Human lymphatic vessel contractile activity is inhibited in vitro but not in vivo by the calcium channel blocker nifedipine.

Calcium channel blockers (CCB) are widely prescribed anti-hypertensive agents. The commonest side-effect, peripheral oedema, is attributed to a larger arterial than venous dilatation causing increased fluid filtration. Whether CCB treatment is detrimental to human lymphatic vessel function and thereby exacerbates oedema formation is unknown. We observed that spontaneous lymphatic contractions in isolated human vessels (thoracic duct and mesenteric lymphatics) maintained under isometric conditions were inhibited by therapeutic concentrations (nanomolar) of the CCB nifedipine while higher than therapeutic concentrations of verapamil (micromolar) were necessary to inhibit activity. Nifedipine also inhibited spontaneous action potentials measured by sharp microelectrodes. Furthermore, noradrenaline did not elicit normal increases in lymphatic vessel tone when maximal constriction was reduced to 29.4 ± 4.9% of control in the presence of 20 nmol l(-1) nifedipine. Transcripts for the L-type calcium channel gene CACNA1C were consistently detected from human thoracic duct samples examined and the CaV1.2 protein was localized by immunoreactivity to lymphatic smooth muscle cells. While human lymphatics ex vivo were highly sensitive to nifedipine, this was not apparent in vivo when nifedipine was compared to placebo in a randomized, double-blinded clinical trial: conversely, lymphatic vessel contraction frequency was increased and refill time was faster despite all subjects achieving target nifedipine plasma concentrations. We conclude that human lymphatic vessels are highly sensitive to nifedipine in vitro but that care must be taken when extrapolating in vitro observations of lymphatic vessel function to the clinical situation, as similar changes in lymphatic function were not evident in our clinical trial comparing nifedipine treatment to placebo.

The human thoracic duct is functionally innervated by adrenergic nerves.

Lymphatic vessels from animals have been shown to be innervated. While morphological studies have confirmed human lymphatic vessels are innervated, functional studies supporting this are lacking. The present study demonstrates a functional innervation of the human thoracic duct (TD) that is predominantly adrenergic. TDs harvested from 51 patients undergoing esophageal and cardia cancer surgery were either fixed for structural investigations or maintained in vitro for the functional assessment of innervation by isometric force measurements and electrical field stimulation (EFS). Electron microscopy and immunohistochemistry suggested scarce diffuse distribution of nerves in the entire vessel wall, but nerve-mediated contractions could be induced with EFS and were sensitive to the muscarinic receptor blocker atropine and the α-adrenoceptor blocker phentolamine. The combination of phentolamine and atropine resulted in a near-complete abolishment of EFS-induced contractions. The presence of sympathetic nerves was further confirmed by contractions induced by the sympathomimetic and catecholamine-releasing agent tyramine. Reactivity to the neurotransmitters norepinephrine, substance P, neuropeptide Y, acetylcholine, and methacholine was demonstrated by exogenous application to human TD ring segments. Norepinephrine provided the most consistent responses, whereas responses to the other agonists varied. We conclude that the human TD is functionally innervated with both cholinergic and adrenergic components, with the latter of the two dominating.

The contribution of K(+) channels to human thoracic duct contractility.

