Biomedical subjects

B J Mulder

Publications and source records attributed to B J Mulder.

28 records · Page 2Linked to original sources

PubMed1994

Effects of low dose aspirin (50 mg/day), low dose aspirin plus dipyridamole, and oral anticoagulant agents after internal mammary artery bypass grafting: patency and clinical outcome at 1 year. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands. Prevention of Coronary Artery Bypass Graft Occlusion by Aspirin, Dipyridamole and Acenocoumarol/Phenprocoumon Study.

OBJECTIVES: This study was performed to compare the efficacy and safety of aspirin, aspirin plus dipyridamole, and oral anticoagulant agents in the prevention of internal mammary artery graft occlusion. BACKGROUND: Antithrombotic drugs increase vein graft patency after coronary artery bypass surgery. Their benefit after internal mammary artery grafting has not been established. METHODS: Angiographic internal mammary artery graft patency at 1 year was assessed in 494 patients who received both internal mammary artery and vein grafts. These patients were a subgroup of a prospective, randomized vein graft patency study in 948 patients assigned to treatment with aspirin, aspirin plus dipyridamole, or oral anticoagulant agents. The design was double-blind for both aspirin groups and open for oral anticoagulant treatment. Dipyridamole (5 mg/kg body weight per 24 h intravenously, followed by 200 mg twice daily) and oral anticoagulant agents (prothrombin time target range 2.8 to 4.8 international normalized ratio) were started before operation, and low dose aspirin (50 mg/day) after operation. Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding or death. RESULTS: Occlusion rates of distal anastomoses were 4.6% in the aspirin plus dipyridamole group and 6.8% in the oral anticoagulant group versus 5.3% in the aspirin group (p = NS). Overall clinical event rates were 23.3% and 13.3% in the aspirin plus dipyridamole group and the aspirin group, respectively (relative risk 1.75, 95% confidence interval 1.09 to 2.81, p = 0.025), and 17.1% in the oral anticoagulant group. CONCLUSIONS: Internal mammary artery graft patency at 1 year is not improved by aspirin plus dipyridamole or oral anticoagulant agents over that obtained with low dose aspirin alone. However, there is evidence that the overall clinical event rate increases if dipyridamole is added to aspirin.

Acenocoumarol↗

PubMed1994

Effect of various antithrombotic regimens (aspirin, aspirin plus dipyridamole, anticoagulants) on the functional status of patients and grafts one year after coronary artery bypass grafting.

From 1987 until 1991 a large prospective randomized multicentre study was performed in The Netherlands, Germany and Switzerland entitled CABADAS (Prevention of Coronary Artery Bypass graft occlusion by Aspirin, Dipyridamole, and Acenocoumarol/Phenprocoumon Study). The aim of CABADAS was to evaluate the relative efficacy of (1) aspirin, (2) aspirin plus dipyridamole, and (3) oral anticoagulants in the prevention of vein graft occlusion during the first year after aortocoronary bypass surgery. No significant difference was observed in the incidence of graft occlusion among the three treatment groups. In a subgroup of 127 CABADAS patients, studied in the Academic Medical Centre in Amsterdam, the relationship between treatment and clinical status (i.e. symptoms of angina pectoris and exercise capacity) was assessed, and the relationship between treatment and functional status of the vein grafts was determined by means of thallium-201 exercise scintigraphy. There were no differences in symptoms among the three treatment groups in the 127 patients studied. There were no significant differences either among the treatment groups, as regards exercise capacity and the number or intensity of perfusion defects, in the 81 patients who underwent thallium-201 exercise scintigraphy. The three antithrombotic treatment regimens had a similar effect on the clinical status of patients and on the functional status of venous bypass grafts one year after coronary bypass surgery. This finding underscores the CABADAS results in that aspirin may be the preferred treatment option in patients following venous bypass surgery.

Acenocoumarol↗

PubMed1994

A comparison of internal mammary artery and saphenous vein grafts after coronary artery bypass surgery. No difference in 1-year occlusion rates and clinical outcome. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.

BACKGROUND: Superior patency rates for internal mammary artery (IMA) grafts compared with vein coronary bypass grafts have been demonstrated by retrospective studies. This difference may have been affected by selection bias of patients and coronary arteries for IMA grafting. METHODS AND RESULTS: To estimate the difference between IMA and vein grafts, we analyzed graft patency data of 912 patients who entered a randomized clinical drug trial. In this trial, 494 patients received both IMA and vein grafts (group 1) and 418 only vein grafts (group 2). Occlusion rates of IMA grafts and IMA plus vein grafts in group 1 were compared with those of vein grafts in group 2. Multivariate analysis was used to compare occlusion rates of IMA and vein grafts while other variables related to graft patency were controlled for. In addition, 1-year clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding, and death. Occlusion rates of distal anastomoses in group 1 versus group 2 were 5.4% (IMA grafts) versus 12.7% (vein grafts) (P < .0001) and 10.4% (IMA plus vein grafts) versus 12.7% (vein grafts) (P = .14). There was no difference in adjusted risk of occlusion between IMA grafts and vein grafts (P = .089). Type and location of distal anastomosis and lumen diameter of the grafted coronary artery were shown to be predictors of occlusion. Clinical events occurred in 17.8% (group 1) and 16.0% (group 2) of patients (P = .53). CONCLUSIONS: The observed difference in 1-year occlusion rates between IMA and vein grafts can be explained by a maldistribution of graft characteristics by selection of coronary arteries for IMA grafting rather than being ascribed to graft material. One-year clinical outcome is not improved by IMA grafting.

