Management of spontaneous coronary artery dissection complicated by cardiogenic shock using mechanical circulatory support with the Impella device.

OBJECTIVE: The aim is to evaluate the feasibility of using mechanical circulatory support, specifically the Impella device, in spontaneous coronary artery dissection (SCAD) patients with cardiogenic shock. BACKGROUND: The therapeutic options for managing SCAD complicated by cardiogenic shock are limited. Risky revascularization procedures are often necessary. METHODS: This was a multicenter case series in the United States. Approximately 20 cases of Impella implantation in patients with SCAD are known. The implanting physician for each of these cases was contacted and de-identified records were requested. The records were analyzed for Impella indications, outcomes, and complications. RESULTS: Records from four cases were received. All patients survived to hospital discharge and no major complications were observed. In two cases, cardiogenic shock developed in the absence of ongoing ischemia, suggesting a Takotsubo-like cardiomyopathy. In these cases, the Impella provided hemodynamic support until the patient's cardiac function recovered. CONCLUSION: Although a small case series, given the scarcity of SCAD cases complicated by cardiogenic shock and the limited therapies available to treat these patients, these data are of clinical value in highlighting the feasibility of Impella use in SCAD. The Impella can be valuable for procedural support and in cardiogenic shock, especially in cases without evidence of ongoing ischemia.

Celiac artery stent placement for coronary ischemia.

INTRODUCTION: The use of endovascular technology for mesenteric interventions has become an increasingly accepted treatment modality. We present an unusual case of celiac artery stent placement for coronary ischemia. CASE DESCRIPTION: A 66-year-old male with a history most notable for coronary artery disease and coronary artery bypass grafting (CABG) x 3 utilizing left internal mammary artery to left anterior descending, radial artery to first diagonal and his right gastroepiploic artery (GEA) to posterior descending artery presented with chest pain. His work-up included a cardiac catheterization that revealed a 90% stenosis at the origin of the celiac axis. A subsequent computerized tomography angiogram confirmed this and noted moderate stenosis of his superior mesenteric artery (SMA) as well as severe inferior mesenteric artery (IMA) stenosis. The patient was taken for mesenteric angiography by vascular surgery at which time he underwent balloon-expandable stent placement in the celiac axis. The patient tolerated this procedure well and was noted to have an improvement in his symptoms postoperatively. DISCUSSION: Use of arterial conduits for CABG have proven to be superior to vein. Long-term viability of the GEA as a conduit is dependent in part on the patency of mesenteric circulation. Our findings demonstrate a viable endovascular treatment option for angina pectoris secondary to mesenteric stenosis in this unique patient population.

Endovascular repair of carotid artery pseudoaneurysm after carotid endarterectomy with self-expanding covered stents-a long-term follow-up.

A 66-year-old Caucasian man with type 2 diabetes mellitus, peptic ulcer disease, peripheral vascular disease, and a 70% symptomatic carotid stenosis underwent a successful carotid endarterectomy with intraoperative shunting and Dacron patch closure in October 2000. Three months later, he developed a pseudoaneurysm at the site of the surgical repair. This was successfully treated with endovascular covered stents and has continued to remain patent at 9-year follow-up. Carotid artery pseudoaneurysms are secondary to trauma, infection, or previous surgery. Open surgical repair has been the treatment of choice for these pseudoaneurysms. However, open repairs are difficult and carry a high morbidity. Thus, endovascular therapy is a valid treatment for carotid artery pseudoaneurysm. Reviewing the published data, this is the first case report with successful endovascular covered stent placement for a carotid pseudoaneurysm with 9-year follow-up.

Early loss of thrombomodulin expression impairs vein graft thromboresistance: implications for vein graft failure.