In smooth muscle cells, K(+) permeability is high, and this highly influences the resting membrane potential. Lymph propulsion is dependent on phasic contractions generated by smooth muscle cells of lymphatic vessels, and it is likely that K(+) channels play a critical role in regulating contractility in this tissue. The aim of this study was to investigate the contribution of distinct K(+) channels to human lymphatic vessel contractility. Thoracic ducts were harvested from 43 patients and mounted in a wire myograph for isometric force measurements or membrane potential recordings with an intracellular microelectrode. Using K(+) channel blockers and activators, we demonstrate a functional contribution to human lymphatic vessel contractility from all the major classes of K(+) channels [ATP-sensitive K(+) (KATP), Ca(2+)-activated K(+), inward rectifier K(+), and voltage-dependent K(+) channels], and this was confirmed at the mRNA level. Contraction amplitude, frequency, and baseline tension were altered depending on which channel was blocked or activated. Microelectrode impalements of lymphatic vessels determined an average resting membrane potential of -43.1 ± 3.7 mV. We observed that membrane potential changes of <5 mV could have large functional effects with contraction frequencies increasing threefold. In general, KATP channels appeared to be constitutively open since incubation with glibenclamide increased contraction frequency in spontaneously active vessels and depolarized and initiated contractions in previously quiescent vessels. The largest change in membrane voltage was observed with the KATP opener pinacidil, which caused 24 ± 3 mV hyperpolarization. We conclude that K(+) channels are important modulators of human lymphatic contractility.

Sympathicotomy for isolated facial blushing: long-term follow-up of a randomized trial.

OBJECTIVES: Thoracoscopic sympathicotomy may be an effective treatment for disabling facial blushing in selected patients. Short- and mid-term results are good but very long-term results are scarce in the medical literature and there is no knowledge which extent of sympathicotomy is better long-term for isolated facial blushing. METHODS: We previously randomized 100 patients between a rib-oriented R2 or R2-R3 sympathicotomy for isolated facial blushing, and reported local effects, side effects and quality of life after 12 months. In the present study, we sent identical questionnaires to all patients after a median of 16 years (interquartile range 15-17 years). RESULTS: The response rate was 66%. Overall, 82% reported excellent or satisfactory results on facial blushing, with significant better local effect after R2 sympathicotomy compared with R2-R3 sympathicotomy. Patients who underwent R2 sympathicotomy were also significantly more satisfied with the operation. We found no significant difference between R2 and R2-R3 sympathicotomy in quality of life or rates of compensatory sweating (77%) and recurrence of blushing (41%) which was milder than preoperatively in most patients. CONCLUSIONS: R2 sympathicotomy should be the preferred approach for isolated facial blushing because of better local effect and higher satisfaction rates. Although this was a very long-term follow-up of the only randomized trial of its kind the response rate was limited leaving a risk of undetected bias.

Identification of interstitial Cajal-like cells in the human thoracic duct.

Interstitial Cajal-like cells (ICLCs) are speculated to be pacemakers in smooth muscle tissues. While the human thoracic duct (TD) is spontaneously active, the origin of this activity is unknown. We hypothesized that ICLCs could be present in the TD and using histological techniques, immunohistochemistry and immunofluorescence we have investigated the presence of ICLCs, protein markers for ICLCs and the cellular morphology of the human TD. Transmission electron microscopy was employed to investigate ultrastructure. Methylene blue staining, calcium-dependent fluorophores and confocal microscopy were used to identify ICLCs in live tissue. Methylene blue stained cells with morphology suggestive of ICLCs in the TD. Immunoreactivity localized the ICLC protein markers c-kit, CD34 and vimentin to many cells and processes associated with smooth muscle cells (SMCs): coexpression of c-kit with vimentin or CD34 was observed in some cells. Electron microscopy analysis confirmed ICLCs as a major cell type of the human TD. Lymphatic ICLCs possess caveolae, dense bands, a patchy basal lamina, intermediate filaments and specific junctions to SMCs. ICLCs were ultrastructurally differentiable from other interstitial cells observed: fibroblasts, mast cells, macrophages and pericytes. Lymphatic ICLCs were localized to the subendothelial region of the wall as well as in intimate association with smooth muscle bundles throughout the media. ICLCs were morphologically distinct with multiple processes and also spindle shapes. Confocal imaging with calcium-dependent fluorophores corroborated cell morphology and localization observed in fixed tissues. Lymphatic ICLCs thus constitute a significant cell type of the human TD and physically interact with lymphatic SMCs.

Epidural analgesia and abnormal coagulation in patients undergoing minimal invasive repair of pectus excavatum.

