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Biomedical subjects

G Berkenboom

Publications and source records attributed to G Berkenboom.

At least 19 recordsLinked to original sources
PubMed2002

[The cardiology department].

Cardiology was present since the very beginning of the Erasme hospital. The Department of Cardiology was created in 1979. This department is made of a hospitalization unit (54 beds), a coronary care unit (12 beds) and a large technical unit. Clinical activity has increased tremendously and this had led to an important research activity in the fields of cardio-respiratory and metabolic adaptation to exercise, particularly after cardiac transplantation, of cardiovascular epidemiology, of clinical pharmacology and in pulmonary as well as systemic hypertension.

Belgium↗
PubMed2001

[Unstable atheromatous plaque. Physiopathology and therapeutic approach to coronary insufficiency].

Plaque disruption promoted by local inflammation and oxidative stress seems to be the triggering mechanisms of acute coronary syndromes. Oxidized low-density lipoproteins (LDL) play a key role in the inflammatory process. Within the inflammatory region, angiotensin-converting enzyme (ACE) accumulation has been described, leading to enhanced production of angiotensin II which stimulates adhesion molecule formation and increases oxidative stress. According to recent clinical trials, drugs like statins or ACE inhibitors seem promising and could stabilize the plaque, probably by attenuation of the inflammatory process. Finally, as thrombus formation also plays a role in these acute coronary syndromes, another approach is the use of antithrombotic therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Early alterations of myocardial blood flow reserve in heart transplant recipients with angiographically normal coronary arteries.

BACKGROUND: The evaluation of the coronary reserve provides valuable information on the status of coronary vessels. Therefore, we studied with positron emission tomography (PET) and 13N-ammonia the myocardial blood flow (MBF) reserve in heart transplant recipients free of allograft rejection and with angiographically normal coronary arteries early after heart transplantation (HTx). The MBF reserve was calculated as the ratio between MBF after dipyridamole injection and basal MBF normalized for the rate-pressure product. METHODS: Patients were studied within 3 months (group A, n = 12) or more than 9 months (group B, n = 12) after HTx. Five patients have been studied both during the early and late period after HTx. Results were compared to those obtained in 7 normal volunteers (NL). RESULTS: Group A recipients had a significantly lower dipyridamole MBF (in ml/min/100 gr of tissue) than that of group B recipients (142+/-34 vs 195+/-59, p<0.05). This resulted in a significant decrease in MBF reserve early after HTx (group A: 1.82+/- 0.33) and a restoration to normal values thereafter (group B: 2.52+/- 0.53 vs NL: 2.62+/-0.51, p = ns). Separate analysis of 5 patients studied twice is consistent with these results. CONCLUSION: This study shows that in heart transplant recipients free of allograft rejection and with normal coronary angiography, MBF reserve is impaired early after HTx. Restoration within one year suggests that this abnormality does not represent an early stage of cardiac allograft vasculopathy.

Adult↗
PubMed1999

Absence of L-arginine effect on coronary hypersensitivity to serotonin in cardiac transplant recipients.

Coronary hypersensitivity to serotonin promotes platelet aggregation and, therefore, the progression of the atherosclerotic process. This abnormality occurs in the early stages of coronary atherosclerosis when the responses to bradykinin are still preserved. To determine whether such changes also occur early after cardiac transplantation, intracoronary injections of bradykinin and serotonin were performed in 7 control patients, in 19 patients with dyslipidemia, and in 15 cardiac transplant recipients (1 year after operation). Coronary angiography was normal in the 3 groups. In the segments where serotonin effects were the most pronounced, the diameter changes were measured by quantitative angiography. Bradykinin (60, 200, and 600 ng) increased in the same way as the coronary diameters in the 3 groups; in contrast, serotonin elicited vasodilation only in the control group (7+/-3%, percentage of baseline) and vasoconstriction in the hyperlipidemic group (-9+/-2%) and in transplant recipients (-15+/-3%). After intracoronary infusion of L-arginine (40 mg/min for 14 minutes), serotonin-induced constriction was attenuated in the hyperlipidemic group but not in transplant recipients. Thus, the response to bradykinin is preserved in the early stages of graft vasculopathy. However, in contrast to patients with hyperlipidemia, the absence of an L-arginine effect on the responses to serotonin suggests the involvement of mechanisms other than a decrease in endothelium-derived nitric oxide availability. Immune processes promoting the release of endothelium-derived contracting factors such as endothelin and/or superoxide anion may play a role.

