The value of subintimal angioplasty in the management of critical lower extremity ischemia: failure is not always associated with a rethreatened limb.

The technique of subintimal angioplasty was developed in Leicester, UK in 1987. Recently a growing number of centers in Europe and the United States have been gaining experience with this technique. Promising results have been reported and the application of the technique expanded to include the iliac and crural arteries. Despite this growing experience, the technique has not gained widespread acceptance. It has been speculated that this may be due in large part to a steep learning curve and/or skepticism regarding the procedure given the relatively low primary patency rates seen in most series. However, limb salvage rates from these same and other series have been considerably higher than the patency rates, and advocates of the technique have urged that the results of clinical series be viewed with these limb salvage rates primarily in mind. Although primary patency rates remain low for patients undergoing subintimal angioplasty limb salvage rates remain high. Given the many advantages of this technique, including reduced anesthesia requirements, a minimally invasive approach, and potential reductions in length of stay and cost subintimal angioplasty will continue to have a role in the treatment of lower extremity ischemia. When applied judiciously, bypass options are preserved. This does not mean that the availability of this technique should be used as justification to lower the threshold for the treatment of mild intermittent claudication. When a subintimal angioplasty fails, it frequently does so without the recurrence of symptoms, especially when a gangrenous lesion or ulcer has healed. Various approaches for the performance of subintimal angioplasty and clinical results will be discussed.

Conservative observational management with selective delayed repair for large abdominal aortic aneurysms in high risk patients.

AIM: Abdominal aortic aneurysms (AAAs) larger than 5.5 cm should generally undergo elective repair. However, some of these patients have serious comorbid conditions, which greatly increase operative risk. This study evaluated the outcomes of nonoperative, observational management and selective delayed AAA repair in high-risk patients with large infrarenal and pararenal AAAs. METHODS: Among 226 patients with AAAs >5.5 cm, we selected 72 with AAAs 5.6-12.0 cm (mean 7.0 cm) for periods of nonoperative management because of their prohibitive surgical risks. Comorbid factors included a low ejection fraction of 15-34% (mean 22%) in 18 patients; FEV1 <50% (mean 38%) in 25; prior laparotomy in 10; and morbid obesity in 22. Follow-up was complete in the 72 patients for the 6-76 months (mean 23 months) that they were treated nonoperatively. Fifty-three patients ultimately underwent repair because of AAA enlargement or onset of symptoms after 6-72 months (mean 19 months) of observational treatment. RESULTS: Of the 72 selected patients, 54 (75%) are living and 18 (25%) are dead. Seven patients undergoing only nonoperative treatment presently survive after 28-76 months (mean 48 months). Of the 18 deaths, AAA rupture occurred in only 3 patients (4%) who had been observed for 12, 31, and 72 months before rupture. Nine other deaths (13%) occurred after 6-72 months from comorbidities unrelated to the patient's AAA. Six of the 53 patients undergoing delayed AAA repair died within 30 days of operation (11% mortality). The mortality for the 154 good risk AAA patients, who underwent prompt open or endovascular repair, was 2.2%. CONCLUSION: These data indicate that some patients with large AAAs and serious comorbidities are acceptably managed for long periods (6-76 months) by nonoperative means. Substantial delays of 12 to 76 months resulted in an AAA rupture rate of only 4%, while 13% of these patients (9 of 72) died of their comorbidities unrelated to AAA rupture or surgery and mortality in this group of patients, when operated on, was 11% (6 of 53). These findings support the selective use of nonoperative observational management in some patients with large AAAs and serious comorbidities.

Overt colon ischemia after endovascular aneurysm repair: the importance of microembolization as an etiology.

