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.

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.

Outcome of thoracoabdominal aortic operations using deep hypothermia and distal exsanguination.

BACKGROUND: Operation of the descending and thoracoabdominal aorta may be affected by a significant perioperative morbidity, mainly because of ischemic damage of the spinal cord and malperfusion of the abdominal organs. METHODS: A comparative analysis was performed on two consecutive series of patients operated between 1982 and 1998. Group 1 consisted of 90 patients operated with moderate hypothermic left heart bypass. Group 2 included 38 patients operated using deep hypothermic cardiopulmonary bypass and a period of circulatory arrest while performing the proximal anastomosis and distal exsanguination during confection of the distal anastomosis. RESULTS: Main demographic factors and causes of the aortic disease were similar in both groups. Early mortality was significantly higher in the group of patients with aortic cross-clamping (15 of 90, 16%) than in those operated with circulatory arrest (2 of 38, 5.2%), p < 0.001. Paraplegia occurred in 8 patients in the group operated with mild hypothermia (8.8%) but in only 1 patient (2.6%) when deep hypothermia had been used. CONCLUSIONS: In our experience, deep hypothermia combined with distal exsanguination significantly improved the early postoperative outcome after operation of the descending and thoracoabdominal aorta. This technique allowed easy confection of proximal and distal anastomoses, and the duration of the operation was not prolonged significantly through this approach.

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.

Perioperative bleeding and thromboembolic risk during non-cardiac surgery in patients with mechanical prosthetic heart valves: an institutional review.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to determine the risk of thromboembolic and bleeding complications in patients with mechanical heart valve prostheses who underwent non-cardiac surgery under different regimens of perioperative anticoagulation. Data were analyzed on the basis of surgery type and underlying disease. METHODS: A series of 235 patients (mean age 63 +/- 4.5 years) with one or two mechanical heart valves underwent subsequent non-cardiac surgery comprising abdominal, vascular and thoracic, orthopedic, urologic, neurosurgery, ENT, plastic and reconstructive, and gynecologic operations. Mean interval between heart valve replacement and non-cardiac surgery was 3.9 +/- 3.3 years. Perioperative oral anticoagulation was managed by discontinuation of oral anticoagulation and intravenous heparin administration; or by discontinuation and early postoperative re-institution of oral anticoagulation without intravenous heparin; or by no withdrawal of oral anticoagulation. Patients with bioprostheses were excluded. RESULTS: Overall hospital mortality during non-cardiac surgery was 2.9%. Thromboembolic events included cerebral embolism with transient deficit (n = 3), residual defect (n = 1) and irreversible defect (n = 1), as well as peripheral embolism (n = 11). Hemorrhagic complications included wound hematoma (n = 10) and increased postoperative bleeding (n = 8) with re-exploration in five patients. Thromboembolic complications occurred most often in patients with prosthetic mitral valve and atrial fibrillation; the lowest risk was in patients with sinus rhythm after aortic valve replacement. Most complications occurred after discharge and in patients with surgery for malignancy, within 10 days of instituting oral anticoagulation, and despite a therapeutic INR value. CONCLUSIONS: Minor surgical procedures can be performed safely without discontinuing anticoagulation. When major non-cardiac surgery is planned, discontinuing oral anticoagulation and starting perioperative intravenous heparin minimizes bleeding and thromboembolic risks. Thromboembolic complications may occur within one month of surgery, despite adequate oral anticoagulation, though permanent morbidity is low.

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.

Intra- and postoperative quality control in minimally invasive direct coronary artery bypass (MIDCAB) surgery.

The introduction of new techniques allowing direct coronary artery revascularisation without sternotomy and extracorporeal circulation--called Minimally (or less) Invasive Direct Coronary Artery Bypass grafting (MIDCAB)--has opened up interesting perspectives for the treatment of patients with limited coronary artery disease. However, like any newer surgical technique, this approach to myocardial revascularisation requires a critical appreciation of the results which may be obtained; when introducing the MIDCAB technique in our institution we developed a quality control protocol based on intraoperative as well as early and late postoperative parameters. This protocol is designed to detect every significant adverse event, exercise capacity and quality of life of our patients. Moreover, several invasive parameters have to be recorded in the protocol, such as intraoperative flow in the internal mammary artery conduit, the angiographic verification of anastomotic patency at one-year follow-up and determination of coronary flow reserve. The results of the first 5 patients observed up to one year postoperatively are presented: all anastomoses were patent and the flow within the internal mammary artery was 69 +/- 40 ml/min at one-year follow-up angiography; this compares very favourably with the flow measured at the end of the operation, which was 31 +/- 8 ml/min. This demonstrates very clearly that internal mammary artery flow is recruitable and usually significantly increases within the first months postoperatively. Coronary flow reserve was 3.4 +/- 1.1 (normal value > 2.5). The results obtained in this pilot study, which was designed to establish a quality control protocol, are very satisfactory and confirm previous experience that this technique may be offered to selected patients with appropriate coronary anatomy.

