Orthopaedic aspects in seventy-two children affected by Marfan syndrome. Correlations between pathological features and fibrillin-1 gene mutations.

Marfan syndrome is an autosomal dominant disorder of the connective tissue caused by mutations of the fibrillin-1 gene (FBN1) that primarly involves the cardiovascular, skeletal and ocular systems. We investigated 72 children affected by Marfan syndrome in order to identify possible correlations between some musculoskeletal features and specific mutations of fibrillin-1 gene. The following FBN-1 gene mutations have been observed: a missense mutation in 21 children, a stop mutation in 9, a splice mutation in 15 and other mutations in the remaining 27 patients. We observed a statistical significant association between chest asymmetry and splice mutation (p=0.031) and between scoliosis >20° or thoracolumbar kyphosis and stop mutation (p=0.039). However, we did not find a true genotype-phenotype correlation between the fibrillin-1 gene mutations observed and the prognosis of the disease. Future studies are necessary to demonstrate further genotype-phenotype correlations in order to identify early prognostic markers of Marfan syndrome and to plan the most appropriate clinical management accordingly.

Obstructive sleep apnea in children with Marfan syndrome: Relationships between three-dimensional palatal morphology and apnea-hypopnea index.

OBJECTIVE: To evaluate the relationship between the severity degree of OSA (apnea/hypopnea index AHI>1) and palatal area and volume, measured by 3D analysis of digital casts in Marfan children. METHODS: Twenty children with a clinical diagnosis of MS were recruited from a tertiary medical center. All the subjects underwent standard nocturnal polygraphy testing. Sixteen Marfan patients (7F,9 M; mean age 8.8yy ±â€¯1.5yy) with AHI>1 were enrolled. Marfan Group (MG) was compared with a control group (CG) of 17 children without Marfan syndrome (9F,8 M; mean age 8.5yy ±â€¯1.7yy) presenting with nose-breathing pattern. For each subject maxillary digital casts were taken and palatal area and volume were measured. Unpaired t-test was used to test significant differences between MG and CG for area and volume measurements. Pearson correlation coefficient (PCC) was used to measure the linear correlation between the degree of OSA (AHI index) and palatal volume and palatal area. RESULTS: 80% of Marfan children presented an AHI>1 and a diagnosis of OSA. MG presented statistically significant lower values of palatal surface area (662.68 mm2; P < 0.0001) and palatal volume (2578.1 mm3; P < 0.0001) with respect to CG (923.0 mm2 and 3756.6 mm3, respectively). Correlation analysis showed that AHI index had no linear correlation with palatal area (r = - 0,07) and with palatal volume (r = - 0,11). CONCLUSION: OSA is highly prevalent in children with Marfan's syndrome (80%). Marfan children present a reduction of palatal area and volume when compared to healthy subjects. OSA in Marfan children is not linear correlated to the palatal morphology and it shows a multifactorial aetiology.

The combination of genetic variants of the FSHB and FSHR genes affects serum FSH in women of reproductive age.

