Structural evaluation of porcine heart valve prostheses with radiofrequency ultrasound.

BACKGROUND: Bioprosthetic heart valve use is limited by progressive degeneration. Early degenerative changes are often occult, making assessment of tissue integrity difficult. Ultrasound tissue characterization may detect alterations in tissue structure and allow early detection of leaflet degeneration. METHODS: Using a modified echocardiographic unit (Acuson), radiofrequency (RF) integrated backscatter amplitude (IBA) (integral/RF/dt) was measured in 38 leaflets from nine explanted and six control porcine valves. Regions of interest in each leaflet were studied using four ultrasound frequencies. Radiographic gray scale mean and leaflet thickness were measured at each region of interest. Percent collagen and mineral were calculated for each region of interest using color-image processing of histologic sections and compared to IBA. RESULTS: IBA values for control vs. explanted leaflets were (mean value+/-standard deviation): 8.2+/-4.69 dB vs. -4.7+/-4.64 dB at 7.0 MHz; -5.8+/-4.34 dB vs. -3.1+/-5.34 dB at 5.0 MHz; -3.8+/-3.38 dB vs. -2.1+/-3.18 dB at 3.5 MHz; and -9.0+/-4.58 dB vs. -7.1+/-4.25 dB at 2.5 MHz. Collagen content was 27.7+/-8.50% vs. 33.2+/-10.90%, mineral content was 0.1+/-0.10% vs. 2.1+/-4.30%, and radiographic gray scale mean was 150.6+/-1.96 vs. 145.3+/-5.14 for control vs. explanted leaflets, respectively. For control and explanted leaflets IBA, collagen content, mineral content, and radiographic gray scale mean were different (control vs. explanted P<0.05). Leaflet thickness was also noted to be different between the two groups. IBA was different among explanted leaflets with low, medium, and high mineral content. CONCLUSION: IBA was found to be a useful technique to differentiate normal from explanted porcine prosthetic valves in vitro. This method may be useful in the serial assessment of bioprosthetic leaflet degenerative properties in vivo.

Mucolipidosis IV in an African American patient with new findings on electron microscopy.

PURPOSE: We report an unusual case of mucolipidosis IV in a patient of African ancestry, with intracytoplasmic inclusions of the corneal endothelium found on electron microscopy. METHOD: Clinical description with light and electron microscopy. RESULTS: We describe a case of mucolipidosis IV diagnosed in a patient of African ancestry after penetrating keratoplasty. Electron microscopic evaluation revealed intracytoplasmic inclusions in both the corneal epithelium and endothelium. CONCLUSION: The diagnosis of mucolipidosis in a patient of African ancestry is unusual, as this genetic disorder is found predominantly in individuals of Jewish descent. Corneal endothelial involvement in mucolipidosis IV has not previously been reported.

A dominant negative CREB (cAMP response element-binding protein) isoform inhibits thyrocyte growth, thyroid-specific gene expression, differentiation, and function.

cAMP mediates the effects of TSH by regulating thyroid follicular cell proliferation, differentiation, and function. To assess the functional importance of the cAMP response element binding protein (CREB) in thyroid follicular cell regulation in vivo, we targeted the expression of a dominant negative (DN) CREB isoform to the thyroid glands of transgenic mice using a tissue-specific promoter. Transgenic mice exhibited severe growth retardation and primary hypothyroidism. Serum levels of TSH were elevated 8-fold above normal levels, and T4 and T3 levels were low. Histologically, the mutant thyroid glands were characterized by poorly developed follicles that were heterogeneous in size with diminished colloid. Ciliated thyroid epithelial cells were observed in the transgenic thyroid glands, suggesting a failure of follicular cell differentiation. Consistent with this hypothesis, the DN CREB transgene inhibited the expression of an array of genes including thyroglobulin, thyroperoxidase, and the TSH receptor in semiquantitative RT-PCR experiments. Altered expression of the thyroid transcription factors Pax-8, TTF-1, and TTF-2 was also observed. These results demonstrate a critical role for CREB in thyroid growth, differentiation, and function in vivo.

Typhlitis complicating autologous blood stem cell transplantation for breast cancer.

