Biomedical subjects

F Gregory Baumann

Publications and source records attributed to F Gregory Baumann.

12 recordsLinked to original sources

PubMed2004

Vein graft arterialization causes differential activation of mitogen-activated protein kinases.

OBJECTIVE: Vascular injury results in activation of the mitogen-activated protein kinases-extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38(MAPK)-which have been implicated in cell proliferation, migration, and apoptosis. The goal of this study was to characterize mitogen-activated protein kinase activation in arterialized vein grafts. METHODS: Carotid artery bypass using reversed external jugular vein was performed in 29 dogs. Vein grafts were harvested after 30 minutes and 3, 8, and 24 hours, and 4, 7, 14, and 28 days. Contralateral external jugular vein and external jugular vein interposition vein-to-vein grafts were used as controls. Vein graft extracts were analyzed for extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38(MAPK) activation. Proliferating cell nuclear antigen expression was investigated as a parameter of cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining and intimal hyperplasia by morphometric examination of tissue sections. RESULTS: Significant intimal hyperplasia was observed at 28 days. Over the time points studied, vein graft arterialization resulted in bimodal activation of both extracellular-signal regulated kinase and p38(MAPK) (30 minutes through 3 hours; 4 days) but did not induce activation of c-jun N-terminal kinase. Proliferating cell nuclear antigen expression increased from days 1 through 28, and apoptosis increased between 8 and 24 hours. CONCLUSION: Vein graft arterialization induces bimodal activation of extracellular-signal regulated kinase and p38(MAPK); however, in contrast with what is described in arterial injury, it does not induce c-jun N-terminal kinase activation. These results provide the first comprehensive characterization of the mitogen-activated protein kinase signaling pathways activated in vein graft arterialization and identify mitogen-activated protein kinases as potential mediators of vein graft remodeling and subsequent intimal hyperplasia.

Animals↗

PubMed2004

Minimally invasive technology for mitral valve surgery via left thoracotomy: experience with forty cases.

BACKGROUND: Recent evolution of minimally invasive technology has expanded the application of the right thoracotomy approach for mitral valve surgery. These same technological advances have also made the left posterior minithoracotomy approach attractive in complex mitral procedures. METHODS: From 1996 to 2003, 921 isolated mitral valve procedures were performed without sternotomy; 40 (4.3%) of these were performed via left posterior minithoracotomy. In the left posterior minithoracotomy group, ages ranged from 18 to 84 years; 36 patients had had previous cardiac surgery (9 on > or =2 occasions). Other factors precluding right thoracotomy included mastectomy/radiation and pectus excavatum. RESULTS: Arterial perfusion was via femoral artery (n = 26) or descending aorta (n = 14); long femoral venous cannulas with vacuum-assisted drainage were used in 39 procedures. Two patients had direct aortic crossclamping, 18 had hypothermic fibrillation, and 20 had balloon endoaortic occlusion. The mean crossclamp and bypass times were 81.9 and 117.2 minutes, respectively. Hospital mortality was 5.0% (2/40); both deaths occurred in octogenarians. There were no injuries to bypass grafts or conversions to sternotomy. Complications included perioperative stroke (2/40; 5.0%), bleeding (2/40; 5.0%), and respiratory failure (1/40; 2.5%); 28 patients (70%) had no postoperative complications. There was no incidence of perioperative myocardial infarction, renal failure, sepsis, or wound infection. The median length of stay was 7 days. CONCLUSIONS: Advances in minimally invasive cardiac surgery technology are readily adaptable to a left-sided minithoracotomy approach to the mitral valve. The left posterior minithoracotomy approach is a valuable option in complicated reoperative mitral procedures with acceptable perioperative morbidity and mortality.

Adolescent↗

PubMed2004

Computer-generated three-dimensional animation of the mitral valve.

