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Biomedical subjects

L Eijsman

Publications and source records attributed to L Eijsman.

54 records · Page 3Linked to original sources
PubMed1995

Hemodynamic effects of the novel selective cAMP-phosphodiesterase III inhibitor R 80122 in anesthetized patients with moderate left ventricular dysfunction before coronary artery bypass grafting.

OBJECTIVE(S): To investigate the hemodynamic effects and safety of R 80122, a novel selective phosphodiesterase (PDE) III inhibitor, and its solvent hydroxypropyl-beta-cyclodextrin. DESIGN: Prospective, randomized study. SETTING: Operating theater of a university hospital in the Netherlands. PARTICIPANTS: Twelve patients with impaired left ventricular function scheduled for coronary artery bypass grafting after induction of anesthesia were included. INTERVENTIONS: R 80122 (n = 6) or its solvent (n = 6) was administered using the same infusion regimen. A bolus of 0.1 mL/kg (= 0.1 mg/kg R 80122) was infused over 10 minutes followed by a maintenance infusion of 5 microliters/kg/min (5 micrograms/kg/min R 80122) over 20 minutes. MEASUREMENTS AND MAIN RESULTS: Compared with the solvent, patients receiving R 80122 did not show any significant changes in heart rate, arterial blood pressure, or pulmonary artery pressures. However, R 80122 produced a marked increase (P < 0.05) in cardiac output (thermodilution) and echocardiographically obtained percentage area reduction. No arrhythmias or ischemic episodes occurred during the infusion period. The plasma half-life of R 80122 was 10.6 +/- 1.9 minutes. CONCLUSIONS: R 80122 appears to be a potent positive inotropic agent in these patients. Its use is not associated with marked vasodilation, it is devoid of positive chronotropic effects, and it can be administered safely in patients with impaired left ventricular function.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1995

Interstitial fluid volume during cardiac surgery measured by means of a non-invasive conductivity technique.

Fluid accumulation in the interstitium is frequently found after cardiac surgery. In extreme this can lead to pulmonary and myocardial oedema. The origin of this accumulation is not exactly known and may be twofold. It is probably a combination of the noninfectious whole body inflammatory response and a change in Starling forces due to a decrease in colloid osmotic pressure (COP) which is caused by the primed extracorporeal circuit. To study the changes in interstitial fluid volume (ISFV) a non-invasive conductivity technique was used. The relationship between temperature and conductivity was first investigated in vitro. A linear relationship was found between conductivity and different saline solutions and temperature. From the in vitro experiments it can be concluded that temperature corrected conductivity does not depend on haematocrit. After the in vitro experiments eleven patients undergoing cardiac surgery were studied. During the first minutes of cardiopulmonary bypass (CPB) a steep significant decrease in COP to 61.4 +/- 6.9% (from 19.6 +/- 1.1 to 12.0 +/- 1.2 mmHg), and a rise in ISFV to 105.5 +/- 2.8% (from 12.3 +/- 1.4 mS to 14.0 +/- 1.3 mS) was noticed. After this decrease COP increased significantly, till the end of the operation, but did not reach the pre-operative level. An increase in ISFV was noticed till the rewarming point. After this point no significant change in ISFV was noticed. Furthermore, a significant correlation was found between the fluid balance and the ISFV increase at the start, at the end of CPB, and at the end of the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Aprotinin preserves hemostasis in aspirin-treated patients undergoing cardiopulmonary bypass.

