Digital image correlation: a novel dynamic three-dimensional imaging technique for precise quantification of the dynamic rhytid and botulinum toxin type a efficacy.

BACKGROUND: Quantification of facial dynamic motion is paramount for improving cosmetic and reconstructive surgical outcomes. The authors introduce digital image correlation using speckle tracking photogrammetry and Aramis software (GOM mbH, Braunschweig, Germany) to study facial dynamics and demonstrate its application in quantifying botulinum toxin efficacy. METHODS: Fourteen subjects were evaluated using a dual camera system and three-dimensional optical analysis. Using Aramis software, the anatomic regions of the glabella, forehead, and total face were identified and highlighted. Tissue strain, defined as either compression or stretch, was measured within these regions over 36 frames during brow furrowing. Each patient was measured before and 2 weeks after injection of 20 units of onabotulinumtoxinA in the glabella. Average stretch and compression in treated areas were analyzed across all available frames. Results were compared using a Wilcoxon signed rank test. RESULTS: After neurotoxin injection, average vertical stretch of the glabella during brow furrowing decreased from 2.51 percent to 1.15 percent (p < 0.05), and average vertical stretch in the forehead decreased from 6.73 percent to 1.67 percent (p < 0.05). Horizontal compression in the glabella decreased from 9.11 percent to 2.60 percent (p < 0.05) and from 4.83 percent to 0.83 percent (p < 0.05) in the forehead. Total facial major strain decreased from 4.41 percent to 3.05 percent (p < 0.05), and total facial minor strain decreased from 5.01 percent to 3.51 percent (p < 0.05). CONCLUSIONS: The authors introduce digital image correlation as a novel technology for measuring dynamic rhytid and neurotoxin efficacy. This technique allows for advancements in the study of dynamic aging and neuromuscular disorders. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Quantified Facial Soft-tissue Strain in Animation Measured by Real-time Dynamic 3-Dimensional Imaging.

BACKGROUND: The aim of this study is to evaluate and quantify dynamic soft-tissue strain in the human face using real-time 3-dimensional imaging technology. METHODS: Thirteen subjects (8 women, 5 men) between the ages of 18 and 70 were imaged using a dual-camera system and 3-dimensional optical analysis (ARAMIS, Trilion Quality Systems, Pa.). Each subject was imaged at rest and with the following facial expressions: (1) smile, (2) laughter, (3) surprise, (4) anger, (5) grimace, and (6) pursed lips. The facial strains defining stretch and compression were computed for each subject and compared. RESULTS: The areas of greatest strain were localized to the midface and lower face for all expressions. Subjects over the age of 40 had a statistically significant increase in stretch in the perioral region while lip pursing compared with subjects under the age of 40 (58.4% vs 33.8%, P = 0.015). When specific components of lip pursing were analyzed, there was a significantly greater degree of stretch in the nasolabial fold region in subjects over 40 compared with those under 40 (61.6% vs 32.9%, P = 0.007). Furthermore, we observed a greater degree of asymmetry of strain in the nasolabial fold region in the older age group (18.4% vs 5.4%, P = 0.03). CONCLUSIONS: This pilot study illustrates that the face can be objectively and quantitatively evaluated using dynamic major strain analysis. The technology of 3-dimensional optical imaging can be used to advance our understanding of facial soft-tissue dynamics and the effects of animation on facial strain over time.

Does breast reconstruction impact the decision of patients to pursue cosmetic surgery?

BACKGROUND: Breast reconstruction is an integral component of breast cancer treatment, often aiding in restoring a patient's sense of femininity. However, many patients choose to have subsequent cosmetic surgery. The purpose of this study is to investigate the reasons that motivate patients to have cosmetic surgery after breast reconstruction. METHODS: The authors performed a retrospective study examining patients who had breast reconstruction and subsequent cosmetic surgery at the University of Pennsylvania Health System between January 2005 and June 2012. This cohort received a questionnaire assessing the influences and impact of their reconstructive and cosmetic procedures. RESULTS: A total of 1,214 patients had breast reconstruction, with 113 patients (9.3%) undergoing cosmetic surgery after reconstruction. Of 42 survey respondents, 35 had autologous breast reconstruction (83.3%). Fifty-two cosmetic procedures were performed in survey respondents, including liposuction (26.9%) and facelift (15.4%). The most common reason for pursuing cosmetic surgery was the desire to improve self-image (n = 26, 61.9%), with 29 (69.0%) patients feeling more self-conscious of appearance after reconstruction. Body image satisfaction was significantly higher after cosmetic surgery (P = 0.0081). Interestingly, a multivariate analysis revealed that patients who experienced an improvement in body image after breast reconstruction were more likely to experience a further improvement after a cosmetic procedure (P = 0.031, OR = 17.83). Patients who were interested in cosmetic surgery prior to reconstruction were also more likely to experience an improvement in body image after cosmetic surgery (P = 0.012, OR = 22.63). CONCLUSION: Cosmetic surgery may improve body image satisfaction of breast reconstruction patients and help to further meet their expectations.

