Richard J. Myung

Preoperative pulmonary venous obstruction affects long-term outcome for survivors of total anomalous pulmonary venous connection repair

BACKGROUND Early outcomes after repair of total anomalous pulmonary venous connection continue to improve; however, little information is available concerning long-term functional status and quality of life. METHODS One hundred patients underwent isolated total anomalous pulmonary venous connection repair at The Childrens Hospital of Philadelphia between 1983 and 2001. Medical records were reviewed and a standardized questionnaire was administered to guardians of survivors. RESULTS Median age at repair was 15.5 days (range, 1 to 563 days). Overall hospital mortality was 14%, decreasing from 19% before 1995 to 5% after 1995. At 15 years after repair, actuarial survival was 84% and freedom from late death or reintervention for hospital survivors was 85%. At a median follow-up of 5.9 years (range, 0 to 17.7 years) 64% of guardians described their childs overall health as excellent, 27% good, 9% fair, and 0% poor. With regard to school performance, 40% of children were characterized as above average, 29% average, 4% below average, and 27% were in special education classes or had repeated grades. By multivariable logistic regression, the presence of associated chromosomal or noncardiac syndromes and pulmonary venous obstruction were found to be significant factors with regard to parental assessment of both overall health and school performance. CONCLUSIONS The majority of children who undergo isolated total anomalous pulmonary venous connection repair can expect an excellent long-term functional outcome. Factors present before operation, such as pulmonary venous obstruction and associated anomalies, can influence overall health and school performance in the long term.

Tissue engineering of arteries by directed remodeling of intact arterial segments.

Traditional approaches to generating tissue-engineered arteries in vitro rely on expansion of cells in culture to seed appropriate scaffolds. In most envisioned applications, small autologous blood vessels would be harvested and used as a source for these cells. We propose that small autologous arteries, not the cells derived from them, may be an attractive starting point for engineered arteries. This approach capitalizes on the ability of intact arteries to grow and remodel in response to chronic changes in their mechanical environment. Carotid arteries from juvenile (approximately 30-kg) pigs were stretched longitudinally in an ex vivo perfusion system over 9 days. This resulted in a 40% increase in artery length at physiological longitudinal stress and a 20 +/- 3% increase when unstressed. Control arteries were perfused for 9 days ex vivo at their physiological loaded length. Control and elongated arteries displayed native appearance (macroscopic and histological), excellent viability (cellularity and mitochondrial activity), normal vasoactivity, and similar mechanical properties (ultimate stress and ultimate strain) as compared with freshly harvested arteries. Growth, as opposed to just redistribution of existing mass, contributed to elongation as evidenced by an increase in artery weight. Results on elongation of arteries from neonatal and adolescent pigs are also presented and discussed.

Influence of On-Pump Versus Off-Pump Techniques and Completeness of Revascularization on Long-Term Survival After Coronary Artery Bypass

BACKGROUND Off-pump coronary artery bypass graft surgery (OPCABG) may be associated with reduced morbidity and in-hospital mortality. In this study, we report the influence of surgery type, number of grafts, and the Index of Completeness of Revascularization (ICOR), namely, the number of grafts/number diseased vessel systems, on long-term survival. METHODS From 1997 to 2006, 12,812 consecutive patients underwent isolated CABG at a single academic center. Ten-year survival data were obtained by cross-referencing patients with the national Social Security Death Index. A propensity score analysis of 46 preoperative characteristics balanced risk factors between surgical groups. A proportional hazards regression analysis modeled the hazard of death as a function of surgery type (on versus off), distal group (1 to 3 versus 4 to 7 vessels), ICOR, and propensity score. RESULTS Proportional hazards regression analysis showed no significant influence of surgery type or number of grafts on long-term survival within the four groups: OPCABG 1 to 3 grafts (n = 3,946; ICOR 1.11), OPCABG 4 to 7 grafts (n = 1,721; ICOR 1.56), on-pump CABG 1 to 3 grafts (n = 3,380; ICOR 1.21), and on-pump CABG 4 to 7 grafts (n = 3,765; ICOR 1.64). Irrespective of technique of revascularization, there was a survival advantage for patients with higher ICOR. CONCLUSIONS Long-term survival was similar for patients receiving 1 to 3 or 4 to 7 grafts by either on-pump or off-pump techniques. However, higher ICOR was associated with improved long- term survival within all groups.

