Vasopressin receptors in human adrenal medulla and pheochromocytoma.

The nature of vasopressin (VP) receptors present in normal and tumoral human adrenal was investigated using various experimental approaches. Specific VP-binding sites were detected by autoradiography using [3H]arginine VP as a radioligand in adrenal cortex and medulla. The V1a receptor subtype was expressed in the two parts of the gland, as shown by pharmacological studies and RT-PCR experiments. By contrast, the V1b receptor subtype was only expressed in medullary chromaffin cells. This was confirmed by the characterization of V1b transcripts detected in adrenal medulla tissues. In pheochromocytoma, we also detected functional V1b receptors. These receptors triggered intracellular calcium mobilization from intracellular pools and were involved in catecholamine secretion. Binding experiments performed on pheochromocytoma plasma membrane preparations also revealed V1a vasopressin-binding sites, whose roles and cellular localization have not yet been determined. RT-PCR experiments confirmed these data; 100% and 80% of the five tumors tested exhibited V1a and V1b transcripts, respectively. Perifusion experiments also demonstrated that some pheochromocytomas may secrete large amounts of VP. Our findings imply that VP locally secreted by human adrenal medulla may regulate adrenal function by acting on V1a or V1b receptors. More interestingly, we demonstrate that one pheochromocytoma oversecretes VP. In this particular case, this may contribute to the increase in blood pressure observed.

Vasopressin regulates adrenal functions by acting through different vasopressin receptor subtypes.

In mammals, vasopressin is known to be synthesized in the hypothalamus and released in the blood stream at the pituitary level. This neuropeptide is also synthesized and secreted by the adrenal medulla in many species including human. Moreover, agents like acetylcholine and corticotropin releasing factor stimulates its basal secretion. V1a vasopressin receptors are present in the adrenal cortex and are involved in steroids secretion (aldosterone in the zona glomerulosa and glucocorticoids in the zona fasciculata of some species). These receptors are coupled to phospholipase C beta and to dihydropyridine-sensitive calcium channels via heterotrimeric G proteins differing by their sensitivities to pertussis toxin. The adrenal medulla, from many species, exhibits V1a vasopressin receptors. In rat adrenal medulla, functional V1b vasopressin receptors could also be characterized. These receptors stimulate catecholamines secretion via activation of phospholipase C beta and subsequent mobilization of intracellular calcium. The adrenal medulla secretes AVP and exhibits functional vasopressin receptors. The adrenal cortex also possesses functional vasopressin receptors and is in contact with adrenal medulla via "medullary rays". We may thus reasonably conclude that AVP physiologically regulates adrenal gland functions via autocrine/paracrine mechanisms.

[Intrinsic sinus node dysfunction in adolescence during anorexia nervosa]. / Dysfonction sinusale intrinsèque de l'adolescence au cours d'une anorexie mentale.

A seventeen year old girl with anorexia nervosa (32 kg; 165 cm) was admitted as an emergency after syncope with severe bradycardia resistant to atropine monitored over a one week period. Autonomic blockade confirmed the intrinsic character of the sinus node dysfunction with chronotropic incompetence on exercise. Secondarily, a Mobitz I second degree AVB was observed. A DDDR pacemaker was implanted with an excellent functional result. With a one year follow-up, the bradycardia persists but body weight has increased. The authors discuss the physiopathology of this case: in the literature, the classical bradycardia of anorexia nervosa is sensitive to vagolytic drugs and only exceptionally as intense as in this patient. Sinus node dysfunction is very rare in the young in the absence of congenital heart disease. It is possible that the bradycardia had become chronic in this case.

[Is atypical sodium current related to arterial pathophysiology?]. / Un courant sodique atypique lié à la patho-physiologie artérielle?