Various clinical trials have shown that hemostasis is improved by the administration of aprotinin during cardiopulmonary bypass. However, this effect has not been proved for those patients treated preoperatively with aspirin. Therefore, a double-blind, placebo-controlled study was conducted to test the efficacy of low-dose aprotinin (2 x 10(6) KIU in the pump prime solution) in preserving hemostasis in 40 aspirin-treated (325 mg) patients undergoing coronary artery bypass grafting. Aprotinin brought about a decrease in the postoperative blood loss (p < 0.05). The in vitro bleeding test (Thrombostat) demonstrated that aprotinin preserved the platelet hemostatic function in aspirin-treated patients during cardiopulmonary bypass (p < 0.05). The inhibitory effects of aspirin on collagen-induced platelet aggregation and thromboxane production were not influenced by aprotinin treatment. The findings from the present study indicate that aprotinin preserves hemostasis in aspirin-treated patients during cardiopulmonary bypass, but aspirin's effect on platelets is maintained. Therefore, aprotinin seems to be a useful adjunct treatment in aspirin-treated patients undergoing coronary artery bypass grafting.

Aprotinin↗
PubMed1994

Perfusion-related factors of endotoxin release during cardiopulmonary bypass.

To investigate whether the release of endotoxin during cardiopulmonary bypass (CPB) is determined by perfusion-related factors, endotoxin concentrations were determined before, during, and after CPB in 21 male patients (age range 45-75 years) undergoing elective coronary artery bypass grafting. Hemodynamic parameters and oncotic pressure were also measured. Significant increases in endotoxin concentrations were observed after the start of CPB (P < 0.005), before aortic cross-clamp release (P < 0.05), and after aortic cross-clamp release (P < 0.05). The median endotoxin concentration after cessation of CPB was 0.264 EU/ml (range < 0.036-0.480 EU/ml). Endotoxin concentrations derived from the prime solutions were not contributory. Positive correlations were found between arterial pressure after the start of CPB and the endotoxin concentration 10 min after (r = 0.58, P < 0.01) and between the duration of aortic cross-clamping and the endotoxin concentration after the cessation of CPB (r = 0.64, P < 0.005). Arterial pressure after the start of CPB, the duration of aortic cross-clamping, and decrease in oncotic pressure appeared to be independent variables in a forward variable selection model that predicted endotoxin concentrations after CPB. We conclude that in patients undergoing elective coronary artery bypass grafting, an early phase of endotoxin release during CPB could be demonstrated, and that this is due to vasoconstriction. The endotoxin concentrations after the cessation of CPB were determined by early vasoconstriction, duration of aortic cross-clamping, and hypo-oncotic hemodilution.

Aged↗
PubMed1993

The influence of oral contraceptives on the time-integral of thrombin generation (thrombin potential).

The thrombin potential (TP) has been defined as the time integral of (i.e. the area under) the thrombin generation curve. It has been shown that this parameter decreases with all types of anticoagulant treatment and increases with ATIII deficiency. We evaluated the use of this parameter for detection of the hypercoagulative state known to accompany oral contraception. In fresh frozen control plasma the TP could be determined with high reproducibility (n = 82, c.v. 2.9%). The TP was linearly diminished by mixing fresh frozen plasma with prothrombin deficient plasma while a high coefficient of correlation was observed (r = 0.997). Women using oral contraceptives showed a significantly (p < 0.0001) higher TP (TP = 569 nM.min, SD = 55, n = 17), compared to men or, to women not using oral contraceptives (TP = 484 nM.min, SD = 52, n = 41). This suggests that the thrombin potential indicates the prethrombotic state known to exist in women using oral contraceptives.

Blood Coagulation Disorders↗
PubMed1993

Transvascular transport of 67Ga in the lungs after cardiopulmonary bypass surgery.