OBJECTIVE: The purpose of this study was to analyze the incidence, severity, and etiologic factors of the development of colon ischemia after endovascular aortoiliac aneurysm repair (EVAR). METHODS: During the last 9 years we performed 278 elective EVARs using a variety of grafts. To facilitate these repairs, one hypogastric artery (HA) was coil embolized in 109 patients and both HAs were coil embolized in 13 patients. The preprocedural status of the inferior mesenteric, hypogastric, and iliac arteries as well as anatomical characteristics of the abdominal aortic aneurysm were determined arteriographically and by computerized tomographic scans. Postoperative colon ischemia was documented by colonoscopy or operative findings. RESULTS: Colon ischemia occurred in eight patients (2.9%). Three patients with colon ischemia died and had evidence of widespread (cutaneous, renal, small bowel, and/or lower extremity) microembolization. One of these three had a colectomy and microscopic emboli were present. One other patient who required a colectomy also had pathologic evidence of colonic microembolization but survived. Four other patients with colon ischemia were treated conservatively and survived. In one patient, previous colectomy with interruption of mesenteric collaterals may have been a contributory cause of colon ischemia. Of the eight patients with colon ischemia, only one had unilateral HA occlusion, and none had bilateral HA occlusion. The other 121 patients with unilateral and bilateral HA occlusion had no evidence of colon ischemia. CONCLUSIONS: Colon ischemia occurs after EVAR with an incidence approximating that of open repair. Colon ischemia was unrelated to HA interruption. Embolization appears to be a major cause of colon ischemia, although inadequate mesenteric collateral circulation may also play an etiologic role. Mortality with colon ischemia accompanied by widespread embolization was high, whereas colon ischemia without it was often mild and amenable to nonoperative management.

Limited role for IVUS in the endovascular repair of aortoiliac aneurysms.

BACKGROUND: To determine the need for routine versus selective intraoperative IVUS during endovascular aortoiliac aneurysm (AIA) repair. METHODS: One-hundred and eighty-eight endovascular AIA repairs performed over a 5-year period were reviewed and included in the study. Surgeon-made aorto-uni-femoral grafts (n=78) and industry-made bifurcated or tube grafts (n=110) were used. In the initial 51 cases IVUS was routinely performed. In the latter 137 cases IVUS was used selectively. In this group graft deformities suspected on completion angiography or pullback pressure measurements were treated with balloon dilatation and stenting. IVUS was then performed only in the presence of a persistent pressure gradient or inconclusive angiographic findings. RESULTS: In the initial 51 cases IVUS revealed 20 lesions of which 8 were not initially detected angiographically and which required further treatment. In the latter 137 cases IVUS was necessary in only 1 case, and guided the treatment of an angiographically undetectable lesion. There have been no late episodes of graft compression, kinking, or thrombosis in the selective IVUS group. CONCLUSIONS: The use of pullback pressure measurements with a low threshold for angioplasty and stenting, especially in unsupported grafts, followed by the selective use of IVUS decreases the overall requirement for IVUS and its associated costs.

Endoscopically assisted in situ lower extremity bypass graft: a preliminary report of a new minimally invasive technique.

OBJECTIVE: Lower extremity arterial reconstructions with in situ greater saphenous vein (GSV) are an important component of limb salvage surgery. Initially, the procedure was performed through continuous skin incisions for side branch occlusion and valve lysis with a wound complication rate of 5% to 25%. To decrease these complications, we used endoscopic GSV harvest equipment in 25 in situ vein bypass grafts in 25 patients performed over 24 months. METHODS: The procedures were performed with three skin incisions: two for arterial access and a 2-cm incision above the knee to insert the Endopath device (Ethicon) to locate and clip the GSV side branches. After completion of the proximal anastomosis, the valves were lysed through the distal end of the vein with a flexible valvulotome. Completion cineangiography was performed to confirm side branch occlusion and evaluate the entire reconstruction. The results of this technique were compared with our last 25 in situ bypass grafts done with standard long incisions. RESULTS: In the endoscopic group there was one (4%) minor wound complication (cellulitis). No postoperative arteriovenous fistulas were detected by means of duplex examination, and the average hospital stay was 6.2 +/- 1 days. One graft closed at 9 months as a result of distal vein hyperplasia, but the other grafts have remained patent, with follow-up from 6 to 30 months (mean, 18 months). Patients with the standard in situ bypass grafts had significantly (P < .05) more wound complications (20%) and longer average hospital stay (9.2 +/- 2 days) than the endoscopic group. Patency rates were comparable for both groups. CONCLUSION: These results show that less invasive endoscopic in situ bypass grafting minimizes wound complications and reduces the need for hospitalization without decreasing patency or increasing operative time.

All sealed endoleaks are not the same: a treatment strategy based on an ex-vivo analysis.

