Biomedical subjects

R G Grabitz

Publications and source records attributed to R G Grabitz.

At least 19 recordsLinked to original sources

PubMed2005

Biocompatibility screening in cardiovascular implants.

BACKGROUND: Interest in information on biocompatibility of implants is increasing. The purpose of this paper is to discuss methods and results of pathological biocompatibility screening of explanted cardiovascular implants. METHODS: Use of standard histology after embedding in paraffin is limited since metallic implants have to be removed during workup with disruption of the specimen. Alternatively, tissue blocks containing an implant can be embedded in methylmethacrylate or hydroxyethylmethacrylate and processed by sectioning with a diamond cutter and grinding, thus leaving the implant in situ and saving the tissue/implant interface for detection of local inflammatory reactions. Another important aspect of evaluation is the progress of thrombus organisation after initial fibrin clotting on the metal surface or in the inner part of occlusion devices. New methacrylate resins and embedding techniques allow for specific immunohistochemical staining of the specimen thus enabling characterisation of tissues surrounding the implant. Information on endothelialisation of the vascular surface of the implant can be obtained by means of immunohistochemistry or by scanning electron microscopy. RESULTS: Illustrating the use of these technologies, we demonstrate findings in tissue specimens from animal studies with different types of devices (i.e. stents, occlusion devices). We present corresponding findings in human specimens with implants that were removed during corrective surgery for congenital heart defects. Early endothelialisation of the vascular surface was seen after implantation in all types of devices. Cells within occlusion devices could be characterised histologically and immunohistochemically as fibromuscular cells as seen in intimal hyperplasia after stent implantation. Inflammatory implant-host reactions ranged from mild to moderate (medical grade stainless steel, nitinol) to severe (polytetrafluoroethylene [PTFE]). CONCLUSIONS: With an optimal work-up of cardiovascular implants, ingrowth and endothelialisation as well as inflammatory reactions in the surrounding tissue can be assessed. This information allows evaluation of individual tissue reactions to the implant and may serve as valuable basis for optimisation of biocompatibility by implant modification.

Animals↗

PubMed2002

Effect of biologically active coating on biocompatibility of Nitinol devices designed for the closure of intra-atrial communications.

Anti-thrombogenicity and rapid endothelialisation are prerequisites for the use of closure devices of intra-atrial communications in order to reduce the risk of cerebral embolism. The purpose of this study was therefore to assess the effect of bioactive coatings on biocompatibility of Nitinol coils designed for the closure of intra-atrial communications. Nitinol coils (n = 10, each) and flat Nitinol bands (n = 3, each) were treated by basic coating with poly(amino-p-xylylene-co-p-xylylene) and then coated with either heparin, r-hirudin or fibronectin. Anti-thrombogenicity was studied in vitro in a dynamic model with whole blood by partial thromboplastin time (PTT), platelet binding and thrombin generation, respectively, and cytotoxicity by hemolysis. Endothelialisation was studied on Nitinol bands with human umbilical venous endothelial cells (HUVEC) by 3-(4,5-dimethylthiazole-2yl)-2,5-triphenyl tetrazolium (MTT) assay and immnuofluorescence analysis of Ki67, vinculin, fibronectin and von Willebrand Factor. Uncoated or coated devices did not influence hemolysis and PTT. r-Hirudin (but not heparin) and fibronectin coating showed lower platelet binding than uncoated Nitinol (p < 0.005, respectively). Heparin and r-hirudin coating reduced thrombin formation (p < 0.05 versus Nitinol, respectively). HUVEC adhesion, proliferation, and matrix formation decreased in the order: fibronectin coating > uncoated Nitinol > r-hirudin coating > heparin coating > basic coating. MTT assay corroborated these findings. In conclusion, r-hirudin and fibronectin coating, by causing no acute cytotoxicity, decreasing thrombogenicity and increasing endothelialisation improve in vitro biocompatibility of Nitinol devices designed for the closure of intra-atrial communications.

Alloys↗

PubMed2001

Time course of cranial ultrasound abnormalities after arterial switch operation in neonates.

