Anomalous origin of the pulmonary artery from the aorta: early diagnosis and repair leading to immediate physiological correction.

INTRODUCTION: Anomalous origin of one pulmonary artery from the ascending aorta is a rare cardiac anomaly in which the pulmonary artery abnormally arises from the ascending aorta. Physiologically, most patients develop signs of cardiac failure due to high flow to both lungs, with systemic or supra-systemic pressures in the normally connected lung. The purpose of this study is to present our experience with this rare anomaly, in which early anatomic repair lead to rapid physiologic correction. MATERIALS AND METHODS: Retrospective case review of all patients with anomalous origin of one pulmonary artery from the ascending aorta at Schneider Children's Medical center of Israel between 1986 and 2007. All clinical operative and echocardiographic charts were analysed. RESULTS: Twelve patients were diagnosed as anomalous origin of one pulmonary artery from the ascending aorta. In 10 patients, the right pulmonary artery rose from the ascending aorta, while in two an anomalous origin of the left pulmonary artery was associated with a right aortic arch. Initial diagnoses was made with two-dimensional echocardiography in all patients. In six patients, diagnostic cardiac catheterisation was performed in order to confirm the diagnosis. Age at diagnosis ranged from 5 to 180 days with a median of 15 days, and patient weight ranged from 780 grams to 5 kilograms, with a median of 3 kilograms. Initial echocardiographic evaluation showed systemic (four patients) or supra-systemic (seven patients) pressures in the right ventricle and normally connected lung. All underwent surgical repair. There was no operative mortality. All reconstructed patients achieved normal right ventricular pressures within days after surgery. The flow pattern in both pulmonary arteries was normalised. CONCLUSIONS: Early surgical repair of anomalous origin of one pulmonary artery from the ascending aorta is feasible and safe even in newborn and premature babies with complete resolution of the pulmonary hypertension and normalisation of pulmonary vascular resistance.

Primary cardiac valve tumors.

To assess the prevalence, characteristics, and outcome of surgical treatment of primary cardiac valve tumors in a single center, we reviewed our experience in 6 women and 1 man, aged 49 to 76 years (mean, 64.7 years) who presented between 1999 and 2006. In one patient, the diagnosis of cardiac valve tumor was made incidentally on transesophageal echocardiography during aortocoronary bypass surgery. The others had clinical symptoms: angina or myocardial infarction in 3, congestive heart failure in 2, dyspnea and cerebrovascular ischemia in 1 patient each. Four of the 7 tumors were benign, and 3 were malignant. All patients survived the operation and recovered uneventfully. Midterm follow-up was available in all patients. Two patients with malignant tumors were considered unsuitable for adjuvant therapy by the oncologist; both died during follow-up from local tumor recurrence. All 5 survivors were categorized at the last follow-up as functional class I, with normal exercise tolerance. Excellent early and midterm surgical results can be obtained in patients with benign cardiac valve tumors, but the prognosis for those with a malignant tumor is poor.

Video-assisted pericardial fenestration for effusions after cardiac surgery.

Delayed-onset pericardial effusion following cardiac surgery can give rise to significant morbidity due to its presentation as well as management by traditional surgical techniques. An institutional experience of a video-assisted thoracoscopic technique to create a pericardial window, with the advantages of a minimally invasive approach combined with excellent visualization in such patients, was reviewed. A retrospective analysis was conducted on all patients undergoing video-assisted thoracoscopic for delayed pericardial effusion after cardiac surgery from January 2001 to January 2006 at our center. Seven patients with echocardiographically diagnosed delayed tamponade underwent video-assisted thoracoscopy; 5 were receiving anticoagulants after valve replacement, and 2 had undergone heart transplantation. Pericardial windows were created under general anesthesia and single-lung ventilation using 2 to 3 trocars. Mean operative time was 45 min. There were no complications of the thoracoscopic technique. Video-assisted thoracoscopic creation of a pericardial window is safe and effective treatment for loculated pericardial effusions secondary to cardiac surgery.

