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Alan Dardik

Publications and source records attributed to Alan Dardik.

34 records · Page 2Linked to original sources
PubMed2004

Early results with infrainguinal cutting balloon angioplasty limits distal dissection.

Infrainguinal angioplasty has less initial and long-term success compared with more proximal sites. These suboptimal initial technical results may be related to the heavy calcific burden in the femoral and popliteal arteries and, subsequently, higher incidence of distal dissection. Cutting balloon angioplasty (CBA) is a newer technique that is thought to limit distal dissection in heavily calcified vessels; although CBA has been evaluated in the coronary circulation, there are few reports of its use in peripheral vessels. This study evaluates our initial experience with CBA for the management of femoropopliteal disease. Eleven patients underwent infrainguinal CBA for symptomatic limb ischemia at a community hospital. Ten procedures (91%) were technically successful, with no distal dissections, iatrogenic vessel perforations, or surgical target vessel revascularizations. In eight patients available for follow-up, the limb salvage rate was 100% and of seven and eight CBA sites (88%) were still widely patent (mean follow-up, 3 months; range, 2-12 months). This preliminary study suggests that CBA is safe and feasible for electively performed femoropopliteal chronic occlusive disease with acceptable success rates on short-term follow-up. Long-term results and comparison with other endovascular modalities require evaluation.

Aged↗
PubMed2004

Improved outcomes of carotid endarterectomy: the critical role of vascular surgeons.

Improved outcomes after carotid endarterectomy (CEA) have been related to preoperative, intraoperative, and postoperative patient and procedural variables. Outcomes after CEA have also been related to other factors that are not clearly related to the patient or the procedure, such as performance of the procedure in high volume hospitals, by high volume surgeons, and by surgeons specializing in vascular surgery. These overlapping surrogate markers of "quality" have been widely quoted and may be used by external parties to limit access to vascular care; however, these markers have unclear significance when examined systematically. Some of the confounding variables that preclude easy interpretation of these markers include interest of the surgeon in the care of vascular patients, surgical talent, surgical judgment, recognition of patients at higher risk for complications, and routine or selective use of adjunctive medications such as beta-blockers, statins, and anti-platelet agents. The practices of vascular surgeons with excellent outcomes after CEA need to be examined critically for these underlying factors that affect not only procedural results but also long-term stroke-free survival.

Aged↗
PubMed2004

Preoperative assessment and management to prevent complications during high-risk vascular surgery.

OBJECTIVE: Most patients requiring vascular surgical reconstruction are at high risk for major morbidity and mortality, with certain vascular procedures at particularly high risk for complications. Although numerous comorbid conditions are precisely the risk factors that determine outcome, we review particular factors for each surgery that may be optimized to alter outcome and minimize postoperative complications. DESIGN: Literature review. RESULTS: Certain aspects of care are common to all vascular surgery procedures, including thoracoabdominal aortic aneurysm repair, pararenal and ruptured abdominal aortic aneurysm repair, mesenteric and renal revascularization, and carotid endarterectomy. Some factors that are important include careful preoperative assessment and optimization of cardiac, pulmonary, and renal function and volume status. In addition, the use of experienced teams during and after the procedure, as well as clear and continuous communication between all surgical team members, may improve outcome. Particular attention to procedural details is also crucial to achieving excellent results. CONCLUSIONS: Patients needing vascular surgery often possess management challenges that increase the risk of perioperative complications. Meticulous attention to details during all phases of care, including preoperative optimization as well as intraoperative procedural conduct and communication, helps achieve optimal results and thus minimize the risk of complications.

Aneurysm↗
PubMed2003

Oscillatory shear stress increases smooth muscle cell proliferation and Akt phosphorylation.

PURPOSE: Hemodynamic forces affect smooth muscle cell (SMC) proliferation and migration both in vitro and in vivo. However, the effects of oscillatory shear stress (SS) on SMC proliferation and signal transduction pathways that control survival are not well described. METHODS: Bovine aortic SMC were exposed to arterial levels of oscillatory SS (14 dyne/cm(2)) with an orbital shaker; control cells were exposed to static conditions (0 dyne/cm(2)). Cell number and (3)[H]thymidine incorporation were measured after 1, 3, or 5 days of SS. Activation of the Akt pathway was assessed with the Western blot technique. Specificity of the phosphatidylinositol 3-kinase (PI3K) pathway was determined with the Western blot technique with the inhibitors LY294002 (10 micromol/L) or wortmannin (25 nmol/L). RESULTS: Arterial levels of oscillatory SS increased SMC cell number by 20.1 +/- 3.7% and (3)[H]thymidine incorporation by 33.4% +/- 6.8% at 5 days. To identify whether SS increased activity of the SMC survival pathway, Akt activation was measured. SMC exposed to SS demonstrated increased Akt phosphorylation compared with control cells, with maximal phosphorylation at 60 minutes. Both PI3K inhibitors specifically inhibited the increase in Akt phosphorylation in SMC exposed to oscillatory SS. CONCLUSION: SMC directly respond to oscillatory SS by increasing DNA synthesis, proliferation, and activation of the PI3K-Akt signal transduction pathway. These results suggest a mechanism of SMC survival and proliferation in response to endothelial-denuding arterial injury.

