Does Increasing Packing Density Using Larger Caliber Coils Improve Angiographic Results of Embolization of Intracranial Aneurysms at 1 Year: A Randomized Trial.

BACKGROUND AND PURPOSE: The impact of increased aneurysm packing density on angiographic outcomes has not been studied in a randomized trial. We sought to determine the potential for larger caliber coils to achieve higher packing densities and to improve the angiographic results of embolization of intracranial aneurysms at 1 year. MATERIALS AND METHODS: Does Embolization with Larger Coils Lead to Better Treatment of Aneurysms (DELTA) was an investigator-initiated multicenter prospective, parallel, randomized, controlled clinical trial. Patients had 4- to 12-mm unruptured aneurysms. Treatment allocation to either 15- (experimental) or 10-caliber coils (control group) was randomized 1:1 using a Web-based platform. The primary efficacy outcome was a major recurrence or a residual aneurysm at follow-up angiography at 12 ± 2 months adjudicated by an independent core lab blinded to the treatment allocation. Secondary outcomes included indices of treatment success and standard safety outcomes. Recruitment of 564 patients was judged necessary to show a decrease in poor outcomes from 33% to 20% with 15-caliber coils. RESULTS: Funding was interrupted and the trial was stopped after 210 patients were recruited between November 2013 and June 2017. On an intent-to-treat analysis, the primary outcome was reached in 37 patients allocated to 15-caliber coils and 36 patients allocated to 10-caliber coils (OR = 0.931; 95% CI, 0.528-1.644; P = .885). Safety and other clinical outcomes were similar. The 15-caliber coil group had a higher mean packing density (37.0% versus 26.9%, P = .0001). Packing density had no effect on the primary outcome when adjusted for initial angiographic results (OR = 1.001; 95% CI, 0.981-1.022; P = .879). CONCLUSIONS: Coiling of aneurysms randomized to 15-caliber coils achieved higher packing densities compared with 10-caliber coils, but this had no impact on the angiographic outcomes at 1 year, which were primarily driven by aneurysm size and initial angiographic results.

Palliation of obstructing gastric carcinoma with metal stents through a gastrostomy.

Gastric cancer is the world's second most common malignancy. In the U.S., patients present with advanced disease, and surgery with curative intent accounts for only 30% of gastric malignancies. Palliative surgery has significant morbidity and mortality. Recently, there have been encouraging reports of self-expanding endoprostheses in obstructing gastrointestinal neoplasms. We report a case of a 70-yr-old woman with inoperable outlet stenosis secondary to a mucinous infiltrating adenocarcinoma involving nearly the entire stomach, except the anterior wall, which provided a percutaneous access site for gastrostomy and subsequently successful management of outlet obstruction with metallic stents.

Fasciotomy in vascular trauma: is it too much, too often?

Fasciotomy has been used as a prophylactic measure against development of compartment syndrome and as a treatment modality when the syndrome has developed in patients suffering vascular trauma. The hospital records of 36 patients who underwent surgical repair of their traumatic vascular injuries were reviewed. All 36 patients had at least one indication for fasciotomy at the time of repair; i.e., ischemic time of more than 6 hours or combined arterial and venous injury. Prophylactic fasciotomies were performed in 18 of the patients at the time of vascular repair; 18 did not have fasciotomies performed at the time of initial repair. The decision to perform a fasciotomy was made by the operating surgeon based on well-defined criteria. Hospital stay was significantly longer for the fasciotomy group. Four of the fasciotomy-related complications were infective in nature. Only one patient who did not undergo fasciotomy at the time of original repair developed a compartment syndrome during the postoperative period. Selective fasciotomy based on well-defined criteria instead of serial physical examinations or measurement of compartment pressures will effectively save limbs; there is an increased hospital stay.

Venous insufficiency: a late sequelae of four-compartment fasciotomy in the lower extremity?

Four-compartment fasciotomies used to relieve abnormally high compartment pressures necessitate interruption of the ensheathing fascial membrane. In the calf, this is considered an important component in maintaining a viable musculovenous pump and preventing venous hypertension, a leading cause of venous insufficiency. Through postoperative physical examination and photoplethysmography evaluation of 47 patients who underwent this procedure, no indication exists that division of the fascial component leads to calf pump dysfunction and chronic venous insufficiency. Of the patients studied, 92 per cent had unchanged musculovenous pump function upon photoplethysmography reevaluation at 19 weeks compared with the initial values recorded 6 weeks postoperatively; 6 per cent had improved venous flow, while only one of the 47 (2%) had venous recovery measurements consistent with diminished venous flow.