BACKGROUND: The object of this study was to investigate the time course and fate of abnormal findings in cranial ultrasound after performing an arterial switch operation in neonates with transposition of the great arteries, and to analyze the relationship to cerebral cell damage. METHODS: Cranial ultrasound was performed prospectively in 35 neonates with transposition of the great arteries before the operation as well as 4 hours, 1, 2, and 3 days, and 1 and 2 weeks postoperatively. Blood levels of neuron-specific enolase, a marker of cerebral cell damage, were determined before, during, and 4 and 24 hours postoperatively. RESULTS: In 17 of 35 neonates (49%), early postoperative cranial ultrasound revealed abnormalities indistinguishable from intraventricular hemorrhage. In 11 neonates findings were transient and were normalized 2 weeks postoperatively, whereas in the remaining 6 neonates there was evidence of resolving hemorrhage. In all neonates there was a rise in neuron-specific enolase blood concentrations during and 4 hours after extracorporal circulation without correlation to sonographic findings. CONCLUSIONS: Enhanced echogenicity of the choroid plexus or dilatation of the cerebral ventricular system is a frequent early postoperative finding that may be caused by transient plexus edema rather than intraventricular hemorrhage and is not related to cerebral cell damage.

Arteries↗

PubMed2000

Evaluation of in vivo biocompatibility of different devices for interventional closure of the patent ductus arteriosus in an animal model.

OBJECTIVE: To evaluate the in vivo biocompatibility of three different devices following interventional closure of a patent ductus arteriosus (PDA) in an animal model. MATERIALS AND METHODS: A medical grade stainless steel coil (n = 8), a nickel/titanium coil (n = 10), and a polyvinylalcohol foam plug knitted on a titanium wire frame (n = 11) were used for interventional closure of PDA in a neonatal lamb model. The PDA had been maintained by repetitive angioplasty. Between one and 278 days after implantation the animals were killed and the ductal block removed. In addition to standard histology and scanning electron microscopy, immunohistochemical staining for biocompatibility screening was also undertaken. RESULTS: Electron microscopy revealed the growth of a cellular layer in a cobblestone pattern on the implant surfaces with blood contact, which was completed as early as five weeks after implantation of all devices. Immunohistochemical staining of these superficial cells showed an endothelial cell phenotype. After initial thrombus formation causing occlusion of the PDA after implantation there was ingrowth of fibromuscular cells resembling smooth muscle cells. Transformation of thrombotic material was completed within six weeks in the polyvinylalcohol plug and around the nickel/titanium coil, and within six months after implantation of the stainless steel coil. An implant related foreign body reaction was seen in only one of the stainless steel coil specimens and in two of the nickel/titanium coil specimens. CONCLUSION: After implantation, organisation of thrombotic material with ingrowth of fibromuscular cells was demonstrated in a material dependent time pattern. The time it took for endothelium to cover the implants was independent of the type of implant. Little or no inflammatory reaction of the surrounding tissue was seen nine months after implantation.

Animals↗

PubMed1999

Mid-term follow-up after multiple system organ failure following cardiac surgery in children.

Multiple system organ failure after cardiac surgery in children is a severe complication with unknown mid- and long-term sequelae. We therefore evaluated 11 children (aged 20-126 mo, median: 67 mo) having survived multiple system organ failure after cardiac operations for congenital cardiac defects in a cross-sectional follow-up study 12-76 mo (median: 32 mo) after surgery. Clinical and laboratory examinations included cardiac, pulmonary, renal, hepatic, neurological and psychological function tests. All patients had adequate cardiac function. Lung mechanics were abnormal in three children and glomerular renal function was abnormal in two patients. Slight elevation of gamma-glutamyl transpeptidase and coagulation factor deficiency was present in six and seven patients, respectively (five of whom had undergone the Fontan operation). Severe neurological sequelae such as diplegia (n = 1) and mental retardation (n = 1) were observed in two patients. In addition, five children presented delayed motor, graphomotor and/or speech development. Two children were found to have abnormal intelligence. We conclude that with the exception of neurological impairment, mid-term sequelae of multiple system organ failure after cardiac surgery in children are mild. However, longer follow-up using an appropriate control group is mandatory.

Cardiac Surgical Procedures↗

PubMed1998

Double-helix coil for occlusion of large patent ductus arteriosus: evaluation in a chronic lamb model.

