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Biomedical subjects

C R Wildevuur

Publications and source records attributed to C R Wildevuur.

At least 19 recordsLinked to original sources
PubMed1992

Low-dose aprotinin in internal mammary artery bypass operations contributes to important blood saving.

The effect on postoperative blood loss and blood use of blood-saving treatment with or without 280 mg of low-dose aprotinin (2 million kallikrein inactivator units) was studied in 200 consecutive patients undergoing either unilateral or bilateral internal mammary artery bypass grafting. Postoperative blood loss and total units of homologous blood products were similar in patients having either bypass procedure without aprotinin treatment. In patients given aprotinin, postoperative blood loss and use of homologous blood products were significantly lower (p < 0.05). The use of any donor blood product was prevented in 78% of the patients given aprotinin versus only 45% of patients treated without aprotinin. None of the aprotinin-treated patients underwent repeat thoracotomy for excessive bleeding; repeat thoracotomy was indicated in 8% of the patients having bilateral internal mammary artery grafting without aprotinin treatment. These results demonstrate that low-dose aprotinin reduces blood loss and blood use significantly and prevents excessive bleeding.

Aprotinin↗
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↗
PubMed1992

Leukocyte activation with increased expression of CR3 receptors during cardiopulmonary bypass.

The effects of cardiopulmonary bypass (CPB) on the expression of leukocyte adhesive receptors, ie, complement receptor type 3 (CR3), were studied in 16 patients. The CR3 expression on leukocytes was determined by time-resolved fluoroimmunoassay on a standardized number of cells isolated from blood samples taken during various times during CPB. The results demonstrated that CR3 expression on leukocytes increased immediately after the start of CPB (p less than 0.05), concomitant with an early sharp increase of plasma concentrations of C3a (p less than 0.01). After release of the aortic cross-clamp, a second peak of leukocyte CR3 expression was induced (p less than 0.05), paralleled by a significant increase of leukotriene B4 (p less than 0.05) and elastase (p less than 0.05) levels in the late period of CPB. In vitro studies with leukocytes isolated from healthy donors (n = 5) showed a dose-dependent increase of CR3 expression stimulated by zymosan-activated plasma, indicating that the rapid CR3 expression on leukocytes is likely mediated by complement activation. However, the mechanisms for the second peak of leukocyte CR3 expression during CPB remain to be further elucidated. In conclusion, CR3 expression on leukocytes increased immediately after the start of CPB and was followed by a second peak of expression in the late phase of CPB. Pharmacological blockage of these adhesive receptors might reduce the leukocyte-mediated deleterious effects of CPB.

Cardiopulmonary Bypass↗
PubMed1992

In vivo fragmentation of microporous polyurethane- and copolyesterether elastomer-based vascular prostheses.

A previous study showed that microporous, compliant and (bio)degradable vascular prostheses prepared from a polyurethane/poly(L-lactic acid) mixture can function as a temporary scaffold for the regeneration of small-calibre arteries. In this study the mechanism of fragmentation of vascular prostheses made of polyurethane, copolyesterether and blends of either polyurethane or copolyesterether with polymers differing in biodegradability, crystallinity and glass transition temperature is investigated. Animal studies revealed that after 6 wk of implantation only the prostheses made of blends containing a second polymer which was non-elastic at 37 degrees C were fragmented extensively, whether the second polymer was (bio)degradable or not. It is concluded that fragmentation of the prostheses is mainly caused by alternating stresses induced by the arterial pulsations and that (bio)degradation plays a minor role.

Animals↗
PubMed1992

Late airway changes caused by chronic rejection in rat lung allografts.

Airway disease after lung or heart-lung transplantation is one of late major complications, affecting the prognosis of the transplants. Little is known about the causes of airway changes. We performed rat lung transplantation and investigated the late airway changes of the long-term surviving lung grafts: allografts, BN to Lewis; isografts, BN to BN rat. All recipients were treated with CsA. We found airway changes, i.e., mucosal ulceration, granulation, submucosal fibrosis, which was located in the large airways, in four of five allografted lungs. The lung isografts showed no pathological abnormalities. Immunopathological studies disclosed the localized expression of MHC class II antigens on the bronchial epithelium of the large airways where recipient type dendritic cells accumulated in the submucosa and CD4 positive predominant lymphocytes infiltrated. These findings support the idea that the late airway changes in lung transplants are caused by immunologically mediated chronic rejection.