STUDY QUESTION: What is the effect of FSHB-211G>T together with the FSHR 2039 A>G on serum FSH in women? SUMMARY ANSWER: Serum FSH levels are affected by the combination of genetic polymorphisms in FSHR and FSHB. WHAT IS KNOWN ALREADY: The relationship between SNPs of the FSHR gene and serum FSH has not been completely clarified. Genetic variants of the FSHB gene have been associated with variation in gene transcription and serum FSH levels in men. No data have been published on the effect of the FSHB-211G>T in women, alone or in combination with the FSHR 2039 A>G. STUDY DESIGN, SIZE, DURATION: This study was a prospective study including 193 healthy women of reproductive age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile and otherwise healthy eumenorrheic women (n = 193) with normal BMI and serum FSH levels were recruited for the study. In all women early follicular phase FSH and AMH were measured by commercial assays, and antral follicle count was measured by transvaginal ultrasound. Genomic DNA was purified from total peripheral blood and genotyping for the two SNPs was performed. MAIN RESULTS AND THE ROLE OF CHANCE: No significant gradients of increasing or decreasing Day 3 FSH across the FSHR 2039 (AA/AG/GG) and FSHB-211 (GG/GT/TT) genotypes, respectively, were observed. When women were stratified according to the FSHR 2039, and FSHB-211 genotypes a statistically significant reduction of d3 FSH was shown in the group of women with the FSHB-211 GT + TT/FSHR2039 AA genotype compared with the FSHB-211 GG/FSHR2039 GG genotype, hence confirming a possible additive effect of the different SNPs in FSHR and FSHB on regulating serum FSH. LIMITATIONS, REASONS FOR CAUTION: This finding requires an independent confirmation. However, it confirms the relationship between serum FSH and FSHB together with FSHR gene polymorphisms already reported in males. WIDER IMPLICATIONS OF THE FINDINGS: The knowledge of the FSHB/FSHR genotype combination is fundamental for the proper interpretation of serum FSH levels in women of reproductive age. STUDY FUNDING/COMPETING INTERESTS: Merck Serono supported the study in the form of a research grant for the laboratory session. None of the authors have any competing interest to declare.

New molecular markers for the evaluation of gamete quality.

PURPOSE: Only 30 % of IVF cycles result in a pregnancy, so that multiple embryos need to be replaced, per treatment cycle, to increase pregnancy rates, resulting in a multiple gestation rate of 25 %. The use of new markers in the gamete selection, could reduce the number of the oocytes to be fertilized and embryos to be produced, but the tools to evidence the gamete competence remain unavailable and more studies are needed to identify bio-markers to select the best oocyte and sperm to produce embryos with higher implantation potentiality. METHODS: To define oocyte competence, the apoptosis of the surrounding cumulus cells and the oxygen consumption rates for individual oocytes before fertilization seems to provide a non-invasive marker of oocyte competence and hence a quantitative assessment of the reproductive potential for the oocyte. The chromatin integrity seems to be used also as biological marker of sperm competence, together with the morphological evaluation of large vacuoles in the head. RESULTS: The apoptosis rate of cumulus cells lower than 25 % and an higher oxygen consumption could be an evidence of an overall metabolic activity, related to a better fertilization ability and embryo cleavage quality. The apoptosis rate of the sperm chromatin, evaluated by direct Tunel in situ analysis, seems to be, also for the male gamete, a marker of competence and implantation potentiality, in particular when it is lower than 20 %. The evaluation of the presence of large vacuoles in the sperm head prior to perform ICSI seems to increase the implantation rate, but it is not associated to chromatin integrity. CONCLUSIONS: The biological concept of competence appears unrelated to any morphological parameters, so that it is necessary to investigate new molecular markers in the gamete selection. Apoptosis of cumulus cells in the oocytes and spermatozoa, revealing the presence of large vacuoles, could help to determine the competence of the gamete to be fertilize.

Graft patency and late outcomes for patients with ST-segment elevation myocardial infarction who underwent coronary surgery.

OBJECTIVE: The aim of our study was to assess the long-term clinical outcomes and the grafts patency rates of patients with ST-segment elevation myocardial infarction (STEMI) who underwent urgent or emergency coronary artery bypass grafting (CABG). MATERIALS: Participants in two previous studies comprising 207 STEMI patients undergoing on-pump (145 patients) or off-pump (62 patients) coronary artery bypass graft (CABG) surgery in our institution were prospectively followed to assess late mortality, graft patency, and major adverse cardiac-related event (MACE) rates. Graft patency was evaluated by multi-detector computed tomography angiography 64-slice scan. Mean times of graft implantation were 38±16 months and 37±14 months in on-pump and off-pump, respectively. Follow-up data were obtained in all patients and was 100% complete. RESULTS: Late mortality rate was 7.4% (10 patients) in the on-pump and 6.5% (4 patients) in off-pump groups (p=0.45). Five-year overall survival rate (±SE) was 93.5±2.1% and 92.6±1.9% in the off-pump vs on-pump, respectively. Five years' freedom from cardiac-related death was 94.9±2.9% in the on-pump group vs 96.8±3.2% in the off-pump group (p=0.25). Five years' freedom from cardiac-related events was 89.7±1.6% in the on-pump group versus 93.5±1.8% in the off-pump group (p=0.32). In all patients, a total of 449/491 (91.5%) grafts were patent. Percentages of overall grafts classified as patent were similar in the on-pump group (90.7% - 322/355 conduits) versus the off-pump group (91% - 133/146 conduits). Graft patency rates were also similar between the two groups with regard to arterial and saphenous vein conduits, and with regard to different branches of the coronary arteries grafted. CONCLUSION: Our data suggest that off-pump CABG patients have the same late mortality, MACEs, and graft patency rates as conventional cardioplegic cardiac arrest CABG patients. In our opinion, urgent or emergency CABG for patients with STEMI can be done either way.