Thrombosis is the major cause of early vein graft failure. Our aim was to determine whether alterations in the expression of the anticoagulant proteins, thrombomodulin (TM) and the endothelial cell protein C receptor (EPCR), impair endothelial thromboresistance that may contribute to vein graft failure. Immunohistochemical staining of autologous rabbit vein graft sections revealed that the expression of TM, but not EPCR, was reduced significantly early after graft implantation. Western blot analysis revealed that TM expression was reduced by >95% during the first 2 weeks after implantation, with gradual but incomplete recovery by 42 days. This resulted in up to a 95% reduction in the capacity of the grafts to activate protein C and was associated with an increase in bound thrombin activity, which peaked on day 7 at 28.7 +/- 3.8 mU/cm(2) and remained elevated for more than 14 days. Restoration of TM expression using adenovirus vector-mediated gene transfer significantly enhanced the capacity of grafts to activate protein C and reduced bound thrombin activity on day 7 to levels comparable to that of normal veins (5.7 +/- 0.4 versus 5.2 +/- 1.1 mU/cm(2), respectively, P=0.74). Surprisingly, neointima formation was not affected by this inhibition of local thrombin activity. These data suggest that the early loss of TM expression significantly impairs vein graft thromboresistance and results in enhanced local thrombin generation. Although enhanced local thrombin generation may predispose to early vein graft failure due to thrombosis, it does not seem to contribute significantly to late vein graft failure due to neointimal hyperplasia.

Estrogen-induced mu-opioid receptor internalization in the medial preoptic nucleus is mediated via neuropeptide Y-Y1 receptor activation in the arcuate nucleus of female rats.

The endogenous peptides beta-endorphin (beta-END) and neuropeptide Y (NPY) have been implicated in regulating sexual receptivity. Both beta-END and NPY systems are activated by estrogen and inhibit female sexual receptivity. The initial estrogen-induced sexual nonreceptivity is correlated with the activation and internalization of mu-opioid receptors (MORs), in the medial preoptic nucleus (MPN). Progesterone reverses the estrogen-induced activation/internalization of MOR and induces the sexual receptive behavior lordosis. To determine whether NPY and endogenous opioids interact, we tested the hypothesis that estrogen-induced MOR activation is mediated through NPY-Y1 receptor (Y1R) activation. Retrograde tract tracing demonstrated Y1Ron beta-END neurons that projected to the MPN. Sex steroid modulation of MOR in the MPN acts through NPY and the Y1R. Estradiol administration or intracerebroventricular injection of NPY activated/internalized Y1R in the arcuate nucleus and MOR in the MPN of ovariectomized (OVX) rats. Moreover, the selective Y1R agonist [Leu31, Pro34]-Neuropeptide Y (LPNY) internalized MOR in the MPN of OVX rats. The Y1R antagonist (Cys31, Nva34)-Neuropeptide Y (27-36)2 prevented estrogen-induced Y1R and MOR activation/internalization. NPY reversed the progesterone blockade of estradiol-induced Y1R and MOR internalization in the arcuate nucleus and MPN, respectively. Behaviorally, LPNY inhibited estrogen plus progesterone-induced lordosis, and the MOR-selective antagonist D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr amide reversed LPNY-induced inhibition of lordosis. These results suggest that a sequential sex steroid activation of NPY and MOR circuits regulates sexual receptivity.

Long-term follow up and prognostic factors for cryotherapy of malignant liver tumors.

BACKGROUND: The aims of this study were to determine the long-term outcomes of cryotherapy in patients with hepatic malignancies and to describe prognostic factors that may affect survival. METHODS: Ninety-eight patients (56 colorectal metastases, 28 noncolorectal metastases, 14 hepatocellular carcinomas) undergoing hepatic cryosurgery were identified in a retrospective review from January 1994 to December 2002. RESULTS: Overall survival rates at 1-, 2-, 3-, and 5- years were 81%, 62%, 48%, and 28%, respectively(median survival, 33 months) compared to a hepatic recurrence-free survival of 76%, 42%, 24%, and 16%, respectively (median hepatic recurrence-free survival, 20 months). Median follow-up was 54 months. Three hundred lesions were cryoablated; the recurrence per cryolesion was 5%. Major complications were the lone factor that significantly reduced overall (P=.0005) and hepatic recurrence-free survival (P=.0005). The number of lesions (TNL) and total estimated area (TEA) cryoablated did not significantly affect overall or hepatic recurrence-free survival. Additionally, outcomes depending on tumor type were not significantly different. CONCLUSIONS: Cryotherapy is an important option for a wide range of unresectable malignant hepatic tumors and provides the potential for long-term survival. Patients with major complications at the time of cryotherapy suffer a decreased overall and hepatic recurrence-free survival.