STUDY OBJECTIVE: To examine the effect of cardiac surgery with cardiopulmonary bypass (CPB) on pulmonary vascular permeability. DESIGN: A prospective, serial study. SETTING: Department of nuclear medicine and intensive care units of a university hospital. PATIENTS: Twelve consecutive patients were studied, before and immediately after elective cardiac surgery using CPB (group 1), and 4 consecutive, artificially ventilated patients with acute cardiogenic pulmonary edema (group 2). MEASUREMENTS AND RESULTS: The kinetics in blood and over both lungs were measured, using two mobile probes at the bedside, of intravenously injected 67Ga, assumed to bind to circulating transferrin, and in vitro 99mTc-labeled red blood cells to account for pulmonary blood volume. From data recorded in time (1 h), a pulmonary leak index (PLI), the time constant of transport of 67Ga from the intravascular to the extravascular space of the lung, was calculated and values for both lungs were averaged. In group 1, the PLI (.10(-3).min-1, mean +/- SD) was 8.2 +/- 3.7 before and 17.0 +/- 13.5 after CPB surgery (p < 0.01) and changes directly related to the duration of CPB. In four patients with a CPB duration > or = 120 min, the PLI, 31.1 +/- 16.3.10(-3).min-1, exceeded 2 SD plus mean preoperative PLI. Changes in PLI tended to relate inversely to changes in arterial WBC, which, in turn, inversely related to CPB duration. The PaO2/FIO2 ratio decreased and tended to relate inversely to PLI after surgery. No patient developed alveolar pulmonary edema on chest radiograph. In group 2, the PLI was 11.1 +/- 3.1.10(-3).min-1 (NS from group 1 preoperative PLI). CONCLUSIONS: Cardiopulmonary bypass induces a pulmonary vascular leak, as assessed by 67Ga kinetics using a bedside detection technique, in some cardiac surgery patients with prolonged CPB. This leak may reflect pulmonary vascular injury and increased permeability, following activation of leukocytes by CPB and subsequent pulmonary sequestration, rather than increased filtration through pressure factors. It may contribute to impaired gas exchange, even in the absence of manifest alveolar edema of the lungs, after surgery.

Acute Disease↗
PubMed1992

Endotoxin release and tumor necrosis factor formation during cardiopulmonary bypass.

Endotoxin, when released into the systemic circulation during cardiopulmonary bypass (CPB), might induce activation of plasmatic systems and blood cells during CPB, in addition to a material-dependent blood activation during CPB. However, the role of endotoxin in the development of this so-called whole-body inflammatory reaction in CPB is still unclear. We investigated the release of endotoxin into the systemic circulation in relation with the activation of the complement system and in particular the formation of tumor necrosis factor in 10 patients undergoing CPB. Immediately after the start of CPB the endotoxin concentrations increased significantly (p less than 0.01), accompanied by increases in C3a concentration (p less than 0.05). After release of the aortic cross-clamp, there was a second increase in endotoxin followed by a continuous increase in tumor necrosis factor, reaching a peak concentration 1 hour after the end of CPB (p less than 0.01). These observations demonstrate a release of endotoxin into the systemic circulation associated with tumor necrosis factor formation, which contributes to the whole-body inflammatory reaction associated with CPB.

Aged↗
PubMed1991

Aprotinin reduces intraoperative and postoperative blood loss in membrane oxygenator cardiopulmonary bypass.

To determine whether aprotinin can provide a significant improvement of hemostasis in cardiopulmonary bypass using a membrane oxygenator, we tested this drug in a prospective, randomized, double-blind, placebo-controlled clinical trial. The subjects were 80 male patients undergoing cardiopulmonary bypass for coronary artery bypass grafting. Forty patients received aprotinin and 40 patients served as placebo controls. Aprotinin (4 x 10(6) KIU) was given as a continuous infusion, starting before operation and continuing until after cardiopulmonary bypass; additionally, 2 x 10(6) KIU aprotinin was added to the pump prime. Intraoperative and postoperative bleeding, respectively two thirds and one third of the total perioperative blood loss, were both significantly reduced in the aprotinin-treated group (p less than 0.01). The total average perioperative blood loss, corrected to a hemoglobin concentration of 7 mmol/L, was 550 mL in the aprotinin-treated patients versus 900 mL in the control patients. This reduction in blood loss, furthermore, significantly decreased the amount of postoperative blood transfusions (p less than 0.05) and increased the percentage of patients who did not receive postoperative donor blood from 42% to 68%. Aprotinin increased the activated clotting time significantly during cardiopulmonary bypass, which led to a reduction in heparin usage. The improved hemostasis during operation, despite the prolonged activated clotting time, might even abolish the need for heparin conversion with protamine at the end of cardiopulmonary bypass, thus allowing retransfusion through cardiotomy suction to be continued, which saves the blood that is currently lost with vacuum suction.