Animals↗
PubMed1992

Blood loss and use of blood in internal mammary artery and saphenous vein bypass grafting with and without adding a single, low-dose of aprotinin (2 million units) to the pump prime.

In comparison with saphenous vein bypass grafting (SVG) without a pleurotomy, internal mammary artery (IMA) bypass surgery might enhance more blood loss by the intrathoracic wound and a wide opened pleura. Low-dose aprotinin (Trasylol) reduces blood loss and consequently, the use of homologous blood. We studied the blood loss and blood requirements peri-operatively in 70 patients, who underwent either SVG-(n = 35) or IMA-surgery (n = 35) without aprotinin and another 70 patients who underwent SVG- (n = 35) or IMA-surgery (n = 35) with a single dose of aprotinin, added to the pump prime. We also determined the hemoglobin and total protein content of the shed blood. Without aprotinin administration, the mean intra-operative and post-operative blood loss was significantly less (p < 0.01) in SVG-patients, than in IMA-patients. We observed no statistical differences in the mean blood requirements between SVG- and IMA-surgery (1.2 units and 1.6 units). The use of any homologous blood product was similarly averted in 39% of the SVG-patients, and in 48% of the IMA-patients. Treatment with aprotinin significantly lessened (p < 0.01) the mean intra-operative blood loss only in IMA-patients. Post-operative blood loss was diminished with 45% in IMA-patients and 33% in SVG-patients, being significantly less (p < 0.01) after SVG, than after IMA-surgery. Blood requirements were significantly lowered (p < 0.01): a total mean of 0.2 units in SVG- and 0.6 units in IMA-patients (NS). Any homologous blood product was prevented in 78% of the IMA-patients and in 87% of the SVG-patients (NS). The mean loss of hemoglobin and total protein per 100 ml of shed blood was similar in IMA-, and SVG-patients with or without aprotinin, although aprotinin diminished the total amounts in both groups with 50% (p < 0.01).

Adult↗
PubMed1992

Rapid endothelialization of vascular prostheses by seeding autologous venous tissue fragments.

A method was developed to obtain rapid endothelialization of a fabric vascular prosthesis by seeding autologous venous tissue fragments into its wall. In an animal study, complete endothelialization was observed in the entire inner surface of the prosthesis within 2 weeks after implantation. A piece of peripheral vein was minced with scissors and then stirred into saline to create a tissue suspension. This suspension was enmeshed into the wall of a highly porous fabric vascular prosthesis by repeated pressurized injections with a syringe. The prostheses (7 mm inside diameter and 5.7 cm in length), seeded with tissue fragments, were implanted into the descending thoracic aorta of 25 dogs, and they were removed from 1 hour to 2 months after implantation. Twenty-five prostheses, preclotted with fresh blood, were used as control prostheses. In the seeded graft, a thin fibrin layer covered the inner surface just after implantation, but countless numbers of endothelial cells migrated from the fragments and came up to the luminal surface like multiple "mushrooms" under the fibrin layer. Smooth muscle cells made multiple layers underneath the endothelial cell layer. The healing proceeded equally at every part. By this active migration and proliferation, the inner surface was completely healed within 2 weeks.

Animals↗
PubMed1992

[Development of a method to prevent degenerative changes of the vein graft for arterial reconstruction].