The extent of cryosurgery increases the complication rate after hepatic cryoablation.

Although there have been many reports on the use of cryosurgery to ablate hepatic malignancies none have specifically examined the relationship of complication rates to the extent of cryoablation. A retrospective review from January 1997 to May 2002 identified 98 patients treated with hepatic cryotherapy. The extent of the cryosurgery was determined by the total number of lesions (TNL) and total estimated area (TEA) of the lesions from preoperative evaluation by CT scan and intraoperative evaluation by ultrasound. The major complication rate was 11 per cent. The 30-day mortality was 0 per cent, but the late procedure-related mortality was 2 per cent. Increasing the extent of cryotherapy measured by intraoperative ultrasound demonstrated significant increases in the complication rate and length of stay (LOS). With cryoablation of TEA > or = 30 cm2 there was a significant increase in the overall complication rate (56% vs 23%; P = 0.003) and LOS (8.8 +/- 6.9 vs 6.1 +/- 4.2; P = 0.022) compared with TEA < 30 cm2. Performance of concurrent procedures also led to a significant increase in complications (69% vs 29%; P = 0.010) and LOS (8.6 +/- 6.8 vs 6.0 +/- 4.0; P = 0.019). Multivariate analysis, however, showed intraoperative TEA > or = 30 cm2 to be the most significant independent predictor of increased complications and prolonged LOS.

Prognostic determinants in duodenal injuries.

A retrospective review of 222 consecutive patients with duodenal injuries admitted to an urban Level 1 Trauma Center who subsequently underwent laparotomy during the period July 1980 to April 2002 was performed in an effort to elucidate factors associated with mortality, infectious morbidity, and length of stay in these patients. Predictably, the patients were predominantly male (92.7%) and young (mean age, 31.6 years). The overall mortality rate was 22.5 per cent, with a mortality rate of 18 per cent seen in the first 48 hours. Penetrating trauma was suffered by 88.3 per cent of the patients. Multivariate analysis revealed the performance of a thoracotomy, initial emergency department (ED) systolic blood pressure (SBP) <90 mm Hg, final operating room (OR) core body temperature less than 35 degrees C, and presence of a splenic injury to be the most important predictors of mortality (all P < 0.05). Mortality in the patients undergoing a resuscitative thoracotomy was 88.9 per cent versus 13.3 per cent in those patients not requiring thoracotomy. An initial SBP in the ED <90 was associated with a 46 per cent mortality rate, as compared with 4 per cent in those patients not in shock. A final OR core body temperature of less than 35 degrees C led to a 60 per cent mortality rate versus 8.3 per cent for warmer patients. Patients with a concomitant splenic injury were noted to have a 62.5 per cent mortality rate; those without had a 19.4 per cent mortality rate. The mean length of stay among survivors greater than 48 hours was 16.0 +/- 24.7 days. Univariate analyses revealed lowest OR core body temperature below 35 degrees C, initial OR SBP <90, presence of infection, >5 transfusions, initial ED SBP <90, final OR core temperature <35 degrees C, colon injury, spleen injury, and an injury severity score (ISS) >25 all to be significantly associated with increased length of stay. Multivariate analysis revealed an initial operating room blood pressure of less than 90 mm Hg systolic, the presence of an infection, and greater than 5 blood transfusions to be the factors most significantly correlated with increased length of stay (all P < 0.02). Of 182 patients surviving 48 hours, 98 (54%) developed an infection. Fifty-seven (31%) patients were noted to have wound-related infections, 92 (51%) patients had nosocomial infections, and 50 (27%) patients had both types. The presence of an abdominal arterial injury, an ISS >25, pancreatic injury, and lowest OR core body temperature <35 degrees C were the factors identified on multivariate analysis most significantly correlated with infectious morbidity (all P < 0.05). This data suggests that early efforts to prevent shock and rapidly control bleeding are the most likely efforts to reduce mortality rates in these patients. Those patients with duodenal injury presenting in shock or requiring a thoracotomy for resuscitation did poorly. Splenic injury was the associated injury found on multivariate analysis to be most closely associated with increased mortality. Early control of bleeding and the prevention of infection provide the most significant opportunity for decreasing length of stay. Infections are common with duodenal injuries, and aggressive surveillance should especially be performed in those patients with an abdominal arterial injury, an ISS >25, pancreatic injury, or lowest OR core body temperature <35 degrees C.

