Matching the diameter of ePTFE bypass prosthesis with a native artery improves neoendothelialization.

BACKGROUND AND AIM: The undersizing of the bypass graft diameter compared to native artery changes blood flow characteristics and velocity which may affect conduit neo-endothelialization, intimal hyperplasia reaction and patency. The aim of this study was to evaluate conduit neoendothelialization, intimal hyperplasia reaction and patency results between undersized and matched ePTFE grafts. MATERIAL AND METHODS: In 16 male Sprague-Dawley rats, undersized (1-mm internal diameter) and matched (2-mm internal diameter) ePTFE grafts were anastomosed end-to-end in the infrarenal abdominal aorta. Blood flow volume per minute was measured and wall shear stress was calculated for each group. After 3 weeks of follow-up, angiography was performed via the left carotid artery just before sacrifice. Conduit neoendothelialization and intimal hyperplasia reaction were measured by computer-assisted morphometry. RESULTS: Wall shear stress was 8 times higher for the undersized group (840.56 vs. 105.07 mPa). Three weeks after implantation, conduit neoendothelialization was better in matched grafts compared to undersized grafts (441 vs. 574 microm, p = 0.008). Intimal hyperplasia reaction was similar for both groups (8.7 vs. 6.7 microm(2)/microm for undersized and matched grafts, respectively). Patency rate was 7/8 for undersized and 8/8 for matched ePTFE grafts. CONCLUSION: Although the graft patency and the intimal hyperplasia reaction were not different between the two groups after 3 weeks, matched grafts had a significantly better endothelialization compared to undersized grafts. This short-term beneficial effect may influence long-term patency results.

ECG-triggered skeletal muscle stimulation improves hemodynamics and physical performance of heart failure patients.

BACKGROUND: Muscular counterpulsation (MCP) was developed for circulatory assistance by stimulation of peripheral skeletal muscles. We report on a clinical MCP study in patients with and without chronic heart failure (CHF). METHODS AND RESULTS: MCP treatment was applied (30 patients treated, 25 controls, all under optimal therapy) for 30 minutes during eight days by an ECG-triggered, battery-powered, portable pulse generator with skin electrodes inducing light contractions of calf and thigh muscles, sequentially stimulated at early diastole. Hemodynamic parameters (ECG, blood pressure and echocardiography) were measured one day before and one day after the treatment period in two groups: Group 1 (9 MCP, 11 no MCP) with ejection fraction (EF) above 40% and Group 2 (21 MCP, 14 no MCP) below 40%. In Group 2 (all patients suffering from CHF) mean EF increased by 21% (p<0.001) and stroke volume by 13% (p<0.001), while end systolic volume decreased by 23% (p<0.001). In Group 1, the increase in EF (6%) and stroke volume (8%) was also significant (p<0.05) but less pronounced than in Group 2. Physical exercise duration and walking distance increased in Group 2 by 56% and 72%, respectively. CONCLUSIONS: Noninvasive MCP treatment for eight days substantially improves cardiac function and physical performance in patients with CHF.

ECG-triggered muscular counterpulsation for treatment of low cardiac output.

BACKGROUND: Skeletal muscular counterpulsation (MCP) has been used as a new noninvasive technique for treatment of low cardiac output. The MCP method is based on ECG-triggered skeletal muscle stimulation. The purpose of the present study was to evaluate acute hemodynamic changes induced by MCP in the experimental animal. METHODS: Eight anaesthetized pigs (43+/-4 kg) were studied at rest and after IV â-blockade (10 mg propranolol) before and after MCP. Muscular counterpulsation was performed on both thighs using trains (75 ms duration) of multiple biphasic electrical impulses with a width of 1 ms and a frequency of 200 Hz at low (10 V) and high (30 V) amplitude. ECG-triggering was used to synchronize stimulation to a given time point. LV pressure-volume relations were determined using the conductance catheter. After baseline measurements, MCP was carried out for 10 minutes at low and high stimulation amplitude. The optimal time point for MCP was determined from LV pressure-volume loops using different stimulation time points during systole and diastole. Best results were observed during end-systole and, therefore, this time point was used for stimulation. RESULTS: Under control conditions, MCP was associated with a significant decrease in pulmonary vascular resistance (-18%), a decrease in systemic vascular resistance (-11%) and stroke work index (-4%), whereas cardiac index (+2%) and ejection fraction (+6%) increased slightly. Pressure-volume loops showed a leftward shift with a decrease in end-systolic volume. After â-blockade, cardiac function decreased (HR, MAP, EF, dP/dt max), but it improved with skeletal muscle stimulation (HR +10% and CI +17%, EF +5%). There was a significant decrease in pulmonary (-19%) and systemic vascular resistance (-29%). CONCLUSIONS: In the animal model, ECG-triggered skeletal muscular counterpulsation is associated with a significant improvement in cardiac function at baseline and after IV â-blockade. Thus, MCP represents a new, non-invasive technique which improves cardiac function by diastolic compression of the peripheral arteries and veins, with a decrease in systemic vascular resistance and increase in cardiac output.

