Deep hypothermic circulatory arrest in cyanotic piglets is associated with increased neuronal necrosis.

BACKGROUND: The contribution of neonatal cyanosis, inherent to cyanotic congenital heart disease, to the magnitude of neurologic injury during deep hypothermic circulatory arrest has not been fully delineated. This study investigates the impact of cyanosis and deep hypothermic circulatory arrest on brain injury. METHODS: Neonatal piglets were randomised to placement of a pulmonary artery to left atrium shunt to create cyanosis or sham thoracotomy. At day 7, animals were randomised to undergo deep hypothermic circulatory arrest or sham. Arterial oxygen tension and haematocrit were obtained. Neurobehavioural performance was serially assessed. The animals were sacrificed on day 14. Brain tissue was assessed for neuronal necrosis using a 5-point histopathologic score. RESULTS: Four experimental groups were analysed (sham, n = 10; sham + deep hypothermic circulatory arrest, n = 8; shunt, n = 9; shunt + deep hypothermic circulatory arrest, n = 7). Cyanotic piglets had significantly higher haematocrit and lower partial pressure of oxygen at day 14 than non-cyanotic piglets. There were no statistically significant differences in neurobehavioural scores at day 1. However, shunt + deep hypothermic circulatory arrest piglets had evidence of greater neuronal injury than sham animals (median (range): 2 (0-4) versus 0 (0-0), p = 0.02). DISCUSSION: Cyanotic piglets undergoing deep hypothermic circulatory arrest had increased neuronal injury compared to sham animals. Significant injury was not seen for either cyanosis or deep hypothermic circulatory arrest alone relative to shams. These findings suggest an interaction between cyanosis and deep hypothermic circulatory arrest and may partially explain the suboptimal neurologic outcomes seen in children with cyanotic heart disease who undergo deep hypothermic circulatory arrest.

Midterm results of David V valve-sparing aortic root replacement in acute type A aortic dissection.

BACKGROUND: The David V valve-sparing aortic root replacement (David V) has been shown to provide excellent long-term valve function and low rates of valve-related complications in the elective treatment of aortic root aneurysms. The safety and durability of the David V in the repair of acute type A aortic dissection (type A) are currently unclear. In this study, the midterm results of David V in the setting of type A aortic dissection were analyzed. METHODS: From 2005 to 2013, 350 patients underwent surgical repair of type A aortic dissection. Outcomes were analyzed in 43 consecutive patients who received a David V during repair of type A aortic dissection. Patients were followed with annual postoperative echocardiograms. Follow-up was 85% complete, with a mean duration of 40 ± 31 months. RESULTS: The mean age of these patients was 46 ± 10 years. There were two operative deaths (4.7%), and 93% of patients required a hemiarch replacement (n = 32) or a total arch replacement (n = 8) using hypothermic circulatory arrest. Cusp repairs were performed in 6 (14%) patients; 51% of patients had 3+ or greater preoperative aortic insufficiency (AI), 83% of patients left the operating room with zero AI, and the remainder had 1+ AI or less. No patient in the follow-up period developed endocarditis or required aortic valve replacement. At midterm follow-up, freedom from 2+ AI was 94%, and freedom from aortic valve replacement was 100%. CONCLUSIONS: The David V can be performed with low morbidity and mortality in young patients presenting with type A aortic dissection who require aortic root replacement. At midterm follow-up, valve function is durable, and the incidence of valve-related complications is low.

Impact of preoperative chronic lung disease on survival after surgical aortic valve replacement.

