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Biomedical subjects

H Wesseling

Publications and source records attributed to H Wesseling.

At least 73 records · Page 4Linked to original sources
PubMed1990

Basic pharmacology of ACE-inhibitors with respect to ischaemic heart disease: prostaglandins and bradykinin.

Experimental evidence suggests that ACE-inhibitors possess cardioprotective properties. Since ACE-inhibitors can prevent bradykinin breakdown and can stimulate prostaglandin production, it is thought that these cardioprotective effects are mediated by bradykinin and prostaglandins. This article summarizes the results indicating that bradykinin and prostaglandins, although not the only factors, do play an important role in cardioprotection by ACE-inhibitors. Special attention is paid to the presence of the sulphydryl moiety of certain ACE-inhibitors. Probably, these sulphydryl group-containing ACE-inhibitors have an additional protective effect through an interaction with bradykinin or through scavenging of free radicals. However, these cardioprotective effects have not yet been shown in patients with ischaemic heart disease, although some studies indicate that ACE-inhibitors are also able to cause anti-ischaemic effects in patients. Further studies are required to establish the clinical importance of cardioprotection by ACE-inhibitors in ischaemic heart disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Different results in cardiopulmonary exercise tests after long-term treatment with felodipine and enalapril in patients with congestive heart failure due to ischaemic heart disease.

We evaluated the cardiopulmonary exercise test results before and after long-term (16 weeks) treatment with the dihydropyridine calcium antagonist, felodipine (10 mg b.i.d., n = 9), and the ACE inhibitor, enalapril (10 mg b.i.d., n = 11), in 20 patients with New York Heart Association class III congestive heart failure. There were no significant differences at baseline. After 16 weeks patients in the enalapril group showed a significant increase in exercise duration and VO2max, without changes in arterial pressures and heart rate. In the felodipine group, exercise duration and VO2max did not change significantly, but arterial pressures and heart rate were significantly reduced at all exercise levels. Between group analysis showed a significant reduction in arterial pressures and heart rate in the felodipine group compared with enalapril, but no differences in aerobic capacity and exercise duration. These results demonstrate that felodipine and enalapril have essentially different effects on cardiopulmonary exercise results in patients with congestive heart failure.

Aged↗
PubMed1990

Quality of life on antihypertensive therapy: a randomized double-blind controlled trial of captopril and atenolol.

A randomized double-blind study lasting 2 months was performed with either 25 mg captopril twice a day or 50 mg atenolol once a day in 125 patients with established diastolic hypertension (diastolic blood pressure greater than 95 mmHg) identified during a population screening programme of subjects aged less than 65 years. Quality of life was assessed from self-completed questionnaires. A significant fall in diastolic blood pressure occurred with both captopril (106.7 +/- 7.0 to 98.6 +/- 8.6 mmHg) and atenolol (107.4 +/- 7.5 to 98.2 +/- 8.1 mmHg) but there was no difference between the two drugs in the size of the fall. A measure of the number of symptomatic complaints, the symptom complaint rate, decreased with both drugs, by 1.3% for captopril and 3.1% for atenolol, but the difference between the drugs was not significant [1.8%; 95% confidence interval (Cl) - 1.3%, 4.9%]. There was a significant increase in the reporting of cough and runny nose in those on captopril compared with atenolol. A health index increased by 1.1% with captopril in comparison with no change on atenolol (difference 1.1%; 95% Cl - 2.0%, 4.2%). Psychological well-being was measured using the Symptom Rating Test. The improvement in total score was 1.4% with captopril and 2.3% with atenolol. The difference of 0.9% was not statistically significant (95% Cl - 1.2%, 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Affect↗
PubMed1990

Effects of isradipine on hemodynamic parameters and ventricular tachycardia in healed myocardial infarction.

