Biomedical subjects

T Sloane Guy

Publications and source records attributed to T Sloane Guy.

10 recordsLinked to original sources

PubMed2005

Surgical treatment of ischemic mitral regurgitation might not influence ventricular remodeling.

OBJECTIVES: Surgical treatment for ischemic mitral regurgitation has become more aggressive. However, no clinical study has demonstrated that surgical correction of chronic ischemic mitral regurgitation improves survival. We used 4 well-developed ovine models of postinfarction left ventricular remodeling to test the hypothesis that ischemic mitral regurgitation does not significantly contribute to postinfarction left ventricular remodeling. METHODS: Infarction of 21% to 24% of the left ventricular mass was induced by means of coronary ligation in 77 sheep. Infarctions varied only by anatomic location in the left ventricle: anteroapical, n = 26; anterobasal, n = 16; laterobasal, n = 9; and posterobasal, n = 20. Six additional sheep had ring annuloplasty before posterobasal infarction. End-systolic and end-diastolic left ventricular volume, end-systolic muscle-to-cavity area ratio, left ventricular sphericity, ejection fraction, and degree of ischemic mitral regurgitation, as determined by means of quantitative echocardiography, were assessed before infarction and at 2, 5, and 8 weeks after infarction. RESULTS: All infarcts resulted in significant postinfarction remodeling and decreased ejection fraction. Anteroapical infarcts lead to left ventricular aneurysms. Only posterobasal infarcts caused severe and progressive ischemic mitral regurgitation. Remodeling because of posterobasal infarcts was not more severe than that caused by infarcts at other locations. Furthermore, prophylactic annuloplasty prevented the development of mitral regurgitation after posterobasal infarction but had no effect on remodeling. CONCLUSION: The extent of postinfarction remodeling is determined on the basis of infarct size and location. The development of ischemic mitral regurgitation might not contribute significantly to adverse remodeling. Ischemic mitral regurgitation is likely a manifestation rather than an important impetus for postinfarction remodeling.

Animals↗

PubMed2004

Prevention of ischemic mitral regurgitation does not influence the outcome of remodeling after posterolateral myocardial infarction.

OBJECTIVES: This study was designed to test the hypothesis that ischemic mitral regurgitation (IMR) results from, but does not influence, the progression of left ventricular (LV) remodeling after posterolateral infarction. BACKGROUND: Surgical correction of chronic IMR is being increasingly recommended. METHODS: Three groups of sheep had coronary snares placed around the second and third obtuse marginal coronary arteries. Occlusion of these vessels in the control group resulted in progressive IMR over eight weeks. In a second group, Merseline mesh was fitted to cover the exposed LV before infarction. In a third group, a ring annuloplasty was placed before infarction to prevent IMR. Remodeling and degree of IMR were assessed with echocardiography at baseline and at 30 min and two, five, and eight weeks after infarction. RESULTS: Eight weeks after infarction, mean IMR grade was significantly higher in control animals than mesh and annuloplasty animals. At eight weeks, LV end-systolic volume and end-systolic muscle-to-cavity-area ratio (ESMCAR) were significantly better in mesh-treated sheep than in control sheep; also, at eight weeks, ESMCAR and akinetic segment length were significantly better in mesh-treated sheep than in annuloplasty sheep. Ejection fraction was significantly higher in the mesh than the annuloplasty group. There was no significant difference in any measure of remodeling between the annuloplasty and control groups. CONCLUSIONS: Prophylactic ventricular restraint reduces infarct expansion, attenuates adverse remodeling, and reduces IMR severity. Prevention of IMR by prophylactic ring annuloplasty does not influence remodeling. Ischemic mitral regurgitation is a consequence, not a cause, of postinfarction remodeling; infarct expansion is the more important therapeutic target.

Animals↗

PubMed2003

Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling.

BACKGROUND: Induction of matrix metalloproteinases (MMPs) contributes to adverse remodeling after myocardial infarction (MI). Whether a region- and type-specific distribution of MMPs occurs within the post-MI myocardium remained unknown. METHODS AND RESULTS: Ten sheep were instrumented with a sonomicrometry array to measure dimensions in 7 distinct regions corresponding to the remote, transition, and MI regions. Eight sheep served as reference controls. The relative abundance of representative MMP types and the tissue inhibitors of the MMPs (TIMPs) was quantified by immunoblotting. Segment length increased from baseline in the remote (24.9+/-5.4%), transition (18.0+/-2.9%), and MI (53.8+/-11.0%) regions at 8 weeks after MI (P<0.05) and was greatest in the MI region (P<0.05). Region- and type-specific changes in MMPs occurred after MI. For example, MMP-1 and MMP-9 abundance was unchanged in the remote, fell to 3+/-2% in the transition, and was undetectable in the MI region (P<0.05). MMP-13, MMP-8, and MT1-MMP increased by >300% in the transition and MI regions (P<0.05). TIMP abundance decreased significantly in the transition region after MI and fell to undetectable levels within the MI region. CONCLUSIONS: The unique findings of this study were 2-fold. First, changes in regional geometry after MI were associated with changes in MMP levels. Second, a region-specific portfolio of MMPs was induced after MI and was accompanied by a decline in TIMP levels, indicative of a loss of MMP inhibitory control. Targeting the regional imbalance between specific MMPs and TIMPs within the post-MI myocardium holds therapeutic potential.