ECG-gated multidetector computed tomography for the assessment of the postoperative ascending aorta.

PURPOSE: This study was undertaken to define the role of electrocardiographically (ECG)-gated multidetector computed tomography (MDCT) in the assessment of the postoperative ascending aorta. MATERIALS AND METHODS: From November 2006 to June 2007, 21 patients, [11 men, ten women; age +/- standard deviation (SD): 62.7+/-10.8 years] with a history of ascending aorta replacement underwent ECG-gated MDCT and were prospectively included in our study. Ascending aorta replacement had been performed with different surgical techniques: Bentall-De Bono (four patients, 19%), Tirone-David (five patients, 23%), and modified Tirone-David with creation of aortic neosinuses (12 patients, 57%). Two patients were excluded from MDCT evaluation because they failed to fulfil the inclusion criteria. Transthoracic echocardiography was used as the reference standard. All patients provided informed consent. RESULTS: In all patients, ECG-gated MDCT provided a clear depiction of the aortic annulus, aortic root and ascending aorta, enabling accurate measurements in all cases. The aortic valve area (3.4+/-0.2 cm(2)), the diameter of the sinotubular junction (31.6+/-1.8 mm), the diameter of the neosinuses in the case of modified Tirone-David procedures (37.3+/-2.1 mm) and the distance between the cusps and the graft wall during systole (3.1+/-0.7 mm) fell within standard ranges and showed a good correlation (r=0.89) with the values obtained with transthoracic echocardiography. CONCLUSIONS: MDCT is currently considered a compulsory diagnostic step in patients with suspected or known aortic pathology. MDCT is a reliable technique for anatomical and functional assessment of the postoperative aortic root and provides cardiac surgeons with new and detailed information, enabling them to formulate a prognostic opinion regarding the outcome of the surgical procedure.

Cryopreservation of biopsied embryos at the blastocyst stage.

BACKGROUND: The availability of an efficient cryopreservation program is especially important in the case of embryos that have undergone blastomere biopsy for PGD. Unfortunately, the freezing/thawing of biopsied embryos has given disappointing results when performed at the cleavage stage. In this study, embryos diagnosed as normal after PGD were grown to the blastocyst stage, frozen and thawed for successive frozen embryo transfer. METHODS: A total of 34 patients performed a thawing cycle in which 47 blastocysts were thawed. The cryopreservation solutions were based on HEPES-buffered medium supplemented with human serum albumin (HSA), sucrose and 1,2-propanediol. The same protocol was applied to embryos from 88 IVF/ICSI patients, which underwent 92 thawing cycles with 150 thawed blastocysts. RESULTS: The survival rate was similar in the two groups (53% after PGD and 58% in IVF/ICSI cycles), as well as the cumulative pregnancy rate per patient (59% after PGD versus 47% in IVF/ICSI cycles), despite a higher maternal age and a lower proportion of embryos available for transfer or cryopreservation in the PGD group. CONCLUSIONS: Neither the survival rate nor the subsequent development and chances of implantation, differed between embryos frozen at the blastocyst stage following biopsy and those frozen intact.

