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Biomedical subjects

A J Smit

Publications and source records attributed to A J Smit.

At least 91 records · Page 5Linked to original sources
PubMed1996

No deterioration of insulin secretion by the potassium channel opener pinacidil in essential hypertension.

Hypertension has been associated with hyperinsulinemia and insulin resistance. The elevations in plasma insulin are the apparent adaptation of the pancreatic beta cell to the resistance to insulin. Maintenance of normal insulin release is therefore of great importance for subjects with hypertension. The potassium channel opener pinacidil has antihypertensive properties. Pinacidil has been shown to inhibit Insulin release in vitro in isolated pancreatic beta cells. We therefore studied the acute effect of pinacidil on insulin secretion and insulin sensitivity in hypertensive and control subjects. The acute effect of pinacidil (25 mg, orally) on plasma insulin was studied during a hyperglycemic clamp (180 min, blood glucose 10 mmol/L) in 10 healthy volunteers and in 10 non-obese hypertensive patients in a randomised, placebo controlled double blind study. Fasting plasma insulin levels were 54.8 +/- 10.9 and 51.1 +/- 8.8 pmol/L in the control group and statistically significantly higher in the hypertensive group: 90.5 +/- 16.6 and 100.0 +/- 16.2 pmol/L (with and without pinacidil, respectively, both P < 0.02 vs control group). Plasma insulin levels rose to maximum levels of 246.7 +/- 44.6 and 267.2 +/- 56.2 pmol/L after 5 min in the control group (with and without pinacidil, respectively, NS) and to maximum levels of 248.9 +/- 37.3 and 238.0 +/- 39.1 pmol/L after 5 min in the hypertensive group (with and without pinacidil, respectively, NS). Areas under the insulin curve (AUCinsulin) of the first and second phase did not differ between the control and hypertensive group, with or without pinacidil. In the control and the hypertensive group separately no statistically significant effect of pinacidil on the mean glucose infusion rate/mean insulin level (M/I) ratio, a measure for insulin sensitivity, was shown. When both groups were taken together, an increase in the M/I ratio under the influence of pinacidil was found for the third hour of the clamp (P < 0.02). In conclusion, fasting insulin levels in the hypertensive subjects were significantly higher than in the control subjects. The potassium channel opener pinacidil did not influence insulin secretion in hypertensive patients and healthy controls. Pinacidil may have an enhancing effect on insulin sensitivity.

Adult↗
PubMed1996

Acceptance and side effects of ambulatory blood pressure monitoring: evaluation of a new technology.

Ambulatory blood pressure (BP) monitoring is probably becoming a clinically useful procedure for the evaluation of hypertensive patients. Previous reports have shown that the devices are safe and serious side effects are rare. Discomfort and inconveniences associated with its use are more frequent. In this study, patient acceptance of ambulatory blood pressure monitoring (ABPM) was compared with acceptance of other diagnostic procedures and their side effects were assessed. Patients were asked to fill in a form and 129 of 166 patients responded. The acceptance was measured with a visual analogue scale which ranged from 'very annoying' on the left to 'not annoying at all' on the right. All forms were collected anonymously. Mean distance (cm) of the visual likert scale was 8.6 to 9.4 for the diagnostic procedures frequently used in routine patient care. Ambulatory BP measurement (ABPM) scored 6.1 cm. Reported side effects (in 27% of patients) were: plan (9%), skin irritation (8%), noisy device (8%), inconvenience with work (3%), haematoma (2%) and other (4%). Reports from the patients on sleep quality were: 23% normal, 61% minor disturbance, 14% had sleep, and 2% did not sleep at all. It can be concluded that ambulatory BP monitoring was the diagnostic procedure with the lowest patient acceptance. Side effects of this new technology were reported by 27% of patients. However, risks are relatively minor. Sleep disturbances were very frequent and was a serious problem for 16% of patients.

Blood Pressure Monitoring, Ambulatory↗
PubMed1995

Potassium channel modulation: effect of pinacidil on insulin release in healthy volunteers.

The effect of a potassium (K+) channel opener (pinacidil) on serum insulin levels and blood glucose levels was investigated in normal volunteers during glucose loading. An intravenous glucose load was used with and without oral pretreatment: pinacidil (25 mg) 11 hours and 1 hour before the 25-g glucose loading. Serum insulin, C-peptide, blood glucose, and plasma catecholamines were measured between t = 0 and t = 180 minutes. Pinacidil led to significantly lower insulin levels, especially in the first phase. Serum C-peptide levels were not significantly lowered, and glucose levels were not changed. Pinacidil inhibits the first phase of insulin release after glucose administration in healthy volunteers. These findings suggest that the safety of the drug regarding glucose tolerance, should be tested separately in patients with diabetes mellitus and essential hypertension.