The calcium-entry blocker isradipine was tested in a closed-chest pig model for chronic myocardial infarction. Ischemia was evoked in anesthetized pigs (25-35 kg) by inflating a catheter balloon in the left anterior descending coronary artery for at least 45 min. Hemodynamic monitoring and signal averaging of X, Y, and Z electrocardiographic leads were performed (150 beats, filtered at 50 Hz). After reperfusion, all animals developed an accelerated idioventricular rhythm and high creatine kinase (CPK) plasma levels. Coronary venous purines and catecholamines increased transiently. Two hours after reperfusion, heart rate was elevated from the initial 87.5 +/- 6.3 to 126 +/- 6.4 beats/min (p less than 0.01) and the pressure-rate product (PRP, an index of oxygen demand) from 9,530 +/- 630 to 11,950 +/- 790 mm Hg/min (p less than 0.05). After 2 weeks, six surviving pigs had a decreased stroke volume (98 +/- 18 versus the initial 124 +/- 14 microliters/kg, p less than 0.05), a prolonged high-frequency signal-averaged QRS duration (81.2 +/- 6.5 versus 65.7 +/- 2.9 ms, initially; p less than 0.05), and ventricular tachycardias (VTs), inducible by programmed electrical stimulation (PES). After the infusion of isradipine (1 microgram/kg/min for 30 min), the cardiac index increased from 92 +/- 14 to 133 +/- 8.7 ml/min.kg (p less than 0.02). Even at a higher heart rate, the PRP dropped from 12,600 +/- 1,900 to 10,560 +/- 1,400 mm Hg/min (p less than 0.05). Sustained monomorphic tachycardias were inducible in five pigs before and in three pigs after isradipine, and no deterioration of the signal-averaged electrocardiogram parameters was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Flecainide: long-term effects in patients with sustained ventricular tachycardia or ventricular fibrillation.

Efficacy of flecainide was investigated in 50 patients with sustained ventricular tachycardia (n = 38) or ventricular fibrillation (n = 12) during a 4-week in-hospital and 1-year follow-up period. Furthermore, the predictive value of programmed electrical stimulation, Holter monitoring, and exercise testing on outcome of long-term treatment was studied. Etiology of the tachyarrhythmia was coronary artery disease in 37 patients and other etiologies in 13 patients. The success rate of flecainide after 1 year, based on intention to treat, was 54%. The success rate during the in-hospital phase was 84% (in six patients flecainide was discontinued because of tachyarrhythmia and in two because of side effects). Calculated after 4 weeks hospitalization, the success rate was 78% for patients with tachyarrhythmias based on coronary artery disease and 55% for patients with tachyarrhythmias based on other etiologies (11 patients showed recurrences and two patients severe side effects). Patients with tachyarrhythmias based on coronary artery disease showed a lower ejection fraction and earlier recurrence than patients with arrhythmias based on other etiologies. Proarrhythmic effects developed in six patients (12%). Electrophysiological evaluation was performed in 28 patients at baseline and after intravenous flecainide. Negative predictive value of the electrophysiological evaluation after intravenous flecainide for patients with inducible tachyarrhythmias at baseline (n = 21) was 40%. For Holter monitoring (n = 24) this value was 86%. Non-ischemia-related induction of tachycardia by exercise was present in two of 30 patients on flecainide; both patients showed recurrence of the tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

The effects of bradykinin and the ischemic isolated rat heart.

The converting enzyme not only converts angiotensin I into angiotensin II but also metabolizes bradykinin. Furthermore, the effects of ischemia on myocardial tissue damage can be modulated by converting enzyme inhibitors. It is unknown whether these effects of ACE-inhibitors are due to increased bradykinin production. In this paper we describe the effects of captopril on bradykinin production in the ischemic isolated rat heart. The reduced deleterious effects of ischemia by captopril were associated with a stimulated bradykinin production. Beneficial effects of bradykinin could be due to an improved perfusion or to an effect on cellular metabolism. Therefore, we conclude that this effect on kinins by ACE-inhibitors is of importance in modulating tissue damage during ischemia.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Groningen Hypertension Service: ten years experience in detecting and treating hypertension in a population of 23,340 persons in rural and urban districts in Holland with a special hypertension service.

The Groningen Hypertension Service (GHS) has demonstrated that provision of training for volunteers, technical assistance and the services of the General Practitioner Laboratory (a private foundation offering laboratory and diagnostic facilities) have enabled large rural and urban districts to be screened for hypertension within a short period of time at low cost. The GHS trained volunteers and paramedics, who assisted with the treatment for six months. The General Practitioner Laboratory evaluated treatment in nearly 600 hypertensive patients, leading to the institution of low-dose therapy and careful investigation of side-effects.

Adult↗
PubMed1989

Oral pharmacokinetics of felodipine in patients with congestive heart failure: variable prediction using intravenous data.

Peak and trough concentrations after 8 weeks oral therapy with felodipine, a vasodilating calcium antagonist of the dihydropyridine group, were predicted from intravenous pharmacokinetic data before therapy in 11 patients, randomly allocated to felodipine treatment 10 mg b.i.d., during a placebo controlled study in patients with congestive heart failure. Peak concentrations were well predictable, but trough levels varied between a good agreement in some patients to a large underestimation in others. Predictability was significantly correlated with half life, plasma clearance and distribution volume of the intravenous pharmacokinetic study. After 8 weeks chronic oral therapy no significant differences could be detected between the oral pharmacokinetics of predictable (n = 6) and unpredictable (n = 5) patients. This demonstrates that felodipine kinetics change during felodipine treatment. Differences in the distribution of blood flow before therapy combined with an interindividual variability in blood flow response during therapy is probably responsible for the observed impossibility to calculate trough levels, and thus oral dosage schedules, from intravenous pharmacokinetic data in patients with congestive heart failure.

