Prevention of perioperative vascular prosthetic infection with a novel triple antimicrobial-bonded arterial graft.

OBJECTIVE: Previously, we investigated a locally developed technique of bonding arterial grafts with three antimicrobials to protect against early (within 2 weeks) perioperative bacterial contamination encountered occasionally during aortic graft prosthetic reconstruction. Vascular graft infections are classified by their appearance time (early [<4 months] vs late [>4 months] after graft implantation), degree of incorporation into the surrounding vessel wall, connectivity to the postoperative wound, and extent of graft involvement. In the current phase of testing, we evaluated the ability of our novel triple antimicrobial-bonded graft to prevent infection in the first 8 weeks after implantation. METHODS: In nine Sinclair miniature pigs, we surgically implanted a 6-mm vascular Dacron patch graft in the infrarenal abdominal aorta. Five pigs received grafts chemically bonded with a 60-mg/mL solution of rifampin, minocycline, and chlorhexidine, and four pigs received unbonded grafts. Before implantation, the five bonded grafts and three of the unbonded grafts were immersed for 15 minutes in a 2-mL solution containing 1-2 × 107 colony-forming units (CFUs)/mL of Staphylococcus aureus (ATCC 29213); the fourth unbonded graft served as a control. RESULTS: At week 9, all of the grafts were explanted. All S aureus-inoculated bonded grafts (n = 5) showed no bacterial growth. The unbonded, uninoculated graft (n = 1) showed low-level bacterial growth (<1.2 × 103 CFUs); S cohnii spp urealyticus, but not S aureus, was isolated, which suggested accidental direct perioperative contamination. Two pigs that received S aureus-inoculated, unbonded grafts were euthanized because of severe S aureus infection (<6.56 × 108 CFUs per graft). Results of histopathologic analysis were concordant with the microbiologic findings. Most intergroup differences were observed in the inflammatory infiltrate in the aortic wall at the site of graft implantation. In all pigs that received bonded grafts, Gram staining showed no bacteria. CONCLUSIONS: Our triple-bonded aortic graft prevented perioperative aortic graft infection for at least 8 weeks in a porcine model. The synergistic antimicrobial activity of this graft was sufficient to prevent and/or eradicate infection during that period. Further studies are needed to assess the graft's ability to combat early-onset vascular graft infection for up to 4 months.

A pilot study of a triple antimicrobial-bonded Dacron graft for the prevention of aortic graft infection.

OBJECTIVE: Perioperative infection of an aortic graft is one of the most devastating complications of vascular surgery, with a mortality rate of 10% to 30%. The rate of amputation of the lower limbs is generally >25%, depending on the graft material, the location of the graft and infection, and the bacterial virulence. In vitro studies suggest that an antibiotic-impregnated graft may help prevent perioperative graft infection. In a pilot animal study, we tested a locally developed technique of bonding Dacron aortic grafts with three antimicrobial agents to evaluate the ensuing synergistic preventive effect on direct perioperative bacterial contamination. METHODS: We surgically implanted a 6-mm vascular knitted Dacron graft in the infrarenal abdominal aorta of six Sinclair miniature pigs. Two pigs received unbonded, uninoculated grafts; two received unbonded, inoculated grafts; and two received inoculated grafts that were bonded with chlorhexidine, rifampin, and minocycline. Before implantation, the two bonded grafts and the two unbonded grafts were immersed for 15 minutes in a 2-mL bacterial solution containing 1 to 2 × 10(7) colony-forming units (CFU)/mL of Staphylococcus aureus (ATCC 29213). Two weeks after graft implantation, the pigs were euthanized, and the grafts were surgically excised for clinical, microbiologic, and histopathologic study. RESULTS: The two bonded grafts treated with S aureus showed no bacterial growth upon explant, whereas the two unbonded grafts treated with S aureus had high bacterial counts (6.25 × 10(6) and 1.38 × 10(7) CFU/graft). The two control grafts (unbonded and untreated) showed bacterial growth (1.8 × 10(3) and 7.27 × 10(3) CFU/graft) that presumably reflected direct, accidental perioperative bacterial contamination; S cohnii ssp urealyticus and S chromogenes, but not S aureus, were isolated. The histopathologic and clinical data confirmed the microbiologic findings. Only pigs that received unbonded grafts showed histopathologic evidence of a perigraft abscess. CONCLUSIONS: Our results suggest that bonding aortic grafts with this triple antimicrobial combination is a promising method of reducing graft infection resulting from direct postoperative bacterial contamination for at least 2 weeks. Further studies are needed to explore the ability of this novel graft to combat one of the most feared complications in vascular surgery.

Flat-panel versus 64-channel computed tomography for in vivo quantitative characterization of aortic atherosclerotic plaques.

