Closure of large intrathoracic airway defects using extrathoracic muscle flaps.

BACKGROUND: Prospective assessment of pedicled extrathoracic muscle flaps for the closure of large intrathoracic airway defects after noncircumferential resection in situations where an end-to-end reconstruction seemed risky (defects of > 4-cm length, desmoplastic reactions after previous infection or radiochemotherapy). METHODS: From 1996 to 2001, 13 intrathoracic muscle transpositions (6 latissimus dorsi and 7 serratus anterior muscle flaps) were performed to close defects of the intrathoracic airways after noncircumferential resection for tumor (n = 5), large tracheoesophageal fistula (n = 2), delayed tracheal injury (n = 1) and bronchopleural fistula (n = 5). In 2 patients, the extent of the tracheal defect required reinforcement of the reconstruction by use of a rib segment embedded into the muscle flap followed by temporary tracheal stenting. Patient follow-up was by clinical examination bronchoscopy and biopsy, pulmonary function tests, and dynamic virtual bronchoscopy by computed tomographic (CT) scan during inspiration and expiration. RESULTS: The airway defects ranged from 2 x 1 cm to 8 x 4 cm and involved up to 50% of the airway circumference. They were all successfully closed using muscle flaps with no mortality and all patients were extubated within 24 hours. Bronchoscopy revealed epithelialization of the reconstructions without dehiscence, stenosis, or recurrence of fistulas. The flow-volume loop was preserved in all patients and dynamic virtual bronchoscopy revealed no significant difference in the endoluminal cross surface areas of the airway between inspiration and expiration above (45 +/- 21 mm(2)), at the site (76 +/- 23 mm(2)) and below the reconstruction (65 +/- 40 mm(2)). CONCLUSIONS: Intrathoracic airway defects of up to 50% of the circumference may be repaired using extrathoracic muscle flaps when an end-to-end reconstruction is not feasible.

Intratracheal suctioning in sick preterm infants: prevention of intracranial hypertension and cerebral hypoperfusion by muscle paralysis.

In a prospective nonrandomized study, using each baby as his or her own control, we compared intracranial pressure (anterior fontanel pressure as measured with the Digilab pneumotonometer), cerebral perfusion pressure, BP, heart rate, transcutaneous Po2, and transcutaneous Pco2 before, during, and after endotracheal suctioning, with and without muscle paralysis, in 28 critically ill preterm infants with respiratory distress syndrome. With suctioning, there was a small but significant increase in intracranial pressure in paralyzed patients (from 13.7 [mean] +/- 4.4 mm Hg [SD] to 15.8 +/- 5.2 mm Hg) but a significantly larger (P less than .001) increase when they were not paralyzed (from 12.5 +/- 3.6 to 28.5 +/- 8.3 mm Hg). Suctioning led to a slight increase in BP with (from 45.3 +/- 9.1 to 48.0 +/- 8.7 mm Hg) and without muscle paralysis (from 45.1 +/- 9.4 to 50.0 +/- 11.7 mm Hg); but there was no significant difference between the two groups. The cerebral perfusion pressure in paralyzed infants did not show any significant change before, during, and after suctioning (31.5 +/- 9.1 mm Hg before v 32.0 +/- 8.7 mm Hg during suctioning), but without muscle paralysis cerebral perfusion pressure decreased (P less than .001) from 32.8 +/- 9.7 to 21.3 +/- 13.1 mm Hg. Suctioning induced a slight decrease in mean heart rate and transcutaneous Po2, but pancuronium did not alter these changes. There was no statistical difference in transcutaneous Pco2 before, during, and after suctioning with and without muscle paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Integrating postoperative value of cardiac Troponin I for a better correlation with in-hospital outcomes after congenital heart surgery.

