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Ram Sharony

Publications and source records attributed to Ram Sharony.

At least 19 recordsLinked to original sources
PubMed2006

[Surgical ventricular restoration--new horizons in the treatment of ischemic cardiomyopathy].

Heart failure is a major health problem with increasing prevalence due to aging of the population and in addition to an increase in effective treatment and early myocardial reperfusion during acute myocardial infarction. Postinfarction left ventricular remodeling is characterized by chamber dilatation with an abnormal spherical shape leading to systolic and diastolic dysfunction frequently associated with mitral valve insufficiency and eventually heart failure. Intensive medical management reduces symptoms and improves survival. However, patients who are in NYHA functional class III or IV still have a poor prognosis. In this review article we will endeavor to summarize the emerging surgical approach "surgical ventricular restoration" for treating ventricular remodeling and ischemic cardiomyopathy. These concepts of restoration of the elliptical shape of the left ventricle and re-establishing the normal structure of the sub-valvular mitral apparatus are performed recently in our department.

Cardiac Surgical Procedures↗
PubMed2005

Anti-proliferative and anti-inflammatory effects of topical MAPK inhibition in arterialized vein grafts.

Vein graft failure following bypass surgery is a frequent and important clinical problem. The vascular injury caused by arterialization is responsible for vein graft intimal hyperplasia, a lesion generated by medial smooth muscle cell proliferation and migration into the intima, increased extracellular matrix deposition, and formation of a thick neointima. Development of the neointima into a typical atherosclerotic lesion and consequent stenosis ultimately result in vein graft failure. Endothelial damage, inflammation, and intracellular signaling through mitogen-activated protein kinases (MAPKs) have been implicated in the early stages of this process. We therefore investigated the effects of topical inhibition of ERK-1/2 MAPK activation on vascular cell proliferation and apoptosis, and on the inflammatory response in a canine model of vein graft arterialization. For this purpose, vein grafts were incubated with the MEK-1/2 inhibitor, UO126, ex vivo for 30 min before grafting. This treatment effectively abolished arterialization-induced ERK-1/2 activation, decreased medial cell proliferation, and increased apoptosis. UO126 treatment also inhibited the vein graft infiltration by myeloperoxidase-positive inflammatory cells that follows vein graft arterialization. Thus, topical ex vivo administration of MAPK inhibitors can provide a pharmacological tool to prevent or reduce the vascular cell responses that lead to vein graft intimal hyperplasia and graft failure.

Administration, Topical↗
PubMed2005

Matrix metalloproteinase expression in vein grafts: role of inflammatory mediators and extracellular signal-regulated kinases-1 and -2.

Matrix metalloproteinases (MMPs) play key roles in vascular remodeling. We characterized the role of inflammatory mediators and extracellular signal-regulated kinases (ERKs) in the control of arterialized vein graft expression of MMP-9, MMP-2, and membrane-type 1-MMP (MT1-MMP) and of the tissue inhibitor of metalloproteinases-2 (TIMP-2). For this purpose we used a canine model of jugular vein to carotid artery interposition graft and analyzed the vein grafts at various postoperative times (30 min to 28 days) using the contralateral vein as a control. To study the role of ERK-1/2, veins were incubated with the mitogen-activated protein kinase kinase (MEK-1/2) inhibitor UO126 for 30 min before being grafted. Vein graft extracts were analyzed for MMPs, TIMP-2, tumor necrosis factor-alpha (TNF-alpha), polymorphonuclear neutrophil (PMN) infiltration, myeloperoxidase (MPO), and thrombin activity, and for ERK-1/2 activation. Vein graft arterialization resulted in rapid and sustained (8 h to 28 days) upregulation of vein graft-associated MMP-9, MMP-2, MT1-MMP, thrombin activity, and TNF-alpha levels with concomitant TIMP-2 downregulation. MMP-2 activation preceded MT1-MMP upregulation. PMN infiltration and vein graft-associated MPO activity increased within hours after arterialization, indicating a prompt, local inflammatory response. In cultured smooth muscle cells, both thrombin and TNF-alpha upregulated MT1-MMP expression; however, only thrombin activated MMP-2. Inhibition of ERK-1/2 activation blocked arterialization-induced upregulation of MMP-2, MMP-9, and MT1-MMP. Thus, thrombin, inflammatory mediators, and activation of the ERK-1/2 pathway control MMP and TIMP-2 expression in arterialized vein grafts.

