Background— Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis. Methods and Results— Fifteen male New Zealand White rabbits (weight, ≈3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell’s viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as “hot spots” after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology. Conclusions— We demonstrate the feasibility of in vivo “molecular” MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke.

Dye-like applications of antibiotics to silk produce infection-resistant materials for potential use in biomedical applications. Two antibiotics, doxycycline (doxy) and cipro floxacin (cipro), are applied under a variety of conditions to silk and to silk that has previously been hydrolyzed at 40°C for 20, 40, and 60 minutes. FTIR spectroscopic analyses indicate that the drastically increased sorption of antibiotics by hydrolyzed silk is attributable to both chemical and conformational changes that occur with the hydrolysis. The high sorption of doxy by hydrolyzed silk does not necessarily yield a more infection- resistant material, as determined by a zone of inhibition test. Conversely, the same hydrolysis considerably increases both the sorption of cipro and the zone of inhibition of cipro-treated silk dyed at 65 and 85°C.

Two antibiotics, doxycycline (Doxy) and ciprofloxacin (Cipro), were applied under a variety of conditions to wool and to hydrolyzed wool at 40degreesC. Nylon was used as a synthetic control. Sorption of Doxy was much higher in wool than in nylon, whereas sorption of Cipro was similar in both fibers. FTIR spectroscopy confirmed that a drastic increase in sorption of antibiotics by hydrolyzed wool was attributed to an increase in polar functional groups by peptide scission and in oxidized sulfur groups by cystine oxidation. Both sorption and zone of inhibition (ZOI) values were improved by hydrolysis of wool. Wool hydrolyzed for 20 or 40 min at 40degreesC and dyed with Doxy at 45degreesC for 3.5 h maintained around 30 mm of ZOI after 24 h of challenge by a simulated flow of blood. Wool hydrolyzed for 60 min at 40degreesC and dyed with Cipro at 45degreesC for 3.5 h also maintained its antibiotic activity for an extended time. For the most part, ZOI values for nylon dyed by both antibiotics were zero within 24 h. This technique produced infection-resistant biomaterials of potential use in extra-corporeal biomedical and biological applications. (C) 2004 Wiley Periodicals, Inc.

Efforts have been made to overcome polyester's hydrophobicity. Alkaline hydrolysis and enzyme treatment have been studied and the resulting creation of surface carboxylic acid groups provides hydrophilicity and functionality. Reaction with these groups has been used to link soil release finishes and biologically active proteins. Ester-amide interchange reactions have also been researched, and surface amine functionality results when diamines are used. The use of ethylenediamine (EDA) for short times under ambient conditions results in the simultaneous creation of both amine and carboxylic acid functional groups on the fiber surface. The same reaction on polyester that has been previously hydrolyzed with alkali results in a different ratio of amine and carboxylic acid groups. The reaction conditions have been studied, as have the effects on various physical properties of the material. The presence of two functional groups provides opportunity for the development of multifunctional biomaterials, and possibly, for unique finishing effects.

Antibiotics will reduce infection in medica I textiles. The uptake of quinoline antibiotic under batch dyeing conditions by a polyurethane containing carboxylic acid groups was compared to that of unmodified material, and optimized by variation of pH, electrolyte, time, temperature, and liquor ratio. The mechanism of interaction is suggested by the dyeing isotherm. Zones of inhibition showed antibiotic release by the "dyed" material beyond 96 hours versus 10 minutes for the unmodified material. A low value for the affinity of the antibiotic for the polyurethane was calculated. On a fiber, this value represents poor fastness, but for medical materials,this provides the desired sustained antimicrobial properties. A potential exists for optimizing release in vitro rather than by using in vivo testing.

Glucose enters the heart via GLUT1 and GLUT4 glucose transporters. GLUT4-deficient mice develop striking cardiac hypertrophy and die prematurely. Whether their cardiac changes are caused primarily by GLUT4 deficiency in cardiomyocytes or by metabolic changes resulting from the absence of GLUT4 in skeletal muscle and adipose tissue is unclear. To determine the role of GLUT4 in the heart we used cre-loxP recombination to generate G4H(-/-) mice in which GLUT4 expression is abolished in the heart but is present in skeletal muscle and adipose tissue. Life span and serum concentrations of insulin, glucose, FFAs, lactate, and beta-hydroxybutyrate were normal. Basal cardiac glucose transport and GLUT1 expression were both increased approximately 3-fold in G4H(-/-) mice, but insulin-stimulated glucose uptake was abolished. G4H(-/-) mice develop modest cardiac hypertrophy associated with increased myocyte size and induction of atrial natriuretic and brain natriuretic peptide gene expression in the ventricles. Myocardial fibrosis did not occur. Basal and isoproterenol-stimulated isovolumic contractile performance was preserved. Thus, selective ablation of GLUT4 in the heart initiates a series of events that results in compensated cardiac hypertrophy.

Szycher, M. Ph.D.; Quist, W. M.D. Ph.D.; Logerfo, F. M.D.; Phaneuf, M. B.S. Author Information

Endothelial injury in a deep dorsal vein graft may result from thermal, ischemic or mechanical trauma during surgical preparation or following exposure to systemic blood pressures and flow. We removed a functioning in situ deep dorsal vein graft section 10 months after microvascular arterial bypass surgery due to glans hyperemia. This section was compared and contrasted histomorphologically with a preoperative deep dorsal vein section that was procured for routine histological examination before the arteriovenous anastomosis. Detailed examination of the vein graft tissues by light microscopy, computer morphometrics and immunological staining demonstrated no evidence of vascular pathology. In the normal, healthy deep dorsal vein graft exposure to systemic arterial blood pressures and flow for 10 months did not result in myointimal proliferative lesions. Such histological changes seem more likely to be attributable to endothelial injury following iatrogenic surgical trauma. In situ vein grafts offer the opportunity to use "no-touch" endothelium preserving vascular techniques. Use of these grafts may improve long-term clinical results in penile microvascular arterial bypass surgery for impotence as it has in other vascular beds.

Prosthetic arterial grafts of knitted polyester are widely used to replace blocked or damaged arteries. Despite all precautions, some grafts fail, proving incompatible with the body or succumbing to infection. Efforts to modify grafts to eliminate these failures have yet to be commercially successful, but co-operation between the disparate worlds of textile chemistry and cardiovascular surgery has led to some novel approaches to the problem.A series of experiments used common textile products and procedures such as alkali treatment, nonionic surfactants, dyes and soil release finishes to modify the surface of the graft and allow binding of anticlotting proteins. Dyes were also examined for antibiotic activity, and antibiotics were modified and applied using both exhaust and pad-heat procedures to provide infection resistant grafts.In a detailed study, two antibiotics were applied to polyester. The treated material was tested both in vitro and in vivo for long term antibiotic activity. The treated products are said to have great promise, and to represent a significant advance.