A preliminary report on the use of antibiotic-impregnated methyl methacrylate in salvage cranioplasty.

In the setting of recurrent infection and multiple failed reconstruction attempts, the choice of the ideal reconstructive material for salvage cranioplasty remains a source of controversy in the literature. The purpose of this study is to establish the safety and utility of antibiotic-impregnated polymethyl methacrylate (PMMA) for salvage cranioplasty.A prospectively maintained database of all patients who underwent salvage cranioplasty using vancomycin and tobramycin-impregnated methyl methacrylate from January 2011 to July 2013 was reviewed. Vancomycin and tobramycin were mixed in PMMA, which was then applied to a rigidly fixed titanium mesh for reconstruction. Patients' demographics, indications, and outcomes of this technique were evaluated.Nine patients (mean age: 47 years) underwent vancomycin and tobramycin-impregnated PMMA reconstruction with a mean follow-up of 9.3 months (range 3.5-23 months). On average, these patients underwent 4 procedures (range: 1-15), which included repeat craniotomy, debridement for infection, and failed reconstructions over the course of 3.6 years (range: 7 months to 14 years) before salvage cranioplasty. All patients required salvage cranioplasty due to infection, with the most common bacteria isolated in culture being Propionibacterium acnes (n = 3), multiresistant coagulase-negative Staphylococcus (n = 3), methicillin-resistant Staphylococcus aureus (n = 2), and Enterobacter (n = 2). The average size of the craniectomy defect was 130 cm(2), and there were no incidences of postoperative infection, postoperative complications, or need for revisions.To conclude, in short-term follow-up, vancomycin and tobramycin-impregnated PMMA reconstruction appears safe and effective in salvage cranioplasty. Our early report represents a proof of concept--the true test is whether these short-term successes translate to stable long-term results.

Fat grafting's past, present, and future: why adipose tissue is emerging as a critical link to the advancement of regenerative medicine.

Fat grafting is a common reconstructive and aesthetic procedure with extensive clinical applications. Recently, significant strides have been made in investigating the biology behind the success of this procedure. Surgeons and scientists alike have advanced this field by innovating fat graft harvesting and injection techniques, expanding the use of adipose tissue and its stem cell components, and broadening our understanding of the viability of fat grafting at the molecular and cellular levels. The objectives of this review are to (1) discuss the clinical applications of fat grafting, (2) describe the cellular biology of fat and the optimization of fat graft preparation, (3) illustrate the significance of adipose-derived stem cells and the potentiality of fat cells, (4) highlight the clinical uses of adipose-derived stem cells, and (5) explore the current and future frontiers of the study of fat grafting. Although collaborative knowledge has increased exponentially, many of the biological mechanisms behind fat grafting are still unknown. Plastic surgeons are in a unique position to pioneer both the scientific and clinical frontiers of fat grafting and to ultimately further this technology for the benefit of our patients.

Beyond fat grafting: what adipose tissue can teach us about the molecular mechanisms of human aging.