Primary cultured human coronary myocytes, derived from patients with end-stage heart failure (NYHA, classes III and IV) caused by an ischemic disease and undergoing heart transplantation, express a voltage-gated tetrodotoxin-sensitive sodium current (INa). This current has atypical electrophysiological and pharmacological properties and regulates intracellular sodium ([Na+]i) and calcium ([Ca2+]i). Our work is aimed at identifying its role and regulation of expression during pathophysiology. We currently investigate whether INa is expressed in vascular smooth muscles cells (VSMCs) isolated from either healthy or diseased (atheromatous) arteries in human and, in parallel, in pig, rabbit and rat. Cells were enzymatically isolated, primary cultured and macroscopic INa were recorded using the whole cell patch clamp technique. We found that INa is expressed in VSMCs grown from human aortic (90%; n = 48) and pulmonary (44%; n = 16) arteries and in the human aortic cell line HAVSMC (94%; n = 27). INa was also detected in pig coronary (60%; n = 25) and rabbit aortic (47%; n = 15) VSMCs, but not in rat aortic myocytes (n = 30). These different INa were activated at similar range of potentials (approximately -45 mV), had similar sensitivity to tetrodotoxin (IC50 around 5 nM) and similar density (2 to 4 pA/pF). Their expression was related to cell dedifferentiation in vitro. However, INa was observed more frequently in human myocytes derived from diseased arteries (ischemic cardiopathy) than in those derived from healthy tissues (dilated cardiopathy). In conclusion, INa may contribute to increase the basal arterial contractility and play a role in pathological situations including hypertension.

[Cardioversion by external electric shock for atrial fibrillation: does patient age affect immediate results?]. / Cardioversion par choc électrique externe de la fibrillation auriculaire: l'âge des patients affecte-t-il les résultats immédiats?

The restoration of sinus rhythm by external electric shock in patients with persistent atrial fibrillation is a well established treatment. However, in current practice this treatment is generally indicated less in the elderly subject although this attitude is not factual. The objective of this work was to evaluate the immediate results of cardioversion by external electric shock, comparing the success rates in four age groups: under 60 years, between 60 and 69 years, between 70 and 79 years, and over 80 years. This study was performed on 182 consecutive patients aged from 25 to 89 years: 35 patients aged less than 60 years, 52 patients aged from 60 to 69 years, 65 patients aged from 70 to 79 years, and 30 patients aged 80 years or over. The success rates were 91.4% before 60 years, 90.4% between 60 and 69 years, 90.8% between 70 and 79 years, and 83.3% after 80 years. There was no significant difference between the success rates in the four age groups (p = 0.68). Among the other factors analysed, only the duration of atrial fibrillation and the body mass index significantly influenced the results of external electric shock in this series. This work suggests that age does not significantly influence the immediate results of external electric shock. According to these data it does not appear justified to contra-indicate cardioversion by external electric shock on the sole criterion of age.

[A multicentre trial of the diagnostic value and cost of electrocardiography in symptoms suggesting arrhythmia with a new event recorder with transtelephonic transmission]. / Etude multicentrique sur l'intérêt et le coût du diagnostic électrocardiographique de symptômes présumés rythmiques utilisant un nouvel enregistreur d'événements avec transmission transtéléphonique.

Events recorders are used for electrocardiographic documentation of symptoms of arrhythmia too sporadic and short lasting to be recorded by 24 hour Holter monitoring. However, there are no French studies comparing the value and cost of event recorders with conventional diagnostic methods. Recently, a new telediagnostic device has become available in France leading to an assessment of the technique. The aim of this study was to determine the value of this event recorder and the cost of diagnostic ECG in the assessment of presumed arrhythmic symptoms such as palpitations or rare tachycardia (<3 episodes per week) of short duration, compared with conventional techniques. Fifty-eight patients with these criteria were randomised, 30 to Survcard (Group I) and 28 to conventional diagnostic methods (Group II). The patients were comparable with respect to age, sex distribution, type of symptoms and associated cardiac disease. The ECG diagnosis of the symptoms was established in 20 cases (66.6%) of patients in Group I in 17 +/- 16 days, and in 14 cases (50.0%) of Group II in 23 +/- 28 days. The difference between the two groups was not statistically significant. The cost of a positive diagnosis for Group I (Survcard) varied from 0 to 228.47 Euro with an average of 71.22 +/- 117.02 Euro. The cost of positive diagnosis in Group II varied from 76.80 to 2340.41 Euro with an average of 480.39 +/- 797.41 Euro. In conclusion, this study showed that the percentage of patients with a positive diagnosis was comparable in the two groups but that the cost was 6 times higher in the group investigated by conventional methods than in the Survcard group because of more costly medical intervention.

[Endovascular treatment of aorto-iliac aneurysms. Made-to-measure endoprotheses increase the feasibility]. / Traitement endovasculaire des anévrismes aorto-iliaques. La confection astisanale sur mesure des endoprothèses augmente le taux de faisabilité.