The inhibition of the human sperm phosphatidylinosytol 3-kinase by LY294002 does not interfere with sperm/oocyte interaction.

It has recently been reported that the selective inhibition of phosphatidylinosytol 3-kinase (PI3K) enhances human sperm motility. However, little information exists on a possible role of PI3K in other sperm functions involved in the fertilization process. In this study, we investigated whether LY294002 could affect human sperm ability to fuse with oocytes, by means of the hamster egg penetration test (HEPT). The effect on acrosome reactions (AR) and on sperm/zona pellucida (ZP) binding was also evaluated. The pre-incubation with scalar doses of LY294002 (0.1, 1 and 10 microm) did not interfere with sperm ability to fuse with oocytes either in the conventional version of the HEPT or in the version enhanced with progesterone (P). No interference with the stimulatory effect on AR exerted by P or mannose-bovine serum albumin (mannose-BSA) was revealed. Finally, LY294002 had no effect on sperm/ZP binding. These results indicate that the inhibition of PI3K by LY294002 does not interfere with sperm interaction with oocytes. This is noteworthy in the view of a possible clinical use of LY294002 as an in vitro stimulator of the sperm motility of asthenozoospermic patients for assisted reproduction techniques.

Ovarian function following radiation and chemotherapy for cancer.

High-dose chemotherapy and radiotherapy have increased the long-term survival of young patients with cancer; nevertheless, the toxic effects on ovarian function causing amenorrhoea, premature menopause and infertility, are still severe.

Factors influencing immediate and long-term results after button's technique.

BACKGROUND: Aim of this study was to evaluate the factors influencing immediate and long-term results in patients undergoing aortic root replacement with a composite graft. METHODS: Between January 1989 and February 1999, 105 patients (83 males, 22 females) who underwent Bentall technique were studied. Preoperative diagnosis was annulo-aortic ectasia in 54, aortic dissection in 27, atherosclerotic aneurysm in 21, and aortitis in 3 cases. Seventeen patients were affected by Marfan's syndrome. All cases, elective, urgent, and emergency were included. Button technique was performed and the associated surgical procedures were coronary artery bypass grafting in 21, total aortic arch replacement in 15, proximal hemi arch in 5, and mitral valve replacement in 5 cases. RESULTS: The overall hospital mortality rate was 7.6% (n=8). Univariate analysis using chi(2) and/or two-sample "t"-test showed that dissection, aortitis, aneurysm rupture into-pleura or pericardium, emergency status, redo, prolonged pump times and circulatory arrest, were predictors influencing in-hospital mortality. Coagulopathy, low cardiac output, stroke, perioperative myocardial infarction, surgical bleeding leading to reoperation, were significantly related to in-hospital mortality (by correlation analysis). A multivariate analysis showed that, emergency status (p=0.027), aortic dissection (p=0.029), perioperative myocardial infarction (p=0.0021), reoperation for bleeding (p=0.0023), and pump time >180 min (p=0.011), were significant. The actuarial survival rate at 10 years follow-up was 84.7%. There were 8 late deaths. The Kaplan-Meier showed significant differences when considering dissection vs non-dissection (p=0.018), but did not reach significance in Marfan vs non-Marfan groups (p=0.83). NYHA class IV (p=0.052), previous cardiac surgery procedure (p=0.041), concomitant CABG (p=0.021), total aortic arch reconstruction (p=0.001), and mitral valve replacement (p=0.016), were identified as significant by Log Rank test. CONCLUSIONS: The Bentall procedure for aortic root replacement is safe and durable; in hospital mortality in elective status it was 1.28%; early and long-term mortality higher in patients with acute dissection. Six late deaths were procedures related. Sixty-six patients (76.4%) were in NYHA I class at follow-up. The incidence of late outcomes, thromboembolism (1.03%), graft infection (2.06%), pseudoaneurysm (0%), reoperation in ascending aorta or aortic valve (3.1%), operations on the remaining aorta (6.7%), and hemorrhage due to anticoagulant therapy (1.03%), are very low.

