Endovascular repair of para-anastomotic aneurysms of the aorta and iliac arteries: preferred treatment for a complex problem.

PURPOSE: Standard surgical repair of para-anastamotic aneurysms (PAAs) of the abdominal and thoracic aorta and the iliac arteries has been associated with high morbidity and mortality rates. We reviewed our continuing experience with endovascular repair of these lesions to determine whether this approach is favorable and durable. METHODS: All patients with PAAs of the aorta or iliac arteries who underwent endovascular treatment of their lesions between August 1993 and July 1999 were prospectively followed up, and data on age, previous aortic pathology and surgery, size of PAA, time to diagnosis, and symptoms at presentation were recorded. Preoperative, intraoperative, and postoperative imaging studies were analyzed. All patients had endovascular stent-grafts placed under digital fluoroscopic guidance in the operating room. Data on intraoperative and postoperative complications, mortality, and endoleaks were reviewed. RESULTS: From August 1993 to July 1999, 28 patients (20 men, 8 women) had 35 PAAs of the aorta or iliac arteries. There were 5 thoracic aortic, 12 abdominal aortic, and 18 iliac artery PAAs. Three patients had a contained rupture of their PAA. All patients who had originally undergone reconstruction for occlusive disease had lesions consistent with false aneurysms, whereas 73% of the aortic or iliac PAAs in patients originally treated for aneurysm disease appeared to be true aneurysms. Thirty-four of 35 PAAs were successfully excluded with stent-grafts (97%). There was one death at 30 days (3.6%) in a patient who was successfully treated endovascularly for a contained rupture of a thoracic PAA. There were four major postoperative complications (14.2%) in the 28 patients who were treated. One patient had continued perfusion of a thoracic aortic PAA (type I endoleak). The in-hospital length of stay after endovascular repair of PAA was 4 days (range, 1-18 days). The mean follow-up period was 21 months (range, 1-68 months). CONCLUSION: Endovascular repair of aortic and iliac artery PAAs is technically feasible and provides a high rate of lesion exclusion. Morbidity and mortality rates appear lower than those reported for open surgical repair. These patients can typically be discharged by the second postoperative day. Endovascular therapy for stable ruptured PAAs can be successfully performed and should be considered as an option only when appropriate devices and expertise are available. For uncomplicated PAAs of the aorta and iliac arteries, endovascular therapy may be more favorable than surgical repair.

Intentional internal iliac artery occlusion to facilitate endovascular repair of aortoiliac aneurysms.

PURPOSE: The safety of intentional occlusion of patent internal iliac arteries (IIAs) to facilitate the endovascular repair of aortoiliac artery aneurysms (abdominal aortic aneurysms [AAAs] and iliac aneurysms [IAs]) was evaluated. METHODS: We analyzed the techniques and clinical sequelae of selective occlusion of one or both IIAs in 103 patients and correlated these findings with the results of preoperative angiograms to identify vascular anatomy that may predict postoperative pelvic ischemia. To quantify the clinical presentation of pelvic ischemia, we developed these criteria: class 0, no symptoms; class I, nonlimiting claudication with exercise; class II, new onset impotence, with or without moderate to severe buttock pain, leading to physical limitation with exercise; class III, buttock rest pain, colonic ischemia, or both. IIA occlusion was achieved in 100% of the patients by means of either catheter-directed embolization or orificial coverage with a stent-graft. No patient in this study had angiographic evidence of significant visceral occlusive disease before the procedure. Sixty-four patients had isolated AAAs, 23 patients had AAAs and IAs, and 16 patients had isolated IAs. Ninety-two patients had one IIA selectively occluded, and 11 patients had both IIAs selectively occluded. RESULTS: After IIA occlusion, 12 patients were categorized in class I, 9 patients were categorized in class II, and 1 patient was categorized in class III, for a total of 22 patients (21%) with pelvic ischemia. Sixteen (17%) of 92 patients had unilateral IIA occlusions, and six (17%) of 11 patients had bilateral IIA occlusions. Five patients in class I improved and had no symptoms within 1 year, and one patient in class II was downgraded to class I because of improved symptoms. Two unique preoperative angiographic findings were identified in the remaining 16 patients (16%) with chronic pelvic claudication: (1) stenosis of the remaining IIA origin (> 70%) with nonopacification of more than three of the six IIA branches (63%); and (2) small caliber, diseased or absent medial and lateral femoral circumflex arteries ipsilateral to the side of the IIA occlusion (25%). One patient with class III ischemia died of cardiovascular collapse associated with colon infarction caused by either acute ischemia or particulate embolization. CONCLUSION: The incidence of pelvic ischemia after IIA occlusion is 20% immediately after endovascular aortoiliac aneurysm repair. A total of 25% of patients had no symptoms within 1 year. Two preoperative radiologic findings may help identify patients who are at risk for pelvic ischemia: stenosis of the patent IIA and disease deep femoral ascending branches ipsilateral to the occluded IIA. The risk of colon ischemia appears to be small after selective IIA occlusion to facilitate endovascular AAA repair.