Administration, Oral↗
PubMed1989

Flecainide acetate in the treatment of supraventricular tachycardias: value of programmed electrical stimulation for long-term prognosis.

Twenty patients with recurrent symptomatic supraventricular tachycardia were studied to estimate the efficacy of flecainide in the long-term treatment of these arrhythmias and to evaluate the prognostic value of programmed electrophysiologic stimulation. All patients had their arrhythmia inducible at baseline evaluation. Nine patients had a Wolff-Parkinson-White (WPW) syndrome, five had a concealed bypass tract, and two had dual atrioventricular (AV) nodal pathways. In the remaining patients there was an intraatrial reentry circuit. Previous medication was no to five antiarrhythmic drugs (mean 2.4 drugs). At baseline, a circus movement tachycardia was induced in 12, AV nodal tachycardia was induced in two, atrial tachycardia was induced in three, atrial fibrillation was induced in five, and a flutter was induced in two patients. After flecainide, 2 mg/kg intravenously in 10 minutes, six patients no longer had their arrhythmia inducible. In the WPW patients, atrial fibrillation was no more inducible. In 65% of the patients there was no recurrence during a follow-up period of 11 +/- 10 months. None of the six patients who no longer had their arrhythmia inducible had a recurrence of the tachycardia over a period of up to 3 years. Seven of the other 14 patients (who still had their arrhythmia inducible) had a recurrence of the tachycardia. Positive and negative predictive values are 50% and 100%, respectively. We conclude that flecainide prevents recurrences of supraventricular tachycardias in 65% of patients with inducible supraventricular tachycardias during a mean follow-up of 11 months. Programmed electrical stimulation has a high negative predictive value in this setting. Flecainide is especially effective in preventing atrial fibrillation in patients with WPW syndrome.

Adult↗
PubMed1989

Acute and chronic effects of ramipril and captopril in congestive heart failure.

We studied the acute and long-term effects of ramipril and captopril in 12 patients with moderate to severe congestive heart failure using an open, parallel design. Drug doses were titrated. Compared with baseline values, maximal haemodynamic and humoral effects after the first dose of both angiotensin converting enzyme inhibitors were similar, but the effects of ramipril (5 mg) demonstrated a slower onset of action and a significantly longer duration than captopril (12.5 mg). After 3 months of treatment a single dose of 5 mg ramipril showed the same 24-hour haemodynamic profile as after the first dose, but the hypotensive effect was less marked. There was no plasma accumulation of ramiprilat. Serum creatinine and potassium remained stable, except for one patient whose renal function deteriorated on captopril treatment. Complex ventricular arrhythmias occurred in 11 patients and were unaffected after treatment with ramipril or captopril. Two patients died suddenly during ramipril therapy and one patient during captopril therapy. In summary, ramipril is an effective, long-acting angiotensin converting enzyme inhibitor, producing long-term haemodynamic effects in patients with congestive heart failure. Using an individualised dosage scheme, neither long-lasting hypotension nor deterioration of renal function occurred. No effect on ventricular arrhythmias was seen.

Aged↗
PubMed1989

The haemodynamic effects of two angiotensin converting enzyme inhibitors, enalaprilat and zofenoprilat, in the rat: evidence for the involvement of bradykinin.

Since angiotensin converting enzyme (ACE) metabolizes bradykinin, the hypotensive effect of ACE inhibitors could be partly due to an increased bradykinin activity. We therefore investigated the influence of HOE K86-4321 [D-Arg-(Hyp2-Thi5,8-DPhe7)-bradykinin], a selective bradykinin-2 receptor antagonist, on the effects of enalaprilat (0.3 and 3.0 mg/kg) and zofenoprilat (0.1 and 1.0 mg/kg) on the heart rate, mean arterial blood pressure, cardiac output and total peripheral resistance in rats. Both enalaprilat and zofenoprilat reduced mean arterial pressure (from 110 +/- 7 to 85 +/- 6 and from 108 +/- 9 to 72 +/- 9 mmHg, respectively; P less than 0.05) and total peripheral resistance (from 515 +/- 35 to 413 +/- 29 and from 495 +/- 45 to 310 +/- 25 x 10(-3) mmHg/litre per min per kg, respectively; P less than 0.05); the heart rate and cardiac output changed little. In the presence of HOE K86-4321, which by itself did not affect the haemodynamic variables measured, the effects of the two ACE inhibitors were significantly reduced. These results suggest that bradykinin-2 receptor-mediated vasodilation, although not involved in blood pressure regulation, influences the reduction in blood pressure induced by enalaprilat and zofenoprilat in normotensive rats. Furthermore, at comparable ACE-inhibiting doses, zofenoprilat was more effective in reducing mean arterial pressure, which might be related to the presence of a sulphydryl group.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Effects of angiotensin II and captopril on inducible sustained ventricular tachycardia two weeks after myocardial infarction in the pig.