Different techniques of distal aortic repair in acute type A dissection: impact on late aortic morphology and reoperation.

OBJECTIVE: To compare three different techniques of distal aortic repair in acute type A (de Bakey type I) aortic dissection and to evaluate their impact on the late morphology of the aortic arch and descending aorta and on the incidence of reoperation. METHODS: From 65 patients operated on due to an acute type A aortic dissection between 1989 and 1993, 54 long-term survivors underwent clinical and radiologic follow-up examination after a mean postoperative interval of 62+/-16 months. The surgical techniques of distal aortic reconstruction included closed repair using Teflon felt reinforcement under moderate hypothermic cardiopulmonary bypass (n = 20) and open repair in deep hypothermic circulatory arrest using either Teflon felt reinforcement (n = 16) or gelatin-resorcin-formaldehyde (GRF) glue (n = 18) to readapt the dissected aortic layers. In all patients, MR imaging was performed on a 1.5-T whole body imaging system for the evaluation of the morphology and function of the heart, aorta and supraaortic branches. RESULTS: Overall hospital mortality following surgical repair of type A aortic dissection was 15.4% during this time period. The highest rate of persistent false lumen perfusion (17/20, 85%) and presence of an intimal flap in the aortic arch (13/20, 65%) was observed in patients following closed repair of acute ascending aortic dissection, whereas the lowest rate of such findings was demonstrated in patients who had undergone open distal aortic repair using biological glue (false lumen perfusion 10/18, 55% and intimal flap in the arch 2/18, 11%). Redo-surgery was significantly reduced in the open repair group using GRF glue (1/18, 5.5%) as compared with the Teflon felt repair group (3/16, 18%) and the closed repair group (6/20, 30%). CONCLUSIONS: In patients with acute type A dissection, open distal aortic repair using GRF-glue favourably influences both (1) the severity of late morphologic alterations in the downstream aorta and (2) the incidence of reoperation.

Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.

Improvement of patency rate in heparin-coated small synthetic vascular grafts.

BACKGROUND: Graft thrombosis and intimal hyperplasia represent the major causes of graft failure. Heparin has been shown to have a beneficial effect on long-term patency and on prevention of intimal hyperplasia. Thus, the purpose of the present study was to evaluate the effect of heparin coating on patency rate and intimal hyperplasia in small synthetic vascular grafts. METHODS AND RESULTS: Two synthetic grafts (expanded polytetrafluoroethylene [ePTFE], and polyurethane) with and without heparin coating were implanted in the infrarenal aorta (diameter, 2 mm) of 40 Whistar rats. Animals survived 8 weeks after implantation. Graft patency, intimal thickness, and percentage of diameter stenosis were determined by light microscopy at the proximal respectively distal anastomosis and in the middle of the graft. Uncoated grafts showed a patency rate of 70% for ePTFE and 60% for polyurethane grafts. Heparin-coated grafts showed a patency rate of 100% for ePTFE and 90% for polyurethane grafts. Intimal hyperplasia was observed in all grafts mainly at the anastomosis site. Intimal wall thickness and percentage of stenosis were significantly more pronounced in the polyurethane than ePTFE grafts (P < 0.01). Heparin coating significantly reduced overall graft thrombosis (P < 0.05) but had no significant effect on intimal hyperplasia. CONCLUSIONS: Small grafts show a high rate of graft thrombosis and an enhanced intimal hyperplasia. ePTFE grafts show significantly less intimal hyperplasia and percentage of stenosis than polyurethane grafts. Heparin coating significantly reduced graft thrombosis but had no significant effect on intimal hyperplasia. Thus, heparin coating seems to be beneficial for graft patency, and ePTFE appears to be superior to polyurethane as graft material.

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.

[Conventional heart surgery with the fast-track-method: experiences from a pilot study]. / Konventionelle Herzchirurgie im Fast-track-Verfahren: Erfahrungen aus einer Pilotstudie.

