Human thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress.

Human mucosal-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor (TCR) Vα7.2 and are restricted by the major histocompatibility complex-Ib molecule MR1. While MAIT cells share similarities with other innate T cells, the extent to which MAIT cells are innate and their capacity to adapt is unknown. We evaluated the function of Vα7.2(+) T cells from the thymus, cord blood, and peripheral blood. Although antigen-inexperienced MAIT cells displayed a naïve phenotype, these had intrinsic effector capacity in response to Mycobacterium tuberculosis (Mtb)-infected cells. Vα7.2(+) effector thymocytes contained signal joint TCR gene excision circles (sjTRECs) suggesting limited replication and thymic origin. In evaluating the capacity of Mtb-reactive MAIT cells to adapt, we found that those from the peripheral blood demonstrated a memory phenotype and had undergone substantial expansion, suggesting that they responded to antigenic stimulation. MAIT cells, an evolutionarily conserved T-cell subset that detects a variety of intracellular infections, share features of innate and adaptive immunity.

Aortic root replacement in patients with Marfan's syndrome: the Southampton experience.

BACKGROUND: The purpose of this study was to evaluate the early and late clinical outcome after aortic root replacement (ARR) in patients with Marfan's syndrome. METHODS: A total of 65 consecutive patients with Marfan's syndrome (mean age 41.7 +/- 10.7 years, range 15 to 76 years) undergoing ARR between 1972 and 1998 in Southampton were studied. Of the patients, 45 had a chronic aneurysm of the ascending aorta and 20 had a type A dissection (16 acute and 4 chronic). The operations were elective in 38 and nonelective in 27 cases (emergency in 22 and urgent in 5). Mean size of the ascending aorta was 6.3 +/- 1.4 cm (3.8 to 12 cm). A Bentall procedure was performed in 62 and a homograft root replacement in 3 patients. Mean follow-up was 8 +/- 4.1 years (0 to 22.9 years). RESULTS: Operative mortality was 6.1% (4 deaths) (for the elective vs nonelective procedures it was 2.6% vs 11%, p = 0.2). The 10-year freedom from thromboembolism, hemorrhage, and endocarditis was 88%, 89.8%, and 98.4% (0.9%, 0.9%, and 0.2% per patient-year) and from late aortic events it was 86.3% (1.3% per patient-year). Aortic root replacement for dissection was an independent predictor of occurrence of late aortic events (p = 0.01). Five patients had a reoperation with one early death. The 10-year freedom from reoperation was 89.2% (1.1% per patient year) (for elective and nonelective procedures, 90.8% vs 84.6%, p = 0.6). The 10-year survival, including operative mortality, was 72.7% (for elective and nonelective procedures, 78% vs 66.5%, p = 0.6). Late aortic events was an independent adverse predictor of survival (p = 0.02). CONCLUSIONS: In patients with Marfan's syndrome, elective ARR, usually for chronic aneurysm, is associated with a low mortality, low rate of aortic complications, and good late survival. Nonelective ARR, mostly for dissection, has a greater operative risk and a significantly higher incidence of late catastrophic aortic events. Early prophylactic surgery in these patients is therefore recommended. Long-term clinical and radiologic follow-up to prevent or to treat late aortic events is highly desirable.

Is there still a place for open surgical valvotomy in the management of aortic stenosis in children? The view from Southampton.

OBJECTIVE: The most appropriate management of aortic stenosis (AS) in children remains controversial. The purpose of this study was to determine the outcome following open valvotomy for AS in children. METHODS: Ninety-seven consecutive, unselected, children (mean age 3.2 +/- 3.6 years, 1 day--15 years) underwent an open valvotomy for critical (n=36) or severe (n=61) AS between 1979 and 2000 in Southampton. Twenty-six were neonates (1--31 days), 27 were infants (1--12 months) and 44 were older children (1--15 years). Mean follow-up was 10 +/- 5.4 years, 1 month--21.9 years. RESULTS: Two neonates died early giving an overall operative mortality of 2.1% (7.7% for the neonates and 0% for infants and older children). The mean aortic gradient was reduced from 76 to 24.5 mmHg (P < 0.0001). Residual or recurrent AS occurred in 17 patients and severe aortic regurgitation in eight patients. Kaplan--Meier 10-year freedom from residual or recurrent AS was 83.1 +/- 4.7% and from severe aortic regurgitation was 95.3 +/- 2.7%. Twenty-five patients required an aortic re-operation or re-intervention, 18 of whom had an aortic valve replacement (AVR) (mean valve size 21.8 +/- 0.9 mm, range 21--25 mm). Ten-year freedom from any aortic re-operation or re-intervention was 78.4 +/- 5.2% and from AVR was 85.1 +/- 4.6%. There were ten late deaths. Overall 10-year survival, including hospital mortality, was 90.2 +/- 3.1% (69.7 +/- 9.7% for the neonates, 92 +/- 5.4% for the infants and 100% for older children, (P < 0.0001). Ten-year survival for children with isolated AS (n = 69) was 100% and for those with associated cardiovascular problems (n = 28) was 67.3 +/- 8.9% (P < 0.0001). All survivors are in New York Heart Association functional class I. CONCLUSIONS: Open valvotomy remains the gold standard in the management of AS in neonates, infants and older children. It is associated with low operative mortality and provides lengthy freedom from recurrent AS and regurgitation. Re-operations are common but if AVR is required, implantation of an adult-sized prosthesis is usually possible. There is a late death-hazard for those with severe associated lesions, but the survival prospects for the patients with isolated AS are excellent.