BACKGROUND: The concept of aging and the mechanisms responsible for soft tissue aging have become progressively more important as the world's population ages and demands a higher quality of life. Although molecular mechanisms of aging have been evaluated in model organisms, specific genomic, genetic, and epigenetic modifications that can be translated to normal human tissue aging have yet to be identified. We propose that adipose tissue is an excellent model with which to investigate molecular aging pathways. The goal of this study is to demonstrate that primary human adipose tissue can serve as a model of human aging, and further, can be used to detect differences in genomic transcriptional profiling between cell types in adipose tissue as well as between youthful and older age groups. METHODS: Subcutaneous adipose tissue was excised during cosmetic procedures from healthy patients. Adipocytes and stromal vascular fractions from the anterior abdomen were isolated from 3 young (26-39 years) and 3 old (52-64 years) patients and analyzed for genome-wide transcriptional differences between varying ages and cell types using the Affymetrix GeneChip Human Gene Chip 1.0ST. RESULTS: Genes specific to adipocytes were more highly expressed in adipocytes than in stromal vascular fractions, validating that adipose tissue should be examined in a cell-specific manner. An increase in overall gene expression was observed among patients in the older age group, consistent with senescence-related chromatin dysregulation. Principal components analysis revealed no clear delineation between age groups and a clear separation by cell type. Analysis of variance revealed cell type as the most significant variable in transcriptional differences, whereas age-related differences were a distant second. Gene Ontology categories of the most significantly modified genes included RNA splicing and mRNA metabolism, plasma membrane, and mitochondrial metabolism. CONCLUSIONS: Primary adipose tissue is an effective model for the study of the molecular mechanisms of human aging. Our findings are consistent with the hypothesis that epigenetic modifications play a more important role than transcriptional modifications in early human adipose tissue aging. Our future studies will examine the contribution of specific epigenetic markers to human adipose tissue aging and promise to advance approaches in regenerative medicine, and the prevention and treatment of aging.

Squamosal suture synostosis: a cause of atypical skull asymmetry.

BACKGROUND: The squamosal suture is markedly different from the major calvarial sutures of the human skull. The unique properties of the suture are a result of the complex developmental biology of the temporal bone and biomechanical force exerted by surrounding structures. The dysmorphic effects of premature fusion of the suture, and possible treatment strategies in cases of synostosis, have received only brief description in the literature. METHODS: A retrospective case series was performed. The study included patients evaluated by one of the senior authors (S.P.B., R.R.R., and D.J.S.) between 1993 and 2009. All pertinent patient data including inpatient and outpatient charts, photographic records, and radiographic scans were reviewed. Any management performed under the direction of a craniofacial surgeon was documented--including orthotic helmet therapy and operative management. RESULTS: The study included 14 patients. Synostosis of the squamosal suture was noted to occur either in an isolated fashion or in the setting of other craniofacial malformations. Patients with isolated squamosal synostosis often suffered from a deformity that was mild in severity and tended to improve with time. However, when occurring in the setting of other forms of craniosynostosis, the deformity was often progressive, and transcranial surgery was frequently required. CONCLUSIONS: Synostosis of the squamosal suture can result in, or contribute to, significant craniofacial dysmorphism. The optimal form of therapy for this disorder is evolving.

The modified V-Y dorsal metacarpal flap for repair of syndactyly without skin graft.

BACKGROUND: Syndactyly repairs that use full-thickness skin grafts risk graft-related complications. The dorsal V-Y advancement flap offers a method of syndactyly release that can eliminate the need for full-thickness skin grafts in some cases of simple syndactyly. METHODS: A retrospective case series of all patients undergoing syndactyly release without skin grafting performed by the senior author (B.C.) between 1998 and 2007 was conducted. All outpatient and inpatient charts were reviewed for pertinent patient demographics and clinical outcomes, including the incidence of web creep, hypertrophic scarring, flexion contracture, infection, angulation deformity, limited range of motion, ischemia, and need for reoperation. RESULTS: A total of 28 syndactylies were included in the study: 25 simple incomplete and three simple complete. Mean follow-up time was 4.2 years. Mean operative time was 68 minutes. Two patients (7.1 percent) experienced postoperative complications; both were corrected by subsequent revision. CONCLUSION: The dorsal V-Y advancement flap without skin graft is an effective method of repair primarily in simple incomplete syndactyly.

Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device.