The authors describe their experience of tailoring endoprostheses for endovascular treatment of aorto-iliac aneurysms with components available on the market. Between January 1996 and December 1999, 188 aorto-iliac aneurysms were treated by tailor-made endoprostheses using self-expanding Z stents made of stainless steel compiled with polyester ligatures and covered with standard commercially available polyester prostheses. These endoprostheses were implanted with an 18 to 24 Fr (usually 20 Fr) introducer and positioned by a surgical approach. This method allows construction of tubular, bifurcated, digressive or occlusive endoprostheses associated with an extra-anatomical bypass graft. It increased the number of endovascular procedures for aorto-iliac aneurysms in the authors' department. This number has been further increased by using endoprostheses with an uncovered proximal or distal stent for cases with particularly short or angled necks and by using hybrid endoprostheses with one or more extremities without a stent, allowing surgical suture of the anastomosis. The authors' results show that tailoring endoprostheses considerably increased the feasibility of endovascular treatment of aorto-iliac aneurysms, even in unselected patients whilst providing an effectiveness and safety to justify the continuation of this experience.

[Acute myopericarditis following laparoscopic treatment of gastroesophageal reflux]. / Myopéricardite aiguë dans les suites d'une cure laparoscopique de reflux gastro-oesophagien.

A 32-year-old patient experienced a postoperative acute myopericarditis following laparoscopic surgery for gastro-oesophageal reflux (Toupet's fundoplication). His medical history was unremarkable, apart from controlled arterial hypertension. Peroperative circulation was stable, except a short hypertensive episode at CO2 insufflation, controlled with nicardipine. A myopericarditis occurred at the fourth postoperative hour, with apical and inferior hypokinesia at ventriculography, ST-segment elevation with unremarkable coronary arteriography. The patient was discharged at day seven, with a NSAIDs treatment. Echocardiography three and nine months later postoperatively, showed an apical akinesia and persistence of the ST-segment modification, without clinical symptoms. Complications of laparoscopic fundoplication is either specific to surgery (gastro-oesophageal injury, diaphragmatic injury, mediastinitis, stenosis) or secondary to pneumoperitoneum (pneumothorax, carbon dioxide embolism). In this case, following an apparently uncomplicated laparoscopy and, except a direct cardiac trauma from a laparoscopic instrument, either coronary artery spasm, or pneumopericardium with CO2, or delayed gas embolism, or preoperative "silent" myopericarditis could be the potential cause of this cardiac complication.

[Quality assurance program for postoperative pain management: impact of the Consensus Conference of the French Society of Anesthesiology and Intensive Care]. / Programme d'assurance qualité de prise en charge de la douleur postopératoire: impact de la Conférence de consensus de la Sfar.

OBJECTIVE: To assess the impact of a pain management quality assurance program (PQAP) after abdominal surgery. The means used were mainly based on the French Society of anaesthesiology's pain management guidelines. STUDY DESIGN: Prospective evaluation using a before after study design: two audits among surgical patients: a first one in 1997 before implementation of PQAP, and a second one year later. PATIENTS AND METHODS: First, standards were defined including objectives about pain relief and patient satisfaction. After analysis of discrepancy observed between these objectives and the data of the first audit, a pain management program was introduced that included education of physicians, nurses and patients, systematic assessment of pain, organized pain relief protocols and implementation of modern analgesic technologies. RESULTS: 201 consecutive inpatients were evaluated in the first audit, and 117 in the second one. Comparing the second audit with baseline, the visual analog pain scores decreased during the five postoperative days, and the rate of very satisfied patients increased (36% versus 26%). 43% of the patients were given a regular analgesic medication in 1998 versus 15% in 1997. 65% of medications were administered with an effective interval between doses versus 47% in 1997. Patient-controlled techniques were used in 28% of the cases in 1998 versus 9% in 1997. CONCLUSION: The PQAP provided an improvement in efficacy of postoperative pain management in our unit, with the help of the overall ward staff, but without requiring personnel specially qualified.

[Thrombopenia increased by heparin and danaparoid]. / Thrombopénie croisée aux héparines et au danaparoïde.

Pathogenesis, frequency, and management of heparin-induced thrombocytopaenia are well-known. They may be related with both unfractioned heparin and low-molecular weight heparin. Suspected heparin must be discontinued as soon as the diagnosis is established. Orgaran (danaparoid sodium) may be used for management of patients with heparin-associated thrombocytopaenia but can itself be associated with a thrombocytopaenia. Our case report allows us to catch in mind such a crossed complication.