Open commissurotomy for critical isolated aortic stenosis in neonates.

BACKGROUND: The optimal management of critical aortic stenosis in early infancy remains controversial. The aim of this study was to assess the early and late outcomes following open surgical valvotomy for critical aortic stenosis in neonates and to provide a framework of data against which current results of other treatment approaches can be evaluated. METHODS: Eighteen consecutive neonates (mean age 9.2 days, range 1 to 26 days) undergoing an open valvotomy for critical isolated aortic stenosis (the standard treatment for this condition in our unit) between 1984 and 2000 were studied. The mean aortic valve gradient was 79.4 mm Hg. Twelve neonates received prostaglandins and 10 received inotropic agents preoperatively. Follow-up was complete (mean 8.1 years, range 1 month to 15 years). RESULTS: There was no operative mortality. At discharge, the mean aortic valve gradient was 37.2 mm Hg, with 6 patients having mild and 2 having moderate aortic regurgitation. Six patients required a reoperation; 3 of these had an aortic valve replacement at 9 to 11 years of age. Kaplan-Meier 5- and 10-year freedoms from any aortic reoperation or reintervention were 85 and 55%, respectively; 5- and 10-year freedoms from aortic valve replacement were 100 and 79%, respectively. A 14-year-old boy died from endocarditis 4 years following an aortic valve replacement in another unit. Kaplan-Meier 10-year survival was 100%. All survivors are in New York Heart Association I class and are leading normal lives. Their mean aortic valve gradient is 34.5 mm Hg, and none has significant aortic regurgitation. CONCLUSIONS: Open valvotomy for critical aortic stenosis in neonates carries a low operative risk and provides lengthy freedom from recurrent stenosis or regurgitation. Reoperations are inevitable, but aortic valve replacement can be delayed until the implantation of an adult-sized prosthesis is possible. Late survival is excellent. We consider open surgical valvotomy to be the treatment of choice for critical neonatal aortic stenosis.

Aortic valve replacement for endocarditis: determinants of early and late outcome.

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine risk factors for operative mortality, recurrent infection, reoperation and long-term survival following aortic valve replacement (AVR) for infective endocarditis. METHODS: Between 1973 and 1997, 109 patients (91 male, 18 female, mean age 52.6 years) underwent isolated AVR for infective endocarditis in our unit. Native valve endocarditis was present in 89 (81.6%) and prosthetic valve endocarditis in 20 (18.4%). Active culture-positive endocarditis was present in 53 (48.6%). Preoperatively, 99 patients (90.8%) were in NYHA classes III and IV. Indications for surgery included cardiac failure in 41 patients, valvular dysfunction in 38, vegetations in 18, sepsis in seven, abscess in six and embolism in four. Mechanical valves were implanted in 69 patients (63.3%) and bioprostheses in 40 (36.7%), including a homograft in 19 (17.4%). Follow up was complete (mean 5.8 years; range: 0-23.8 years; total 633.5 patient-years). RESULTS: The operative mortality was 10.1% (11 deaths). At ten years, freedom from recurrent infection was 94.2%, and freedom from reoperation 83.6%. Biological valve and younger age were significant adverse parameters for freedom from reoperation (p = 0.01 and p = 0.01). There have been 21 late deaths, 15 due to cardiac causes. Kaplan-Meier survival, including operative mortality, at five and ten years was 77.4% and 68.0%, respectively. On Cox proportional hazards regression, Staphylococcus aureus infection (p = 0.008) and older age (p = 0.04) were independent adverse predictors of survival. CONCLUSION: AVR for endocarditis carries a relatively high operative mortality, but can result in a satisfactory freedom from recurrent infection, reoperation and long-term survival. Analysis of our series demonstrates that implantation of a biological valve limits the freedom from reoperation and that infection by Staph. aureus reduces the probability of long-term survival.

Surgery for active culture-positive endocarditis: determinants of early and late outcome.