OBJECTIVES: We sought to evaluate the efficacy and tissue reaction of a new miniature interventional device for occlusion of large patent ductus arteriosus (PDA) in a neonatal lamb model. BACKGROUND: A variety of devices are used to close PDAs by interventional measures. Spring coils found to have a high cumulative occlusion rate have thus far been limited to smaller PDAs because of the physical limitation of grip forces. METHODS: Memory-shaped double-cone stainless steel coils with enhanced stiffness of the outer rings by a double-helix configuration were mounted on a titanium/nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 4F or 5F Teflon catheter. A chronic lamb model (n = 8) of PDA (>5 mm) was used in which ductus patency was secured by a protocol of repetitive angioplasty procedures. The animals were killed after 1 to 181 days, and the ductal region was examined by inspection as well as by light and electron microscopy. RESULTS: Placement of the coils within the PDA was possible in all lambs. Before final detachment, the coils were retrieved or repositioned, or both, up to 12 times. In all but one animal the ductus was closed within 6 days after the procedure. The coils caused no infections or aortic and pulmonary artery obstruction. Histologic and electron microscopic studies revealed endothelial coverage of the implants but no foreign body reaction or local or systemic inflammation or erosion of the implant. CONCLUSIONS: The device effectively closed large PDAs in our model and may overcome the previous limitations of coils. Clinical trials are indicated.

Angiography↗

PubMed1998

The production of pro- and anti-inflammatory cytokines in neonates assessed by stimulated whole cord blood culture and by plasma levels at birth.

The capability of neonates to achieve cytokine balance was evaluated. Production of the pro-inflammatory cytokines TNF alpha and IL-8, of the natural anti-inflammatory cytokine IL10 and of the regulator of the acute phase response IL6 was assessed after whole blood stimulation by lipopolysaccharide in cord blood (n = 10), adult volunteers serving as control (n = 17). Additionally, circulating cytokines were determined in cord and in maternal blood immediately after delivery (n = 27, respectively). Significant production of TNF alpha, IL8, IL10 and IL6 was observed in cord blood after lipopolysaccharide stimulation and was similar to cytokine production in adult blood. The plasma concentrations of TNF alpha were significantly higher in cord than in maternal blood, while plasma concentrations of IL10 and IL6 were significantly lower. Our results demonstrate fully developed capability of whole cord blood to synthesize pro- and anti-inflammatory cytokines in response to a pro-inflammatory stimulation in vitro. In vivo, however, higher circulating TNF alpha and lower IL10 and IL6 levels in cord blood suggest that the inflammatory stress associated with normal delivery does not induce detectable anti-inflammatory response in neonates at birth.

Adult↗

PubMed1997

Quantitative analysis of the morphology of secundum-type atrial septal defects and their dynamic change using transesophageal three-dimensional echocardiography.

BACKGROUND: A noninvasive method for the determination of size and spatial relationships of atrial septal defects to adjacent cardiac structures, which would be advantageous to those contemplating device closure, is described. The aim of the study was to examine the value of transesophageal three-dimensional echocardiography for this purpose. METHODS AND RESULTS: Three-dimensional reconstruction of transesophageal two-dimensional echocardiography was performed in 17 patients. Left-to-right shunt (by oximetry in 16 of 17 patients) was 2.4 to 16.2 L/min, and the Qp/QS ratio was 1.4 to 4.7. The defect area of the atrial septal defect was measured throughout the whole cardiac cycle each 40 ms from the three-dimensional data set. Results were compared with shunt parameters by oximetry and with intraoperative measurements. Distances between atrial septal defect and mitral and tricuspid annulus and the orifices of the caval and pulmonary veins were also measured. The atrial septal defect area ranged from 0.2 to 2.4 cm2 (diastole) to 0.5 to 5.6 cm2 (systole). The maximal area at end-systole was 108% of the area at beginning of systole, and the minimal area at end-diastole was 43%. The defect area correlated significantly with the Qp/QS ratio (r=.70), and the maximal atrial septal defect diameters as measured by using three-dimensional echocardiography correlated well with intraoperative measurements (r=.87). Distances to mitral and tricuspid annulus and to the superior caval vein were determined in all patients. Distances to orifice of the inferior caval vein were measured in 12 patients, and orifices of right pulmonary veins were visible in 5 patients. CONCLUSIONS: Transesophageal three-dimensional echocardiography of atrial septal defects allows the determination of the instantaneous defect area and its dynamic changes and thus provides valuable information about the distances to adjacent cardiac structures. This may have clinical implications for the selection of patients suitable for interventional closure and for the assessment of procedural success.