Three cases of typhlitis occurring during autologous blood stem cell transplantation (ABSCT) for metastatic breast cancer are described. Typhlitis is a rare complication of neutropenia and has uncommonly been reported in the autologous transplant setting. Although it has been most commonly described in children with leukemia, typhlitis has increasingly been reported in adult leukemias and in association with neutropenia secondary to chemotherapy for a number of solid tumors. Only five previous cases of typhlitis in the setting of ABSCT have been described. Whereas diarrhea and fever are common toxicities associated with high-dose chemotherapy, it is likely that many cases of typhlitis go unrecognized. Bone Marrow Transplantation (2000) 25, 321-326.

Effects of electrically charged particles in enhancement of rat wound healing.

BACKGROUND: Many studies have show that various growth factors enhance wound healing in animal models. However, growth factors are expensive and complex and their wound pharmacokinetics are unknown. The clinical trials with growth factors in the treatment of chronic wounds have produced unsuccessful results. A viable alternative to growth factors may be certain biomaterials such as hydrophilic, carbohydrate beads. MATERIALS AND METHODS: Positively charged, negatively charged, or uncharged beads were applied to paired 6-cm rat incisions. The following key aspects of the wound healing process were examined: wound breaking strength and histological analysis. RESULTS: Our data show that wounds treated with positively charged, DEAE Sephadez beads had a 46-50% (P < 0.001) increase in breaking strength over untreated control wounds. A variety of other positively charged, anion exchange materials also elicited a wound healing response, despite the fact that the positively charged chemical moieties as well as the bead matrix were different. In conjunction with the increase in wound breaking strength, an increase in wound macrophage was observed in wounds treated with anion exchangers (P < 0.01). Negatively charged or uncharged beads showed no significant difference from the untreated controls. CONCLUSION: We conclude from this study that the enhancement of wound healing seen with positively charged beads is due principally to the positive charge on the beads; we postulate that the anion exchange between the positively charged beads and tissue is responsible for this enhancement.

Transforming growth factor-beta1 fails to stimulate wound healing and impairs its signal transduction in an aged ischemic ulcer model: importance of oxygen and age.

Clinical trials of exogenous growth factors in treating chronic wounds have been less successful than expected. One possible explanation is that most studies used animal models of acute wounds in young animals, whereas most chronic wounds occur in elderly patients with tissue ischemia. We described an animal model of age- and ischemia-impaired wound healing and analyzed the wound-healing response as well as the transforming growth factor (TGF)-beta1 effect in this model. Rabbits of increasing ages were made ischemic in the ear where dermal ulcers were created. Histological analysis showed that epithelium ingrowth and granulation tissue deposition were significantly impaired with increased age under ischemia. TGF-beta1 stimulated wound repair under both ischemic and non-ischemic conditions in young animals, although it showed no statistical difference in aged animals. Procollagen mRNA expression decreased under ischemic conditions and with aging. Neither TGF-beta1 nor procollagen alpha1(I) mRNA expression increased in response to TGF-beta1 treatment under ischemia in aged animals. Therefore, the wound-healing process is impaired additively by aging and ischemia. The lack of a wound-healing response to TGF-beta1 in aged ischemic wounds may play a role in the chronic wounds.

Anatomy and histological characteristics of the spinoglenoid ligament.

The spinoglenoid (inferior transverse scapular) ligament, when present, is located at the spinoglenoid notch. The ligament originates on the spine of the scapula and inserts on the superior margin of the glenoid neck. Because of discrepancies in the literature, we sought to determine its prevalence and to define its histological characteristics. We dissected 112 shoulders of seventy-six cadavera and classified the ligament as absent or an insubstantial structure, a thin fibrous band (type I), or a distinct ligament (type II). We found no distinct ligamentous structure in twenty-two shoulders (20 percent), a type-I ligament in sixty-eight shoulders (61 percent), and a type-II ligament in twenty-two shoulders (20 percent). Overall, ninety (80 percent) of the shoulders had a fibrous band of tissue that, together with the spine of the scapula, formed a narrow fibro-osseous tunnel through which the suprascapular nerve traveled. The bone-spinoglenoid ligament-bone complexes from three specimens were analyzed histologically. There were two type-I ligaments and one type-II ligament; all three ligaments were composed of collagen fibers. One type-I ligament and the type-II ligament demonstrated Sharpey fibers at their origin on the spine of the scapula. The other type-I ligament attached to the spine of the scapula through the periosteum. All three ligaments inserted into the periosteum of the glenoid neck.