Animals↗
PubMed2003

Antisense basic fibroblast growth factor alters the time course of mitogen-activated protein kinase in arterialized vein graft remodeling.

PURPOSE: Neointimal hyperplasia (NIH) is complete by 3 weeks in rabbit vein grafts implanted into the arterial circulation. Activation of the mitogen-activated protein kinase (MAPK) family of protein kinases is thought to be critical in remodeling events such as cellular proliferation, differentiation, and migration, as found in NIH. We previously demonstrated that antisense basic fibroblast growth factor (ASbFGF) inhibited the synthesis of basic fibroblast growth factor (bFGF) in the balloon injury model of NIH. We examined the effect of ASbFGF on NIH and the time course of MAPK, extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal protein kinase (JNK), and p38 kinase activation in arterialized vein grafts. METHODS: Carotid interposition of a vein bypass graft was performed in 75 New Zealand White rabbits. Segments of the external jugular vein were transfected with a replication-deficient adenovirus containing the messenger RNA sequence for rat ASbFGF at 1 x 10(10) plaque-forming units per milliliter; control animals were given phosphate-buffered saline solution (PBS) alone. Rabbits were killed at 30 minutes, 4 days, 7 days, and 21 days (n = 8). Four grafts in each group were fixed with formalin and embedded in paraffin, then processed with elastin-collagen and hematoxylin-eosin stains. The other four grafts were individually frozen, and total protein was extracted. Phosphorylation of MAPK, ERK1/2, JNK, and p38, was determined with Western blot analysis and immunohistochemistry. Groups were compared with analysis of variance. RESULTS: The thickness of neointima in the PBS group and the ASbFGF group at 21 days was 60.2 +/- 2.1 and 39.4 +/- 2.1 microm, respectively (P <.01). In both the control and ASbFGF groups, all 3 MAPKs demonstrated activation compared with preimplantation levels. However, when compared with the PBS group the ASbFGF group showed greater than 33% inhibition of all three MAPKs by day 4 and day 7 (P <.05), but no significant difference in any MAPK activation by day 21 (P >.05, all groups). Cells staining positive for activated MAPK were found in the neointima and adventitia of vein grafts in both the PBS and ASbFGF groups. CONCLUSION: MAPKs are activated during the first week after vein graft implantation. Grafts treated with ASbFGF demonstrated reduced MAPK activation and less neointimal thickening. These results suggest that the process of vein graft adaptation to the arterial circulation, and subsequent NIH, may depend on basic fibroblast growth factor activity, which is mediated, at least in part, by a MAPK-dependent mechanism.

Animals↗
PubMed2003

Shear stress and cyclic strain may suppress apoptosis in endothelial cells by different pathways.

Endothelial cells (ECs) are exposed to hemodynamic forces such as shear stress (SS) and cyclic strain (CS) in vivo. Alterations in these forces may stimulate EC growth and intimal hyperplasia, possibly by promotion of cell survival through inhibition of apoptosis. The authors examined the effect of SS and CS on inhibition of apoptosis and phosphorylation of Akt and its downstream target Bad in bovine aortic ECs in vitro. Arterial levels of laminar SS (14 dyne/cm(2)) or CS (10%) suppressed apoptosis due to serum withdrawal in EC; this suppression due to SS or CS was completely inhibited by phosphatidylinositol 3'-kinase (PI3K) inhibition. Phosphorylation of Akt in EC exposed to SS or CS was time dependent but with maximal stimulation at 30 min (SS) or 5 min (CS); SS- or CS-induced Akt phosphorylation was inhibited in the presence of PI3K inhibition. SS-induced, but not CS-induced, phosphorylation of Bad was inhibited by PI3K inhibition. These results suggest that hemodynamic forces suppress apoptosis in ECs via phosphorylation of Akt and that SS and CS differentially activate the downstream phosphorylation of Bad, possibly by stimulating an alternate pathway. This suggests an additional mechanism by which hemodynamic forces can differentially regulate transcription in ECs, and thereby possibly maintain the viability of normal endothelium.