BACKGROUND: An increasing number of patients requiring surgical aortic valve replacement (SAVR) present with chronic pulmonary obstructive disease (COPD). The purpose of this study was to compare patients who had a range of COPD from normal to severe and were undergoing SAVR. METHODS: Retrospective review of 2,379 patients undergoing SAVR ± coronary artery bypass grafting (CABG) from January 2002 to April 2012 at a US academic institution was performed. COPD was defined according to the Society of Thoracic Surgeons (STS) adult cardiac database: normal (forced expiratory volume [FEV] > 75% predicted), mild (FEV in 1 second [FEV1] 60%-75%), moderate (FEV1 50%-59%), and severe (FEV1 < 50%). Multivariable logistic and Cox regression methods were used to determine independent association between COPD and short- and long-term outcomes. Selection bias adjustment was achieved using the STS predicted risk of mortality (PROM). Adjusted odds ratios (AORs) and adjusted hazard ratios (AHR) were calculated using the normal lung function group as the reference. Kaplan-Meier curves were created to estimate long-term survival. RESULTS: One thousand five hundred seventeen of 2,379 patients (63.8%) had isolated SAVR, whereas 862 of 2,379 (36.2%) patients underwent SAVR + CABG. Preoperative COPD was common among patients (21.9%) undergoing SAVR ± CABG and included 332 (14.0%) patients with mild COPD, 89 (3.7%) patients with moderate COPD, and 101 (4.2%) patients with severe COPD. Unadjusted in-hospital mortality rose significantly with COPD class, from 3.9% for those with no COPD to 9.6% to patients with severe COPD. After adjustment, in-hospital mortality was not statistically different in normal patients and in those with COPD. In contrast, when compared with normal patients, adjusted long-term survival was worse across levels of COPD: mild (AHR, 1.70; p < 0.001), moderate (AHR, 2.25; p < 0.001), and severe (AHR, 2.28; p < 0.001). CONCLUSIONS: Preoperative COPD is common in the SAVR population and is associated with diminished long-term but not short-term survival.

Aortic arch surgery using moderate hypothermia and unilateral selective antegrade cerebral perfusion.

BACKGROUND: Cerebral protection and circulatory management remains a controversial issue in aortic arch surgery. The present study reported surgical outcomes of arch repair using moderate hypothermic circulatory arrest (MHCA) and unilateral selective antegrade perfusion (uSACP). METHODS: From January 2004 and December 2012, 500 patients underwent hemiarch repair (HARCH) and 124 underwent total arch replacement (TARCH) utilizing moderate hypothermic circulatory arrest with unilateral selective antegrade cerebral perfusion of the right axillary artery. Emergent surgery was required in 142 (28.4%) of HARCH patients and 18 (14.5%) of TARCH patients. Mean arrest temperature ranged from 25.6-27.2 °C for elective and emergent operations in both groups. Mean circulatory arrest was 26.8 minutes for hemiarch repairs and 54.2 minutes for total arch replacement. RESULTS: Overall mortality was 6.6% for hemiarch repairs and 9.7% for total arch replacements. Hospital mortality was 4.5% (16/358) and 10.4% (11/106) in elective cases, and 12% (17/142) and 5.6% (1/18) in elective cases, for hemiarch and total arch replacements respectively. Permanent neurological deficit (PND) occurred in 3 total arch replacement cases (2.4%). Multivariate analysis demonstrated that temperature was not found to be an independent risk factor during hemiarch or total arch replacements for mortality, permanent or neurological deficits, or renal failure. CONCLUSIONS: Our approach for hemiarch and total arch repair utilizing MHCA and uSACP via the right axillary artery was associated excellent neurological and survival outcomes. Moderate hypothermia did not adversely impact cerebral or visceral organ protection.

Sternotomy versus nonsternotomy LIMA-LAD grafting for single-vessel disease.

BACKGROUND: Single-vessel disease of the left anterior descending (LAD) coronary artery may be surgically revascularized by left internal mammary artery (LIMA) grafting either through a sternotomy or a nonsternotomy approach. Nonsternotomy approaches are used in the hope of achieving a less invasive operation. It is unknown whether nonsternotomy approaches impact in-hospital or midterm outcomes. METHODS: The institutional Society of Thoracic Surgeons (STS) database at a single US academic center was reviewed for 597 consecutive patients treated surgically for single-vessel LAD disease from January 1, 2002 to June 30, 2011. In-hospital adverse events and length of stay (LOS) were compared between patients who had LIMA-LAD grafting performed through a sternotomy (sternotomy patients) versus patients who had this procedure performed through a nonsternotomy approach (nonsternotomy patients), adjusted for propensity score (likelihood of receiving sternotomy, calculated on 33 variables). Midterm survival between groups was compared using Kaplan-Meier and Cox regression analysis by referencing the National Social Security Death Index. RESULTS: There were 597 consecutive patients who underwent single-vessel grafting by LIMA-LAD coronary artery grafting. Of these patients, 234 underwent sternotomy, whereas 363 patients had nonsternotomy procedures: 239 patients had endoscopic LIMA harvest and left anterolateral thoracotomy, 106 patients had robot LIMA harvest and left anterolateral thoracotomy, and 18 patients had minimally invasive direct coronary artery bypass. There were no strokes in the nonsternotomy group and 3 (1.3%) in the sternotomy group (p = 0.031). Thirty-day mortality, incidence of myocardial infarction, hospital LOS, and midterm survival were similar between groups. Operative time was significantly longer in the nonsternotomy group (1.8 hours, 95% confidence interval [CI], 1.5-2.1). CONCLUSIONS: In this propensity-adjusted comparison, sternal-sparing incisions were associated with similar 30-day adverse events and midterm survival compared with sternotomy for single-vessel LIMA-LAD artery grafting.