Aprotinin↗
PubMed1990

Aprotinin protects platelets against the initial effect of cardiopulmonary bypass.

Remarkable improvement in hemostasis after cardiopulmonary bypass has been achieved by treatment with the proteinase inhibitor aprotinin, but the mechanism is still unclear. The present study is designed to elucidate the importance of platelet adhesive (glycoprotein Ib) or aggregatory (glycoprotein IIbIIIa) receptors on this hemostatic function in cardiopulmonary bypass and its improvement by aprotinin treatment. To determine whether the first pass of blood through the circuit or a continuous proteolytic attack is the main cause of platelet damage, we gave two different dose regimens of aprotinin treatment to patients undergoing coronary artery bypass grafting. Part I of the study consisted of a double-blind trial on 60 patients. Patients received placebo or aprotinin infusion (total 6.10(6) KIU) before and during bypass. A consecutive group of 22 matching patients received one single bolus of aprotinin in the pump prime (2.10(6) KIU). Blood samples were collected before and during operation to assess the effect of bypass and aprotinin on platelets and the activation of the various proteases in relation to hemostasis expressed in blood loss and blood requirements. The adhesive platelet membrane Ib glycoproteins were decreased by 50% in the untreated patients within 5 minutes of cardiopulmonary bypass and remained low during bypass, whereas glycoprotein Ib did not decrease in either group of aprotinin-treated patients. The platelet membrane IIbIIIa glycoproteins did not significantly change during bypass in either group, but fibrinogen binding to these receptors improved significantly in the 6.10(6) KIU aprotinin-treated group at the end of bypass as compared with initial values. The high continuous dose of 6.10(6) KIU aprotinin inhibited the clotting and kallikrein/kinin system throughout the operation; the pump prime dose of 2.10(6) KIU inhibited these systems only initially. Although the fibrinolytic activity was effectively inhibited in both aprotinin groups, fibrinolytic activity became apparent only at the end phase of bypass in the placebo group. However, improved hemostasis was observed intraoperatively from the start of bypass and resulted in a 40% lower blood loss intraoperatively and postoperatively and consequently a 40% lower total blood requirement in the aprotinin-treated patients than in the untreated patients. Our results therefore demonstrate that the improved hemostasis during and after bypass in patients treated with aprotinin has specifically to be attributed to a preserved adhesive capacity of platelets that was affected in the first pass of blood through the cardiopulmonary bypass circuit.

Aprotinin↗
PubMed1990

Increased anticoagulation during cardiopulmonary bypass by aprotinin.

In this prospective study, the effect of the antiproteinase aprotinin on anticoagulation during cardiopulmonary bypass was compared with placebo treatment in a randomized double-blind fashion. The kallikrein-inhibiting capacity was significantly increased in aprotinin-treated patients and decreased in the control patients. The intrinsic clotting system was also inhibited by aprotinin. We demonstrated during cardiopulmonary bypass and in vitro a significantly prolonged activated clotting time and a remarkable prolongation of the activated partial thromboplastin time by aprotinin at low heparin concentrations, whereas the antithrombin III consumption was significantly reduced. Aprotinin synergistically enhanced the anticoagulation by heparin, which allowed reduced heparinization. This is of clinical importance for use in both heparin-resistant and heparin-sensitive patients undergoing cardiopulmonary bypass and may also have advantages for routine use during bypass to reduce the adverse effects of heparin-protamine complexes.

Antithrombin III↗
PubMed1989

Platelet preservation during cardiopulmonary bypass with aprotinin.