Improved neo-endothelialization of small diameter ePTFE grafts with titanium coating.

BACKGROUND: Patency of small synthetic bypass grafts is inferior compared to autologous grafts for revascularization procedures. Titanium coating of foreign surfaces has shown to decrease thrombogenicity, enhance biocompatibility and promote adhesion of endothelial cells. The aim of this study was to test the effect of titanium coating of small diameter ePTFE grafts on short term patency, neo-endothelialization and neointimal proliferation. METHODS: Bilateral carotid graft interposition was performed in 5 pigs with uncoated (n=5) and titanium-coated (n=5) ePTFE grafts (internal diameter=4 mm, length=5 cm), thus each pig served as its own control. At the end of the study (30 +/- 3 days), patency and stenosis severity was assessed by carotid angiography. Animals were sacrificed and grafts were excised for histology and scanning electron microscopy. Morphometry of histologic sections was carried out to determine neointimal proliferation and percentage of neo-endothelial coverage. RESULTS: Patency rate was 80% for uncoated and titanium-coated grafts. Quantitative angiography did not show any significant difference in lumen size between two groups. Morphometry revealed a significantly higher cellular coverage with CD31 positive endothelial cells for titanium-coated (84 +/- 19%) than uncoated grafts (48 +/- 26%, p<0.001). There was a non significant trend (p=0.112) towards increased neointimal proliferation in titanium-coated (94 +/- 61 micron2/micron) compared to uncoated grafts (60 +/- 57 micron2/micron). CONCLUSIONS: Patency rate in uncoated and titanium-coated ePTFE grafts is similar at one month. However, titanium coated grafts show a significant improvement in neo-endothelialization compared to uncoated grafts.

PPS-PEG surface coating to reduce thrombogenicity of small diameter ePTFE vascular grafts.

AIMS: Patency failure of small vascular synthetic grafts is still a major problem for coronary and peripheral revascularization. Thus, three new surface coatings of small synthetic grafts were tested in an acute pig model to evaluate their thrombogenicity (extracorporeal arterio-venous shunt) and in a chronic rat model to evaluate the tissue reaction they induced (subcutaneous implantation). METHODS: In five domestic pigs (25-30 kg) an extracorporeal femoro-femoral arterio-venous shunt model was used. The study protocol included first a non-heparinized perfusion sequence followed by graft perfusion after 10,000 UI iv heparin. Grafts were perfused for 3 and 9 minutes. The following coatings were tested on ePTFE grafts: poly-propylene sulphide (PPS)--poly-ethylene glycol (PEG) (wet and dry applications) as well as carbon. Two sets of control were used, one dry and one wet (vehicle only). After perfusion grafts were examined by scanning electron microscopy for semi-quantitative assessment (score 0-3) of cellular and microthrombi deposition. To assess tissue compatibility, pieces of each material were implanted subcutaneously in 16 Wistar rats. At 2, 4, 8, 12 weeks four animals each were sacrificed for semi-quantitative (score 0-3) histologic evaluation of tissue reaction. RESULTS: In the pig model, cellular deposition and microthrombi formation increased over time. In non- heparinized animals, the coatings did not improve the surface characteristics, since they did not prevent microthrombi formation and cellular deposition. In heparinized animals, thrombogenicity was lowest in coated grafts,especially in PPS -PEG dry (p<0.05), and highest in controls. Cell deposition was lowest in PPS-PEG dry, but this difference was not statistically significant vs.controls. In the rat model,no significant differences of the tissue reaction could be shown between materials. CONCLUSION: While all coatings failed to add any benefit for lowering tissue reaction, surface coating with PPS -PEG (dry application) reduced thrombogenicity significantly (in heparinized animals) and thus appears to be promising for improving graft patency of small synthetic vascular prostheses.