Increased glycogen stores due to gamma-AMPK overexpression protects against ischemia and reperfusion damage.

During ischemia, endogenous glycogen becomes the principal substrate for energy through glycolysis. Cardiac-specific manipulation of AMP-activated protein kinase (AMPK) by over-expression of its regulatory gamma-subunit induces glycogen storage. The aim of this study was to examine whether heart glycogen in transgenic mice overexpressing PRKAG2 may protect from ischemia and reperfusion injury. Isolated hearts were mounted on Langendorff apparatus and subjected to 30 min 'no-flow' or 'low-flow' ischemia and 60 min reperfusion. Hemodynamic measurements, tetrazolium staining, glycogen and lactate were used to monitor ischemia reperfusion damage. After low-flow ischemia, left ventricular pressure, coronary flow (CF) and the area of viable myocardium were 20-30% higher in PRKAG2 mice compared to controls. The basal levels of glycogen in PRKAG2 were 9.2 microg/g, markedly higher than in controls, but after low-flow ischemia they declined concomitantly with increased lactate washout in the coronary effluent. During no-flow ischemia there was neither protection nor consumption of glycogen in PRKAG2 hearts. Cardioprotection was also eliminated when PRKAG2 hearts were depleted of glycogen prior to low-flow ischemia. AMPK alpha Thr172 phosphorylation did not differ between PRKAG2 hearts and controls either during low-flow ischemia or reperfusion. We conclude that PRKAG2 hearts resist low-flow ischemia injury better than controls. Improved recovery was associated with increased consumption of glycogen, and was unrelated to AMPK activation. These findings demonstrate the potential of heart protection from ischemia and reperfusion injury through metabolic manipulation increasing the level and utilization of myocardial glycogen.

Limb performance and patient satisfaction after radial artery harvesting: endoscopic versus open techniques.

BACKGROUND: The differences in hand functionality after harvesting the radial artery for coronary artery bypass grafting (CABG) in an endoscopic technique relative to open technique are unclear. METHODS: One hundred and sixty-four patients who had CABG and their non dominant hand radial artery was harvested either in an open technique (n = 92) or in an endoscopic technique (n = 72) in a period of 9.8 +/- 3.5 months after the operation were studied. Surgical technique was surgeon specific. Patients were asked either five questions (endoscopic group), or six questions (open group), to assess how radial artery harvesting affected them. RESULTS: Significantly more patients in the open group experienced significant limitations in their work and regular daily activities (12% versus 0%, p = 0.02), social activities (13% versus 0%, p = 0.005), and experienced significant pain (8% versus 0%, p = 0.04) compared with the endoscopic group. More patients in the open group complained that their arm incision disturb them (24% versus 10%, p = 0.01). Forty-two patients (46%) in the open group would prefer smaller incision. A "limitation score" variable was created from the first four questions to reflect overall functionality. Severe limitation was present in 3% of the open group versus 0% in the endoscopic group (p = 0.04). Female sex and open harvesting technique were found to be independently associated with higher limitation score. CONCLUSIONS: After a mean of 9.8 months after surgery, patients reports good overall upper-limb function. However, more patients in the open technique had significant disabilities and dissatisfaction.

[AMP-activated protein kinase: how a mistake in energy gauge causes glycogen storage].