Anastomosis, Surgical↗
PubMed2005

Pharmacological preconditioning with monophosphoryl lipid A improves post ischemic diastolic function and modifies TNF-alpha synthesis.

OBJECTIVE: Pharmacologic preconditioning represents an attractive myocardial protection strategy. Tumor necrosis factor-alpha plays an important role in myocardial ischemia-reperfusion injury. We aimed to determine the effect of Monophosphoryl lipid A-induced delayed preconditioning on diastolic and systolic left ventricular function and tumor necrosis factor-alpha synthesis during ischemia and reperfusion. METHODS: Rats (n=10) were pretreated with Monophosphoryl lipid A (350 microg/kg) or vehicle (n=9). Twenty-four hours later, the hearts were isolated and perfused on a Langendorff apparatus. Hemodynamic measurements, tumor necrosis factor-alpha mRNA expression and protein content were studied after stabilization (baseline), after 35 min of global ischemia and at 40 min of reperfusion. RESULTS: Left ventricular developed pressure and peak rate of left ventricular developed pressure (dP/dt) rise were comparable between the animals in the control and Monophosphoryl lipid A treated groups during baseline but were higher in Monophosphoryl lipid A group at reperfusion (74+/-4 vs 51+/-5 mmHg, 3340+/-172 vs 2240+/-156 mmHg/s, respectively, P<0.01). dP/dt fall was significantly lower in the MLA group (2630+/-225v 1580+/-210 mmHg/s, P<0.01) at 40 min of reperfusion as well as end diastolic pressure. Baseline tumor necrosis factor-alpha mRNA (expressed as arbitrary densitometry units) were higher in the Monophosphoryl lipid A group (1.3+/-0.1 vs 0.5+/-0.03, P<0.05) but remained constant after ischemia and reperfusion (1.3+/-0.1 and 1.4+/-0.03, P=0.2), while further increase was observed in the control group (from 1.0+/-0.1 to 1.4+/-0.1, P<0.05). Tumor necrosis factor-alpha protein content from heart effluent in the control group was increased during reperfusion (79+/-30 and 200+/-22pg/ml, P<0.05) but was undetectable in the Monophosphoryl lipid A group. Marked TNF-alpha immunostaining of left ventricular tissue was observed only in the control group but no TNF-alpha staining was evident in the Monophosphoryl lipid A treated group at 40 min of reperfusion. CONCLUSION: Monophosphoryl lipid A-induced preconditioning renders the heart more tolerant to ischemia-reperfusion in terms of left ventricular diastolic and systolic function, and prevents tumor necrosis factor-alpha production during ischemia, through aborting the translation phase of tumor necrosis factor-alpha synthesis.

Animals↗
PubMed2005

Modification of surgical planning based on cardiac multidetector computed tomography in reoperative heart surgery.