Background: Epidural analgesia (EA) is effective in patients undergoing minimal invasive repair of pectus excavatum (MIRPE) but is associated with major complications such as epidural hematomas. It is recommended to assess coagulation status in patients receiving anticoagulant therapy prior to EA, although no consensus exists in patients without a history of bleeding tendency or anticoagulant therapy. Thus, the aim of this paper was to assess 1) the prevalence of abnormal routine coagulation parameters, i.e., international normalized ratio (INR) and platelet count, and 2) the safety of EA in patients undergoing MIRPE. Methods: In this retrospective study, we identified 1,973 patients undergoing MIRPE at our center between 2001 and 2019. Complications related to EA were registered for all patients. Information on coagulation parameters was present in 929 patients. Patients with spontaneously elevated INR ≥1.5 were referred for assessment of coagulation factor VII in order to assess the cause of the elevated INR. Results: Of 929 patients with coagulation information available, 18 patients had spontaneously elevated INR ≥1.5 (1.9%). In patients with INR ≥1.5, 12 patients underwent further assessment of factor VII, with all patients having a slightly reduced factor VII close to the lower reference range. The majority of the 1,973 patients undergoing MIRPE received EA (99.6%) with very low complication rates (0.2%) and no incidence of epidural hematomas. Conclusion: In patients undergoing MIRPE, coagulation screening prior to EA should not be mandatory as it revealed no clinically relevant consequences. EA is safe with very low complication rates.

Prevalence of comorbidities in a surgical pectus excavatum population.

BACKGROUND: Pectus excavatum is the most common chest wall deformity and is associated to various connective tissue, cardiopulmonary, and skeletal abnormalities. Several conditions and syndromes have been associated to pectus excavatum, although the overall health implications of the pectus excavatum phenotype are unclear. Therefore, in this study we aimed to examine the health implications of the pectus excavatum phenotype by assessing all comorbidities and previous medical conditions in a cohort of patients undergoing pectus excavatum surgery. METHODS: This single-centre retrospective prevalence study included 1,046 patients undergoing minimal invasive repair of pectus excavatum from 2001 to 2012. Hospital medical charts were assessed and comorbidities and previous medical conditions were registered systematically and categorized according to the affected organ system. RESULTS: In our study population of 1,046 patients, we registered 623 conditions. The median age was 17 years and the majority of patients (56%) had no previous or present conditions. Notable prevalence of asthma (8.8%), allergies (12.3%), previous hernia surgery (5.2%), and psychiatric conditions (4.9%) were found. CONCLUSIONS: The majority of patients undergoing pectus excavatum surgery have no comorbidities or previous medical conditions. It seems that this patient category is comparable to the background population in this regard and our findings do not support screening this patient category for associated conditions.

Incidence and severity of surgical complications after pectus excavatum bar removal.

OBJECTIVES: Pectus bar removal is the final step of minimally invasive repair of pectus excavatum. Complication rates related to bar removal have been reported in 2-15% of patients and severe, near-fatal and fatal complications have been reported. No systematic assessment of complication severity or risk factors associated with bar removal has been reported in large study populations. The aim of this paper is to investigate the safety of the bar removal procedure with regard to complication rates and severities as well as assessment of risk factors. METHODS: Between 2003 and 2019, 1574 patients underwent the bar removal procedure. Medical records were assessed retrospectively and complications registered. Complications were categorized in infections, bleedings and other complications. The severity of the surgical complications was systematically classified using the validated Clavien-Dindo classification. Furthermore, risk factors associated with complications were assessed. RESULTS: The overall complication rate was 4.1% (Clavien-Dindo classification I-IV), mainly consisting of bleedings (1.3%) and infections (1.5%). Five cases of severe bleedings were registered (0.3%, Clavien-Dindo classification IV). Risk factors associated with complications during bar removal were greater age and removal of more than one bar. CONCLUSIONS: The bar removal procedure is a safe and effective procedure. Both age and number of bars inserted should be considered prior to surgical correction of pectus excavatum as these factors predict complications related to bar removal.