BACKGROUND: Flat-panel computed tomography (FpCT) provides better spatial resolution than 64-channel CT (64-CT) and may improve in vivo quantitative assessment of atherosclerotic plaques. METHODS AND RESULTS: Lesions in 184 aortic histology sections from 6 Watanabe heritable hyperlipidemic rabbits were quantitatively compared with 64-CT (image thickness, 0.625 mm) and FpCT (image thickness, 0.150 mm) images. Images were re-oriented perpendicular to the vessel centerline. For detecting plaque, FpCT and 64-CT were not significantly different (sensitivity, 76% vs 66%; P=NS). Although FpCT was significantly more sensitive (42% vs 0%; P=<0.001) for detecting eccentric lesions, the area under the curve (AUC) for FpCT (0.6) was not significantly different from that for 64-CT (0.45; P=NS). In detecting plaques with ≤ 10% lipid (low attenuation foci), FpCT was significantly more sensitive than 64-CT (24% vs 0.7%; P<0.00) and had a significantly greater AUC (0.6 vs 0.5; P<0.006). Additionally, FpCT was more sensitive (65% vs 0%; P<0.00) in detecting plaques with ≤ 5% calcium (high attenuation foci) but not in detecting branch points. Both FpCT and histology allowed us to detect low-attenuation foci as small as 0.3mm in diameter, whereas 64-CT allowed us to detect only low-attenuation foci ≥ 1.5mm in diameter. CONCLUSIONS: Flat-panel CT seemed to have more potential for quantitatively screening low-risk small atherosclerotic lesions, whereas 64-CT was apparently more useful when imaging established, well-characterized lesions, particularly when measuring the vascular wall thickness in a rabbit model of atherosclerosis.

Decreasing body temperature predicts early rehospitalization in congestive heart failure.

BACKGROUND: In congestive heart failure (CHF), a low body temperature at hospital admission predicts in-hospital mortality. We hypothesized that a postdischarge reduction in body temperature predicts early CHF rehospitalization and death. METHODS: We reviewed the records of 198 patients discharged after CHF hospitalization. We categorized the patients as hypothermic or normothermic (cutoff point, 36.3 degrees C/97.4 degrees F) according to body temperature at discharge. We classified the 2 groups according to the direction of temperature change between discharge and the first follow-up visit: normothermic/non-decreasing temperature (N+), normothermic/decreasing temperature (N-), hypothermic/non-decreasing temperature (H+), and hypothermic/decreasing temperature (H-). RESULTS: Ninety-three patients (47%) had decreasing temperatures, and 105 patients (53%) had non-decreasing temperatures. Kaplan-Meier analysis revealed a significant intergroup difference in survival (P = .01) and rehospitalization time (P = .005). On logistic regression, a decreasing temperature was significantly associated with rehospitalization within 180 days (odds ratio, 4.01; 95% confidence interval, 1.63-10.02; P = .003). On Cox regression, the hazard ratios for death were 3.19 (P = .07), 6.49 (P = .004), and 5.17 (P = .07), for the N-, H+, and H- groups, respectively, versus the N+ group. For rehospitalization time, the hazard ratios were 7.02 (P = .01), 4.24 (P = .08), and 13.43 (P = .005) for the N-, H+, and H- groups, respectively, versus the N+ group. CONCLUSION: Decreasing body temperatures can predict readmission, decreased time to rehospitalization, and (in combination with hypothermia) decreased survival.

Three-dimensional isotropic wavelets for post-acquisitional extraction of latent images of atherosclerotic plaque components from micro-computed tomography of human coronary arteries.

RATIONALE AND OBJECTIVES: The capability of wavelet transforms to separate signals into frequency bands is the basis for its use in image compression and storage, data management and transmission, and, recently, extraction of latent images of tissue components from noisy medical images. Analysis of temporal variations of radiofrequency backscatter of intravascular ultrasound with one-dimensional wavelets can detect lipid-laden plaque in coronary arteries with a sensitivity and specificity of >80%. In this study we evaluate the capability of a novel, 3-dimensional isotropic wavelet analysis to perform high resolution, non-directionally biased, statistically reliable, non-invasive discrimination between components of human coronary atherosclerotic plaques in micro-CT. MATERIALS AND METHODS: Coronary artery segments (5-15 mm) were excised at necropsy from 18 individuals with advanced coronary atherosclerosis. Specimens were imaged using a GE Locus SP ex vivo micro-CT scanner and processed for histological correlation (833 sections). The isotropic wavelet constructs were applied to the entire volume of CT data of each arterial segment to distinguish tissue textures of varying scales and intensities. Voxels were classified and plaque characterization achieved by comparing the relative magnitudes of these wavelet constituents to that of several reference plaque tissue components. RESULTS: Processing of micro-CT images via these isotropic wavelet algorithms permitted 3-D, color-coded, high resolution, digital discrimination between lumen, calcific deposits, lipid-rich deposits, and fibromuscular tissue providing detail not possible with conventional thresholding based on Hounsfield intensity units. Using the isotropic wavelets (with histology as the gold standard), lipid-rich pools approaching the size of the filter for the isotropic wavelet algorithm (0.25 mm [250 microns] in length) were identified with 81% sensitivity and 86% specificity. Calcific deposits, fibromuscular tissue, and lumen equal to or larger than the wavelet filter size were detected without error (100% sensitivity and specificity). CONCLUSION: Isotropic wavelet analysis permits high resolution, multi-dimensional identification of coronary atherosclerotic plaque components in micro-CT with sensitivity and specificity similar to that achieved with data obtained invasively (from IVUS in vivo) using one-dimensional wavelets. Further studies are necessary to test the applicability of this technology to clinical, multi-detector scanners.

