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Biomedical subjects

Robert E Michler

Publications and source records attributed to Robert E Michler.

At least 19 recordsLinked to original sources
PubMed2006

Vacuum-assisted apical suction devices induce passive electrical changes consistent with myocardial ischemia during off-pump coronary artery bypass graft surgery.

OBJECTIVE: Off-pump coronary artery bypass graft surgery is common therapy to completely revascularize diseased hearts. In order to graft posterior arteries in this procedure, the heart must be lifted from the chest cavity and manipulated to expose the surgical field using an apical suction device. This suction device may cause unwanted myocardial ischemia. METHODS: In this observational study, we measured myocardial electrical impedance, a parameter that responds to myocardial ischemia, as well as ST-segment changes during off-pump coronary artery bypass graft surgery in 12 patients with two-vessel coronary artery disease undergoing revascularisation of the left anterior descending and the posterior descending coronary arteries. During the posterior descending artery revascularisation phase of the procedure the apical suction device was oriented over the electrodes used to measure myocardial electrical impedance, thus allowing us the opportunity to assess myocardial ischemia in this region of the heart. RESULTS: In these 12 patients, myocardial electrical impedance progressively increased under the suction device during posterior coronary artery revascularisation, suggesting that myocardial ischemia developed in this region of the myocardium. ST-segment changes were negligible while the heart was vertically displaced (and the suction device attached), but increased immediately when the heart was returned to the neutral anatomical position. CONCLUSION: Our data suggest that the apical suction device may cause ischemia while the heart is vertically displaced and electrically disconnected from the body. Under these conditions, ST-segment changes may not detect myocardial ischemia. Myocardial electrical impedance has the potential to reliably detect intraoperative myocardial ischemia under these circumstances.

Coronary Artery Bypass, Off-Pump↗
PubMed2006

Surgical aspects of congestive heart failure.

Despite tremendous advances in the medical management of congestive heart failure the gold standard for the treatment of end stage congestive heart failure remains cardiac transplantation. The acknowledged critical limitation of sufficient suitable organ donors has resulted in the refinement and development of novel surgical alternatives for the treatment of congestive heart failure. These approaches include the extension of current conventional cardiac operations such as mitral valve repair to the failing ventricle, surgically reconstructing the size and shape of the failing left ventricle in order to optimize geometry and render it a more efficient pump, and partial or complete replacement of the ventricle with a mechanical device. The continued evolution of such therapies is likely to one day have a significant epidemiologic impact on patients suffering from end stage heart failure.

Aortic Valve↗
PubMed2006

Technical considerations for myocardial revascularization in congenital bilateral hypoplasia of the pericardium.

Congenital hypoplasia of the pericardium is a rare clinical condition that is typically encountered as an incidental finding during routine thoracic imaging or cardiothoracic surgery. Chest pain symptoms, when they occur, are often initially attributed to coronary ischemic syndromes, but herniation of cardiac structures through the pericardial defect, ischemia from torsion of great vessels, or compression of pulmonary parenchyma through defects between the aortic and pulmonary arteries can occur. Careful attention to cannulation techniques, conduit length, and the aberrant course of the phrenic nerves, typically through pericardial fibrous bands, is critical to the successful conduct of cardiac surgery.

Aged↗
PubMed2005

Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up.

BACKGROUND: Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device (LVAD) implantation. In addition, we sought to gain preliminary information on graft survival and any associated changes in cardiac function. METHODS AND RESULTS: Thirty patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twenty-four patients with a history of previous myocardial infarction and a left ventricular ejection fraction <40% were enrolled in the CABG arm. In a second arm, 6 patients underwent LVAD implantation as a bridge to heart transplantation, and patients donated their explanted native hearts for testing at the time of heart transplantation. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term, unexpected adverse events. Follow-up positron emission tomography scans showed new areas of glucose uptake within the infarct scar in CABG patients. Echocardiography measured an average change in left ventricular ejection fraction from 28% to 35% at 1 year and of 36% at 2 years. Histological evaluation in 4 of 6 patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. CONCLUSIONS: These results demonstrate the survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality offers a potential therapeutic treatment for end-stage heart disease.

Adult↗
PubMed2005

Correlation of autologous skeletal myoblast survival with changes in left ventricular remodeling in dilated ischemic heart failure.