Magnetic resonance spectroscopy for assessing myocardial rejection in the transplanted rat heart.

Traditionally, detection of heart rejection after heart transplantation is based on histologic grading of endomyocardial biopsy specimens. The value of magnetic resonance spectroscopy for determining heart rejection was assessed in rejecting and nonrejecting isografts and allografts using energy-rich phosphate spectroscopy. In 46 rats a heterotopic abdominal heart transplantation was performed, and animals were divided into the following groups: six isografts (no rejection), five untreated allografts (severe rejection), and 35 immunosuppressed allografts (mild to moderate rejection). One week after transplantation magnetic resonance spectroscopy was performed, and data were correlated to histologic findings (rejection grades according to Stanford and the New International Working Formulation classifications and relative volume of viable myocardium). Magnetic resonance spectroscopy allows detection of moderate to severe rejection with significant alterations in the energy-rich phosphates such as a decrease in the ratio of phosphocreatine/inorganic phosphate, phosphomonoester/inorganic phosphate, and beta-adenosine triphosphate/inorganic phosphate. A significant correlation was found between spectroscopic changes (phosphocreatine/inorganic phosphate) and histologic rejection (correlation coefficient r = 0.47, p < 0.005) and/or the amount of relative volume of viable myocardium and phosphocreatine/inorganic phosphate (r = 0.58) or beta-adenosine triphosphate/inorganic phosphate (r = 0.63), respectively. In conclusion magnetic resonance spectroscopy permits detection of moderate to severe degrees of heart rejection with a sensitivity of 85% and a specificity of 61%. Changes in the energy-rich phosphates correlate with the histologic grading of heart rejection and the relative volume of viable myocardium. Magnetic resonance spectroscopy appeared to be a valid technique for detecting myocardial rejection after heart transplantation in the reported experimental model.

Transit time flow measurement: experimental validation and comparison of three different systems.

BACKGROUND: Bloodflow measurements are of major clinical importance for quality control in vascular surgery. They allow detection of low-flow situations which may influence outcome adversely. The purpose of the present study was to validate three different flow systems for measuring absolute blood flow. METHODS: Measurements were performed in an experimental flow model using arteries and veins and blood or saline at two different temperatures. As a reference method true flow was measured by volume sampling. RESULTS: Correlation coefficients between transit time flow and true flow measurements ranged between 0.71 and 0.92. Systematic overestimation and underestimation of transit time flow were observed, but after second-order correction all correlations were excellent, ranging from 0.93 to 0.95 irrespective of flow medium and temperature. CONCLUSIONS: Transit time flow measurements are exact and reproducible. Second-order correction yields good accuracy and high precision, with minimal differences among the three systems evaluated.

Transit-time flow measurement for detection of early graft failure during myocardial revascularization.

BACKGROUND: A low-flow situation in arterial and venous grafts has been associated with high rates of perioperative infarction and mortality. This study was designed to look at intraoperative graft flow and resistance in patients with coronary artery disease. METHODS: Coronary artery bypass graft flow was measured in 46 patients. Transit-time flow was used for coronary flow measurements at rest as well as after maximal vasodilation with adenosine infusion. RESULTS: Forty-three of the 46 patients showed normal internal mammary artery graft flow (>20 mL/min); 3 patients had no or minimal graft flow. Redoing the graft anastomosis in these 3 patients resulted in normalization of graft flow. The mean flow increased significantly after correction from 0.5 +/- 0.7 mL/min to 15.7 +/- 9.6 mL/min (p < 0.02). Conversely, vascular resistance decreased significantly from 138 +/- 10 to 4.8 +/- 1.8 Ohmv (p < 0.0001), as did the pulsatility index (from 146.9 +/- 95.7 to 3.4 +/- 1.8; p < 0.001). After correction, coronary flow reserve was 2.5 +/- 1.1. CONCLUSIONS: Measurements of intraoperative flow and resistance as well as derived variables allow assessment of early graft function and thus help prevent graft failure and reduce perioperative infarction. Transit-time volume flow might be a simple tool for quality control in coronary bypass procedures.