Animals↗

PubMed2003

Adenovirus-catheter compatibility increases gene expression after delivery to porcine myocardium.

Endomyocardial injection of adenoviral gene vectors enables localized delivery to comprised myocardial tissue. However, many materials used in endomyocardial delivery catheters may not be compatible with adenoviral gene vectors. In this study, a series of catheter-based endocardial and epicardial (direct visualization) procedures were performed to assess catheter-adenovirus compatibility in an in vivo model. A standard Nitinol-stainless steel (Ni-SS) catheter was compared with a novel Stiletto catheter designed for improved biocompatibility. In 4 animals 40 endocardial injections of adenovirus encoding beta-galactosidase (beta-Gal) were performed with the 2 catheters. After sectioning of the hearts only 8 of 20 Ni-SS beta-Gal+ sites could be identified (40% retrieval) whereas 16 of the 20 Stiletto injection sites were identified (80%). Within these areas successful transfection was observed (12.2 +/- 4.0 beta-Gal+ cells/high-power field [HPF] in the Ni-SS group vs. 30.1 +/- 6.8 beta-Gal+ cells/HPF in the Stiletto group; p = 0.03). After epicardial delivery to distinct areas of the myocardium adenoviral delivery as assayed by beta-galactosidase protein activity was >21 +/- 16-fold (range, 5 to >43-fold) greater than after Stiletto delivery. In conclusion, this study highlights the importance of adenovirus-material compatibility in gene delivery to the myocardium. Efficiency was greater when using the catheter designed to enhance biocompatibility.

Adenoviridae↗

PubMed2003

Extended left colon interposition for esophageal replacement using arterial augmentation.

Gastric necrosis after esophagectomy is a difficult clinical problem. Remedial operations to reestablish gut continuity usually rely on the use of the left colon as the neo-esophagus. Previous resection of the necrotic stomach, adhesions associated with a multiple redo-laparotomy and the need to use a substernal route to reach the cervical esophagus all conspire to produce a requirement for increased conduit length. We present a case in which the "arterial supercharge technique" was used to provide a colonic interposition with extended length in such a clinical situation.

Anastomosis, Surgical↗

PubMed2002

Extension of borderzone myocardium in postinfarction dilated cardiomyopathy.

This study tests the hypothesis that hypocontractile, borderzone myocardium adjacent to an expanding infarct becomes progressively larger and more hypocontractile as remodeling continues. Early infarct expansion following anteroapical myocardial infarction (MI) is associated with progressive ventricular dilation and heart failure. The contribution of perfused, hypocontractile, borderzone myocardium to this process is unknown. Using a sheep model of anteroapical infarction, sonomicrometry array localization and serial microsphere injections were used to track changes in regional myocardial contractility, geometry, and perfusion. Eight sheep were studied before and after infarction and two, five, and eight weeks later. Thirty intertransducer chord lengths were analyzed to measure regional contractility and serial changes in regional geometry at end systole. Beginning as a narrow band of fully perfused hypocontractile myocardium adjacent to the infarction, borderzone myocardium extends to involve additional contiguous myocardium that progressively loses contractile function as the heart remodels. Three distinct myocardial zones develop as a result of transmural MI: infarct, borderzone (perfused but hypocontractile), and remote (perfused and normally functioning).This study demonstrates that hypocontractile, fully perfused borderzone myocardium extends to involve contiguous normal myocardium during postinfarction remodeling. This borderzone myocardium is a unique type of perfused, hypocontractile myocardium, which is distinct from hibernating or stunned myocardium. Preventing extension of borderzone myocardium by medical or surgical means offers the prospect of preventing late-onset heart failure following transmural expanding MIs.

Animals↗

PubMed2002

Correction of traumatic tricuspid regurgitation using the double orifice technique.

We present a case of acute traumatic tricuspid regurgitation in a 39-year-old man who was involved in a motor vehicle accident. A large ecchymotic region over the anterior chest wall prompted evaluation by both transthoracic and transesophageal echocardiography which confirmed the valvular injury. At surgery, valvular incompetence was found to be the result of a flail anterior leaflet due to papillary muscle rupture. The valve was successfully repaired using a single stitch double orifice technique in combination with a ring annuloplasty. The valve remains competent 18 months after surgery.

Accidents, Traffic↗

PubMed2002

Current presentation and optimal surgical management of sternoclavicular joint infections.