Comparative effects of endothelin (ET-1) and U46619 on human saphenous vein and gastroepiploic artery, sources of human autologous grafts.

The effects of endothelin (ET-1) on smooth muscle contractile activity were investigated and compared in human saphenous vein and gastroepiploic artery, vessels frequently used in revascularization procedures. ET-1 contracted saphenous vein and gastroepiploic artery in a concentration-dependent manner. The peptide produced a greater maximal effect in the vein than in the artery and, in both preparations, ET-1 was less efficacious than U46619, an agent which mimics the actions of thromboxane A2 at the thromboxane A2/prostaglandin H2 receptor. The contractile response to ET-1 declined spontaneously at a more rapid rate in the artery than in the vein. The present data indicate that ET-1 has significant contractile activity in both vessels which are used for coronary arterial bypass surgery and suggest that although, a weaker vasoconstrictor than U46619, the peptide could induce vasospasm in both graft vessels.

Differential recovery of prostacyclin and endothelium-derived relaxing factor after vascular injury.

Differential recovery of prostacyclin and endothelium-derived relaxing factor after vascular injury. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H1449-H1457, 1992. The recovery of prostacyclin (prostaglandin I2, PGI2) synthesis and endothelium-derived relaxing factor (EDRF) activity, as demonstrated by acetylcholine (ACh)-induced relaxation, by rabbit aorta was examined up to 8 wk after balloon catheter-induced injury. Following injury, basal 6-keto-PGF1 alpha formation was decreased acutely; however, after 3 wk it was not different from control. Arachidonic acid-stimulated 6-keto-PGF1 alpha formation was decreased, returning to control levels at 3 and 8 wk for thoracic and abdominal aorta, respectively. ACh-induced relaxation did not return to control levels over the 8-wk study. Initiation of reendothelialization with a layer of hyperplastic endothelial cells overlying subendothelial fibrosis and intimal hyperplasia were present at 2-3 wk. Intimal hyperplasia appeared 2 wk after injury and progressed throughout the period of the study. These data indicate that following balloon catheter-induced injury the formation of both PGI2 and EDRF is reduced and that recovery follows a differential time course. In addition, the recovery of PGI2 formation did not coincide with the attenuation of intimal hyperplasia, whereas the relationship between EDRF formation and intimal hyperplasia is uncertain.

Actions of SQ 29,548 on contractile responses and arachidonic acid metabolism of intrapulmonary arteries, in vitro.

This study was undertaken to investigate the influence of SQ 29,548, a thromboxane (TX) A2 receptor antagonist, on contractile responses and arachidonic acid (AA) metabolism of bovine intrapulmonary arterial (IPA) rings. The contractile responses to 5-hydroxytryptamine (5-HT), histamine, phenylephrine, and potassium chloride (KC1) were not significantly altered by 10(-8) M SQ 29,548 in either endothelium-intact or denuded IPA. The concentration of SQ 29,548 was chosen as it reduced the response to 10(-7) M U46619, a TXA2 mimetic, by 50%. AA metabolism by IPA produced more PGI2 whereas that by intrapulmonary vein (IPV) produced more PGE2. SQ 29,548 in concentrations of 10(-8) to 10(-5) M did not affect the activity of PGI2 synthase or GSH-dependent PGE2 isomerase in IPA or IPV microsomal fractions. No microsomal TXA2 synthase activity was detectable. SQ 29,548 had no effect on PGH synthase activity of IPA or IPV. The data indicate the presence of a TXA2-mediated contractile response in the IPA which is endothelium-independent and is selectively antagonized by SQ 29,548. The data further indicate that the contractile responses of IPA to 5-HT, histamine, phenylephrine, and KCl do not have a TXA2-mediated component. It is suggested that SQ 29,548 is a pharmacological probe to determine the role of TXA2 n pathophysiologic states in the pulmonary vascular bed and may be a therapeutic agent to treat pulmonary hypertensive disorders in which TXA2 is involved.

Sulotroban selectively inhibits thromboxane-receptor-mediated responses in the peripheral vascular bed of the cat.