Autologous vein graft is frequently used for arterial reconstruction in vascular surgery. Its' long-term patency rate, however, is low because of the degenerative changes of the vein wall. Of the basis of our hypothesis that the degenerative changes are mainly caused by an over-distension of vein wall in arterial system, in this study, autologous vein grafts of rabbit (N = 56) were implanted in the carotid arteries. To prevent overdistension, some of the grafts were covered with prosthesis which was made of microporous, compliant biodegradable polyurethane and were compared with those without prosthesis. The integrity of the architecture of the vein wall covered with prosthesis was well preserved at 6 weeks after implantation, where the biodegradation of prosthesis induced an optimal arterialization of the vein grafts. The results indicate that this method may prevent the degenerative changes of vein wall such as fibrosis and intimal hyperplasia, which would cause poor long-term patency of vein graft used for arterial reconstruction.

Animals↗
PubMed1992

Improved healing of small-caliber polytetrafluoroethylene vascular prostheses by increased hydrophilicity and by enlarged fibril length. An experimental study in rats.

This study was undertaken to test whether increasing the hydrophilicity of small-caliber polytetrafluoroethylene vascular prostheses by alcohol pretreatment or increasing their fibril length might improve their healing without affecting their patency. Polytetrafluoroethylene vascular prostheses (length 1 cm, inside diameter 1.2 mm) (1) with a fibril length of 30 microns (control group; n = 18), (2) pretreated with alcohol (n = 18), or (3) with a fibril length of 60 microns (n = 18) were implanted into the abdominal aorta of rats. The prostheses were evaluated by means of routine light and scanning electron microscopy during a 6-week period after implantation. All prostheses were patent at harvesting. On implantation, the control polytetrafluoroethylene vascular prostheses were only scarcely covered with platelets. At 6 weeks they had healed in a small area adjacent to the anastomoses only. In contrast, both the alcohol-pretreated polytetrafluoroethylene prostheses and the polytetrafluoroethylene prostheses with a fibril length of 60 microns were completely covered by a thin clot layer on implantation. At 6 weeks after implantation these prostheses had almost completely healed as a result of organization of the thin clot layer by ingrowth of both endothelial and smooth muscle cells. These results demonstrate that increasing hydrophilicity of polytetrafluoroethylene vascular prostheses by alcohol pretreatment or enlarging their fibril length improves their healing by induction of a thin luminal clot layer. This clot layer provides a suitable matrix for ingrowth of both endothelial and smooth muscle cells and does not lead to thromboembolic complications.

Animals↗
PubMed1991

Activation of plasma systems and blood cells by endotoxin in rabbits.

Endotoxin plays an important role in the pathogenesis of septicaemia by activation of cellular and plasmatic systems. This study was performed to investigate the effects of infusion of endotoxin in rabbits by measuring the activation of cellular and plasma systems. Endotoxin was infused at a rate of 1 mg/kg body wt for 10 min, which caused death of all rabbits within 72 h. Endotoxin induced early leukopenia and thrombopenia, increased plasma levels of beta-glucuronidase and leukotriene B4 (LTB4), and decreased complement total hemolytic activity (CH50) and tissue plasminogen activator (t-PA) activity. These observations correlate with the cellular and plasma changes that have been documented in severely ill endotoxemic patients. Therefore, we conclude that this endotoxin model in rabbits is a valuable tool for investigation of pathophysiology and treatment of endotoxic shock.

Animals↗
PubMed1991

Methylprednisolone prophylaxis protects against endotoxin-induced death in rabbits.

Endotoxemia in patients can lead to sepsis and shock by activation of cellular and plasmatic systems. Corticosteroids are described to have a beneficial effect on these phenomena. In this study of controlled endotoxic shock, we investigated the protective effects of prophylactic corticosteroid treatment against activation of cellular and plasmatic systems. In this respect, a low-dose methylprednisolone (1 mg/kg body wt) treatment was compared with that of a high-dose methylprednisolone (40 mg/kg body wt) treatment. Endotoxin infusion induced death of all rabbits, which was associated with leukopenia, thrombopenia, increased levels of beta-glucuronidase, and leukotriene B4 (LTB4) and decreased levels of complement total hemolytic activity (CH50) and tissue plasminogen activator (t-PA) activity. Both methylprednisolone regimens prevented death of the rabbits after endotoxin infusion, which correlated with a significant decrease of the granulocyte release product beta-glucuronidase (P less than 0.01). The early leukopenia and thrombopenia were not prevented; however, both cell numbers returned more rapidly to baseline values than in the placebo group (P less than 0.01, P less than 0.05). The LTB4 and CH50 concentration and t-PA activity did not differ significantly between the treated and placebo groups. These results indicate that although methylprednisolone has no inhibitory effect on the activation of the complement, arachidonic acid, and fibrinolytic systems, it protected the animals from the deleterious effects of endotoxin shock by inhibition of leukocyte activation. In this regard a low dosage of methylprednisolone is equally effective as the most often recommended high dose.