Effect of human sperm exposure to progesterone on sperm-oocyte fusion and sperm-zona pellucida binding under various experimental conditions.

In this study, the effect of human sperm exposure to progesterone on sperm/oocyte fusion, using the hamster egg penetration test, and on sperm/zona pellucida (ZP) binding, using the hemizona assay, was investigated under various experimental conditions. A brief exposure of human spermatozoa to progesterone exerted a stimulatory effect on sperm/oocyte fusion which was dose-dependent, capacitation-dependent, influenced by the source of serum albumin in capacitating medium, and was higher than that produced by the exposure to progesterone from the onset of capacitation. The exposure of capacitated spermatozoa to progesterone during 20 min-spermatozoa/ZP-coincubation produced an enhancement of ZP-binding, which was not significantly influenced by the source of serum albumin in capacitating medium. A significantly lower ZP-binding was exhibited by spermatozoa exposed to progesterone from the beginning of capacitation. These results indicate that progesterone exerts a stimulatory effect on human sperm's fertilizing ability, which occurs mainly in post-capacitation events directly involved in sperm/oocyte fusion and in ZP-binding. Conditions optimizing these effects are provided. They should be taken into account in the standardization of experimental and clinical studies designed to evaluate the response of human spermatozoa to progesterone.

Left ventricular thrombosis after blunt chest trauma.

A 22-year-old man was admitted to our observation with left ventricular thrombus arising after blunt chest trauma occurring during a ski accident one year before. None was obtained from a review of instrumental and laboratory data at trauma time. Transesophageal echocardiography showed an intraventricular thrombus and severe hypokinesia at the apex. Standard cardiac surgery procedure was performed and postoperative period was uneventful. Echocardiography controls at 6/12 months showed a normal apex kinesia. This case shows the importance of hospitalization, hemodynamics monitorization and late serial echocardiographic controls for timely diagnosis and management of myocardial contusion and consecutive ventricular thrombus formation to prevent life-threatening complications.

Genetic, andrological and clinical characteristics of patients with congenital bilateral absence of the vas deferens.

The possibility of retrieving spermatozoa from the epididymis allows patients with congenital bilateral absence of the vas deferens (CBAVD) to father a child by means of assisted reproduction techniques. This has, however, increased the chance of transmitting a mutated allele of the cystic fibrosis transmembrane conductance regulator (CFTR) gene which increases the risk of generating offspring with cystic fibrosis (CF). Because of the increased heterogeneity of the CFTR locus, the study of a discrete number of mutations, as usually carried out in a diagnostic work-up, is unable to ascertain the presence of a mutation in a relatively high proportion of the patients screened. In an attempt to increase the chance of detecting the presence of CFTR gene abnormalities, 37 patients with CBAVD and one patient with congenital unilateral agenesis of the vas deferens (CUAVD) underwent an enlarged diagnostic protocol, which included screening for the most expected mutations of the CFTR gene in our population, evaluation of the five thymidine (5T) allelic variant, sweat test, respiratory function tests, evaluation of steatocrit, and an accurate evaluation of the history of the patient to search for symptoms commonly found in patients with CF. A single CFTR gene mutation was found in 18 patients (48.6%) with CBAVD and in the patient with CUAVD. The most frequent mutation observed was the Delta F508. Eleven patients (45.8%) had the 5T variant and in five of them it was not associated with any detectable mutation of the CFTR gene. Two female partners were found to be carriers of a mutation, whereas 5 (18.5%) had the 5T variant. As many as 71% of CBVAD patients had the simultaneous presence of at least two signs and/or symptoms suggestive of CF, albeit they were of mild intensity and the patients felt fit and healthy. In conclusion, these results suggested that some patients with CBAVD without CFTR gene mutation or 5T variant, even when their sweat test is negative, may show clinical suspicion of carrying a CFTR gene mutation and therefore are at risk of generating children affected by CF if the partner carries a mutation as well. The screening for mutations and a careful clinical examination may contribute to better identification of patients with CFTR-related CBAVD.