Macrophage colony-stimulating factor accelerates wound healing and upregulates TGF-beta1 mRNA levels through tissue macrophages.

Macrophage colony-stimulating factor (M-CSF) is produced by many cell types involved in wound repair, yet it acts specifically on monocytes and macrophages. The monocyte-derived cell is thought to be important in wound healing, but the importance of the role of tissue macrophages in wound healing has not been well defined. Dermal ulcers were created in normal and ischemic ears of young rabbits. Either rhM-CSF (17 microg/wound) or buffer was applied to each wound. Wounds were bisected and analyzed histologically at Days 7 and 10 postwounding. The amounts of epithelial growth and granulation tissue deposition were measured in all wounds. The level of increase of TGF-beta1 mRNA level in M-CSF-treated wounds was examined using competitive RT-PCR. M-CSF increased new granulation tissue formation by 37% (N = 21, P < 0.01) and 50% (P < 0.01) after single and multiple treatments, respectively, in nonischemic wounds. TGF-beta1 mRNA levels in rhM-CSF-treated wounds increased 5.01-fold (N = 8) over vehicle-treated wounds under nonischemic conditions. In contrast, no effect could be detected in ischemic wounds treated with rhM-CSF, and these wounds only showed a 1.66-fold increase in TGF-beta1 mRNA levels when compared to ischemic wounds treated with vehicle alone. GAPDH, a housekeeping gene, showed no change. As mesenchymal cells lack receptors for M-CSF, the improved healing of wounds treated with topical rhM-CSF must reflect a generalized enhancement of activation and function of tissue macrophages, as demonstrated by upregulation of TGF-beta. The lack of effect under ischemic conditions suggests that either macrophage activity and/or response to M-CSF is adversely affected under those conditions; this may suggest the pathogenesis of impaired wound healing at the cellular level.

Acute and chronic animal models for excessive dermal scarring: quantitative studies.

Excessive scarring in the form of keloids and hypertrophic scars continues to be a clinical problem for some patients. The lack of an animal model for such scarring has been an obstacle to studying the cellular and molecular biology of these entities. Previous observations made by the authors that some surgical scars in the rabbit ear remain raised for months after wounding prompted us to investigate whether the rabbit ear might provide a model by which to study excessive dermal scarring. After establishing the model in preliminary study, 40 excisional wounds, 6 mm in diameter, were created over the ventral surface of rabbit ears. Elevated scars were treated with either intralesional triamcinolone acetonide or saline at day 16 postwounding. On day 22, 25 scar wounds were used for thorough histomorphometric analysis, 15 wounds were eliminated prior to analysis because of invagination of epithelial tissue, which made analysis difficult. Total area of scar and Hypertrophic Index, a ratio comparing scar prominence with the thickness of adjacent unwounded tissue, were measured for 25 (62 percent) of the resulting scars. Both total area of scar and Hypertrophic Index were found to be significantly decreased in the steroid-treated group (p < 0.02 and < 0.03, respectively). In a chronic form of this model, in which larger excisions were taken, an excessive accumulation of both new collagen and cartilage over 9 months was observed. An animal model for excessive dermal scarring that allows quantitation of scar formation and, at an early stage, can be modulated in a predictable way with intralesional corticosteroid treatment is presented. This model may parallel hypertrophic scarring in humans and thus might provide a tool by which to study its pathophysiology and objectively evaluate therapeutic modalities.

The effect of chemosurgical peels and dermabrasion on dermal elastic tissue.