Objective: Cardiac Troponin-I (cTnI) is a well-recognized early postoperative marker for myocardial damage in adults and children after heart surgery. The present study was undertaken to evaluate whether the integrated value (area under the curve(AUC)) of postoperative cTnI is a better mode to predict long-term outcome than post operative cTnI maximum value, after surgery for congenital heart defects (CHD). Methods: retrospective cohort study. 279 patients (mean age 4.6 years; range 0-17 years-old, 185 males) with congenital heart defect repair on cardiopulmonary by-pass were retrieved from our database including postoperative cTnI values. Maximal post operative cTnI value, post operative cTnI AUC value at 48h and total post operative cTnI AUC value were calculated and then correlated with duration of intubation, duration of ICU stay and mortality. Results: the mean duration of mechanical ventilation was 5.1+/-7.2 days and mean duration of ICU stay was 11.0+/- 13.3 days,11 patients (3.9%) died in post operative period. When comparing survivor and deceased groups, there was a significant difference in the mean value for max cTnI (16.7+/- 21.8 vs 59.2+/-41.4 mcg/l, p+0.0001), 48h AUC cTnI (82.0+/-110.7 vs 268.8+/-497.7 mcg/l, p+0.0001) and total AUC cTnI (623.8+/-1216.7 vs 2564+/-2826.0, p+0.0001). Analyses for duration of mechanical ventilation and duration of ICU stay by linear regression demonstrated a better correlation for 48h AUC cTnI (ventilation time r+0.82, p+0.0001 and ICU stay r+0.74, p+0.0001) then total AUC cTnI (ventilation time r+0.65, p+0.0001 and ICU stay r+0.60, p+0.0001) and max cTnI (ventilation time r+0.64, p+0.0001 and ICU stay r+0.60, p+0.0001). Conclusion: Cardiac Troponin I is a specific and sensitive marker of myocardial injury after congenital heart surgery and it may predict early in-hospital outcomes. Integration of post operative value of cTnI by calculation of AUC improves prediction of early in-hospital outcomes. It probably takes into account, not only the initial surgical procedure, but probably also incorporates the occurrence of hypoxic-ischemic phenomena in the post-operative period.

Postischemic recovery of heart metabolism and function: role of mitochondrial fatty acid transfer.

Postischemic recovery of contractile function is better in hearts from fasted rats than in hearts from fed rats. In this study, we examined whether feeding-induced inhibition of palmitate oxidation at the level of carnitine palmitoyl transferase I is involved in the mechanism underlying impaired recovery of contractile function. Hearts isolated from fasted or fed rats were submitted to no-flow ischemia followed by reperfusion with buffer containing 8 mM glucose and either 0.4 mM palmitate or 0.8 mM octanoate. During reperfusion, oxidation of palmitate was higher after fasting than after feeding, whereas oxidation of octanoate was not influenced by the nutritional state. In the presence of palmitate, recovery of left ventricular developed pressure was better in hearts from fasted rats. Substitution of octanoate for palmitate during reperfusion enhanced recovery of left ventricular developed pressure in hearts from fed rats. However, the chain length of the fatty acid did not influence diastolic contracture. The results suggest that nutritional variation of mitochondrial fatty acid transfer may influence postischemic recovery of contractile function.

Congenital heart disease affects local gyrification in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a common genetic condition associated with cognitive and learning impairments. In this study, we applied a three-dimensional method for quantifying gyrification at thousands of points over the cortical surface to imaging data from 44 children, adolescents, and young adults with 22q11.2DS (17 males, 27 females; mean age 17y 2mo [SD 9y 1mo], range 6-37y), and 53 healthy participants (21 males, 32 females; mean age 15y 4mo [SD 8y 6mo]; range 6-40y). Several clusters of reduced gyrification were observed, further substantiating the pattern of cerebral alterations presented by children with the syndrome. Comparisons within 22q11.2DS demonstrated an effect of congenital heart disease (CHD) on cortical gyrification, with reduced gyrification at the parieto-temporo-occipital junction in patients with CHD, as compared with patients without CHD. Reductions in gyrification can resemble mild polymicrogyria, suggesting early abnormal neuronal proliferation or migration and providing support for an effect of hemodynamic factors on brain development in 22q11.2DS. The results also shed light on the pathophysiology of acquired brain injury in other populations with CHD.

Hypertension differentially affects the expression of the gap junction protein connexin43 in cardiac myocytes and aortic smooth muscle cells.

Electrical and mechanical coupling of myocytes in heart and of smooth muscle cells in the aortic wall is thought to be mediated by intercellular channels aggregated at gap junctions. Connexin43 (Cx43) is one of the predominant membrane proteins forming junctional channels in the cardiovascular system. This study was undertaken to assess its expression during experimental hypertension. Rats were made hypertensive by clipping one renal artery (two-kidney, one-clip renal hypertension) or by administering deoxycorticosterone and salt (DOCA-salt hypertension). After four weeks, rats from both models showed a similar increase in intra-arterial mean blood pressure, as well as in the thickness of both aorta and heart walls. Northern blot analysis showed that, compared to controls, hypertensive rats expressed twice more Cx43 in aorta, but not in heart. These results suggest that localized mechanical forces induced by hypertension are major tissue-specific regulators of Cx43 expression.