The effects of angiotensin II (AII) and captopril (C) on the inducibility of ventricular tachyarrhythmias were investigated 14 days after infarction in pigs. In 27 pigs, ischemia was induced by 60-min occlusion of the left coronary artery. Four pigs died of ventricular fibrillation during ischemia, and six others died within 24 h due to pump failure. Of the 17 survivors, eight pigs developed a sustained (greater than 30 s) monomorphic ventricular tachycardia (sVT) after programmed electrical stimulation. In nine noninducible pigs, an AII infusion (0.6 microgram/kg/min) caused inducible sVT in three animals and nonsustained VT in two animals (greater than 10 reentrant beats). In two of the remaining four animals, spontaneous premature ventricular beats appeared during the infusion. In a group of five healthy pigs, the electrophysiological effects of AII were evaluated. Infusion of AII caused a rapid and sustained increase in arterial blood pressure to 161 +/- 6.4% (p less than 0.001). The sinus cycle length decreased to 74 +/- 5.2% (p less than 0.02). The effective refractory period of the right ventricle decreased significantly to 82 +/- 5.5% (p less than 0.05). These results show that modulation of the renin-angiotensin system after myocardial infarction influences the inducibility of malignant ventricular tachyarrhythmias, as shown by the increased inducibility of sustained ventricular tachycardia. This may be related to a decreased ventricular refractoriness. Therefore, it is suggested that C can reduce malignant ventricular tachycardia late after myocardial infarction by preventing the deleterious arrhythmogenic effects of AII.

Angiotensin II↗
PubMed1989

Plasma concentration-effect relationship of felodipine intravenously in patients with congestive heart failure.

The pharmacodynamics of felodipine were analyzed in patients with congestive heart failure in a randomized, double-blind, placebo-controlled study. Felodipine at a dose of 1 mg (n = 11) or placebo (n = 12) was given intravenously during a 60-min period. Hemodynamic measurements and plasma samples were obtained every 15 min during a 2-hour period. An increase in heart rate (HR, +8%, p less than 0.01) and cardiac output (CO, +36%, p less than 0.001), and a decrease in mean arterial pressure (MAP, -24%, p less than 0.001) and systemic vascular resistance (SVR, -46%, p less than 0.001), were found. Pulmonary artery, right atrial, wedge pressure, and stroke-work index did not change. Linear regression analysis showed a significant correlation between felodipine plasma levels and changes in HR (r = 0.71, p less than 0.05), MAP (r = 0.94, p less than 0.01), CO (r = 0.73, p less than 0.05), and SVR (r = 0.88, p less than 0.01). A strong hyperbolic correlation was demonstrated between individual plasma levels and changes in MAP (r = 0.97, p less than 0.001). Hysteresis analysis showed that plasma levels are directly related to the concentration at the receptor site. A clockwise hysteresis was found in HR, CO, and SVR, but not in MAP. It is concluded that changes in flow and resistance are based on a physiological adjustment, a baroreflex-mediated response to vasodilation induced by felodipine, resulting in MAPs that remain closely related to felodipine plasma levels over a wide range.

Aged↗
PubMed1989

Pharmacokinetics of felodipine after intravenous and chronic oral administration in patients with congestive heart failure.

1. In a randomized, parallel, double-blind study felodipine was administered to 11 and placebo to 12 patients with congestive heart failure. The kinetics of felodipine were studied after acute intravenous administration and after chronic oral treatment for 8 weeks. The relationship between cardiac output and pharmacokinetics was analyzed. The pharmacokinetic data were compared with data from young healthy individuals and hypertensive patients. 2. After oral therapy, significant correlations were found between cardiac output and AUC and systemic bioavailability (F). Furthermore, cardiac output before therapy was also significantly correlated with absorption characteristics. No relationship could be demonstrated between cardiac output and i.v. pharmacokinetics. A comparison of patients with heart failure and young healthy individuals revealed that the AUC was three times higher in heart failure patient, while Vss and the ratio of the AUC of the pyridine metabolite to that of felodipine were similar. Oral clearance was reduced by 50% and the terminal half-life was concomitantly increased. Pharmacokinetic data for felodipine are similar in patients with heart failure to published data from elderly hypertensive patients. 3. An increase in liver blood flow during chronic oral therapy, induced by felodipine itself, appears to explain an increase in bioavailability and thus to higher plasma drug concentrations. Thus, it is advisable to start felodipine treatment at a low dosage in patients with congestive heart failure.