Chemosurgical peel is a technique that has been used widely by plastic surgeons and dermatologists to remove fine and deep wrinkles of the skin. However, the reaction of elastic tissue to the cutaneous application of commonly used chemical peeling agents has not been defined. This study comparatively assessed the alteration in dermal histology and mechanical properties of skin following treatment with 25% and 50% trichloroacetic acid, Baker's phenol solution, and dermabrasion. Yucatan minipigs served as the animal model. The skin was analyzed at five intervals over 6 months after treatment using histologic, quantitative, and mechanical analysis (hematoxylin and eosin, elastic tissue, and Sirius red stains, computerized digital morphometry, and a tensiometer). At 6 months we found no change in the quality, structure, or arrangement of elastic fibers in skin treated with a single application of 25% and 50% trichloroacetic acid or dermabrasion when compared with untreated skin. Skin treated with Baker's phenol solution showed a marked morphologic change in the elastic fibers. The fibers within the regenerated zone of dermis were sparse, wispy, and immature at 6 months after treatment. Preliminary tensiometric analysis of phenol-treated skin at 6 months indicated that the skin was stiffer and weaker. This study questions the possibility of long-term change to the skin by the deep penetration of caustic chemicals to remove wrinkles and rejuvenate the skin.

Transforming growth factor beta 3 (TGF beta 3) accelerates wound healing without alteration of scar prominence. Histologic and competitive reverse-transcription-polymerase chain reaction studies.

BACKGROUND: Transforming growth factor (TGF) beta 3 is a new isoform of the TGF beta superfamily and is presumed to play an important role in wound repair and scarring. OBJECTIVE: To examine the effects of TGF beta 3 on wound healing and on reducing scarring. DESIGN AND INTERVENTIONS: Dermal ulcers were created on the ears of 75 anesthetized young female rabbits. Either TGF beta 3 or vehicle was applied topically to the wounds. Wounds were bisected and analyzed histologically at postwounding day 7. A second group of wounds was treated with topical TGF beta 3 and TGF beta 2 or vehicle at days 0 and 3 and harvested at days 21 through 42 as an excessive scarring model. The third group of wounds was treated with TGF beta 1, TGF beta 2, and TGF beta 3 and vehicle. The granulation tissue was harvested at day 7, and cellular RNA was extracted for performing competitive reverse-transcription polymerase chain reaction. MAIN OUTCOME MEASUREMENT: The amount of new epithelium and granulation tissue was measured in TGF beta 3- and vehicle-treated wounds. The hypertrophic index was calculated for scarring wounds treated with TGF beta 2 and TGF beta 3 or vehicle. Levels of TGF beta 1 messenger RNA were measured in those wounds that were treated with TGF beta 1, TGF beta 2, and TGF beta 3 and in their controls. RESULTS: The use of TGF beta 3 (0.3-0.75 microgram per wound) increased granulation tissue formation by more than 100% (P < .005). Epithelialization showed a biphase, either increasing 30% (P < .04) or decreasing 25% (P < .001) dependent on dose. No significant difference in the hypertrophic index was noted in TGF beta 3-treated wounds compared with controls. Levels of TGF beta 1 messenger RNA increased (7.1- to 14.9-fold) in those wounds treated with TGF beta s compared with controls at day 7. CONCLUSIONS: Exogenous TGF beta 3 displays substantial vulnerary properties in wound healing and may be useful in treating nonhealing wounds. However, the observation that TGF beta 3 can reduce scarring was not confirmed in this study, and the messenger RNA level in response to TGF beta 3 suggests that it behaves similarly to TGF beta 1.

Differential effects of platelet-derived growth factor BB in accelerating wound healing in aged versus young animals: the impact of tissue hypoxia.

Platelet-derived growth factor BB (PDGF-BB) plays a central role in wound healing. Platelet-derived growth factor has been shown to accelerate healing in preclinical and clinical studies, but its wound-healing effects in older animals have not been examined. An ischemic incisional model in young female (5 months) and aged male (60 months) rabbits was used to determine the influence of platelet-derived growth factor on day 14 postwounding with reduced blood supply. Wounds in aged ischemic animals were severely impaired in breaking strength compared with their nonischemic control wounds and wounds in young animals (p < 0.001). Topical platelet-derived growth factor (10 microg per wound) partially reversed the reduction in breaking strength in aged ischemic animals but was ineffective in young animals. Histologic studies showed that new granulation tissue deposition and mononuclear cell infiltration was dramatically lower in ischemic wounds of aged animals compared with their control wounds as well as wounds from young animals under both nonischemic and ischemic conditions. Platelet-derived growth factor partially reversed this deficit in old ischemic wounds but not in young ischemic wounds. Epithelial growth was reduced in wounds from aged animals compared with wounds from young animals after 14 days of healing. Platelet-derived growth factor treatment increased ischemic wound epithelial growth in aged ischemic animals about threefold compared with paired controls. In conclusion, wound healing in aged rabbits was severely impaired by ischemia, and a single topical platelet-derived growth factor treatment partially reversed this deficit.