Ancillary techniques to facilitate endovascular repair of aortic aneurysms.

PURPOSE: The ability to treat abdominal aortoiliac aneurysms and thoracic aortic aneurysms may be limited by coexisting arterial disease. Device deployment may be impaired by occlusive disease and tortuosity of the arteries used to access the aneurysm or by suitability of the implantation sites. In this study we describe the auxiliary procedures performed to circumvent these obstacles and thereby enable endovascular aneurysm repair. PATIENTS AND METHODS: Between January 1, 1993, and December 31, 1999, 390 patients treated for aneurysm of the aorta with endovascular devices were entered prospectively in a vascular registry. Fifty (12%) of the 390 patients required adjunctive surgical techniques to (1) create or extend the length of the proximal or distal device implantation site or (2) permit device navigation through diseased iliac arteries. Auxiliary techniques used to extend or enhance implantation sites were elephant trunk graft (n = 2), the construction of renovisceral bypass grafts (n = 1), and subclavian artery transposition (n = 2). Plication of the common iliac artery at its bifurcation was performed in conjunction with femorofemoral bypass graft in nine patients to allow preservation of pelvic circulation by avoiding internal iliac artery sacrifice. Construction of a bypass graft to transpose the internal iliac artery orifice was performed in one patient. The auxiliary techniques used to facilitate device navigation were iliac artery angioplasty or stenting (n = 8), external iliac artery endovascular endarterectomy or straightening (n = 14), endoluminal iliofemoral bypass conduit (n = 5), and the construction of an open iliofemoral bypass conduit (n = 8). RESULTS: Successful deployment of the endovascular devices was achieved in 49 (98%) of 50 patients. Auxiliary techniques were successful in providing access for endovascular device deployment in all 35 patients (100%). Mean follow-up for techniques to facilitate device navigation is 26 months for endovascular procedures and 42 months for the open bypass graft construction patients; no occlusions were observed at this moment. There were five patients with incisional hematomas that did not necessitate intervention. Fourteen (94%) of 15 patients underwent successful device implantation after the auxiliary maneuvers to enhance implantation site. Mean follow-up for implantation site manipulation is 28 months. One of the subclavian transpositions had a new onset of Horner's syndrome, two of nine patients who had common iliac artery ligated had retroperitoneal hematomas that did not necessitate interventions, and no colon ischemia was seen. The patient who underwent nonanatomic bypass grafting of viscero-renal arteries had a retroperitoneal hematoma that necessitated reexploration. CONCLUSIONS: Significant coexisting arterial disease may be encountered in patients with aortic or iliac aneurysms. Identification of coexisting arterial diseases is essential to help tailor the appropriate supplemental surgical procedure to allow the performance of endovascular aneurysm repair in patients who would otherwise require open surgical repair.

Patient selection for endovascular repair of aortoiliac aneurysms.

PURPOSE: This study was conducted to establish criteria to aid in the selection of patients for endovascular repair of aorto-iliac aneurysms. METHODS: Characterization of pertinent factors used to determine whether a patient is eligible to undergo stent-graft repair of an aorto-iliac aneurysm. PRINCIPAL FINDINGS AND CONCLUSIONS: The determinant factor that dictates whether or not one is eligible to undergo endovascular repair of aorto-iliac aneurysm is the arterial anatomy of the affected area and its surrounding vessels. Some of the initial limitations imposed in this technology have changed such as an acceptance of much shorter neck than initially conceptualized, by the use of supra-renal stent deployment. However, unsolved issues remain regarding the differentiation of thrombus and atherosclerotic plaque in the infra-renal aortic region, iliac artery disease, and the need to have an enhanced flexibility of the delivery system for proper deployment in tortuous aortic necks. The question of long-term device durability remains the most important issue that has to be taken into consideration before one chooses minimally invasive endovascular approaches.

