Robert Matheny

Extracellular Matrix Scaffold for Cardiac Repair

Background—Heart failure remains a significant problem. Tissue-engineered cardiac patches offer potential to treat severe heart failure. We studied an extracellular matrix scaffold for repairing the infarcted left ventricle. Methods and Results—Pigs (n=42) underwent left ventricular (LV) infarction. At 6 to 8 weeks, either 4-layer multilaminate urinary bladder-derived extracellular matrix or expanded polytetrafluoroethlyene (ePTFE) was implanted as full-thickness LV wall patch replacement. At 1-week, 1-month, or 3-month intervals, pigs were terminated. After macroscopic examination, samples of tissue were prepared for histology, immunocytochemistry, and analysis of cell proportions by flow cytometry. One-week and 1-month patches were intact with thrombus and inflammation; at 1 month, there was also tissue with spindle-shaped cells in proteoglycan-rich and collagenous matrix. More α-smooth muscle actin-positive cells were present in urinary bladder matrix (UBM) than in ePTFE (22.2±3.3% versus 8.4±2.7%; P=0.04). At 3 months, UBM was bioresorbed, and a collagen-rich vascularized tissue with numerous myofibroblasts was present. Isolated regions of α-sarcomeric actin-positive, intensely α-smooth muscle actin-immunopositive, and striated cells were observed. ePTFE at 3 months had foreign-body response with necrosis and calcification. Flow cytometry showed similarities of cells from UBM to normal myocardium, whereas ePTFE had limited cardiomyocyte markers. Conclusions—Appearance of a fibrocellular tissue that included contractile cells accompanied biodegradation of UBM when implanted as an LV-free wall infarction patch. UBM appears superior to synthetic material for cardiac patching and trends toward myocardial replacement at 3 months.

Improvement in cardiac function with small intestine extracellular matrix is associated with recruitment of C-kit cells, myofibroblasts, and macrophages after myocardial infarction.

OBJECTIVES This study tested the hypothesis that modulation of angiogenesis and cardiac function by injecting small intestine extracellular matrix emulsion (EMU) into myocardium is associated with recruitment of c-kit cells, myofibroblasts, and macrophages after myocardial infarction. BACKGROUND Degradation of native extracellular matrix has been associated with adverse cardiac remodeling after infarction. METHODS Sixty-four rats were subjected to 45 min ischemia followed by 3, 7, 21, and 42 days of reperfusion, respectively. Saline or EMU (30 to 50 microl) was injected into the area at risk myocardium after reperfusion. Histological examination was performed by immunohistochemical staining, and cardiac function was analyzed using echocardiography. RESULTS The population of c-kit-positive cells in infarcted myocardium with the EMU injection increased significantly relative to the saline control at 7 days of reperfusion. Along with this change, alpha-smooth muscle actin expressing myofibroblasts and macrophages accumulated to a significant extent compared with the saline control. Increased vascular endothelial growth factor protein level and strong immunoreactivity of vascular endothelial growth factor expression were observed. Angiogenesis in the EMU area was significantly enhanced relative to the saline control, evidenced by increased density of alpha-smooth muscle actin positive vessels. Furthermore, echocardiography showed significant improvements in fractional shortening, ejection fraction, and stroke volume in the EMU group. The wall thickness of the infarcted middle anterior septum in the EMU group was significantly increased relative to the saline control. CONCLUSIONS We show for the first time that injection of EMU into the infarcted myocardium increases neovascularization and preserves cardiac function, potentially mediated by enhanced recruitment of c-kit-positive cells, myofibroblasts, and macrophages.

Right heart circulatory support facilitates coronary artery bypass without cardiopulmonary bypass

BACKGROUND Revascularization of the posterior wall often causes hemodynamic instability in beating heart coronary artery bypass (CAB). Our previous clinical studies have shown that tilting the heart primarily alters right-heart hemodynamics. The purpose of this study was to evaluate right-heart support in clinical cases. METHODS Seventeen patients underwent beating heart CAB with right-heart support. The right-heart support system (A-Med Systems, West Sacramento, CA) consisted of a coaxial cannula placed through the right atrium and the tip of the cannula positioned in main pulmonary artery. Blood was removed from the right atrium and returned to the main pulmonary artery. RESULTS Elective beating heart CAB was accomplished successfully in 17 patients with right-heart support. Anastomoses performed were left anterior descending coronary artery (11), diagonal (3), circumflex (5), obtuse marginal artery (11), and right coronary artery (10). Right-heart support between 1 and 3 L/min improved hemodynamics especially in the circumflex position. No device-related patient incidents occurred, nor were there incidents of infection or air embolism. All 17 patients were discharged to their homes. CONCLUSIONS The right-heart support system was safe without complications. Exposure of the posterior wall was possible in all cases without hemodynamic compromise.