Arginine↗
PubMed1999

Absence of nitrate tolerance after long-term treatment with ramipril: an endothelium-dependent mechanism.

To determine whether nitrate tolerance is attenuated on aortas isolated from rats treated in the long term with an angiotensin-converting enzyme (ACE) inhibitor, five groups of rats were studied in parallel. Group 1 received ramipril, 1 mg/ kg/day, p.o., for 6 weeks; group 2 received ramipril at the same dose for 4 weeks, and the last 2 weeks, a cotreatment with ramipril plus HOE 140 (a bradykinin B2 antagonist, 500 microg/ kg/day, s.c. injections); group 3 received losartan, 2 mg/kg/day, p.o., for 6 weeks; group 4 received losartan at the same dose, and the last 2 weeks, a cotreatment with losartan plus HOE 140; and group 5 served as control. Rings of thoracic aorta from these groups were studied in organ baths. After nitroglycerin preincubation (10 microM for 30 min) in vitro, the dose-response curves to nitroglycerin were significantly shifted to the right in the control group but not in group 1. This protective effect was partially present in group 3; it was completely abolished in groups 2 and 4. In groups 1 and 3, it also was abolished after nitric oxide synthase (cNOS) inhibition (L-NMMA incubation) or removal of the endothelium. Superoxide anion accumulation (assessed by lucigenin chemiluminescence) was increased by nitroglycerin incubation in the control group but not in groups 1 and 3. After in vivo exposure to nitroglycerin (50 mg/kg subcutaneously twice daily for 4 days), this protection against nitrate tolerance also was observed in groups 1 and 3. Thus long-term ACE inhibition prevents nitrate tolerance by an endothelium-dependent mechanism involving mainly an enhanced NO availability via B2-kinin receptor. This effect on the cNOS pathway seems to attenuate the superoxide anion accumulation induced by nitroglycerin exposure (probably via a downregulation of oxidative enzyme).

Adrenergic beta-Antagonists↗
PubMed1999

[Vascular endothelium: target organ of cardiovascular pathologies].

The endothelium plays an essential role in regulation of vascular tone. It has vasodilator, antiaggregating, anti-thrombotic and anti-inflammatory properties. In the case of endothelial dysfunction (induced by hypercholesterolaemia, hypertension and/or diabetes), all of these properties are reversed; it becomes thrombogenic, it secretes vasoconstrictor substances promoting platelet aggregation and penetration of white blood cells into the vessel wall. This endothelial dysfunction then allows the development of the atheromatous lesion. The therapeutic approach must be based on restoration of the normal physiological properties of the endothelium.

Adult↗
PubMed1998

Endothelial function of internal mammary artery in patients with coronary artery disease and in cardiac transplant recipients.

The objective of this study was to examine the endothelial function of internal mammary artery in patients with coronary artery disease and in heart transplant recipients. Therefore the response of this artery to increasing concentrations of acetylcholine (1, 10, 20 microg/min for 2.5 minutes each) was assessed in 6 patients in a control group, 16 patients with coronary artery disease (CAD group) matched for risk factors with 16 heart graft recipients (who underwent transplantation for nonischemic heart failure), and 12 patients with coronary artery disease and peripheral vascular disease (PVD group). Diameters of proximal and middle segments of internal mammary artery were measured by quantitative angiography. The responses to the first concentration of acetylcholine were attenuated in these three groups compared with the control group. At the highest concentration of acetylcholine the diameter increase was similar in the control and CAD groups, whereas the responses remained significantly impaired in the transplant and PVD groups. However, after selective infusion of L-arginine (30 mg/min for 11 minutes), the precursor of endothelium-derived nitric oxide, was performed, the responses to acetylcholine were restored in these two latter groups. Endothelin plasma levels were significantly enhanced in the PVD group, which exhibited the most severe impairment in acetylcholine-induced vasodilation. Thus some patients with CAD, mainly those with advanced atherosclerosis, and cardiac transplant recipients exhibit internal mammary artery endothelial dysfunction, and this abnormality seems reversible.

