Deep Hypothermic Circulatory Arrest Activates Neural Precursor Cells in the Neonatal Brain.

BACKGROUND: Use of antegrade cerebral perfusion (ACP) as an alternative neuroprotection strategy to deep hypothermic circulatory arrest (DHCA) in the setting of cardiopulmonary bypass in neonates has become a common approach, although the value of ACP over DHCA remains highly debated. This study investigated the disruption to neonatal brain homeostasis by DHCA and ACP. METHODS: Neonatal pigs (7 days old) undergoing bypass were assigned to 4 groups: DHCA at 18°C and ACP at 18°, 25°, and 32° for 45 minutes (n = 6 per group). ACP was initiated through the innominate artery and maintained at 40 mL/kg/min. After bypass, all animals were maintained sedated and intubated for 24 hours before being euthanized. Brain subventricular zone tissues were analyzed for histologic injury by assessing apoptosis and neural homeostasis (Nestin). RESULTS: Histologic examination showed no significant ischemic/hypoxic neuronal death at any cooling temperature among the 4 treatment groups. However, we detected a significantly higher apoptotic rate in DHCA compared with ACP at 18°C (P = .003-.017) or 25°C (P = .012-.043), whereas apoptosis at 32°C was not different from DHCA. Of note, we identified increased Nestin expression in the DHCA group compared with all ACP groups (P range = .011-.041). CONCLUSIONS: Neonatal piglet ACP at 18° or 25°C provides adequate protection from increased brain cellular apoptosis. In contrast to ACP, however, DHCA induces brain Nestin expression, indicating activation of neural progenitor cells and the potential of altering neonatal neurodevelopmental progression. DHCA has potential to more profoundly disrupt neural homeostasis than does ACP.

Safe Use of Glutaraldehyde to Repair the Destroyed Valve in Active Infective Mitral Valve Endocarditis.

BACKGROUND: The aim of this study was to review our experience of mitral valve (MV) repair for acute and active infective endocarditis (AAIE) and to identify the feasibility of a new approach together with the mid-term results. Methods and Results: A retrospective analysis was performed on 35 consecutive AAIE patients surgically treated in the isolated mitral position. Mean follow-up after the surgery was 4.3±3.7 years. 30 of the 35 patients were successfully treated by MV plasty (MVP); however, MV replacement (MVR) was necessary in the remaining 5 patients. Our novel approach included resection of the infective lesion, approximation with direct suture and/or patch repair with bovine or autopericardium after 2-min treatment of it and the defective leaflet edge(s) with 0.625% glutaraldehyde solution, reconstruction with artificial chordae and ring annuloplasty. The success rate of MVP was 85.7%. The longest postoperative follow-up echocardiography showed no mitral regurgitation (MR) in 4, trivial MR in 4, mild MR in 16 and moderate MR in 5 patients in the MVP group. The 5-year survival rate in the MVP group was 89±6%. MVR was required in 1 patient 2 months after MVP because of increasing MR. Recurrence of endocarditis has not been observed in any case. CONCLUSIONS: Glutaraldehyde was safely used in a surgical intervention for AAIE in the mitral position with acceptable early and mid-term results.

Effect of Inhaled Nitric Oxide on Hemodynamics in Lambs with 1½ Ventricle Circulation.

Inhaled nitric oxide (NO) is widely used to treat postoperative pulmonary hypertension in congenital heart disease. It is believed that NO increases cardiac output (CO) by decreasing pulmonary vascular resistance (PVR), leading to increased left ventricular preload. However, the effect of NO on CO in patients with 1½ ventricle circulation remains unclear. To evaluate this, a superior cavopulmonary (SCP) shunt was constructed in 10 juvenile sheep. A PTFE graft was inserted between the superior vena cava (SVC) and the main pulmonary artery (PA). The SVC was clamped at the right atrial junction to establish a 1½ ventricle circulation. Flows, pressures, and arterial blood gases were recorded before and during inhalation of NO. Mean arterial pressure (46.6 ± 5.4 to 44.6 ± 5.9 mm Hg; p = 0.06) and left atrial pressure (4.0 ± 2.5 to 4.0 ± 2.3 mm Hg; p = 1.0) did not change. Mean PA pressure (13.6 ± 2.4 to 11.7 ± 2.9 mm Hg; p = 0.006) and PVR (5.47 ± 2.99 to 4.54 ± 2.61 Wood Units; p = 0.037) decreased significantly. SVC flow (24.8 ± 11.3 to 22.0 ± 9.7 ml/min/kg; p = 0.09) did not change, and CO decreased (140.2 ± 37.2 to 132.1 ± 39.2 ml/min/kg; p = 0.033). Arterial PO2 improved (103.72 ± 29.30 to 132.43 ± 47.02 mm Hg; p = 0.007). In this 1½ ventricle model, NO surprisingly decreased cardiac output (CO) and did not increase left ventricular preload.

