Editor's Choice - The National Norwegian Carotid Study: Time from Symptom Onset to Surgery is too Long, Resulting in Additional Neurological Events.

OBJECTIVE/BACKGROUND: The objective was to observe for 1 year all patients in Norway operated on for symptomatic carotid stenosis with respect to (i) the time from the index event to surgery and neurological events during this time; (ii) the level in the healthcare system causing delay of surgical treatment; and (iii) the possible relationship between peri-operative use of platelet inhibitors and neurological events while awaiting surgery. METHODS: This was a prospective national multicentre study of a consecutive series of symptomatic patients. Patients were eligible for inclusion when referred for surgery. An index event was defined as the neurological event prompting contact with the healthcare system. All 15 departments in Norway performing carotid endarterectomy (CEA) participated. RESULTS: Three hundred and seventy one patients were eligible for inclusion between 1 April 2014 and 31 March 2015, and 368 patients (99.2%) were included. Fifty-four percent of the patients contacted their general practitioner on the day of the index event. Primary healthcare referred 84.2% of the patients to hospital on the same day as examined. In hospital median time from admission to referral for vascular surgery was 3 days. Median time between referral to the operating unit and actual CEA was 5 days. Overall, 61.7% of the patients were operated on within 2 weeks of the index event. Twelve patients (3.3%) suffered a new neurological event while awaiting surgery. The percentage of patients on dual antiplatelet therapy was lower (25.0%) in this group than among the other patients (62.6%) (p = .008). The combined 30 day mortality and stroke rate was 3.8%. CONCLUSION: This national study with almost complete inclusion and follow-up shows that the delays occur mainly at patient level and in hospital. The delay is associated with new neurological events. Dual antiplatelet therapy is associated with reduced risk of having a new neurological event before surgery.

Prevention of retrosternal adhesions after pericardiotomy.

Because repeat sternotomies are becoming much more prevalent with repeat coronary bypass operations, prevention of direct adhesions of the heart and grafts to the back of the sternum by use of synthetic or xenograft material to close the pericardiotomy has become a matter for investigation. In this study bovine and equine glutaraldehyde-processed xenografts were implanted bilaterally in dogs for implant intervals of 6 weeks and 3, 6, 9, and 12 months. The bovine and equine xenografts both performed well in resisting the adhesion of the heart to their inner surfaces and less well in resisting adhesion of the lung and chest wall to their outer surfaces. The bovine xenograft had a higher percentage of adhesion-free surface on all the surfaces evaluated; however, one of our 12-month bovine pericardial xenograft implants exhibited significant multifocal calcific degeneration. Although pericardial xenografts generally have performed well when implanted in the dog, Gallo, Artiñano, and Duran recently expressed concern about their performance in humans. Along with our finding of calcification, their concern suggests a cautious approach to clinical application.

Healing basis and surgical techniques for complete revascularization of the left ventricle using only the internal mammary arteries.

Long-term follow-up data from several leading centers concerning patients undergoing coronary artery bypass clearly demonstrate the superiority of the internal mammary artery (IMA) with patency rates of 83 to 94% at 7 to 12 years compared with the saphenous vein and its patency rates of 41 to 53%. Our experimental studies provide a biological basis for understanding this difference. Thin-walled arterial autografts undergo no histological change after being implanted in the arterial system, while venous autografts undergo major changes with an initial scattered loss of endothelium and marked thickening due to a proliferative reaction. The challenge to the cardiac surgeon is to revascularize the entire left ventricle with the IMAs. We have found this possible in most patients with advanced three-vessel disease by using both IMAs either as in situ grafts or free grafts with as many sequential anastomoses as necessary to achieve full revascularization. Our use of the term in situ refers to the graft's origin from the subclavian artery as opposed to a free IMA graft arising from another site.

Carvedilol reduces ischaemic skeletal muscle necrosis.

Carvedilol is an alpha1 and nonselective beta-adrenergic receptor antagonist with antioxidative properties known to protect against reperfusion injury in the heart, brain, and kidneys. The aim of this study was to test the hypothesis that carvedilol improves postischaemic reperfusion and tissue survival in skeletal muscle. Sixteen Wistar rats underwent tourniquet ischaemia of the left hindlimb for 3 hours and 15 minutes at 27 degrees C. Single-fiber laser Doppler probes were inserted in the left and right anterior tibial muscles, and microvascular perfusion was measured until 2 hours after removal of the tourniquet. Perfusion indices for each 15-minute interval were calculated for the left hindlimb (tourniquet ischaemia) by dividing the postischaemic by the pre-ischaemic laser Doppler flowmetry values, and the geometrical areas under the curves representing a plot of perfusion index relative to time, measured in arbitrary units, were compared. Laser Doppler flowmetry values for the right anterior tibial muscle were compared. Tissue damage was measured by histomorphometry of necrotic areas and no-reflow zones in cross sections from the anterior tibial muscle 72 hours after ischaemia. Neutrophils were counted in the same sections. The treatment group received 1 mg carvedilol/kg body weight before ischaemia and 1 mg/kg immediately before removal of the tourniquets. The areas under the curves representing the plot of perfusion index relative to time were larger for the rats treated with carvedilol: 9.5 compared with 3.0 arbitrary units (p = 0.0003). Treatment did not change the laser Doppler flowmetry values for the right hindlimbs. The histomorphometric areas of necrosis in cross sections from the muscles were reduced from 88% (38-96%) in the control animals to 41% (7-85%) in those treated with carvedilol (p = 0.01), and the area of no-reflow was reduced from 20% (2-52%) to 0% (0-7%) (p = 0.006). The number of neutrophils did not differ between groups. The study supports the hypothesis that carvedilol improves early reperfusion and protects skeletal muscle subjected to 3 hours and 15 minutes of ischaemia.