Adult↗
PubMed1995

Cardiac asystole post-exercise: a report of two cases.

Two patients are described with reproducible cardiac asystole post-exercise. No structural heart disease was demonstrable. At autonomic function testing no abnormal responses were noted. Also, head-up tilt tests were normal. However, electrophysiologic testing and heart rate variability during 24-h Holter monitoring were indicative of a high vagal tone in both patients. The findings suggest that post-exertional asystole may not be due solely to a vasovagal mechanism; excessive rebound vagotonia per se may also play a role.

Adult↗
PubMed1995

Clinical relevance of ATP-dependent potassium channels.

Many cells are equipped with so-called potassium (K+) channels which have an important role in maintaining transmembrane potential. Closure of these channels leads to membrane depolarization, which can be followed by cell-specific activity such as contraction of vascular smooth muscle, or secretion of insulin from pancreatic beta-cells. Therefore, it is not surprising that a number of drugs have been introduced which influence K+ channels by either blocking or opening them. The treatment of type 2 (non-insulin-dependent) diabetes mellitus with sulphonylurea derivatives (SU), which exert their insulinotropic effect by closing the K+[ATP] channels of the pancreatic beta-cell, is customary. Slight differences are described in the insulinotropic action of the various SU. Claims in the past that treatment with SU increases cardiovascular mortality are not supported by sound evidence. SU may even reduce cardiovascular mortality by protecting against ventricular arrhythmias during cardiac ischaemia. K+[ATP]-channel-opening drugs are under investigation for the treatment of essential hypertension and angina pectoris. They are at least as effective in achieving adequate blood pressure control as calcium channel blockers. The recently introduced coronary vasodilating drug, nicorandil, exerts its effect by two mechanisms of action: opening K+[ATP] channels in vascular smooth muscle cells of coronary arteries and activation of guanidyl cyclase by its nitro-group in these cells. A proarrhythmic effect of K+[ATP] channel openers has only been observed at very high doses, but not in the low doses used in angina pectoris and hypertension. In vivo no negative effect of K+[ATP]-channel-opening drugs on insulin secretion is found.

Adenosine Triphosphate↗
PubMed1995

The effects of ibopamine on glomerular filtration rate and plasma norepinephrine remain preserved during prolonged treatment in patients with congestive heart failure.

UNLABELLED: In acute studies ibopamine, an a selective dopamine agonist, induces moderate increases of GFR and ERPF, and a fall in plasma norepinephrine levels in patients with congestive heart failure (CHF). We evaluated acute and chronic effects of ibopamine on renal haemodynamics, sodium excretion, PRA, plasma aldosterone (ALD) and norepinephrine levels in an open controlled study in 10 patients aged (51-79 years) with mild CHF, NYHA class II-III. All patients used digoxin and frusemide. After a control study day, the second study day involved the administration of 100 mg ibopamine. Subsequently the patients continued to take ibopamine 100 mg three times daily for one month, at which time the chronic effects were measured on the third study day. RESULTS: On the second day ERPF rose from a baseline of 288 +/- 32 to a mean of 308 +/- 32 ml.min-1 x 1.73 m-2 (P < 0.05) during the 4 h after the first administration of ibopamine and GFR rose from 77 +/- 8 to a mean of 84 +/- 8 ml.min-1 x 1.73 m-2 (P < 0.05). The ratio GFR/ERPF, representing the filtration fraction (FF) remained unchanged. On the third study day GFR and ERPF at baseline were similar to those before ibopamine treatment. After the acute on chronic administration we observed an increase in GFR (from 76 +/- 6 to a mean of 85 +/- 7 ml.min-1 x 1.73 m-2 (P < 0.05)), and in ERPF (from 279 +/- 27 to a mean of 293 +/- 29 ml.min-1 x 1.73 m-2 (P < 0.05)). Plasma norepinephrine levels fell from 2.63 +/- 0.48 to 1.92 +/- 0.27 nmol.l-1 (P < 0.05) after the acute administration of ibopamine, and remained unchanged after the acute on chronic ibopamine administration (C: 1.80 +/- 0.42 nmol.l-1). No changes in sodium excretion were observed, either in blood pressure, heart rate, PRA or ALD. We conclude that renal function is preserved during chronic ibopamine treatment and the acute moderate increase of ERPF and GFR after a single dose of 100 mg of ibopamine is still present after one month of treatment with ibopamine in patients with CHF. Ibopamine lowered plasma norepinephrine levels in our patients with CHF, and these values remained unchanged after the acute on chronic administration of ibopamine.