Structure-activity relationship of newly synthesized quinoline derivatives for reversal of multidrug resistance in cancer.

The effect of 24 newly synthesized quinoline derivatives on tumor cell multidrug resistance (MDR) was examined in vitro. At low concentrations, these compounds enhanced the accumulation of [3H]vincristine in K562/ADM cells and reversed tumor cell MDR. The results of the structure-activity relationship analysis indicate that in highly active compounds the two aryl rings in the hydrophobic moiety deviate from a common plane, so they are capable of interacting with hydrogen bond donors of P-170 glycoprotein (P-gp) via pi-hydrogen-pi interactions. Other major structural features which influence the MDR-reversing activities of these compounds are a quinoline nitrogen atom and a basic nitrogen atom in piperazine. Furthermore, in highly active compounds, the distance between the hydrophobic moiety and the basic nitrogen atom (an atom connected to 2-hydroxypropoxyquinoline) must be at least 5 A. Several compounds were found to reverse vincristine resistance in K562/ADM cells in vitro, and compound 16 (MS-209) was selected for clinical studies.

A novel quinoline derivative, MS-209, overcomes drug resistance of human lung cancer cells expressing the multidrug resistance-associated protein (MRP) gene.

PURPOSE AND METHODS: MS-209 is a newly synthesized quinoline compound used orally to overcome human P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). The multidrug resistance-associated protein (MRP) gene is thought to play an important role in MDR in lung cancer. To investigate whether MS-209 could also overcome MRP-mediated MDR, we examined the effect of the compound using a cytotoxicity assay on MDR1 gene-negative drug-selected MDR and wildtype lung cancer cells with various levels of MRP gene expression. The effects of MS-209 were compared with those of verapamil (VER) and cyclosporin A (CsA). The level of MRP gene expression in the cells was evaluated semiquantitatively by RT-PCR. For vincristine (VCR), intracellular accumulation of [3H]-VCR was measured with or without MS-209. RESULTS: In MDR UMCC-1/VP small-cell lung carcinoma cell line, 5 microM of MS-209 and VER enhanced the cytotoxicity of etoposide, doxorubicin (DOX) and VCR more than twofold, and completely reversed the resistance to VCR. The mean reversing effects of MS-209 on DOX and VCR were significantly stronger than those of VER and CsA. In wildtype non-small-cell lung carcinoma cells, the effects of MS-209 were almost equal to those of VER and CsA. The effect of these three agents correlated with the level of MRP gene expression. The MS-209-induced increase in intracellular accumulation of VCR was proportional to the level of MRP gene expression in these cells. CONCLUSION: Our results indicate that MS-209 is a potentially useful drug that can overcome MRP-mediated intrinsic and acquired MDR in human lung cancer.

Validation of right and left ventricular conductance and echocardiography for cardiac function studies.

BACKGROUND: Continuous estimation of left ventricular volume from instantaneous conductance has compared favorably with "gold standards," is less labor intensive, and provides real-time data. Little information exists, however, correlating right ventricular conductance with such gold standards or examining the effects of an electrical field generated in the opposite ventricle. METHODS: In open-chested sheep, right and left ventricular conductance, two-dimensional echocardiography, and thermodilution cardiac outputs were measured at steady-state conditions. After these measurements, postmortem pressure-volume relations, ventricular mass, and ventricular casting were performed. RESULTS: The corrected end-diastolic volume measured by conductance correlated well with volumes measured by echocardiography (r = 0.89), postmortem pressure-volume relations (r = 0.84), and casts (r = 0.85). Left ventricular end-diastolic volume measured by conductance did not differ significantly from other standards by analysis of variance. The presence of an electrical field in the opposite ventricle did not affect measured conductance in the studied ventricle. CONCLUSIONS: Conductance is useful for the measurement of right and left ventricular end-diastolic volumes in the beating heart and is not affected by the presence of an electrical field in the opposite ventricle. Hence, conductance is a useful tool in studies involving interventricular dependence and function.

Does blood flow through holmium:YAG transmyocardial laser channels?