Inertia of Success A Response to Minimally Invasive Coronary Bypass: A Dissenting Opinion

“To exist is to change, to change is to mature, to mature is to go on creating oneself endlessly.” Henri Bergson In a recent editorial, Bonchek and Ullyot1 raised concerns regarding minimally invasive coronary bypass surgery. Their purpose was to “stimulate discussion and debate,” and to that end, we wish to challenge several of their assertions. While we totally agree that unbridled enthusiasm with a blind eye toward critical analysis is dangerous, equally precarious is taking the stance that we have a perfect operation that cannot or should not be made better. We believe that we are at a strategic inflection point in cardiac surgery and are in danger of becoming obsolete. In the history of information systems, the typewriter made a valuable contribution; however, it subsequently was made obsolete by computers. Although there is no question that coronary artery bypass surgery has changed the management of coronary artery disease dramatically, we need to realize that we are in the field of coronary revascularization and not just coronary artery surgery. Incremental progress, carefully measured, documented, and reported, should be encouraged rather than always accepting the status quo. The authors begin by limiting the obvious successes of minimally invasive surgery to technically simple operations that require “a minimum of precision and almost no sewing.” Our colleagues in general surgery would most likely disagree that their successes in laparoscopic Nissen procedures and inguinal hernia repairs were not precise and did not requiring sewing. Although cardiac operations are technically more complex, this does not mean that we should ignore the principles, techniques, and enabling technology developed from technically simpler operations and extend them to more complex procedures. Is this not the nature of evolution? The authors relate their own experience of isolated internal mammary artery (IMA)–to–left anterior descending coronary artery (LAD) grafting …

Myocardial tissue replacement with extracellular matrix scaffolds

Backaround Heart failure from Ml is a major health problem. Recent evidence suggests myocardiaf repair and recovery of LV function might be possible through tissue engineering such as autologous skeletal myoblast transplant. An alternative strategy is repair of infarcted regions with acellular biological matrix scaffolds.. -We implanted porcine urinary bladder extracellular matrix scaffolds (UBM) as full-thickness RV outflow tract replacement patches in 4 pigs and 1 dog; 1 pig received glutaraldehyde-treated pericardium as control. At 6 wk gross and microscopic structure was studied; immunohistochemistry was performed to assess cellular recruitment. m No postoperative signs of cardiac insufficiency were seen. Implant sates were pearly white at the epicardial aspect. Endocardial surfaces of UBM showed pearly white tissue interdigitated with abundant brown-colored tissue whereas GP showed mostly pearly white with sparse brown tissue. GP was a discrete foreign body in a fibrotic capsule with extensive inflammation including many giant cells. UBM was undiscernrble and the site was mixed tissue including myocardium, fibrosis, and extensive neovascularization. UBM immunohistochemistry showed myeloid cells at the endocardial aspect. Cells expressing muscle actin, with two morphologies were seen in UBM sites: stellateispindle-shaped resembling myofibrobfasts, and striated cells resembling cardiomyocytes. Neovascularization with vWfand smooth muscle actin-positive cells was abundant. Extensive replication was evident by PCNA immunostaining. The endocardium was vWf-positive endothelial cells. Conchsions UBM implants were incorporated into RV free wall by a tissue replacement process involving recruitment of circulating cells as well as appearance of muscle cells that may derive from adjacent myocardium. In contrast, GP was incorporated into a fibrotic capsule without a replacement process. Further research into potential utility of UBM for myocardial tissue repair and mechanisms of the replacement process is warranted.

Enhanced Antimicrobial Effects of Decellularized Extracellular Matrix (CorMatrix) with Added Vancomycin and Gentamicin for Device Implant Protection

The incidence of cardiac implantable electronic device (CIED) infections has risen significantly over the past years. Although several devices are currently available to decrease the incidence of infection, most are made from nonviable synthetic material and are more prone to infection than vascularized tissue.