OBJECTIVE: It is generally accepted that patients who require biventricular assist device support have poorer outcomes than those requiring isolated left ventricular assist device support. However, it is unknown how the timing of biventricular assist device insertion affects outcomes. We hypothesized that planned biventricular assist device insertion improves survival compared with delayed conversion of left ventricular assist device support to biventricular assist device support. METHODS: We reviewed and compared outcomes of 266 patients undergoing left ventricular assist device or biventricular assist device placement at the University of Pennsylvania from April 1995 to June 2007. We subdivided patients receiving biventricular assist devices into planned biventricular assist device (P-BiVAD) and delayed biventricular assist device (D-BiVAD) groups based on the timing of right ventricular assist device insertion. We defined the D-BiVAD group as any failure of isolated left ventricular assist device support. RESULTS: Of 266 patients who received left ventricular assist devices, 99 (37%) required biventricular assist device support. We compared preoperative characteristics, successful bridging to transplantation, survival to hospital discharge, and Kaplan-Meier 1-year survival between the P-BiVAD (n = 71) and D-BiVAD (n = 28) groups. Preoperative comparison showed that patients who ultimately require biventricular support have similar preoperative status. Left ventricular assist device (n = 167) outcomes in all categories exceeded both P-BiVAD and D-BiVAD group outcomes. Furthermore, patients in the P-BiVAD group had superior survival to discharge than patients in the D-BiVAD group (51% vs 29%, P < .05). One-year and long-term Kaplan-Meier survival distribution confirmed this finding. There was also a trend toward improved bridging to transplantation in the P-BiVAD (n = 55) versus D-BiVAD (n = 22) groups (65% vs 45%, P = .10). CONCLUSION: When patients at high risk for failure of isolated left ventricular assist device support are identified, proceeding directly to biventricular assist device implantation is advised because early institution of biventricular support results in dramatic improvement in survival.

Risk score derived from pre-operative data analysis predicts the need for biventricular mechanical circulatory support.

BACKGROUND: Right ventricular (RV) failure after left ventricular assist device (LVAD) placement is a serious complication and is difficult to predict. In the era of destination therapy and the total artificial heart, predicting post-LVAD RV failure requiring mechanical support is extremely important. METHODS: We reviewed patient characteristics, laboratory values and hemodynamic data from 266 patients who underwent LVAD placement at the University of Pennsylvania from April 1995 to June 2007. RESULTS: Of 266 LVAD recipients, 99 required RV assist device (BiVAD) placement (37%). We compared 36 parameters between LVAD (n = 167) and BiVAD patients (n = 99) to determine pre-operative risk factors for RV assist device (RVAD) need. By univariate analysis, 23 variables showed statistically significant differences between the two groups (p < or = 0.05). By multivariate logistic regression, cardiac index < or =2.2 liters/min/m(2) (odds ratio [OR] 5.7), RV stroke work index < or =0.25 mm Hg . liter/m(2) (OR 5.1), severe pre-operative RV dysfunction (OR 5.0), pre-operative creatinine > or =1.9 mg/dl (OR 4.8), previous cardiac surgery (OR 4.5) and systolic blood pressure < or =96 mm Hg (OR 2.9) were the best predictors of RVAD need. CONCLUSIONS: The most significant predictors for RVAD need were cardiac index, RV stroke work index, severe pre-operative RV dysfunction, creatinine, previous cardiac surgery and systolic blood pressure. Using these data, we constructed an algorithm that can predict which LVAD patients will require RVAD with >80% sensitivity and specificity.

Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression.

Apelin interacts with the APJ receptor to enhance inotropy. In heart failure, apelin-APJ coupling may provide a means of enhancing myocardial function. The alterations in apelin and APJ receptor concentrations with ischemic cardiomyopathy are poorly understood. We investigated the compensatory changes in endogenous apelin and APJ levels in the setting of ischemic cardiomyopathy.Male, Lewis rats underwent LAD ligation and progressed into heart failure over 6 weeks. Corresponding animals underwent sham thoracotomy as control. Six weeks after initial surgery, the animals underwent hemodynamic functional analysis in the presence of exogenous apelin-13 infusion and the hearts were explanted for western blot and enzyme immunoassay analysis. Western blot analysis of myocardial APJ concentration demonstrated increased APJ receptor protein levels with heart failure (1890750+/-133500 vs. 901600+/-143120 intensity units, n=8, p=0.00001). Total apelin protein levels increased with ischemic heart failure as demonstrated by enzyme immunoassay (12.0+/-4.6 vs. 1.0+/-1.2 ng/ml, n=5, p=0.006) and western blot (1579400+/-477733 vs. 943000+/-157600 intensity units, n=10, p=0.008). Infusion of apelin-13 significantly enhanced myocardial function in sham and failing hearts. We conclude that total myocardial apelin and APJ receptor levels increase in compensation for ischemic cardiomyopathy.

Therapeutic delivery of cyclin A2 induces myocardial regeneration and enhances cardiac function in ischemic heart failure.