Accidental deep hypothermia with cardiopulmonary arrest: extracorporeal blood rewarming in 11 patients.

Sixteen patients (age 13-53 years) with accidental deep hypothermia have been rewarmed in our clinic during the last 10 years, 14 by femoro-femoral cardiopulmonary bypass (CPB) of whom 11 had a cardiopulmonary arrest (asystole in 5 and ventricular fibrillation in 6). On admission, the latter were clinically dead showing wide non-reactive pupils and being supported by ventilation and external heart massage. In the survivors, the mean length of cold exposure was 4.4 h (2-5.5 h) and mean arrest interval until initiation of CPB was 2.5 h (1.4-3.7 h). Rectal temperature on admission ranged from 17.5 degrees C to 26 degrees C (mean 22.5 degrees C). The causes for hypothermia were fall into a crevasse (5), avalanche (1), drowning (2) and cold exposure (3) including 2 suicide attempts. Results are summarized in the following table: [table: see text] Eight of the 11 patients with deep hypothermia and cardiac arrest were rewarmed and resuscitated successfully with CPB. Three patients, including 2 cases of asphyxia (avalanche and drowning), could not be weaned from CPB despite adequate rewarming. The other drowned patient (53 years) died on the 3rd postoperative day (POD) from ARDS. The main complication was pulmonary edema (57%) and transient neurological deficits. All survivors became conscious during the first POD and resumed, their professional activity. We conclude that patients with accidental deep hypothermia and even prolonged cardiopulmonary arrest should be rewarmed and resuscitated rapidly by cardiopulmonary bypass. These measures are very promising particularly if the cause of accident and the circumstances suggest that cardiopulmonary arrest was induced by hypothermia alone without other asphyxiating mechanisms.

Intraoperative internal mammary artery transit-time flow measurements: comparative evaluation of two surgical pedicle preparation techniques.

OBJECTS: Myocardial revascularization is performed preferentially with internal mammary artery grafts. Pedicle preparation and pharmacologic vasodilatory treatment vary greatly. Objective measurements are difficult since peripheral and later coronary vascular resistance and possible competitive flow of the native bypassed coronary artery will influence the results significantly. Our objectives were: (1) measurement of internal mammary artery graft flow with the transit-time flow technique; (2) comparison of two surgical take-down techniques (skeletonizing vs standard pedicle preparation); (3) quantitation of transit-time flow compared to the free pedicle flow and (4) the vasodilatory effect of papaverine on internal mammary artery flow. METHOD: Consecutive elective cases of coronary artery bypass grafting, performed by two surgeons using routinely either skeletonizing of the internal mammary artery (group A, n = 10) or classical pedicle preparation technique (group B, n = 10), were studied prospectively. Anesthesia, cardiopulmonary bypass and operative data were otherwise comparable; likewise, hemodynamic parameters showed no statistical differences between the two groups. Transit-time flow (CardioMed, Medi-Stim, Norway) was measured at the following time points: beginning (1) and end of take-down (2); after papaverine soaking: before (3) and on cardiopulmonary bypass (4); free flow into a beaker (5); after anastomosis; on (6) and off cardiopulmonary bypass (7). RESULTS: Measurement of mean flow showed the following results: (1) severe vasoconstruction of the internal mammary artery was detected in both groups regardless of the preparation technique (occurring earlier in group A); (2) papaverine soaking caused a moderate flow increase (up to 40%); (3) with corresponding cardiopulmonary bypass flow (4.4 vs. 4.1 l/min in group B) a higher free flow in group A was evident (67.7 vs. 50.7 ml/min); (4) after coronary grafting, transit-time flow showed no significant differences between the two groups and (5) using a 3 mm probe, a linear correlation was demonstrated between transit-time flow and simultaneously measured free flow (r = 0.89). CONCLUSION: Intraoperative transit-time flow measurement is a reliable method for assessing internal mammary artery and coronary artery bypass flow; considering the simple technical application, the procedure may be regarded as a valuable instrument of quality control.