Animals↗
PubMed2002

Transcription factor Sp1 phosphorylation induced by shear stress inhibits membrane type 1-matrix metalloproteinase expression in endothelium.

Membrane type 1-matrix metalloproteinase (MT1-MMP) plays a key role in endothelial cell migration, matrix remodeling, and angiogenesis. Previous studies demonstrated that a mechanical force, cyclic strain, increases MT1-MMP expression by displacing Sp1 with increased Egr-1 expression and binding to the promoter site. However, the effect of shear stress (SS) on MT1-MMP expression is poorly understood. Although Egr-1 mRNA transcription and protein was induced (7.6-fold) in response to SS (n = 5, 0-8 h, p < 0.05), SS decreased MT1-MMP mRNA transcription and protein levels in a time-dependent fashion (10, 50, and 90% reduction at 1, 4, and 8 h, respectively; n = 5, p < 0.05). Egr-1 protein was increased after SS and cyclic strain, but Sp1 was serine-phosphorylated only after SS. SS increased Sp1 DNA binding (3.8-, 5.8-, and 2.4-fold increase at 1, 4, and 8 h, respectively; n = 5, p < 0.05) that was inhibitable by calf intestinal phosphatase. Thus, SS inhibits MT1-MMP expression despite Egr-1 up-regulation by inducing the serine phosphorylation of Sp1, which in turn increases its binding affinity for its site on the MT1-MMP promoter, reducing the ability of Egr-1 to displace it. These data illustrate the complex control of microvascular endothelial cell MT1-MMP expression in response to distinct environmental stimuli (cyclic strain versus shear stress), consisting of both the modulation of specific transcription factor expression (Egr-1) as well as transcription factor post-translational modification (serine phosphorylation of Sp1).

Animals↗
PubMed2002

Cells in focus: endothelial cell.

The endothelial cell is thought to arise from the splanchnopleuric mesoderm. Endothelial cells form the inner lining of a blood vessel and provides an anticoagulant barrier between the vessel wall and blood. In addition to its role as a selective permeability barrier, the endothelial cell is a unique multifunctional cell with critical basal and inducible metabolic and synthetic functions. The endothelial cell reacts with physical and chemical stimuli within the circulation and regulates hemostasis, vasomotor tone, and immune and inflammatory responses. In addition, the endothelial cell is pivotal in angiogenesis and vasculogenesis. Endothelial cell injury, activation or dysfunction is a hallmark of many pathologic states including atherosclerosis, loss of semi-permeable membrane function, and thrombosis. Cell facts: (1) Endothelium consists of approximately (1-6) x 10(13) endothelial cells forming an almost 1 kg organ. (2) They uniquely contain Weibel-Palade bodies, 0.1 microm wide, 3 microm long membrane-bound structures that represent the storage organelle for von Willebrand factor (vWF). (3) The endothelial cell is not only a permeability barrier but also a multifunctional paracrine and endocrine organ. It is involved in the immune response, coagulation, growth regulation, production of extracellular matrix components, and is a modulator of blood flow and blood vessel tone.

Animals↗
PubMed2002

Subdural hematoma after thoracoabdominal aortic aneurysm repair: an underreported complication of spinal fluid drainage?

OBJECTIVE: Cerebrospinal fluid (CSF) drainage is a commonly used adjunct to thoracoabdominal aortic aneurysm (TAAA) repair that improves perioperative spinal cord perfusion and thereby decreases the incidence of paraplegia. To date, little data exist on possible complications, such as subdural hematoma caused by stretching and tearing of dural veins, should CSF drainage be excessive. We reviewed our experience with patients in whom postoperative subdural hematomas were detected. METHODS: The records of 230 patients who underwent TAAA repair at the Johns Hopkins Hospital between January 1992 and February 2001 were reviewed. RESULTS: Eight patients had subdural hematomas (3.5%). The four men and four women had a mean age of 60.6 years; two of these patients had a connective tissue disorder. All patients had lumbar drains placed before surgery, including one patient who underwent an emergency operation for rupture. Drains were set to allow drainage for CSF pressure greater than 5 cm H(2)O in all but one patient set for 10 cm H(2)O; spinal cooling was not performed in any patient. All drains were removed on the third postoperative day. In patients in whom subdural hematomas developed, the mean amount of CSF removed after surgery was 690 +/- 79 mL, which was significantly greater than the amount drained from patients in whom subdural hematomas did not develop (359 +/- 24 mL; P =.0013, Mann-Whitney U test). Six patients had postoperative subdural hematomas detected during hospitalization (mean postoperative day, 9.3; range, 2 to 16), and two patients were seen in delayed fashion after discharge from the hospital at 1.5 and 5 months. Four patients died of the subdural hematoma (50%); only one of these patients had neurosurgical intervention. All four survivors responded to neurosurgical intervention and are neurologically healthy. Two patients, both of whom were seen in delayed fashion, needed a lumbar blood patch. Multivariate logistic regression identified the volume of CSF drained as the only variable predictive of occurrence of subdural hematoma (P =.01). CONCLUSION: Subdural hematoma is an unusual and potentially catastrophic complication after TAAA repair. Prompt recognition and neurosurgical intervention is necessary for survival and recovery after acute presentation. Epidural placement of a blood patch is recommended if a chronic subdural hematoma is detected. Care should be taken to ensure that excessive CSF is not drained perioperatively, and higher (10 cm H(2)O) lumbar drain popoff pressures may be necessary together with meticulous monitoring of patient position and neurologic status.