Aged↗

PubMed1994

Oral anticoagulation in the prevention of one-year vein graft occlusion after aortocoronary bypass surgery: optimal therapeutic range and practical limitations. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.

To assess the optimal level of oral anticoagulation to prevent occlusion of vein coronary bypass grafts, 318 patients from a graft patency trial were analysed retrospectively. Oral anticoagulant therapy was started one day before surgery and continued for one year, after which graft occlusion was assessed by angiography. The aimed level of anticoagulation was 2.8-4.8 International Normalized Ratio (INR). Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis and major bleeding. The observed anticoagulation level was 2.8-4.8 INR for 54%, and 1.8-3.8 INR for 75% of time per patient. Occlusion rates in patients who spent < 35, 35-70, and > or = 70% of time within INR range 2.8-4.8 were 10.5%, 10.8% and 11.8%, respectively (differences not statistically significant). Patients who spent > or = 70% of time within INR range 1.8-3.8 versus 2.8-4.8 showed comparable occlusion rates. The risk of graft occlusion was not related to quality of anticoagulation early (0-3 months) or late (3-12 months) after surgery. Myocardial infarction, thrombosis and major bleeding occurred in 1.3%, 2.0% and 2.9% of patients. To maintain vein graft patency in the first postoperative year by oral anticoagulation, a level within INR range 1.8-3.8 for > or = 70% of time seems to be sufficient.

Administration, Oral↗

PubMed1993

Prevention of one-year vein-graft occlusion after aortocoronary-bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants. The CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.

Aspirin, alone or in combination with dipyridamole, is known to prevent occlusion of aortocoronary vein grafts. The benefit of dipyridamole in addition to aspirin remains controversial, and the efficacy and safety of oral anticoagulants for prevention of vein-graft occlusion have not been established. We assessed one-year angiographic vein-graft patency after aortocoronary-bypass surgery in 948 patients assigned to receive aspirin, aspirin plus dipyridamole, or oral anticoagulants in a prospective, randomised trial. The design was double-blind and placebo-controlled for the aspirin groups, but open for oral anticoagulant treatment. Dipyridamole (5 mg/kg per 24 h intravenously for 28 h, followed by 200 mg twice daily) and oral anticoagulants (desired prothrombin time range 2.8-4.8 international normalised ratio) were started before surgery, and aspirin (50 mg per day) was started after surgery. Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding, or death. Occlusion rate of distal anastomoses was 11% in the aspirin plus dipyridamole group versus 15% in the aspirin group (relative risk 0.76, 95% CI 0.54-1.05) and 13% in the oral anticoagulants group. Clinical events occurred in 20.3% of patients receiving aspirin plus dipyridamole compared with 13.9% of the aspirin group (relative risk 1.46, 95% CI 1.02-2.08) and 16.9% of the oral anticoagulants group. Our data provide no convincing evidence that addition of dipyridamole to 50 mg aspirin per day improves aortocoronary vein-graft patency. Moreover, there is evidence that the combination increases the overall clinical-event rate. Compared with aspirin, oral anticoagulants provided no benefit.

Acenocoumarol↗

PubMed1990

An ultracompliant glass microelectrode for intracellular recording.

We describe the simple fabrication of a glass microelectrode that was designed for the stable impalement of contracting isolated cardiac preparations. The electrodes can be made with the aid of a standard pipette puller. The design uses a long-shanked glass electrode that is stepped below the shoulder at 70 degrees to the shaft and again near the tip. The electrodes are of marginally higher resistance than equivalent length straight electrodes (34.9 vs. 26.0 M omega). The stepped design imparts a low stiffness to the electrode in the vertical and horizontal planes, and the mechanical basis for this performance is described and discussed with regard to measured behavior. The duration of impalements with stepped electrodes is significantly longer than for straight electrodes and can usually be maintained for indefinite periods with minimal damage to small, highly contractile muscle preparations.

Animals↗

PubMed1989

Spontaneous and propagated contractions in rat cardiac trabeculae.