Failed coronary artery bypass anastomosis detected by intraoperative coronary flow measurement.

OBJECTIVES: To assess intraoperative flow of arterial and venous coronary grafts after myocardial revascularization which may allow early detection of low flow situations, especially during minimally invasive coronary bypass surgery (MIDCAB), and lead to immediate correction of technical problems. METHODS: In two patients with severe and diffuse multi-vessel disease the left internal mammary artery (IMA) was connected to the left anterior descending artery (LAD). During reperfusion, the flow was measured in the IMA and vein grafts using a transit time flow meter. RESULTS: In both cases the IMA showed only a systolic pendulating flow curve with a mean flow of 0-1 ml/min and a high resistance. Manual IMA assessment revealed an adequate pulsation. Both distal IMA anastomoses were re-explored on cardiopulmonary bypass yielding an initial flow of 7 and 14 ml/min, respectively. After treatment with papaverine/adenosine the IMA flow increased from 7 to 26 ml/min (coronary flow reserve (CFR) = 3.7) and from 14 to 46 ml/min (CFR = 3.3), respectively. CONCLUSION: Intraoperative flow assessment of IMA and venous bypass grafts can be recommended to monitor flow; especially during MIDCAB procedures.

Assessment of cardiac rejection by MR-imaging and MR-spectroscopy.

BACKGROUND: Detection of cardiac rejection is a major problem in cardiac transplantation. The gold standard is, and remains, endomyocardial biopsy. PURPOSE: Evaluation of MR-imaging and MR-spectroscopy for detection of cardiac rejection. METHODS: Orthotopic cardiac transplantation (HTX) was performed in 13 pigs (body weight 30 kg). All animals obtained immunosuppressive (triple) therapy for 1 week after the operation. Thereafter immunosuppression was stopped to induce cardiac rejection. MRI and MRS (1.5 Tesla General Electrics Signa) were performed pre- and post-operatively on days 10, 17, 24 and 31. The degree of rejection was determined post-operatively using endomyocardial biopsy (Texas grading score). RESULTS: (1) MR-imaging: LV function remained unchanged after HTX. LV mass increased (+42%; P < 0.05) with cardiac rejection. (2) MR-spectroscopy: a marked reduction in the ratio of phosphocreatine and adenosine triphosphate, respectively, to inorganic phosphate was observed in the rejecting hearts. (3) Histologic grading confirmed cardiac rejection after stopping immunosuppression. The Texas score was 5.7+/-0.8 at autopsy. CONCLUSIONS: MR-imaging and MR-spectroscopy allow the detection of changes associated with cardiac rejection. Both techniques are correlated with histologic rejection. However, endomyocardial biopsy remains the gold standard for reliable detection of cardiac rejection.

Prevention of neointimal proliferation by immunosuppression in synthetic vascular grafts.