BACKGROUND: Heart failure is a global health concern. As a novel therapeutic strategy, the induction of endogenous myocardial regeneration was investigated by initiating cardiomyocyte mitosis by expressing the cell cycle regulator cyclin A2. METHODS AND RESULTS: Lewis rats underwent left anterior descending coronary artery ligation followed by peri-infarct intramyocardial delivery of adenoviral vector expressing cyclin A2 (n =32) or empty adeno-null (n =32). Cyclin A2 expression was characterized by Western Blot and immunohistochemistry. Six weeks after surgery, in vivo myocardial function was analyzed using an ascending aortic flow probe and pressure-volume catheter. DNA synthesis was analyzed by proliferating cell nuclear antigen (PCNA), Ki-67, and BrdU. Mitosis was analyzed by phosphohistone-H3 expression. Myofilament density and ventricular geometry were assessed. Cyclin A2 levels peaked at 2 weeks and tapered off by 4 weeks. Borderzone cardiomyocyte cell cycle activation was demonstrated by increased PCNA (40.1+/-2.6 versus 9.3+/-1.1; P<0.0001), Ki-67 (46.3+/-7.2 versus 20.4+/-6.0; P<0.0001), BrdU (44.2+/-13.7 versus 5.2+/-5.2; P<0.05), and phosphohistone-H3 (12.7+/-1.4 versus 0+/-0; P<0.0001) positive cells/hpf. Cyclin A2 hearts demonstrated increased borderzone myofilament density (39.8+/-1.1 versus 31.8+/-1.0 cells/hpf; P=0.0011). Borderzone wall thickness was greater in cyclin A2 hearts (1.7+/-0.4 versus 1.4+/-0.04 mm; P<0.0001). Cyclin A2 animals manifested improved hemodynamics: Pmax (70.6+/-8.9 versus 60.4+/-11.8 mm Hg; P=0.017), max dP/dt (3000+/-588 versus 2500+/-643 mm Hg/sec; P<0.05), preload adjusted maximal power (5.75+/-4.40 versus 2.75+/-0.98 mWatts/microL2; P<0.05), and cardiac output (26.8+/-3.7 versus 22.7+/-2.6 mL/min; P=0.004). CONCLUSIONS: A therapeutic strategy of cyclin A2 expression via gene transfer induced cardiomyocyte cell cycle activation yielded increased borderzone myofilament density and improved myocardial function. This approach of inducing endogenous myocardial regeneration provides proof-of-concept evidence that cyclin A2 may ultimately serve as an efficient, alternative therapy for heart failure.

Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy.

BACKGROUND: Ischemic cardiomyopathy is a global health concern with limited therapy. We recently described endogenous revascularization utilizing granulocyte-macrophage colony stimulating factor (GMCSF) to induce endothelial progenitor cell (EPC) production and intramyocardial stromal cell-derived factor-1alpha (SDF) as a specific EPC chemokine. The EPC-mediated neovascularization and enhancement of myocardial function was observed. In this study we examined the regional biologic mechanisms underlying this therapy. METHODS: Lewis rats underwent left anterior descending coronary artery (LAD) ligation and developed ischemic cardiomyopathy over 6 weeks. Three weeks after ligation, the animals received either subcutaneous GMCSF and intramyocardial SDF injections or saline injections as control. Six weeks after LAD ligation circulating EPC density was studied by flow cytometry. Quadruple immunofluorescent vessel staining for mature, proliferating vasculature was performed. Confocal angiography was utilized to identify fluorescein lectin-lined vessels to assess perfusion. Ischemia reversal was studied by measuring myocardial adenosine triphosphate (ATP) levels. Myocardial viability was assayed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling detection of apoptosis and quantitation of myofilament density. RESULTS: The GMCSF/SDF therapy enhanced circulating leukocyte (13.1 +/- 4.5 x 10(6) vs 3.1 +/- 0.5 x 10(6)/cc, p = 0.001, n = 6) and EPC (14.2 +/- 6.6 vs 2.2 +/- 2.1/cc, p = 0.001, n = 6) concentrations. Tetraimmunofluorescent labeling demonstrated enhanced stable vasculature with this therapy (39.2 +/- 8.1 vs 25.4 +/- 5.1%, p = 0.006, n = 7). Enhanced perfusion was shown by confocal microangiography of borderzone lectin-labeled vessels (28.2 +/- 5.4 vs 11.5 +/- 3.0 vessels/high power field [hpf], p = 0.00001, n = 10). Ischemia reversal was demonstrated by enhanced cellular ATP levels in the GMCSF/SDF borderzone myocardium (102.5 +/- 31.0 vs 26.9 +/- 4.1 nmol/g, p = 0.008, n = 5). Borderzone cardiomyocyte viability was noted by decreased apoptosis (3.2 +/- 1.4% vs 5.4 +/- 1.0%, p = 0.004, n = 10) and enhanced cardiomyocyte density (40.0 +/- 5.6 vs 27.0 +/- 6 myofilaments/hpf, p = 0.01, n=10). CONCLUSIONS: Endogenous revascularization for ischemic cardiomyopathy utilizing GMCSF EPC upregulation and SDF EPC chemokinesis upregulates circulating EPCs, enhances vascular stability, and augments myocardial function by enhancing perfusion, reversing cellular ischemia, and increasing cardiomyocyte viability.

