Ch.R.H. Wildevuur

Clinical evaluation of duraflo II heparin treated extracorporeal circulation circuits (2nd version): The European working group on heparin coated extracorporeal circulation circuits

OBJECTIVES To evaluate whether the application of heparin treated circuits for elective coronary artery surgery improves postoperative recovery, a European multicenter randomised clinical trial was carried out. METHODS In 11 European heart centers, 805 low-risk patients underwent cardiopulmonary bypass (CPB) with either an untreated circuit (n = 407) or an identical but heparin treated circuit (n = 398, Duraflo II). RESULTS Significant differences were found among participating centers with respect to patient characteristics, blood handling procedures and postoperative care. The use of heparin treated circuits revealed no overall changes in blood loss, blood use, time on ventilator, occurrence of adverse events, morbidity, mortality, and intensive care stay. These results did not change after adjustment for centers and (other) prognostic factors as analysed with logistic regression. In both groups no clinical or technical (patient or device related) side effects were reported. Because female gender and aortic cross clamp time appeared as prognostic factors in the logistic regression analysis, a subgroup analysis with these variables was performed. In a subpopulation of females (n = 99), those receiving heparin treated circuits needed less blood products, had a lower incidence of rhythm disturbances and were extubated earlier than controls. In another subgroup of patients with aortic cross clamp time exceeding 60 min (n = 197), the amount of patients requiring prolonged intensive care treatment (> 24 h) was significantly lower when they received heparin treated circuits versus controls. CONCLUSION These findings suggest that improved recovery can be expected with heparin treated circuits in specific higher risk patient populations (e.g. females) and when prolonged aortic cross clamp time is anticipated. Further investigations are recommended to analyses the clinical benefit of heparin treated circuits in studies with patients in different well defined risk categories and under better standardised circumstances.

In vivo quantification of cell-polymer interactions

An in vivo rat model was developed to determine cell-polymer interactions under physiological conditions. Microporous tubular grafts, made of polytetrafluoroethylene, a polyetherurethane, a polyesterurethane and also a modified polyetherurethane were implanted intraperitoneally in rats. The grafts were filled with cultured rat smooth muscle cells prior to implantation. At t = 0, 2 and 48 h, the grafts were evaluated macroscopically and also prepared for light microscopy and for cell count of their contents. At t = 0 no cellular attachment was observed on the lumenal side of the capsules. At t = 2 h a monolayer of smooth muscle cells could be observed on all materials except PTFE, on which only small patches of cells were observed. At t = 48 h a multilayer of cells was seen on all materials except PTFE. Cell counts at 48 h demonstrated no multiplication in the PTFE graft but a 1.4, 2.3 and 2.0-fold multiplication in the polyetherurethane, polyesterurethane and the modified polyurethane grafts respectively. These in vivo results show a clear linear relationship with our in vitro results in which it has been proved that cell spreading increased with increasing substratum surface free energy. This rat model allows the study of cell-polymer interactions in vivo, in a standardized way, under controlled physiological conditions.

In vivo fragmentation of microporous polyurethane- and copolyester 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.

Incorporation of microporous Teflon tracheal prostheses in rabbits: Evaluation of surgical aspects

Because tracheal prostheses made of nonporous silicone rubber develop granulation tissue at the anastomoses, we tested a prosthesis made of a microporous material (polytetrafluoroethylene, Teflon) to see whether this problem could be avoided and the prosthesis could be successfully incorporated (luminal side covered by connective tissue and epithelium). At various times after implantation in the cervical trachea of rabbits, the prostheses were inspected macroscopically for obstruction of the prosthesis lumen (lumen reduced by one-third or more) and microscopically for incorporation and inflammatory reaction (concentration of inflammatory cells) of the prosthesis. The prosthesis was successfully incorporated within 2-4 weeks in most rabbits without granulation tissue at the anastomoses. Two complications were infection of the prosthesis before incorporation was completed and obstruction of the lumen in the center of the prosthesis by granulation tissue or a deformed prosthesis wall. Both problems can be overcome, the first by giving an appropriate antibiotic for a longer period and the second by making a stiffer prosthesis. Thus, the microporous Teflon prosthesis is potentially useful as a tracheal prosthesis in rabbits.