BACKGROUND: The purpose of this study was to describe a single unit experience in the surgical treatment of active culture-positive endocarditis and identify determinants of early and late outcome. PATIENTS AND METHODS: One hundred eighteen consecutive patients with positive blood culture up to 3 weeks before operation (or positive valve culture) and macroscopic evidence of lesions typical for endocarditis, undergoing operation between January 1973 and December 1996 in Southampton, were evaluated. The aortic valve was infected in 53 (48.9%), the mitral in 46 (39%), both aortic and mitral in 12 (10.1%), the tricuspid in 4 (3.9%), and the pulmonary valve in 3 (2.5%). Native valve endocarditis was present in 83 (70.3%) and prosthetic valve endocarditis in 35 (29.7%). Streptococci and staphylococci were the most common pathogens. Mean follow-up was 5.6 years (range, 0 to 25 years). RESULTS: Operative mortality was 7.6% (9 patients). Endocarditis recurred in 8 (6.7%). A reoperation was required in 12 (10.2%). There was 24 late deaths, 17 of them cardiac. Actuarial freedom from recurrent endocarditis, reoperation, late cardiac death, and long-term survival at 10 years were 85.9%, 87.2%, 85.2%, and 73.1%, respectively. On multiple regression analysis the following were independent adverse predictors: pulmonary edema (p = 0.007) and impaired left ventricular function (p = 0.02) for operative mortality; prosthetic valve endocarditis (p = 0.01) for recurrent infection; myocardial invasion by the infection (p = 0.01) and reoperation (p = 0.04) for late cardiac death; and coagulase-negative staphylococcus (p = 0.02), annular abscess (p = 0.02), and longer intensive care unit stay (p = 0.02) for long-term survival. CONCLUSIONS: Operation for active culture-positive endocarditis carries an acceptable mortality. Freedom from recurrent infection, reoperation, and long-term survival are satisfactory. In our data, patients' hemodynamic status at operation was the major determinant of operative mortality. Prosthetic valve endocarditis, coagulase-negative staphylococcus, and annular or myocardial infectious invasion were the critical adverse determinants of late outcome.

Surgical treatment of infective mitral valve endocarditis: predictors of early and late outcome.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to review our experience in surgical treatment of infective mitral valve endocarditis, and to identify predictors of early and late outcome. METHODS: Ninety-one consecutive patients (52 males, 39 females, mean age 55.6 years) underwent surgery between 1973 and 1997 for endocarditis of isolated mitral (n = 65, 71%), mitral and aortic (n = 25, 28%) and mitral, aortic and tricuspid valves (n = 1, 1%). Native valve endocarditis (NVE) was present in 60 patients (66%) and prosthetic valve endocarditis (PVE) in 31 (34%). The main indications for surgery were heart failure in 32 patients, valve dysfunction in 23, vegetations in 21, and persistent sepsis in 11. Eighty-six patients (95%) were in NYHA classes III-IV, and 58 (64%) had active culture-positive endocarditis at surgery. Mechanical valves were implanted in 73 patients and bioprosthetic valves in 13; valves were repaired in five patients. The impact of 46 parameters on early and late outcome was defined by means of univariate and multivariate statistical analysis. Follow up was complete (mean 5.5 years; range: 0-23.1 years; total 507.3 patient-years). RESULTS: Operative mortality rate was 11% (n = 10). Recurrent infection was recorded in five patients (6%), and reoperation was required in eight (9%). Freedom from recurrent infection and reoperation at 10 years was 89.1% and 87.8% respectively. There were 22 late deaths, 15 from cardiac causes. Actuarial survival rates for all patients at 5, 10 and 15 years were 73.0%, 62.7% and 58.7% (for hospital survivors, the corresponding rates were 81.9%, 69.7% and 66.0%). On multiple logistic regression and Cox proportional hazards models, the following were independent predictors: preoperative pulmonary edema (p = 0.01) for operative mortality; PVE (p = 0.02) for recurrence; younger age (p = 0.02) and PVE (p = 0.02) for reoperation; male gender (p = 0.004) and longer ITU stay for survival (if all patients were included); male gender (p = 0.01) and myocardial invasion by infection (p = 0.02) for survival (if only the hospital survivors were analyzed). CONCLUSION: Surgery for infective mitral valve endocarditis carries a relatively high, though acceptable, risk but provides satisfactory freedom from recurrent infection, reoperation and improved long-term survival. Analysis of these data demonstrated that the preoperative hemodynamic status was the major predictor of in-hospital outcome, PVE increased the risk for recurrent infection and reoperation, whereas male gender and myocardial invasion by the infective process critically reduced the probability of long-term survival. The type of offending pathogen, the activity of infection and the involvement of more than one valve did not appear to influence early and/or late outcome.

The effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest.