Human thoracic duct in vitro: diameter-tension properties, spontaneous and evoked contractile activity.

The current study characterizes the mechanical properties of the human thoracic duct and demonstrates a role for adrenoceptors, thromboxane, and endothelin receptors in human lymph vessel function. With ethical permission and informed consent, portions of the thoracic duct (2-5 cm) were resected and retrieved at T(7)-T(9) during esophageal and cardia cancer surgery. Ring segments (2 mm long) were mounted in a myograph for isometric tension (N/m) measurement. The diameter-tension relationship was established using ducts from 10 individuals. Peak active tension of 6.24 +/- 0.75 N/m was observed with a corresponding passive tension of 3.11 +/- 0.67 N/m and average internal diameter of 2.21 mm. The equivalent active and passive transmural pressures by LaPlace's law were 47.3 +/- 4.7 and 20.6 +/- 3.2 mmHg, respectively. Subsequently, pharmacology was performed on rings from 15 ducts that were normalized by stretching them until an equivalent pressure of 21 mmHg was calculable from the wall tension. At low concentrations, norepinephrine, endothelin-1, and the thromboxane-A(2) analog U-46619 evoked phasic contractions (analogous to lymphatic pumping), whereas at higher contractions they induced tonic activity (maximum tension values of 4.46 +/- 0.63, 5.90 +/- 1.4, and 6.78 +/- 1.4 N/m, respectively). Spontaneous activity was observed in 44% of ducts while 51% of all the segments produced phasic contractions after agonist application. Acetylcholine and bradykinin relaxed norepinephrine preconstrictions by approximately 20% and approximately 40%, respectively. These results demonstrate that the human thoracic duct can develop wall tensions that permit contractility to be maintained across a wide range of transmural pressures and that isolated ducts contract in response to important vasoactive agents.

Reconstruction using free jejunal transfer after resection of cancer of the upper oesophagus.

INTRODUCTION: Treatment of cancer of the upper part of the oesophagus is challenging. Even after intended curative treatment, less than half of the patients are alive after five years. This retrospective study evaluates all the patients who had the upper oesophagus reconstructed by use of a free jejunal transfer following cancer resection from February 2000 to May 2008 at the University Hospital of Aarhus. MATERIAL AND METHODS: Twenty patients aged 46-75 years were included. In all 20 cases, the diagnosis was squamous cell carcinoma, T3 or T4. All patients suffered from severe dysphagia prior to surgery. The median follow-up time was 23 months at 31 January 2010. RESULTS: No perioperative mortality was experienced. Thirteen patients are now dead; nine due to the cancer of the oesophagus and four due to other causes. The median survival time of the 13 diseased patients was 15.3 months. The seven patients who remain alive have a median survival time of 40.2 months. None of these patients have shown signs of recurrence of the oesophageal cancer. All the patients regained their capacity to swallow and thereby increased their quality of life. No complications were experienced in relation to the abdominal procedure of harvesting the jejunal transfer. Three patients developed a fistula and in one case this required minor surgery. Eight patients needed to have a dilatation procedure performed. CONCLUSION: Reconstruction of the oesophagus with a free jejunal transfer is a suitable treatment for selected patients with cancer in the upper oesophagus.

Combining Correction of Pectus Excavatum and Open Heart Surgery in a Single-Stage Procedure.

The presence of pectus excavatum in patients undergoing open heart surgery is rare, and no consensus has been reached regarding the surgical approach. Thus, this paper describes a single-stage procedure for correction of pectus excavatum with the modified Nuss procedure ad modum Pilegaard in 4 patients undergoing open heart surgery. Three of 4 patients successfully underwent the single-stage procedure. At follow-up after bar removal, all patients had no complications related to the Nuss bar, and all had excellent cosmetic results.