BACKGROUND: Repeat open heart surgery is associated with an increased risk of injury to old conduits and cardiac structures. To reduce this risk, we evaluated the contribution of multidetector computed tomography angiography in planning repeat cardiac operations. METHODS: Fifteen patients who had previous coronary artery bypass grafting procedures underwent retrospective-gated computed tomographic angiography with a 16-slice multidetector computed tomography. Relation of the grafts to the expected median sternotomy line, graft patency and anatomic course, possible aortic cannulation and cross-clamp sites, distances between the right ventricle to the sternum, and calcification of the ascending aorta were assessed. RESULTS: Multidetector computed tomography demonstrated 45 conduits (mean, 3 +/- 1.1); 18 arterial grafts and 13 saphenous vein grafts that were patent, and 2 internal mammary artery grafts and 12 saphenous vein grafts that were occluded. Significant narrowing was shown in 3 of the patent internal mammary arteries and 4 of the patent saphenous vein grafts. Adherence of the right ventricle, left internal mammary artery, and saphenous vein graft to the sternum (0 to 3 mm in the midline) was demonstrated in 8, 2, and 1 patients, respectively. Two patients had a heavily calcified aorta. During surgery, all multidetector computed tomographic findings were confirmed. Three aspects of the operative plans of 4 patients were modified according to multidetector computed tomographic findings: median sternotomy approach (3 patients), cannulation site (2 patients), and myocardial preservation technique (3 patients). On the basis of multidetector computed tomographic evaluations, surgery was cancelled in 2 patients in whom repeat operation was judged to be associated with increased risk: 1 patient, scheduled for coronary artery bypass grafting, had an extremely calcified aorta, and the other, scheduled for aortic valve replacement, had grafts that were adherent to the sternum. CONCLUSIONS: Multidetector computed tomography is a new noninvasive tool for three-dimensional preoperative assessment of complex cardiac and graft anatomy. Our initial experience suggests that it may provide information to warrant modifying surgical planning, thus contributing to the safety of reoperative heart surgery.

Aged↗
PubMed2005

No-touch aorta off-pump coronary surgery: the effect on stroke.

OBJECTIVE: Studies examining the neuroprotective effects of off-pump coronary artery bypass grafting have shown inconsistent results. Most studies, however, have not differentiated between clampless and clamp off-pump techniques. The aim of this study was to evaluate the effect of avoiding aortic manipulation on major neurologic outcomes after off-pump coronary artery bypass grafting. METHODS: A total of 700 consecutive patients undergoing multiple-vessel off-pump coronary artery bypass grafting between 2000 and 2003 were included. The 429 patients undergoing aortic no-touch technique were compared with 271 patients in whom partial aortic clamps were applied. The aorta was screened by manual palpation, and epiaortic ultrasonography was used selectively. RESULTS: The frequency of detected atherosclerotic aortic disease was higher in the no-touch group (17.4% vs 5.1%, P < .0001). No-touch revascularization was achieved with arterial conduits, arranged in T-graft or in situ configurations (50%). The respective graft/patient ratios were 2.5 +/- 0.6 and 2.6 +/- 0.6 in the side-clamp and no-touch groups ( P = .009); however, revascularization of the posterolateral myocardial territory was comparable (87% vs 90%, difference not significant). The incidence of stroke (0.2% vs 2.2%, P = .01) was significantly lower in the no-touch group (1/429). Logistic regression identified partial aortic clamping as the only independent predictor of stroke (odds ratio 28.5, confidence interval 0.22-333, P = .009), increasing this risk 28-fold. Peripheral vascular disease ( P = .068), diabetes ( P = .072), and history of stroke ( P = .074) trended toward stroke. CONCLUSIONS: Avoiding partial aortic clamping during off-pump coronary artery bypass grafting provides superior neurologic outcome. The results are reproducible and irrespective of the severity of aortic disease or the method of aortic screening. This technique is recommended whenever technically feasible.

Adult↗
PubMed2005

Thermo-wrap technology preserves normothermia better than routine thermal care in patients undergoing off-pump coronary artery bypass and is associated with lower immune response and lesser myocardial damage.