PURPOSE: factors contributing to pressure transmission through thrombosed or sealed endoleaks have not been elucidated. The purpose of this investigation was to create an ex-vivo model that mimics patent and sealed endoleaks and that can quantitatively analyse the effects of length, diameter and thrombus on pressure transmission to the interior of the aneurysm sac. METHODS: In the ex-vivo model, endoleak channels (ELCs) of various lengths (2 cm, 6 cm, 10 cm) and diameters (0.6 cm, 1.0 cm, 1.4 cm) were constructed using polytetrafluoroethylene (PTFE) grafts and attached to an artificial aneurysm sac. These ELCs were incorporated within a mock circulation made of rubber tubing connected to a pulsatile pump. Peak systolic pressure (PSP) was recorded in the aneurysm sac, distal to each ELC. Subsequently the ELCs were filled with human thrombus, and the pressure measurements repeated (n =5). Data was evaluated by regression analysis. RESULTS: Peak systolic pressure in the artificial circulation was maintained at 150 mmHg. In the absence of thrombus pressure did not change across the ELC, regardless of its length or diameter. In the presence of organised thrombus, the pressure curves distal to the ELC were dampened, and the pressure reduction was directly proportional to the length and inversely proportional to the diameter of the ELC. Regression analysis indicated statistical significance. CONCLUSION: In the absence of thrombosis, pressure transmitted via an ELC to the aneurysm sac is unchanged regardless of its length or diameter. All sealed endoleaks also transmit pressure. However, when an endoleak has thrombosed, pressure reduction is directly proportional to the length and inversely proportional to the diameter of its channel. This ex-vivo model suggests that Type 2 endoleaks with longer channels and smaller diameters would derive a greater benefit from adjunctive manoeuvres (coil embolisation) that hasten thrombosis. On the other hand, thrombosis of endoleaks with short and wide channels (e.g. Type 1) may not result in substantial pressure reduction within the aneurysm sac and a successful outcome.

Fluoroscopically assisted thromboembolectomy: should it be routine?

The treatment of acute limb ischemia secondary to thromboembolic disease has become significantly more difficult because of the increased proportion of elderly patients presenting with complex patterns of atherosclerotic disease. The presence of multiple medical comorbidities also complicates operative and perioperative management in these patients. Neither the techniques nor catheter designs have changed significantly since the introduction of the balloon embolectomy catheter in 1963, which permitted extraction of clot from remote sites. The authors believe that the use of intraoperative fluoroscopy and the performance of fluoroscopically assisted thromboembolectomy (FATE) greatly improves the results of this treatment in many cases. FATE facilitates catheter passage through tortuous, diseased arteries, identifies residual thrombus and underlying lesions, reduces vessel damage caused by balloon overinflation, and decreases the risk of catheter-induced dissection or atherosclerotic plaque displacement. Intraoperative fluoroscopy helps determine the need for as well as guides adjunctive procedures such as angioplasty and stenting. Such procedures can be performed at the time of the thromboembolectomy simplifying and expediting treatment.

Unilateral and bilateral hypogastric artery interruption during aortoiliac aneurysm repair in 154 patients: a relatively innocuous procedure.

OBJECTIVE: Hypogastric artery (HA) occlusion during aortic aneurysm repair has been associated with considerable morbidity. We analyzed the consequences of interrupting one or both HAs in the standard surgical or endovascular treatment of aortoiliac aneurysms (AIAs). METHODS: From 1992 to 2000, 154 patients with abdominal aortic aneurysms (n = 66), iliac aneurysms (n = 28), or AIAs (n = 60) required interruption of one (n = 134) or both (n = 20) HAs as part of their endovascular (n = 107) or open repair (n = 47). Endovascular treatment was performed with a variety of industry- or surgeon-made grafts in combination with coil embolization of the HAs. The standard surgical techniques included oversewing or excluding the origins of the HAs and extending the prosthetic graft to the external iliac or femoral artery. RESULTS: There were no cases of buttock necrosis, ischemic colitis requiring laparotomy, or death when one or both HAs were interrupted. Persistent buttock claudication occurred after 16 (12%) of the unilateral and 2 (11%) of the bilateral HA interruptions. Impotence occurred in 7 (9%) of the unilateral and 2 (13%) of the bilateral HA interruptions. Minor neurologic deficits of the lower extremity were observed in 2 (1.5%) of the patients with unilateral HA interruption. CONCLUSIONS: Although HA flow should be preserved if possible, selective interruption of one or both HAs can usually be accomplished safely during endovascular and open repair of anatomically challenging AIAs. We believe other comorbid factors such as shock, distal embolization, or the failure to preserve collateral branches from the external iliac and femoral arteries may have contributed to the morbidity in other reports of HA interruption.