Adult↗

PubMed1997

[A new system for transvenous occlusion of persistent ductus arteriosus].

An Ivalon-plug (PDA-plug) has been developed for transvenous closure of patent ductus arteriosus. It can be introduced into the ductus through standard venous sheaths with a diameter of 8-16 French. The plug is fixed in its target position by means of four distal (aortal) and two proximal (pulmonary) nitinol struts. In case of malpositioning the system can be pulled back into and retrieved through the sheath. In animal experiments endothelialization of the implanted material was demonstrated. PDA-closure was attempted in 58 patient; the procedure was successful in 57 cases; a residual ductal flow was present in eight patients. During a follow-up of up to 24 months there were no complications.

Adolescent↗

PubMed1997

Interventional atrioseptostomy by application of monopolar high-frequency alternating current. In vitro evaluation of a new device.

RATIONALE AND OBJECTIVES: The authors evaluate the use of a new device for interventional creation of atrial septal defects (ASD) working with high-frequency alternating current in an in vitro study with porcine atria. METHODS: The device consists of a symmetrical cage of six superelastic monofile wires, including a microthermistor that is placed via a catheter into a punctured hole in the porcine foramen ovale. The device is used as a differential electrode for monopolar, temperature-controlled application of high-frequency alternating current for thermal modelling of ASD. RESULTS: Application of current for 60 seconds caused temperature-dependent, sized ASDs. CONCLUSION: In vivo animal studies to evaluate possible side effects and long term patency of the ASDs are justified and warranted.

Animals↗

PubMed1997

Retrievable patent ductus arteriosus plug for interventional, transvenous occlusion of the patent ductus arteriosus. Evaluation in lambs and preliminary clinical results.

RATIONALE AND OBJECTIVES: The clinically most widely used devices (Porstmann-plug, Rashkind-umbrella, Botallooccluder) have inherent specific limitations (eg, transarterial approach, residual shunts, limited retrieval). The authors assess practicability, efficacy, and tissue reaction of the new retrievable transvenous plug device for the occlusion of the persistent patent ductus arteriosus (PDA). METHODS: A foam plug (polyvinyl alcohol) is mounted on a titanium core pin where, at both ends, small legs (titanium nickel alloy) with titanium heads are anchored, to ensure safe fixation in the ductus. The device is introduced transvenously through a long sheath (Mullins sheath) and held by a modified biopsy forceps allowing complete retrieval until final release. A common lamb model of large PDAs (n = 11) was used to test for practicability and the histomorphologic outcome. Clinical results were obtained from a consecutive series of 16 patients (aged 13 to 71 years). RESULTS: In all lambs, placement of the plug within the PDA was possible. Histopathology (follow-up 10 to 215 days; mean 112 days) revealed an adequate ingrowing of the device and no pathologic foreign body reaction. The diameter of the human PDAs ranged from 3 to 7 mm (mean 5 mm). The size of the sheath used for introducing the plug (diameter 8 to 16 mm) ranged from 8 to 16 French. Fourteen of 16 PDAs were closed immediately after or on day 1 after implantation, 1 was closed after the 12-month follow-up, and 1 needed an additional plug after 30 months for definitive closure. CONCLUSIONS: The device demonstrated practicability and biocompatibility in our experimental lamb model and effectively closed the PDA in a consecutive series of 16 patients. A greater number of patients and a longer follow-up period are necessary for the definitive clinical assessment of the new device.

Adolescent↗

PubMed1997

Coil on the loop and selectively enhanced stiffness for improved control: feasibility study in the neonatal ovine model of the large patent ductus arteriosus.

RATIONALE AND OBJECTIVES: Several devices have been suggested and tested for interventional closure of the persistent ductus arteriosus. Coils were found effective only in small ducts due to their lack of maneuverability and physical limitation of grip forces leading to risk of embolization. The authors evaluated the feasibility to place single coils with selectively enhanced stiffness into high shunting ductus arteriosus, the coils being deployed and controlled through a veno-arterial loop in a bovine model. METHODS: "Double-cone" shaped, stainless steel coils with enhanced stiffness of the outer rings were mounted on either end on a nitinol core wire. A snap-in mechanism attaches the coil to this delivery wire and is freed by a pusher system of coiled steel wire that is advanced over the core wire. Forming a veno-arterial loop across the patent ductus allows for repositioning into the pulmonary artery or aortic catheter. A chronic lamb model of large patent ductus arteriosus (PDAs) (> or = 9 mm) was used in which ductus patency was secured by a protocol of repetitive angioplasties. Different systems (n = 10) were placed having retrieved the previous coil by a snare after definitive release. RESULTS: Placement of coils was possible in all 10 attempts. The coils were pulled back into the catheters between five and eight times before definitive release. CONCLUSIONS: The device allows controlled placement of single coils in our model of large PDAs and may lead the way to overcome previous limitations of coils. Clinical trials are warranted.