BACKGROUND: Early reports indicate that transmyocardial laser revascularization improves symptoms in patients with refractory angina. However, there is little experimental evidence of whether blood flow through channels is the mechanism of action. METHODS: Endocardial channels were made in the distribution of the left anterior descending coronary artery in canine hearts (n = 5) using a holmium:yttrium-aluminum garnet laser. Hearts were excised acutely while perfused in a retrograde fashion from a second dog so that the aortic valve always remained closed. The proximal left anterior descending coronary artery was ligated. To measure direct transmyocardial blood flow, colored microspheres were injected into the left ventricular chamber. RESULTS: The number of spheres per gram of tissue in the channel region was significantly higher than in the control region (low load, 302.5 +/- 169.0 versus 41.8 +/- 59.4; high load, 208.4 +/- 138.3 versus 5.8 +/- 11.7; both, p < 0.05). However, the estimated regional blood flow through the channels was extremely low (<0.01 mL/g/min. In the chronic setting (n = 4) (2-week survival), no flow as detected through the channels, and the endocardial entry points were closed. CONCLUSIONS: Transmyocardial blood flow does not appear to occur through channels made with the holmium:yttrium-aluminum garnet laser. It remains to be determined whether this is the case with other types of lasers.

Microsurgery in a rat lung transplant model: analysis of benefit.

With the use of microsurgery, we have developed a method of measuring hemodynamic parameters in a rat not possible with previous technology. Three groups of rats were studied: a chemically induced pulmonary hypertensive group (PH); a chemically induced pulmonary hypertensive group treated with single lung transplantation (LT); and an untreated, control group (C). Cardiac output, heart rate, and pulmonary vascular resistance were then calculated in each group from data obtained by 1 mm high fidelity micromanometers and an ultrasonic flow probe. The results show that the data collected from the rodent model are reproducible within each group, and data quality is comparable to large animal models. With this new method, data can be collected in a small animal model at a fraction of the time and cost of large animal studies. Additionally, the complications of graft rejection in large animal studies are eliminated in an isogenic rodent model.

Discriminating between preservation and reperfusion injury in human cardiac allografts using heart weight and left ventricular mass.

BACKGROUND: Myocardial edema caused by injury during preservation or reperfusion can affect cardiac function after heart transplantation. This study was designed to distinguish these forms of injury in human allografts. METHODS AND RESULTS: In 15 donor hearts preserved in University of Wisconsin solution, heart weight (HW) was obtained immediately after explantation and after transport before implantation. Left ventricular mass (LVM) was calculated separately in 18 patients with the use of epicardial two-dimensional echocardiograms obtained both before explantation from the donor and after transplantation and weaning from cardiopulmonary bypass. While changes in LVM could be due to preservation or reperfusion injury, changes in HW can only be due to edema occurring during transport. HW averaged 339 +/- 24 g (mean +/- SE) before and 340 +/- 24 g after transport (P = NS); however, LVM increased 14 g, from 164 +/- 8 to 178 +/- 11 g (P < .05, paired t test). LVM increased in 10 of 18 patients (56%). No correlation was demonstrated between duration of ischemia (mean, 172 +/- 13 minutes) and changes in HW or LVM. Two patients died as a result of primary graft failure. In the first, HW increased 54 g, 2 SD above the mean. In the second, LVM increased 66 g, 2 SD above the mean, but HW changed minimally. CONCLUSIONS: While current preservation methods result in minimal change in HW during transport, reperfusion injury frequently increases LVM. LVM determination by two-dimensional echocardiography may prove valuable in detecting allograft injury.

Creation of a controlled venoarterial shunt. A surgical intervention for right-side circulatory failure.

BACKGROUND: Right-side circulatory failure (RSCF), a common complication of heart transplant and left ventricular assist device recipients, results in decreased cardiac output because of diminished flow across the pulmonary circuit. We hypothesized that creation of a controlled venoarterial shunt would result in decompression of the right ventricle and improved systemic cardiac output at tolerable oxygen saturations. METHODS AND RESULTS: A venoarterial shunt was created in a large-animal model (calf, n = 6). RSCF was induced by banding the pulmonary artery. Hemodynamic measures and blood gas determinations were obtained during nonshunted and shunted states. Pulmonary artery banding increased mean right ventricular systolic pressure from 44.9 +/- 2.1 mm Hg (mean +/- SEM) to 85.9 +/- 6.9 mm Hg (P < .05, paired t test) and decreased mean aortic flow from 7.8 +/- 1.0 to 4.2 +/- 1.1 L/min (P < .05). Flow through a venoarterial shunt at approximately 40% of cardiac output resulted in a decrease in right ventricular end-systolic pressure from 85.9 +/- 6.9 to 72.1 +/- 5.6 mm Hg (P < .01, ANOVA), a decrease in mean pulmonary artery pressure from 42.9 +/- 5.0 to 37.2 +/- 3.8 mm Hg (P < .01), and an increase in aortic flow from 4.2 +/- .05 to 5.1 L/min (P < .01). Left ventricular stroke work decreased from 2.22 +/- 0.28 to 1.55 +/- 0.88 (P < .05). Carotid artery oxygen saturation did not change significantly (99.9 +/- .02 to 97.6 +/- 1.7) during shunting. CONCLUSIONS: A controlled venoarterial shunt improved hemodynamics and cardiac output in a large animal model with RSCF. This strategy may be useful in the management of transplant and left ventricular assist device recipients with perioperative RSCF.