Does the endovascular repair of aortoiliac aneurysms pose a radiation safety hazard to vascular surgeons?

OBJECTIVES: Endovascular aortoiliac aneurysm (EAIA) repair uses substantial fluoroscopic guidance that requires considerable radiation exposure. Doses were determined for a team of three vascular surgeons performing 47 consecutive EAIA repairs over a 1-year period to determine whether this exposure constitutes a radiation hazard. METHODS: Twenty-nine surgeon-made aortounifemoral devices and 18 bifurcated devices were used. Three surgeons wore dosimeters (1) on the waist, under a lead apron; (2) on the waist, outside a lead apron; (3) on the collar; and (4) on the left ring finger. Dosimeters were also placed around the operating table and room to evaluate the patient, other personnel, and ambient doses. Exposures were compared with standards of the International Commission on Radiological Protection (ICRP). RESULTS: Total fluoroscopy time was 30.9 hours (1852 minutes; mean, 39.4 minutes per case). Yearly total effective body doses for all surgeons (under lead) were below the 20 mSv/y occupational exposure limit of the ICRP. Outside lead doses for two surgeons approximated recommended limits. Lead aprons attenuated 85% to 91% of the dose. Ring doses and calculated eye doses were within the ICRP exposure limits. Patient skin doses averaged 360 mSv per case (range, 120-860 mSv). The ambient (> 3 m from the source) operating room dose was 1.06 mSv/y. CONCLUSIONS: Although the total effective body doses under lead fell within established ICRP occupational exposure limits, they are not negligible. Because radiation exposure is cumulative and endovascular procedures are becoming more common, individuals performing these procedures must carefully monitor their exposure. Our results indicate that a team of surgeons can perform 386 hours of fluoroscopy per year or 587 EAIA repairs per year and remain within occupational exposure limits. Individuals who perform these procedures should actively monitor their effective doses and educate personnel in methods for reducing exposure.

Overview of techniques and devices for endovascular abdominal aortic aneurysm repair.

The endovascular treatment of abdominal aortic aneurysms (AAAs) is rapidly evolving. Since the onset of clinical investigations in 1990 there has been a rapid proliferation in the number of available devices, both surgeon-made and industry-made. This chapter reviews endovascular AAA repair with regard to available devices, patient selection for each device based on anatomic criteria, and techniques for graft deployment.

Angiographic criteria reliably predict when carotid endarterectomy can be safely performed without a shunt.

BACKGROUND: Selective shunting during carotid endarterectomy is widely performed, but the optimal approach for predicting when a shunt is unnecessary remains uncertain. We evaluated the ability of preoperative cerebral angiography to predict when carotid endarterectomy could be safely performed without a shunt. STUDY DESIGN: Eighty-seven patients undergoing carotid endarterectomy between August 1991 and December 1997 had preoperative cerebral angiograms. The angiograms were evaluated for the presence of collateral flow from the contralateral carotid through the anterior communicating artery and from the posterior circulation through the posterior communicating artery. Patients then underwent endarterectomy and were selectively shunted based on somatosensory evoked potential changes. Internal carotid artery stump pressure was routinely measured in all patients. RESULTS: Nine patients (10%) had a shunt placed based on somatosensory evoked potential changes and none of the 87 patients had a perioperative (30 days) stroke. Angiography revealed that 36 patients (41%) had no cross-filling from the contralateral carotid through the anterior communicating artery. Nine of these patients (25%) required a shunt; none of the 51 patients with adequate cross-filling (p < 0.001) did. Furthermore, 94% of the patients without cross-filling but with a patent ipsilateral posterior communicating artery did not require a shunt using somatosensory evoked potential changes as the standard for shunt insertion. Stump pressure measurements (> or = 25 mmHg) or (> or = 50 mmHg) did not reliably exclude the need for a shunt. Only 2 of 15 patients with contralateral carotid occlusion and 1 of 16 patients with a prior ipsilateral stroke required shunts. CONCLUSIONS: In the presence of cross-filling from the contralateral carotid artery, shunt insertion was uniformly unnecessary. In addition, routine shunting of patients with previous ipsilateral strokes or contralateral carotid occlusion was not always necessary. Stump pressures were less sensitive than angiographic criteria in determining when a shunt was unnecessary. Evaluation of cross-filling from the contralateral carotid artery on preoperative angiography can predict with certainty which patients will not require a shunt.