Quantification of roughness of calcific deposits in computed tomography scans of human coronary arteries.

OBJECTIVES: The incidence of coronary artery disease has been shown to be greater in patients with calcific deposits than in those without. It has been suggested that the pattern of distribution of coronary calcific deposits within coronary arteries is of greater predictive value for acute coronary events than the overall quantity. Whether roughness of calcific deposits is a predictor of acute coronary events is not known. We derived and tested an algorithm, Voxel-Based Bosselation (VBB), for noninvasive quantification of roughness of calcific deposits in human coronary arteries imaged by computed tomography (CT). METHODS AND RESULTS: VBB was tested on 213 coronary calcific deposits from electron beam CT scans of 27 patients. This algorithm evaluates the 3-dimensional connectedness of surface voxels of each deposit: smooth masses have low VBB and rough masses high VBB. The algorithm was calibrated with artificially generated phantoms as well as background noise mimicking calcific deposits and surrounding heart tissue. The VBB algorithm is applicable to calcific deposits of all scales and gradations. The VBB values of the deposits in this study did not correlate with deposit size further supporting its validity as a measurement of roughness. The VBB index corresponded directly with visual reconstruction using Phong-shaded algorithms. CONCLUSIONS: The VBB index, derived here, is a noninvasive method of quantifying the roughness of calcific deposits in CT scan data which can now be used in future clinical studies to determine possible correlations with increased plaque vulnerability and major acute coronary events.

Usefulness of multidetector computed tomography for noninvasive evaluation of coronary arteries in asymptomatic patients.

This editorial addresses the capabilities, limitations, and potential of multidetector computed tomography (MDCT) for the noninvasive evaluation of coronary arteries in asymptomatic patients. The quantification of coronary calcium with MDCT correlates highly with that obtained by electron-beam computed tomography, but to date, neither has the capability of assessing the distribution of various morphologic patterns of calcium and their relation to other "soft" plaque components. Although MDCT can assess the thickness of the atherosclerotic wall and can readily identify calcific deposits, further plaque characterization (e.g., lipid pools and fibrous tissue), a prerequisite for the identification of most vulnerable lesions, is not yet a workable reality, even with the 64-slice machines in their current configuration. The noninvasive identification by MDCT of plaque components subtending vulnerable lesions will require additional improvement in the primary instrumentation, the use of hybrid constructs (e.g., with positron emission tomography and magnetic resonance imaging), the development of novel methods of post-acquisitional analysis to extract latent images of plaque components (e.g., signal analysis based on 3-dimensional wavelets), or the adaptation of molecular imaging techniques at the cell and gene levels to computed tomography. Such unique approaches may soon contribute a long list of additional parameters that could be evaluated on a noninvasive basis as predictors of acute coronary syndromes and overall patient vulnerability.

Influenza and cardiovascular disease: is there a causal relationship?

There is mounting evidence in support of a significant role for influenza infection in the development of atherosclerosis and the triggering of its complications. Here we review the biologic basis of this relationship, with special emphasis on the pro-inflammatory and pro-thrombotic effects of influenza infection. We also discuss the related epidemiologic findings and discuss in detail the possible causal relationship between influenza and cardiovascular disease. We appraise the relationship between influenza and coronary heart disease, on the basis of Bradford Hill's criteria of causality. We show that our proposed relationship meets the following criteria: strength of association, consistency, temporal sequence, coherence, biologic plausibility, experimental evidence, and analogy. Further studies are needed to assess whether it meets the criterion of biologic gradient. Specificity is not met, but meeting that criterion is of least importance in the study of multifactorial chronic diseases such as coronary heart disease. These criteria do not yield indisputable evidence for or against cause-and-effect, but they can help researchers appraise available evidence and determine the areas that need further research. The case for expanding the research on the effect of influenza on cardiovascular disease is a strong one, for most of Hill's criteria are met.