Emergency operation for acute type A aortic dissection: neurologic complications and early mortality.

BACKGROUND: Acute type A aortic dissection is a surgical emergency still associated with high postoperative complications. The aim of this study was to investigate factors for hospital mortality and neurologic deficit in patients undergoing emergency operation for acute type A aortic dissection. METHODS: Eighty-five consecutive patients (age range, 20 to 82 years) operated on for acute type A aortic dissection over a 6-year period were evaluated. Univariate and stepwise multiple logistic regression analyses were conducted among 32 perioperative variables. RESULTS: All patients underwent surgical procedures under deep hypothermic circulatory arrest. Antegrade or retrograde cerebral perfusion was used in 23 patients (27.1%) and 18 patients (21.2%), respectively. Forty-three patients underwent arch/hemiarch replacement and the ascending aorta was replaced in 42 patients. Overall mortality rate was 25.9% (22 of 85 patients). Multiple logistic regression analysis showed that lack of cerebral perfusion (p = 0.021) and postoperative renal failure (p = 0.006) were the best predictors for hospital death. Twenty-one patients (24.7%) experienced neurologic accidents. The risk factor for postoperative neurologic complication was lack of cerebral perfusion (p = 0.013). Hospital mortality was 13% (3 of 23 patients) and 16.7% (3 of 18 patients) in the antegrade and retrograde cerebral perfusion groups (p > 0.05) and neurologic deficit was 13% (3 of 23 patients) and 11.1% (2 of 18 patients), respectively (p > 0.05). CONCLUSIONS: Hospital mortality and neurologic complications in patients undergoing emergent operation for acute type A aortic dissection were reduced when cerebral perfusion was used with deep hypothermic circulatory arrest.

Nitric oxide synthase inhibition in human sperm affects sperm-oocyte fusion but not zona pellucida binding.

There is recent evidence that mouse and human spermatozoa contain constitutive nitric oxide synthase (cNOS) and can synthesize nitric oxide. The aim of this study was to investigate whether the inhibition of human sperm cNOS could affect sperm-oocyte fusion and sperm binding to the zona pellucida (ZP). N(G)-nitro-L-arginine methyl ester (L-NAME) was used as cNOS inhibitor. Sperm-oocyte fusion was evaluated using the hamster egg penetration test (HEPT). The ZP binding was evaluated using the hemizona assay. L-NAME added from the onset of capacitation strongly inhibited sperm-oocyte fusion. This inhibitory effect was dose dependent, stereospecific, and suppressed by L-arginine in a dose-dependent manner. L-NAME also inhibited sperm-oocyte fusion in the HEPT enhanced with progesterone (P), where P (5 microM) was added for 15 min to capacitated sperm. A lesser but significant inhibition was also observed when sperm suspensions were exposed to L-NAME following capacitation in both versions of HEPT. On the contrary, L-NAME did not affect ZP binding. In conclusion, the present study provides the evidence that cNOS plays a role in the human sperm's capacity to fuse with oocyte but not in the ZP binding.

Intraoperative flow measurement in composite Y arterial grafts.

OBJECTIVE: Total arterial myocardial revascularization may be achieved by using the 'Y-graft' techniques with different free arterial conduits anastomosed off the side of an in situ internal thoracic artery to reach distal coronary segments. This study was assessed to measure intraoperative graft flow, resistance and clinical outcomes. METHODS: Seventy-six patients who underwent coronary artery bypass grafting during a time period of 27 months were enrolled in this prospective study. All patients received sequential grafting by using both internal thoracic arteries, inferior epigastric and right gastroepiploic artery joined as a composite Y graft. Intraoperative graft flow, resistance and derived variables were measured. RESULTS: All patients except one showed good flow (ml/min and waveform) in either branch of composite graft. In one case, a low-flow situation through the graft was registered requiring surgical correction. Temporary occlusion of either branch did not significantly affect flow in the other side of the arterial Y. Mid-term follow-up (3 and 15 months) and angiographic studies showed a high graft patency rate. CONCLUSION: Composite arterial grafts provide excellent early and mid-term clinical results. Flow reserve of the left internal thoracic artery did not affect blood flow and resistance on either branch of the Y graft when temporary occlusion on the other side of the arterial Y was performed.