High-frequency oscillation affects surfactant phospholipid metabolism in rabbits

Surfactant phospholipid metabolism was studied in anesthetized rabbits ventilated with high-frequency oscillation at a frequency of 5 Hz and a mean airway pressure of 5 cm H2O. Blood gases were normal although some atelectasis was evident after 1 h. The static compliance of the lungs and amount and composition of surfactant phospholipids of the lamellar body and alveolar lavage fraction were comparable to values found for spontaneously breathing rabbits. The data obtained for the incorporation of radioactively labeled palmitate into phospholipids are compatible with intracellular degradation of newly synthesized surfactant phospholipids. This hypothesis is supported by two observations. First, the rapid initial increase in specific activity of SPC and PC of the lamellar body fraction is not accompanied by a similar rapid increase in specific activity of SPC and PC of the lamellar body fraction is not accompanied by a similar rapid increase in specific activity of the alveolar lavage fraction. Second, a dissociation occurs between the metabolism of PC and SPC for the lamellar body fraction but not for the alveolar lavage fraction. The change in metabolism might be caused by the absence of large pressure swings during this pattern of ventilation.

Transthoracic electrical impedance: artifacts associated with electrode movement.

The applicability of transthoracic impedance measurements for estimating thoracic fluid volume and tidal volume is limited by large variations associated with electrode movement, repeated application of electrodes and inter-individual differences. These sources of variation were studied with a four-electrode impedance-measuring device in anaesthetized dogs. Electrode movement artifacts affecting both the resting expiratory value of impedance (Zo) and the respiratory change of impedance (deltaZ/VT) could be largely eliminated by rigidly fixing the distances between the current-supplying and the potential-sensing electrodes. The reproducibility of Zo and deltaZ/VT was found to be affected adversely by local conductivity changes in the skin induced by repeated removal of the glued electrodes. Inter-individual variations in Zo and deltaZ/VT correlated with the thickness of thoracic subcutaneous fat (r = 0.86) and thoracic circumference (r = -0.95) respectively. Correction for these sources of inter-individual variation allowed the standard deviations of Zo and deltaZ/VT to be reduced from 18% to 7% and from 51% to 17% of their respective mean values.

ASSESSMENT OF BRAIN OXYGENATION - A COMPARISON BETWEEN AN OXYGEN-ELECTRODE AND NEAR-INFRARED SPECTROPHOTOMETRY

The inability of the brain to withstand more than a brief period of hypoxia is often the limiting factor determining survival for a variety of clinical conditions, most notably the adult respiratory distress syndrome and the hypoxic-hypotension related to major trauma. The capability for continuously and non-invasively monitoring cerebral oxygen availability within the mitochondria would be extremely desirable. Prior to the introduction of nearinfrared spectrophotometry (niroscopy) by Jobsis (1977) such a capability did not exist. Subsequent work (Proctor et al., 1982) demonstrated the feasibility of monitoring cerebral cytochrome a,a3 redox states using in vivo spectrophotometry in a variety of experimental models, designed to mimic frequently encountered clinical conditions. An immediate problem became the interpretation and validation of the data in terms of a more conventional and commonly accepted method of assessing tissue oxygenation. As one of a series of investigations designed to clarify the role of niroscopy with regard to future applications, the present study correlates cytochrome a,a3 redox state and the intracerebral hemoglobin (HbO2) as measured by niroscopy with simultaneously performed measurements of cerebral cortex surface Po2 obtained using a Polarographic oxygen electrode.

Platelet Behavior in Extracorporeal Circulation (ECC)

Compatibility of blood with nonphysiologic materials is of increasing importance. The basis of estimating such compatibility has shifted from the determination of hemolysis to the estimation of the clotting capacity. This can be specified in terms of number and function of circulating thrombocytes and the resulting bleeding time. In this study components of commonly used standard equipment for open heart surgery have been compared to alternatives. The parameters studied yield more relevant information for ranking materials in relation to their blood compatibility than does estimation of hemolysis alone. The behavior of the thrombocytes showed an initial dip (acute aggregation phenomenon), a plateau (equilibrium between aggregation and desaggregation) and a secondary dip (elimination of irreversibly damaged cells). Correlated to criteria of major hematological differences as observed between membrane‐oxygenators and bubble‐oxygenators, the percentage of circulating thrombocytes at the moment of the secondary dip gives the best overall information about hemocompatibility.

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 ofβ-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.

Preserved Hemostasis During the Combined Use of Aprotinin and Aspirin in CABG Operations

After the remarkable improvement of hemostasis in cardiopulmonary bypass (CPB) obtained with the proteinase inhibitor aprotinin [17], its use spread rapidly in cardiac clinics throughout Europe [2, 3]. Although the mode of action has not been completely revealed, we concurrently showed the relation of improved hemostasis with preserved platelet adhesive receptors [18, 19]. Increasing numbers of patients with coronary artery diseases are now treated with aspirin [14] and are submitted with this treatment for coronary artery bypass grafting operation (CABG).