OBJECTIVE: Three-dimensional motion-capture data offer insight into the mechanical differences of mitral valve function in pathologic states. Although this technique is precise, the resulting time-varying data sets can be both difficult to interpret and visualize. We used a new technique to transform these 3-dimensional ovine numeric analyses into an animated human model of the mitral apparatus that can be deformed into various pathologic states. METHODS: In vivo, high-speed, biplane cinefluoroscopic images of tagged ovine mitral apparatus were previously analyzed under normal and pathologic conditions. These studies produced serial 3-dimensional coordinates. By using commercial animation and custom software, animated 3-dimensional models were constructed of the mitral annulus, leaflets, and subvalvular apparatus. The motion data were overlaid onto a detailed model of the human heart, resulting in a dynamic reconstruction. RESULTS: Numeric motion-capture data were successfully converted into animated 3-dimensional models of the mitral valve. Structures of interest can be isolated by eliminating adjacent anatomy. The normal and pathophysiologic dynamics of the mitral valve complex can be viewed from any perspective. CONCLUSION: This technique provides easy and understandable visualization of the complex and time-varying motion of the mitral apparatus. This technology creates a valuable research and teaching tool for the conceptualization of mitral valve dysfunction and the principles of repair.

Animals↗

PubMed2003

Induction of stromelysin-1 (MMP-3) by fibroblast growth factor-2 (FGF-2) in FGF-2-/- microvascular endothelial cells requires prolonged activation of extracellular signal-regulated kinases-1 and -2 (ERK-1/2).

Basic fibroblast growth factor (FGF-2) and matrix metalloproteinases (MMPs) play key roles in vascular remodeling. Because FGF-2 controls a number of proteolytic activities in various cell types, we tested its effect on vascular endothelial cell expression of MMP-3 (stromelysin-1), a broad-spectrum proteinase implicated in coronary atherosclerosis. Endothelial cells (EC) from FGF-2-/- mice are highly responsive to exogenous FGF-2 and were therefore used for this study. The results showed that treatment of microvascular EC with human recombinant FGF-2 results in strong induction of MMP-3 mRNA and protein expression. Upregulation of MMP-3 mRNA by FGF-2 requires de novo protein synthesis and activation of the ERK-1/2 pathway. FGF-2 concentrations (5-10 ng/ml) that induce rapid and prolonged (24 h) activation of ERK-1/2 upregulate MMP-3 expression. In contrast, lower concentrations (1-2 ng/ml) that induce robust but transient (<8 h) ERK-1/2 activation are ineffective. Inhibition of ERK-1/2 activation at different times (-0.5 h to +8 h) of EC treatment with effective FGF-2 concentrations blocks MMP-3 upregulation. Thus, FGF-2 induces EC expression of MMP-3 with a threshold dose effect that requires sustained activation of the ERK-1/2 pathway. Because FGF-2 controls other EC functions with a linear dose effect, these features indicate a unique role of MMP-3 in vascular remodeling.

Animals↗

PubMed2003

Minimally invasive aortic valve surgery in the elderly: a case-control study.

INTRODUCTION: Although minimally invasive aortic valve surgery (MIAVR) is performed in many centers, few studies have compared its results to a standard sternotomy (SS) approach. We assessed the hypothesis that, when compared with SS in the elderly population, MIAVR has similar morbidity and mortality and allows faster hospital recovery. METHODS AND RESULTS: From January 1995 through February 2002, 515 patients over age 65 underwent isolated aortic valve replacement. Using data gathered prospectively, 189 MIAVR patients were matched with 189 SS patients by age, ventricular function, valvular pathology, urgency of operation, diabetes, previous cardiac surgery, renal disease, and history of stroke. In each group, 56.1% of patients underwent non-elective procedures, and 28% were >or=80 years old. Hospital mortality (6.9%) and freedom from postoperative morbidity (82.5% versus 81.5%, P=0.79) were similar. Multivariate analysis revealed that urgent procedures [Odds Ratio (OR)=3.97; P=0.03], congestive heart failure (OR=3.94; P=0.03), and ejection fraction <30% (OR=4.16; P=0.03) were significant predictors of hospital mortality. Prolonged length of stay was associated with age (P=0.05), preoperative stroke (OR=3.5,P=0.001), CHF (OR=2.2, P=0.004), and sternotomy approach (OR=2.3,P=0.002) by multivariate analysis. More MIAVR patients were discharged home (52.6% versus 38.6%,P=0.03) rather than to rehabilitation facilities. Three year actuarial survival revealed no difference between groups. CONCLUSIONS: Minimally invasive aortic valve surgery is safe in elderly patients, with morbidity and mortality comparable to sternotomy approach. The shorter hospital stay and greater percentage of patients discharged home after MIAVR reflect enhanced recovery with this technique.