Adult↗
PubMed1995

Effects of spirapril and captopril on regional blood flow in chronic congestive heart failure: a comparison between a short- and a long-acting angiotensin-converting enzyme inhibitor.

Spirapril is a new angiotensin-converting enzyme (ACE) inhibitor with a long duration of action. To determine whether duration of inhibition of serum ACE activity may affect regional blood flow (RBF), we compared spirapril with captopril, an ACE inhibitor with a short duration of action. Both the short- and long-term effects were studied in patients with mild to moderate congestive heart failure (CHF). Calf, renal, and hepatic BF measurements were performed in the morning before intake of the study medication; 24 h after the previous dose of spirapril (n = 9 patients) and 12 h after the previous dose of captopril (n = 9 patients). Serum ACE activity after 1, 6, and 12 weeks was significantly reduced in patients receiving spirapril, but not in those receiving captopril. The decrease in mean arterial pressure (MAP) was more pronounced in the spirapril group. Calf BF showed a slight but not significant increase in both spirapril- and captopril-treated patients. Effective renal BF increased significantly only in patients treated with spirapril. Although filtration fraction (FF) tended to decrease in the spirapril group, the decrease was significant only in the captopril group. No changes were observed in hepatic BF. Cerebral BF (CBF) measurements were performed after intake of the first dose of study medication and after 12 weeks, immediately after drug intake. Significant reduction in MAP in the two treatment groups both after the first dose and after 12 weeks did not affect CBF. Despite a significantly prolonged decrease in MAP and serum ACE activity in spirapril-treated patients, no marked differences in RBF were noted between the two ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Renal and systemic hemodynamic effects of ibopamine in patients with mild to moderate congestive heart failure.

To study the hemodynamic and renal effects of the orally (p. o.) active dopamine (DA) agonist ibopamine, we examined 10 patients with mild to moderate congestive heart failure (CHF), who were stable while treated with digoxin and diuretics. All patients were in New York Heart Association (NYHA) functional class II-III; their mean age was 63 years (range 51-79 years), and mean left ventricular ejection fraction (LVEF) was 28% (range 18-36%). The protocol consisted of a control study-day with measurements of renal characteristics including glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction (FF). One week later, systemic and renal hemodynamics were measured simultaneously before and after patients received one 100-mg tablet of ibopamine. Ibopamine caused a slight but significant increase in both ERPF (from 288 +/- 32 ml/min/1.73 m2 at baseline to 316 +/- 32 ml/min/1.73 m2 after ibopamine) and GFR (from 77 +/- 8 to 85 +/- 8 ml/min/1.73 m2; both p < 0.05); FF was not affected (mean value 0.26 +/- 0.02). Sodium excretion was not influenced by ibopamine, but diuresis increased significantly. Cardiac output (CO) increased significantly (from 4.0 +/- 0.4 L/min at baseline to a maximum of 5.0 L/min after ibopamine, p < 0.05), mainly due to decreased systemic vascular resistance (SVR). Heart rate (HR) and blood pressure (BP) were unchanged throughout the studies. The percentage of contribution of CO to renal blood flow (RBF) was not significantly affected by ibopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Comparative effects of diltiazem and lisinopril on left ventricular structure and filling in mild-to-moderate hypertension.