Adult↗
PubMed2002

Durability of thoracoabdominal aortic aneurysm repair in patients with connective tissue disorders.

OBJECTIVE: Thoracoabdominal aortic aneurysm (TAAA) repair is a durable procedure performed with reasonable perioperative mortality and morbidity in patients with atherosclerotic aortic disease. However, the long-term outcome and durability of TAAA repair performed in patients with a connective tissue disorder (CTD) is not well known. METHODS: The records of 257 patients who underwent TAAA repair at the Johns Hopkins Hospital between January 1992 and December 2001 were reviewed. Survival analysis was performed with Kaplan-Meier analysis, and subgroups were compared with the log-rank test. Multivariable analysis was performed with the Cox proportional hazards model and logistic regression. RESULTS: Patients with CTD (n = 31) were seen earlier (mean age, 48.6 +/- 2.9 years) than patients without CTD (mean age, 69.1 +/- 0.6 years; P <.0001, Mann-Whitney U test) and had a greater incidence rate of aortic dissection (52% versus 19%; P <.0001, chi(2) test) and extent I or II aneurysm (77% versus 64%; P =.04). The perioperative (30-day) mortality rate was 6.5% in patients with CTD, which was similar to the rest of the cohort (P =.39, Fisher exact test). The incidence rate of paraparesis/paraplegia was 12.9%/6.5% in patients with CTD, and CTD was the only factor predictive of paraparesis (P =.03; odds ratio, 9.3; logistic regression). The cumulative survival rate among the entire cohort was 53.4% +/- 4.4% at 5 years (Kaplan-Meier), and no difference was seen among patients with or without CTD (P =.16, log-rank test) or among different Crawford extents (P =.29). Of the two late (>6 months) deaths in patients with CTD, none were from aortic rupture or dissection, compared with two of 31 late deaths in patients without CTD. Multivariable analysis confirmed that postoperative renal failure (P =.03) predicted mortality but neither CTD (P =.93), nor Crawford extent (P =.21, Cox regression) predicted mortality. Among survivors, no mean difference was found in largest aortic diameter on follow-up imaging in patients with or without CTD (4.7 +/- 0.3 cm versus 4.4 +/- 0.3 cm; P =.47, Mann-Whitney U test). The cumulative graft patency rate, representing long-term graft stability and with death, rupture, dissection, or recurrent aneurysm as endpoints, was 47.5% +/- 4.6% at 5 years (Kaplan-Meier) and was similar in patients with or without CTD (P =.10, log-rank test). CONCLUSION: TAAA repair appears to be a durable operation, with a reasonable 5-year patient survival rate and a low risk of postoperative paraplegia or additional aortic events. Patients with CTD can expect their outcome, including long-term survival and aortic stability, to be similar to patients without CTD.

Aged↗
PubMedDate not supplied

A contemporary assessment of carotid body tumor surgery.

Carotid body tumor resection remains a surgical challenge traditionally associated with a 15-30% incidence of cranial nerve injury. The authors reviewed their experience with carotid body tumor surgery to determine whether contemporary awareness of carotid body tumors is leading to earlier detection and operation, resulting in a lower incidence of postoperative cranial nerve injury. Twenty-seven carotid body tumors were resected in 25 patients between 1990 and 2000. No patient died and no patient had postoperative baroreflex failure syndrome. There was 1 stroke (4%) in a patient who required ligation of the internal carotid artery. There were 9 cranial nerve injuries (33%), most commonly to the vagus or hypoglossal nerves, which was not significantly different from the rate of cranial nerve injury (44%) in the 9 patients operated upon between 1984 and 1989 (p=0.37, Fisher's exact test). Multivariate analysis demonstrated that tumor size was the only significant factor predicting cranial nerve injury (p=0.045, logistic regression). Since carotid body tumors with large size or higher Shamblin grades had predictably high operative blood loss and rates of postoperative cranial nerve injury, a high index of suspicion and aggressive surgical management may lead to earlier detection and operation on smaller tumors, ultimately reducing the risk of nerve injury. Nevertheless, carotid body tumor surgery appears to be relatively free of mortality and major morbidity in contemporary practice.