Acetylcholine↗
PubMed1998

Assessment of coronary flow reserve by transesophageal echocardiography in cardiac transplant recipients.

This study investigated the feasibility of dipyridamole Doppler transesophageal echocardiography to assess coronary flow reserve in 26 patients with orthotopic heart transplantation and compared it with positron emission tomography. We found an 85% success rate in obtaining Doppler flow signals in the proximal left anterior descending coronary artery. Our data also showed that the correlation between transesophageal echocardiography and dipyridamole N-13 ammonia positron emission tomography increases when respective resting rate-pressure products are taken into account. However, comparison between the two methods should be made with caution because coronary flow reserve derived from transesophageal echocardiography tends to be higher than that obtained with positron emission tomography.

Adult↗
PubMed1998

Unstable atherosclerotic plaque. Pathophysiology and therapeutic guidelines.

Plaque disruption promoted by local inflammation and oxidative stress seem to be the triggering mechanisms of acute coronary syndromes. Oxidized low-density lipoproteins (LDL) play a key role in this inflammatory process. Within the inflammatory region, angiotensin-converting enzyme (ACE) accumulation has been described, leading to enhanced production of local angiotensin II which stimulates adhesion molecule expression and increases oxidative stress (leading to excessive degradation of EDNO). According to recent clinical trials, drugs like statins or ACE inhibitors seem promising and could stabilize the plaque, probably by attenuation of the inflammatory process. Finally, as thrombus formation also plays a role in these acute coronary syndromes, another approach may be the use of antithrombotic therapy.

Coronary Artery Disease↗
PubMed1997

Prevention by selenium supplementation of cyclosporin-A-induced vascular toxicity.

OBJECTIVE: The aim was to determine whether selenium supplementation, an important component of glutathione peroxidase, might attenuate cyclosporin (Cx)-induced vascular toxicity. METHODS: Four groups of rats were treated in parallel: the first group was supplemented with selenium (sodium selenite, 0.5 mg.kg-1) orally (p.o.) for 5 weeks and the same dose of selenium plus Cx 20 mg.kg-1 (i.m.) during the 6th week; group 2 received Cx only (20 mg.kg-1 i.m. for 1 week); group 3 was supplemented with selenium (0.5 mg.kg-1 p.o., for 6 weeks) and group 4 served as control. Thoracic aortas isolated from these various groups were studied in organ baths. RESULTS: In comparison with the control group, selenium supplementation did not modify acetylcholine (Ach)- and nitroprusside-induced relaxations. In group 2, endothelium-dependent relaxations (Ach) were markedly impaired and endothelium-independent relaxations (nitroprusside) were shifted to the right; with selenium supplementation (group 1), the responses to Ach were partially restored whereas the rightward shift of the concentration-response curves to nitroprusside persisted. Incubation with superoxide dismutase (SOD, 150 IU.ml-1) or selenium (1 microgram.ml-1) (but not with selenium plus an inhibitor of the glutathione redox cycle) improved the relaxations to Ach in group 2. CONCLUSIONS: The vascular toxicity of Cx seems related to generation of oxygen-derived radicals promoting EDRF destruction and is attenuated by selenium supplementation.

Acetylcholine↗
PubMed1997

Ramipril prevents endothelial dysfunction induced by oxidized low-density lipoproteins: a bradykinin-dependent mechanism.