Mechanical Environment, Donor Age, and Presence of Endothelium Interact to Modulate Porcine Artery Viability Ex Vivo

AbstractThough ex vivo culture of arteries is a widely used model of native arteries and is closely aligned with efforts to generate tissue-engineered arteries, the effects of culture conditions on artery viability are poorly characterized. To investigate factors regulating long-term viability of cultured arteries, carotid arteries from neonatal and adolescent pigs were perfused for up to 27 days with steady laminar flow ranging from ∼2% to ∼200% of physiological flow rates. Arteries from neonatal animals (2 weeks old, ∼5 kg) were susceptible to spontaneous progressive endothelial denudation followed by deterioration of the vessel wall that spread from luminal to abluminal regions. Subphysiological levels of flow and pressure abrogated this deterioration. Arteries harvested from adolescent (6 months old, ∼100 kg) animals maintained viability and retained structure for at least 9 days as assessed by normal histology, presence of intact endothelium, normal mitochondrial activity, and low levels of cell death and proliferation, unless the vessels were subjected to superphysiological levels of flow or the endothelium was intentionally denuded. Adolescent arteries perfused at subphysiological, but not physiological, flow rates maintained viability and normal structure for at least 27 days. These data indicate that under the appropriate conditions, arteries may be cultured long term but careful attention to the viability is merited.

Hemodynamic conditions alter axial and circumferential remodeling of arteries engineered ex vivo.

We previously demonstrated that growth and remodeling was stimulated in arteries elongated ex vivo using step increases in axial strain. Viability and vasoactivity were similar to fresh arteries, however there was a substantial decrease in the ultimate circumferential stress. To test the hypothesis that the subphysiological perfusion conditions (i.e., low pressure and flow) previously used caused the reduction, arteries were subjected to the identical elongation protocol (50% increase over 9 days) while being perfused with physiological levels of flow, viscosity and pulsatile pressure. A significant increase in unloaded length was achieved by elongation under both perfusion conditions, although the increase was less under physiological (7 ± 1%) than under subphysiological conditions (19 ± 2%, p < 0.005). When length at physiological stress was estimated using mechanical testing data the values were similar. The ultimate circumferential stress of arteries elongated under physiological conditions was increased (33%), whereas the ultimate axial stress was decreased (50%) as compared with arteries elongated under subphysiological conditions. Elongated arteries under both perfusion conditions showed significant increases in proliferation and collagen mass, and similar viability and appearance to fresh arteries. These data suggest that there is substantial cross-talk between perfusion conditions and axial strain that modulates arterial remodeling and length.

Modified ultrafiltration may not improve neurologic outcome following deep hypothermic circulatory arrest.

OBJECTIVE Modified ultrafiltration (MUF) improves systolic blood pressure and left ventricular performance, as well as lowering transfusion requirements, after cardiopulmonary bypass (CPB). MUF has also been shown to enhance acute cerebral metabolic recovery after deep hypothermic circulatory arrest (DHCA), but whether this improves neurologic outcome is unknown. METHODS Sixteen neonatal piglets underwent CPB and 90 min of DHCA. The hematocrit was maintained between 25 and 30%. Alpha-stat blood gas management was used. After separation from CPB, animals were randomized to 15 min of MUF (n = 8) or no intervention (n = 8). Neurologic injury was assessed with behavior scores and histologic examination. Standardized behavior scores were obtained on post-operative days 1, 3, and 6 (0 = no deficit to 95 = brain death). The percentage of injured neurons by hematoxylin and eosin staining and the degree of reactive astrocytosis by glial filbrillary acidic protein (GFAP) immunohistochemistry were assessed to determine histologic scores in the neocortex and hippocampus (0 = no injury to 4 = diffuse injury). RESULTS There were no statistically significant differences between groups during CPB. After MUF, the hematocrit was significantly higher (40% +/- 5.7 vs. 28% +/- 3.9, P < 0.001). There were no significant differences in behavior scores between groups (p > 0.1). There was resolution of deficits by day 6 in all animals. Neuronal injury was present in 81% (13/16) of the animals with no statistically significant differences between groups in incidence or severity. CONCLUSIONS Use of MUF after DHCA does not prevent neuronal injury or improve neurologic outcome in this neonatal swine model.