Endovascular graft repair of ruptured aortoiliac aneurysms.

BACKGROUND: The feasibility of endovascular graft (EVG) repair of ruptured aortoiliac aneurysms (AIAs) has yet to be demonstrated. There are inherent limitations in EVG repair, including the need for preoperative measurements of the aneurysmal and adjacent arterial anatomy to determine the appropriate size and type of graft and the inherent delay to obtain proximal occlusion. We developed an EVG system with broad versatility that largely eliminates these problems. STUDY DESIGN: Between 1993 and 1998, within an experience of 134 endovascular AIA repairs, 12 ruptured AIAs were treated using EVGs that facilitated intraoperative customization and eliminated the need for preoperative measurements. The EVGs consisted of either a Palmaz stent and a PTFE graft deployed by a compliant balloon (n = 9) or a self-expanding covered stent graft (n = 3). Both grafts were cut to the appropriate length intraoperatively. The mean age of the patients was 72 years (range 40 to 86 years). The mean size of the aneurysms was 7.6 cm (range 3 to 16 cm). Preoperative symptoms were present in all patients and included abdominal or back pain (n = 9), syncope (n = 4), and external bleeding (n = 2). All patients were high surgical risks because of comorbid disease (n = 10) or previous abdominal operations (n = 6), and nine experienced hypotension. RESULTS: All EVGs were inserted successfully and excluded the aneurysms from the circulation. The mean operating time was 263 minutes, the mean blood loss was 715 mL, and the mean length of hospital stay was 6.5 days. There were two deaths (16%), one from the preexisting acute myocardial infarction and one from multiple organ failure. There were three minor complications (25%). Two patients required evacuation of an intraabdominal hematoma from the initial rupture. All but one of the grafts was functioning at a mean followup of 18 months. CONCLUSIONS: This study demonstrates the feasibility of EVG repair for ruptured AIAs using a graft that can be customized intraoperatively for each patient. Such repairs currently are valuable in patients with ruptured AIAs and serious comorbidities and may be applicable in other circumstances as well.

Should initial clamping for abdominal aortic aneurysm repair be proximal or distal to minimise embolisation?

OBJECTIVES: to determine whether clamping proximally or distally on the infrarenal aorta during abdominal aortic aneurysm (AAA) repair increases the overall embolic potential. MATERIALS AND METHODS: a sheath was placed in the mid-infrarenal aorta of 16 dogs. In eight animals a cross-clamp was placed at the aortic trifurcation, and in another eight animals it was placed in the immediate subrenal position. Under fluoroscopy blood flow within the infrarenal aorta was evaluated by contrast and particle injections. Grey-scale analysis was used to calculate contrast density. Particle distribution was followed fluoroscopically and confirmed pathologically. RESULTS: fifty-seven+/-24% of injected contrast remained within the aorta with distal clamping while 97+/-7% did so with proximal clamping (p<0.01). With distal aortic clamping 6.2+/-1. 3 out of 10 injected particles remained within the aorta after 15 seconds and only 0.8+/-0.8 remained after 5 min. With proximal aortic clamping, all 10 of the particles remained within the aortic lumen for the full 5 minutes (p<0.001). CONCLUSIONS: initial distal clamping minimises distal embolisation, but may result in renal and/or visceral embolisation. Initial proximal clamping prevents proximal embolisation and does not promote distal embolisation. We recommend initial proximal clamping in aortic aneurysm surgery to minimise the overall risk of embolisation.

Systolic ventricular interaction in normal and diseased explanted human hearts.

OBJECTIVE: The purpose of this study was to quantify the magnitude of interaction between the right and left ventricles in conditions of heart failure. METHODS: Human hearts were taken from transplant recipients diagnosed with diluted cardiomyopathy at the time of transplantation and were restored to beating condition with use of an isolated perfusion circuit. Left ventricular-right ventricular interaction was determined by ramping volume in the left ventricle while holding right ventricular volume constant. Right ventricular pressure gain was plotted against left ventricular pressure and the slope of the linear regression determined the left ventricular-right ventricular interaction. A similar procedure was used to determine right ventricular-left ventricular interaction. Two normal hearts were obtained from transplant donors not suitable for cardiac donation to serve as control hearts. RESULTS: Mean left ventricular-right ventricular interaction was 0.22 in the hearts with dilated cardiomyopathy compared with 0.06 in the control hearts. Mean right ventricular-left ventricular interaction was 0.14 in the hearts with dilated cardiomyopathy compared with 0.09 in the control hearts. A marked increase in left ventricular-right ventricular interaction was noted in the hearts with dilated cardiomyopathy compared with control hearts. Although observed values of right ventricular-left ventricular interaction also correspond to previously published results, no significant increase was observed in the dilated cardiomyopathy condition. CONCLUSIONS: These studies confirm previously published values for systolic ventricular interaction obtained with animal models and demonstrate a marked increase in the dependence of the right ventricle on left ventricular function to maintain systolic pressure generation during conditions of dilated cardiomyopathy.