Hemiarch replacement at 28°C: an analysis of mild and moderate hypothermia in 500 patients.

BACKGROUND: During the past decade, use has increased of moderate hypothermic circulatory arrest with antegrade cerebral perfusion for cerebral protection during aortic arch operations. This study examined the use of mild hypothermia in conjunction with unilateral selective antegrade cerebral perfusion (uSACP) for hemiarch replacement for proximal aortic arch reconstruction. METHODS: A retrospective review of the Emory Aortic Database identified 708 patients who underwent aortic arch replacement between 2004 and 2011. Of these, 500 underwent hemiarch replacement at temperatures of 22°C or higher with uSACP. Outcomes were analyzed and compared between 277 patients undergoing hemiarch at a temperature of 28.6°C (mild) and 233 undergoing hemiarch at a temperature of 24.3°C (moderate). Propensity scores were generated and analyzed between the groups to adjust for confounding factors such as selection bias. RESULTS: Operative mortality was equivalent between mild and moderate groups in elective (4.2% vs 4.8%, p=0.80) and emergency (7.7% vs 11.7%, p=0.43) settings. No differences occurred in the incidence of temporary neurologic dysfunction, dialysis-dependent renal failure, or mediastinal reexploration for bleeding between mild and moderate patients. The incidence of permanent neurologic deficit was significantly reduced in mild (2.5%) vs moderate patients (7.2%, p=0.01), which was confirmed by the propensity score analysis (adjusted odds ratio, 0.28; p=0.02). CONCLUSIONS: Hemiarch replacement can be safely performed at 28°C with uSACP in emergency and elective settings. Mild hypothermia with uSACP offers adequate levels of neurologic protection compared with deeper levels of hypothermia.

Risk factors for conversion to cardiopulmonary bypass during off-pump coronary artery bypass surgery.

BACKGROUND: Off-pump coronary artery bypass graft (OPCAB) may be associated with improved hospital outcomes compared with on-pump coronary artery bypass graft. However, intraoperative conversion to on-pump coronary artery bypass graft has been associated with adverse outcomes. The purpose of this study was to identify preoperative risk factors for intraoperative conversion in nonemergent patients undergoing isolated OPCAB. METHODS: From 2002 to 2010, 8,077 consecutive OPCAB cases were performed at a single US academic center. Of these, 200 (2.5%) required intraoperative conversion. Standard variables from The Society of Thoracic Surgeons database were analyzed. A multivariable logistic model with adjusted odds ratios (OR) and 95% confidence intervals was used to identify independent risk factors for conversion. Adjusted in-hospital and long-term survival between converted and nonconverted patients were determined using multiple logistic regression and Cox proportional hazards regression, respectively. RESULTS: Converted patients had a higher Society of Thoracic Surgeons predicted risk of mortality (2.8% versus 2.1%; p<0.001). Surgeon identity was the most significant multivariable predictor of conversion. After adjustment for surgeon identity, the following independent risk factors were associated with intraoperative conversion: previous coronary artery bypass graft (OR, 3.43; p=0.018), congestive heart failure (OR, 1.51), myocardial infarction (OR, 1.86), number of grafts (OR, 1.45), left main disease (OR 1.41), and urgent status (OR, 1.77; all p<0.05). Conversion to on-pump coronary artery bypass graft was associated with increased in-hospital (OR, 4.8; p<0.001) and long-term mortality (hazard ratio, 1.65; p<0.001). CONCLUSIONS: Conversion to cardiopulmonary bypass during OPCAB is associated with increased in-hospital and long-term mortality and may be related to surgeon experience. Recognition of the preoperative risk factors associated with an increased risk of conversion may allow for better patient selection and reduce the incidence of intraoperative conversion during OPCAB.