OBJECTIVE: The purpose of this study was to determine the effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest. METHODS: Sixteen 1-week-old piglets underwent cardiopulmonary bypass, were cooled to 18 degrees C, and underwent 60 minutes of circulatory arrest, followed by 60 minutes of reperfusion and rewarming. Global and regional cerebral blood flow, cerebral oxygen metabolism, and renal blood flow were determined before cardiopulmonary bypass, after the institution of cardiopulmonary bypass, and at 1 hour of deep hypothermic circulatory arrest. In the study group (n = 8 piglets), a leukocyte-depleting arterial blood filter was placed in the arterial side of the cardiopulmonary bypass circuit. RESULTS: With cardiopulmonary bypass, no detectable change occurred in the cerebral blood flow, cerebral oxygen metabolism, and renal blood flow in either group, compared with before cardiopulmonary bypass. In control animals, after deep hypothermic circulatory arrest, blood flow was reduced to all regions of the brain (P <.004) and the kidneys (P =.02), compared with before deep hypothermic circulatory arrest. Cerebral oxygen metabolism was also significantly reduced to 60.1% +/- 11.3% of the value before deep hypothermic circulatory arrest (P =.001). In the leukocyte-depleting filter group, the regional cerebral blood flow after deep hypothermic circulatory arrest was reduced, compared with the value before deep hypothermic circulatory arrest (P <.01). Percentage recovery of cerebral blood flow was higher in the leukocyte filter group than in the control animals in all regions but not significantly so (P >.1). The cerebral oxygen metabolism fell to 66.0% +/- 22.3% of the level before deep hypothermic circulatory arrest, which was greater than the recovery in the control animals but not significantly so (P =.5). After deep hypothermic circulatory arrest, the renal blood flow fell to 81.0% +/- 29.5% of the value before deep hypothermic circulatory arrest (P =.06). Improvement in renal blood flow in the leukocyte filter group was not significantly greater than the recovery to 70.2% +/- 26.3% in control animals (P =.47). CONCLUSIONS: After a period of deep hypothermic circulatory arrest, there is a significant reduction in cerebral blood flow, cerebral oxygen metabolism, and renal blood flow. Leukocyte depletion with an in-line arterial filter does not appear to significantly improve these findings in the neonatal piglet.

Preoperative high dose methylprednisolone attenuates the cerebral response to deep hypothermic circulatory arrest.

OBJECTIVE: The aim of this study was to assess the effects of preoperative high dose methylprednisolone on cerebral recovery following a period of deep hypothermic circulatory arrest (DHCA). METHODS: Sixteen 1-week-old piglets were randomized to placebo (n=8), or 30 mg/kg intramuscular methylprednisolone sodium succinate (MPRED) given at 8 and 2 h before induction of anaesthesia. All piglets underwent cardiopulmonary bypass, cooling to 18 degrees C, 60 min of circulatory arrest followed by 60 min of reperfusion and rewarming. The radiolabelled microsphere method was used to determine the global and regional cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) at baseline before DHCA and after 60 min of reperfusion. RESULTS: In controls, mean global CBF (+/-1 standard error) before DHCA was 53.7+/-2.4 ml/100 g per min and fell to 23.8+/-1.2 ml/100 g per min following DHCA (P<0.0001). This represents a post-DHCA recovery to 45.1+/-3.3% of the pre-DHCA value. In the MPRED group recovery of global CBF post-DHCA was significantly higher at 63.6+/-5.2% of the pre-DHCA value (P=0.009). The regional recovery of CBF in the cerebellum, brainstem and basal ganglia was 80, 75 and 69% of pre-DHCA values in the MPRED group respectively compared to 66, 60 and 55% in controls (P<0.05). Global CMRO(2) in controls fell from 3.9+/-0.2 ml/100 g per min before to 2. 3+/-0.2 ml/100 g per min after DHCA (P=0.0001). This represents a post-DHCA recovery to 58.6+/-4.4% of the pre-DHCA value. In the MPRED group, however, recovery of global CMRO(2) post-DHCA was significantly higher at 77.9+/-7.1% of the pre-DHCA value (P=0.04). CONCLUSIONS: Treatment with high dose methylprednisolone at 8 and 2 h preoperatively attenuates the normal cerebral response to a period of deep hypothermic ischaemia. This technique may therefore offer a safe and inexpensive strategy for cerebral protection during repair of congenital heart defects with the use of DHCA.

Aortic valve replacement in children: are mechanical prostheses a good option?