Open repair and endovascular covered stent placement in the management of bilateral axillary artery aneurysms.

A 72-year-old male with chronic obstructive pulmonary disease and hyperlipidemia presented with acute right upper limb ischemia. Arterial occlusion was found to be secondary to a thrombosed axillary artery aneurysm. An open repair was performed with a polytetrafluoroethylene (PTFE) graft. On further workup, the patient was found to have an asymptomatic axillary artery aneurysm on the left-hand side. Endovascular repair with a covered stent was chosen to treat this aneurysm.

Takayasu's arteritis presenting as uveitis in a 5-year-old girl.

A 5-year-old patient presented with uveitis as initial manifestation of Takayasu's arteritis. Our patient is unique not only in the initial presentation but also in the extent of arteritis in the aortic arch and great vessels. This is only the second case reported in the literature with this unusual presentation.

Effects of cilostazol on human venous smooth muscle.

In this study, we evaluated the effect of therapeutic doses of cilostazol on human venous smooth muscle. Saphenous vein rings (two to four per patient sample) were suspended in tissue baths for isometric tension recordings. At the beginning of the experiment, optimal tension for isometric contraction was achieved for each ring in a stepwise fashion in the presence of norepinephrine (10(-2) M). Norepinepherine was then added cumulatively in half-molar increments and isometric tension developed by the rings was measured, thereby obtaining a dose-response curve. Following washout and reequilibration, the rings were precontracted with a 30-50% submaximal dose of norepinepherine determined from the dose-response curve and allowed to contract until a stable plateau was reached. Cilostazol was then added in a cumulative manner (680-2,720 microg/L), and the tension generated was recorded. A total of 76 venous rings were tested, and all relaxed in the presence of cilostazol. The amount of relaxation increased as the concentration of cilostazol increased. Relaxation of 15 +/- 1.9% (mean +/- SEM) at low cilostazol doses (680 microg/L) to 37+/-3% at high cilostazol doses (2,720 microg/L) was demonstrated. A second finding of this study was demonstrated when the patient samples were divided according to the presence or absence of risk factors for arteriosclerosis. The specific risk factors examined included diabetes mellitus, smoking, hypercholesterolemia, and hypertension. The presence or absence of hypertension (n = 52) or hypercholesterolemia (n = 18) did not affect the amount of relaxation of the venous rings. Smokers (n = 46) had less relaxation 16 +/- 2.4% (680 microg/L) to 41 +/- 3.6% (2,720 microg/L) compared to nonsmokers (n = 53) who relaxed 22 +/- 3.5% (680 microg/L) to 48 +/- 5.7% (2720 microg/L). This did not reach statistical significance at any concentration cilostazol (p = 0.11-0.18). Diabetics (n = 53) did have statistically significantly less relaxation at every concentration of cilostazol compared to nondiabetics (n = 11, p < 0.05). All venous rings relaxed in the presence of cilostazol. Veins of nondiabetics relaxed statistically significantly more than those of diabetics. Smokers had less relaxation than non-smokers, but this was not statistically significant. We are the first to demonstrate that human venous smooth muscle cells undergo relaxation when exposed to therapeutic concentrations of cilostazol.