Pectus excavatum requiring temporary pacemaker implantation before Nuss procedure: a case report.

Pectus excavatum is the most common chest wall deformity, and some patients also have it combined with cardiac arrhythmias. It is a rare occurrence for there to be a severe conduction block that requires a temporary pacemaker implantation before the surgical correction. Here we reported a case of pectus excavatum with a second-degree atrial-ventricular (AV) block (Mobitz II) who had temporary pacemaker implantation before the Nuss procedure. The young patient had a chest wall deformity for 6 years and it got worse with age. The Haller index was 4.21, and we evaluated that he should receive the Nuss procedure. An AV block was found during the preoperative electrocardiogram examination; furthermore, Holter monitor proved that he had first-degree AV block and a second-degree AV block (Mobitz II). After consultation with the anesthesiologist and cardiologist, we suggested that a temporary pacemaker placement should be performed under local anesthesia before the minimally invasive operation and removed as soon as the patient revived from general anesthesia. A postoperative Holter monitor was implemented, and the conduction defect disappeared shortly after the operation. However, the Holter monitor showed that the conduction defect was still existed during the follow-up period, which indicated that severe conduction defects should be originated from the conduction system itself, rather than the compression to the heart. The temporary pacemaker was essential to ensure the conducting of the operation went smoothly.

Single-stage tracheal and cricotracheal segmental resection with end-to-end anastomosis: Outcome, complications, and risk factors.

OBJECTIVE: Management of tracheal stenosis remains controversial. Endoscopic interventions commonly provide immediate relief of symptoms, but are associated with high recurrence rates. In contrast, high success rates have been reported in patients undergoing tracheal resection. However, well-defined indications and contraindications for tracheal resection are lacking and previous studies commonly ignore patient-related outcomes (e.g. dyspnoea). We aimed to evaluate the outcome of tracheal resection at our institution and identify risk factors for complications. METHODS: All adult patients undergoing tracheal resection at Aarhus University Hospital between January 2009 and September 2016 were included RESULTS: Twenty-seven patients were included. The most frequent aetiologies for tracheal stenosis were previous tracheostomy (n=8), prolonged intubation (n=3), a combination of the two (n=5), and intraluminal tumour (n=7). Sixteen patients underwent high tracheal resection, seven patients low tracheal resection, and four patients partial cricotracheal resection. Surgical success (no dyspnoea and no need for additional intervention) was achieved in 74% of patients. Four of six patients undergoing resection because of malignant disease were recurrence-free during the follow-up period. Fifteen (56%) patients suffered complications (transient or permanent). Four (15%) patients had recurrent stenosis and underwent reintervention. Other permanent complications included idiopathic hoarseness (15%), unilateral recurrent nerve palsy (11%), and dysphagia (7%). Previous treatment (endoscopic and open surgery) (OR=5.5, p=0.06) and chronic diseases (OR=8.3, p=0.02) were associated with increased risk for complications. CONCLUSIONS: Tracheal resection was efficient treatment for the alleviation of dyspnoea in adults with tracheal stenosis. However, complications were frequent and careful preoperative patient selection and information are crucial.

Cardiovascular magnetic resonance assessment of biventricular changes during vacuum bell correction of pectus excavatum.