The comparative effects on echocardiographically determined left ventricular (LV) mass and pulsed Doppler derived indexes of LV diastolic filling were studied in previously untreated hypertensive patients after 6 months of treatment with diltiazem 300 mg once daily (o.d.) (n = 16), and lisinopril 20 mg o.d. (n = 20). LV mass index decreased in the lisinopril group (from 98 to 96 g/m2; mean difference after 6 months of treatment with diltiazem-lisinopril was 13.7 g/m2 [95% confidence interval (CI) 0.8 to 26.6, p < 0.05]. In both groups diastolic filling parameters improved, but there was no statistically significant difference between the groups. Both treatment regimens showed a similar decrease in office and maximal exercise systolic blood pressure (SPB). Ambulatory daytime BP was lower after lisinopril treatment (from 147/96 to 126/83 mm Hg) than after diltiazem treatment (from 142/93 to 135/87 mm Hg); mean difference between diltiazem and lisinopril after 6 months of treatment was 9.7 (95% CI 3.4 to 16.0, p < 0.05)/9.4 (95% CI 2.5 to 16.3, p < 0.05) mm Hg. Nighttime BP decreased from 129/81 to 113/70 mm Hg in the lisinopril group, but not in the diltiazem group (from 125/79 to 122/77 mm Hg); mean difference between diltiazem and lisinopril after 6 months of treatment was 4.4 (95% CI - 0.2 to 8.9)/6.6 (95% CI 1.1 to 12.0) mm Hg. Changes in diastolic filling parameters were significantly correlated with changes in LV mass index in the lisinopril group, suggesting that the improvements in diastolic filling in the diltazem group may be partly due to an effect on factors other than LV mass.

Adult↗
PubMed1995

Alterations in cortisol metabolism in insulin-dependent diabetes mellitus: relationship with metabolic control and estimated blood volume and effect of angiotensin-converting enzyme inhibition.

11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the interconversion of cortisol and its inactive metabolite, cortisone, and protects the mineralocorticoid receptor from activation by cortisol. Sodium and fluid retention is a well documented phenomenon in insulin-dependent diabetes mellitus (IDDM), but it is not known whether diabetes-associated alterations in cortisol metabolism contribute to its pathogenesis. Therefore, we evaluated some aspects of cortisol metabolism by measuring urinary metabolites of cortisol and cortisone in eight microalbuminuric and eight normoalbuminuric IDDM patients and eight matched control subjects. In both IDDM groups, the overnight excretion of tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), and tetrahydrocortisone (THE) was lower than that in the control group (P < 0.05 to P < 0.01). Both the allo-THF/THF ratio, a parameter of 5 alpha/5 beta-reduction of cortisol, and the cortisol to cortisone metabolite ratio (THF+allo-THF/THE), which reflects the overall direction of the cortisol to cortisone interconversion, were lower in the IDDM groups (P < 0.05 to P < 0.01). In the combined subjects (n = 24), allo-THF, allo-THF/THF, and THF+allo-THF/THE were inversely correlated with hemoglobin A1c (r = -0.69, P < 0.001; r = -0.61, P < 0.01; and r = -0.58, P < 0.01, respectively). Upper arm segmental blood volume, estimated by an electrical impedance technique, was positively correlated with the cortisol to cortisone metabolite ratio in both the control subjects (r = 0.77; P < 0.05) and the IDDM patients in whom it was measured (r = 0.56; P < 0.05; n = 13), whereas the regression line was shifted leftward in IDDM (i.e. a lower ratio at the same blood volume; P < 0.03, by analysis of covariance). In seven microalbuminuric IDDM patients, the angiotensin-converting enzyme inhibitor, enalapril (10 mg daily for 6-12 weeks), resulted in a moderate further lowering of the cortisol to cortisone metabolite ratio (P < 0.05). The present data suggest a chronic hyperglycemia-related impairment in the reduction of corticoids to tetrahydro metabolites and an imbalance in 11 beta HSD. Altered 11 beta HSD activity is unlikely to be primarily responsible for the sodium and fluid retention in IDDM. Moreover, an additional mechanism of action of angiotensin-converting enzyme inhibition might be provided by an effect on 11 beta HSD activity.

Adrenal Cortex Hormones↗
PubMed1995

Dopaminergic modulation of physiological and pathological neurohumoral activation in man.

Close relations exist between the peripheral dopaminergic system, and the sympathetic nervous and renin-angiotensin-aldosterone system: D1 dopamine receptor stimulation-induced vasodilation may activate the sympathetic nervous and renin-angiotensin system in vivo, presynaptic D2 dopamine receptor stimulation is known to inhibit stimulated norepinephrine release from sympathetic nerve terminals, in experimental conditions both in vitro and in vivo. Endogenous dopamine has a tonic inhibitory effect on aldosterone release. Conversely, basal sympathetic activity has been found to be required for the natriuretic effect of dopamine in proximal renal tubules. Other relations include the conversion of dopamine to other catecholamines, and co-release. This review considers the reflection of some of these relations and their clinical significance in man in physiological and pathophysiological conditions, especially congestive heart failure. An inhibitory effect of the nonselective dopamine agonist ibopamine on plasma norepinephrine levels was found in normal man during exercise but not at rest, and in patients with several degrees of congestive heart failure, both at rest and during exercise. Infusions of dopamine 1 microgram/kg/min, but not 3 micrograms/kg/min were found to lower plasma norepinephrine levels during sympathetic stimulation by exercise or by a cold pressor test in normal man. Dopamine antagonists enhance the rise in plasma norepinephrine levels during exercise, indicating that endogenous dopamine also inhibits norepinephrine release. Both phentolamine and prazosin abolish the natriuretic effects of dopamine in man, even when the renal hemodynamic effect of dopamine is unaffected. In conclusion, it is important to be aware of clinically significant interactions between the peripheral dopaminergic and sympathetic nervous system at different levels.