Endogenous nitric oxide and pulmonary vascular tone in the neonate.

PURPOSE: In newborns, inhaled nitric oxide (NO) has been shown to ameliorate increased pulmonary vascular resistance (PVR) precipitated by hypoxia. The role of endogenous NO production in this response is not clear. The contribution of endogenous NO to resting PVR in normoxic newborns also has not been well studied. The authors used an isolated, in situ, neonatal piglet lung-perfusion model, devoid of systemic detractors in which endogenous NO could be selectively inhibited, to determine whether (1) endogenous NO plays a role in the maintenance of PVR with normoxia, (2) endogenous NO plays a role in the response to hypoxia, and (c) inhaled NO can reverse changes induced by inhibition of endogenous NO. METHODS: Sixteen neonatal piglets underwent occlusive tracheostomy and pressure-cycled ventilation. After heparinization and ligation of the ductus arteriosus, left atrial and pulmonary arterial cannulation were performed, without ischemia, via a median sternotomy. The aorta was ligated, and lung perfusion was set at 80 mL/kg/min via an extracorporeal membrane oxygenation circuit. Hematocrit (40% to 45%), pH (7.37 to 7.44), Pco2 (35 to 40 mm Hg), and peak inspiratory pressures (20 mm Hg) were constant. Pulmonary artery pressure (PPA), left atrial pressure (PLA), and circuit flow (QPA) were recorded continuously. PVR calculated as follows: PVR[(dynes x seconds x cm(-5)) x 1,000] = [(PPA-PLA/(QPA x 1,000/60)] x 1,332. The experimental animals were ventilated with normoxic gas (FIO2, 0.21), followed by hypoxic gas (FIO2, 0.07), returned to normoxia, and then divided into two groups of eight animals each. One group remained normoxemic (FIO2, 0.21; SPA02, 100%) while the other group was made hypoxemic by ventilation with hypoxic gas (FIO2, 0.07; SPA02, 50%). Endogenous NO was suppressed with L-arginine-N-omega methyl ester (L-NAME) at 40 mg/kg in both groups. Inhaled NO was given at 40 ppm in both groups. Analysis of variance for repeated measures was used to test for statistical significance. RESULTS: Baseline normoxic PVR (3,403 +/- 1,169) was increased significantly by hypoxia (6,524 +/- 1,018, P < .01) and was fully resorted to baseline by normoxia (3,497 +/- 1,079; P = NS). In normoxic animals, inhibition of endogenous NO production by L-NAME increased PVR to levels similar to those seen during hypoxic stress (6,345 +/- 1,441, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to normoxic baseline values (3,986 +/- 1,363, P = NS). In hypoxic animals, inhibition of endogenous NO production by L-NAME also increased PVR from hypoxic baseline (9,655 +/- 1,642, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to hypoxic baseline (6,450 +/- 1,796, P = NS). CONCLUSION: In this piglet model, endogenous NO is important in the regulation of pulmonary vascular tone during both normoxia and hypoxia. Inhaled NO completely reversed the elevations in PVR caused by inhibition of endogenous NO and may normalize PVR in diseases in which the production of endogenous NO is compromised.

Use of explanted human hearts as a model for the study of cardiac pathophysiologic conditions.