OBJECTIVES: The effect of autologous skeletal myoblast transplantation has not been rigorously studied in the setting of end-stage ischemic heart failure free of concomitant coronary revascularization. The aims of the present study were to determine autologous skeletal myoblast survival and its effects on left ventricular function and remodeling in sheep with dilated ischemic heart failure. METHODS: Ischemic heart failure (left ventricular ejection fraction, 30% +/- 2%; left ventricular end-systolic volume index, 82 +/- 9 mL/m2) was created in sheep (n = 11) with serial left circumflex coronary artery microembolizations. Instruments were inserted for the long-term determination of left ventricular global and regional dimensions, hemodynamics, and pressure-volume analysis after autologous skeletal myoblast transplantation (approximately 3.0 x 10(8) myoblasts; heart failure plus autologous skeletal myoblast group, n = 5) or without (heart failure-control group, n = 6). Measurements were performed in conscious animals. RESULTS: Autologous skeletal myoblast-derived skeletal muscle was found in all injected animals at 6 weeks. In ischemic heart failure, autologous skeletal myoblast cardiomyoplasty failed to improve systolic (left ventricular ejection fraction, 29% +/- 4%; dP/dT(max), 2863 +/- 152 mm Hg/s; end-systolic elastance, 1.6 +/- 0.22) or diastolic (left ventricular end-diastolic pressure, 21 +/- 2 mm Hg; time constant of relaxation (Tau), 34 +/- 4 ms; dP/dT(min), -1880 +/- 68 mm Hg/s) function. There was, however, attenuation in the left ventricular dilatation after autologous skeletal myoblast transplantation (change in end-systolic volume index, 14% +/- 4% vs 32% +/- 6%; P < .05). The effects of autologous skeletal myoblast-derived skeletal muscle were exclusive to the left ventricular short-axis dimension and dependent on autologous skeletal myoblast survival (R2 = 0.59, P = .006, n = 11). CONCLUSIONS: Autologous skeletal cardiomyoplasty was able to attenuate left ventricular remodeling in sheep with end-stage ischemic heart failure.

Animals↗
PubMed2005

Early time course of myocardial electrical impedance during acute coronary artery occlusion in pigs, dogs, and humans.

Changes in myocardial electrical impedance (MEI) and physiological end points have been correlated during acute ischemia. However, the importance of MEI's early time course is not clear. This study evaluates such significance, by comparing the temporal behavior of MEI during acute total occlusion of the left anterior descending coronary artery in anesthetized humans, dogs, and pigs. Here, interspecies differences in three MEI parameters (baseline, time to plateau onset, and plateau value normalized by baseline) were evaluated using Kruskal-Wallis ANOVA and post hoc tests (P < 0.05). Noteworthy differences in the MEI time to plateau onset were observed: In dogs, MEI ischemic plateau was reached after 46.3 min (SD 12.9) min of occlusion, a significantly longer period compared with that of pigs and humans [4.7 (SD 1.2) and 4.1 min (SD 1.9), respectively]. However, no differences could be observed between both animal species regarding the normalized MEI ischemic plateau value (15.3% (SD 4.7) in pigs, vs. 19.6% (SD 2.6) in dogs). For all studied MEI parameters, only swine values resembled those of humans. The severity of myocardial supply ischemia, resulting from coronary artery occlusion, is known to be dependent on collateral flow. Thus, because dogs possess a well-developed collateral system (unlike humans or pigs), they have shown superior resistance to occlusion of a coronary artery. Here, the early MEI time course after left anterior descending coronary artery occlusion, represented by the time required to reach ischemic plateau, was proven to reflect such interspecies differences.

Acute Disease↗
PubMed2005

Recommendations of the National Heart, Lung, and Blood Institute Working Group on Future Direction in Cardiac Surgery.

New surgical procedures, imaging modalities, and medical devices have improved therapy for many patients and made treatment possible for others who have had few options in the past. In February 2004, the National Heart, Lung, and Blood Institute's (NHLBI) Advisory Council proposed that the institute evaluate the status and future directions in cardiac surgery. In response to this recommendation, the NHLBI convened a working group of cardiac surgeons on May 7 and 8, 2004, to assess the state of cardiac surgery research, identify critical gaps in current knowledge, determine areas of opportunity, and obtain specific recommendations for future research activities. The working group discussed surgical revascularization, novel surgical approaches, valvular research directions, biotechnology and cell-based therapy, heart failure, imaging modalities, and barriers to clinical research and presents its recommendations here.