Animals↗
PubMed1991

Membrane oxygenator prevents lung reperfusion injury in canine cardiopulmonary bypass.

The effect of blood activation on lung reperfusion injury during cardiopulmonary bypass was investigated in 20 dogs with the use of a bubble oxygenator (n = 10) or a membrane oxygenator (n = 10). In the bubble oxygenator group, significant leukocyte and platelet right to left atrium gradients were found 15 minutes after lung reperfusion (p less than 0.05, p less than 0.01) accompanied by a sharp increase in plasma malondialdehyde concentration 5 minutes after lung reperfusion, whereas no significant right to left atrium gradient of leukocytes or platelets nor significant increase in plasma malondialdehyde concentration was observed in the membrane oxygenator group. In both the bubble oxygenator and membrane oxygenator group, similar mild to moderate lung histological changes were found before lung reperfusion. After lung reperfusion, however, more endothelial cell swelling (p less than 0.05), leukocyte (p less than 0.01) and platelet (p less than 0.01) accumulation in lung capillaries, leakage of erythrocytes into the alveolar space (p less than 0.05), and type I cell damage (p less than 0.05) were found only in the bubble oxygenator group. Eventually, a significantly higher lung water content was found in the bubble oxygenator group than in the membrane oxygenator group (p less than 0.01) after cardiopulmonary bypass. This study indicated that lung injury during cardiopulmonary bypass starts mainly after lung reperfusion, which was correlated with lung leukocyte and platelet sequestration associated with different types of oxygenators.

Animals↗
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↗
PubMed1991

The role of different types of corticosteroids on the inflammatory mediators in cardiopulmonary bypass.

In a placebo-controlled double-blind study on patients undergoing cardiopulmonary bypass (CPB) we studied the inhibiting effects of dexamethasone, a high dose of methylprednisolone, and a low dose of prednisolone on the inflammatory reaction induced by CPB. During CPB two episodes of blood activation were noticed. First, the blood-material interaction caused a significant increase in complement C3a and elastase concentrations after the start of bypass (p less than 0.01). Secondly, the reperfusion of the ischemic heart, lungs, and peripheral tissue, after release of the aortic cross-clamp, caused an additional increase in C3a and elastase concentration and a statistically significant increase in leukotriene B4 (LTB4) concentration and tissue plasminogen activator (t-PA) activity (p less than 0.01, p less than 0.05, respectively). Dexamethasone treatment effectively inhibited the increase in LTB4 concentration and t-PA activity after release of the cross-clamp (significant differences to the placebo group, p less than 0.01, p less than 0.05, respectively). High-dose methylprednisolone treatment was almost as effective as dexamethasone treatment, whereas low-dose prednisolone treatment was less effective than methylprednisolone in the inhibition of the inflammatory mediators (DM greater than MP greater than P). None of the corticosteroid regimens was able to inhibit the increase in complement C3a and elastase. We therefore conclude that corticosteroids do not have an effect on complement activation during CPB. However, leukocyte activation and t-PA activity after release of the aortic cross-clamp are effectively inhibited by corticosteroid treatment, in a dose-dependent way. The inhibition of this inflammatory reaction will have a favourable effect on the postoperative course in patients who have undergone CPB.

Acute-Phase Proteins↗
PubMed1991

Reduction of granulocyte-mediated lung injury in canine cardiopulmonary bypass by anisodamine infusion.