OBJECTIVE: The choice of the most appropriate substitute in children with irreparable aortic valve lesions remains controversial. The aim of this study was to assess early and late outcomes following aortic valve replacement (AVR) with mechanical prostheses in children. PATIENTS: Fifty-six patients (42 male, 14 female, mean age 11.2, range 1-16 years) undergoing AVR with mechanical prostheses between October 1972 and January 1999 were evaluated. Thirty-six patients (64.2%) underwent previous cardiac surgery. Disease aetiology was congenital in 47 patients (congenital aortic stenosis in 33, and other congenital abnormalities in 14) (83.9%), infective in four (7. 1%), rheumatic in two (3.4%), and three (5.3%) had connective tissue disorders. Haemodynamic indication for AVR was aortic regurgitation (AR) in 24 (42.8%), aortic stenosis (AS) in 22 (39.2%) and mixed disease in ten (17.8%). Twenty-eight patients (50.0%) were in New York Heart Association (NYHA) class III-IV before surgery. Concomitant procedures were performed in 31 patients (55.3%), including aortic root enlargement in 28 (50%). The mean size of implanted valves was 22.4 mm (range 17-27 mm). All patients received long-term anticoagulation treatment with sodium warfarin, aiming to maintain an international normalized ratio (INR) between 2.5-3.0. The mean follow-up was 7.3 years (range 0-26, total 405 patient-years). RESULTS: Operative mortality was 5.3% (three patients). Three patients developed complete heart block requiring pacing, two of them permanently. Late events included valve thrombosis (one), transient stroke (one), paravalvular leak of a mitral prosthesis (one), aneurysm of sinus of Valsalva (one) and pannus ingrowth (one). There was no major haemorrhagic event. Five patients required re-operation (8.9%), but none due to outgrowth of the valve. Regarding actuarial freedom from thrombo-embolism, any valve-related event and re-operation at 20 years was 93, 86.6 and 86. 4%. There were three late deaths. Actuarial survival, including operative mortality, at 10 and 20 years was 91 and 84.9%. The actuarial survival for the group of the patients with congenital AS (n=33) at 10 and 20 years was 93.5%, whereas for the children with other congenital heart problems (n=14) this was 85.7 and 64.3% (P=0. 09). At the latest clinical evaluation, 44 children were in NYHA class I and six were in class II. The mean gradient across the aortic prosthetic valve on echocardiography was 17.9 mmHg (range 0-47 mmHg). CONCLUSIONS: Mechanical AVR, with enlargement of the aortic root if necessary, remains an excellent treatment option in children. It is associated with acceptable operative mortality, low incidence of late events and re-operation, and provides good long-term survival. It clearly represents a good alternative to available biological substitutes, including the pulmonary autograft (Ross procedure).

The free radical spin trap alpha-phenyl-tert-butyl nitrone attenuates the cerebral response to deep hypothermic ischemia.

OBJECTIVE: The aim of this study was to assess the role of reactive oxygen species in the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. METHODS: Twelve 1-week-old piglets were randomized to placebo (control group; n = 6) or 100 mg x kg(-1) intravenous alpha-phenyl-tert -butyl nitrone, a free radical spin trap (PBN group; n = 6). All piglets underwent cardiopulmonary bypass, cooling to 18 degrees C, 60 minutes of circulatory arrest followed by 60 minutes of reperfusion, and rewarming. Cerebral blood flow and metabolism were determined at baseline before deep hypothermic circulatory arrest and after 60 minutes of reperfusion. RESULTS: In control animals, mean global cerebral blood flow (+/- 1 standard error) before circulatory arrest was 48.4 +/- 3.6 mL x 100 g(-1) x min(-1) and fell to 25.1 +/- 3.6 mL x 100 g(-1) x min(-1) after circulatory arrest (P =.001). Global cerebral metabolism fell from 3.5 +/- 0.2 mL x 100 g(-1) x min(-1) before arrest to 2.2 +/- 0.2 mL x 100 g(-1) x min(-1) after circulatory arrest (P =.0002). In the PBN group after circulatory arrest, the mean global cerebral blood flow and metabolism of 37.2 +/- 4.9 and 3.6 +/- 0.5 mL. 100 g(-1). min(-1), respectively, were significantly higher than in the control group (P <.05). Recovery of cerebral blood flow in the PBN group was 78% of pre-arrest level compared with 52% in the control group (P =.002). Global cerebral metabolism after circulatory arrest was 100% of the pre-arrest value compared with 61% in the control group (P =.01). Regional recovery of cerebral metabolism in the cerebellum, brain stem, and basal ganglia was 131%, 130%, and 115%, respectively, of pre-arrest values in the PBN group compared with 85%, 78%, and 70% in the control group (P <.04). CONCLUSIONS: Reactive oxygen species contribute to the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. The use of alpha-phenyl-tert -butyl nitrone before the arrest period attenuates the normal response to ischemia and improves recovery by affording protection from free radical-mediated damage.

Replacement of the proximal aorta and aortic valve using a composite bileaflet prosthesis and gelatin-impregnated polyester graft (Carbo-Seal): early results in 143 patients.