Cardiac Surgical Procedures↗
PubMed2005

Smooth muscle cell expression of a constitutive active form of human Rac 1 accelerates cutaneous wound repair.

BACKGROUND: Hyperoxia has been shown to improve wound healing; however, the mechanism for such therapeutic effects of oxygen remains hypothetical. Rac 1 regulates a wide variety of cellular activities, including cell proliferation and migration, and also is a key regulator for the activity of the nicotinamide dinucleotide phosphate oxidase the enzyme complex responsible for the production of a large fraction of cellular superoxide. METHODS: We generated transgenic mice that express either the cDNA of a constitutively active mutant of human Rac 1 (V12 mutant or Rac CA) or the dominant negative isoform (V12 and N17 mutant or Rac DN) in the blood vessels using mouse vascular smooth muscle promoter for alpha-actin. We placed 2 wounds of 6 mm in diameter at the middorsal region of each mouse and allowed about 3 weeks for the wounds to heal. RESULTS: The size of the wounds in Rac CA transgenic mice was reduced relative to wild type mice; healing of Rac DN mice was slower than wild type and Rac CA ( P < .05). Blood vessel formation appeared faster in Rac CA mice, a finding associated with enhanced expression of some angiogenic growth factors. CONCLUSION: The current studies suggest that Rac 1 activation accelerates the wound healing process and is associated with more efficient angiogenesis at the wound site.

Actins↗
PubMed2005

Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy.

Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device implantation (LVAD). In addition, we sought to gain preliminary information on graft survival and any potential improvement of cardiac function. Eighteen patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twelve patients with a history of previous myocardial infarction (MI) and a left ventricular ejection of less than 30% were enrolled in the CABG arm. In a second arm, six patients underwent LVAD implantation as a bridge to heart transplantation and were required to donate their heart for testing at the time of heart transplant. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term unexpected adverse events. Follow-up PET scans showed new areas of viability within the infarct scar in CABG patients. Echocardiography measured an average improvement in left ventricular ejection fraction (LVEF) from 25% to 34%. Histological evaluation in four out of five patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. These interim results demonstrate survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality may offer a potential therapeutic treatment for end-stage heart disease.

Adult↗
PubMed2004

Myocardial electrical impedance responds to ischemia and reperfusion in humans.

Myocardial electrical impedance (MEI) is correlated to ischemia and reperfusion of the heart muscle. The entire body of work with MEI to this point has been carried out in animal subjects in vivo and excised tissue samples. In this study, we measured MEI clinically for the first time in human patients who were undergoing off-pump coronary artery bypass (OPCAB) surgery. MEI was measured with a monitor designed in this laboratory and approved by the FDA for use on human subjects. Our patient population (n = 18) had a 70%-100% stenosis of the diseased coronary artery targeted for bypass. We measured MEI continuously during surgery and at 3, 6, 24, and 72 h postoperatively from two temporary pacing electrodes attached to the heart muscle. Absolute baseline impedance ranged from 173 to 729 ohms. MEI increased with occlusion of the diseased artery prior to bypass. The percent increase from baseline was inversely correlated to the percent stenosis of the diseased artery. MEI decreased below baseline immediately on reperfusion following bypass in all patients and continued decreasing over the measurement period. MEI is a reliable clinical indicator of ischemia and reperfusion in humans and may indicate the effectiveness of coronary artery surgery. The parameter may have monitoring and diagnostic value in heart disease in humans.

Adult↗
PubMed2004

Clinical trials in the surgical management of congestive heart failure: surgical ventricular restoration and autologous skeletal myoblast and stem cell cardiomyoplasty.