Arrhythmia prophylaxis after coronary artery bypass grafting: regimens of magnesium sulfate administration.

BACKGROUND: Arrhythmias are common after open heart surgery and may be related to hypomagnesaemia due to cardiopulmonary bypass. Although perioperative prophylactic Mg2+ administration may prevent arrhythmias after coronary artery bypass grafting (CABG), clear indications as well as the timing of Mg2+ substitution and dose regimen need to be clarified. Aim of this study was to evaluate the antiarrhythmic effects of Mg2+ infusion in patients who underwent elective CABG. METHOD: Ninety-seven patients who underwent elective CABG were divided in four Groups. In Group A 1 g of magnesium sulfate was added to the pump prime, Group B received 1 g in the pump prime plus 5 mmol/L in the cardioplegic solution, Group C received 5 mmol/L in the cardioplegic solution, and Group D was a placebo control Group. Groups A, B, and C also received 24 h continuous infusion of magnesium sulfate at 10 mmol/L. Three-channel electrocardiogram (II-V5-V6) continuous monitoring was performed 12 hours preoperatively and 48 hours postoperatively. Blood samples were taken for subsequent Serum magnesium measurements, at five different time points before, during and after CBP. RESULTS: In all Groups serum Mg2+ levels were reduced during CPB (Time 2) and statistically significant differences from pre-anaesthesia levels (Time 1) were noted (p <0.05). In Groups A, B, and C Serum Mg2+ levels increased progressively from Time 3 to Time 5; in Group D serum Mg2+ levels were still much lower at Time 5. Significant differences (p<0.05) were noted for Groups B and C vs Groups A and D in atrial ectopics, atrial fibrillation, and ventricular arrhythmic events. CONCLUSION: Our results demonstrate that Mg2+ sulfate administration regimens used in Group B and C reduce postoperative arrhythmic events in patients undergoing CABG.

Adenosine triphosphate-dependent potassium channel modulation and cardioplegia-induced protection of human atrial muscle in an in vitro model of myocardial stunning.

OBJECTIVES: Although adenosine triphosphate-dependent potassium channel openers have been shown to enhance cardioplegic protection in animal myocardium, there is a lack of data on human cardiac tissues. We aimed at determining, on human atrial muscle, whether adenosine triphosphate- dependent potassium channels are involved in protection caused by high-potassium cardioplegia and whether adenosine triphosphate-dependent potassium channel activation might improve cardioplegic protection in an in vitro model of myocardial stunning. METHODS: Human atrial trabeculae were obtained from adult patients undergoing cardiac operations. In an organ bath at 37 degrees C, the preparations were subjected to 60 minutes of hypoxia at a high stimulation rate either in Tyrode solution (control, n = 17) or in St Thomas' Hospital solution without additives (n = 6) or associated with 100 nmol/L bimakalim (n = 7) or 1 micromol/L glibenclamide (n = 7), followed by 60 minutes of reoxygenation and 15 minutes of positive inotropic stimulation with 1 micromol/L dobutamine. RESULTS: Atrial developed tension was reduced by hypoxia to 27% +/- 5% of baseline and incompletely recovered after reoxygenation to 38% +/- 7%, whereas dobutamine restored contractility to 74% +/- 7% of basal values. St Thomas' Hospital solution with or without bimakalim improved developed tension after reoxygenation and dobutamine (P <.0001 vs control), whereas glibenclamide inhibited these protective effects of cardioplegic arrest (P =.001 vs St Thomas' Hospital solution). After reoxygenation, the protective effect of bimakalim disappeared at a high pacing rate (400- and 300-ms cycle length) but recovered during dobutamine superfusion. CONCLUSIONS: Adenosine triphosphate-dependent potassium channels are likely involved in the cardioprotective effects of cardioplegia in human atrial trabeculae and adenosine triphosphate-dependent potassium channel activation with bimakalim used as an additive to cardioplegia enhanced protection.