[Identification of risk factors for allogenic transfusion in cardiac surgery from an observational study]. / Identification des facteurs prédictifs de transfusion sanguine homologue en chirurgie cardiaque à partir d'une étude observationnelle.

OBJECTIVE: To determine perioperative variables for predicting allogenic transfusion in adult cardiac surgery. STUDY DESIGN: Prospective study. PATIENTS: We included 335 consecutive patients undergoing cardiac surgery between February and April 2001. METHODS: Perioperative variables were prospectively collected in a database. For each patient who received transfusion, hemoglobin threshold for transfusion and total number of units of red cell concentrates were collected. Univariate and multivariate analysis were performed. RESULTS: The two strategies for blood conservation which were predominantly used were aprotinin therapy (78%) and blood salvage from the extracorporeal circuit (68%). During perioperative period, 42% of patients [95% CI: 37-47%] received allogenic transfusion. The haemoglobin threshold for transfusion was 7.4 +/- 1.1 and 8.0 +/- 0.7 g x dl(-1) in operating room and in intensive care unit, respectively. On average, 3.4 +/- 2.7 units of red cell concentrates were transfused perioperatively per patient. Using multivariate analysis, perioperative allogenic transfusion was significantly associated with the following variables: preoperative haemoglobin level < 12 g x dl(-1) (odds ratio 8.9; p = 0.001), emergency procedure (odds = 3.7, p = 0.01), reoperation (odds ratio = 3.3; p = 0.002), chronic obstructive pulmonary disease (odds ratio = 2.5; p = 0.03) and complex surgery (odds ratio = 2.4; p = 0.01). The age, the gender, and body mass index were only independent risk factors by univariate analysis. CONCLUSION: In despite of techniques to limit requirement of allogenic transfusion, a large proportion of cardiac surgical patients remains transfused. Independent risk factors of perioperative transfusion are haemoglobin level < 12 g x dl(-1), emergency procedure, reoperation, chronic obstructive pulmonary disease and complex surgery.

[Perianaesthetic concerns for the new robot-assisted transaxillary thyroid surgery: a report of seven first cases]. / Implications anesthésiques de la chirurgie thyroïdienne ou parathyroïdienne par voie axillaire sous robot-assistance : à propos de sept premiers cas.

The gasless transaxillary robot-assisted endoscopic thyroid surgery is recently proposed and developed in South Corea and USA. We reported the perianaesthestic concerns for the seven first patients scheduled to undergo this innovative surgical technique in France. The anaesthetic considerations focused on the length of surgery according to the learning curve, the risk of the arm posture and the postoperative painful evaluation and relief.

The preoperative administration of ketoprofen improves analgesia after laparoscopic cholecystectomy in comparison with propacetamol or postoperative ketoprofen.

BACKGROUND: Non-opioid analgesics, paracetamol and non-steroid anti-inflammatory drugs (NSAIDs) are proposed for pain relief after laparoscopy. We compared perioperative propacetamol (P) and ketoprofen (K) to provide analgesia after laparoscopic cholecystectomy. METHODS: After ethical committee approval, we included 104 ASA I-II patients, without preoperative analgesic drugs, who were scheduled to undergo laparoscopic cholecystectomy. Anaesthesia was standardized using propofol, fentanyl, atracurium, isoflurane and N(2)O 50%. Ketoprofen 100 mg or propacetamol 2 g or a saline drip (a 100-ml unit of saline in 10 min) was infused blindly and randomly. Patients received either ketoprofen (group K1) or propacetamol (group P1) before induction of anaesthesia and saline after surgery, or saline before surgery and ketoprofen (group K2) or propacetamol (group P2) after surgery. Postoperative visual analogue pain scores (VAS 0-100 mm) were recorded during 24 h. If VAS was >30, a second dose (placebo, ketoprofen or propacetamol) was infused. Nalbuphine 0.2 mg kg(-1) i.v. was given as rescue analgesic if VAS was > or =50. RESULTS: Ninety-eight patients were studied The number of patients not requiring the second analgesic was greater in K1 (33.5%) than the others (K2 0%, P1 0%, P2 7.5%). VAS scores were significantly lower in K1 (P=0.001), with less nalbuphine consumption compared with P1. VAS and opioid request were similar in K2 and P2. CONCLUSION: Preoperative administration of ketoprofen improves postoperative analgesia after laparoscopic cholecystectomy compared with its postoperative administration and pre- and postoperative propacetamol.