OBJECTIVE: Perioperative hypothermia might be detrimental to the patient undergoing off-pump coronary artery bypass surgery. We assessed the efficacy of the Allon thermoregulation system (MTRE Advanced Technologies Ltd, Or-Akiva, Israel) compared with that of routine thermal care in maintaining normothermia during and after off-pump coronary artery bypass surgery. METHODS: Patients undergoing off-pump coronary artery bypass surgery were perioperatively and randomly warmed with the 2 techniques (n = 45 per group). Core temperature, hemodynamics, and troponin I, interleukin 6, interleukin 8, and interleukin 10 blood levels were assessed. RESULTS: The mean temperature of the patients in the Allon thermoregulation system group (AT group) was significantly ( P < .005) higher than that of the patients receiving routine thermal care (the RTC group); less than 40% of the latter reached 36 degrees C compared with 100% of the former. The cardiac index was higher and the systemic vascular resistance was lower ( P < .05) by 16% and 25%, respectively, in the individuals in the AT group compared with in the individuals in the RTC group during the 4 postoperative hours. End-of-surgery interleukin 6 levels and 24-hour postoperative troponin I levels were significantly ( P < .01) lower in the patients in the AT group than in the RTC group. The RTC group's troponin levels closely correlated with their interleukin 6 levels at the end of the operation ( R = 0.51, P = .002). CONCLUSIONS: Unlike routine thermal care, the Allon thermoregulation system maintains core normothermia in more than 80% of patients undergoing off-pump coronary artery bypass surgery. Normothermia is associated with better cardiac and vascular conditions, a lower cardiac injury rate, and a lower inflammatory response. The close correlation between the increased interleukin 6 and troponin I levels in the routine thermal care group indicates a potential deleterious effect of lowered temperature on the patient's outcome.

Aged↗
PubMed2005

Off-pump coronary revascularization of the circumflex system: comparison between sequential and nonsequential arterial grafts.

BACKGROUND: Sequential grafting increases the availability of arterial grafts. This study aims to determine the safety and efficacy of sequential grafting of the circumflex coronary distribution performed off-pump. METHODS: Between 2000 and 2003, 136 patients undergoing off-pump sequential arterial grafting of the circumflex territory were compared to 278 patients who received nonsequential grafts to the same area. RESULTS: The grafts/patient ratio was higher in the sequential than the nonsequential group (3.2 +/- .4 and 2.3 +/- .2, respectively, P < .0001). Radial artery conduits and T-grafts were used more often in the sequential group; conversely, bilateral internal thoracic artery configurations were more frequent in the nonsequential groups (P < .0001). There were 1.2 sequential anastomoses per patient. Early mortality (2.2% versus 2.5%), myocardial infarction (2.2% versus 1.1%) and stroke (.7% versus none) rates were comparable. Use of sequentials or other operative confounders had no independent effect on the occurrence of early adverse events (stepwise logistic regression). At 3.5 years, survival was 95.9% and 84.2% in the sequential and nonsequential groups, respectively (P = .231, log-rank). Despite comparable incidence of major adverse cardiac events (MACE) (6.6% versus 8.6%, P = .470) and similar 3.5-year freedom from MACE (88.7% for both groups, P = .682), Cox regression analysis identified sequential grafting as an independent predictor of MACE (P < .0001, HR 19.9), increasing this risk by 20-fold. CONCLUSIONS: Off-pump sequential grafting of the circumflex system may be safely performed. The use of sequentials, however, had an independent effect on increased midterm MACE. The distribution of events suggests culpability of surgical factors and may reflect a learning curve.

Adult↗
PubMed2004

Semirigid partial annuloplasty band allows dynamic mitral annular motion and minimizes valvular gradients: an echocardiographic study.