Mutation in PRKAG2 encoding the gamma2 subunit of the AMP activated protein kinase (AMPK) cause human cardiomyopathy characterized by hypertrophy, Wolff-Parkinson-White syndrome, conduction system disease and glycogen storage in the myocardium. AMPK is a master metabolic regulator activated by hormones and energy deficient states. A heterotrimer enzyme comprising the catalytic alpha- and regulatory beta-and gamma-subunits was preserved through evolution and is ubiquitously expressed among mammalian tissues. AMPK is activated by AMP and inhibited by ATP that competes for binding to the regulatory sites on the gamma-subunit. Upstream kinases which phosphorylate Thr172 on the catalytic subunit activate the enzyme during exercise, ischemia, in response to sympathetic stimulation and hormones such as leptin and adiponectin. AMPK operates by phosphorylating its target proteins such as Acetyl CoA Carboxylase. Its classic functions include decreased fat synthesis in liver and adipose tissues, increased fatty acid oxidation, stimulating muscle glucose uptake and glycolysis. Altogether, these activities serve to restore the cellular and whole body energy balance. Human mutations which disrupt the nucleotide-binding affinity of the gamma2 subunit lead to loss of inhibition by ATP and inappropriate activate AMPK under resting conditions. As a result, myocytes recruit energy metabolites in excess of demand, causing storage of glycogen. Will AMPK ever emerge as a therapeutic target? Bench experiments suggest its potential in treating diabetes, ischemia and cell cycle regulation but much work is needed until these developments reach the bedside.

The protective effect of prior ischemia reperfusion adenosine A1 or A3 receptor activation in the normal and hypertrophied heart.

OBJECTIVES: The increased susceptibility to ischemic injury of hypertrophied hearts has long been recognized. The purpose of this study was to investigate the effects of pre-ischemic pharmacological preconditioning (PC) with adenosine A(1) or A(3) receptor activation, on the recovery of the isolated myocardium post cardioplegic ischemia. In addition, we examined the p38 MAPK activation in this process. MATERIALS AND METHODS: WKY and SHR hearts were subjected to two different modes of treatment. (1) In the perfusion mode- (the first window of PC) isolated rat hearts were perfused for 10 min with Krebs Henseleit solution and then A(1) receptor agonist (CCPA) or A(3) receptor agonist (Cl-IB-MECA), 10 nM for 20 min, followed by 30 min of warm cardioplegic ischemia and 30 min of reperfusion. (2) In the injection mode (the second window of PC) 100 microg/kg CCPA or Cl-IB-MECA, were administered 24 h before the experiment. Isolated hearts were perfused for 30 min with KH and then subjected to the same protocol as described above. RESULTS: Recovery of hemodynamic parameters was always better in the normal vs. hypertrophied hearts. CCPA improved recovery of left ventricular developed pressure, coronary flow and ATP levels of the hearts (normal and hypertrophied) in both modes of treatment. Cl-IB-MECA was partially beneficial especially in the injected mode. Increased phosphorylation of p38 MAPK relative to baseline, in both early (perfused) and late (injected) modes of treatment especially in the WKY hearts, is demonstrated. CONCLUSION: CCPA in both modes of treatment and Cl-IB-MECA, especially in the injected mode, were beneficial in protecting the normal and hypertrophied perfused isolated rat heart subjected to normothermic cardioplegic ischemia. This protection was partially related to the increased phosphorylation of p38 MAPK.

Bax ablation protects against hepatic ischemia/reperfusion injury in transgenic mice.

Apoptosis appears to be a central mechanism of cell death following reperfusion of the ischemic liver. The aim of this study was to determine the effect of decreased expression of the proapoptotic Bax gene on hepatic apoptotic warm ischemia/reperfusion (I/R) injury. Three groups of mice were studied: homozygotic knockout mice (Bax-/-); heterozygotic (Bax+/-); and wild type (Bax+/+). Isolated mouse livers were subjected to 90 minutes of ischemia (37 degrees C) followed by 15 minutes of reperfusion. Bax and Bcl-2 expression in liver tissue homogenates was measured by Western blot. Serum liver enzyme levels were measured and intrahepatic caspase-3 activity was determined by fluorimetric assay. Oil red O (ORO) staining was performed for fat detection. Apoptotic cells were identified by morphological criteria, immunohistochemistry for caspase-3, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) assay. At 1 minute of reperfusion, the ischemic (Bax-/-) livers were characterized by statistically significantly lower liver enzyme levels and lower caspase-3 activity than the ischemic (Bax+/+) livers (P<0.05 for both). The reduction in postischemic apoptotic hepatic injury in the ischemic Bax-/- livers group was confirmed morphologically, by the significantly reduced microvesicular steatosis as determined by ORO staining, fewer apoptotic hepatocyte cells detected (P<0.05); immunohistochemically, by the significantly weaker activation of caspase-3 compared to the ischemic group (P<0.05); and by TUNEL assay (P<0.05). Similar levels of antiapoptotic Bcl-2 protein expression were detected in all 3 groups of ischemic livers on Western blots. Bax protein was not expressed in Bax-deficient livers and was detected in Bax+/+ normal livers. In the Bax+/- livers, levels of the damage markers were moderate. In conclusion, The better tolerance of Bax knockout livers to I/R injury suggests that the Bax gene may serve as a potential target for therapeutic intervention in hepatic I/R injury.

