Cerebral intolerance during flow arrested carotid angioplasty.

INTRODUCTION: The use of flow arrest as a means of providing cerebral protection during carotid angioplasty offers the advantages of improved efficiency of debris removal and the ability to provide protection under unfavorable (tortuous) anatomic circumstances. However, in contrast to the filtration methods of cerebral protection, this modality requires complete interruption of antegrade carotid artery flow during balloon angioplasty and stent deployment. METHODS: We report our experience with 9 patients undergoing carotid angioplasty with the Mo.Ma device, which utilizes common and external carotid artery balloon occlusion during the angioplasty procedure. We assessed the clinical outcomes and intraprocedural hemodynamic data. RESULTS: The average duration of carotid occlusion was 8.3 minutes. Of the 9 patients, 2 patients (22%) experienced cerebral intolerance. No stroke occurred in this patient cohort. There appeared to be a poor relationship between procedure intolerance and the presence of significant contralateral stenosis or low carotid back pressure. Furthermore, the incidence of postangioplasty hypotension was not clearly related to cerebral intolerance. CONCLUSION: Carotid angioplasty with stenting can be safely conducted with flow arrest as an alternative to filter-type cerebral protection devices. However, because cerebral intolerance is not an infrequent occurrence with this approach, clinicians must be cognizant of management strategies for transient cerebral intolerance.

Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

OBJECTIVES: Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). METHODS: This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. RESULTS: The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P < .05). However, no significant differences in perioperative outcomes in terms of overall length of stay, myocardial infarction, acute renal failure, wound infections, or mortality were noted between obese and nonobese patients underoing open AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). CONCLUSIONS: The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.

Crossing an ultracritical carotid stenosis for carotid angioplasty.

Carotid angioplasty requires early placement of a cerebral protection device in an effort to minimize cerebral embolization during the conduct of the subsequent angioplasty and stenting procedure. In patients who exhibit a very critical internal carotid artery (ICA) stenosis (approximately 99%), initial passage of the lesion may not be possible with a standard 0.014-inch wire system. In this report, the authors describe an approach using a 0.012-inch hydrophilic system to overcome this technical obstacle.

Predictors of clinically significant postprocedural hypotension after carotid endarterectomy and carotid angioplasty with stenting.

OBJECTIVES: Significant hypotension after carotid endarterectomy (CEA) and carotid angioplasty with stenting (CAS) has been correlated with adverse outcomes. The objective of this study was to determine risk factors that predict hypotension after patients undergo CEA and CAS. METHODS: The review included 1474 CEA patients and 157 CAS patients who underwent procedures from 2002 to 2008. Specific patient characteristics, such as comorbid diseases, degree of carotid stenosis, presence of neurologic symptoms, and preprocedure medications, were assessed. Also reviewed were specific postprocedural clinical outcomes, including hypotension requiring pressors, myocardial infarction, stroke, death, and hospital length of stay. RESULTS: The incidence of clinically significant hypotension was 12.6% in CEA patients and 35% in CAS patients (P < .001). Clinically significant hypotension was correlated with increased postprocedural myocardial infarction (2.1% vs 0.5%, P = .022), increased mortality (2.1% vs 0.1%, P < .001), and length of stay >2 days (46.3% vs 27.4%, P = .01). Hypotension was not associated with increased postprocedural strokes (0.8% vs 0.6%, P = .75) or recurrent neurologic symptoms (0.4% vs 0.3%, P = .55). Preoperative nitrate use predicted a greater incidence of postprocedural hypotension (P = .043). A history of tobacco use was correlated with postprocedure hypotension (P = .033). Preprocedural strokes, the use of calcium channel blockers, beta-blockers, angiotensin-converting enzyme inhibitors, prior myocardial infarction, degree of preprocedural carotid stenosis, type of stent, previous ipsilateral and contralateral interventions, and female gender did not correlate with postprocedural hypotension (P >.05). CONCLUSIONS: Postprocedural hypotension occurs more commonly with CAS than CEA and is associated with increased postprocedural myocardial infarction and length of stay, and death. Nitrates and tobacco use predict a higher incidence of postprocedural hypotension. High-risk patients should be aggressively managed to prevent the increased morbidity and mortality due to postprocedural hypotension.

No gender influences on clinical outcomes or durability of repair following carotid angioplasty with stenting and carotid endarterectomy.

