Intramyocardial implantation of CD133+ stem cells improved cardiac function without bypass surgery.

INTRODUCTION: Cell transplantation for myocardial regeneration has been shown to have beneficial effects on cardiac function after myocardial infarction. Most clinical studies of intramyocardial cell transplantation were performed in combination with coronary artery bypass grafting (CABG). The contribution of implanted stem cells could yet not be clearly distinguished from the effect of the CABG surgery. Our current phase 1 clinical study has focused on the safety and feasibility of CD133+-enriched stem cell transplantation without CABG and its potential beneficial effect on cardiac function. METHOD AND RESULTS: Ten patients with end-stage chronic ischemic cardiomyopathy (ejection fraction <22%) were enrolled in the study. Bone marrow (up to 380 mL) was harvested from the iliac crest. CD133+ cells were purified from bone marrow cells using the CliniMACS device with purities up to 99%. Autologous bone marrow CD133+ cells (1.5-9.7 X 106 cells) were injected into predefined regions. Cardiac functions prior to and 3, 6, and 9 months after cell transplantation were assessed by cardiac magnetic resonance imaging. Stem cell transplantation typically improved the heart function stage from New York Heart Association/Canadian Cardiovascular Society class III-IV to I-II. The mean preoperative and postoperative ventricular ejection fractions were 15.8 +/- 5% and 24.8 +/- 5%, respectively. CONCLUSION: CD133+ injection into ischemic myocardium was feasible and safe. Stem cell transplantation alone improved cardiac function in all patients. This technique might hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization.

Autologous transplantation of CD133+ BM-derived stem cells as a therapeutic option for dilatative cardiomyopathy.

We report the case of a 58-year-old man with end-stage non-ischemic cardiomyopathy. Baseline transthoracic echocardiography (TTE) and cardiac magnetic resonance (cMRI) revealed a markedly depressed left ventricle systolic function. He underwent autologous CD133+ BM-derived cell transplantation through a minimally invasive approach. During surgery 19 x 10(6) BM-derived stem cells were injected by the transepimyocardial route. Six months after the operation TTE and cMRI showed a clear improvement in left ventricular contractility.

Intraaortic balloon pump counterpulsation after implantation of infrarenal and thoracoabdominal aortic protheses.

Highly complex vascular surgery interventions have nowadays become possible due to sophisticated operative techniques and modern intra- and postoperative anesthesiological strategies. Accordingly, the number of high risk vascular surgery interventions rises continuously and thus, the number of secondary complications after high risk interventions increases as well and requires likewise extraordinary treatment concepts. We report of a 68-year old patient who 6 months previously was operated on a ruptured abdominal aneurysm, before he was admitted to our institution for the treatment of a type IIIb (Crawford classification) thoracoabdominal aneurysm. Intraoperatively we implanted a 26 mm Dacron prosthesis which was anastomosed with the previously existing infrarenal graft. Postoperatively the patient suffered from a hemodynamically significant myocardial infarction and acute coronary catheter intervention was necessary. However, circulatory stability could not be reestablished by interventional measures and we therefore decided to implant the intraaortic balloon pump despite the presence of two synthetic aortic grafts. However, the chance of success of such a manoeuver as well as the effectiveness of intraprosthetic counterpulsation was unclear and our literature research undertaken to predict the risk of such a manouver was unsatisfactory. We therefore want to report this case and compile the literature dealing with perceptions and complications of intraaortic counterpulsation after the implantation of synthetic aortic prostheses, since such a treatment option comes to an increased clinical application in comparable constellations.

Mechanical assist devices as bridging systems to transplantation: A current review, possible risks, and perspectives.

Mechanical circulatory support is of increasing interest because of its considerable demographic importance concerning myocardial failure and because of stagnant transplantation volumes. This study offers an overview of the present state of the art. Institutions with a mechanical circulatory assist program usually dispose of a decision chart for the various systems. There are devices with intra- or extracorporeal pump positions and with long- or short-term application. The various possibilities of mechanical circulatory assistance are presented, along with their technical properties, indications, and results. Currently, the application is concerned with technical reliability and limited biocompatibility with thrombembolic, neurological, and infectious complications. With some further developments, the present state of the art is supposed to enable a widespread application as bridging systems and as long-term therapy of heart failure within the next few years.

Myocardial protection with monophosphoryl lipid-A against aortic cross clamping-induced global stunning.

BACKGROUND: Monophosphoryl lipid-A (MLA) has a late window (24 hours) of cardioprotection against acute myocardial infarction. It is not known whether MLA, administered, 24 hours before surgery, attenuates intraoperative ventricular dysfunction "stunning" associated with aortic cross-clamping and reperfusion during elective cardiac surgery. We determined the dose-response relationship between MLA and ventricular function in a canine model of global myocardial stunning in the absence of necrosis. The role of expression of inducible heat shock protein 70 (HSP 70i) was also investigated. METHODS: Mongrel dogs (n = 32) were intravenously injected with either a vehicle solution or 3, 5, 10, 35 ug/kg MLA. Twenty four hours later, dogs were anesthetized and instrumented, in situ, to monitor the left ventricular performance (the slope of regression between stroke-work and end diastolic length). Tissue samples were obtained to determine HSP70i using immunoblot analysis. After a period of equilibration on cardiopulmonary bypass, the aortic cross-clamp was applied at normothermia for 30 minutes followed by 60 minutes of reperfusion. ATP and catabolites were determined in transmural myocardial biopsies. Triphenyl-tetrazolium chloride (TTC) staining was used to determine myocardial necrosis. RESULTS: MLA treatment did not alter myocardial contractility or ATP metabolism. Global ischemia resulted in about 50% depletion of ATP and remained depressed during reperfusion in all groups. MLA-treated hearts had improved functional recovery in a dose dependent-manner. Significant recovery was observed at the highest dose (35 ug/kg) compared to the control group. Immunoblot analysis demonstrated significant increase in HSP 70i in the MLA-treated hearts. CONCLUSIONS: MLA exhibits a delayed (24 hours) window of protection against myocardial stunning associated with aortic cross-clamping. HSP70i expression may play a role in MLA-mediated cardioprotection.

Decreased expression of tissue inhibitor of metalloproteinase 1 in stunned myocardium.

Ultrastructural studies of stunned myocardium have shown disorganization and loss of extracellular collagen and increased collagenase activity early after ischemia and reperfusion. The interplay between matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) regulates the turnover of cardiac extracellular matrix fibrillar collagens. However, the gene expression of MMP-1 and TIMP-1 in stunned myocardium is not known. Here, we determined whether altered expression of MMP-1 and TIMP-1 occurs in globally stunned hearts. An isolated nonworking rabbit heart preparation, perfused with a bovine erythrocyte suspension in modified Krebs solution, was used. Two groups were studied: the stunned group was subjected to 20 min of normothermic global ischemia followed by 120 min of normal reperfusion (n = 8), and the control group underwent 140 min of uninterrupted perfusion (n = 7). The developed pressures at the end of reperfusion for ischemic and control hearts were 67.0 +/- 2.73 and 83.1 +/- 1.52 mm Hg (P < 0. 006) respectively. Ribonuclease protection assays of total left ventricular RNA using riboprobes for MMP-1, TIMP-1, and 18S rRNA were performed. A significant decrease (twofold, P < 0.03) in TIMP-1 gene expression was found in the stunned hearts, while MMP-1 mRNA expression was unchanged. Thus, in early stunning, the decrease in TIMP-1 expression could tip the balance favoring enhanced metalloproteinase activity, promoting collagen turnover, and initiating extracellular matrix remodeling. This may contribute to delayed recovery from myocardial stunning.