Terlipressin for treating intraoperative hypotension: can it unmask myocardial ischemia?

IMPLICATIONS: After administration of terlipressin to treat hypotension related to induction of general anesthesia, profound hypertension occurred in association with myocardial ischemia and occlusion of the left anterior descending coronary artery. The authors emphasize cautious use of this drug because of such adverse events.

Haemodynamic and renal effects of intravenous enalaprilat during coronary artery bypass graft surgery in patients with ischaemic heart dysfunction.

Renal dysfunction occurring after open heart surgery is multifactorial in origin but activation of the renin-angiotensin system may have a prominent role. Fourteen patients with ischaemic heart dysfunction scheduled for elective coronary artery bypass graft (CABG) surgery were allocated to a treatment group [enalaprilat for 2 days; ACEI (angiotensin-converting enzyme inhibitor) group, n=7] or a control group (n=7). The cardiac index was significantly higher in ACEI-treated patients than in the controls before and after cardiopulmonary bypass (CPB) (P<0.05) and on postoperative day 2 (P<0.05). The systemic vascular resistance was significantly lower in the ACEI-treated patients than in the controls before and after CPB (P<0.05). Renal plasma flow, measured as [131I]orthoiodohippuran clearance (ClH), was higher in the ACEI group than in the control group before CPB, as was endogenous creatinine clearance after CPB (P<0.05). On post-operative day 7, ClH was significantly higher in the ACEI group than in the control group (P<0.05). Plasma renin activity and vasopressin concentration increased in both groups during CPB (P<0.05). The study demonstrates that administration of an i.v. ACEI, enalaprilat, improves cardiac output during CABG surgery in patients with ischaemic heart dysfunction. Moreover, renal perfusion was better maintained during surgery, and this effect was sustained up to post-operative day 7.

Evidence for tetrodotoxin-sensitive sodium currents in primary cultured myocytes from human, pig and rabbit arteries.

Primary cultured human coronary myocytes express a tetrodotoxin-sensitive sodium current (I(Na)). Here, we have investigated whether I(Na) is expressed in vascular smooth muscles cells (VSMCs) isolated from other large arteries, and other mammals. VSMCs were enzymatically dissociated, kept in primary culture, and macroscopic I(Na) was recorded using the whole-cell patch-clamp technique. We found that I(Na) is expressed in VSMCs grown from human aortic (90%; n=50) and pulmonary (44%; n=19) arteries, and in the human aortic myocyte cell line HAVSMC (94%; n=27). I(Na) was also detected in pig coronary (60%; n=33), and rabbit aortic (47%; n=15), but not in rat aortic VSMCs (n=20). These different I(Na) had similar voltage thresholds for activation (approximately equal to -50 mV), and were highly sensitive to extracellularly applied tetrodotoxin. We conclude that I(Na) is expressed in VSMCs grown from various types of large arteries in humans, pig and rabbit.

The detection of carbon dioxide embolism during laparoscopy in pigs: a comparison of transesophageal Doppler and end-tidal carbon dioxide monitoring.

BACKGROUND: The aim of the study was to compare the value of transesophageal Doppler and end-tidal carbon dioxide monitoring to detect venous carbon dioxide embolism in pigs during laparoscopic cholecystectomy. METHOD: Ten pigs were anesthetized under constant ventilation, and instrumented for laparoscopic cholecystectomy. CO2 pneumoperitoneum was performed at 15 mmHg and then, successive increased intravenous gas boluses of 0.1 to 4 ml/kg injected through the femoral vein using a 55-mm long catheter. The responses indicative of embolism were defined as: 1) a change in Doppler tone placed facing the junction of the right atrium and inferior vena cava; 2) a change in end-tidal CO2 > or = 0.4 kPa. RESULTS: Doppler was more sensitive in detecting 0.1, 0.2 and 0.4 ml/mg of CO2 embolism than end-tidal CO2 (P < 0.05). Over 0.4 ml/mg no differences in sensitivity were found but the Doppler signal modifications occurred earlier than the changes in end-tidal CO2. Moreover, these changes always consisted of a reduction of the value. CONCLUSION: During laparoscopic cholecystectomy in pigs, transesophageal Doppler was a highly sensitive monitor which provided an earlier detection of CO2 embolism and at lower doses than end-tidal CO2 monitoring.