In vitro targeting of antibody-conjugated echogenic liposomes for site-specific ultrasonic image enhancement.

Tissue-specific ultrasonic enhancement can be used for the detection and characterization of atherosclerosis. We have previously demonstrated the generation of inherently echogenic (acoustically reflective) liposomes solely by varying lipid composition and controlling the method of production. In this study, echogenic liposomes composed of phosphatidylcholine (PC), 4-(p-maleimidophenyl) butyryl phosphatidylethanolamine (MPB-PE), phosphatidylglycerol (PG), and cholesterol were conjugated to human gamma globulin to determine the effect of antibody conjugation on liposomal acoustic reflectivity. The liposomes remained highly echogenic following antibody conjugation. Echogenic liposomes were also conjugated to rabbit antihuman fibrinogen to study their ability to target fibrin. Antibody-conjugated liposomes were targeted to fibrin-coated filter paper and slides, thrombi made in vitro, and segments of atheroma in an animal model of atherosclerosis. Liposomes were detected by scanning electron microscopy, radiolabeling, and imaging with intravascular ultrasound. Electron microscopy revealed attachment of antibody-conjugated liposomes to fibrin on slides and to the fibrous plaques of the arterial segments, whereas unconjugated liposomes did not attach. Similarly, conjugated liposomes did not attach to normal arteries, indicating their binding to the arterial segment is directed towards a component of the fibrous plaque. Ultrasound imaging of the thrombi demonstrated surface attachment of the acoustic conjugated liposomes. 125I-Labeled liposomes conjugated to rabbit anti-human were targeted to fibrin-coated paper. Counting specifically bound radioactivity showed that > 84% of applied liposomes remained attached to the fibrin after washing with saline. These results demonstrate the potential of acoustically reflective liposomes for site-specific targeting and acoustic enhancement.

Ventricular tachycardia in healing canine myocardial infarction: evidence for multiple reentrant mechanisms.

Prior studies have demonstrated that unimorphic VT, sometimes due to epicardial reentry, can be induced in healing canine MI; however, the characterization of the types of reentry involved has differed among prior studies. The purpose of this study was to further characterize the spectrum of epicardial reentrant circuits during induced VT in experimental canine MI. Experimental MI was created by total occlusion of the LAD in dogs. Five days later, programmed stimulation was used to induce VT, which was mapped on the epicardium using a combination of vector and isochronal techniques. Pathological analysis was used to determine regions of transmural MI. Epicardial reentrant circuits were identified in eight dogs. The mean cycle length of induced VT was 212 +/- 32 ms. In 3 of 8 experiments, a region of transmural MI was present, which formed at least a portion of a central zone of block around which reentrant impulses circulated. In five experiments, reentry was functional in nature, although the characteristics of the region of functional conduction block were variable. Long lines of functional block, short lines of block with slow conduction transverse to fiber orientation, and leading circle reentry were each observed in different experiments. Although a zone of slow conduction was identified in seven of the experiments, slow conduction transverse to fiber orientation appeared crucial in maintaining reentry in only three experiments. Multiple reentrant mechanisms of VT may be present in this single canine infarction model. Although a zone of slow conduction is usually present, the characteristics of the region of block are highly variable. However, epicardial reentry accounted for only a minority of induced arrhythmia episodes.

Regional vascular mechanical properties by 3-D intravascular ultrasound with finite-element analysis.