The effect of infusing the M-cholinergic receptor blocker anisodamine during cardiopulmonary bypass (CPB) on granulocyte-mediated lung injury was evaluated in sixteen dogs undergoing CPB for 120 min with the aorta crossclamped for 90 min. The treated dogs (n = 8) received a total dose of 15 mg/kg anisodamine hydrochloride before and during CPB whereas the controls (n = 8) received saline only. A significantly reduced sequestration of granulocytes in the lungs was found in the treated dogs as indicated by a lower right-to-left atrium granulocyte gradient 15 minutes after pulmonary recirculation during CPB (p less than 0.05) and less granulocyte accumulation in the lung capillaries after CPB, as shown by histological examination (p less than 0.01). Moreover, oxygen free radical release as indicated by plasma malondialdehyde concentrations was significantly lower (p less than 0.05) in the treated dogs than in the controls towards the end of CPB. Finally, a significantly reduced lung-water content was found 30 min after CPB in the treated dogs as compared with the controls (p less than 0.01). These results suggest that anisodamine administration in this experimental model significantly inhibits pulmonary granulocyte sequestration in CPB and the consequent lung injury induced.

Animals↗
PubMed1991

Morphologic activation of lymphocytes in blood during rejection of heart and lung grafts in rats.

We investigated morphologic activation of lymphocytes in blood in a standardized, infection-free rat model and compared lymphocyte activation during rejection of heart grafts and that of lung grafts with other parameters of rejection. For heart grafts the other parameters were histology and palpation, and for lung grafts they were histology, bronchoalveolar lavage, and chest roentgenography. During acute rejection of heart grafts, lymphocyte activation in blood increased when histology of the heart grafts showed already moderate-to-severe rejection with myocyte necrosis. Lymphocyte activation in blood detected acute heart rejection clearly later than histology but somewhat earlier than palpation. During acute rejection of lung grafts, lymphocyte activation in blood increased when histology of the lung grafts showed the (early) vascular phase of rejection, without apparent tissue damage. Lymphocyte activation in blood detected acute lung rejection only slightly later than histology, at approximately the same time as bronchoalveolar lavage and earlier than chest roentgenograms. Lymphocyte activation was higher during acute lung rejection than during acute heart rejection. During "chronic" rejection of long-surviving heart grafts and lung grafts, lymphocyte activation in blood did not increase consistently. The early and strong increase of morphologic activation of lymphocytes in blood during acute lung rejection may imply for clinical transplantation that monitoring of lymphocyte activation in blood is more useful for early detection of acute rejection after lung transplantation than after heart transplantation.

Acute Disease↗
PubMed1991

Lung transplantation in the rat. A morphometric analysis of the gas exchange region.

Single-lung transplantation in the rat provides a model that allows investigators to study immunologic, cellular, and morphologic changes associated with allograft rejection. We performed morphometric analysis of transplanted and nontransplanted lungs removed from recipients having received isografts, allografts, or hilus-stripping up to six months previously, and having received cyclosporine on the first postoperative day, the second postoperative day, the first five days, or not at all. When CsA was not administered, there was extensive and rapid destruction of the alveolar septa with consolidation and rejection of the transplanted lung within one week. In contrast, the allografts from rats treated with CsA were not obviously changed compared with the control lung. To evaluate whether or not these CsA-treated allografts had even subtle injury to alveolar septal cells, a morphometric analysis using transmission electron microscopy was used. There were no significant changes between control (nontransplanted or hilus-stripped) lungs and isografted or allografted lungs for most parameters measured. Exceptions included type I epithelial cell volume, which increased in rats treated with CsA on postoperative day 1 only, and the tissue component of diffusing capacity, which decreased in rats treated with CsA on postoperative day 2 only. We conclude that CsA treatment of rats given lung allografts effectively blocks the development of injury in the gas exchange region. The effect is achieved when the CsA is given during the first five days following transplantation in rats, and may be influenced by the timetable of administration and cumulative dosage.

Animals↗