Assessment of right ventricular contractile state with the conductance catheter technique in the pig.

OBJECTIVE: Since the conductance catheter method has facilitated evaluation of left ventricular contractile state in both laboratory and clinical studies, the aim of this study was to determine whether the technique is similarly useful for the right ventricle. METHODS: A series of right ventricular pressure-volume loops was obtained in seven open chest pigs during transient vena caval occlusion using a 12-electrode conductance catheter. End systolic pressure-volume relationships, stroke work-end diastolic volume relationships, and dP/dt-end diastolic volume relationships were compared at control and during infusion of dobutamine and esmolol. RESULTS: Right ventricular pressure-volume loops generated with the conductance catheter were of a shape consistent with those previously reported by other volume measurement techniques, and responded to changes in inotropic state in a predictable fashion. Dobutamine shifted the three contractile relationships leftward, whereas esmolol shifted them rightward. Comparisons of stroke volume derived with the conductance catheter and with a pulmonary artery flow probe demonstrated the ability of the conductance technique to measure relative volume changes. CONCLUSIONS: The conductance catheter provides a continuous measure of right ventricular volume that was used to detect changes in right ventricular contractile state in pigs. This represents a promising and much needed method for the evaluation of right ventricular function.

Nitroglycerin maintains graft vascular homeostasis and enhances preservation in an orthotopic rat lung transplant model.

Transplanted lungs often fail during the peritransplantation period for poorly understood reasons. Because the nitric oxide pathway regulates pulmonary vascular tone, helps to maintain the integrity of the endothelial barrier, and modulates neutrophil adhesivity and activation, we hypothesized that perturbation of this pathway during the preservation and reperfusion of transplanted lungs might play a critical role in mediating early graft failure. To evaluate whether supplementing the preservation solution with the nitric oxide donor nitroglycerin enhances lung preservation for transplantation, we obtained hemodynamic measurements in a model of orthotopic left lung transplantation in the rat after ligation of the native right pulmonary artery. In these experiments, recipient survival and hemodynamics depended solely on the transplanted lung. The left lung was harvested from 22 rats, flushed with either lactated Ringer's solution alone (control, n = 11) or Ringer's solution supplemented with nitroglycerin (0.1 mg/ml, n = 11), preserved for 4 hours at 4 degrees C, and then transplanted using a rapid cuff technique for bronchial and vascular anastomoses. Nitroglycerin significantly improved arterial blood oxygenation (339 +/- 66 versus 130 +/- 12 mm Hg, p < 0.05), increased pulmonary arterial flow (7.6 +/- 1.9 versus 0.9 +/- 0.2 ml/min, p < 0.005), decreased pulmonary vascular resistance (1.7 +/- 0.4 versus 6.6 +/- 1.9 x 10(3) Wood units, p < 0.05), and enhanced recipient survival (64% versus 0%, p < 0.05). Control grafts had significantly greater neutrophil accumulation (50% greater as quantified by myeloperoxidase activity, p < 0.05) than grafts preserved in the presence of nitroglycerin. These studies show that supplementation of the preservation solution with the nitric oxide donor nitroglycerin maintains graft vascular homeostasis and significantly improves pulmonary function and recipient survival after transplantation.

Reversal of multidrug resistance by a novel quinoline derivative, MS-209.