Expanding the indications for the David V aortic root replacement: early results.

OBJECTIVE: To examine the early results of the David V valve-sparing aortic root replacement procedure in expanded, higher risk clinical scenarios with appropriately selected patients. METHODS: From 2005 to 2011, 150 David V valve-sparing aortic root replacements were performed within Emory Healthcare. A total of 78 patients (expanded group) had undergone the David V in expanded, difficult clinical settings such as emergent type A dissection (n = 29), grade 3+ or greater aortic insufficiency (AI) (n = 53), or reoperative cardiac surgery (n = 14). These patients were evaluated and compared with a group of 72 patients (traditional group) with less than grade 3+ AI who underwent a David V in a traditional, elective setting. The mean follow-up was 19 months (range, 1-72), and the follow-up data were 88% complete. RESULTS: There were 3 operative deaths (2.2%), all occurring in the expanded group. The overall patient survival at 6 years was 95%. Three patients required aortic valve replacement: two for severe AI and one for fungal endocarditis. Both groups had concomitant cusp repairs performed in conjunction with the David V (traditional, n = 10; and expanded, n = 16; P = .27). At follow-up, freedom from moderate AI was 93%, and the freedom from aortic valve replacement was 98%. No significant difference was observed in the freedom from moderate AI between the expanded and traditional groups (91% vs 95%, respectively; P = .16). CONCLUSIONS: In selected patients possessing appropriate aortic cusp anatomy, the David V can be safely and effectively performed for the expanded indications of aortic dissection, severe AI, and reoperative cardiac surgery with low operative risk. Valve function has remained excellent in the short term, providing evidence of durability and a low rate of valve-related complications.

Mediastinal coelomic cyst.

Coelomic cysts are rare cysts of mesothelial origin. This is a case report of a thoracic coelomic cyst presenting as atypical chest pain.

Moderate hypothermia and unilateral selective antegrade cerebral perfusion: a contemporary cerebral protection strategy for aortic arch surgery.

BACKGROUND: Cerebral protection techniques during aortic arch surgery include deep hypothermic circulatory arrest, retrograde cerebral perfusion, and (or) antegrade cerebral perfusion. It is unclear whether unilateral selective antegrade cerebral perfusion (uSACP) in the setting of moderate hypothermic circulatory arrest (MHCA) constitutes an effective cerebral protective strategy during aortic arch reconstruction. METHODS: A retrospective review was performed for all aortic arch cases involving uSACP between January 2004 and December 2009. Of these 412 patients, 97 (24%) were treated emergently. Adverse outcomes included operative mortality, permanent neurologic dysfunction, temporary neurologic dysfunction, and renal failure requiring dialysis. Potential selection bias was controlled by the inclusion of 11 covariates. Multivariable logistic regression analysis was used to model adverse outcome as a function of MHCA and the covariates. Adjusted odds ratios were formulated along with 95% confidence intervals. RESULTS: Three hundred forty-four patients underwent hemiarch reconstruction and 68 patients underwent total arch replacement. The mean core body temperature at the initiation of uSACP was 25.7 degrees C + or - 2.8 degrees C with a uSACP time of 30 + or - 15 minutes. Overall operative mortality occurred in 29 (7.0%) patients. The incidence of permanent neurologic dysfunction and temporary neurologic dysfunction were 3.6% and 5.1%, respectively. Nineteen (4.6%) patients suffered postoperative renal failure requiring dialysis. In the adjusted analysis, MHCA was not found to be an independent predictor of mortality, permanent neurologic dysfunction, temporary neurologic dysfunction, or renal failure requiring dialysis. CONCLUSIONS: The MHCA with adjunctive uSACP is not an independent risk factor for adverse outcomes after aortic arch surgery. These data suggest that MHCA combined with uSACP represents an effective cerebral protective strategy in patients undergoing arch reconstruction in both the elective and emergent settings.