Aged↗

PubMed2003

Off-pump coronary artery bypass grafting reduces mortality and stroke in patients with atheromatous aortas: a case control study.

BACKGROUND: Patients with severe atheromatous aortic disease (AAD) who undergo coronary artery bypass (CABG) have an increased risk of death and stroke. We hypothesized that in these high risk patients, off-pump coronary artery bypass (OPCAB) technique is associated with lower morbidity and mortality. METHODS AND RESULTS: Between June 1993 and January 2002, 5737 patients undergoing CABG had routine intra-operative TEE with 913 (15.9%) found to have severe AAD in the aortic arch or ascending aorta. Of these, 211 patients who underwent OPCAB were matched with 211 on-pump CABG patients by age, ejection fraction, history of stroke, cerebrovascular disease, diabetes, renal disease, nonelective operation, and previous cardiac surgery. Hospital mortality was 11.4% (24/211) for on-pump CABG and 3.8% (8/211) for OPCAB (P=0.003). Multivariate analysis revealed that increased mortality was associated with on-pump CABG (P=0.001), acute MI (P=0.03), number of grafts (P=0.01), age (P=0.01), history of stroke or cerebrovascular disease (P=0.04), CHF (P=0.02), and peripheral vascular disease (P=0.03). Multivariate analysis showed that OPCAB technique was associated with decreased stroke (P=0.05). Freedom from any complication was 78.7% for on-pump CABG and 91.9% for OPCAB (P<0.001). At 36 month follow-up multivariate analysis revealed that increased mortality was associated with age (P=0.001), previous MI (P=0.03), and renal disease (P=0.04), whereas increased survival was associated with increased number of grafts (P=0.001) and OPCAB (P=0.01). CONCLUSIONS: OPCAB surgery in patients with severe AAD is associated with lower risk of death, stroke and complications and improved mid-term survival. Routine intra-operative TEE allows identification of these patients and directs choice of appropriate surgical technique.

Aged↗

PubMed2003

A quantitative in vitro model of smooth muscle cell migration through the arterial wall using the human amniotic membrane.

OBJECTIVE: The development of intimal hyperplasia involves smooth muscle cell (SMC) migration into the intima and proliferation. Matrix metalloproteinases and their tissue inhibitors play important roles in this process. In this study, we describe a novel in vitro model for studying SMC migration through the vessel wall. METHODS AND RESULTS: Human aortic SMCs (hASMCs) labeled with 125I-iododeoxyuridine or unlabeled were grown on the stromal aspect of the human amniotic membrane. Mechanical damage to endothelial cells grown on the basement membrane and addition of growth factors or platelets were characterized for their effect on SMC migration into the stroma both by histological methods and by measuring the radioactivity associated with the membrane after removal of noninvasive SMCs. To assess the reliability of the model, the cells were infected with a recombinant adenovirus encoding the tissue inhibitor of metalloproteinase-1 (TIMP-1). Addition of a platelet-derived growth factor gradient stimulated hASMC infiltration into the stroma. This effect was abolished with TIMP-1-transduced hASMC, confirming that TIMP-1 overexpression blocks SMC invasion of the stroma. CONCLUSIONS: This in vitro model of SMC migration in the vessel wall provides an inexpensive, quantitative, and reliable tool to study the molecular and cellular mechanisms of intimal hyperplasia.

Adenoviridae↗

PubMed2003

Aortic valve replacement in patients with impaired ventricular function.