The purpose of this paper is to describe an isolated heart model that uses human hearts to study cardiomyopathy. Techniques of organ preparation and perfusion are described that result in successful restoration of explanted human hearts to a beating condition. Native hearts of transplant recipients were placed on an isolated perfusion circuit immediately after explant. After appropriate organ and circuit preparation these hearts were restored to a functional state. Studies were done to assess the stability over time and response to inotropic stimulation. Six of seven hearts were returned to a functional condition. Left ventricular pressure generation ranged from 56 to 118 mm Hg (mean 84.8 +/- 34.11) at physiologic loading conditions. Hearts remained functional from 67 to 271 minutes (mean 152 +/- 71.7) and retained up to 70% of functional capacity after 120 minutes. Hearts performed in isovolumic and ejecting modes. Hearts had a marked response to inotrope administration not previously described. We conclude that human hearts can be reproducibly restored to a functional condition after explant from transplant recipients and can be maintained in a beating state with reasonably stable pressure generation for an extended period of time, which makes this a useful model with which to study cardiac pathophysiologic conditions. These hearts demonstrate an appropriate response to inotropes not previously observed, most likely because of improved myocardial preservation and stringent control of perfusate chemical make-up.

Cholelithiasis in pediatric cardiac transplant patients on cyclosporine.

From June 1984 to June 1993, symptomatic chlolethiasis was observed in six (6.7%) of 90 cases of pediatric heart or heart-lung transplants at the author's institution. The incidence of cholelithiasis for all children under 16 years of age is estimated to be less than 1%. Previously, information on cholelithiasis in pediatric transplant patients on cyclosporine therapy had been limited. Studies concerning the incidence of gallstones in adult kidney and cardiac transplant patients have shown that there is an increase associated with cyclosporine, possibly related to elevated levels and hepatoxicity. Five patients underwent uneventful cholecystectomy. There was only one death, which occurred after emergency cholecysostomy tube placement for biliary sepsis. If indicated, biliary tract surgery can be performed safely in cardiac transplant patients. The authors report on their experience with symptomatic cholelithiasis in pediatric cardiac transplant patients and review the current literature on the hepatotoxic effects of cyclosporine.

CT of 338 active professional boxers.

Computed tomography (CT) was performed in 338 active professional boxers. CT scans were abnormal in 25 boxers (7%). The most common CT abnormality was brain atrophy (22 cases). Focal lesions of low attenuation consistent with posttraumatic encephalomalacia were noted in only three boxers. Boxers with abnormal CT scans did not differ from those with borderline or normal CT scans in regard to age, win-loss record, number of bouts, or history of an abnormal electroencephalogram. Thirty-seven boxers with borderline CT scans (49%) and 17 with abnormal CT scans (68%) reported a previous technical knockout (TKO) or knockout (KO), compared with only 89 (37%) of the 238 boxers with normal CT scans (P < .01). Brain atrophy was noted more frequently in boxers with a large cavum septum pellucidum (CSP) than in those with a small or no CSP (P < .05). Boxers with abnormal or borderline CT scans who experienced a TKO or KO were slightly older than those with normal CT scans and a history of a TKO or KO (P < .05).

Chlamydia trachomatis-induced production of interleukin-1 by human monocytes.

Human diseases caused by the intracellular bacterium Chlamydia trachomatis include genital tract infections and blinding trachoma. Chlamydial infections are characterized by chronic inflammation and scarring, and development of such complications is thought to be immunologically mediated. In this study, we show that coculture of C. trachomatis (serovar L2) with human blood monocytes induced the production of interleukin-1 (IL-1), an important mediator of inflammation, tissue remodeling, and scarring. IL-1 was produced in response to UV-inactivated elementary bodies containing from 0.1 to 50 micrograms of protein per ml, with a maximal response at 5 to 10 micrograms/ml. IL-1 activity was detected by 6 h of incubation and was maximal by 24 h. Peak levels were maintained throughout 96 h of incubation. Rabbit antibody to human IL-1(alpha + beta) effectively neutralized the thymocyte-stimulating activity of the supernatants. The apparent molecular weight of chlamydia-induced IL-1 was 16,000, as determined by gel filtration on a Bio-Gel P-60 column. Isoelectric focusing yielded two peaks of activity, with pIs of 5.5 and 6.9. Neutralization studies with antisera against human IL-1 alpha and IL-1 beta showed that the acidic and neutral peaks corresponded to IL-1 alpha and IL-1 beta, respectively, with IL-1 beta predominating. Heat-killed chlamydiae, which are not internalized by monocytes, were effective IL-1 inducers, indicating that phagocytosis was not required for IL-1 induction. Purified C. trachomatis lipopolysaccharide was also an effective IL-1 inducer, suggesting that the response to intact organisms may be largely a response to chlamydial lipopolysaccharide. Finally, purified chlamydial major outer membrane protein induced low but detectable IL-1 activity.