OBJECTIVE: Immunosuppressive agents have been proposed to reduce neointimal hyperplasia in synthetic vascular grafts. Thus, the purpose of the present study was to evaluate the safety and efficacy of rapamycins (systemic vs. local vs. oral administration) and mycophenolate mofetil (MMF) to reduce intimal hyperplasia in infrarenal synthetic vascular grafts of the rat. METHODS: Fifty-four Wistar rats (250 g) completed the study after a synthetic vascular graft (ePTFE, Gore-tex, 2 mm diameter, 10 mm length) was implanted end-to-end in the infrarenal aorta. The animals were divided into three groups: group 1 consisted of 12 control animals, group 2 consisted of 37 rats receiving rapamycins, either per os (RAD, 1.5 or 3 mg/kg), intraperitoneally (RPM, 1.5 or 3 mg/kg) or locally (RPM soaking of the graft); and in group 3 (n=5), MMF (40 mg/kg) was administered orally. The animals were followed weekly with weight controls and signs of toxicity for 30 (n=37) and 60 (n=17) days, respectively. All animals were sacrificed and underwent histological examination at completion of the study. RESULTS: All animals survived in groups 1 and 3, but five died in group 2. The weight gain was normal in all groups, except for the subgroup 2a receiving high dose rapamycins orally. All rats in group 3 suffered from diarrhea, whereas animals receiving high dose rapamycins showed toxic signs (hair loss, wound healing problems). Histological examination showed a significant increase in intimal hyperplasia in group 1 (0.03+/-0.01 and 0.14+/-0.05 microm after 30 and 60 days, respectively; P<0.01). Rapamycins in either application or dosage had no significant effect on intimal hyperplasia. CONCLUSIONS: Local or systemic administration of rapamycins has no effect on intimal hyperplasia in synthetic vascular grafts. In contrast, toxic signs with weight loss were observed in animals treated with high dose rapamycins, but not in those treated with MMF. Thus, in the rat model, immunosuppression with rapamycins or MMF cannot be recommended for the prevention of intimal hyperplasia in the synthetic vascular graft model.

Evaluation of coronary bypass flow with color-Doppler and magnetic resonance imaging techniques: comparison with intraoperative flow measurements.

OBJECTIVES: After coronary artery bypass surgery, patency and flow assessment is based on invasive methods such as angiography and intravascular ultrasound or flow wire techniques. The aim of the study was to compare intraoperative transit time flow measurements of coronary bypass grafts with early postoperative color-Doppler and MR-imaging assessment. METHODS: In 22 patients (62+/-8.5 years) undergoing elective coronary bypass surgery the flow was measured in all internal mammary artery grafts (IMA) and saphenous vein grafts using the transit time flow technique. Postoperatively (days 5-7) all patients had a color-Doppler IMA graft assessment followed by a MR-angiography and flow measurement (navigator echo phase contrast technique with and without contrast bolus application) to determine patency and graft flow. RESULTS: Data are expressed as the mean +/- SD). (1) In all patients the left IMA graft to the left anterior descending coronary artery (LAD) could be identified and flow could be assessed with both color-Doppler and MRI. Venous grafts could only be visualized by MRI. The use of an intravenous contrast bolus enhanced the visualization of coronary artery bypass grafts. (2) The mean IMA to LAD flow was 33+/-17 ml/min intraoperatively by transit time and postoperatively 36+/-25 ml/min by MR respectively 66+/-54 ml/min by color-Doppler technique. (3) The systolic/diastolic flow ratio was 0.44+/-0.12 intraoperatively and 0.43+/-0.17 postoperatively by MR respectively 0.67+/-1.0 by color-Doppler. (4) A statistically significant correlation could be demonstrated between intraoperative transit time and postoperative MR flow measurements (r = 0.57; P < 0.04), whereas the correlations to color-Doppler flow were poor. Postoperatively MR and color-Doppler showed a good correlation of systolic/diastolic flow ratio (r = 0.88; P < 0.008). CONCLUSIONS: The color-Doppler method during echocardiography and MR-imaging are useful non-invasive techniques to visualize postoperative IMA grafts for patency assessment. The quantification of IMA flow is still difficult with either technique, but MR flow measurements showed the best correlation to the intraoperatively measured transit time flow. The MR technique is the most promising non-invasive method for postoperative evaluation of coronary bypass grafts, since it allows visualization and reliable flow quantification.