The effects of Sulotroban (BM 13.177, SK&F 95587) were investigated under conditions of controlled blood flow in the hindquarters and mesenteric vascular beds of the cat. Injections of the thromboxane (TX) A2 mimics, U46619 and U44069, caused dose-related increases in perfusion pressure. After administration of SK&F 95587, vasoconstrictor responses to the TXA2 mimics were reduced significantly, and the dose-response curves were shifted to the right in a parallel fashion. Responses to norepinephrine, phenylephrine, tyramine, endothelin-1, angiotensin II, BAY K8644, acetylcholine, sodium nitroprusside, isoproterenol, lemakalim, prostaglandin (PG) E1, and PGF2 alpha, agents which alter vascular resistance by a variety of mechanisms, were not changed by the TXA2 receptor antagonist. However, SK&F 95587 reduced mesenteric vasoconstrictor responses to PGD2. Results of the present study indicate that SK&F 95587 blocks TX-receptor-mediated responses in the hindquarters circulation of the cat in a competitive and selective manner and reduces mesenteric vascular responses to the TXA2 mimics, as well as PGD2. These data suggest that this antagonist would be useful in studies on the role of TXA2 in physiologic and pathophysiologic processes in the systemic vascular bed of the cat.

Analysis of pulmonary and systemic vascular responses to cromakalim, an activator of K+ATP channels.

Cardiovascular and pulmonary responses to cromakalim, a member of a novel class of antihypertensive agents that open ATP-sensitive K+ (K+ATP) channels, were investigated in the anesthetized cat. Intravenous injections of cromakalim in doses of 30-300 micrograms/kg decreased arterial pressure (AP), pulmonary arterial pressure (PAP), and increased cardiac output (CO), while producing small changes in right and left atrial pressures. Pulmonary and systemic vascular resistances were decreased and vasodilator responses to cromakalim were blocked by glybenclamide, a K+ATP channel-blocking agent. The low dose of cromakalim caused a reflex increase in heart rate (HR) and right ventricular contractile force (RVCF), whereas the high dose decreased HR and RVCF. Under constant-flow conditions the K+ATP channel opener caused dose-dependent decreases in hindquarters perfusion pressure, and when tone was elevated in the pulmonary vascular bed, dose-dependent decreases in pulmonary lobar arterial perfusion pressure. Hindquarters and pulmonary lobar vasodilator responses to cromakalim were inhibited in a specific manner by glybenclamide. The present data show that cromakalim has significant vasodilator activity in both the systemic and pulmonary vascular beds and suggest that responses to this agent result from activation of glybenclamide-sensitive K+ATP channels. These data show that cromakalim can cause substantial decreases in systemic and pulmonary vascular resistance in a dose that has little effect on RVCF.

Influence of vasoactive intestinal contractor on the feline pulmonary vascular bed.

Pulmonary vascular responses to vasoactive intestinal contractor (VIC) (endothelin-B) were investigated in the feline pulmonary vascular bed under constant and natural flow conditions. Injection of VIC, 0.3 nmol/kg i.v., increased pulmonary arterial and left atrial pressures and cardiac output and caused a biphasic change in pulmonary vascular resistance. VIC and endothelin-1 (ET-1) caused a similar pattern of response and under constant flow conditions, VIC increased lobar arterial pressure in a dose-related manner and was similar in potency and duration of action to ET-1. The thromboxane mimic, U46619, was far more potent than VIC, and a monocyclic ET-analog had no activity in the pulmonary vascular bed. The present data show that VIC has significant vasoconstrictor activity in the pulmonary vascular bed of the cat.

Comparative responses to endothelin-2 and sarafotoxin 6b in the pulmonary vascular bed of the cat.

Pulmonary vascular responses to endothelin-2 and sarafotoxin 6b were investigated in the feline pulmonary vascular bed under natural flow and constant flow conditions. Injections of endothelin-2 and sarafotoxin 6b in a dose of 0.3 nmol/kg iv increased pulmonary arterial and left atrial pressures and cardiac output, and caused a biphasic change in calculated pulmonary vascular resistance. Endothelin-2 caused a biphasic change in systemic arterial pressure, while sarafotoxin 6b only decreased arterial pressure. Under constant flow conditions in the intact-chest cat, injections of endothelin-2 and sarafotoxin 6b in doses of 0.1-1 nmol into the perfused lobar artery increased lobar arterial pressure in a dose-related manner but were less potent than the thromboxane A2 mimic, U46619. An ET analog with only the Cys1-Cys15 disulfide bond and an amidated carboxy terminus had no significant activity in the pulmonary vascular bed. The present data show that endothelin-2 and sarafotoxin 6b have significant vasoconstrictor activity in the pulmonary vascular bed of the cat.