We wished to determine whether the acute toxic effects of oxidized LDL are attenuated in aortas isolated from rats chronically treated with an angiotensin-converting enzyme (ACE) inhibitor. In aortic rings incubated with human oxidized LDL (300 microg/mL), the endothelium-dependent relaxations to acetylcholine were attenuated, but not those to A23187 and to nitroprusside. This toxic effect of oxidized LDL was completely prevented in preparations coincubated with oxidized LDL and the nitric oxide (NO) precursor L-arginine (0.3 mmol/L). In aortas isolated from rats orally treated for 6 weeks with 10 mg/kg ramipril (group 1) or 1 mg/kg ramipril (group 2), this toxic effect of oxidized LDL was also markedly attenuated. In contrast, in aortas isolated from rats cotreated with ramipril (10 mg/kg) for 6 weeks and subcutaneous injections of Hoe 140 (a B2 kinin antagonist), 500 microg/kg per day for the last 2 weeks (group 3) or from rats orally treated for 6 weeks with losartan (an AT1-type angiotensin II receptor antagonist), 20 mg/kg (group 4), the inhibitory effect of oxidized LDL on acetylcholine-induced relaxations was similar to that observed in the control group (group 5). Moreover, long-term treatment with ramipril increased relaxations to acetylcholine in groups 1 and 2 and also relaxations to A23187 and aortic cGMP content in group 1, suggesting an enhanced NO availability. Thus, the protective effect of long-term ACE inhibition against the acute vascular toxicity of oxidized LDL is bradykinin dependent and seems to involve a facilitation of NO release via endothelial B2 kinin receptors.

Acetylcholine↗
PubMed1996

Coronary vasomotility and myocardial blood flow early after heart transplantation.

Serotonin constricts coronary arteries with endothelial dysfunction, a common abnormality in cardiac transplant recipients. To assess whether endothelial dysfunction is associated with myocardial blood flow (MBF) abnormalities, 24 patients were studied 1 to 12 months after transplantation. Serotonin in increasing doses (1, 10, and 20 micrograms/min for 2.5 min each) was infused into the coronary circulation. Diameters were measured by quantitative angiography. Fourteen patients (group A) had a pronounced artery constriction (diameter reduction > 40%), while in 10 other patients (group B), such a constriction was never reached. No patient had evidence of rejection and all had angiographically normal coronary arteries. MBF was measured at rest and after intravenous dipyridamole with dynamic nitrogen-13 ammonia positron emission tomography (PET). The resting MBF was higher in group A than in group B (94 +/- 12 vs 74 +/- 15 ml/min/100 g of tissue; p < 0.05). During dipyridamole, MBF was not significantly different (191 +/- 53 vs 184 +/- 64 ml/min/100 g; p = NS). Coronary flow reserve (the ratio of perfusion after dipyridamole to perfusion at rest) was significantly lower in group A than in group B (2.08 +/- 0.54 vs 2.66 +/- 0.57; p < 0.05). Thus, coronary hypersensitivity to serotonin in cardiac transplant recipients is associated with elevated resting MBF and reduced coronary flow reserve. Immune mechanisms inducing endothelial injuries and inflammation-related hyperemia may account for these abnormalities.

Coronary Circulation↗
PubMed1996

Coronary vasomotor responses in cyclosporine-treated piglets.

Chronic treatment with cyclosporine A (Cx) seems to produce a decreased ability of the endothelium to secrete nitric oxide. However, its effect on the coronary arterial system remains controversial. Therefore, coronary arteries isolated from piglets treated by intramuscular injections of Cx (10 mg/kg/day, IM, for 22 days) were studied in organ baths and compared with those isolated from control animals (IM injections of the Cx solvent). Depolarization-induced contractions (KCl 120 mM) were similar in both groups, whereas the acetylcholine-induced contractions (percent of 120 mM KCl) were enhanced: The area under the curve (AUC) was 245 +/- 51 in the Cx group versus 110 +/- 15 in the control group (p < 0.05). Removal of the endothelium did not significantly modify the acetylcholine-induced contractions in both groups and, therefore, did not attenuate the enhanced responsiveness to acetylcholine in the Cx group. On unrubbed rings contracted with prostaglandin F2 alpha, the endothelium-dependent relaxations from serotonin (in the presence of 1 microM ketanserin) were reduced: The AUC was 479 +/- 24 in the Cx group versus 385 +/- 22 in the control group (p < 0.02). Larger AUC values were also found for bradykinin and substance P in the Cx group: 158 +/- 18 versus 55 +/- 17 (in the control group, p < 0.01) and 198 +/- 8 versus 145 +/- 12 (p < 0.01), respectively. Nevertheless, no alteration in calcium ionophore-induced relaxations was observed: The AUC was 217 +/- 10 in the Cx group and 224 +/- 18 in the control group (NS). Indomethacin incubation (10 microM) did not prevent the impairment in endothelium-dependent relaxations and did not attenuate the cyclosporine-induced augmentation of acetylcholine-induced contractions. Thus, chronic administration of cyclosporine to piglets impairs the coronary endothelial function and produces functional changes in smooth muscle cells. These alterations may play a role in the occurrence of cardiac graft vasculopathy.