A method employing intravascular ultrasound (IVUS) and simultaneous hemodynamic measurements, with resultant finite element analysis (FEA) of accurate three-dimensional IVUS reconstructions (3-DR), was developed to estimate the regional distribution of arterial elasticity. Human peripheral arterial specimens (iliac and femoral, n = 7) were collected postmortem and perfused at three static transmural pressures: 80, 120, and 160 mmHg. At each pressure, IVUS data were collected at 2.0-mm increments through a 20.0-mm segment and used to create an accurate 3-DR. Mechanical properties were determined over normotensive and hypertensive ranges. An FEA and optimization procedure was implemented in which the elemental elastic modulus was scaled to minimize the displacement error between the computer-predicted and actual deformations. The "optimized" elastic modulus (Eopt) represents an estimate of the component element material stiffness. A dimensionless variable (beta), quantifying structural stiffness, was computed. Eopt of nodiseased tissue regions (n = 80) was greater than atherosclerotic regions (n = 88) for both normotensive (Norm) and hypertensive (Hyp) pressurization: Norm, 9.3 +/- 0.98 vs. 3.5 +/- 0.30; Hyp, 11.3 +/- 0.72 vs. 8.5 +/- 0.47, respectively (mean +/- SE x 10(6) dyn/cm2; P < 0.01 vs. nondiseased). No differences in beta between nondiseased and atherosclerotic tissue were noted at Norm pressurization. With Hyp pressurization, beta of atherosclerotic regions were greater than nondiseased regions: 21.5 +/- 2.21 vs. 14.0 +/- 2.11, respectively (P < 0.03). This method provides a means to identify regional in vivo variations in mechanical properties of arterial tissue.

Unsuspected vasculitis and intracranial hemorrhage following thrombolysis.

Treatment with thrombolytic agents such as streptokinase or tissue plasminogen activator (TPA) is an accepted standard for the treatment of patients with acute myocardial infarction (MI). A devastating sequel of thrombolytic therapy may be the development of a hemorrhagic complication, particularly intracranial bleeding, which, although rare, is usually associated with significant neurologic sequelae or death. While various risk factors have been correlated with the development of intracranial hemorrhage following thrombolysis, a possible relationship between bleeding and a clinically unsuspected underlying vasculitis has not been previously reported. This report deals with the case of a 49-year-old man who died of multiple intracranial hemorrhages after thrombolytic therapy for acute MI and who was found at autopsy to have had polyarteritis nodosa of the coronary arteries and vasculitis of the meningeal vessels.

Interaction between the insulin-like growth factor family and the integrin receptor family in tissue repair processes. Evidence in a rabbit ear dermal ulcer model.

We have determined previously that IGF-I is dependent on the presence of IGF binding protein-1 (IGFBP-1) to act as a wound healing agent. We sought to determine the mechanism whereby IGFBP-1 is able to enhance IGF-I bioactivity. As IGFBP-1 binds both the alpha5beta1 integrin as well as IGF-I in vitro, we asked which of the following interactions were important: (a) the ability of IGFBP-1 to interact with an integrin receptor, and/or (b) the binding of IGF-I by IGFBP-1. We used an IGF-1 analogue (des(1-3)IGF-I) with a > 100-fold reduction in affinity for IGFBP-1 as well as an IGFBP-1 mutant (WGD-IGFBP-1) which does not associate with the alpha5beta1 integrin to selectively abrogate each of these interactions. We also tested the ability of IGFBP-2, a related binding protein which has an arginine-glycine-aspartate sequence but does not associate with integrin family members, to enhance IGF-I bioactivity. Full-thickness dermal wounds were created on rabbit ears; various combinations of native IGF-I, native IGFBP-1, native IGFBP-2, and their respective analogues/mutants were applied to each wound. Wounds were harvested 7 d later for analysis. Only native IGF-I in combination with native IGFBP-1 was effective as a wound healing agent, enhancing reepithelialization and granulation tissue deposition by 64+/-5 and 83+/-12% over controls (P = 0.008 and 0.016, respectively). The same doses of IGF-I/WGD-IGFBP-1, des(1-3)IGF-I/IGFBP-1, and IGF-I/IGFBP-2 were ineffective. We propose that IGF-I physically interacts with IGFBP-1 and that IGFBP-1 also binds to an integrin receptor, most likely the alpha5beta1 integrin. This interaction is unique to IGFBP-1 as the closely related IGFBP-2 had no effect, a finding consistent with its inability to bind to integrin receptors. Our results suggest that activation of both the IGF-I receptor and the alpha5beta1 integrin is required for IGF-I to stimulate wound healing.

Accurate three-dimensional reconstruction of intravascular ultrasound data. Spatially correct three-dimensional reconstructions.