Effect of normothermic versus hypothermic cardiopulmonary bypass on cytokine production and platelet function.

BACKGROUND: Proinflammatory cytokines and platelets play a key role in the systemic inflammatory response associated with cardiopulmonary bypass (CPB). The aim of this study was to evaluate the effects of both hypothermic and normothermic CPB on platelet activation, cytokine production, as well as their possible correlations. METHODS: Twenty patients who underwent CABG were randomly assigned into two groups receiving hypothermic and normothermic CPB. Blood samples were obtained through a venous catheter at 6 time points. The following parameters were measured: in vitro platelet aggregation, in vivo platelet activation, complete and differential blood cell counts, plasma soluble P-selectin levels, plasma IL-6, IL-1beta and TNFalpha levels. RESULTS: The results demonstrated that platelet abnormalities could be observed to a greater extent during hypothermic rather than normothermic CPB. The occurrence of in vivo platelet activation was suggested by the presence of a significantly increased percentage of platelets expressing CD62P on their surface, as well as by a decreased in vitro platelet aggregation induced by different agonists. Complete and differential blood cell counts showed no substantial decrease in platelet number without differences between groups. The results obtained also showed the presence of a significant release of sP-selectin during CPB, as well as a more pronounced increase of plasma sP-selectin levels in patients undergoing hypothermic compared to normothermic CPB. A comparison of cytokine levels demonstrated a significant elevation of plasma IL-6 levels during either hypothermic or normothenmic CPB, paralleling the neutrophil rise, while no differences were observed for TNF-alpha levels. Conversely, plasma IL-1beta levels were significantly elevated during hypothermic, but not during normothermic CPB. CONCLUSIONS: Hypothermic CPB is responsible for a greater platelet activation and endothelial dysfunction than normothermic CPB, leading to more profound changes in the hemostatic and inflammatory systems, which, in turn, might be responsible for the higher incidence of postoperative complications reported during hypothermic CPB.

Cicletanine prevents the excitation-conduction blocks induced by terfenadine in ischemic myocardium.

Terfenadine, a histamine H(1) receptor antagonist, has been associated with clinical ventricular arrhythmias and in vitro excitation-conduction blocks, whereas anti-ischemic and antiarrhythmic effects have been shown with cicletanine, a prostacyclin generation stimulator. We aimed at determining in vitro if cicletanine can protect the ischemic myocardium from excitation-conduction blocks and specifically those induced by terfenadine. In a double-chamber bath, isolated guinea pig ventricular strips were partly exposed to normoxia and partly to ischemic, then reperfused, conditions, in the presence of 10 microM terfenadine, 10 microM indomethacin (prostacyclin generation blocker) or the solvent (dimethylsulfoxide 1:100, control) randomly allocated, and thus either in the absence (n=20) or presence (n=21) of 10 microM cicletanine during the total protocol duration. The multivariate Cox's model was used to predict the excitation-conduction block events and to assess the estimated survival of preparations (excitation-conduction block-free rate). Cicletanine protected the preparations (relative risk=0.08, t=-3.28) from the ischemia-induced excitation-conduction blocks (estimated survival=0.83 versus 0.30 in control), and this effect was abolished by indomethacin (estimated survival=0.35). Terfenadine enhanced 3. 58-fold the risk of occurrence of excitation-conduction blocks during ischemia (t=2.10) and this effect was inhibited by cicletanine pretreatment (estimated survival=0.40 versus 0.10 in untreated preparations). In conclusion, these in vitro findings have provided evidence for (1) protective effects of cicletanine against ischemia-induced excitation-conduction blocks, possibly related to its stimulating activity on local prostacyclin generation, and (2) efficacy of cicletanine to prevent excitation-conduction blocks induced by terfenadine in ischemic cardiac tissue.