BACKGROUND: Evidence of cardiac dysfunction in patients with pectus excavatum (PE) remains controversial. A growing number of studies report increased exercise tolerance following surgery. Nevertheless, many consider the correction of PE a cosmetic intervention, with post-operative changes ascribed to the concurrent growth of the young patient population. No studies have investigated non-invasively the immediate cardiac changes following relief of the deformity. The aim of this study was to assess cardiac function before and during temporary sternal elevation using the non-invasive vacuum bell (VB) device on young adults with PE. METHODS: Adult patients scheduled for surgical correction of PE underwent cardiac magnetic resonance imaging (CMRI) before and during the application of the VB. Steady-state free precession sequences were used for the evaluation of biventricular volume and function. Phase contrast sequences measured the aortic and pulmonary flow to calculate stroke index (SI). Scans were analyzed post hoc by the same investigator. A control group of healthy individuals was assessed in the same way. RESULTS: In total, 20 patients with PE (mean age 23±10 years) and 10 healthy individuals (mean age 25±6 years) underwent CMR before and during VB application. Before intervention, baseline cardiac volumes and function were similar between the groups, with patient-values in the low-to-normal range. Following VB application, PE patients revealed a 10% increase in biventricular SI. Furthermore, left ventricular end-diastolic volume index (LV EDVI) improved by 8% and right ventricular ejection fraction (RV EF) increased by 7%. These findings were not mirrored in the healthy individuals. No correlations were found between improved cardiac parameters and the baseline Haller index (HI) of PE patients. CONCLUSIONS: Non-invasive, momentary correction of PE is associated with an immediate improvement in SI, RV EF and LV EDVI, not observed in controls. The findings suggest that sternal depression in PE patients affects cardiac function.

Management of facial blushing.

Patients complaining of facial blushing should be investigated by a dermatologist or an internist to rule out serious underlying disorders. Patients with emotionally triggered blushing should be encouraged to try nonsurgical options as the first line of treatment. Provided there is still an indication for treatment, facial blushing may be treated effectively by thoracoscopic sympathectomy. The type of blushing likely to benefit from sympathectomy is mediated by the sympathetic nerves and is the uncontrollable, rapidly developing blush typically elicited when one receives attention from other people. Side effects are frequent, but most patients are satisfied with the operation. In the short term, the key to success in sympathetic surgery for facial blushing lies in a meticulous and critical patient selection and in ensuring that the patient is thoroughly informed about the high risk of side effects. In the long term, the key to success in sympathetic surgery for facial blushing lies in more quality research comparing surgical, pharmacologic, and psychotherapeutic treatments.

Pain and sensory disturbances following surgical repair of pectus carinatum.

BACKGROUND/PURPOSE: The purpose of this study was to assess the characteristics of persistent postoperative pain and sensory disturbances following surgical repair of pectus carinatum. METHODS: Using a prospective observational design, 28 patients were assessed before, 6 weeks and 6 months after a modified Ravitch operation for pectus carinatum. Postoperative pain was assessed using the Short Form McGill Pain Questionnaire. Sensory testing was conducted to detect brush-evoked allodynia and pinprick hyperalgesia. Additionally, generic and disease-specific quality of life was assessed using the Short Form-36 Health Survey and the Nuss Questionnaire Modified for Adults before and after surgery. RESULTS: Six weeks after surgery, ten patients reported mild pain or discomfort. Six months after surgery, four patients reported only mild pain. Allodynia was detected in two patients 6 weeks and 6 months after surgery. Hyperalgesia was detected in eight patients 6 weeks after surgery, and in six patients 6 months after surgery. Generic quality of life was significantly improved over time. CONCLUSIONS: The study showed no significant pain problems, a tendency to reduced sensory disturbances and significant improvements in quality of life 6 months after surgical repair of pectus carinatum. Future studies should include a longer follow-up period to determine if these positive results are persistent. LEVELS OF EVIDENCE: 1 (Prognosis Study).

Evaluating interest in narrative therapy for decision making about pectus excavatum treatment.

OBJECTIVES: The decision to proceed with surgical treatment for pectus excavatum (PE) is rarely clear-cut. Patients interested in treatment are referred for evaluation by numerous different specialists, but psychosocial counselling is currently not included in this process. Our objective was to assess whether PE patients would be interested in formal assistance with the decision-making process surrounding PE surgery using narrative therapy principles. METHODS: Ninety-seven untreated PE patients at 5 different institutions in 4 countries completed a questionnaire consisting of 13 questions, with 3 questions specifically evaluating interest in narrative therapy. RESULTS: Eighty-two percent of participants were interested in narrative therapy to assist with the decision-making process surrounding PE surgery. Individuals most interested in narrative therapy tend to be more interested in correction (P < 0.05) to improve the way they feel about their body (P < 0.05). CONCLUSIONS: The majority of PE patients are interested in narrative therapy to aid the decision-making process about treatment. We propose that narrative therapy should be offered to PE patients during the treatment evaluation process to address the psychosocial difficulties associated with PE and the surgical decision-making process overall. Future studies should assess the effectiveness of this interdisciplinary model.