INTRODUCTION: To determine if gender influences clinical outcomes and durability of repair after carotid angioplasty with stenting (CAS) or carotid endarterectomy (CEA), an analysis of patient records was performed. METHODS: This study included 89 CAS patients (47 men and 42 women) and 93 CEA patients (53 men and 40 women). Patients underwent duplex scans 6, 12, 24 months post procedure. The outcomes of periprocedural mortality, major adverse events, strokes, and myocardial infarctions were assessed. Incidence of critical restenosis and recurrence of symptoms was also assessed. RESULTS: No significant differences were noted between men and women who had undergone either CAS or CEA (P > .05) for clinical outcomes and durability of repair. No differences for periprocedural mortality, major adverse events, critical restenosis, recurrent neurologic symptoms, and adverse event free survival were found. CONCLUSIONS: These results do not indicate substantial gender influences on clinical outcomes or durability of repair following CAS and CEA.

Follow-up results of carotid angioplasty with stenting as assessed by duplex ultrasound surveillance.

BACKGROUND: Carotid artery stenting (CAS) has become an alternative modality to carotid endarterectomy (CEA) for the treatment of carotid occlusive disease. We report a retrospective review of our institution's experience with CAS versus CEA. METHODS: Postprocedure surveillance duplex, recurrent symptoms, postprocedure strokes, progression of lesions, and rates of re-operation were analyzed in 46 patients who underwent CAS and 48 patients who underwent CEA. The mean length of follow-up evaluation was 13 months. All CAS procedures included neuroprotection devices. RESULTS: Statistically significant differences in progression to critical restenosis (2% vs 2%, P = 1.0), rate of subsequent symptoms or stroke (2% vs 10%, P = .1), or rate of re-interventions were not observed between CAS and CEA groups (2% vs 4%, P = .98). Total mortality (0% vs 2%, P = .33), and the occurrence of major adverse events (2% vs 10%, P = .18) also were not significantly different in the CAS compared with the CEA patients. The average rate of increase in internal carotid velocity at 6 to 12 months (-1% vs 1.1%, P = NS) and 12 to 24 months (-5% vs -6.5%, P = NS) also were equivalent. CONCLUSIONS: Our observed results indicate that CAS may be performed with comparable clinical outcomes and durability of repair comparable with CEA.

Clinical outcomes and cost comparison of carotid artery angioplasty with stenting versus carotid endarterectomy.

BACKGROUND: Recently, carotid angioplasty with stenting (CAS) has evolved as an alternative to carotid endarterectomy (CEA) for the treatment of carotid occlusive disease. Some concerns have arisen regarding the high cost of stents and neuroprotection devices, which may inflate the overall procedural costs relative to CEA. We report here a review and analysis contrasting the clinical outcomes and associated hospital costs incurred for patients treated with either CAS or CEA. METHODS: Ninety-four consecutive patients with surgically amenable carotid stenosis were offered CAS or CEA. Forty-six patients elected CAS, and 48 patients underwent CEA. CAS was performed with the Smart Precise or Acculink stents, and all procedures included neuroprotection (Filter Wire or Accunet). CEA was performed with patients under general anesthesia with routine shunting and with Dacron or bovine pericardium patches. Clinical outcomes such as perioperative mortality, major adverse events (myocardial infarction, stroke, and death), length of stay, and the incidence of hemodynamic instability were analyzed. Total costs, indirect costs, and direct procedural costs associated with hospitalization were also reviewed. RESULTS: CAS was associated with a shorter length of stay compared with CEA (1.2 vs 2.1 days; P = .02). Differences in perioperative mortality (0% vs 2%; P = NS), major adverse events (2% vs 10%; P = .36), strokes (2% vs 4%; P = NS), myocardial infarctions (0% vs 4%; P = .49), and hypotension necessitating pressor support (21% vs 18%; P = NS) were not statistically significant. By using cost to charge ratio methodology according to the Medicare report, CAS was associated with higher total procedural costs (US dollars 17,402 vs US dollars 12,112; P = .029) and direct costs (US dollars 10,522 vs US dollars 7227; P = .017). The differences in indirect costs were not significant (US dollars 6879 vs US dollars 4885; P = .063). CONCLUSIONS: CAS with neuroprotection was associated with clinical outcomes equivalent to those with CEA but had higher total hospital costs. These higher costs reflect the addition of expensive devices that have improved the technical success and the clinical outcomes associated with CAS.

Carotid angioplasty for the management of extracranial carotid occlusive disease.