Influence on healing in the canine thoracic aorta of three substances used to close the interstices of macroporous Dacron grafts.

The influence on healing of three materials for closure of interstices in a macroporous Dacron arterial prosthesis were evaluated by 56-day implantation in the canine descending thoracic aorta. The materials studied were: the nondenatured fibrin deposited as a result of a 4-step preclot with autogeneic blood (n = 6), heat-coagulated autogeneic blood deposited by autoclaving the blood-soaked prosthesis (n = 6), and cross-linked human albumin (n = 6). Healing of autogeneic fibrin was superior with little difference between the other two materials.

An experimental study of eight current arterial prostheses.

Eight currently used arterial prostheses with differing constructions and materials were implanted in the descending thoracic aorta of mongrel dogs. The prostheses were Gore-Tex (polytetrafluoroethylene), DeBakey Woven, Cooley Woven, Meadox Woven Double Velour, Cooley Knitted Double Velour, Microvel, Vasculour II, and Bionit II. Five series of these eight prostheses were serially implanted in heparinized subjects. During the 40 implantations, attention was focused on three major characteristics: preclotting efficiency, surgical handling characteristics, and healing. Gore-Tex is impervious to blood. The DeBakey and Cooley woven grafts are nearly so. The remaining prostheses required preclotting. The Meadox Woven Double Velour became impervious after two preclotting steps, the Cooley Knitted Double Velour and the Bionit II required three, and the Vasculour II and the Microvel required four. The surgical handling characteristics of the knitted prostheses clearly surpassed those of the DeBakey and Cooley woven and Gore-Tex prostheses. Although the Meadox Woven Double Velour prosthesis had better conformability than the nonveloured woven, the tendency of its cut edge to fray was more pronounced. Healing was much more advanced in the knitted and woven prostheses than in the Gore-Tex.

[Primary peritonitis in children]. / Primaer peritonitt hos barn.

Primary peritonitis occurs rarely in childhood. The causative microbe is usually either streptococcus or pneumococcus. However, the incidence of gram negative anaerobic bacteria is increasing. The bacteria are cultured from fluid taken from the abdominal cavity during celiotomy. The abdominal viscera are normal, which excludes secondary peritonitis. We discuss the case of an infant who presented this disease entity.

Protective effect of the endothelin antagonist Bosentan against ischemic skeletal muscle necrosis.

We tested the hypothesis that blocking of the endothelin system by Bosentan, a combined endothelin-A and -B receptor antagonist (Hoffmann La Roche, Basel, Switzerland), improves postischemic skeletal muscle reperfusion and reduces tissue damage. 16 Wistar rats were subjected to 3 h and 15 min hindlimb tourniquet ischemia at 27 degrees C. Perfusion was continuously measured with Laser Doppler Flowmetry (LDF) in the anterior tibial muscle during ischemia and the first 2 h of reperfusion. Perfusion indices were calculated for each 15 min, by dividing each LDF value by the preischemic LDF value of the leg. The areas under the perfusion index curves were compared. 72 h after ischemia, histomorphometry of necrosis and no-reflow zones, and counting of neutrophils were done in cross-sections of the muscles. The animals were randomized into two groups. The treatment group received an injection of Bosentan 15 mg/kg 10 min before ischemia, and this dose was repeated 5 min before reperfusion of the hindlimbs. The treatment group obtained an improved reperfusion (4.48 vs. 1.72, p = 0.02). The median cross-sectional area of necrosis was smaller in the treatment group, 70% vs. 93% (p = 0.02), while neither the areas of no-reflow nor the neutrophil counts in reperfused necrotic areas were different. This study supports the hypothesis that Bosentan seems to improve reperfusion and reduces postischemic skeletal muscle damage.

A new combination therapy for selective and prolonged antiplatelet effect: results in the dog.

This study characterizes the effect of dazmegrel, a thromboxane synthetase inhibitor, on platelet function in the dog and introduces its potential use in combination with aspirin therapy. Ex vivo testing of dazmegrel alone was performed with three dosages and three administration regimens. Platelet aggregation response, malondialdehyde formation and prostaglandin metabolites generation were evaluated. To maintain complete thromboxane A2 inhibition, dazmegrel had to be given 3 times per day at dosages of not less than 6 mg/kg. The same result was achieved with a single daily administration of combined dazmegrel and aspirin in equal dosages of 3 mg/kg. Dazmegrel, both alone and with aspirin, increased and sustained heightened levels of prostacyclin, unlike the simultaneous inhibition of both prostaglandin metabolites seen with aspirin therapy alone. Because the combination of dazmegrel and aspirin effectively blocks thromboxane A2 formation and also enhances prostacyclin formation, the synergistic action of these agents increases their combined antiplatelet effect to a level not attainable by either agent alone. The significance of this combined therapy warrants further experimental study and may soon merit clinical trial for the prevention of stroke and other major thrombotic complications.