Qualitative assessment of blood washing with the continuous autologous transfusion system (CATS)

A number of different blood-processing methods can be used at the end of cardiopulmonary bypass (CPB) to improve the quality of autologous blood. They include centrifugation, hemofiltration and cell-washing. They differ in processing time required, cost of disposables and the quality of the processed autologous blood product. The newly developed continuous auto-transfusion system (CATS: Fresenius AG, Bad Homburg) uses a continuous cell-washing method. In a prospective study, the oxygenator blood of 10 patients was processed at the end of cardiac surgery with CATS and the quality of autologous blood before and after processing was compared. The processing volumes and the time required were recorded. The concentrations and elimination rates of blood parameters and waste products such as activated coagulation and complement products were measured. At the end of CPB a mean volume of 1,010 +/- 174 ml diluted oxygenator blood was processed and concentrated to 310 +/- 88 ml in 11.0 +/- 2.2 mins. Cellular elements such as erythrocytes and leucocytes were mostly retained and their concentration showed a significant increase after processing (250% and 210% respectively; p < 0.01). Thus, the blood processing with CATS resulted in an excellent hemoconcentration (hematocrit 62 +/- 3 vs. 24 +/- 4% before processing) with a consistent reproducibility. On the other hand, the CATS concentrate showed a significant loss of autologous plasma proteins. Likewise, all water soluble elements such as waste products are significantly lower in concentration after processing and, if calculated by quantity, they show a high elimination rate (> 93%). In conclusion, the continuous autologous transfusion system permits an automated, rapid and continuous processing of autologous blood yielding a standardised high quality erythrocyte concentrate.

Left heart bypass in the pig with a centrifugal pump using cannulae prepared for percutaneous placement.

A rapid and efficient circulatory support system may save a patient in cardiogenic shock. Left heart bypass with percutaneous and trans-septal placement of the aspiration cannula simplifies the circuit and eliminates the need for an oxygenator. In this pre-clinical study we assessed left heart bypass support with a centrifugal pump using new cannulae prepared for percutaneous placement (14 F arterial catheter and 16 F left atrial aspiration line) in 5 anaesthetized pigs. Animals were supported for two hours at a mean flow of 3.2 l/min (4,033 rpm), a mean haematocrit of 29% and low heparinisation (ACT double baseline). Hemodynamic measurements and blood samples were taken at baseline (A), 10 minutes (B), one hour (C) and 2 hours (D) on support. Results show maintenance of hemodynamic parameters throughout the 2 hour support period. Only systolic arterial and left ventricular pressure decreased by 12% and 20% respectively from baseline to the end of the support period with a 13% increase in cardiac output. When the pump was turned on (0-3 l/min) there was usually a decrease in heart rate, systolic pressure and left ventricular pressure, with unchanged cardiac output (non failing model). Potassium increased from 3.9 to 4.2 mmol/l (ns), and plasma hemoglobin from 6.0 to 18.2 mg/dl (p<0.05). Thrombocytes decreased from 187 to 155 10(9)/l (ns). In conclusion, this preclinical study demonstrated the feasibility of an efficient left heart bypass of short duration with a centrifugal pump using cannulae prepared for percutaneous placement. Left heart bypass was well tolerated hemodynamically and no significant laboratory change occurred within the two hours of support. This opens several possibilities for the short term support of patients in cardiogenic shock and eventually also for patients submitted to minimally invasive cardiac surgery.

Effects of unprocessed and processed cardiopulmonary bypass blood retransfused into patients after cardiac surgery.

BACKGROUND: The aim of this prospective study was to compare the effect of autologous unprocessed to processed residual cardiopulmonary bypass blood (CPB) on patients' laboratory and clinical parameters and outcome. METHODS: 20 patients undergoing elective coronary artery bypass surgery were randomized to receive either unprocessed CPB blood (control group) or processed CPB blood employing the Continuous AutoTransfusion System (CATS; Fresenius, Bad Homburg, Germany). We have shown that this method eliminated >93% of activated mediators. Serial laboratory parameters including complement activation, coagulation factors and the stimulation of IL-6 and IL-8 were compared with clinical side effects and patients' outcome. RESULTS: Compared to control patients, retransfusion of unprocessed CBP blood significantly increased heparin, free plasma hemoglobin and D-Dimers. Postoperatively, three patients in the control group and two patients in the CATS group required prolonged mechanical ventilation or developed infections associated respectively with elevated C3a (desArg) or IL-6 concentration. CONCLUSIONS: CATS-processing of CPB blood provided a high-quality red blood cell concentrate, resulting in a reduced load of retransfused activated mediators.