Animals↗

PubMed1996

Influence of low-dose aprotinin on the inflammatory reaction due to cardiopulmonary bypass in children.

BACKGROUND: The serine protease inhibitor aprotinin inhibits trypsin, kallikrein, and plasmin and enhances the complement hemolytic activity of the first complement component C1. We tested whether low-dose aprotinin influences the inflammatory reaction related to cardiopulmonary bypass. METHODS: In an open, randomized study, 25 children undergoing cardiac operations were investigated prospectively. The treated group comprised 11 patients receiving low-dose aprotinin (20,000 kIU/kg [2.8 mg/kg]), and the control group included 14 patients. Complement activation, cytokine production, and leukocyte stimulation were analyzed before, during, and after cardiopulmonary bypass. RESULTS: In all children, significant C3 conversion and C5a generation, interleukin-6 synthesis, and myeloperoxidase, eosinophil cationic protein, and histamine liberation occurred in relation to cardiopulmonary bypass. This was not influenced by aprotinin treatment. In contrast, neutrophil kinetic studies at the end of cardiopulmonary bypass showed a significantly lower increase in the aprotinin as compared with the control group. CONCLUSIONS: Our results suggest that low-dose aprotinin has little influence on the inflammatory reaction induced by cardiopulmonary bypass. Aprotinin affects neutrophil mobilization but not white blood cell degranulation related to cardiopulmonary bypass, and has no influence on complement activation and interleukin-6 synthesis.

Analysis of Variance↗

PubMed1996

Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations.

We studied the inflammatory reaction related to cardiopulmonary bypass in 24 neonates (median age 6 days) undergoing the arterial switch operation for simple transposition of the great arteries, with respect to the development of postoperative capillary leak syndrome. Complement proteins, leukocyte count, tumor necrosis factor-alpha, and histamine levels were determined before, during, and after cardiopulmonary bypass. Additionally, protein movement from the intravascular into the extravascular space during cardiopulmonary bypass was assessed by the measurement of plasma concentrations of proteins with molecular weights ranging from 21,200 to 718,000. Capillary leak syndrome developed in 13 of the 24 neonates. Patients with capillary leak syndrome, as compared with those without, had preoperatively higher C5a levels (C5a, 3.0 +/- 0.6 microgram/L vs 0.9 +/- 0.2 microgram/L) (mean +/- standard error of the mean) (p < 0.05) and higher leukocyte counts (leukocytes, 17.9 +/- 2.1 X 10(3) cells/ml versus 11.7 +/- 0.8 X 10(3) cells/ml) (p < 0.05), suggesting in these neonates a preoperative inflammatory state. Preoperative clinical and operative data were identical in both patient groups. Before cardiopulmonary bypass, serum protein concentrations were similar in all patients. Ten minutes after institution of cardiopulmonary bypass, protein concentrations fell to significantly lower values in patients with capillary leak syndrome than in those without: albumin (19% +/- 1.5% vs 30% +/- 6% of the prebypass value, p < 0.05), immunoglobulin G (17% +/- 1.5% vs 29% +/- 5.5%, p < 0.001), and alpha 2-macroglobulin (15% +/- 1.2% vs 25% +/- 4%, p < 0.02). During cardiopulmonary bypass, albumin concentrations remained significantly lower in patients with capillary leak syndrome than in those without, whereas hematocrit values were similar in both groups. During cardiopulmonary bypass, patients with capillary leak syndrome also had lower concentrations of complement proteins C3 and C4 but not C1 inhibitor. C3d/C3 ratio and C5a levels were similar in both patient groups. In contrast, histamine liberation during cardiopulmonary bypass was significantly more pronounced in patients with capillary leak syndrome than in those without (725.2 +/- 396.7 pg/ml vs -54.1 +/- 58.4 pg/ml, p < 0.05). Tumor necrosis factor-alpha levels after protamine administration were also significantly higher in patients with capillary leak syndrome (38.1 +/- 10.0 pg/ml vs 15.3 +/- 3.4 pg/ml, p < 0.05). Leukocyte count during and after cardiopulmonary bypass was similar in both patient groups. This study demonstrates increased protein leakage as early as 10 minutes after initiation of.

