We studied the in vivo persistence of hypoxia-inducible factor-1alpha (HIF-1alpha), main transducer of hypoxia, the differential response in organs exposed to the same degree of hypoxemia and the relationship with apoptosis. We measured HIF-1alpha (immunohistochemistry peroxidase and Western blot) and apoptosis (TUNEL) in heart, liver, kidney, gastrocnemius, and brain of rats exposed to chronic normobaric hypoxia (10% O2) or normoxia (21% O2) for 2 weeks. Despite same arterial O2 pressure and increased hemoglobin concentration (219 +/- 5 vs. 124 +/- 4 g/L), the organs responded differently. While marked in brain, muscle, and kidney cortex, HIF-1alpha was undetectable in heart and liver. In kidney medulla, HIF-1alpha was high in both normoxia and hypoxia. By contrast, apoptosis was marked in heart, slight in kidney medulla, and undetectable in other organs. We conclude that the HIF-1alpha response to chronic hypoxia can be a sustained phenomenon, but not in all organs, and that apoptosis responds differently from HIF-1alpha.

Material and Methods: A pericardial valve mounted onto a self-expanding stent (3f) was evaluated A) in-vitro in a pulsatile mock loop with 3 to 5 l/min flow and an afterload of 70mmHg and B) in vivo in six calves (74.3±2.4 Kg). Implantation was on-pump into orthotopic aortic position. In vivo assessment was performed with intracardiac- (AcuNav™) and intravscular-ultrasound (IVUS) including: leaflet motion, planimetric valve orifice, coronary-blood-flow-characteristics, transvalvular gradient, regurgitation and paravalvular leaking, in combination with continuous cardiac output measures. Macroscopic analysis was performed at necropsy.

Cardiopulmonary bypass (CPB) remains the key technology for more complex cardiac operations. The perfusion equipment used nowadays has seen tremendous progress since its introduction into clinical practice 50 years ago. However, overall, CPB is still far from perfect. Major haemodilution is not only a problem for red cell-dependent gas transport, but also for the platelet and humeral factor-dependent coagulation, the protein-dependent intravascular oncotic pressure and so forth. Reduction of the priming volume through further miniaturization of CPB equipment is, therefore, the most obvious next step. A systematic approach needs to optimize all CPB components, including pumps, oxygenator/heat exchanger structures, filters, reservoirs, cardiotomy suction, tubings and cannulas. This report provides an update of already commercially available low prime perfusion devices (e.g., the CORx integrated pump-oxygenator) as well as promising prototypes like the smart suction system and the smartcanula.™

Aortic access problems due to diseased or small peripheral vessels are a major issue in endovascular aneurysm repair (EVAR). In the emergency setting, like aortic rupture after blunt trauma, or in patients with a hostile abdomen, a more proximal access to the aorta is not a pleasant perspective. We developed in situ introducer sheath dilatation as a bail-out technique for patients with difficult aortic access under various circumstances including EVAR, intra-aortic balloon pump insertion and cannulation for perfusion. The method described allows to increase the access vessel diameter by 50% (from 6 to 9 mm) or the luminal circumference from 18 to 27 F. We have used this technique in five patients without complication, very much in contrast to the traditionally practiced 'forced device insertion'.