Selective antegrade cerebral perfusion via right axillary artery cannulation reduces morbidity and mortality after proximal aortic surgery.

INTRODUCTION: Selective antegrade cerebral perfusion is a well-described neuroprotective technique used in proximal aortic surgery. This study investigated whether selective antegrade cerebral perfusion is associated with improved outcomes in both emergency and elective settings compared with deep hypothermic circulatory arrest alone. METHODS: Retrospective review was performed for all cases of proximal aortic surgery between January 2004 and May 2007. Of these 271 patients, 105 had emergency and 166 had elective operation. Selection bias was controlled using propensity scoring methods. Multivariable logistic regression analysis was used to model adverse outcomes as a function of selective antegrade cerebral perfusion, emergency status, and their interaction, adjusted for the propensity score. Adjusted odds ratios were formulated with 95% confidence intervals. RESULTS: Operative mortality occurred in 12.1% (33/271) of patients: 8.8% (18/205) in patients with selective antegrade cerebral perfusion versus 22.7% (15/66) in those with deep hypothermic circulatory arrest alone (P = .003). Temporary neurologic dysfunction occurred in 5.9% (15/255) of patients: 4.5% (9/198) in selective antegrade cerebral perfusion versus 10.5% (6/57) in deep hypothermic circulatory arrest alone (P = .09). Stroke occurred in 4.3% (11/255) of patients with no difference between groups. In the elective setting, selective antegrade cerebral perfusion was associated with a significant decrease in operative mortality compared with deep hypothermic circulatory arrest alone. Overall, selective antegrade cerebral perfusion was associated with shorter intensive care unit and ventilator times and fewer renal and pulmonary complications. Significant multivariable predictors of operative mortality were emergency status, previous coronary surgery, and cardiopulmonary bypass time. CONCLUSIONS: Use of selective antegrade cerebral perfusion confers a survival advantage during proximal aortic surgery that is most apparent in the elective setting. Improved resource utilization and fewer pulmonary and renal complications were observed in patients with selective antegrade cerebral perfusion.

One thousand repeat sternotomies for congenital cardiac surgery: risk factors for reentry injury.

BACKGROUND: Reentry injury is a risk associated with repeat sternotomy for cardiac surgery. This risk has been well defined for adults, but there is less information available for patients with congenital heart disease. The goal of this review was to identify the incidence, risk factors, and outcomes for reentry injury in patients with congenital heart disease. METHODS: Eight hundred two patients with congenital heart disease had 1,000 consecutive repeat sternotomies between August 2000 and November 2007. Records were reviewed for demographics, history, operative techniques, and outcomes. Univariate risk factors for reentry injury and operative mortality were assessed. RESULTS: Median age and weight were 2.1 years (range, 0.1 to 34.6 years) and 11 kg (range, 2.5 to 123 kg). There were 639 second, 287 third, and 74 fourth or higher sternotomies. There were 13 reentry injuries (1.3%) involving right ventricle-pulmonary artery conduits (n = 4), aorta or aortic conduits (n = 3), right ventricular outflow tract patches or pseudoaneurysms (n = 3), and others (n = 3). Risk factors for injury were presence of a right ventricle-pulmonary artery conduit (6 of 115 with conduit [5.2%] versus 7 of 885 without [0.8%]; p < 0.001) and sternotomy number (relative risk, 2.28; p < 0.001). Reentry injury was associated with longer procedure times (median, 420 minutes with injury versus 248 without; p < 0.001). Operative mortality occurred in 18 patients and was associated with sternotomy number and procedure time (p < 0.001), but not reentry injury (p = 0.2). CONCLUSIONS: Risk of reentry injury during repeat sternotomy for congenital heart disease is low. Increasing sternotomy number and the presence of a right ventricle-pulmonary artery conduit are risk factors for reentry injury. However, reentry injury is not associated with increased risk of operative mortality.

Long-term outcomes after isolated aortic valve replacement in octogenarians: a modern perspective.