A remarkable reduction of postoperative blood loss after cardiopulmonary bypass (CPB) has been achieved by prophylactic treatment with the proteinase inhibitor aprotinin. To reveal the mode of action of aprotinin, 23 CPB patients were randomised for aprotinin (2 x 10(6) KIU in the pump prime) or placebo treatment during CPB. Blood samples were collected before and during operation. Blood loss and blood requirements were 50% lower in the aprotinin treated patients than in the untreated patients. The adhesive capacity of platelets assessed by the amount of platelet membrane glycoprotein Ib (GP Ib) decreased by 50% in the untreated patients within 5 min of CPB and remained low during CPB, whereas GP Ib did not decrease in the aprotinin treated patients. Fibrinogen degradation products indicating plasmin activity could only be measured after 30 min of CPB in the untreated, but not in the aprotinin treated patients. The kallikrein inhibiting capacity was 34% decreased in the untreated patients within 5 min of CPB, while it increased by 84% and remained high during CPB in the aprotinin treated patients. Our results demonstrate that the improved haemostasis during and after CPB in patients treated with aprotinin can be attributed to the preserved adhesive capacity of platelets. It remains to be found whether aprotinin has a primary effect on platelets or a secondary effect by plasmin or kallikrein inhibition.

Aprotinin↗
PubMed1981

Hemodynamic side effects of prostaglandin E1 in patients before and during cardiopulmonary bypass.

Animal experiments have shown that the administration of prostaglandin E1 (PGE1) during cardiopulmonary bypass (CPB) reduces platelet damage and the tendency to bleeding disorders. Because PGE1 also has a strong vasodilating action, a clinical trial was started to evaluate its hemodynamic side-effects. PGE1 was studied during 3 different periods: 1. a 10-minute period before bypass, 2. a hemodynamically stable period during CPB, 3. during the whole period of CPB. 1. Before CPB, a consistent fall of mean arterial pressure (MAP) was observed (26 mmHg). 2. During the stable period of CPB, the blood pressure fall was dependent on the pre-existing systemic vascular resistance. 3. PGE1 infusion during the whole CPB period was, in general, badly tolerated. Increased perfusion flow was not sufficient to compensate for the resulting blood pressure drop. In most of the 13 cases vasopressors had to be given continuously. In 7 patients PGE1 had to be reduced, and in 4 patients the infusion had to be stopped altogether. Because of the marked vasodilator effects of PGE1 it appears impossible to give patients doses adequate to achieve platelet preservation during clinical CPB with safety.

Adult↗
PubMedDate not supplied

Surgical sealant in the prevention of early vein graft injury in an ex vivo model.

BACKGROUND: The amelioration of the adaptation process (arterialisation) of the vein graft wall to the arterial circulation in coronary artery bypass surgery by using extravascular support is clearly established in animal models and in in vitro and ex vivo set-ups. This support consists of some form of external graft-supporting modality like a prosthetic graft of stent. The clinical application of perivenous support, however, is hampered due to the fact that no easy applicable external support is available. Considering that application in the form of a spray is the most convenient modality, we evaluated whether polyethylene glycol is capable of providing adequate perivenous support. Polyethylene glycol is a synthetic, biodegradable product, used in cardiac surgery as a sealant, and is commercially available in the form of a spray. METHODS: Segments of human saphenous vein graft obtained during coronary artery bypass graft (CABG) procedures were placed in an ex vivo model, a side loop of the extracorporeal perfusion circuit, and perfused with autologous blood, making the circumstances identical to the implanted saphenous vein grafts concerning pressure, temperature, level of complement and leukocyte activation and blood pressure. Alternately around every other study vein graft segment polyethylene glycol was applied. Unsupported grafts served as control. After 1 min of solidification, perfusion was started with a pressure of about 60 mmHg (nonpulsatile flow). Perfusion was maintained for 60 min, after which the grafts were collected for light microscopy and electron microscopy. RESULTS: Light microscopy and electron microscopy showed remarkable attenuation of endothelial cell loss and less injury of smooth muscle cells of the circular and longitudinal layer of the media in the supported group compared to the nonsupported vein graft segments. CONCLUSION: Polyethylene glycol is able to provide adequate external vein graft support, preventing overdistension, in an ex vivo model. This provides a basis for clinical application. Further investigation is warranted to evaluate long-term effects.