BACKGROUND: The geometrical accuracy of conventional three-dimensional (3D) reconstruction methods for intravascular ultrasound (IVUS) data (coronary and peripheral) is hampered by the inability to register spatial image orientation and by respiratory and cardiac motion. The objective of this work was the development of improved IVUS reconstruction techniques. METHODS AND RESULTS: We developed a 3D position registration method that identifies the spatial coordinates of an in situ IVUS catheter by use of simultaneous ECG-gated biplane digital cinefluoroscopy. To minimize distortion, coordinates underwent pincushion correction and were referenced to a standardized calibration cube. Gated IVUS data were acquired digitally, and the spatial locations of the imaging planes were then transformed relative to their respective 3D coordinates, rendered in binary voxel format, resliced, and displayed on an image-processing workstation for off-line analysis. The method was tested by use of phantoms (straight tube, 360 degrees circle, 240 degrees spiral) and an in vitro coronary artery model. In vivo feasibility was assessed in patients who underwent routine interventional coronary procedures accompanied by IVUS evaluation. Actual versus calculated point locations were within 1.0 +/- 0.3 mm of each other (n = 39). Calculated phantom volumes were within 4% of actual volumes. Phantom 3D reconstruction appropriately demonstrated complex morphology. Initial patient evaluation demonstrated method feasibility as well as errors if respiratory and ECG gating were not used. CONCLUSIONS: These preliminary data support the use of this new method of 3D reconstruction of vascular structures with use of combined vascular ultrasound data and simultaneous ECG-gated biplane cinefluoroscopy.

Electrical activation during ventricular fibrillation in the subacute and chronic phases of healing canine myocardial infarction.

BACKGROUND: Little information is available regarding the effects of myocardial infarction on the characteristics of ventricular fibrillation (VF). Epicardial activation during VF can be characterized by the cycle length and by the characteristics of activation wave fronts. METHODS AND RESULTS: VF was induced by programmed stimulation in 6 dogs with subacute healing (1 week) myocardial infarction (MI), 5 dogs with chronic (8 week) healing MI, and 6 dogs without MI. Using a plaque electrode array with a 2.5-mm interelectrode distance, 112 electrograms were recorded and 91 vector loops were created for each cycle of VF from either the anterior (infarcted) or lateral (noninfarcted) wall. Direction of maximum epicardial activation was determined at each site for the first 10 cycles of VF (early) and for 10 cycles after 5 seconds of VF (late). Wave front size was determined based on a similarity in epicardial activation directions within a given area and by a statistical analysis that determined the degree of spatial linking at varying distances over the recording plaque. VF cycle length was defined as the mean interval of 10 consecutive local activation times. Differences among groups and differences between the anterior and posterolateral walls were determined by ANOVA. The mean wave front area was significantly larger in the presence of subacute MI (97 +/- 4 mm2, early; 78 +/- 3 mm2, late) or chronic MI (94 +/- 5 mm2, early; 78 +/- 5 mm2, late) than in noninfarcted animals (73 +/- 5 mm2, early; 61 +/- 3 mm2, late). The degree of linking of epicardial activation directions was similar in the three groups at distances of 2.5 and 5.0 mm but was lower at a distance of 7.5 mm among animals without infarction, confirming a smaller wave front size and suggesting less organization of activation. VF cycle length was significantly longer in the presence of infarction (98 +/- 5 ms, normal control animals; 121 +/- 13 ms, subacute MI; 127 +/- 13 ms, chronic MI). VF cycle length was significantly longer over the anterior than the lateral wall in the presence of subacute MI (131 +/- 8 ms, anterior; 109 +/- 5 ms, lateral) or chronic MI (136 +/- 9 ms, anterior; 119 +/- 6 ms, lateral) but not in noninfarcted animals (99 +/- ms, anterior; 97 +/- 5 ms, lateral). The prolongation of VF cycle length among animals with infarction was associated with slower estimated conduction velocities during VF. CONCLUSIONS: During VF, in animals with subacute or chronic healing MI, (1) the size of activation wave fronts is larger, (2) the cycle length of VF is longer, (3) the conduction velocities are slower, and (4) the degree of organization is greater than in control animals. Thus, the characteristics of VF throughout the heart are altered by the presence of regional myocardial infarction. The implications of these findings for the initiation and maintenance of VF in the presence of different underlying myocardial substrates require further study.