BACKGROUND: With the recent advent of percutaneous valve therapy, an increased need for the evaluation of outcomes after open aortic valve replacement (AVR) in elderly patients is warranted. This study compares the short- and long-term survival outcomes of octogenarians after AVR with younger age groups in the modern surgical era. METHODS: A retrospective review was performed on patients who underwent isolated, primary AVR from 1996 to 2006 at the Emory Healthcare Hospitals. Five-hundred fifteen patients were divided into three age groups: 60 to 69 (n = 206), 70 to 79 (n = 221), and 80 to 89 years of age (n = 88). Outcomes were compared among the age groups using logistic regression and analysis of variance techniques. Long-term survival between age groups was compared using the Cox proportional hazards model. Kaplan-Meier plots were used to determine survival rates. RESULTS: The groups were similar with respect to in-hospital mortality (p = 0.66) and hospital length of stay (p = 0.08). Preoperative predictors of in-hospital mortality included stroke (odds ratio [OR] 5.36), chronic lung disease (OR 4.51), and renal failure (OR 1.39). As expected, age significantly impacted long-term survival (hazard ratio [HR] 1.06). Other predictors of long-term survival included stroke (HR 2.15), current smoker (HR 2.03), diabetes (HR 1.53), and renal failure (HR 1.4). The Kaplan-Meier estimate of median survival for octogenarians was 7.4 years. CONCLUSIONS: In the modern era, octogenarians have acceptable short- and long-term results after open AVR. Comparisons of less invasive techniques for AVR should rely on outcomes based in the modern era and decisions regarding surgical intervention in patients requiring AVR should not be based on age alone.

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.

The roles of chronic pressure and volume overload states in induction of arrhythmias: an animal model of physiologic sequelae after repair of tetralogy of Fallot.

OBJECTIVE: Sudden death occurs in as many as 8% of patients after repair of tetralogy of Fallot and has been attributed to arrhythmias. The purpose of this study was to establish an animal model to evaluate the individual contribution of different physiologic sequelae after tetralogy of Fallot repair in the development of late-onset arrhythmias. METHODS: Forty-nine piglets were divided into 5 groups: (1) pulmonary artery band; (2) pulmonary valvotomy; (3) pulmonary artery band plus pulmonary valvotomy; (4) infundibular scar; and (5) age-matched control animals. Baseline and follow-up electrocardiograms were obtained and recorded, as well as changes in QRS duration. A total of 45 animals underwent hemodynamic evaluation and programmed electrical stimulation at 5.6 months postoperatively. RESULTS: Sustained ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation) were induced in 31.1%, and atrial arrhythmias were induced in 33.3%. The pulmonary valvotomy group was 30 times more likely to evidence arrhythmias than control animals for sustained ventricular tachycardia/ventricular fibrillation, as well as atrial arrhythmias (P = .01). The pulmonary artery band group was 15 times more likely to evidence atrial arrhythmias than control animals (P = .02). Prolonged QRS duration was predictive of inducibility of both atrial arrhythmias (P < .01) and sustained ventricular tachycardia/ventricular fibrillation (P = .01). Mean right atrial (P = .01) and capillary wedge (P = .01) pressures predicted atrial arrhythmia inducibility. Right ventricular end-diastolic pressure predicted atrial arrhythmia (P= .01) and sustained ventricular tachycardia/ventricular fibrillation inducibility (P = .05). Right ventricular systolic pressure did not predict inducibility of either atrial arrhythmias (P = .10) or sustained ventricular tachycardia/ventricular fibrillation (P = .94). CONCLUSIONS: Chronic right ventricular volume overload resulted in an increased incidence of inducible ventricular and atrial arrhythmias.

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.

Shear stress and pressure modulate saphenous vein remodeling ex vivo.