Anastomosis, Surgical↗
PubMedDate not supplied

Comparison of three commercially available hollow fiber oxygenators: gas transfer performance and biocompatibility.

The new generation of oxygenators have improved blood flow pathways that enable reduction in priming volume and, thus, hemodilution during cardiopulmonary bypass (CPB). We evaluated three oxygenators and two sizes of venous reservoirs in relation to priming volume, gas transfer, and blood activation. To compare priming volume, gas transfer, and biocompatibility of three hollow fiber oxygenators and two different size venous reservoirs, 60 patients were randomly allocated in groups to undergo cardiopulmonary bypass. In each group, an oxygenator with a different surface area and priming volume was used: 1.8 m2 and 220 ml (group 1, n = 23), 2.2 m2 and 290 ml (group 2, n = 20), and 2.5 m2 and 270 ml (group 3, n = 17). In groups 1 and 3, a large soft shell (1900 ml) venous reservoir was used, whereas in group 2, a smaller soft shell (600 ml) venous reservoir was used. Gas transfer was assessed by calculating the oxygen transfer rate for each group and per square meter for each oxygenator group. Partial arterial oxygen pressure (paO2) and partial arterial carbon dioxide pressure (paCO2) between the groups were assessed with forward stepwise regression analysis. Biocompatibility was evaluated through measurement of platelet numbers, complement activation products (C3b/c), coagulation (thrombin anti-thrombin III complex), and fibrinolysis (plasmin anti-plasmin complex). No differences were found in oxygen transfer rate per group. However, when correcting the oxygen transfer rate for surface area, group 1 demonstrated a higher oxygen transfer rate compared with group 2 (p < 0.05) at an FiO2 of 40 and 60% and compared with group 3 at an FiO2 of 60 and 70%. The regression analysis showed that the average arterial PO2 was the highest in group 3, i.e., 79.2 mm Hg higher than in group 1 (p < 0.001) and 73.5 mm Hg higher than in group 2 (p < 0.001). Group 3 also had the lowest average arterial pCO2, 0.57 mm Hg lower than in group 1 (p = 0.004) and 0.81 mm Hg lower than in group 2 (p < 0.001). During CPB, platelet numbers decreased significantly in all groups (p < 0.001), without differences between the groups. C3b/c levels increased in all groups during CPB. At cessation of CPB the C3b/c level in group 2 (398 nmol/L(-1)) was significantly higher compared to group 1(251 nmol/L(-1); p < 0.05) and group 3 (303 nmol/L(-1); p < 0.05). Thrombin anti-thrombin III complexes and plasmin anti-plasmin complex complexes increased during CPB to significantly high levels at cessation of CPB, but there were no differences between the groups. The oxygenator with the smallest surface area and lowest priming volume (group 1) had the highest oxygen transfer rate per square meter and showed the least blood damage, as depicted by complement activation. The oxygenator with the largest blood contact surface area and improved geometric configuration (group 3) showed the lowest oxygen transfer rate per square meter. However, this oxygenator elevated oxygen partial pressure the most and reduced carbon dioxide partial pressure the most. In group 2, where a smaller venous reservoir was used, the highest blood activation was observed.

Aged↗
PubMedDate not supplied

Influence of heparin, protamine and polybrene on the time integral of thrombin generation (endogenous thrombin potential).

We investigated the anticoagulating and heparin-neutralizing properties of protamine and polybrene (hexadimethrine bromide), using the endogenous thrombin potential (ETP) as the parameter to access plasma coagulability. The hypocoagulability induced by high doses of heparin (3 IU/ml) could be reversed by addition of protamine to a very limited extent only. Polybrene on the other hand did neutralize heparin at the equivalent concentration and a two-fold excess did not influence the ETP parameters. In vivo neutralization of high-dose heparin with protamine should therefore be reconsidered. Our experiments suggest polybrene to be superior over protamine with respect to neutralization of high doses of heparin.

Anticoagulants↗