Early release after cardiac surgery can be promoted by implementation of a standard protocol for accelerated perioperative and early postoperative care, with optimal education and support of the patient playing a key role. We report on our preliminary experience with 100 selected patients who underwent a "fast track" protocol following coronary artery bypass (n = 61), valve replacement or reconstruction (n = 34) or closure of an atrial septal defect (n = 5) between 1996 and 1998. Surgery was performed through a midline sternotomy using normothermic or mild hypothermic cardiopulmonary bypass. Patients undergoing cardiac surgery with less invasive techniques were excluded from this study. The following criteria had to be fulfilled for early hospital discharge: sinus rhythm, temperature below 37.5 degrees C, stable haematocrit around 0.30, uncomplicated wound healing and complete mobilisation including stair exercises. Mean duration of the operation was 137 +/- 24 minutes and mean intubation time was 4.5 +/- 3 hours. Mean duration of hospitalisation from the day of the operation was 4.9 +/- 2.1 days. There was no early or late mortality in this group of patients and only 2 patients had to be re-admitted on postoperative day 10 and 14 because of atrial fibrillation in one and a wound healing problem in the other. Accelerated recovery and early hospital discharge is highly attractive in selected patients; in helps to promote early cardiac rehabilitation and the costs of the procedure can be substantially reduced. According to our experience and the most recent literature, this approach does not expose patients to higher mortality or morbidity. In addition, fast-tracked patients have shown a higher level of satisfaction. Under optimal cooperation between surgery, anaesthesiology and intensive care unit, the fast-track protocol can be applied in approximately 30% of overall adult cardiac surgery patients.

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.

Definitive cure of recurrent prosthetic endocarditis using silver-coated St. Jude Medical heart valves: a preliminary case report.

Despite progress in the area of antimicrobial treatment and the surgical use of homografts, prosthetic valve endocarditis (PVE) remains one of the most dangerous complications following heart valve replacement. We present the case of a patient treated for acute endocarditis which affected the mitral valve and who developed recurrent PVE and native aortic valve endocarditis. After multiple valve surgery, the infection was controlled following aortic and mitral valve replacement using silver-coated prostheses. The St. Jude Medical (SJM) mechanical heart valve Masters Series with Silzone coating is intended to protect heart valve patients against microbial infection. The Silzone coating is formed by an ion beam-assisted deposition process that incorporates silver into the sewing cuff of the SJM heart valve. It has also been suggested that silver treatment may improve the healing characteristics of the heart valve sewing cuff. This technology may be a valuable option to prevent or cure PVE, in addition to homografts. Although the present patient is an isolated case, it was encouraging to find not only a well-healed mitral valve silver-coated prosthesis but also no persistent or recurrent infection during a nine-month follow up.

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.

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.

Cytostatic lung perfusion by use of an endovascular blood flow occlusion technique.

BACKGROUND: Different modalities of cytostatic lung perfusion were compared regarding plasma and tissue drug concentrations to assess the efficacy of an endovascular blood flow occlusion technique. METHODS: A cytostatic lung perfusion study with doxorubicin hydrochloride was performed on large white pigs (n = 12). Plasma and tissue concentrations of doxorubicin were compared for isolated lung perfusion with open cannulation (ILP), blood flow occlusion perfusion with open cannulation of the pulmonary artery alone (BFO), and intravenous drug administration (i.v.). In a fourth group, thoracotomy-free BFO perfusion was performed by endovascular balloon catheterization of the pulmonary artery (endovascular BFO). The 3 animals in this group were used to compare the doxorubicin-perfused pulmonary tissue with the contralateral nonperfused lobes after 1 month. RESULTS: The mean lung tissue doxorubicin concentration at the end of perfusion was 19.8 +/- 1.6 microg/g after ILP, 27.6 +/- 2.2 microg/g after BFO (p = not significant), and 3.0 +/- 0.8 microg/g after i.v. perfusion (p < 0.01). Whereas doxorubicin was not detectable in the plasma in the ILP group, concentrations ranged from not detectable to 0.44 microg/mL in the BFO group and from 0.31 to 0.84 microg/mL in the i.v. group (p < 0.05). Mean myocardial tissue concentration was not significantly different after BFO than i.v. perfusion (1.1 +/- 0.5 microg/g and 1.8 +/- 0.1 microg/g, respectively). In the endovascular BFO group, balloon-blocked pulmonary artery perfusion was successfully performed in all animals, and after 1 month, lung tissue showed no cytostatic-induced histologic changes. CONCLUSIONS: Compared with ILP, BFO cytostatic lung perfusion produced an insignificantly higher lung-tissue concentration, corresponding to a sixfold to ninefold higher level than after i.v. perfusion. Plasma drug levels during BFO perfusion were lower than during i.v. perfusion. Endovascular BFO may be a promising technique for repeated cytostatic lung perfusion.

Assessment of troponin-T for detection of clinical cardiac rejection.