[Atrial Septal Defect with Hereditary Deficiency of Antithrombin III].

A 41-year-old female with hereditary deficiency of antithrombin III (ATIII) was diagnosed with atrial septal defect( ASD) and scheduled for the closure of ASD. She had been taking warfarin since she suffered from deep vein thrombosis 10 years ago. Preoperative management of anticoagulation included discontinuation of warfarin, and supplementation of antithrombin with heparin infusion. On the day of operation, antithrombin activity was maintained above 80% by administering antithrombin, and closure of ASD was carried out under standard cardiopulmonary bypass support using heparin. Heparin infusion was continued with antithrombin supplementation until prothrombin time-international normalized ratio(PT-INR) recovered to around 2.5 with warfarin. Her intra-and postoperative courses did not show any thromboembolic events, and she was discharged 20 days after the surgery.

Hemodynamic monitoring of large animal chronic studies after median sternotomy: experiences with different telemetric physiological devices.

Telemetric physiological monitoring systems (TPMS) have enabled accurate continuous measurement of animal blood pressures and flows. However, few studies describe approaches for use of TPMS in the great vessels or inside the heart. We describe our initial experiences using two types of TPMSs. Twelve lambs (20-37 kg) underwent sternotomy. Two lambs were not instrumented and were killed at 14 days to confirm normal sternal wound healing (sham group, n = 2). Ten lambs underwent placement of either standard indwelling pressure-monitoring catheter and perivascular-flow-probe (CFP group, n = 3) or TPMS implantation (TPMS group, n = 7). The TPMS used were EG1-V3S2T-M2 (EG1, n = 5; Transonic Endogear Inc.) and Physio Tel Digital L21 (PTD, n = 2; Data Sciences Inc.). Two deaths because of respiratory problems occurred in TPMS group, attributed to lung compression by the implanted device. In TPMS group, more consistent trends of blood pressures and flows were recorded, and management of animals was easier and less labor-intensive. Comparing the two TPMSs, the initiation and renewal costs for each case was $28 K vs. $20 K and $1,700 vs. $0, (PTD versus EG1, respectively). In conclusion, TPMS implantation was feasible via median sternotomy in lambs. Telemetric physiological monitoring systems significantly improve reliability of hemodynamic monitoring in chronic survival animal study. EG1 was less costly than PTD.

Inflammatory response to hyperoxemic and normoxemic cardiopulmonary bypass in acyanotic pediatric patients.

BACKGROUND: Hyperoxemic management during cardiopulmonary bypass (CPB) is still common, and there is no consensus about physiologic oxygen tension strategy (normoxemic management) during pediatric CPB. In this study, we compared the postoperative conditions and measures of inflammatory response among patients with acyanotic congenital heart disease subjected to either hyperoxemic or normoxemic management strategy during CPB. METHODS: We studied 22 patients with a ventricular septal defect and pulmonary artery hypertension. The patients were divided into two groups. Group I (n=9) received normoxemic management (PaO2=100-150 mm Hg) and group II (n=13) received hyperoxemic management (PaO2=200-300 mm Hg) during CPB. There was no difference between groups with regard to age, body weight, duration of CPB, and aorta clamping time or preoperative pulmonary hypertension (pulmonary pressure/systemic pressure [Pp/Ps]). In each group, the blood samples to measure the cytokine levels were collected before and after the CPB. RESULTS: Although we observed no statistically significant differences in postoperative intubation time, alveolar-arterial oxygen difference, creatine kinase MB level, and pulmonary hypertension (Pp/Ps) between group I (10.7±13.4 hours, 197±132 mm Hg, 148±58.6 IU/L, 42.8%±22.1%, respectively) and group II (27.8±36.5 hours, 227±150 mm Hg, 151±72.6 IU/L, 50.4%±16.0%, respectively), levels of median interleukin 6 and tumor necrosis factor α were lower in group I (129.8 and 17.0 pg/mL, respectively) than that in group II (487.8 and 22.5 pg/mL, respectively). CONCLUSION: During the CPB in acyanotic pediatric patients, normoxemic management can minimize the systemic inflammatory response syndrome associated with CPB. We can apply this physiologic oxygen tension strategy to surgical advantage during heart surgeries in acyanotic pediatric patients.