Despite the progress made in the development of cardiopulmonary bypass (CPB) equipment, systemic anticoagulation with unfractioned heparin and post-bypass neutralization with protamine are still used in most perfusion procedures. However, there are a number of situations where unfractioned heparin, protamine or both cannot be used for various reasons. Intolerance of protamine can be addressed with extracorporeal heparin removal devices, perfusion with (no) low systemic heparinization and, to some degree, by perfusion with alternative anticoagulants. Various alternative anticoagulation regimens have been used in cases of intolerance to unfractioned heparin, including extreme hemodilution, low molecular weight heparins, danaparoid, ancrod, r-hirudin, abciximab, tirofiban, argatoban and others. In the presence of heparin-induced thrombocytopenia (HIT) and thrombosis, the use of r-hirudin appears to be an acceptable solution which has been well studied. The main issue with r-hirudin is the difficulty in monitoring its activity during CPB, despite the fact that ecarin coagulation time assessment is now available. A more recent approach is based on selective blockage of platelet aggregation by means of monoclonal antibodies directed to GPIIb/IIIa receptors (abciximab) or the use of a GPIIb/IIIa inhibitor (tirofiban). An 80% blockage of the GPIIb/IIIa receptors and suppression of platelet aggregation to less than 20% allows the giving of unfractioned heparin and running CPB in a standard fashion despite HIT and thrombosis. Likewise, at the end of the procedure, unfractioned heparin is neutralized with protamine as usual and donor platelets are transfused if necessary. GPIIb/IIIa inhibitors are frequently used in interventional cardiology and, therefore, are available in most hospitals.

We propose modified warm blood antegrade-retrograde reperfusion (WBARR) of arrested hearts as a metabolic model with which to study substrate exchange and energy metabolism during the recovery phase after 90 min of ischaemia in man. Eleven anaesthetized patients undergoing aorto-coronary bypass were studied during WBARR. The protocol was designed as follows: period 1, a warm blood reperfusion with potassium (3 min); period 2, a warm blood reperfusion without potassium (2 min). The perfusion flow rate averaged 250±2 ml/min at the beginning of period 1 and 218±19 ml/min at the beginning and at the end of period 2; the perfusion was performed antegradely and retrogradely in the arrested hearts. Samples were simultaneously taken from the coronary venous sinus (CVS) and from the aortic root needle (AR). At the beginning of WBARR lactate release was 85±44 μmol/min and at the end it had significantly decreased to 21±99 μmol/min (P<0.03). Simultaneously, non-esterified fatty acids (NEFA) and β-hydroxy-butyrate were initially released (71±61 and 22±66 μmol/min, respectively), while at the end of the WBARR there was an uptake of both NEFA (20±22 μmol/min; P<0.01) and β-hydroxy-butyrate (12±35 μmol/min; P=0.290). Alanine, glycerol and branched chain amino acid balance across the heart did not significantly change. In summary after 90 min of ischaemia the heart energy metabolism is mainly anaerobic and based on glucose consumption, with lactate, NEFA and amino acids, which are mainly released. After 5 min of WBARR (recovery from ischaemia), lactate release is significantly reduced and NEFA becomes the energy supply of the heart. In conclusion, (1) WBARR is a valuable method with which to study myocardial metabolism in anaesthetized humans and may be combined with the use of tracers; (2) the study of myocardial metabolism in arrested hearts eliminates the imprecisions arising from the non-continuous coronary blood flow; (3) NEFA become an important source of energy utilized by human hearts in the recovery phase from ischaemia.

The association of left isomerism with interruption and azygos continuation of the inferior caval vein, anomalous connection of the right pulmonary veins to the right atrium, an interatrial communication of sinus venosus type, and tetralogy of Fallot with right aortic arch and anomalous coronary artery has been observed in a 6-month-old patient. As far as we are aware, the association of these congenital cardiac malformations has not previously been reported in patients with isomeric left atrial appendages.