Acute-Phase Reaction↗

PubMed1996

Effect of sodium nitroprusside on complement activation induced by cardiopulmonary bypass: a clinical and experimental study.

Complement activation and leukocyte stimulation were prospectively studied during and after cardiopulmonary bypass in 16 children receiving sodium nitroprusside--a nitrovasodilator releasing nitric oxide--for vasodilation during the cooling and rewarming periods of extracorporeal circulation. Results were compared with those in 29 patients who were not treated with sodium nitroprusside during the operation. Patients treated with sodium nitroprusside had significantly less C3 conversion during cardiopulmonary bypass as measured by the ratio C3d/C3 (p <0.05) and significantly less C5a liberation immediately after cardiopulmonary bypass (p < 0.005) than patients not treated with sodium nitroprusside. C4 was not overtly consumed in our series. Leukocyte count during the rewarming period of cardiopulmonary bypass, but not leukocyte elastase release during cardiopulmonary bypass, was significantly reduced in patients treated with sodium nitroprusside (p <0.05). In vitro experiments were conducted to analyze the effect of sodium nitroprusside on complement hemolytic activity initiated by the classic and the alternate pathways and on zymosan-induced C3 conversion by the activation of the alternate pathway. The in vitro experiments clearly demonstrate inhibition of complement hemolytic activity by sodium nitroprusside in the sera tested. The 50% inhibitory concentration of sodium nitroprusside on the available complement hemolytic activity was less through the alternate pathway than through the classic one (4.2 +/- 0.8 mmol/L and 14.0 +/- 2.88 mmol/L, respectively). The decrease of complement hemolytic activity measured was dose-dependent and was enhanced by the sodium nitroprusside preincubation of the sera tested. This effect was related to the duration of preincubation. Sodium nitroprusside photodegradation (enhancing nitric oxide release) increased the anticomplementary effect of the drug, reducing the 50% inhibitory concentration on complement hemolytic activity to 0.24 to 0.02 mmol/L for the alternate pathway and 2.74 o 0.3 mmol/L for the classic pathway. the zymosan-induced C3 conversion was inhibited by sodium nitroprusside. Nitroglycerin and isosorbide dinitrate (other nitric oxide donors) had in vitro effects on complement hemolytic activity similar to those of nonphotodegraded sodium nitroprusside at similar concentrations (1 mmol/L). Our results suggest that sodium nitroprusside, both in vitro and in vivo, has an inhibiting effect on complement activation initiated by both classic and alternate pathways and that this effect is mediated by nitric oxide release from sodium nitroprusside. This is the first report on the anticomplementary effect of sodium nitroprusside by nitric oxide release.

Cardiopulmonary Bypass↗

PubMed1996

Histamine liberation related to cardiopulmonary bypass in children: possible relation to transient postoperative arrhythmias.

Tumor necrosis factor-alpha production and products of mast cell, basophil, and eosinophil degranulation (prostaglandin D2, histamine, and eosinophil cationic protein) were prospectively studied in 26 children undergoing cardiac operations. The relationship between inflammatory response to cardiopulmonary bypass and transient postoperative arrhythmias was analyzed. Cardiopulmonary bypass was conducted with circulatory arrest and deep hypothermia in 10 patients and with continuous low-flow and moderate hypothermia in 16 patients. Transient postoperative arrhythmias diagnosed on standard or atrial electrocardiograms (or both) were seen in eight of the 26 examined children: accelerated junctional rhythm (n = 3), junctional ectopic tachycardia (n = 3), second-degree atrioventricular block (n = 1), and third-degree atrioventricular block (n = 1). Children with transient postoperative arrhythmias were younger than those without (p < 0.05). Compared with baseline values, there was in all patients a significant release of histamine and eosinophil cationic protein (p < 0.05) related to cardiopulmonary bypass, reaching peak values 4 hours after the operation. In contrast, tumor necrosis factor-alpha production and prostaglandin D2 release were not significant. This suggests that activated basophils but not mast cells are the major sources of histamine liberated during and after cardiopulmonary bypass. Histamine release but not eosinophil cationic protein release correlated with circulatory arrest and deep hypothermia (p < 0.05), suggesting the participation of physicochemical alterations of circulating basophils leading to histamine liberation. Four hours after the operation, patients with transient postoperative arrhythmias had significantly higher blood concentrations of histamine (p < 0.02) and eosinophil cationic protein (p < 0.05) than did those without transient postoperative arrhythmias. On the first postoperative day, four of the eight patients with transient postoperative arrhythmias had persisting elevated histamine levels, whereas in patients without transient postoperative arrhythmias histamine reached baseline values. The multivariate analysis retained histamine release and eosinophil cationic protein variations related to cardiopulmonary bypass for the emerging model to predict transient postoperative arrhythmias. The results of this study show significant histamine release related to cardiopulmonary bypass. Furthermore, they document a possible relationship between circulating histamine and transient postoperative arrhythmias. The latter may therefore be suspected among the consequences of the inflammatory response to cardiopulmonary bypass.