Reversal of oxidant-mediated biochemical injury and prompt functional recovery after prolonged single-dose crystalloid cardioplegic arrest in the infantile piglet heart by terminal warm-blood cardioplegia supplemented with phosphodiesterase III inhibitor.

PURPOSE: The benefit of terminal blood cardioplegia (TWBCP) is insufficient after prolonged ischemia associated with inevitable oxidant-mediated injury by this modality alone. We tested the effects of TWBCP supplemented with high-dose olprinone, which is a phosphodiesterase III inhibitor, a clinically available compound with the potential to reduce oxidant stress and calcium overload. We evaluated the effects with respect to avoiding oxidant-mediated myocardial reperfusion injury and prompt functional recovery after prolonged single-dose crystalloid cardioplegic arrest in a infantile piglet cardiopulmonary bypass (CPB) model. METHODS: Fifteen piglets were subjected to 90 min of cardioplegic arrest on CPB, followed by 30 min of reperfusion. In group I, uncontrolled reperfusion was applied without receiving TWBCP; in group II, TWBCP was given; in group III, TWBCP was supplemented with olprinone (3 µg/ml). Myocardial performance was evaluated before and after CPB by a left ventricular (LV) function curve and pressure-volume loop analyses. Biochemical injury was determined by measurements of troponin-T and lipid peroxide (LPO) in coronary sinus blood. RESULTS: Group III showed significant LV performance recovery (group I, 26.5% ± 5.1%; group II, 42.9% ± 10.8%; group III, 81.9% ± 24.5%, P < 0.01 vs. groups I and II), associated with significant reduction of troponin-T and LPO at the reperfusion phase. No piglets in group III needed electrical cardioversion. CONCLUSION: We concluded that TWBCP with olprinone reduces myocardial reperfusion injury by reducing oxidant-mediated lipid peroxidation, and it accelerates prompt and persistent LV functional recovery with suppression of reperfusion arrhythmia.

Ischemic postconditioning promotes left ventricular functional recovery after cardioplegic arrest in an in vivo piglet model of global ischemia reperfusion injury on cardiopulmonary bypass.

OBJECTIVE: An in vivo study of piglets on cardiopulmonary bypass was performed to determine whether postconditioning has a cardioprotective effect after cardioplegic arrest in large animals. METHODS: Eighteen piglets were subjected to 90 minutes of cardioplegic arrest followed by 30 minutes of reperfusion. In 6 animals (control), there was no intervention at reperfusion. In 6 other animals, 6 cycles of unclamping and reclamping for 10 seconds each were done before reperfusion (postconditioning 10), whereas 3 cycles of unclamping and reclamping for 30 seconds each were performed in another 6 piglets (postconditioning 30). RESULTS: Recovery of left ventricular contractility and diastolic function (percent of preischemic value) was significantly better in both postconditioning groups (contractility: 89.2% and 118.2; diastolic function: 142.3% and 120.4; in the postconditioning 10 and 30 groups, respectively) compared with the control (contractility: 46.1%; diastolic function: 218.5%). Recovery of global cardiac function (ventricular function curve analysis) was improved only in the postconditioning 30 group. Troponin-T release during reperfusion was significantly reduced in the postconditioning 10 group compared with all groups (plasma troponin-T was 0.58 ng/mL in postconditioning 10, 1.85 in postconditioning 30, and 2.54 in control). The myocardial lipid peroxide was significantly higher in the control group than in both postconditioning groups after reperfusion (199% vs 112% and 131%). CONCLUSIONS: Both postconditioning algorisms promoted functional recovery after cardioplegic arrest in a large animal model along with the limitation of lipid peroxidation with or without the reduction of troponin-T release.

Reconsideration of patient-prosthesis mismatch definition from the valve indexed effective orifice area.