BACKGROUND: Traditional mitral annuloplasty devices include both rigid rings, which restrict annular motion, and soft rings and bands, which can locally deform. Conflicting data exist regarding their impact on annular dynamics. We studied mitral annuloplasty with a semirigid partial band and with a nearly complete rigid ring. METHODS: Intraoperative three-dimensional transesophageal echocardiograms (n = 14) and predischarge transthoracic echocardiograms were retrospectively analyzed in patients undergoing mitral valve repair for degenerative disease with either a rigid ring (n = 77) or a semirigid partial band (n = 38). Each transesophageal echocardiogram was analyzed with TomTec three-dimensional software to produce cardiac cycle frame planimetry and to measure device geometry. Actual device sizes provided reference dimensions. Blinded analysis of Doppler data from transthoracic echocardiograms was performed. RESULTS: Validation of the quantitative transesophageal echocardiogram methodology revealed a 1.3% +/- 0.3% (mean +/- standard error of the mean) underestimation of actual linear dimension. With the semirigid partial band, systolic valve orifice area and intertrigonal distance decreased from 6.14 +/- 0.37 to 5.55 +/- 0.24 cm(2) (-9.6%; p = 0.01) and from 2.69 +/- 0.08 to 2.55 +/- 0.13 cm (-5.2%; p = 0.03), respectively. Systolic anterior-posterior distance decreased from 2.1 +/- 0.10 to 1.95 +/- 0.06 cm (-7.1%; p = 0.01) compared with diastole. In contrast, rigid ring orifice area was unchanged (4.12 +/- 0.15 to 4.10 +/- 0.16 cm(2); -0.5%; p = 0.48) during the cardiac cycle. Transthoracic echocardiography revealed significantly lower mitral inflow gradients with semirigid partial band (mean gradients compared with rigid ring, 4.0 +/- 0.3 versus 5.0 +/- 0.3 mm Hg; p = 0.02; peak gradients, 8.9 +/- 0.5 versus 11.1 +/- 0.5 mm Hg; p = 0.01). CONCLUSIONS: Three-dimensional transesophageal echocardiographic measurements of annular dynamics are valid and reliable when discrete annuloplasty devices are present. In contrast to the rigid ring, the semirigid partial band permits more physiologic geometric changes and is associated with lower postoperative mitral valve gradients.

Echocardiography, Doppler↗
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

Propensity case-matched analysis of off-pump coronary artery bypass grafting in patients with atheromatous aortic disease.

OBJECTIVE: Atheromatous aortic disease is a risk factor for excessive mortality and stroke in patients undergoing coronary artery bypass grafting. Outcomes of off-pump coronary artery bypass grafting and coronary artery bypass grafting with cardiopulmonary bypass in patients with severe atheromatous aortic disease were compared by propensity case-match methods. METHODS: Routine intraoperative transesophageal echocardiography identified 985 patients undergoing isolated coronary artery bypass grafting with severe atheromatous disease in the aortic arch or ascending aorta. Off-pump coronary artery bypass grafting was performed in 281 patients (28.5%). Propensity matched-pairs analysis was used to match patients undergoing off-pump coronary artery bypass grafting (n = 245) with patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. RESULTS: Univariate analysis revealed decreased hospital mortality (16/245, 6.5% vs 28/245, 11.4%; P =.058) and stroke prevalence (4/245, 1.6% vs 14/245, 5.7%; P =.03) in off-pump coronary artery bypass grafting compared with coronary artery bypass grafting with cardiopulmonary bypass. Freedom from any postoperative complication was higher in off-pump coronary artery bypass grafting compared with coronary artery bypass grafting with cardiopulmonary bypass (226/245, 92.2% vs 196/245, 80.0%; P <.001). Multivariable analysis of preoperative risk factors showed that increased hospital mortality was associated with coronary artery bypass grafting with cardiopulmonary bypass (odds ratio = 2.7; P =.01), fewer grafts (P =.05), acute myocardial infarction (odds ratio = 11.5; P <.001), chronic obstructive pulmonary disease (odds ratio = 2.4; P =.03), previous cardiac surgery (odds ratio = 10.2, P =.05), and peripheral vascular disease (odds ratio = 2.1; P =.05). Cardiopulmonary bypass was the only independent risk factor for stroke (odds ratio = 3.6, P =.03). At 36 months' follow-up, comparable survival was observed in the off-pump coronary artery bypass grafting and coronary artery bypass grafting with cardiopulmonary bypass groups (74% vs 72%). Multivariable analysis revealed that renal disease (P <.001), advanced age (P <.001), previous myocardial infarction (P =.03), and lower number of grafts (P =.02) were independent risks for late mortality. CONCLUSIONS: Patients with severe atherosclerotic aortic disease who undergo off-pump coronary artery bypass grafting have a significantly lower prevalence of hospital mortality, perioperative stroke, and overall complications than matched patients who underwent coronary artery bypass grafting with cardiopulmonary bypass. Routine intraoperative transesophageal echocardiography identifies severe atheromatous aortic disease and directs the choice of surgical technique.