OBJECTIVE: We report the combined early results from two centers in the United Kingdom using a composite conduit consisting of a bileaflet mechanical valve incorporated into a gelatin-impregnated, ultra-low porosity, woven polyester graft (Carbo-Seal; Sulzer Carbomedics, Inc, Austin, Tex). METHODS: Between August 1992 and March 1997, 143 patients underwent aortic root replacement with the Carbo-Seal composite prosthesis. The indication for surgery was acute type A dissection in 31 (22%), chronic type A dissection in 9 (6%), ascending aortic aneurysm without dissection in 100 (70%), and false aneurysm of the ascending aorta in 3 (2%). Twenty-seven patients (19%) had undergone previous sternotomy, and 40 (28%) were seen as emergencies. Concomitant procedures were performed in 38 (27%), including 18 aortic arch or hemiarch replacements. Total follow-up is 270 patient-years. Follow-up is 100% complete. RESULTS: The early (30-day) mortality was 7% (10 patients). Permanent neurologic events occurred in 2%. At a mean follow-up of 23 months, 94% of survivors were in New York Heart Association functional class I. Freedom from reoperation was 97.2% +/- 1.6% (1 standard error [1 SE]) at 12 months and 95.7% +/- 2.2% at 48 months. Including early mortality, survival was 90.1% +/- 2.6% at 12 months and 83.1% +/- 3. 5% at 48 months. CONCLUSIONS: Aortic root replacement with use of the Carbo-Seal prosthesis can be undertaken with a relatively low early mortality and morbidity. A low reoperation rate and high intermediate-term survival can be expected, but continued follow-up is needed to determine the long-term efficacy of this prosthesis.

Platelet-activating factor receptor antagonism improves cerebral recovery after circulatory arrest.

BACKGROUND: The aim of this study was to determine the effects of antagonism of platelet-activating factor receptors on cerebral recovery after deep hypothermic circulatory arrest (DHCA). METHODS: Fourteen 1-week-old piglets were randomly assigned to either placebo (n = 7), or 10 mg/kg intravenous ginkgolide B (BN52021), a naturally occurring platelet-activating factor receptor antagonist. All piglets had cardiopulmonary bypass, cooling to 18 degrees C, 60 minutes of circulatory arrest followed by 60 minutes of reperfusion and rewarming. Global and regional cerebral blood flow, cerebral oxygen metabolism and renal blood flow were determined at baseline before DHCA and after 60 minutes of reperfusion. RESULTS: Blood flow was significantly reduced in all regions of the brain (p < 0.001) and the kidneys (p = 0.02) after DHCA in control animals. Cerebral oxygen metabolism was also significantly reduced after DHCA to 59.2% +/- 3.2% of the pre-DHCA value (p = 0.0003). In the ginkgolide B group, recovery of global cerebral blood flow to 60.4% +/- 2.8% of pre-DHCA level and of global cerebral oxygen metabolism to 77.1% +/- 5.8% of pre-DHCA value were significantly higher than the recovery in the control group (p < 0.02). Regional recovery of cerebral blood flow and oxygen metabolism in the gingkolide B group was greatest in the cerebellum and brainstem. Renal blood flow did not decrease significantly after DHCA in the gingkolide B group (p = 0.23). CONCLUSIONS: These results suggest that production of platelet-activating factor is increased in the brain after DHCA. Platelet-activating factor receptor antagonism with ginkgolide B before the circulatory arrest period can significantly improve recovery of cerebral blood flow and oxygen metabolism and renal blood flow after DHCA.

Intermittent perfusion protects the brain during deep hypothermic circulatory arrest.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) has been shown to cause impairment in recovery of cerebral blood flow (CBF) and cerebral metabolism (CMRO2) proportional to the duration of the DHCA period. This effect on CMRO2 may be a marker for brain injury, because CMRO2 recovers normally after cardiopulmonary bypass (CPB) when DHCA is not used. The aim of this study was to investigate the effects of intermittent perfusion during DHCA on the recovery of CMRO2 after CPB and to correlate these findings with electron microscopy (EM) of the cerebral microcirculatory bed. METHODS: Fifteen neonatal piglets were placed on CPB and cooled to 18 degrees C. Each animal then underwent either: (1) 60 minute continuous CPB (control), (2) 60 minute uninterrupted DHCA (UI-DHCA), or (3) 60 minute DHCA with intermittent perfusion (1 minute every 15 minutes) (I-DHCA). All animals were then rewarmed and weaned from CPB. Measurements of CBF and CMRO2 were taken before and after CPB. A further 9 animals underwent CPB without DHCA (2 animals) or with DHCA (7 animals), under various conditions of arterial blood gas management, intermittent perfusion, and reperfusion time. RESULTS: UI-DHCA resulted in significant impairment to recovery of CMRO2 after CPB (p < 0.05). Regardless of the blood gas strategy used, the EM after UI-DHCA revealed extensive damage characterized by perivascular intracellular and organelle edema, and vascular collapse. I-DHCA, on the other hand, produced a pattern of normal CMRO2 recovery identical to controls, and the EM was normal for both these groups. CONCLUSIONS: Intermittent perfusion during DHCA is clinically practical and results in normal cerebral metabolic and ultrastructural recovery. Furthermore, the correlation between brain structure and CMRO2 suggests that monitoring CMRO2 during the operation may be an outstanding way to investigate new strategies for neuroprotection designed to reduce cerebral damage in children undergoing correction of congenital cardiac defects.