BACKGROUND: Patients with reduced ventricular function undergoing aortic valve replacement have increased operative risks, but the impact of valvular pathophysiology and other risk factors has not been clearly defined. METHODS: From June 1992 through June 2002, 1,402 consecutive patients underwent isolated aortic valve surgery with or without coronary artery bypass grafting; of these patients, 416 had an ejection fraction less than 40% and are the subject of this report. These patients (mean age, 68.6) had severe stenosis (62.5%), severe regurgitation (30.3%), or mixed disease (7.2%). Aortic valve replacement plus coronary artery bypass grafting was performed in 48.4% of patients, and 27% had previous cardiac surgery. Follow-up included echocardiography and survival analysis. RESULTS: Hospital mortality was 10.1% (42 of 416), with no difference between aortic stenosis (9.6%) and regurgitation (11.1%). Multivariate analysis revealed that age (p = 0.002) and renal disease (odds ratio = 4.2; 95% confidence interval, 1.9 to 9.3; p = 0.001) were independently associated predictors of mortality. Valvular pathophysiology had no impact on mortality. Peripheral vascular disease, multivessel coronary disease, and renal disease were associated risks for any postoperative complication. Peripheral vascular disease (odds ratio = 12.3, p = 0.02), history of cerebrovascular disease (odds ratio = 4.8, p = 0.038), and diabetes (odds ratio = 2.7, p = 0.04) were associated risks for stroke. The ejection fraction was more than 40% in 52% of the patients who had postoperative echocardiography (mean follow-up, 6 months). Actuarial survival revealed no difference between pathophysiologic groups. CONCLUSIONS: Aortic valve surgery in patients with impaired ventricular function carries an acceptable operative risk that can be stratified by age and comorbidities. The type of valvular pathophysiology does not significantly affect mortality.

Aged↗

PubMed2003

Activation of mitogen-activated protein kinases during preparation of vein grafts and modulation by a synthetic inhibitor.

OBJECTIVE: Long-term durability of saphenous vein grafts used for coronary artery bypass grafting is limited by neointimal formation. Arterial vascular injury is known to activate intracellular mitogen-activated protein kinases, including extracellular signal-regulated kinases and c-jun N-terminal kinases, that affect cell differentiation, proliferation, migration, and apoptosis. This study tests the hypothesis that these mitogen-activated protein kinases are activated in saphenous veins during preparation for coronary artery bypass grafting. METHODS: Saphenous veins were harvested from 10 patients undergoing coronary artery bypass grafting. A specimen from each vein was placed in ice-cold lysis buffer immediately after harvesting (t = 0). The remaining tissue was incubated at room temperature in normal saline, 0.1% dimethylsulfoxide (vehicle), or 50 mmol/L PD98059 (mitogen-activated protein kinase kinase-1/2 inhibitor) until the vein was grafted (mean 50 minutes). To study kinetics of intracellular signaling pathways, canine saphenous veins were harvested, and mitogen-activated protein kinases and PI-3 kinase pathways were studied after different incubation time intervals. Extracted proteins were analyzed by Western blotting or in vitro kinase assay. RESULTS: The human saphenous veins showed elevated levels of active extracellular signal-regulated kinase after harvesting (t = 0) and prior to implant (t = 1). Incubation with PD98059 resulted in decreased activation of extracellular signal-regulated kinase. Kinetics of canine saphenous veins showed extracellular signal-regulated kinase and c-jun N-terminal kinase activation, in a time-dependent manner, along with activation of the growth factor-regulated PI3 kinase pathway. CONCLUSIONS: This study characterizes activation of extracellular signal-regulated kinases and c-jun N-terminal kinases during vein graft preparation and demonstrates the ability to inhibit extracellular signal-regulated kinase activation by simple incubation with a specific inhibitor. Further studies are needed to evaluate the significance of these findings with respect to graft durability.

Animals↗

PubMed2002

Minimally invasive mitral valve surgery: a 6-year experience with 714 patients.

