases these elevations had a true cyclic character. Our findings indicate that patients with a catecholamine-producing tumor may exhibit a normal diurnal blood pressure variation with a decrease in blood pressure during the night, suggesting that factors responsible for this diurnal variation remain operative in this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Lack of desensitization of alpha- and beta-adrenoceptor function during chronic treatment of healthy volunteers with ibopamine, an orally active dopamine receptor agonist.

In 18 healthy volunteers, in a double-blind placebo-controlled study, we investigated of whether 14 days treatment with a therapeutic dose of ibopamine (3 x 100 mg/day p.o.), respectively its active metabolite epinine, would desensitize lymphocyte beta 2- or platelet alpha 2-adrenoceptors, or alpha 1- and beta-adrenoceptor mediated (phenylephrine- and isoprenaline infusions, respectively), changes in systolic and diastolic blood pressure and heart rate. Ibopamine-treatment, which resulted in peak plasma epinine concentrations of 4-5 nmol.l-1, neither affected resting heart rate or blood pressure, nor any of the alpha- or beta-adrenoceptor parameters measured. Since in man in general long-term administration of alpha- and beta-adrenoceptor agonists desensitizes alpha- and beta-adrenoceptors, the lack of any alpha- and beta-adrenoceptor desensitizing effect of ibopamine suggests that, in the dose employed (3 x 100 mg per day), ibopamine does not exert alpha- or beta-adrenoceptor agonistic effect in humans.

Adult↗