BACKGROUND: The objective of this study was to reassess the validity of defining patient-prosthesis mismatch (PPM) in the aortic position on the basis of an indexed effective orifice area (iEOA) less than 0.85 cm(2)/m(2). METHODS: From June 1996 to March 2008, 342 patients underwent aortic valve replacement with a Carpentier-Edwards Perimount valve. From the data collected, the transvalvular pressure gradient was determined by the modified Bernoulli equation, and EOA was calculated from the standard continuity equation. RESULTS: The actuarial survival rate at 10 years after surgery was 84.0% +/- 8.2%. The prevalence of PPM was 6.1% when a projected iEOA less than 0.85 cm(2)/m(2) was defined as indicating significant PPM. There was no difference between patients with moderate PPM (85.2% +/- 9.8%) and patients without PPM (81.0% +/- 8.7%; p = 0.44). The relation between mean transvalvular pressure gradient and iEOA demonstrated a gentler slope than that reported previously. Postoperative mean transvalvular pressure gradient was 17.4 +/- 5.6 mm Hg and 14.5 +/- 5.6 mm Hg in patients with an iEOA less than 0.85 and 0.85 or greater, respectively. Most patients had a postoperative mean transvalvular pressure gradient more than 10 mm Hg regardless of PPM. CONCLUSIONS: Our analysis suggested that an iEOA less than 2.0 cm(2)/m(2) might be the threshold for PPM, which should not be passed to achieve a low mean transvalvular pressure gradient (less than 10 mm Hg) with the Carpentier-Edwards Perimount valve. The implications of these findings include the necessity for reassessing the hemodynamic performance of each type of prosthesis when attempting to define PPM, to avoid residual significant transvalvular pressure gradient.

Prevention of ischemia/reperfusion-induced pulmonary dysfunction after cardiopulmonary bypass with terminal leukocyte-depleted lung reperfusion.

OBJECTIVE: Pulmonary ischemia and reperfusion during routine open heart surgery with cardiopulmonary bypass can lead to pulmonary dysfunction and vasoconstriction, resulting in a high morbidity and mortality. We investigated whether ischemia/reperfusion-induced pulmonary dysfunction after full-flow cardiopulmonary bypass could be prevented by the infusion of leukocyte-depleted hypoxemic blood during the early phase of reperfusion (terminal leukocyte-depleted lung reperfusion) and whether the benefits of this method were nullified by using hyperoxemic blood for reperfusion. METHODS: Twenty-one neonatal piglets underwent 180 minutes of full-flow cardiopulmonary bypass with pulmonary artery occlusion, followed by reperfusion. The piglets were divided into 3 groups of 7 animals. In group I, uncontrolled reperfusion was achieved by unclamping the pulmonary artery. In contrast, pulmonary reperfusion was done with leukocyte-depleted hyperoxemic blood in group II or with leukocyte-depleted hypoxemic blood in group III for 15 minutes at a flow rate of 10 mL/min/kg before pulmonary artery unclamping. Then the animals were monitored for 120 minutes to evaluate post-cardiopulmonary bypass pulmonary function. RESULTS: Group I developed pulmonary dysfunction that was characterized by an increased alveolar-arterial oxygen difference (204 + or - 57.7 mm Hg), pulmonary vasoconstriction, and decreased static lung compliance. Terminal leukocyte-depleted lung reperfusion attenuated post-cardiopulmonary bypass pulmonary dysfunction and vasoconstriction when hypoxemic blood was used for reperfusion (alveolar-arterial oxygen difference, 162 + or - 61.0 mm Hg). In contrast, no benefit of terminal leukocyte-depleted lung reperfusion was detected after reperfusion with hyperoxemic blood (alveolar-arterial oxygen difference, 207 + or - 60.8 mm Hg). CONCLUSION: Reperfusion with leukocyte-depleted hypoxemic blood has a protective effect against ischemia/reperfusion-induced pulmonary dysfunction by reducing endothelial damage, cytokine release, and leukocyte activation.

Myocardial cyclic AMP augmentation with high-dose PDEIII inhibitor in terminal warm blood cardioplegia.

PURPOSE: Phosphodiesterase (PDE) III inhibitors have been reported in various cellular protective activities via the cyclic adenosine monophosphate (cAMP) pathway. We investigated the effects of amrinone on ischemia/reperfusion injury and intracellular calcium (Ca2+) handling if utilized as a component of terminal warm blood cardioplegia (TWBCP). METHODS: Anesthetized pig hearts were subjected to 90-min global ischemia with single-dose crystalloid cardioplegia, followed by 30-min reperfusion under cardiopulmonary bypass. The animals were divided into three groups according to the contents of TWBCP (n = 5 each): Control, no TWBCP; TWBCP, no additive; Amrinone, TWBCP with amrinone. The time course of cardiac function and biochemical samples were measured. Further, coronary perfusion and ventricular arrhythmia were evaluated during reperfusion. RESULTS: Cardiac function improved with amrinone. Specifically, the amrinone group showed an increase of myocardial cAMP (p <0.05) and a suppression of creatine kinase, troponin-T, and lipid peroxide after reperfusion (p <0.05); many cases also showed much improvement of coronary perfusion and spontaneous resuscitation after global ischemia. CONCLUSION: Ischemia and/or reperfusion deplete myocardial cAMP, leading to impaired Ca2+ handling and further to cardiac dysfunction. High-dose PDEIII inhibitor in TWBCP may replenish myocardial cAMP and promote rapid and sustained cardiac functional recovery with various cellular protective effects after open-heart surgery.