In the November 1994 issue of the Journal, Feng and Singh1Feng WC Singh AK Intraoperative use of end-tidal carbon dioxide tension to assess cardiac output.J THORAC CARDIOVASC SURG. 1994; 108: 991-992PubMed Scopus (8) Google Scholar reported the use of end-tidal carbon dioxide tension as an index of cardiac output. They monitored end-tidal carbon dioxide to facilitate weaning from cardiopulmonary bypass in adults having cardiac operations. This approach seems to be quite reductive, because a more extensive evaluation can be obtained by adding the following (generally available) metabolic and ventilatory parameters: arterial oxygen tension, arterial carbon dioxide tension, mixed expiratory partial pressure of carbon dioxide, arterial-alveolar carbon dioxide gradient (obtained from arterial carbon dioxide tension and end-tidal carbon dioxide), alveolar-arterial oxygen gradient (evaluated with an inspired oxygen tension of 0.5), oxygen consumption, carbon dioxide production, compliance per kilogram of body weight (from the ventilator measurements tidal volume/plateau pressure in milliliters per centimeter of water per kilogram of body weight), and rest energy expenditure (REE = carbon dioxide production × 5.52). All these parameters can be monitored both during the operation and during the postoperative period, to obtain a more comprehensive evaluation of the metabolic, ventilatory, and circulatory situations. Literature reports exist on this type of monitoring, particularly with regard to postoperative evaluation in adult cardiac surgery.2Chiara O Giomarelli P Biagioli B Rosi R Gattinoni L. Hypermetabolic response after hypothermic cardiopulmonary bypass.Crit Care Med. 1987; 15: 1071-1075Crossref Scopus (74) Google Scholar, 3Corno A Giomarelli P Biagioli B Barbini P Grossi A. Postoperative cardiopulmonary monitoring with a computer-based system.J Am Coll Cardiol. 1990; 15: 260AAbstract Full Text PDF Google Scholar In pediatric cardiac surgery, the aforementioned methods of monitoring have been used to differentiate among the perioperative variations after correction of congenital heart defects with preoperative left-to-right shunt, with right-to-left shunt, or without intracardiac shunt. In fact, such methods have been reported in this JOURNAL.4Giomarelli P Biagioli B Lisi G Santoro F Corno A On-line metabolic and ventilatory monitoring in pediatric cardiac operations.J THORAC CARDIOVASC SURG. 1989; 97: 939-940PubMed Google Scholar Therefore, monitoring of end-tidal carbon dioxide tension not only should be used as a routine evaluation in adult and pediatric cardiac surgery, but also should be applied to more complex situations (e.g., assisted mechanical circulation, unusual palliative procedures) to expand the horizon of its potential use.

out in his editorial [3], in our eagerness to decrease transfusion conservation techniques with a "first do something" approach.We congratulate Dr Ward and his co-workers on an excellent article and a scientific study whose design was superior to our relatively simple report.We, to this day, do not use unprocessed shed mediastinal blood for reinfusion and note that, based on the accummulating evidence, this is gradually becoming a standard practice.

Assessing the role of O-2 supply in the regulation of cardiac function in O-2-limited hearts is crucial to understanding myocardial ischemic preconditioning and adaptation to hypoxia. We exposed isolated Langendorff-perfused rat hearts to either ischemia (low coronary flow) or hypoxemia (low PO2 in the perfusing medium) with matched O-2 supply (10% of baseline). Myocardial contractile work and ATP turnover were greater in hypoxemic than in ischemic hearts (P < 0.05; n = 12). Thus, the energy demand was higher during hypoxemia than during ischemia, suggesting that ischemic hearts are more downregulated than hypoxemic hearts. Venous PO2 was 12 +/- 2 and 120 +/- 15 Torr (P < 0.0001) for ischemic and hypoxemic hearts, respectively, but O-2 uptake was the same. Lactate release was higher during hypoxemia than during ischemia (9.7 +/- 0.9 vs. 1.4 +/- 0.2 mu mol/min, respectively; P < 0.0001). Electrical stimulation (300 min(-1); to increase energy demand) increased performance in ischemic (P < 0.005) but not in hypoxemic hearts without changes in venous PO2 or O-2 uptake. However, venous lactate concentration and lactate release increased in ischemic (P < 0.002) but not in hypoxemic hearts, suggesting that anaerobic glycolysis provides the energy necessary to meet the increased energy demand in ischemic hearts only. We conclude that high intracellular lactate or H+ concentration during ischemia plays a major role as a downregulating factor. Downregulation disappears in hypoxemic hearts secondary to enhanced washout of lactate or H+.