The impact of intraoperative transesophageal echocardiography in infective endocarditis.

BACKGROUND: [corrected] The use of intraoperative transesophageal echocardiogram in patients with infective endocarditis is usually reserved for cases of inadequate preoperative testing or suspected extension to perivalvular tissue. OBJECTIVES: To explore the impact of routine intraoperative TEE in patients with infective endocarditis. METHODS: The impact of intraoperative TEE on the operative plan, anatomic-physiologic results, and hemodynamic assessment or de-airing was analyzed in 59 patients (38 males, 21 females, mean age 57.7 +/- 16.8 years, range 20-82) operated for active infective endocarditis over 56 months. RESULTS: Immediate pre-pump echocardiography was available in 52 operations (86.7%), and changed the operative plan in 6 of them (11.5%). Immediate post-pump study was available in 59 patients (98.3%) and accounted for second pump-run in 6 (10.2%): perivalvular leak (3 cases), and immobilized leaflet, significant mitral regurgitation following vegetectomy, and failing right ventricle requiring addition of vein graft (1 case each). Prolonged de-airing was necessary in 6 patients (10.2%). In 5 patients (8.5%) the postoperative study aided in the evaluation and treatment of difficult weaning from the cardiopulmonary bypass pump. In 21 patients (35.6%) the application of intraoperative TEE affected at least one of the four pre-specified parameters. CONCLUSIONS: Intraoperative TEE has an important role in surgery for infective endocarditis and should be routinely implemented.

Bilateral skeletonized internal mammary versus single-pedicled internal mammary grafting in the elderly.

BACKGROUND: The use of the bilateral internal mammary arteries has been reserved mainly for younger and low risk patients. AIM: To assess the safety and efficacy of BIMA grafting in older patients (> or = 70 years). METHODS: We reviewed the records of all consecutive patients > or = 70 years old who underwent coronary artery bypass surgery with a BIMA graft in our institute over a 2 year period. Demographic data, operative data, perioperative morbidity and mortality were recorded. Findings were compared with a matched-size group of patients who underwent CABG with a left internal mammary artery graft to left anterior descending artery. RESULTS: The study sample included 136 patients, of whom 68 underwent BIMA grafting and 68 LIMA grafting. Baseline demographic and clinical characteristics were similar in the two groups. There was no significant difference in operative mortality between the BIMA and LIMA groups (1.5% vs. 0%, P = 0.3) or in mortality during follow-up at a mean of 16 months (4.4% vs. 2.9%, P = 0.4, respectively). There was no difference between the groups in the incidence of perioperative complications, readmission and reintervention rates during follow-up. Significant between-group differences were noted for mean cardiopulmonary bypass time (93.2 +/- 34.7 min with BIMA vs. 108.8 +/- 40.7 min with LIMA, P = 0.02) and for red blood cell transfusion (1.9 +/- 1.9 vs. 4.3 +/- 2.8 packed cells/patient, P < 0.001). CONCLUSIONS: The performance of mainly arterial revascularization with BIMA grafting in patients 70 years or older is as safe as LIMA grafting, with the added advantage of being a better conduit than saphenous vein graft, requiring fewer blood transfusions, and shorter cardiopulmonary bypass time.