MS-209, a novel quinoline derivative, was examined for its reversing effect on multidrug-resistant tumor cells. MS-209 at 1-10 microM completely reversed resistance against vincristine (VCR) in vitro in multidrug-resistant variants of mouse leukemia P388 cells (VCR-resistant P388/VCR and Adriamycin (ADM)-resistant P388/ADM) and human leukemia K562 cells (VCR-resistant K562/VCR and ADM-resistant K562/ADM). MS-209 at 1-10 microM also completely reversed resistance against ADM in vitro in P388/VCR cells, K562/VCR cells, and K562/ADM cells. In ADM-resistant P388 (P388/ADM) cells, however, ADM resistance was only partially reversed at the MS-209 concentrations tested. MS-209 enhanced the chemotherapeutic effect of VCR in P388/VCR-bearing mice. When MS-209 was given p.o. at 80 mg/kg twice a day (total dose, 160 mg/kg per day) with 100 micrograms/kg VCR, a treated/control (T/C) value of 155% was obtained. MS-209 also enhanced the chemotherapeutic effect of ADM in P388/ADM-bearing mice. The most prominent effects were obtained when MS-209 was given with 2 mg/kg ADM, yielding T/C values of 150%-194% for the combined treatment at an MS-209 dose of 200-450 mg/kg. MS-209 inhibited [3H]-azidopine photolabeling of P-glycoprotein efficiently. Furthermore, the accumulation of ADM in K562/ADM cells was increased more efficiently by MS-209 than by verapamil. These results indicate that MS-209, like verapamil, directly interacts with P-glycoprotein and inhibits the active efflux of antitumor agents, thus overcoming multidrug resistance in vitro and in vivo.

Relationship between multidrug resistant gene expression and multidrug resistant-reversing effect of MS-209 in various tumor cells.

MS-209 is a novel quinoline compound which can overcome multidrug resistance (MDR) both in vitro and in vivo, while having a low level of side effects, and is now being evaluated in a clinical phase II study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantitate the expression levels of MDR genes in various mouse and human tumor cell lines. The MDR gene and the beta actin gene, as the internal reference standard, were coamplified separately, and the relative expression of the MDR gene was represented by the MDR/beta actin ratio. The in vitro MDR-reversing effect of MS-209 was then compared with the MDR gene expression (MDR/beta actin ratio). We found a significant correlation between these two parameters. Moreover, a significant correlation was also observed between the level of expression of the MDR1 gene and that of P-glycoprotein in human cell lines. Therefore, the efficacy of MS-209 seems to specifically depend on the level of MDR gene expression (P-glycoprotein). From these observations, it is suggested that RT-PCR assays of MDR1 gene in tumor biopsy specimens might be an effective means to predict the response of tumor cells to combination therapy with MS-209.

Studies on the constituents of Calliandra anomala (Kunth) Macbr. I. Structure elucidation of two acylated triterpenoidal saponins.

Two novel triterpenoidal saponins, called calliandra saponins A and E, were isolated from the branches of Calliandra anomala (Kunth) Macbr. On the basis of the chemical and physiocochemical evidence, their structures were defined as 3-O-alpha-L-arabinopyranosyl-(1-->2)-alpha-L-arabinopyranosyl++ +-(1-->6)-2- acetamido-2-deoxy-beta-D-glucopyranosyl echinocystic acid 28-O-(beta-D-glucopyranosyl-(1-->3)-[beta-D-xylopyranosyl-(1-->3)-beta-D - xylopyranosyl-(1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-[(6S)-2-trans- 2,6-dimethyl-6-O-beta-D-xylopyranosyl-2,7-octadienoyl-(1-->6)]-bet a-D- glucopyranosyl) ester (4) and 3-O-alpha-L-arabinopyranosyl-(1-->2)-alpha-L-arabinopyranosyl++ +-(1-->6)-2- acetamido-2-deoxy-beta-D-glucopyranosyl echinocystic acid 28-O-[beta-D-glucopyranosyl-(1-->3)-[beta-D-xylopyranosyl-(1-->3)-beta-D - xylopyranosyl-(1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-[(6'S)-2'-trans- 2',6'-dimethyl-6'-O-(2-O-(6S)-2-trans-2,6-dimethyl-6-hydroxy-2,7-octa dienoyl)- beta-D-xylopyranosyl-2',7'-octadienoyl-(1-->6)]-beta-D-glucopyr ano syl] ester (5), respectively.

Thoracoscopic placement of implantable cardioverter-defibrillator patch leads in sheep.