Impaired glucose metabolism in the heart of obese Zucker rats after treatment with phorbol ester.

OBJECTIVE: To investigate the influence of obesity on the regulation of myocardial glucose metabolism following protein kinase C (PKC) activation in obese (fa/fa) and lean (Fa/?) Zucker rats. DESIGN: Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) for different time periods prior to the evaluation of PKC and GLUT-4 translocation. For metabolic studies isolated hearts from 48 h starved Zucker rats were perfused with an erythrocytes-enriched buffer containing increased concentrations (10-100 nM) of PMA. MEASUREMENTS: Immunodetectable PKC isozymes and GLUT-4 were determined by Western blots. Glucose oxidation and glycolysis were evaluated by measuring the myocardial release of 14CO2 and 3H2O from [U-14C]glucose and [5-3H]glucose, respectively. RESULTS: PMA (200 nM) induced maximal translocation of ventricular PKCalpha from the cytosol to the membranes within 10 min. This translocation was 2-fold lower in the heart from obese rats when compared to lean rats. PMA also induced a significant translocation of ventricular GLUT-4 from the microsomal to the sarcolemmal fraction within 60 min in lean but not in obese rats. Rates of basal cardiac glucose oxidation and glycolysis in obese rats were approximately 2-fold lower than those of lean rats. Perfusion with increasing concentrations of PMA (10-100 nM) led to a significant decrease of cardiac glucose oxidation in lean but not in obese rats. CONCLUSION: Our results show that in the heart of the genetically obese Zucker rat, the impairment in PKCalpha activation is in line with a diminished activation of GLUT-4 as well as with the lack of PMA effect on glucose oxidation.

Modalities and future prospects of gene therapy in heart transplantation.

Heart transplantation is the treatment of choice for many patients with end-stage heart failure. Its success, however, is limited by organ shortage, side effects of immunosuppressive drugs, and chronic rejection. Gene therapy is conceptually appealing for applications in transplantation, as the donor organ is genetically manipulated ex vivo before transplantation. Localised expression of immunomodulatory genes aims to create a state of immune privilege within the graft, which could eliminate the need for systemic immunosuppression. In this review, recent advances in the development of gene therapy in heart transplantation are discussed. Studies in animal models have demonstrated that genetic modification of the donor heart with immunomodulatory genes attenuates ischaemia-reperfusion injury and rejection. Alternatively, bone marrow-derived cells genetically engineered with donor-type major histocompatibility complex (MHC) class I or II promote donor-specific hyporesponsiveness. Genetic engineering of naïve T cells or dendritic cells may induce regulatory T cells and regulatory dendritic cells. Despite encouraging results in animal models, however, clinical gene therapy trials in heart transplantation have not yet been started. The best vector and gene to be delivered remain to be identified. Pre-clinical studies in non-human primates are needed. Nonetheless, the potential of gene therapy as an adjunct therapy in transplantation is essentially intact.

Métabolisme énergétique et traumatisme crâniocérébral [Energy metabolism and craniocerebral injury]

Severe head injury induces major hormonal, humoral and metabolic changes, characterized by increases in stress hormone secretion, lymphokines production, associated with high lipid and protein catabolism as well as changes in energy expenditure (EE). Numerous factors influence EE in head-injured patients, particularly anthropometric data, body temperature, nutritional support, level of consciousness, muscular tone and activity. Resting EE is usually increased following brain trauma; however, normal or decreased metabolic rates can be observed in curarized patients on mechanical ventilation or in patients receiving high doses of barbiturates.

Effects of propranolol on resting metabolic rate after severe head injury.