Despite continued advances in medical and surgical approaches for patients with ischemic cardiomyopathy, congestive heart failure (CHF) remains a growing cause of morbidity and mortality. Historically, surgical options for end-stage CHF have been limited. However, there are several surgical therapies now under clinical investigation that appear promising in the effort to reverse or restore the remodeled left ventricle. This review will focus on early but current clinical studies examining surgical ventricular restoration and autologous skeletal myoblast and stem cell transplantation. Although these emerging therapeutic options remain in the early stages of study and development, they hold promise in providing options to those patients with end-stage CHF.

Animals↗
PubMed2003

Off-pump coronary artery bypass grafting does not decrease the incidence of atrial fibrillation.

BACKGROUND: Postoperative atrial fibrillation remains a significant source of morbidity after coronary artery bypass grafting. We reviewed the data on 2,569 patients to determine if the absence of cardiopulmonary bypass resulted in a lower incidence of atrial fibrillation. METHODS: All patients undergoing coronary artery bypass grafting without cardiopulmonary bypass from January 1, 1997 through June 30, 2001 were evaluated for postoperative atrial fibrillation. The data of 252 patients with no cardiopulmonary bypass (group 1) were reviewed and compared with three other patient groups. Group 2 consisted of 1,470 patients using cardiopulmonary bypass during the same study period. Group 3 consisted of 841 patients with a similar number of grafts as the study group but using cardiopulmonary bypass. Group 4 consisted of historical data for 847 patients operated on using cardiopulmonary bypass collected from January 1995 through December 1996. Prophylactic beta-blockade was instituted in January 1997. Groups 1 to 3 received this treatment, but group 4 did not. RESULTS: Group 1 had an incidence of atrial fibrillation of 8.8%. Groups 2, 3, and 4 had incidences of atrial fibrillation of 11.6%, 9.4%, and 28.0%, respectively. When compared with group 1, the incidence of atrial fibrillation in group 4 was statistically different (p <. 0001). CONCLUSIONS: Avoiding cardiopulmonary bypass did not aid the reduction of atrial fibrillation at our institution.

Aged↗
PubMed2002

Overexpression of soluble fas attenuates transplant arteriosclerosis in rat aortic allografts.

BACKGROUND: The killing of vascular cells by activated macrophages is an important step in the process of destabilization of the arterial wall. The death receptor Fas is implicated in vascular cell death. Hence, we extended our studies in a rat aortic allograft model, using adenovirus-mediated overexpression of soluble Fas (sFas) to block Fas binding to Fas ligand (Fas-L). The contribution of Fas to vascular cell injury and consequent transplant arteriosclerosis was investigated. METHODS AND RESULTS: Activated monocytes in the presence of macrophage colony-stimulating factor induce endothelial cell apoptosis in vitro, which was significantly inhibited by adenovirus-mediated sFas overexpression. Next, donor rat abdominal aortas were either untreated or transduced with adenoviruses encoding (1) rat soluble Fas (Ad3rsFas), (2) no insert (Ad3Null), and (3) beta-galactosidase (Ad3nBg). A total of 175 aortic grafts were harvested 2 to 90 days after transplantation. Vascular cell apoptosis and CD45+ cell infiltration were significantly reduced in Ad3rsFas-transduced aortas, as compared with control allografts. Moreover, the control allografts developed marked intimal thickening, whereas Ad3rsFas-transduced allografts had significantly less neointima until the 90-day time point. CONCLUSIONS: sFas overexpression protects the integrity of the vessel wall from immune injury and attenuates transplant arteriosclerosis.

Adenoviridae↗
PubMed2002

Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles.