Fructose 1,6-diphosphate administration attenuates post-ischemic ventricular dysfunction.

BACKGROUND: Cardiomyocyte energy production during ischemia depends upon anaerobic glycolysis inefficiently yielding two ATP per glucose. Substrate augmentation with fructose 1,6-diphosphate (FDP) bypasses the ATP consuming steps of glucokinase and phosphofructokinase thus yielding four ATP per FDP. This study evaluated the impact of FDP administration on myocardial function after acute ischemia. METHODS: Male Wistar rats, 250-300 g, underwent 30 min occlusion of the left anterior descending coronary artery followed by 30 min reperfusion. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of FDP or saline control. After 30 min reperfusion, myocardial function was evaluated with a left ventricular intracavitary pressure/volume conductance microcatheter. For bioenergetics studies, myocardium was isolated at 5 min of ischemia and assayed for ATP levels. RESULTS: Compared to controls (n=8), FDP animals (n=8) demonstrated significantly improved maximal left ventricular pressure (100.5+/-5.4 mmHg versus 69.1+/-1.9 mmHg; p<0.0005), dP/dt (5296+/-531 mmHg/s versus 2940+/-175 mmHg/s; p<0.0028), ejection fraction (29.1+/-1.7% versus 20.4+/-1.4%; p<0.0017), and preload adjusted maximal power (59.3+/-5.0 mW/microL(2) versus 44.4+/-4.6 mW/microL(2); p<0.0477). Additionally, significantly enhanced ATP levels were observed in FDP animals (n=5) compared to controls (n=5) (535+/-156 nmol/g ischemic tissue versus 160+/-9.0 nmol/g ischemic tissue; p<0.0369). CONCLUSIONS: The administration of the glycolytic intermediate, FDP, by intravenous injection, resulted in significantly improved myocardial function after ischemia and improved bioenergetics during ischemia.

Minimally invasive aortic valve papillary fibroelastoma resection.

The standard approach to the resection of aortic valve papillary fibroelastoma has involved traditional full median sternotomy. In this case series, we demonstrate a minimally invasive approach to the resection of these cardiac tumors to decrease operative trauma, reduce postoperative bleeding, decrease pulmonary complications, and expedite recovery from surgery. All patients recovered without incident.

Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy.