Sarcomere length measurement by microscopic and laser diffraction techniques in trabeculae of rat heart, superfused with Krebs-Henseleit solution at 21 degrees C, showed spontaneous local sarcomere shortening after electrically stimulated twitches. The contractions originated in a region of several hundred micrometers throughout the width of the muscle close to the end of the preparation that was damaged by dissection. The contractions propagated at a constant velocity along the trabeculae. The velocity of propagation increased from 0 to 10 mm/s in proportion to the number of stimuli (3-30) in a train of electrically evoked twitches at 2 Hz and at an external calcium ion concentration ([Ca++]o) of 1.5 mM. At a constant number of stimuli (n), the velocity of propagation increased from 0 to 15 mm/s with [Ca++]o increasing from 1 to 7 mM. In addition, increase of n and [Ca++]o led to an increase of the extent of local sarcomere shortening during the spontaneous contractions, and the occurrence of multiple contractions. Spontaneous contractions with much internal shortening and a high velocity of propagation frequently induced spontaneous synchronized contractions and eventually arrhythmias. Propagation of spontaneous contractions at low and variable velocity is consistent with the hypothesis that calcium leakage into damaged cells causes spontaneous calcium release from the overloaded sarcoplasmic reticulum in the damaged cells. This process propagates as a result of diffusion of calcium into adjacent cells, which triggers calcium release from their sarcoplasmic reticulum. We postulate that the propagation velocity depends on the intracellular calcium ion concentration, with increases with n and [Ca++]o.

Animals↗

PubMed1989

A model of propagating calcium-induced calcium release mediated by calcium diffusion.

The effect of sudden local fluctuations of the free sarcoplasmic [Ca++]i in cardiac cells on calcium release and calcium uptake by the sarcoplasmic reticulum (SR) was calculated with the aid of a simplified model of SR calcium handling. The model was used to evaluate whether propagation of calcium transients and the range of propagation velocities observed experimentally (0.05-15 mm s(-1)) could be predicted. Calcium fluctuations propagate by virtue of focal calcium release from the SR, diffusion through the cytosol (which is modulated by binding to troponin and calmodulin and sequestration by the SR), and subsequently induce calcium release from adjacent release sites of the SR. The minimal and maximal velocities derived from the simulation were 0.09 and 15 mm s(-1) respectively. The method of solution involved writing the diffusion equation as a difference equation in the spatial coordinates. Thus, coupled ordinary differential equations in time with banded coefficients were generated. The coupled equations were solved using Gear's sixth order predictor-corrector algorithm for stiff equations with reflective boundaries. The most important determinants of the velocity of propagation of the calcium waves were the diastolic [Ca++]i, the rate of rise of the release, and the amount of calcium released from the SR. The results are consistent with the assumptions that calcium loading causes an increase in intracellular calcium and calcium in the SR, and an increase in the amount and rate of calcium released. These two effects combine to increase the propagation velocity at higher levels of calcium loading.

Calcium↗

PubMed1988

Aftercontractions and excitation-contraction coupling in rat cardiac muscle.

Calcium loading in cardiac muscle may cause spontaneous contractions (SC). We observed that SC move at a constant rate (Vsc) through isolated rat myocytes and trabeculae. Factors that influence the properties of SC were studied with Nomarsky microscopy and laser diffraction techniques. Myocytes and trabeculae were superfused with Krebs-Henseleit solution (21 degrees C, pH 7.35; Ca2+, 0.5-7 mM). Vsc in myocytes and within cells of trabeculae ranged between 50 and 150 micron/s. After a train of 3-25 stimuli at 2 Hz, SC in trabeculae started at a site of damage in a region 250 micron in length throughout the muscle. This regional contraction then moved at a constant rate (Vsc) along the length of the muscle. Vsc increased from 0.1 to 15 mm/s with stimulation and Ca2+. Under conditions of calcium loading, spontaneous twitches also occurred throughout the trabeculae, often as triggered arrhythmias. These twitches were always preceded by SC. The range of observed Vsc could be predicted by the Ca2+-induced Ca2+ release hypothesis. We postulated that the contraction by virtue of focal calcium release from the sarcoplasmic reticulum (SR) and was stimulated this process together with the processes of diffusion into the cytosol, binding to calmodulin and troponin, sequestration by the SR, and subsequent induction of Ca2+ release from the adjacent SR. The parameters used for the kinetics of binding, release, and sequestration were obtained from those reported in the literature. The minimal and maximal velocities derived from the simulation were 0.09 and 25 mm/s, respectively. The method of solution involved writing the diffusion equation as a difference equation in the spatial coordinates. Thus, bounded, coupled, and ordinary differential equations in time were generated. The coupled equations were solved by using Gear's sixth order predictor--corrector algorithm for stiff equations along with reflective boundaries. These calculations were performed on the Cyber 205 at the University of Calgary.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

PubMed1981

[Insulinoma].

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Adenoma, Islet Cell↗