Adrenergic alpha-Antagonists↗
PubMed1995

The effects of different doses of dopamine and domperidone on increases of plasma norepinephrine induced by cold pressor test in normal man.

The effect of dopamine 1 and 3 micrograms/kg/min i.v., of dopamine 1 and 3 micrograms/kg/min i.v. combined with domperidone 30 mg per os and of placebo infusion on plasma norepinephrine concentration before and during sympathetic stimulation by a cold pressor test was investigated in 10 healthy volunteers (1 female, 9 males, mean age 28, range 19-41). Dopamine 1 microgram/kg/min resulted in a blunting of the rise in plasma norepinephrine concentration during the cold pressor test, compared with placebo infusion. The addition of domperidone to dopamine 1 microgram/kg/min abolished this effect. Plasma norepinephrine levels during dopamine 3 micrograms/kg/min infusion, both with and without domperidone, were not different from placebo, but significantly higher compared to dopamine 1 microgram/kg/min infusion. Dopamine 1 and 3 micrograms/kg/min infusion, both with and without domperidone resulted in a blunted increase in blood pressure compared to placebo infusion. Dopamine 1 microgram/kg/min infusion resulted in a lower systolic blood pressure during the cold pressor test compared to dopamine 3 micrograms/kg/min infusion. No significant changes in heart rate occurred during the cold pressor test comparing the different circumstances. We conclude that in healthy volunteers only dopamine 1 microgram/kg/min, but not dopamine 3 micrograms/kg/min, blunts the increase in plasma norepinephrine concentration during a cold pressor test; this effect is abolished by pretreatment with domperidone. We presume that for dopamine 1 microgram/kg/min the inhibitory effects of presynaptic DA-2 receptor or alpha-2 adrenoceptor stimulation on plasma norepinephrine concentration predominate. When dopamine 3 micrograms/kg/min is infused, the inhibitory effects might be counteracted by uptake-1 inhibition or enhanced synthesis and release of norepinephrine, either directly or indirectly.

Adult↗
PubMed1995

Esophageal hypomotility in primary and secondary Raynaud's phenomenon: comparison of esophageal scintigraphy with manometry.

UNLABELLED: Esophageal motility was assessed by manometry and scintigraphy in 25 patients with primary Raynaud's phenomenon and 24 patients with secondary Raynaud's phenomenon as part of a connective tissue disorder. METHODS: For each scintigraphic study, transit time was evaluated after three separate swallows. Scintigraphy was abnormal if transit time was longer than 15 sec for two or three measurements. RESULTS: In the case of primary Raynaud's phenomenon, manometry was normal in 24 of 25 patients. A similar ratio was found with scintigraphy. In the case of secondary Raynaud's phenomenon manometry was abnormal in 15 of 24 patients, while scintigraphy was abnormal in 13 of 24 patients. Considering manometry as gold standard, overall sensitivity of scintigraphy was 86%, specificity 89%, positive predictive value 75% and negative predictive value 94%. CONCLUSION: Esophageal dysfunction is common in patients with connective tissue disorders but rare in patients with primary Raynaud's phenomenon. Esophageal scintigraphy is a useful noninvasive initial screening test for esophageal dysfunction in patients with Raynaud's phenomenon.

Adolescent↗
PubMed1995

Relationship between blood pressure during haemodialysis and ambulatory blood pressure in between dialyses.