Adult↗
PubMedDate not supplied

Arterial wall shear stress: observations from the bench to the bedside.

Shear stress is the tangential force of the flowing blood on the endothelial surface of the blood vessel. Shear is described mathematically or ideal fluids, and in vitro models have enabled researchers to describe the effects of shear on endothelial cells. High shear stress, as found in laminar flow, promotes endothelial cell survival and quiescence, alignment in the direction of flow, and secretion of substances that promote vasodilation and anticoagulation. Low shear stress, or changing shear stress direction as found in turbulent flow, promotes endothelial proliferation and apoptosis, shape change, and secretion of substances that promote vasoconstriction, coagulation, and platelet aggregation. The precise pathways by which endothelial cells sense shear stress to promote their quiescent or activated pathways are currently unknown. Clinical applications include increasing shear stress via creation of an arteriovenous fistula or vein cuff to promote bypass graft flow and patency. Since an abnormal level of shear stress is implicated in the pathogenesis of atherosclerosis, neointimal hyperplasia, and aneurysmal disease, additional research to understand the effects of shear stress on the blood vessel may provide insight to prevent vascular disease.

Animals↗
PubMedDate not supplied

Do vascular surgeons improve the outcome of carotid endarterectomy? An analysis of 12,618 elective cases in the state of Connecticut.

Because cardiac complications may predict long-term survival after carotid endarterectomy (CEA), this study evaluates contemporary outcome, including cardiac complications, after CEA. Patients in Connecticut hospitals undergoing CEA between 1991 and 2002 were identified using the state discharge database (Chime, Inc.; ). Of the 12,618 CEAs performed, there were 53 (0.4%) deaths, 155 (1.2%) neurologic complications, and 300 (2.4%) cardiac complications. Despite an increase in patient age (p < .0001, Kruskal-Wallis test) over time, there were decreases in mortality (p = .0001, chi-square), postoperative stroke (p = .001), and cardiac complications (p = .0003). Vascular surgeons performed a minority of the procedures in the state (11%), but there were fewer cardiac complications after CEA performed by vascular surgeons than general surgeons (0.8% vs 3.0%; p < .0001). Multivariable logistic regression demonstrated that the risk of a cardiac complication was elevated in patients operated on by a nonvascular surgeon, patients with previous heart disease or stroke, and the elderly. In a state with very high performance of CEA by general and nonvascular surgeons, postoperative mortality and neurologic complications remain low. However, there were fewer cardiac complications when a vascular surgeon performed the procedure. These results suggest that increased referral to vascular surgeons could improve procedural safety.

Age Factors↗
PubMedDate not supplied

Adjunctive pharmacologic use in carotid endarterectomy: a review.

Although carotid endarterectomy (CEA) is now widely accepted as the surgical therapy for carotid stenosis, the role of and indications and evidence for many pharmacologic agents that are used adjunctively in the perioperative setting have not been conclusively established. Aspirin (acetylsalicylic acid) is the pharmaceutical agent that has been studied most extensively in conjunction with CEA; other than aspirin and dextran, the use of many agents before, during, and after CEA has not been standardized. Prospective randomized trials are still needed to demonstrate efficacy, predict outcome, and determine the optimal use of these medications in their adjunctive use during CEA to improve patient care and obtain optimal surgical outcomes.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Emerging vascular applications of magnetic resonance imaging: a picture is worth more than a thousand words.

Vascular applications of magnetic resonance (MR) imaging are reviewed, with emphasis on algorithms that use nonpictorial information contained in the MR data set. Current clinical vascular practice generally limits use of MR angiography and three-dimensional vessel images to qualitative pictorial rendering without routinely using the available quantitative information contained within the MR data. This review is dedicated to recent advances that include characterization of vessel histology, assessment of carotid plaque vulnerability, characterization of blood flow dynamics, quantitative analysis of disease severity, and prediction of vascular intervention outcome. Examples from histologic preparation, in vitro and in vivo experiments, are discussed, with an emphasis on potential clinical applications and advances in acquisition technology.

Algorithms↗