BACKGROUND: The exact role of adrenoceptors in norepinephrine (NE)-mediated regulation of the human coronary circulation has yet to be elucidated. Thus, the goals of this study were to characterize the adrenoceptors involved in the responses to NE in isolated human coronary arterioles and small arteries. METHODS AND RESULTS: Arterioles (n=39) and small arteries from the left ventricle of explanted human hearts were isolated and cannulated. Vessels from the hearts of 21 patients were studied: 15 males and 6 females, aged 0.5 to 63 years. Nineteen patients were considered to be New York Heart Association class 4. All hearts exhibited hypertrophy (190+/-20%). The passive diameter of arterioles was 167+/-8 microm (range 97 to 323 microm). NE (10(-7) to 3x10(- 7) mol/L) elicited concentration-dependent dilations (47+/-4 microm) that were unaffected by endothelium removal, N(omega)-nitro-L-arginine (10(- 4) mol/L, an NO synthase inhibitor), or practolol (10(-6) mol/L, a beta1-receptor blocker). However, administration of propranolol (10(-5) mol/L, a combined beta1- and beta2-blocker) or butoxamine (10(-6) mol/L, a beta2-receptor blocker) completely eliminated the NE-induced dilation. Constrictions to NE (2 of 39 vessels) were inhibited by prazosin (10(-6) mol/L, an alpha1-receptor blocker). Methoxamine (10(-9) to 10(-5) mol/L, an alpha1-agonist) had no effect, whereas U44619, a thromboxane mimetic, elicited dose-dependent constriction of vessels. CONCLUSIONS: Our data indicate that isolated human coronary arterioles and small arteries dilate to NE via beta2-receptors on smooth muscle. These findings are important to our understanding of the mechanisms action of NE in the human coronary circulation.

Adolescent↗
PubMed2002

Ex-vivo mitral valve repair prior to orthotopic cardiac transplantation.

Mitral valve annuloplasty was performed prior to orthotopic cardiac transplantation in two donor hearts which were diagnosed with moderate to severe mitral regurgitation. The technical aspects are reviewed of ex-vivo mitral valve repair with concomitant heart transplantation. The recipients were classified as United Network for Organ Sharing (UNOS) I and both patients have had an excellent postoperative recovery. Over 2-year follow-up demonstrates normal mitral valve function without regurgitation.

Heart Failure↗
PubMed2002

An alternative surgical approach to facilitate minimally invasive mitral valve surgery.

An alternative approach to minimally invasive mitral valve surgery is described that permits direct great vessel cannulation and direct aortic clamp occlusion through a 6- to 8-cm incision. This approach reduces the complexity of the procedure, and hopefully, will contribute to more widespread adoption of less invasive techniques in mitral valve surgery.

Cardiopulmonary Bypass↗
PubMed2002

Short- and long-term results of open heart surgery in patients with abdominal solid organ transplant.

OBJECTIVES: Cardiac disease is a common cause of mortality and morbidity in patients with abdominal solid organ transplant. Improvement of the results of abdominal organ transplantation has contributed to an increasing pool of patients who require open heart surgery. We investigated short- and long-term results of open heart surgery in patients with functioning abdominal solid organ transplants. METHODS: We retrospectively examined 60 patients (52.5 years in average) undergoing coronary artery bypass grafting and/or valve surgery since July 1988 after abdominal organ transplantation. There were 22 females (37%). They consisted of 46 kidney, nine kidney-pancreas and five liver recipients. Cardiac surgery was performed 68.9 months after transplantation. Preoperative serum creatinine level was 2.1 mg/dl, and 11 patients (18%) had creatinine level more than 3.0 mg/dl. Eleven patients (18%) were operated upon on non-elective basis. Twelve patients (20%) were not given stress-dose steroids postoperatively. RESULTS: Three patients died early after surgery (5.0%). Twenty-six major complications were seen in 17 patients (28%), including deterioration of renal function in seven (three patients required temporary hemodialysis), three major infections, two bleeding complications, and two strokes. No graft loss was encountered. No differences were seen in mortality and morbidity between patients with or without stress-dose steroids. Multivariate analysis identified cardiopulmonary bypass time (P<0.05) as a risk factor for operative death, preoperative creatinine level (P<0.05), cardiopulmonary bypass time (P<0.05) and the amount of fresh frozen plasma used (P<0.05) for major complication, non-elective surgery (P<0.01) for deterioration of renal function. Thirteen patients died and five kidney allografts failed late after surgery. Three- and 5-year patient and graft survivals were 70.8 and 66.8, 84.5 and 84.5%, respectively. Multivariate regression analysis identified female gender (P<0.05), body mass index (P<0.001) and non-elective surgery (P<0.001) as risk factors for late death, and preoperative creatinine level (P<0.05) for late graft loss. CONCLUSIONS: Open heart surgery can be performed with acceptable short- and long-term results in patients with functioning abdominal transplants. Stress-dose steroid may be unnecessary in selected patients. Aggressive use of open heart surgery in this patient population to avoid non-elective surgery may further improve early and late surgical outcomes.

Adult↗