Advantages of bilayered vascular grafts for surgical applicability and tissue regeneration.

Nanofibrous scaffolds are part of an intense research effort to design the next generation of vascular grafts. With electrospinning, the production of micro- and nano-fiber-based prostheses is simple and cost effective. An important parameter for tissue regeneration in such scaffolds is pore size. Too small pores will impede cell infiltration, but too large pores can lead to problems such as blood leakage. In this study, bilayered grafts were made by electrospinning a high-porosity graft with a low-porosity layer on either the luminal or the adventitial side. Grafts were characterized in vitro for fiber size, pore size, total porosity, water and blood leakage, mechanical strength, burst pressure and suture retention strength, and were evaluated in vivo in the rat abdominal aorta replacement model for 3 and 12 weeks. In vitro blood leakage through these bilayered grafts was significantly reduced compared with a high-porosity graft. All grafts had an excellent in vivo outcome, with perfect patency and no thrombosis. Cell invasion and neovascularization were significantly reduced in the grafts with a low-porosity layer on the adventitial side, and there was no significant difference between the grafts in endothelialization rate or intimal hyperplasia. By tailoring the microarchitecture of biodegradable vascular prostheses, it is therefore possible to optimize the scaffold for tissue regeneration while preventing blood leakage, and thus facilitating applicability in the clinic.

[Tissue engineering of vascular prostheses]. / Tissue Engineering von Gefäßprothesen.

Vascular tissue engineering represents a new but rapidly growing field due to the need for better vascular prostheses for coronary or peripheral revascularization procedures. Current synthetic prostheses have a high incidence of failure due to thrombosis and/or intimal hyperplasia especially in small caliber artificial vascular prostheses. New approaches such as decellularized, natural or synthetic, 3-D stable/degradable scaffolds are being developed for acellular or cell-based vascular replacements. The drawbacks of cellular bioreactor matured prostheses are delayed availability and that they are, labor and cost-intensive. However, some research groups have shown limited clinical applications. The acellular approach is based on a biodegradable, electrospun, porous 3-D structure made of nano- and micro-sized polycaprolactone fibers. Animal studies in rats and pigs have shown good short and long-term results after arterial replacement with autologous cellular and matrix ingrowth, angiogenesis, confluent endothelialization and absence of occlusions or aneurysm formation. Therefore, the in vivo vascular tissue engineering approach produces shelf-ready biodegradable vascular prostheses which might be an option for future clinical applications.

Antithymocyte globulin induction therapy in heart transplantation: prospective randomized study of high vs standard dosage.

BACKGROUND: In cardiac transplantation, high-dose antithymocyte globulin (ATG) induction therapy as short-term rejection prophylaxis has not been used. OBJECTIVE: To evaluate the efficacy and safety of intraoperative use of single high-dose ATG induction therapy after heart transplantation. PATIENTS AND METHODS: Fourteen patients received single high-dose ATG therapy plus shortened standard therapy (group1), and 16 patients received ATG standard therapy (group2). RESULTS: No perioperative deaths were reported. During follow-up, 3 deaths were recorded. Five-year patient survival was 92.8% in groupl vs 85.7% in group2 (P = .34). The mean (SD) number of acute rejection episodes per patient was 2.5 (2.2) in the high-dose ATG group vs 2.7 (2.5) in the standard therapy group (P = .83), with 5-year freedom from acute rejection of 45.5% in group 1 vs 35.6% in group 2 (P = .85). Infections were observed in 6 patients in group1 and in 8 patients in group2 (P = .69). Malignant disease was diagnosed in 1 patient in the high-dose group and 3 patients in the standard therapy group (P = .35). Chronic allograft vasculopathy was recognized in 4 patients (28%) in group1 and 8 (50%) in group2 (P = .05). Five-year actuarial freedom from allograft vasculopathy was 69.2% in the high-dose ATG group vs 50.0%% in the standard therapy group (P = .35). CONCLUSIONS: High-dose ATG for prevention of rejection episodes is safe and efficacious, with a lower rate of early and late complications, in particular, graft vasculopathy.