Postabsorptive resting metabolic rate (RMR), measured by indirect calorimetry, and the effect of iv propranolol administration were studied in 12 nonseptic patients with severe head injury by means of indirect calorimetry. Before propranolol RMR was moderately increased (126 +/- 10.4% of predicted values) whereas urinary excretion of catecholamines was markedly elevated (p less than .01 vs. normal values). RMR was significantly correlated with both resting heart rate (HR) (r = .72, p less than .01) and 24-h urinary N excretion (r = .85, p less than .001). The administration of iv propranolol (0.1 mg/kg) produced a rapid decrease in HR (-10 +/- 4%, p less than .001) and in RMR (-6.1 +/- 2.3%, p less than .001). Further administration of propranolol produced no additional reduction in either HR or RMR. We conclude that severely head-injured patients are moderately hypermetabolic in resting and postabsorptive conditions, and that acute iv propranolol administration induces a reduction of about one quarter of the resting hypermetabolism.

Shoulder strength imbalances as injury risk in handball.

This study was conducted to analyze whether internal (IR) and external (ER) rotator shoulder muscles weakness and/or imbalance collected through a preseason assessment could be predictors of subsequent shoulder injury during a season in handball players. In preseason, 16 female elite handball players (HPG) and 14 healthy female nonathletes (CG) underwent isokinetic IR and ER strength test with use of a Con-Trex® dynamometer in a seated position with 45° shoulder abduction in scapular plane, at 60, 120 and 240°/s in concentric and at 60°/s in eccentric, for both sides. An imbalanced muscular strength profile was determined using -statistically selected cut-offs from CG values. For HPG, all newly incurred shoulder injuries were reported during the season. There were significant differences between HPG and CG only for dominant eccentric IR strength, ER/IR ratio at 240°/s and for IRecc/ERcon ratio. In HPG, IR and ER strength was higher, and ER/IR ratios lower for dominant than for nondominant side. The relative risk was 2.57 (95%CI: 1.60-3.54; P<0.05) if handball players had an imbalanced muscular strength profile. In youth female handball players IR and ER muscle strength increases on the dominant side without ER/IR imbalances; and higher injury risk was associated with imbalanced muscular strength profile.

High Specificity of C4d/CD68 Staining for the Diagnosis of Late Antibody-Mediated Rejection in Heart Transplantation.

In heart transplantation (HTx), acute antibody-mediated rejection (AMR) is infrequent but carries high mortality and increased risk of graft vasculopathy. The diagnosis requires evidence of acute graft dysfunction, capillary lesions on endomyocardial biopsy (EMB), and immunopathological criteria of antibodymediated injury. Multiple markers of antibody-mediated injuries have been proposed, but there is ample debate on their usefulness. In kidney transplantation, C4d deposition in peritubular capillaries is a reliable marker of alloantibody-dependant graft injury. In this study, we prospectively screened all EMBs for C4d and CD68 in new HTx recipients, and correlated pathological fi ndings with immunological evidence of donor-specifi c antibodies (DSA) and graft dysfunction. Methods Between Nov 05 and Aug 08, we had 22 HTx, and 17 cases were analysed. All recipients received polyclonal rabbit anti-thymocytes globulin, calcineurin inhibitors, mycophenolate mofetil, and corticosteroids (weaning in 6 -12 months). They had EMB every 1-2 weeks in the fi rst 3 months, and then monthly for 9 months. C4d and CD 68 were assessed by immunochemistry. Echocardiography and DSA assessment or crossmatch (early phase) were realised if C4d or CD68 staining was positive. Results There was 1 early and 1 late AMR. Table 1 C4d and CD68 positive, at least 1 EMB 6 / 17; 35% 1 treated C4d and CD68 positive, at least 2 consecutive EMBs 3 / 17; 17.5% 1 treated C4d and CD68 positive, and graft dysfunction 1 / 17; 6% 1 treated C4d and CD68 positive, with DSA and crossmatch + 1 / 17; 6% 1 treated Table 2 C4d and CD68 positive, at least 1 EMB 1 / 17; 6% 1 treated C4d and CD68 positive, at least 2 consecutive EMBs 1 /17; 6% 1 treated C4d and CD68 positive and graft dysfunction 1 / 17; 6% 1 treated C4d and CD68 positive, and + DSA 1 / 17; 6% 1 treated Conclusion In this single-center experience, C4d / CD68 positive staining was frequent in the early phase and raised the question of false positive cases of AMR. However, these markers showed high specifi city for the diagnosis of AMR in the late phase. Of course these data need to be confi rmed in larger multi-center studies.