Journal Article Recovery of hypoxic neonatal hearts after cardioplegic arrest Get access MICHELE SAMAJA, MICHELE SAMAJA Search for other works by this author on: Oxford Academic PubMed Google Scholar ANTONIO CORNO ANTONIO CORNO Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 11, November 1993, Pages 2083–2084, https://doi.org/10.1093/cvr/27.11.2083a Published: 01 November 1993

Of 353 children who underwent surgical repair of a congenital heart defect, including closure of a ventircular septal defect (VSD), 12 patients (four with tetralogy of Fallot, five with a VSD, and three with a double-outlet right ventricle) developed subaortic stenosis, which was diagnosed one to six years after the surgical procedure. Five patients required surgical treatment of the subaortic stenosis, and one required percutaneous balloon angioplasty. Postsurgical subaortic stenosis appears to be an uncommon progressive acquired disease.

BackgroundTotal cavopulmonary connection has been proposed as a rational alternative to atriopulmonary connection for complex Fontan operations. In addition to fluid dynamic advantages proposed by de Leval, total right heart bypass may address an emerging important issue after repair of single ventricle: late atrial arrhythmias. The purpose of this study is to document the postoperative hemodynamic findings in 22 consecutive patients who received a total extracardiac right heart bypass with an inferior vena cava-to-pulmonary artery extracardiac Dacron conduit with a modified Glenn anastomosis (superior vena cava-topulmonary artery anastomosis). Methods and ResultsTwenty-eight patients with complex congenital heart disease underwent this surgical procedure. One patient died (early mortality, 3.5%). Mean follow-up was 13.9 months. Postoperative cardiac catheterization and echo Doppler studies were performed in 22 of the 27 survivors. In 18 of 22 patients, hemodynamic data were satisfactory; a preferential direction of caval flows to both lungs was observed. Echo Doppler assessments show that forward cavopulmonary flow appears as a predominant early diastolic event, in contrast to what occurs in atriopulmonary connections. This hemodynamic model emphasizes the possible role of the diastolic ventricular performance (as a “suction pump”) in Fontan circulation. Early postoperative atrial arrhythmias were observed in two of the survivors. ConclusionsThe technical advantages and the hemodynamic benefits of this form of right heart bypass are encouraging. Although the use of artificial material in this procedure is extensive, none of the survivors showed thromboembolic complications or peel formations with narrowing and/or obstruction. Further investigations during a longer follow-up are needed to confirm the early and intermediate results, especially the reduction of late atrial arrhythmias.

OBJECTIVE--To study electrocardiographic changes in infants and children in whom topical cooling was used during surgical repair of congenital heart defects. DESIGN--A retrospective study of all patients who had surgical repair of congenital heart disease during cold blood cardioplegia and topical cooling from January to August 1990. Eleven patients (group 1) had topical cooling with ice and 15 (group 2) with cold saline. PATIENTS--All 36 paediatric patients operated on during this period. All the available electrocardiographic records were analysed. Ten patients in whom reliable records were not available were excluded. Twenty six patients entered in this retrospective study. INTERVENTIONS--Topical cooling with ice or with a slush of cold saline. MAIN OUTCOME MEASURE--Recordings from all the precordial leads were examined and scored as the sum of the maximum ST elevation (mV) in each precordial lead. The score obtained for each electrocardiogram was recorded together with the timing of the electrocardiogram (preoperative, arrival in intensive care unit immediately after surgery, postoperatively in the intensive care unit, and at discharge). RESULTS--There were no differences between the two groups in terms of demographic data, diagnosis, duration of ischaemia, and postoperative myocardial performance. There was temporary ST elevation during the first 48 postoperative hours in all the children in group 1 but in only seven of the 15 children in group 2 (Fisher's test, p less than 0.005). The mean (SD) score for maximum ST elevation was 1.34 (0.83) mV in group 1 and 0.52 (0.64) mV in group 2 (Student's t test, p less than 0.01). CONCLUSIONS--These temporary electrocardiographic changes in the presence of adequate myocardial performance were attributed to epicardial damage induced by hypothermicosmotic injury. The use of ice for topical cooling may damage the epicardium in children.