OBJECTIVE: Ischemic heart failure is an increasingly prevalent global health concern with major morbidity and mortality. Currently, therapies are limited, and novel revascularization methods might have a role. This study examined enhancing endogenous myocardial revascularization by expanding bone marrow-derived endothelial progenitor cells with the marrow stimulant granulocyte-monocyte colony-stimulating factor and recruiting the endothelial progenitor cells with intramyocardial administration of the potent endothelial progenitor cell chemokine stromal cell-derived factor. METHODS: Ischemic cardiomyopathy was induced in Lewis rats (n = 40) through left anterior descending coronary artery ligation. After 3 weeks, animals were randomized into 4 groups: saline control, granulocyte-monocyte colony-stimulating factor only (GM-CSF only), stromal cell-derived factor only (SDF only), and combined stromal cell-derived factor/granulocyte-monocyte colony-stimulating factor (SDF/GM-CSF) (n = 10 each). After another 3 weeks, hearts were analyzed for endothelial progenitor cell density by endothelial progenitor cell marker colocalization immunohistochemistry, vasculogenesis by von Willebrand immunohistochemistry, ventricular geometry by hematoxylin-and-eosin microscopy, and in vivo myocardial function with an intracavitary pressure-volume conductance microcatheter. RESULTS: The saline control, GM-CSF only, and SDF only groups were equivalent. Compared with the saline control group, animals in the SDF/GM-CSF group exhibited increased endothelial progenitor cell density (21.7 +/- 3.2 vs 9.6 +/- 3.1 CD34 + /vascular endothelial growth factor receptor 2-positive cells per high-power field, P = .01). There was enhanced vascularity (44.1 +/- 5.5 versus 23.8 +/- 2.2 von Willebrand factor-positive vessels per high-power field, P = .007). SDF/GM-CSF group animals experienced less adverse ventricular remodeling, as manifested by less cavitary dilatation (9.8 +/- 0.1 mm vs 10.1 +/- 0.1 mm [control], P = .04) and increased border-zone wall thickness (1.78 +/- 0.19 vs 1.41 +/- 0.16 mm [control], P = .03). (SDF/GM-CSF group animals had improved cardiac function compared with animals in the saline control group (maximum pressure: 93.9 +/- 3.2 vs 71.7 +/- 3.1 mm Hg, P < .001; maximum dP/dt: 3513 +/- 303 vs 2602 +/- 201 mm Hg/s, P < .05; cardiac output: 21.3 +/- 2.7 vs 13.3 +/- 1.3 mL/min, P < .01; end-systolic pressure-volume relationship slope: 1.7 +/- 0.4 vs 0.5 +/- 0.2 mm Hg/microL, P < .01.) CONCLUSION: This novel revascularization strategy of bone marrow stimulation and intramyocardial delivery of the endothelial progenitor cell chemokine stromal cell-derived factor yielded significantly enhanced myocardial endothelial progenitor cell density, vasculogenesis, geometric preservation, and contractility in a model of ischemic cardiomyopathy.

Active thermoregulation improves outcome of off-pump coronary artery bypass.

During off-pump coronary artery bypass grafting, hypothermia increases vasoconstriction, myocardial afterload, coagulopathy and postoperative bleeding. Traditional thermoregulatory techniques do not maintain core body temperature intraoperatively. The efficacy of a commercially available, computer-controlled, water-circulating, dorsal surface, active warming system for thermoregulatory control was evaluated. All patients who underwent non-emergency off-pump coronary bypass grafting by a single surgeon in a 1-year period were studied: the thermoregulation device was used in 50 cases and unavailable for use in 19. The patients who underwent active thermoregulation demonstrated significantly improved core body temperatures compared to the controls: lowest intraoperative, 35.8 degrees C +/- 0.1 degrees C vs. 35.0 degrees C +/- 0.2 degrees C; immediately postoperative, 36.5 degrees C +/- 0.1 degrees C vs. 35.6 degrees C +/- 0.2 degrees C; and 1-hour postoperative, 36.6 degrees C +/- 0.1 degrees C vs. 35.9 degrees C +/- 0.2 degrees C. Thermoregulated patients had significantly reduced 24-hour chest tube drainage (764 +/- 38 vs. 1227 +/- 183 mL), packed red blood cell transfusions (1.4 +/- 0.2 vs. 3.3 +/- 0.7 units), time to extubation (6.8 +/- 0.5 vs. 11.4 +/- 2.3 hours), intensive care unit stay (1.3 +/- 0.1 vs. 2.0 +/- 0.3 days), and hospital stay (4.3 +/- 0.1 vs. 5.1 +/- 0.3 days).

One year transgene expression with adeno-associated virus cardiac gene transfer.

BACKGROUND: Adeno-associated virus (AAV) has shown promise as a vector for cardiac gene transfer given its ability to stably integrate into the host genome and its lack of immune reactivity. This study examined the feasibility of AAV-mediated myocardial gene transfer in mice, the animal which, because of transgenic technology, has become the disease model of choice for cardiovascular research. METHODS: AAV encoding the cytomegalovirus promoter driven LacZ reporter gene (10(7) LacZ-forming units per animal) or vehicle control was injected into the hearts of young adult C57Bl/6 mice by a transdiaphragmatic approach. At one, two, three, six, and twelve months post-injection, cardiac function was assessed by transthoracic echocardiography and hearts were assayed by X-gal histochemical staining. RESULTS: Echocardiography revealed normal left ventricular function in both AAV and control groups at all time points. X-gal staining of cryostat sections of hearts revealed uniform LacZ expression at all time points. There were minimal signs of immunologic infiltration by hematoxylin and eosin staining. CONCLUSIONS: AAV-mediated myocardial gene transfer by transdiaphragmatic injection can be conducted safely and results in long-term expression of the LacZ gene for at least one year without causing significant inflammatory response or adversely affecting LV systolic function.