INTRODUCTION: Carotid endarterectomy (CEA) has become established as the preferred approach to the management of critical carotid stenosis. Carotid angioplasty with stenting (CAS) has recently arisen as an alternative in the treatment of carotid occlusive disease. This report describes our experience with carotid angioplasty applied to an unselected patient population suffering from high-grade carotid occlusive disease. METHODS: All patients suffering from carotid stenosis (> 50% symptomatic or > 80% asymptomatic) were offered CAS or CEA. The first 39 patients who underwent attempted CAS over this last year are reported here. CAS was performed with the SMART PRECISE or ACCULINK stents. All procedures were performed with cerebral protection. RESULTS: The planned procedure success rate was 97% and the major adverse event (MAE) rate was 2.6% in 38 patients who underwent successful CAS. This included a minor stroke and a subendocardial myocardial infarction in the same individual. Both events were attributed to sustained postprocedural hypotension probably induced by increased carotid sinus activity. CONCLUSION: CAS can be accomplished with a MAE rate comparable to CEA and will likely become the dominant alternative to CEA for the management of carotid stenosis. In the setting of equivalent morbidity, it appears likely that a nonsurgical option will be preferred by patients.

Carotid artery angioplasty with stenting and postprocedure hypotension.

INTRODUCTION: Although carotid endarterectomy (CEA) has become established as the preferred approach to the management of critical carotid stenosis, carotid angioplasty with stenting (CAS) has arisen as a competitive modality. We report here a nonindustry-supported experience using CAS in a nonselected patient population suffering from critical carotid stenosis. METHODS: All patients suffering from carotid stenosis (>50% symptomatic or >80% asymptomatic) were offered CAS or CEA. The first 36 patients who underwent attempted CAS over this last year are reported here. CAS was performed with the SMART PRECISE (Cordis, Inc, Miami Lakes, FL) or ACCULINK (Guidant, Inc, St Paul, MN) stents. All procedures were performed with cerebral protection. RESULTS: The planned procedure success rate was 97%, and the major adverse event (MAE) rate was 3.0% in 35 patients who underwent successful CAS. This included a minor stroke and a subendocardial myocardial infarction in the same individual. Both events were attributed to sustained postprocedure hypotension. The most frequent intraprocedure complications observed were bradycardia and hypotension. Persistent postprocedure hypotension requiring vasopressor support complicated 23% of cases. The average duration of vasopressor support in this group was 21 hours. CONCLUSION: CAS can be accomplished with an MAE comparable to CEA and will likely become the dominant alternative to CEA for the management of carotid stenosis. Management of periprocedural cardiovascular instability represents one of the most important elements in the safe conduct of CAS.

Influence of enteral and parenteral nutrition on splanchnic hemodynamics in septic patients.

BACKGROUND: Enteral nutrition is believed to augment splanchnic perfusion, thereby preserving splanchnic integrity, whereas parenteral nutrition does not offer this benefit. In an effort to study this, we compared splanchnic oxygen exchange and blood flow in critically ill, septic patients to normal controls during enteral or total parenteral nutrition. METHODS: Splanchnic oxygen exchange and hepatic blood flow characteristics in 14 critically ill, septic patients were compared to 19 normal controls while fasting and during nutrient administration. Nutrients were delivered as intraduodenal feedings or parenteral nutrition. Splanchnic hemodynamics were measured at baseline, 90 min, and 210 min during nutrient administration. Hepatic blood flow index (HBFI) by indocyanine green dye (ICG) clearance, splanchnic oxygen consumption index (SplVO(2)I), and hepatic venous oxygen saturation (ShvO(2)) were measured using hepatic venous catheterization. Plasma volume (PV) was measured from the volume of ICG distribution. Results were analyzed using population means (+/-SD) and one-way analysis of variance. RESULTS: There was no statistical change in HBFI, SplVO(2)I, PV or ShvO(2) over the study time interval within any group (p < 0.05), irrespective of whether enteral or parenteral nutrition was the nutrient source. Septic patients, whether fasting or receiving nutrition, demonstrated higher HBFI and SplVO(2)I levels, whereas ShvO(2) levels were uniformly lower throughout the study compared to normal controls. CONCLUSIONS: Critically ill patients exhibited a hyperdynamic splanchnic state as indicated by the marked increase in HBFI and SplVO(2)I. However, neither nutrient regimen at clinically relevant rates altered splanchnic hemodynamics over the course of study. Thus, enteral nutrients do not appear to offer hemodynamic protection to the splanchnic system in critically ill patients.