Early oral analgesia after fast-track cardiac anesthesia.

PURPOSE: Oral analgesia after "fast-track" cardiac anesthesia has not been explored. The aim of this study was to compare two oral oxycodone analgesic regimens. METHODS: One hundred-twenty patients scheduled for coronary artery bypass grafting were randomly assigned postoperatively to receive immediate-release oxycodone 5 mg and acetaminophen 325 mg (Percocet-5) (group I) per os four times daily, or controlled-release oxycodone 10 mg (OxyContin) (group II) per os every 12 hr and placebo twice daily. Acetaminophen 500 mg per os was used as first-line rescue medication, and immediate-release oxycodone (syrup form) 5 mg per os as second-line rescue medication. Pain intensity was assessed with a visual analogue scale on the first postoperative day, the morning after extubation, and thereafter four times daily for four days. Use of rescue medication and adverse events were recorded. RESULTS: Baseline demographic and operation-related characteristics were similar in both groups. While pain control was good in both groups, the immediate-release group experienced less pain on all postoperative days (P = 0.003), required significantly less rescue medication, and had fewer adverse effects such as somnolence and nausea. CONCLUSION: Peroral oxycodone is effective for early pain control after fast-track cardiac anesthesia. Immediate-release oxycodone/ acetaminophen appears to provide better analgesia and fewer side effects compared to controlled-release oxycodone.

Primary pulmonary amyloidosis due to low-grade B cell lymphoma.

Pulmonary involvement is not an infrequent complication of systemic amyloidosis, although affected patients rarely have significant pulmonary symptoms. In contrast, localized (primary) pulmonary amyloidosis is rare. We report a case of pulmonary low-grade B cell lymphoma with amyloid production, causing localized pulmonary amyloidosis.

Takotsubo cardiomyopathy: expanding the differential diagnosis in cardiothoracic surgery.

We describe a case of takotsubo cardiomyopathy in a 69-year-old woman after right upper lobectomy, without cardiac antecedents. The immediate course of recovery was uneventful. On the first postoperative day, clinical symptoms of acute coronary syndrome developed in association with ischemic electrocardiographic changes and a mild elevation in creatinine phosphokinase levels. Echocardiography showed moderate left ventricular dysfunction, with a typical takotsubo pattern. Coronary angiography revealed no abnormalities. After 2 days of supportive treatment, the patient recovered completely. The clinical presentation, instrumental findings, additional cardiac and noncardiac diseases, and the potential pathomechanism of takotsubo cardiomyopathy are described according to the current medical literature.

Uridine-5'-triphosphate (UTP) reduces infarct size and improves rat heart function after myocardial infarct.

We have previously found that uridine 5'-triphosphate (UTP) significantly reduced cardiomyocyte death induced by hypoxia via activating P2Y(2) receptors. To explore the effect of UTP following myocardial infarction (MI) in vivo we studied four groups: sham with or without LAD ligation, injected with UTP (0.44microg/kg i.v.) 30min before MI, and UTP injection (4.4microg/kg i.v.) 24h prior to MI. Left ventricular end diastolic area (LVEDA), end systolic area (LVESA) fractional shortening (FS), and changes in posterior wall (PW) thickness were performed by echocardiography before and 24h after MI. In addition, we measured different biochemical markers of damage and infarct size using Evans blue and TTC staining. The increase in LVEDA and LVESA of the treated animals was significantly smaller when compared to the MI rats (p<0.01). Concomitantly, FS was higher in groups pretreated with UTP 30min or 24h (56+/-14.3 and 36.7+/-8.2%, p<0.01, respectively). Ratio of infarct size to area at risk was smaller in the UTP pretreated hearts than MI rats (22.9+/-6.6, 23.1+/-9.1%, versus 45.4+/-7.6%, respectively, p<0.001). Troponin T and ATP measurements, demonstrated reduced myocardial damage. Using Rhod-2-AM loaded cardiomyocytes, we found that UTP reduced mitochondrial calcium levels following hypoxia. In conclusion, early or late UTP preconditioning is effective, demonstrating reduced infarct size and superior myocardial function. The resulting cardioprotection following UTP treatment post ischemia demonstrates a reduction in mitochondrial calcium overload, which can explain the beneficial effect of UTP.