Surgery for infective valve endocarditis in children.

OBJECTIVE: Surgery for endocarditis in children is relatively uncommon. Our aim is to assess operative mortality, recurrent infection, re-operation and long-term survival rates following surgery for infective valve endocarditis in children. PATIENTS: Sixteen consecutive children (ten female, six male, mean age 11.8 years, range 25 days-16 years) undergoing surgery between 1972 and 1999 in Southampton were studied. The aortic valve was affected in five, mitral in four, aortic and mitral in one, tricuspid in five and a pulmonary homograft in one patient. Prosthetic valve endocarditis was present in three. Twelve surgical interventions were emergency and four urgent. Indications for operation included cardiac failure in five, severe valvular dysfunction in nine, vegetations in nine, persistent sepsis in four and embolization in four patients. The offending micro-organism was identified in 13. Valve replacement was performed in 11 and excision of vegetations in two and excision of vegetations and repair in three. Follow-up was complete (mean 11.2 years, range 2 months to 26.3 years, total 179.5 patient years). RESULTS: There was one operative death (6.2%) in a 25-day-old neonate who presented in a moribund condition. Endocarditis recurred in one patient (6.25%). Freedom from recurrent infection at 10 and 20 years was 100.0 and 87.5%. Seven surgical re-interventions were required in four (25.0%) patients with no operative mortality. Freedom from re-operation at 1, 5, 10 and 20 years, was 84.6, 76.1, 76.1 and 60.9%, respectively. Two patients died 15 and 23 years after their first operation. The cause of the late deaths was non-cardiac in the first and unknown in the other. Actuarial survival, including operative mortality, at 1, 15 and 20 years was 93.7, 93.7 and 78.1%. CONCLUSIONS: Surgery in children with infective valve endocarditis can be performed with low operative mortality. Although some patients may require re-operation, freedom from recurrent infection and long-term survival are satisfactory.

Twenty-year follow-up of aortic valve replacement with antibiotic sterilized homografts in 200 patients.

The aim of this study was to determine long-term results from one unit of subcoronary homograft aortic valve replacement (AVR) using the same sterilization and preservation techniques in each case. Between 1973 and 1983, 200 patients underwent AVR using an unstented homograft previously sterilized in antibiotics and preserved at 4 degrees C. Surviving patients were monitored for a minimum of 15 years to the end of 1998. Mean age was 50.0+/-14 (1 standard deviation) years; 121 patients were men (60.5%). Mean patient follow-up time was 15.6+/-6.7 years, with a total follow-up time of 3,115 patient years. Follow-up was 95.6% complete. There were three early deaths (1.5%). At autopsy, the homograft was anatomically normal and in a satisfactory position. Kaplan-Meier survival, including early death, was 81.2%+/-2.8% (1 standard error) at 10 years, 68.1%+/-3.4% at 15 years, and 58.0%+/-3.7% at 20 years. Repeat AVR was undertaken in 74 patients, giving a freedom from reoperation for any reason of 86.5%+/-2.6%, 69.6%+/-3.8%, and 38.8%+/-5.3% at 10, 15, and 20 years, respectively. Freedom from structural valve degeneration at 10, 15, and 20 years was 81.1%+/-2.9%, 61.7%+/-3.9%, and 31.2%+/-4.7%, respectively. Freedom from endocarditis at 10, 15, and 20 years was 98.7%+/-0.9%, 96.0%+/-1.8%, and 94.6%,+/-2.3%, respectively. Homograft AVR with an antibiotic-sterilized valve stored at 4 degrees C and implanted in the subcoronary position offers low operative mortality and good long-term outcome for patients.

When is extracorporeal life support worthwhile following repair of congenital heart disease in children?

BACKGROUND: Although the use of extracorporeal life support (ECLS) following repair of congenital heart defects in children is increasing, the criteria for ECLS usage in these patients is not well defined. The overall survival of such patients is disappointingly low and may depend on both the indication for support and the time at which ECLS is commenced. METHODS: Between January 1993 and December 1996, 727 children underwent surgery for congenital heart defects at our institution with an overall hospital mortality of 5.8% (42 children). Nine of these children were treated with ECLS postoperatively. There were seven males and two females with a mean age of 7.2 months (range 2 weeks-3 years). Seven children could not be weaned from cardiopulmonary bypass (CPB) in the operating theatre. A further two were treated with ECLS later on during the postoperative period (commenced at 14 and 48 h). Full veno-arterial extra corporeal membrane oxygenation (ECMO) support was used in all children except one in whom a left ventricular assist device (LVAD) was used. RESULTS: The median duration of support was 121 h (range 15-648 h). Four children (44%) were weaned from support and two of these are long-term survivors. Of the seven children in whom ECLS was instituted because of failure to wean from CPB, there was one long term survivor (LVAD support). Of the two patients in whom ECLS was instituted during the post-operative period there is one long-term survivor. CONCLUSIONS: Weaning form ECLS and decannulation in 44% of our patients is comparable to other series of post-cardiotomy patients requiring ECLS. However, full veno-arterial ECMO instituted because of a failure to wean from CPB during corrective surgery is associated with an extremely poor outcome (zero long-term survivors in six patients).