The influence of denier and porosity on performance of a warp-knit Dacron arterial prosthesis.

The study objective was to determine the optimal water porosity for a warp-knit, externally veloured Dacron arterial prosthesis. Preclotting efficiency, surgical handling characteristics, thrombogenicity, and 56-day healing in the descending thoracic aorta of mongrel dogs were measured for seven different arterial prostheses of the same basic design constructed to test the influence of decreased porosity produced by increased yarn denier at a constant needle density. The six prototypes tested were 160, 180, 200, 220, 240, and 280 denier. The 140 denier prosthesis (Bionit, C. R. Bard, Inc., Billerica, MA) served as the control. The water porosity of these prostheses varied from 2036 ml/cm2/min at 120 mmHg for the control to 286 for the 280 prototype. The preclotting efficiency increased with decreased water porosity and with increased outer-wall filamentousness. Desirability of surgical handling characteristics decreased with lowered water porosity, while the degree of outer-wall filamentousness had little influence. All the prostheses showed excellent through-wall healing at 56 days, including endothelialization. The 160 prototype represented an optimal blend of high preclotting efficiency, desirable surgical handling characteristics, and excellent 56-day healing. These studies are pertinent to the future development of porous, warp-knit Dacron arterial prostheses.

A rapid in vitro test of the in vivo healing potential of vascular prostheses.

An in vitro method for comparing the penetration of bovine fibroblasts seeded on the external surface of porous vascular prostheses was devised. The effects of water porosity reduction and differing manufacturing constructions (warp-knit Dacron, woven Dacron and polytetrafluoroethylene) on the ability of the bovine fibroblasts to penetrate transmurally was investigated. Of the warp-knit external-veloured Dacron prostheses, the highest porosity 140-denier prototype had the highest luminal surface cell count and the lowest porosty 280-denier prototype the lowest luminal surface cell count. The intermediate prototypes had values between these two extremes. The woven Dacron prostheses, which were of even lower porosity but with a much thinner wall, had cell counts midway between the 140-denier and the 280-denier prototypes. The microporous polytetrafluoroethylene prostheses did not allow fibroblast penetration despite adherence of cells to the outer surface. These findings agree with in vivo healing studies of the same materials in the descending thoracic aorta of the dog, demonstrating that this rapid in vitro assay method can help predict the healing potential of a vascular prosthesis.

The effect of predetermined thrombotic potential of the recipient on small-caliber graft performance.

This study was designed to establish the influence of the recipient's thrombotic potential on the patency of small-caliber prostheses and to evaluate the subsequent improvement of graft performance by medicinally altering the prostaglandin balance in subjects predisposed to graft occlusion. Mongrel dogs were pretested and classified as low and high responders according to their thrombotic potential, measured as prostaglandin metabolite balance and platelet aggregability. High responders were randomly divided into two groups. Those assigned to serve as the medicated subjects were pretreated 1 week before surgery with a single oral daily administration of combined dazmegrel (UK-38,485) and aspirin in equal dosages of 3 mg/kg. Medication was continued throughout the experiment. Dacron grafts were implanted bilaterally in the carotid artery site in all subjects. Following a 3-week implantation period, the patency rate for the group with low thrombotic potential was 100%. In the animals with high thrombotic potential the patency rate was 10% for nonmedicated subjects and 100% for medicated subjects. These data support the concept that the thrombotic potential largely determines the capacity of the recipient's blood to thrombose small-caliber prostheses. Effective medicinal alteration of prostaglandin balance results in exceptionally increased patency of synthetic grafts.

A five- to seven-year experience with externally-supported Dacron prostheses in axillofemoral and femoropopliteal bypass.

We have examined the clinical results of 56 externally-supported (EXS) Dacron grafts in the axillofemoral position and 117 in the femoropopliteal position. Results have been analyzed from two perspectives: primary patency concerns only those grafts that had never occluded; extended patency refers to all open grafts including those whose continued patency is the result of thrombectomy. The 5-to 7-year life-table patency rates are: axillofemoral 8 mm and 6 mm bypass: primary 75% and extended 97%; above-knee femoropopliteal 6 mm bypass: primary 78% and extended 93%; below-knee 6 mm femoropopliteal bypass: primary 41% and extended 91%. In contrast, the results for the 5 mm grafts used for femoropopliteal bypass were inferior to the 6 mm grafts: femoropopliteal 5 mm bypasses had an above-knee primary patency rate of 44% and an extended rate of 55%, with a below-knee primary patency rate of 15% and an extended rate of 32%. Rendering the noncrimped porous Dacron prosthesis kink and compression resistant by an external support coil appears to increase its potential for successful use, especially in 8 mm axillofemoral and 6 mm femoropopliteal bypasses.