BACKGROUND: Ambulatory blood pressure measurements in haemodialysis patients are relevant in view of the high cardiovascular morbidity and mortality in chronic haemodialysis patients. METHODS: Twelve normotensive patients were studied from the beginning of one dialysis until the end of the next (mean 64 h, SD 19 h) using a Spacelabs oscillometric blood-pressure recorder. RESULTS: A circadian blood pressure rhythm was present in six of the 12 patients. In seven patients the lowest pressure recorded (including the dialysis sessions) occurred 5-6 h after dialysis (late post-dialysis dip). Blood pressure did not increase sharply in the hours before dialysis although it increased slightly in the interdialytic interval as a whole, at a mean rate of 5.6 mmHg per 24 h (SD 4.1, P < 0.001). We could not find a blood pressure measurement during dialysis (or combination of measurements) which reliably reflects interdialytic blood pressure: the 95% confidence intervals were 25 mmHg or higher. CONCLUSION: Ambulatory blood pressure measurements are needed for adequate monitoring of the control of blood pressure in haemodialysis patients.

Adult↗
PubMed1994

Familial hypokalemic periodic paralysis. Clinical, diagnostic and therapeutic aspects.

Five generations of a family with hypokalemic periodic paralysis (HOPP) were studied. Of the 120 screened family members, 64 were found to have HOPP of which 38 were suffering from attacks. In the other 26 the diagnosis was made on account of vacuolar myopathy, a reduced muscle fiber conduction velocity or the signs of permanent muscle weakness (PMW) in combination with (grand)children with attacks. Applying these criteria skipping of generations did not occur in this family. When defined properly, PMW was found in all patients at older age, independent of the previous occurrence of paralytic attacks. Dynamometry and muscle CT-scanning appeared valuable in the diagnosis and the progression of PMW. In 2 patients autopsy was performed. Characteristics vacuolization was found in the striated muscle tissue in various degrees. Heart and smooth muscle tissue were not involved. Therapy is limited. Potassium salts shortening and preventing the paralytic attacks are tolerated well. Acetazolamide is more effective in the prevention of the paralytic attacks, but is not tolerated very well. HOPP can be considered as a myopathy characterized by PMW at older age in all patients, combined with paralytic attacks in more than half the patients.

Acetazolamide↗
PubMed1994

Serial nailfold capillary microscopy in primary Raynaud's phenomenon and scleroderma.

Eighty-four patients with long-standing Raynaud's phenomenon (RP) were evaluated by nailfold capillary microscopy (NCM) in a cross-sectional and longitudinal study. The patients were classified in five diagnostic groups: primary familial RP (n = 16), primary nonfamilial RP (n = 20), possible scleroderma (n = 27), scleroderma (n = 16), and the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome (n = 8). In the cross-sectional study, NCM showed gradually decreasing numbers of capillary loops and increasing numbers of widened and giant loops in the following order: primary RP, possible scleroderma, and scleroderma/CREST, suggesting that these diseases are part of a continuing spectrum of RP. In the longitudinal study there was a decrease in the total number of nailfold capillary loops in scleroderma/CREST but not in primary RP and possible scleroderma.

Adult↗
PubMed1994

Effects of acetylsalicylic acid on peripheral hemodynamics in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors.

Cyclooxygenase inhibitors may affect the hemodynamic status of patients with heart failure adversely and may also block the vasodilatory effects of angiotensin-converting enzyme (ACE) inhibitors in such patients. Relatively low doses of the cyclooxygenase inhibitor acetylsalicylic acid (ASA) are now used routinely in ischemic heart disease, the most important cause of heart failure. Therefore, we investigated the hemodynamic interaction between ASA and captopril in heart failure. In a randomized, cross-over study, 13 patients with congestive heart failure (CHF) who were already receiving maintenance treatment with an ACE inhibitor received a single dose of 25 mg captopril combined with 236 mg ASA or placebo. Peripheral blood flow was studied noninvasively by venous occlusion plethysmography of the calves. Liver blood flow was estimated from indocyanine green (ICG) clearance. Administration of captopril alone significantly decreased blood pressure (BP), and ICG clearance. Calf blood flow remained unchanged. However, after arterial occlusion, hyperemic calf blood flow persisted for longer. Captopril alone did not significantly change the plasma levels of the vasodilating prostaglandins PGI2 and PGE2 or the vasoconstricting thromboxane A2 (TXA2). In contrast, captopril combined with ASA reduced the plasma levels of these vasoactive substances, with significant decreases in PGE2 and TXA2 as compared with captopril alone, yet the hemodynamic alterations after captopril plus ASA were similar to those observed after captopril alone. A single antithrombotic dose of ASA (236 mg) in 13 patients with CHF [New York Heart Association (NYHA) class II-IV] undergoing chronic treatment with ACE inhibitors had no discernible effect on hemodynamic status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