Administration, Oral↗
PubMed1989

Impaired renal hemodynamic but conserved natriuretic response to dopamine in patients with renal disease.

Renal hemodynamics and sodium excretion were determined before and during infusion of dopamine in doses ranging from 0.25 to 8 micrograms/kg/min in healthy volunteers (n = 15) and in patients with renal disease and moderately impaired renal function (n = 21, baseline glomerular filtration rate 34-85 ml/min). While in normal volunteers dopamine resulted in marked renal vasodilation (maximal fall in filtration fraction 24%), in patients with moderately impaired renal function, the renal vasodilatory response to dopamine was impaired (maximal fall in FF 13%) and was found to depend on baseline glomerular filtration rate. Infusion of dopamine in doses of 2 micrograms/kg/min and higher resulted in an increase in urinary sodium excretion, which was comparable for healthy volunteers and patients with renal disease. We conclude that dopamine results in a predominantly efferent glomerular vasodilation and, therefore, may be salutary in lowering intraglomerular hypertension. However, in patients with renal disease the renal hemodynamic response to dopamine infusion is impaired compared to healthy volunteers, while the natriuretic response is maintained.

Blood Pressure↗
PubMed1989

Cardiac arrhythmias--a new indication for angiotensin-converting enzyme inhibitors?

Ventricular arrhythmias (VA) are a major cause of sudden death. Life-threatening VA may be present in a variety of both acute and chronic conditions in which cardiac function is compromised: during acute myocardial infarction and subsequent reperfusion; some weeks after acute myocardial infarction, due to residual damage (scar formation with zones of heterogeneity); and as a consequence of congestive heart failure (CHF) resulting from myocardial infarction, dilated cardiomyopathy, hypertension or other causes. Symptomatic suppression of potentially life-threatening VA is unlikely to decrease mortality, since classical antiarrhythmic drugs have failed, so far, to improve life expectancy. Drugs that influence the underlying causes of CHF seem to have a better chance of reducing mortality. There is evidence that ACE inhibitors may exert beneficial effects on arrhythmogenicity by several mechanisms in these situations. Under acute ischaemic conditions both cellular damage and undue increases in circulating catecholamines and angiotensin II may be prevented. This has been demonstrated in various animal models and confirmatory clinical evidence is emerging. Two week after experimental myocardial infarction, the pig heart is less vulnerable to programmed electrical stimulation when ACE inhibitors are administered. Finally, in CHF a variety of proarrhythmic factors, such as left ventricular dysfunction, raised catecholamine levels and, in particular, decreased potassium concentrations, are influenced beneficially by ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Protective effects of captopril against ischemia/reperfusion-induced ventricular arrhythmias in vitro and in vivo.

The effects of the converting enzyme inhibitor captopril on the susceptibility of the heart to ventricular arrhythmias following ischemia, both in vitro and in vivo, were studied. In isolated rat hearts, captopril, administered either before or at the end of ischemia, reduced ventricular fibrillation upon reperfusion after 15 minutes of local ischemia. Reduction of purine overflow, improvement in contractility, and increase in coronary blood flow occurred concomitantly. In vivo, a closed-chest pig model was used to determine the effects of captopril, administered at the end of ischemia and continued orally, on the susceptibility to ventricular arrhythmias during the chronic phase of myocardial infarction. Myocardial ischemia was induced by 60-minute inflation of a balloon catheter in the left anterior descending coronary artery. Upon reperfusion, an accelerated idioventricular rhythm occurred, both in 10 untreated and in 10 captopril-treated animals. Creatine kinase levels during the reperfusion period were significantly lower after captopril treatment. Two weeks after the short-term experiments, monomorphic ventricular tachycardia could be induced with programmed electrical stimulation in six of eight surviving untreated pigs. In contrast, in none of the six surviving captopril-treated animals was ventricular tachycardia inducible. Thus, early intervention with captopril during the development phase of myocardial infarction may have beneficial effects on the subsequent development of ventricular arrhythmias. Salvage of ischemic myocardium, improvement in ventricular function, beneficial effects on coronary flow, and decreased activity of the sympathetic nervous system may all contribute.

Animals↗