Biometal muscles to restore contractile function of weak heart

Objectives: Existing VADs are single-ventricle pumps needing anticoagulation. We developed a bi-ventricular external assist device that partially reproduces the physiological muscle function of the heart. This artificial muscle could wrap the heart and improve its contractile force.Methods: The device has a carbon fiber skeleton fitting a 30-40kg patient's heart, to which a Nitinol based artificial muscle is connected. The artificial muscle wraps both ventricles. The Nitinol fibers are woven on a Kevlar mesh surrounding each ventricle. The fibers are electrically driven with a dedicated control unit developed for this purpose. We assessed hemodynamic performances of this device using a previously described dedicated bench test. Volume ejected and pressure gradient have been measured with afterload ranging from 10 to 50mmHg.Results: With an afterload of 50mmHg the system has an ejection fraction of 4% on the right side and 5% on the left side. The system is able to generate a systolic ejection of 2.2mL on the right side and 3.25mL on the left side. With an afterload of 25mmHg the results are reduced of about 20%. The activation frequency can reach 80/minute resulting in a total volume displacement of 176mL/minute on the right side and 260mL/minute on the left side.Conclusions: These preliminary studies confirmed the possibility of improving the ejection fraction of a failing heart using artificial muscle for external cardiac compression avoiding anticoagulation therapy. This device could be helpful in weaning cardio-pulmonary bypass and/or for short-term cardio-circulatory support in pediatric population with cardiac failure.

Management of diplopia secondary to neurosurgical injury of the orbital roof

BACKGROUND: Diplopia related to neurosurgical procedures is often consecutive to oculomotor nerve lesions. We hereby report an oculomotor dysfunction secondary to an orbital roof effraction and its treatment. HISTORY AND SIGNS: Following surgery for a left anterior communicating artery aneurysm, a 45-year-old woman reported vertical diplopia associated with a left orbital hematoma. The diagnosis of third cranial nerve palsy was excluded by orbital imaging which revealed an orbital roof defect with incarceration of the levator palpebrae and superior rectus. THERAPY AND OUTCOME: As neurosurgeons advised against muscle adhesiolysis, diplopia was corrected by a two-step procedure on the oculomotor muscles. We first corrected horizontal and torsional deviations by operating on the healthy eye, before correcting the vertical deviation on the fellow eye. This two-step extraocular muscle surgery allowed restoration of binocular single vision in a useful field of gaze. CONCLUSIONS: Diplopia can occur as a rare orbital complication during neurosurgical procedures. Surgery of extraocular muscles can provide good functional results

Gene deletion of dopamine beta-hydroxylase and alpha1-adrenoceptors demonstrates involvement of catecholamines in vascular remodeling.

In vitro studies have shown that stimulation of alpha1-adrenoceptors (ARs) directly induces proliferation, hypertrophy, and migration of arterial smooth muscle cells and adventitial fibroblasts. In vivo studies confirmed these findings and showed that catecholamine trophic activity becomes excessive after experimental balloon injury and contributes to neointimal growth, adventitial thickening, and lumen loss. However, past studies have been limited by selectivity of pharmacological agents. The aim of this study, in which mice devoid of norepinephrine and epinephrine synthesis [dopamine beta-hydroxylase (DBH-/-)] or deficient in alpha1-AR subtypes expressed in murine carotid (alpha1B-AR-/- and alpha1D-AR-/-) were used, was to test the hypothesis that catecholamines contribute to wall hypertrophy after injury. At 3 wk after injury of wild-type mice, lumen area and carotid circumference increased significantly, and hypertrophy of media and adventitia was in excess of that needed to restore circumferential wall stress to normal. In DBH-/- and alpha1B-AR-/- mice, increases in lumen area, circumference, and hypertrophy of the media and adventitia were reduced by 50-91%, resulting in restoration of wall tension to nearly normal (DBH-/-) or normal (alpha1B-AR-/-). In contrast, in alpha1D-AR-/- mice, increases in lumen area, circumference, and wall hypertrophy were unaffected and wall thickening remained in excess of that required to return tension to normal. When examined 5 days after injury, proliferation and leukocyte infiltration were inhibited in DBH-/- mice. These studies suggest that the trophic effects of catecholamines are mediated primarily by alpha1B-ARs in mouse carotid and contribute to hypertrophic growth after vascular injury.