Double switch operation for congenitally corrected transposition of the great arteries after two-staged pulmonary artery banding.

We describe a case of congenitally corrected transposition of the great arteries (cc-TGA) successfully performed by the double switch operation after two-staged pulmonary artery banding (PAB). An eleven-year old boy diagnosed with cc-TGA underwent the first PAB at that age, followed by the second PAB one year later. Because of severe ventricular dysfunction and arrhythmia of the anatomic left ventricle, the intension of one-stage PAB was abandoned. Cardiac catheterization data from after the adequate second PAB provided the surgical indication for the anatomical correction and double switch operation (Senning+Jatene procedure) and this was successfully performed at age 14. Although cardioversion was required to treat supraventricular tachycardia in the early period after surgery, the patient was discharged from hospital and remains in good clinical condition at the last follow-up at 5 years with normal sinus rhythm and good biventricular function.

Long-term results of triple-valve procedure.

Triple-valve procedures are associated with high early and late mortality. We reviewed our experience in 25 patients who underwent combined mitral and aortic valve replacement with tricuspid valve repair or replacement between 1979 and 2004. The mean follow-up was 7.8 years (range, 10 days to 24.5 years). The mean age at operation was 52 years (range, 31 to 72 years). Four patients underwent triple-valve replacement and 21 had double-valve replacement and tricuspid annuloplasty. Perioperative mortality was 20% and late mortality was 24%. Cumulative survival, calculated taking perioperative mortality into account, was 71% +/- 10% at 10 years and 36% +/- 15% at 15 years after surgery. Only 1 of 20 perioperative survivors required re-operation for prosthetic valve dysfunction. Double-valve replacement with tricuspid annuloplasty offers satisfactory long-term survival with freedom from thromboembolism and re-operation.

Carpentier-Edwards pericardial aortic valve in middle-aged patients: comparison with the St. Jude Medical valve.

OBJECTIVE: The objective of the present study was to compare long-term results of single aortic valve replacement (AVR) with mechanical (St. Jude Medical valves: standard) and biologic (the Carpentier-Edwards pericardial) prostheses. METHOD: Between 1995 and 2002, 95 patients who underwent single AVR with mechanical (n= 46) or biologic (n= 49) prostheses were enrolled in this study. The mean age at the operation was 54.0 +/- 9.6 years (range: 20 to 69 years) with the mechanical and 68.8 +/- 7.1 years (range: 44 to 85 years) with the biologic prosthesis. RESULTS: The 9-year actuarial survival rate, which was calculated by taking perioperative mortality into account, was 90.3 +/- 4.6% for patients with mechanical valves and 87.6 +/- 4.8% for patients with bioprostheses, with no difference between the two groups (p=0.342). The 9-year freedom rate from thromboembolism, reoperation, endocarditis was 94.8 +/- 3.6%, 100% and 97.8 +/- 2.2% for patients with mechanical valves and 98.0 +/- 2.0%, 97.5 +/- 3.4% and 95.0 +/- 3.4% for those with bioprostheses, respectively. After 9 years, freedom from cardiac death averaged 97.8% in the group with mechanical valves compared with 95.3% in those with bioprostheses (p=0.541). CONCLUSION: We conclude that the mid-term durability of the Carpentier-Edwards pericardial valve in the aortic position for the elderly is excellent. Nevertheless, the risk of tissue valve reoperation progressively increases with time, and a longer follow-up may be necessary to provide its value compared with the mechanical valves in a country like Japan with a high life expectancy.

Thoracoabdominal coarctation of the aorta: surgical repair in a 7-year-old boy.

Atypical coarctation of the lower descending or the abdominal aorta is a relatively rare disease which occurs in about 0.5 to 2% of all coarctation cases. The majority of these diseases present with circumscribed narrowing of the abdominal aorta. However, we treated a 7-year-old boy with a rare form: a long, diffuse hypoplasia of the thoracoabdominal aorta.