Regulation of endothelial thrombomodulin expression by inflammatory cytokines is mediated by activation of nuclear factor-kappa B.

Inflammation and thrombosis are increasingly recognized as interrelated biologic processes. Endothelial cell expression of thrombomodulin (TM), a key component of the anticoagulant protein C pathway, is potently inhibited by inflammatory cytokines. Because the mechanism underlying this effect is largely unknown, we investigated a potential role for the inflammatory transcription factor nuclear factor-kappa B (NF-kappaB). Blocking NF-kappaB activation effectively prevented cytokine-induced down-regulation of TM, both in vitro and in a mouse model of tumor necrosis factor-alpha (TNF-alpha)-mediated lung injury. Although the TM promoter lacks a classic NF-kappaB consensus site, it does contain tandem Ets transcription factor binding sites previously shown to be important for both constitutive TM gene expression and cytokine-induced repression. Using electrophoretic mobility shift assay and chromatin immunoprecipitation, we found that multiple Ets species bind to the TNF-alpha response element within the TM promoter. Although cytokine exposure did not alter Ets factor binding, it did reduce binding of p300, a coactivator required by Ets for full transcriptional activity. Overexpression of p300 also prevented TM repression by cytokines. We conclude that NF-kappaB is a critical mediator of TM repression by cytokines. Further evidence suggests a mechanism involving competition by NF-kappaB for limited pools of the transcriptional coactivator p300 necessary for TM gene expression.

Intravenous valproate sodium in the treatment of daily headache.

BACKGROUND: Treatment of chronic daily headache/transformed migraine is challenging, especially when it is complicated by overuse of analgesics, triptans, or both. One common approach involves the use of repetitive intravenous dihydroergotamine. We investigated the use of intravenous valproate sodium in the treatment of chronic daily headache/transformed migraine in patients who had contraindications to the use of or had failed treatment with dihydroergotamine. METHODS: We administered intravenous valproate sodium (Depacon) to patients with chronic daily headache/transformed migraine (loading dose 15 mg/kg, followed by 5 mg/kg every 8 hours). All analgesics and triptans were discontinued prior to treatment with divalproex sodium, and preventative medications for migraine were begun or continued. All patients received instruction in behavioral modification and the proper use of analgesics and triptans. RESULTS: Improvement in headache was reported by 80% of the patients treated, and valproate sodium was tolerated well by most. CONCLUSION: Intravenous valproate sodium may be of assistance in the initial management of patients with chronic daily headache/transformed migraine and analgesic/triptan overuse, especially when dihydroergotamine is ineffective or contraindicated.

Augmentation of wound healing with translation initiation factor eIF4E mRNA.

BACKGROUND: Initiation of translation is the rate-limiting step in protein synthesis; eIF4E increases translational efficiency by facilitating ribosome scanning. eIF4E is present in cells in rate-limiting amounts; chronic overexpression of eIF4E causes cell transformation by upregulating growth-related proteins. Biolistic delivery of epidermal growth factor (EGF) increases wound healing; transiently increasing wound eIF4E levels with biolistic mRNA transmission may further augment wound healing without oncogenesis. PATIENTS AND METHODS: Midline fascial wounds were created in rats and biolistically treated with gold particles carrying mRNA encoding for hEGF with or without eIF4E prior to suture closure; control animals received blank bullets. The animals were sacrificed at 7 or 14 days for determination of peak wound bursting strength on a tensiometer. Results are expressed as means +/- standard deviation; statistics were via analysis of variance. RESULTS: [Table: see text]. CONCLUSIONS: Simultaneous biolistic delivery of EGF mRNA with eIF4E mRNA significantly increases wound breaking strength compared to that in control animals or treatment with EGF mRNA alone without risk of cellular transformation. Further studies of translational activation to augment wound healing are warranted.