Minimal Invasive Repair of Pectus Excavatum and Carinatum.

Minimal invasive surgery has become the gold standard for surgical repair of pectus excavatum. The procedure can be performed as fast-track surgery and cosmetic results are excellent. In addition, cardiac performance improves after correction. With increased awareness on the Internet, the number of patients who seek help continues to rise, primarily for cosmetic reasons. Pectus carinatum is much less frequent than pectus excavatum. Over the past decade surgery has largely been replaced by compression techniques that use a brace, and cosmetic results are good. Rare combinations of pectus excavatum and carinatum may be treated by newer surgical methods.

Pectus excavatum repair after sternotomy: the Chest Wall International Group experience with substernal Nuss bars.

OBJECTIVES: Patients with pectus excavatum (PE) after prior sternotomy for cardiac surgery present unique challenges for repair of PE. Open repairs have been recommended because of concerns about sternal adhesions and cardiac injury. We report a multi-institutional experience with repair utilizing substernal Nuss bars in this patient population. METHODS: Surgeons from the Chest Wall International Group were queried for experience and retrospective data on PE repair using sub-sternal Nuss bars in patients with a history of median sternotomy for cardiac surgery (November 2000 to August 2015). A descriptive analysis was performed. RESULTS: Data for 75 patients were available from 14 centres. The median age at PE repair was 9.5 years (interquartile range 10.9), and the median Haller index was 3.9 (interquartile range 1.43); 56% of the patients were men. The median time to PE repair was 6.4 years (interquartile range 7.886) after prior cardiac surgery. Twelve patients (16%) required resternotomy before support bar placement: 7 pre-emptively and 5 emergently. Sternal elevation before bar placement was used in 34 patients (45%) and thoracoscopy in 67 patients (89%). Standby with cardiopulmonary bypass was available at 9 centres (64%). Inadvertent cardiac injury occurred in 5 cases (7%) without mortality. CONCLUSIONS: Over a broad range of institutions, substernal Nuss bars were used in PE repair for patients with a history of sternotomy for cardiac surgery. Several technique modifications were reported and may have facilitated repair. Cardiac injury occurred in 7% of cases, and appropriate resources should be available in the event of complications. Prophylactic resternotomy was reported at a minority of centres.

Intracellular smooth muscle [Ca2+] in acetylcholine and nitric oxide-mediated relaxation of human small arteries.

In human resistance arteries the role of intracellular calcium during receptor agonist and nitric oxide (NO)-mediated vasorelaxation is almost unknown. We examined changes in smooth muscle calcium concentration ([Ca2+]i) caused by acetylcholine and the NO donor S-nitroso-N-acetylpenicillamine (SNAP) in isolated human subcutaneous small arteries. In arteries constricted with 50 mM KCl, acetylcholine and SNAP induced relaxation without any change in [Ca2+]i, whereas in noradrenaline constricted vessels, both acetylcholine and to a lesser degree also SNAP-mediated relaxation were associated with a decrease in [Ca2+]i. Furthermore incubation with SNAP (1 microM) induced a rightward shift in the [Ca2+]i-force relationship. These results suggest that relaxation mediated by endothelium derived hyperpolarizing factors (EDHF) is associated with reduction in [Ca2+]i, whereas NO-mediated relaxation can take place without changes in [Ca2+]i. This finding seems to be, at least partly, due to NO-mediated desensitization of the contractile apparatus to calcium.