BACKGROUND: This study analyzes a single institutional experience with minimally invasive mitral valve operations of 6 years, reviewing short-term morbidity and mortality and long-term echocardiographic follow-up data. METHODS: Seven hundred fourteen consecutive patients had minimally invasive mitral valve procedures between November 1995 and November 2001; concomitant procedures included 91 multiple valves and 18 coronary artery bypass grafts. Of these 714 patients, 561 patients had isolated mitral valve operations (375 repairs, 186 replacements). Mean age was 58.3 years (range, 14 to 96 years; 30.1% > 70 years), and 15.4% of patients had previous cardiac operations. Arterial cannulation was femoral in 79.0% and central in 21%, with the port access balloon endo-occlusion used in 82.3%. Cardioplegia was transjugular retrograde (54.1%) or antegrade (29.4%). Right anterior minithoracotomy was used in 96.6% and left posterior minithoracotomy in 2.2%. RESULTS: Hospital mortality for primary isolated mitral valve repair was 1.1% and 5.8% for isolated mitral valve replacement. Overall hospital mortality was 4.2% (30 of 714). Mean cross-clamp time was 92 minutes and mean cardiopulmonary bypass time was 127 minutes. Postoperatively, median ventilation time was 11 hours, intensive care unit time was 19 hours, and total hospital stay was 6 days. Complications for all patients included permanent neurologic deficit (2.9%), aortic dissection (0.3%); there was no mediastinal infection (0.0%). Follow-up echocardiography demonstrated 89.1% of the repair patients had only trace or no residual mitral insufficiency. CONCLUSIONS: This study demonstrates that the minimally invasive port access approach to mitral valve operations is reproducible with low perioperative morbidity and mortality and with late outcomes that are equivalent to conventional operations.

Adolescent↗

PubMed2002

Lack of ERK activation and cell migration in FGF-2-deficient endothelial cells.

The formation of blood capillaries from preexisting vessels (angiogenesis) and vascular remodeling secondary to atherosclerosis or vessel injury are characterized by endothelial cell migration and proliferation. Numerous growth factors control these cell functions. Basic fibroblast growth factor (FGF-2), a potent angiogenesis inducer, stimulates endothelial cell proliferation, migration, and proteinase production in vitro and in vivo. However, mice genetically deficient in FGF-2 have no apparent vascular defects. We have observed that endothelial cell migration in response to mechanical damage in vitro is accompanied by activation of the extracellular signal-regulated kinase (ERK) pathway, which can be blocked by neutralizing anti-FGF-2 antibodies. Endothelial cells from mice that are genetically deficient in FGF-2 neither migrate nor activate ERK in response to mechanical wounding. Addition of exogenous FGF-2 restores a normal cell response, which shows that impaired migration results from the genetic deficiency of this growth factor. Injury-induced ERK activation in endothelial cells occurs only at the edge of the wound. In addition, FGF-2-induced ERK activation mediates endothelial cell migration in response to wounding without a significant effect on proliferation. These data show that FGF-2 is a key regulator of endothelial cell migration during wound repair.

Animals↗

PubMed2002

Evolving techniques for mitral valve reconstruction.

OBJECTIVE: To analyze the effectiveness of new techniques of mitral valve reconstruction (MVR) that have evolved over the last decade, such as aggressive anterior leaflet repair and minimally invasive surgery using an endoaortic balloon occluder. SUMMARY BACKGROUND DATA: MVR via conventional sternotomy has been an established treatment for mitral insufficiency for over 20 years, primarily for the treatment of patients with posterior leaflet prolapse. METHODS: Between June 1980 and June 2001, 1,195 consecutive patients had MVR with ring annuloplasty. Conventional sternotomy was used in 843 patients, minimally invasive surgery in 352 (since June 1996). Anterior leaflet repair was performed in 374 patients, with increasing use over the last 10 years. Follow-up was 100% complete (mean 4.6 years, range 0.5-20.5). RESULTS: Hospital mortality was 4.7% overall and 1.4% for isolated MVR (1.1% for minimally invasive surgery vs. 1.6% for conventional sternotomy; =.4). Multivariate analysis showed the factors predictive of increased operative risk to be age, NYHA functional class, concomitant procedures, and previous cardiac surgery. The 5-year results for freedom from cardiac death, reoperation, and valve-related complications among the 782 patients with degenerative etiology are, respectively, as follows ( >.05 for all end points): for anterior leaflet repair, 93%, 94%, 90%; for no anterior leaflet repair, 91%, 92%, 91%; for minimally invasive surgery, 97%, 89%, 93%; and for conventional sternotomy, 93%, 94%, 90%. CONCLUSIONS: These findings indicate that late results of MVR after minimally invasive surgery and after anterior leaflet repair are equivalent to those achievable with conventional sternotomy and posterior leaflet repair. These options significantly expand the range of patients suitable for mitral valve repair surgery and give further evidence to support wider use of minimally invasive techniques.

Adult↗