Suppression of cytochrome P450 3A protein levels by proteasome inhibitors.

We have previously reported that CYP3A cross-links with polyubiquitinated proteins in microsomes from nicardipine-treated rats in a process that is distinct from classical polyubiquitination. To further examine the role of the proteasome in CYP3A degradation, we investigated the effects of proteasome inhibitors lactacystin, MG132, proteasome inhibitor 1, and hemin in primary cultures of rat and human hepatocytes. With the exception of hemin, these agents increased the total pool of ubiquitinated proteins in microsomes isolated from rat hepatocytes, indicating that lactacystin, MG132, and proteasome inhibitor 1 effectively inhibited the proteasome in these cells. All four agents caused a reduction in the amount of the major approximately 55-kDa CYP3A band, opposite to what would be expected if the ubiquitin-proteasome pathway degraded CYP3A. Only hemin treatment caused an increase in high molecular mass (HMM) CYP3A bands. Because hemin treatment did not alter levels of ubiquitin in CYP3A immunoprecipitates, the HMM CYP3A bands formed in response to hemin treatment clearly were not due to proteasome inhibition. Rather, because hemin treatment also caused an increase in HMM CYP3A in the detergent-insoluble fraction of the 10,000g pellet, the HMM CYP3A seems to represent a large protein complex that is unlikely to primarily represent ubiquitination.

Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytes.

The effects of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin on the contents of cytochrome p450 mRNAs were examined in primary cultures of human hepatocytes prepared from three different livers. Treatment of 2- to 3-day-old human hepatocyte cultures with 3 x 10(-5) M lovastatin, simvastatin, fluvastatin, or atorvastatin for 24 h increased the amounts of CYP2B6 and CYP3A mRNA by an average of 3.8- to 9.2-fold and 24- to 36-fold, respectively. In contrast, pravastatin treatment had no effect on the mRNA level of either CYP2B6 or CYP3A, although treatment with pravastatin did produce the expected compensatory increase in HMG-CoA reductase mRNA content, indicating effective inhibition of cholesterol biosynthesis. Although treatment with the active (+), but not the inactive (-), enantiomer of atorvastatin increased the amount of HMG-CoA reductase mRNA, treatment with each enantiomer significantly induced both CYP2B6 and CYP3A mRNA levels. Treatment of primary cultured rat hepatocytes with the atorvastatin enantiomers effectively increased the amount of CYP3A mRNA, but had no effect on CYP2B or CYP4A mRNA levels, in contrast to fluvastatin, which increased both. Findings for p450 proteins by Western blotting were consistent with the mRNA results. These findings indicate that the ability of a drug to inhibit HMG-CoA reductase activity does not predict its ability to produce p450 induction in primary cultured human hepatocytes, and demonstrate that some, but not all, of the effects of these drugs that occur in primary cultured rat hepatocytes are conserved in human hepatocyte cultures.

Effects of dexamethasone on aryl (SULT1A1)- and hydroxysteroid (SULT2A1)-sulfotransferase gene expression in primary cultured human hepatocytes.

To determine whether the dexamethasone (DEX)-inducible hepatic sulfotransferase gene expression that has been described in the rat is conserved in humans, the effects of DEX treatment on hydroxysteroid sulfotransferase (SULT2A1) and aryl sulfotransferase (SULT1A1) gene expression were investigated in primary cultured human hepatocytes. Hepatocytes were prepared from nontransplantable human livers by collagenase perfusion of the left hepatic lobe, and cultured in Williams' medium E that was supplemented with 0.25 U/ml insulin. As reported in the rat, DEX treatment produced concentration-dependent increases in SULT2A1 mRNA and protein expression, with maximum increases observed at concentrations of DEX that would be expected to activate the pregnane X receptor (PXR) transcription factor. In contrast to the rat, in which DEX-inducible SULT1A1 expression has been demonstrated, SULT1A1 expression in primary cultured human hepatocytes was not measurably increased by DEX. In transient transfections conducted in primary cultured rat hepatocytes, the PXR ligands DEX and pregnenolone-16 alpha-carbonitrile significantly induced transcription of human and rat SULT2A reporter gene constructs. Cotransfection of either the human or rat SULT2A reporter gene with a PXR dominant negative construct significantly reduced DEX-inducible transcription. These results underscore that while certain features of rat hepatic sulfotransferase gene regulation are conserved in humans, important differences exist across species. The findings also implicate a role for the PXR transcription factor in DEX-inducible rat and human SULT2A gene expression.