Non-invasive detection of cardiac rejection still remains a challenge after heart transplantation. We assessed troponin-T as a new serum marker to diagnose cardiac rejection. Twenty-five heart transplant patients (Berne) were monitored prospectively for up to 2 years, and compared to 89 retrospectively assessed patients (Stanford). Blood samples (392 Berne and 320 Stanford) were analyzed (creatine kinase, isoenzymes MB activity and MB mass, troponin-T and troponin-I). Regression analysis between the results of these blood samples and cardiac rejection grading from simultaneously performed endomyocardial biopsies was carried out. Troponin-T tests done in two different laboratories showed a good correlation (r = 0.91; P < 0.0001), whereas troponin-T versus troponin-I showed a lower correlation (r = 0.53; P < 0.0001). Troponin-T and -I in contrast to other enzymes were elevated for a longer period (up to 4 weeks before returning to baseline) after transplantation than during conventional cardiac surgery. Beyond 3 months the following correlations were found between troponin-T (new or old test) and the other enzymes (creatine kinase: r = 0.26, MB activity: r = 0.4, and MB mass: r = 0.68). The correlation between the degree of rejection and the enzyme release is poor, however, the best results were obtained for troponin-T (r = 0.22; P < 0.001). We found a low correlation between troponin-T and the degree of rejection beyond 3 months after heart transplantation. Despite a troponin-T elevation in some patients with rejection, the new test is not sensitive enough to be used alone for the non-invasive diagnosis of cardiac rejection.

Photosensitizing effects of m-tetrahydroxyphenylchlorin on human tumor xenografts: correlation with sensitizer uptake, tumor doubling time and tumor histology.

The photodynamic effects of m-tetrahydroxyphenylchlorin (mTHPC) were assessed on human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts grown in nude mice and were correlated with mTHPC uptake, histology and doubling time of the tumors. Non-thermal laser light was delivered to the tumor as surface radiation 4 days after intraperitoneal administration of 0.1 and 0.3 mg mTHPC/kg body weight, respectively. The extent of tumor necrosis was measured by histomorphometry. The mTHPC concentration in non-irradiated tumors was assessed by high-performance liquid chromatography (HPLC). The tumors were graded according to their doubling time and their vascular architecture as assessed by histology. The 0.1 mg/kg dose of mTHPC resulted in an equal uptake for all 3 tumor types but revealed a larger extent of photosensitized necrosis for adenocarcinoma, which displayed a delicate tumor stroma with numerous small capillary vessels, than for mesothelioma and squamous cell carcinoma, which were both poor in stroma and vessels. The 0.3 mg/kg dose of mTHPC resulted in a 2-fold higher tumor uptake for all 3 tumor types and in a larger extent of necrosis for mesothelioma and squamous cell carcinoma, but not for adenocarcinoma xenografts, compared with the lower drug dose. Our results demonstrate that different tumor xenografts respond differently to mTHPC-PDT for a given drug-light condition. In this setting, the photosensitizing effect was more closely related to the vascular architecture of the tumors than to the sensitizer uptake and doubling time of the different tumors

Isolated lung perfusion: single-pass system versus recirculating blood perfusion in pigs.

BACKGROUND: Cytostatic isolated lung perfusion has been advocated for treating pulmonary metastasis of soft tissue sarcoma. Different techniques of isolated lung perfusion have been developed. METHODS: Isolated lung perfusion with and without doxorubicin was performed on white pigs during 15 minutes either by a single-pass system (n = 7) or by a recirculating-blood perfusion system (n = 7). Three animals with endovenous drug application served as controls. Leakage was assessed using isotopic tracers. Perfusion-induced lung tissue injury was determined by postperfusion chest radiographs, by angiotensin-converting enzyme-to-protein ratio in the plasma and in the bronchioalveolar lavage fluid, and by wet-to-dry weight ratio and histologic examination of lung biopsy specimens at 20 and 50 minutes. Doxorubicin concentration in lung tissue and plasma was compared between the three study groups. RESULTS: All isolated lung perfusion studies were successfully performed without significant systemic leakage (< 0.6%). Wet-to-dry weight ratio was significantly lower after single-pass as compared with recirculating-blood perfusion and endovenous drug application at both time points (5.0 +/- 1.1 and 5.3 +/- 0.8 for single-pass versus 6.6 +/- 1.1 and 6.9 +/- 0.5 for recirculating-blood versus 6.6 +/- 0.2 and 5.9 +/- 0.7 for the control group, respectively; p < 0.05). Angiotensin-converting enzyme-to-protein plasma ratio in the single-pass group was significantly lower only at 20 minutes (6.3 +/- 2.4 versus 9.3 +/- 1.0 versus 9.7 +/- 1.9, respectively; p < 0.05) but not at 50 minutes. Angiotensin-converting enzyme-to-protein ratio in bronchoalveolar lavage fluid, histology of lung biopsy specimens, and chest radiographs did not differ significantly between the three groups. Doxorubicin lung tissue concentration was not significantly different after single-pass (17.5 micrograms/g) and recirculating-blood perfusion (21.9 micrograms/g), but was significantly higher than after endovenous drug application (3.0 micrograms/g; p < 0.01). CONCLUSIONS: Both isolated lung perfusion techniques resulted in a sixfold to sevenfold higher doxorubicin lung tissue concentration than after endovenous application. Isolated lung perfusion-induced lung injury was similar for both techniques, but recirculating-blood perfusion appeared to result in more acute lung injury and was technically more demanding than single-pass perfusion.