Aged↗
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↗
PubMed2004

Off-pump coronary artery bypass grafting: single center experience with 1,000 consecutive patients.

BACKGROUND: Advances in surgical techniques and retractor-stabilizer devices allowing access to all coronary segments have resulted in increased interest in off-pump coronary artery bypass. The residual motion in the anastomotic site and potential hemodynamic derangements, however, render this operation technically more demanding. OBJECTIVES: To evaluate the OPCAB experience in a single Israeli center. METHODS: Between 2000 and 2003 in our institution, 1,000 patients underwent off-pump operations. Patients were grouped by the type of procedure, i.e., minimally invasive direct coronary artery bypass or mid-sternotomy OPCAB. RESULTS: One hundred MIDCAB operations were performed. Of the 900 OPCAB, 767 patients received multiple grafts with an average of 2.6 +/- 0.6 grafts per patient (range 2-4) and the remaining patients underwent single grafting during hybrid or emergency procedures. In the multiple-graft OPCAB group, complete revascularization was achieved in 96%. Multiple arterial conduits were used in 76% of the patients, and total arterial revascularization without aortic manipulation, using T-graft (35%) or in situ configurations, was performed in 61%. The respective rates for early mortality, myocardial infarction and stroke in the MIDCAB were 1%, 0% and 2%, and 2%, 1.3% and 0.9% in the multiple-vessel OPCAB groups. Multivariate analysis identified renal dysfunction (odds ratio 11.5, confidence interval 3.02-43.8; P < 0.0001) and emergency operation (OR 8.74, CL 1.99-38.3; P = 0.004) as predictors of mortality. The proportion of off-pump procedures increased from 9% prior to the study period to 59%. CONCLUSIONS: The use of OPCAB does not compromise the ability to achieve complete myocardial revascularization. Our procedure of choice is OPCAB using arterial conduits, preferably the 'no-touch' aorta technique.

Aged↗
PubMed2004

Propensity score analysis of a six-year experience with minimally invasive isolated aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Although minimally invasive aortic valve replacement (MIAVR) is becoming an accepted technique, additional outcome evaluation is required. To correct for non-randomized treatment, the propensity score was used to analyze the present authors' experience with MIAVR compared to standard sternotomy (SS). METHODS: Between January 1995 and December 2002, a total of 921 consecutive patients underwent isolated AVR; 438 of these patients had MIAVR. Two matched cohorts each of 233 patients, and with comparable distributions of risk factors, were constructed using propensity analysis of prospectively collected data. Matching variables included left ventricular ejection fraction <30%, previous myocardial infarction, congestive heart failure, previous cardiac surgery, renal insufficiency, age, gender, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, previous stroke or carotid disease, urgent/emergent operation, valvular pathophysiology, and atheromatous aortic disease. RESULTS: Hospital mortality and major morbidity were similar in the MIAVR and SS groups: 5.6% versus 7.3% (p = 0.45) and 13.3% versus 14.2% (p = 0.79), respectively. Multivariable analysis of all patients revealed increased mortality with severe atheromatous aortic disease (p = 0.001), COPD (p = 0.002), and urgent operation (p = 0.02). Freedom from any major perioperative morbidity was similar in both groups (86.7% versus 85.8%; p = 0.79). However, the median length of stay was shorter with MIAVR (6 versus 8 days; p <0.001). During the past three years, a greater percentage of MIAVR patients than SS patients was discharged home rather than sent to rehabilitation facilities or nursing homes (65.7% versus 52.9%; p = 0.05). CONCLUSION: MIAVR can be performed safely, with morbidity and mortality outcomes similar to those of standard sternotomy. MIAVR is associated with a decreased length of hospital stay, and a greater proportion of patients are discharged home directly.

Aged↗
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↗