Adolescent↗

PubMed1996

A small interventional device to occlude persistently patent ductus arteriosus in neonates: evaluation in piglets.

OBJECTIVES: We attempted to evaluate the efficacy and tissue reaction of a new miniature interventional ductal occlusion device in neonatal pigs. BACKGROUND: A variety of devices are used to close persistent ductus arteriosus (PDA) by interventional measures. Because of the size of these devices, they have not been applied to term or preterm neonates. Newborn piglets are comparable in size and fragility to human term and preterm neonates. METHODS: Memory-shaped double-cone stainless steel coils were mounted on a titanium-nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 3F Teflon catheter. Two piglet models of PDA were used: 1) ductal patency maintained by stents (n = 6), and 2) ductal patency produced by angioplasty (n = 7) to avoid stent-coil interaction. RESULTS: Placement of the coils within the PDA was possible in all piglets. Before final detachment, the coils were retrieved or repositioned, or both, up to eight times. In all but two piglets the ductus was closed within 1 h of the procedure. The coils were never dislocated and caused no infections or relevant aortic and pulmonary artery obstruction (95% confidence interval for missing complications [0 of 13] extends to 23%). Histologic and electron microscopic studies revealed endothelial coverage of the implants and histiocytic reaction but no local or systemic inflammation or erosion of the implant. CONCLUSIONS: The device was effective in experimental models of PDA. The information obtained warrants initial trials of the device in neonates.

Animals↗

PubMed1996

Enhanced occlusion of vessels combining retrievable, detachable coils as differential electrodes with percutaneous, intravascular radiofrequency electrocoagulation. An experimental study.

RATIONALE AND OBJECTIVES: The authors evaluate the feasibility to accelerate occlusion of high-velocity flow vessels by a combination of transcutaneous coil placement and application of radiofrequency current. METHODS: Piglets (n = 8) were anesthetized and acutely instrumented via cutdowns in both carotid and one brachial arteries. Two identical cylindrically shaped coils (length, 3 mm; outer diameter, 2.4 mm; inner diameter, 1.4 mm) were mounted on titanium-nickel core wire and placed via 3-French Nylon catheters in both iliac arteries. The coils were kept connected to the delivery wire, which is isolated from the surrounding tissue by the catheter. The first-placed system served as control, the contralateral coil was connected to a radiofrequency generator closing electrical circuit via an external indifferent electrode. Angiograms via the brachial artery demonstrated the adequate placement of the coils and the status of the iliac arteries without and with current application. In 6 of the 8 cases, 25 watts of radiofrequency current were applied repeatedly over 10 seconds to the coil on one side at 4-minute intervals until occlusion was demonstrated. In 2 of 8 cases. 25 watts were applied continuously over 30 seconds. The coils were detached from the wire the catheters removed. Additional angiograms were performed after 5, 15, 45, and 60 minutes to show the patency of the control setting. RESULTS: Complete occlusion was achieved in all cases after a maximum of three consecutive applications of current for 10 seconds. The control remained patent for a minimum of 45 minutes. On gross and histologic examination the arteries on both sides remained intact. Disruption and charring occurred only after continuous application of current over 30 seconds. CONCLUSIONS: It is feasible to use detachable coils in conjunction with high-frequency electrocoagulation to promote coil fixation and accelerate occlusion of vessels with high blood flow.

Angiography↗