Should coronary artery bypass grafting be performed at the same time as repair of a post-infarct ventricular septal defect?

OBJECTIVE: The value of coronary artery bypass grafting (CABG) at the time of repair of a post-infarct ventricular septal defect (VSD) remains controversial. The aim of this study was to analyse the effect of CABG on early mortality and survival following repair of an acquired VSD. METHODS: Over 23 years, 179 patients, 118 male, 61 female, mean age 66 years (range 43-80), have undergone repair of a post-related VSD in our unit. A total of 29 patients, who predominantly form the earlier part of the series, were operated on greater than 1 month after the infarct and are, therefore, excluded. Coronary angiography was performed in 98 (65.3%) of the remaining 150 patients. Of these, 41 had coronary artery disease (CAD) limited to the infarct-related vessel and 57 had additional significant CAD. Those with CAD limited to the infarct-related vessel were not grafted (Group A). Of those, 40 with significant CAD underwent CABG at the time of VSD repair (Group B) and 17 did not (Group C). In 52 patients the coronary anatomy was not documented (Group D). Risk factors for early mortality were evaluated using logistic regression. Actuarial survival was compared using log rank and Wilcoxon tests. Cox's proportional hazards method was used to determine factors affecting survival. RESULTS: Overall, 30 day mortality was 32%. CABG did not significantly decrease operative mortality (logistic regression). There was no statistically significant difference in early mortality or actuarial survival between the four groups. CABG was not associated with an increased survival (Cox's method). CONCLUSIONS: Concomitant CABG at the time of VSD repair does not affect early mortality nor confer survival benefits. There seems to be no demonstrable benefit in revascularisation at the time of repair and, therefore, it may be unnecessary to perform CABG or coronary angiography in these patients.

Degenerative mitral regurgitation: when should we operate?

BACKGROUND: Left untreated, severe mitral regurgitation in asymptomatic patients can lead to irreversible cardiac damage, which can develop with little warning. Over the period of this study, we have tended to operate earlier in the disease process and on less symptomatic patients. We report here our experience. METHODS: Between January 1985 and June 1996, 710 patients with mitral regurgitation underwent operations. Three hundred twenty-nine (213 male and 116 female with a mean age of 65.5 years) had degenerative mitral valve disease and of this group, 169 patients underwent repair and 160, replacement. RESULTS: The overall operative mortality was 4 patients (1.2%). There were no operative deaths among patients having isolated mitral valve repair. Survival at 1 year, 5 years, and 10 years was 94%+/-1.4% (+/- the standard error of the mean), 77%+/-2.9%, and 41%+/-5.8%, respectively. Survival was significantly better in the group having repair (p < 0.05). Ten patients (6%) in the repair group and 13 (8%) in the replacement group required reoperation. Increased age, worse left ventricular function, type of operation (replacement worse than repair), and increased left ventricular size were significantly associated with poorer survival. CONCLUSIONS: These data confirm the superior results achieved with mitral valve repair and support early mitral valve repair before functional deterioration.

Surgical treatment of acquired ventricular septal defects in the elderly.

OBJECTIVE: As the population continues to age, older patients are being referred for repair of acquired ventricular septal defect (VSD) following myocardial infarction (MI). The purpose of this study was to assess the effect of age (> or = 70 years) on operative risk and long term survival following repair of an acquired VSD. METHODS: Between January 1972 and December 1995, 179 patients have undergone repair of acquired VSDs following MI in our unit. There were 118 males and 61 females (age range 43-80 years) of whom 60 were aged 70 years or above. RESULTS: The overall early mortality was 27%. On univariate analysis risk factors for early death included shorter time from both MI and detection of murmur to operation (P < 0.01, P = 0.04), site of MI (P < 0.01), higher NYHA class (P < 0.01), lower preoperative blood pressure (P < 0.01) and longer cardiopulmonary bypass and cross clamp times (P < 0.01, P = 0.03). Non significant variables included age, sex, concomitant CABG and preoperative renal function. Early mortality was 28.6% (34/119) in patients under 70 and 25.0% (15/60) in those over 70. This difference was not significant. The only significant differences between the age groups were sex distribution (females > males, P < 0.01), in the older group, and shorter time from both MI and detection of murmur to operation (P = 0.04, P = 0.02). Cardiopulmonary bypass was the only statistically significant variable on multivariate analysis (P = 0.01). CONCLUSIONS: There was no significant difference in early mortality between the two age groups. As shorter times from both MI and detection of murmur to operation adversely affect early mortality, age over 70 years should not be used to determine suitability for surgery.