Lung transplantation in patients with cystic fibrosis: the Israeli experience.

BACKGROUND: Lung transplantation is a well-established therapeutic option for end-stage lung disease in cystic fibrosis. Although it confers a clear survival advantage, outcome differs among centers according to local experience, patient selection, transplantation procedure, and postoperative care. OBJECTIVES: To evaluate the national Israeli experience with lung transplantation in patients with CF. METHODS: We reviewed the medical charts of all CF patients who underwent lung transplantation between January 1996 and June 2005 at the two Israeli centers that perform this procedure. RESULTS: Eighteen transplantations were performed in 17 patients. Mean patient age at transplantation was 25.3 +/- 9.1 years, and mean duration of follow-up in survivors (n=14) was 37.2 months (range 1-113 months). The actuarial survival rate was 88% at 1 year and 74% at 5 years. Pulmonary function, expressed as percent of predicted normal forced expiratory volume in 1 sec, improved from 22.4 +/- 8.1% to 76 +/- 16.8% at one year after transplantation. Bronchiolitis obliterans syndrome was diagnosed in 5 patients (29%), of whom 2 died and 2 are currently candidates for retransplantation. Median time to onset of BOS was 34.2 months (range 17-64 months). CONCLUSION: In Israel, the early and intermediate-term results of lung transplantation for cystic fibrosis are encouraging. BOS remains a major complication that threatens long-term outcome.

Bilateral diaphragm paralysis following cardiac surgery in children: 10-years' experience.

OBJECTIVE: To review the incidence and complications of conservative management of bilateral diaphragm paralysis following pediatric cardiac surgery. DESIGN AND SETTING: Retrospective clinical review based on computerized database with daily follow-up in a pediatric cardiac intensive care unit in a tertiary care center. PATIENT AND PARTICIPANTS: Were reviewed the data on nine patients with bilateral diaphragm paralysis from the 3,214 consecutive children (0.28%) after operations performed between 1995 and 2004. MEASUREMENTS AND RESULTS: A fluoroscopy-confirmed diagnosis of bilateral diaphragm paralysis was made in all nine patients. Mechanical ventilation was required for 14-62 days; maximum time to recovery was 7 weeks. Three patients underwent unilateral plication. Patients with a complicated postoperative course required longer mechanical ventilation. All patients were managed with a nasotracheal tube. One patient had minor subglottic stenosis. All patients survived. CONCLUSIONS: Bilateral diaphragm paralysis can be managed conservatively with good prognosis and minor complications. The recovery time is relatively short, less than 7 weeks.

Relationship between changes in thyroid hormone level and severity of the postoperative course in neonates undergoing open-heart surgery.

BACKGROUND: Our aim was to determine whether the changes in thyroid function after open-heart surgery in neonates depend on the postoperative course. METHODS: Twenty neonates undergoing open-heart surgery for congenital heart disease were prospectively studied in the cardiac intensive care unit of a university-affiliated children's hospital. The patients were divided into two groups by level of inotropic support (high or mild). RESULTS: The groups were similar in age, bypass time and ultrafiltration volume. In both groups, there was a significant reduction in levels of thyroid-stimulating hormone and FT4 at 24 h postoperatively. However, in the high inotropic support group, FT4 was lower for a longer time. This group also had a significantly higher score on The Pediatric Risk of Mortality (PRISM; P < 0.042) and a longer duration of ventilation (P < 0.014). CONCLUSIONS: Neonates after open-heart surgery undergo changes in thyroid function characteristic of euthyroid sick syndrome. The degree of hypothyroxinemia may be related to the severity of illness and the postoperative course.