BACKGROUND: Infection of the stemoclavicular joint is unusual, and treatment of this entity has not been standardized. We sought to characterize the current presentation and optimal management of this disease. METHODS: We retrospectively reviewed the records of the last 7 patients undergoing operation for suppurative infections of the stemoclavicular joint at this institution. Patients were interviewed regarding upper extremity function after formal joint resection. RESULTS: Predisposing factors were common and included diabetes mellitus (n = 2), clavicular fracture (n = 1), human immunodeficiency virus infection (n = 1), immunosuppression (n = 1), and pustular skin disease (n = 1). All patients presented with local symptoms including clavicular mass and tenderness. Diagnosis and evaluation were facilitated by cross-sectional imaging. Organisms isolated included Staphylococcus aureus, group G streptococcus, and Proteus and Propionibacterium species. Antibiotic therapy and simple drainage and debridement were generally ineffective, leading to recurrence of infection in 5 of 6 patients treated initially in this manner. Six patients were treated with resection of the stemoclavicular joint and involved portions of first or second ribs with soft tissue coverage by advancement flap from the ipsilateral pectoralis major muscle. Response to this therapy was excellent, with cure in all patients, no wound complications, and excellent upper extremity function at long-term follow-up. CONCLUSIONS: Aggressive surgical management including resection of the sternoclavicular joint and involved ribs with pectoralis flap closure would appear to be the preferred treatment for all but the most minor infections of the sternoclavicular joint. This approach has minimal impact on upper extremity function.

Adult↗

PubMed2002

Infarct restraint attenuates remodeling and reduces chronic ischemic mitral regurgitation after postero-lateral infarction.

BACKGROUND: Chronic ischemic mitral regurgitation (IMR) is produced by adverse postinfarction ventricular remodeling. We hypothesize that restraining infarct expansion reduces left-ventricular (LV) dilatation and the severity of mitral regurgitation. METHODS: Two groups of 6 sheep had coronary snares placed around the second and third obtuse marginal coronary arteries and four piezoelectric transducers sutured within myocardium across the mid short axis of the LV. In one group, a patch of Marlex mesh was precisely fitted and lightly sutured to myocardium destined for infarction (determined by temporary snare occlusion). Two weeks after instrumentation, coronary snares were tied tight to infarct approximately 24% of the posterolateral LV mass. Transdiaphragmatic echocardiograms were obtained in all animals at baseline, and 30 minutes, and 2, 5, and 8 weeks after infarction. RESULTS: Echocardiograms confirmed similar infarct sizes and locations in both groups. Eight weeks after infarction, IMR grade averaged 3.6+ (scale: 0, no MR; 4, severe MR) in control sheep and 1.9+ in mesh-restrained animals (p = 0.0001). LV end-diastolic and end-systolic volumes at the eighth week were less in mesh-treated sheep (87 +/- 11.3 vs 113 +/- 18.3; 61 +/- 10.6 vs 77 +/- 14.1, respectively), but differences were not significant. Data from mid short axis piezoelectric transducers indicated significantly less strain in the infarcted myocardium in mesh-restrained sheep than in control. CONCLUSIONS: Early restraint of postero-lateral infarct expansion attenuates the severity of ischemic mitral regurgitation and slows ventricular dilatation. However, the remodeling process is not arrested 8 weeks after infarction.

Animals↗

PubMed2002

An ovine model of postinfarction dilated cardiomyopathy.

BACKGROUND: Coronary arterial disease is the major cause of congestive heart failure, but suitable animal models of postinfarction, dilated cardiomyopathy do not exist. This article describes an ovine model that develops after an anterobasal infarction. METHODS: The distribution of ovine myocardium supplied by the first two diagonal branches of the left homonymous artery were determined in 20 slaughterhouse hearts and eight live sheep using methylene blue and tetrazolium injections, respectively. Seven additional animals had the infarction and underwent serial hemodynamic, microsphere and echocardiographic studies more than 8 weeks and histologic studies at the eighth week. Infarcts represented 24.6% +/- 4.7% and 23.9% +/- 2.2% of the left ventricular mass in slaughterhouse and live hearts, respectively. RESULTS: During remodeling, left ventricular end-systolic and end-diastolic volumes increased 115% and 73%, respectively, ejection fraction decreased from 41.2% +/- 6.7% to 29.1% +/- 5.7%, systolic wall thickening remote from the infarct decreased by 68%, sphericity index increased from 0.465 +/- 0.088 to 0.524 +/- 0.038, and left ventricular end-diastolic pressure increased from 1.7 +/- 1.0 to 8.2 +/- 3.5 mm Hg. Serial microsphere measurements documented normal blood flow (1.34 mL/g per minute) to all uninfarcted myocardium and 22% of normal to the infarct. Viable myocardium showed mild interstitial fibrosis. CONCLUSIONS: This ovine model meets all criteria for postinfarction, dilated cardiomyopathy and has the advantages of controlling for variations in coronary arterial anatomy, collateral vascularity, and differences in the numbers, location, and severity of atherosclerotic lesions that confound human studies of the pathogenesis of this disease. This simple model contains only infarcted and fully perfused, hypocontractile myocardium produced by a moderate-sized, regional infarction.

Animals↗