Acetylcholine↗
PubMed1996

Effect of dietary supplementation with fish oil on cyclosporine A-induced vascular toxicity.

We wished to determine whether dietary supplementation with fish oil prevents the vascular toxicity of cyclosporine (Cx). In a first set of experiments, we assessed the endothelial function of aortas isolated from rats supplemented for 6 weeks with fish oil (FO), administered by gavage, and providing 150 mg/kg/day of eicosapentaenoic acid and 100 mg/kg/day of docosahexaenoic acid. FO treatment altered neither acetylcholine- and histamine-induced relaxations, nor serotonin-induced contractions (NS vs. control group). Thereafter, three groups of rats were treated in parallel. Group 1 received FO supplementation (by gavage) for 6 weeks, and Cx (10 mg/kg/day po) was added during the last 2 weeks, group 2 received Cx only (10 mg/kg/day po) for 2 weeks, and group 3 served as a control. Both acetylcholine-and histamine-induced relaxations were reduced in group 2 compared with the control group, as indicated by the area under the curve (AUC), which was significantly higher: 296 +/- 17 vs. 138 +/- 32, and 392 +/- 38 vs. 318 +/- 25 for acetylcholine and histamine, respectively. In group 1, AUC for acetylcholine remained significantly different from the control (241 +/- 31 vs. 138 +/- 32), whereas AUC for histamine was 367 +/- 28 (NS vs. control). The serotonin-induced contractions were also enhanced in group 2 compared with those of the control group, and this alteration was not attenuated in group 1. After mechanical removal of the endothelium, the increased responsiveness to serotonin persisted in groups 1 and 2, suggesting this functional alteration to be located in the smooth muscle cells. Thus, in the rat the attenuation of Cx-induced vascular toxicity by fish oil supplementation is only partial, that is, it involves a slight improvement in endothelial function, but with persistence of functional changes in smooth muscle.

Administration, Oral↗
PubMed1995

Plasma endothelin and early coronary endothelial dysfunction in recipients of a cardiac transplant.

Serotonin constricts coronary arteries with endothelial dysfunction, possibly through reduced endothelial release of nitric oxide or enhanced production of constricting factors such as endothelin. Because the plasma levels of this peptide are increased in the early months after cardiac transplantation, we assessed whether a coronary hypersensitivity to the vasoconstrictor effect of serotonin is associated with high plasma endothelin levels. One to 3 months after cardiac transplantation, serotonin (1, 10, or 20 micrograms/min for 2.5 min each) was infused into the coronary circulation in 32 patients. Changes in coronary diameters were determined by quantitative angiography. A > or = 40% reduction in coronary diameter for a dose of serotonin < or = 10 micrograms/min was observed in group A (n = 14) whereas in group B (n = 18), this diameter reduction was never reached even for a 20 micrograms/min infusion of serotonin. Plasma endothelin levels were significantly higher (p < 0.01) in the coronary ostium and coronary sinus in group A, at 23.4 +/- 1.3 pg/ml and 24.9 +/- 0.9 pg/ml versus 12.6 +/- 0.9 pg/ml and 13.8 +/- 1.1 pg/ml, respectively, in group B. These endothelin levels did not significantly change after intracoronary infusion of serotonin. A significant correlation was found between plasma endothelin levels in the coronary ostium and peak coronary constriction (percentage diameter reduction) in both groups (r = 0.77 for group A and r = 0.92 for group B). Thus, early after cardiac transplantation, serotonin-induced coronary constriction is a common finding, and the severity of this abnormality seems to be influenced by plasma endothelin levels.

Blood Pressure↗