BACKGROUND: A thoracoscopic technique was developed for the placement of commercially available implantable cardioverter-defibrillator (ICD) patch leads in sheep. METHODS AND RESULTS: Small ICD patch leads (13.5 cm2, A-67) were placed thoracoscopically in sheep (n = 5) that had survived coronary artery ligation from a previous experiment. The technique used three small incisions in the left chest. After lysis of adhesions, the ICD patch lead was introduced through a mediastinoscope. The ICD patch lead was secured in the extrapericardial position with surgical clips placed in the four corners of the ICD patch lead. After 2 weeks, a median sternotomy was performed, and ICD patch leads were reexamined for positioning. Extensive fibrosis was noted to adhere the ICD patch lead to the pericardium. The surgical clips were found intact in all animals without noticeable migration of patch lead position. There was no mortality related to ICD patch lead placement, and estimated blood loss was less than 30 mL without use of cautery. CONCLUSIONS: Commercially available ICD patch leads may be reliably and safely placed with minimal patch migration in sheep using thoracoscopic techniques.

Prevention of acute regional ischemia with endocardial laser channels.

Laser myocardial revascularization has been shown to reduce mortality and infarct size after left anterior descending coronary artery (LAD) ligation in dogs. It has not been shown to improve myocardial contractility in acute ischemia. In this study a holmium-yttrium-aluminum garnet laser (wavelength, 2.14 microns) was used to create nontransmural myocardial channels from the endocardial surface in the ischemic regions of the canine left ventricle. Twelve mongrel dogs (6 controls, 6 laser myocardial revascularizations) underwent 90 minutes of LAD ligation followed by 6 hours of reperfusion. The ischemic region was determined by methylene blue injection during brief LAD occlusion. Laser myocardial revascularization averaged three channels per square centimeter in the ischemic region created using 12 J/channel (600 mJ/pulse, 10 Hz) before LAD ligation. Contractility was assessed from regional preload recruitable stroke work (RPRSW), using pairs of segment length ultrasonic transducers in the ischemic and the nonischemic regions. Two-dimensional echocardiography corroborated with segmental length findings. In control dogs, the ischemic region was dyskinetic during LAD ligation and reperfusion. Dyskinesis of the ischemic region during systole produced negative values for regional stroke work, and RPRSW was considered zero. In 4 of 6 laser-revascularized dogs, RPRSW remained positive in the ischemic region. Two dogs had intermittent dyskinesis. The difference between laser-revascularized and control dogs in ischemic region RPRSW was significant (p < 0.01 by Fischer's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

Oligonucleotide sequences required for natural killer cell activation.

Based on the previous finding that certain 30-mer single-stranded oligodeoxyribonucleotides (oligonucleotides) having particular 6-mer palindromic sequences could induce interferon-alpha and -gamma, and enhance natural killer activity, the present study was carried out to clarify the entire relationship between the activity and the sequence of 30-mer oligonucleotides. The results indicated that the activity depended critically on the presence of particular palindromic sequences including the 5'-CG-3' motif(s). The size and the number of palindromes as well as the extra-palindromic sequences also influenced the activity. An oligonucleotide with a 10-mer palindrome and extra-palindromic oligoguanylate sequences showed the strongest activity among the oligonucleotides tested.

Changes of host cell infiltration into Meth A fibrosarcoma tumor during the course of regression induced by injections of a BCG nucleic acid fraction.

MY-1, which consists of DNA and RNA extracted and purified from Mycobacterium bovis strain BCG, causes the regression of various experimental syngeneic tumors when injected intratumorally. In order to identify the host cells involved in the antitumor mechanism(s) of MY-1, we examined Meth A tumors inoculated intradermally to BALB/c mice, which were given multiple injections of MY-1 following tumor inoculation. Histological and immunohistochemical examinations were performed at several time points. On day 4 after inoculation, the MY-1-treated tumors were heavily infiltrated with a heterogeneous population of mononuclear cells with low density nuclei. The MY-1-injected tumors contained asialo-GM1-positive cells and Mac-1-positive cells, which indicated that the infiltrating mononuclear cells were natural killer cells and macrophages. On day 14 after inoculation, the tumors were infiltrated with a large number of L3T4-positive cells and fewer Lyt-2-positive cells, both of which were more abundant in the MY-1-treated tumors than in the control tumors. The observed sequence of host cell infiltration corresponded well with our previous studies which have indicated that the antitumor mechanism of MY-1 is divided into two phases, i.e. the early phase when natural killer cells and macrophages inhibit tumor growth, and the late phase when L3T4-positive cells act to induce tumor regression via a delayed-type hypersensitivity against tumor cells.