Vein graft failure remains an important clinical challenge, but factors contributing to vein graft failure have not clearly been defined. We investigated the role of the mechanical environment in vein remodeling in an ex vivo perfusion system. Porcine saphenous veins were subjected to five different ex vivo hemodynamic environments, including one mimicking an arterial bypass graft, for one week in order to independently assess the effects of shear stress and pressure on vein remodeling. The extent of intimal hyperplasia decreased with culture under increasing shear stress, with veins cultured under the lowest levels of shear stress exhibiting the greatest ratio of intimal/medial area, 0.15+/-0.03, which was greater than that of fresh veins (0.06+/-0.01, p<0.05). All perfused veins displayed characteristics of both medial hypertrophy and eutrophic remodeling, with those veins cultured under elevated pressures showing greater increases in mass and area than those cultured under venous pressures. Medial area correlated with the average pressure under which veins were cultured (R2=0.95, p<0.001), with veins cultured under bypass graft conditions, which were exposed to the greatest pressure during the one week culture, exhibiting the largest medial area (1.69+/-0.15 mm2), which was significantly greater than that of fresh veins (1.08+/-0.05 mm2, p<0.05). However, pulsatility was not a necessary stimulus for medial growth, as increases in medial area were observed in culture conditions in which steady flow and pressure were present. Our results suggest that pressure and shear stress act independently to regulate vein remodeling, influencing changes in vessel size as well as the nature of the remodeling.

Mechanical properties of native and ex vivo remodeled porcine saphenous veins.

When grafted into an arterial environment in vivo, veins remodel in response to the new mechanical environment, thereby changing their mechanical properties and potentially impacting their patency as bypass grafts. Porcine saphenous veins were subjected for one week to four different ex vivo hemodynamic environments in which pressure and shear stress were varied independently, as well as an environment that mimicked that of an arterial bypass graft. After one week of ex vivo culture, the mechanical properties of intact saphenous veins were evaluated to relate specific aspects of the mechanical environment to vein remodeling and corresponding changes in mechanics. The compliance of all cultured veins tended to be less than that of fresh veins; however, this trend was more due to changes in medial and luminal areas than changes in the intrinsic properties of the vein wall. A combination of medial hypertrophy and eutrophic remodeling leads to significantly smaller (p<0.05) wall stresses measured in all cultured veins except those subjected to bypass graft conditions relative to stresses measured in fresh veins at corresponding pressures. Our results suggest that the mechanical environment effects changes in vessel size, as well as the nature of the remodeling, which contribute to altering vein mechanical properties.

Regional low-flow perfusion improves neurologic outcome compared with deep hypothermic circulatory arrest in neonatal piglets.

BACKGROUND: Regional low-flow perfusion is an alternative to deep hypothermic circulatory arrest, but whether regional low-flow perfusion improves neurologic outcome after deep hypothermic circulatory arrest in neonates remains unknown. We tested neurologic recovery after regional low-flow perfusion compared with deep hypothermic circulatory arrest in a neonatal piglet model. METHODS: Sixteen neonatal piglets underwent cardiopulmonary bypass, were randomized to 90 minutes of deep hypothermic circulatory arrest or regional low-flow perfusion (10 mL.kg(-1).min(-1)) at 18 degrees C, and survived for 1 week. Standardized neurobehavioral scores were obtained on postoperative days 1, 3, and 7 (0 = no deficit to 90 = brain death). Histopathologic scores were determined on the basis of the percentage of injured and apoptotic neurons in the neocortex and hippocampus by hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (0 = no injury to 4 = diffuse injury). Differences between groups were tested by using the Wilcoxon rank sum test, and results are listed as medians within a range. RESULTS: There were no significant differences between groups during cardiopulmonary bypass. Postoperative neurobehavioral scores were abnormal in 25% (2/8) of the regional low-flow perfusion animals versus 88% (7/8) of controls. Regional low-flow perfusion animals had significantly less neurologic injury compared with controls on postoperative day 1 (0.00 [range, 0-5] vs 12.5 [range, 0-52]; P <.008). There was a trend for less severe injury in the regional low-flow perfusion group (2.0 [range, 1-4] vs 0.0 [range, 0-50]; P =.08) on hematoxylin and eosin. The degree of apoptosis was significantly less in the regional low-flow perfusion group (0.0 [range, 0-1] vs 2.5 [range, 0-4]; P =.03). CONCLUSIONS: Regional low-flow perfusion decreases neuronal injury and improves early postoperative neurologic function after deep hypothermic circulatory arrest in neonatal piglets.

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.