Search

Objectives: To assess the efficacy of reoperative frozen elephant trunk (FET) surgery for treating residual type A aortic dissections., Methods: Between 04/2015 and 10/2023, 237 patients underwent elective redo surgical aortic arch replacement via the FET technique to treat residual type A aortic dissection in eleven European aortic centres. Data were pooled and analysed retrospectively., Results: The time between an acute type A dissection repair to FET implantation was 5 [1, 9] years. More than half of all patients (54%) presented with an entry within the aortic arch, and 174 patients (73%) presented residual dissections of supra-aortic vessels During FET repair, the axillary artery was cannulated in 181 patients (76%), while 83 patients (35%) underwent additional cardiac procedures including 39 root replacements (16%) and 15 coronary bypass procedures (6%). Zone 2 was the most common arch anastomosis site (n = 163, 69%) and bilateral antegrade cerebral perfusion was most frequent (n = 159, 67%). Fifteen patients (6%) suffered in-hospital mortality. Age in years (p < 0.001, OR: 1.069) proved to be predictive for overall mortality in our COX regression model., Conclusions: Elective redo surgical aortic arch replacement using the FET technique for treating residual type A aortic dissection following ascending aortic replacement revealed a favourable outcome. The decision to undertake stage-two therapy of a residually dissected aortic arch should be made by an aortic team on a patient-by-patient basis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background and Objectives: The predictive value of changes in C-reactive protein (CRP), procalcitonin, and leukocyte levels, which are commonly used in the diagnosis of infection in sepsis and septic shock, remains a topic of debate. The aim of this study was to evaluate the effectiveness of changes in CRP, procalcitonin, and leukocyte counts on the prognosis of 230 patients admitted to the intensive care unit (ICU) with the diagnosis of sepsis and pneumonia-related septic shock between 1 April 2022 and 31 December 2023, and to investigate whether any of these markers have a superior predictive value over the others in forecasting prognosis. Materials and Methods: This single-center, retrospective, cross-sectional observational study included patients who developed sepsis and septic shock due to community-acquired pneumonia and were admitted to the ICU. Demographic data, 1-month and 90-day mortality rates, length of stay in the ICU, discharge to the ward or an outside facility, need for dialysis after sepsis, need for invasive or noninvasive mechanical ventilation during the ICU stay and the duration of this support, whether patients admitted with sepsis or septic shock required inotropic agent support during their stay in the ICU and whether they received monotherapy or combination therapy with antibiotics during their admission to the ICU, the Comorbidity Index score (CCIS), CURB-65 score (confusion, uremia, respiratory rate, BP, age ≥ 65), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score were analyzed. Additionally, CRP, procalcitonin, and leukocyte levels were recorded, and univariate and multivariate logistic regression analyses were performed to evaluate their effects on 1- and 3-month mortality outcomes. In all statistical analyses, a p -value of <0.05 was accepted as a significant level. Results: According to multivariate logistic regression analysis, low BMI, male gender, and high CCIS, CURB-65, and APACHE-II scores were found to be significantly associated with both 1-month and 3-month mortality ( p < 0.05). Although there was no significant relationship between the first-day levels of leukocytes, CRP, and PCT and mortality, their levels on the third day were observed to be at their highest in both the 1-month and 3-month mortality cases ( p < 0.05). Additionally, a concurrent increase in any two or all three of CRP, PCT, and leukocyte values was found to be higher in patients with 3-month mortality compared with those who survived ( p = 0.004). Conclusions: In patients with pneumoseptic or pneumonia-related septic shock, the persistent elevation and concurrent increase in PCT, CRP, and leukocyte values, along with male gender, advanced age, low BMI, and high CCIS, CURB-65, and APACHE-II scores, were found to be significantly associated with 3-month mortality.

We provide an audio-visual step-by-step guide to the preparation of a donor heart for the application of normothermic, ex situ cardiac perfusion on the TransMedics Organ Care System using a heart donated after brain death. The use of the Organ Care System increases heart transplantation activity by enabling the utilization of hearts donated after circulatory death, the use of extended criteria grafts and the extension of out-of-body time, which can help overcome geographic or surgical barriers. Ex situ cardiac perfusion is a new technique and is therefore not yet routinely performed in many centres. However, it can be assumed that this technique will become more established and widespread in the future. Our video tutorial, which summarizes all important steps, can therefore be of benefit to surgical teams for planning, training or as a refresher., (© The Author 2024. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: We aim to evaluate the impact of antegrade stenting of the distal arch and proximal descending aorta combined with non-total arch procedures in acute type A aortic dissection., Methods: From 2005 to 2022, 733 nonsyndromic patients presented with acute DeBakey type I aortic dissection and underwent non-total arch procedure. Ninety-five patients underwent antegrade stenting and 638 did not. Propensity-score analysis was performed, and 95 optimal pairs were created. Survival was estimated using the Kaplan-Meier method and cumulative incidence of reintervention with death as a competing event was calculated and compared using Gray's method., Results: Survival estimates at 10 years after propensity score matching were similar between both groups, 58.9% (95% CI, 46.5%-74.5%) vs 58.4% (95% CI, 48.3%-70.6%) (P = .6) in the non-stented vs stented group. Cumulative incidence of reintervention with competing risk of death at 10 years after propensity matching was 27% (95% CI, 17%-37%) vs 22% (95% CI, 14%-32%) (P = .44), respectively., Conclusions: Antegrade thoracic endovascular aortic repair may be beneficial for remodeling and facilitating future endovascular reinterventions and reduces the occurrence of reintervention for malperfusion., Competing Interests: Disclosures Joseph E. Bavaria reports a relationship with WL Gore and Associates that includes: consulting or advisory; with Abbott that includes: consulting or advisory; with Edwards Lifesciences Corporation that includes: consulting or advisory; with Medtronic Inc that includes: consulting or advisory; and with Terumo Aortic that includes: consulting or advisory. Wilson Y. Szeto reports a relationship with Terumo Aortic that includes: consulting or advisory and speaking and lecture fees; with Medtronic Inc that includes: consulting or advisory and speaking and lecture fees; with Edwards Lifesciences Corporation that includes: consulting or advisory and speaking and lecture fees; and with Artivion, Inc. that includes: consulting or advisory and speaking and lecture fees. Nimesh D. Desai reports a relationship with Terumo Aortic that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Mitral valve regurgitation and left ventricular dysfunction are cardiovascular symptoms of Marfan syndrome. There is a paucity of information on tricuspid valve regurgitation and right ventricular function. In patients with Marfan syndrome, we looked at long-term changes in right ventricular function, tricuspid valve regurgitation and freedom from tricuspid valve repair., Methods: Retrospective-observational single-centre analysis on right ventricular function and tricuspid regurgitation in Marfan patients who underwent surgery with cardioplegic arrest between 1995 and 2020. Patients were followed-up from 1st operation until death, with echocardiographic changes analysed longitudinally. Composite end point was tricuspid annular plane systolic excursion (TAPSE) ≤16 mm, severe tricuspid regurgitation or tricuspid repair., Results: The study included 135 patients who underwent 193 operations, 58 of those were reoperations in 40 patients. Median age at 1st operation was 35 years [interquartile range (IQR) 26-46], median follow-up was 8.0 years (IQR 3.0-16.0) and median time to 1st reoperation was 7.5 years (IQR 3.4-12.5). The composite end point occurred in 81 observations in 40 patients, mostly as a recurrent event, after median 7.0 years (IQR 1.0-13.0). Ten-year cumulative incidence for composite end point was 22.0% (95% CI 15-31) and 9.0% (95% CI 4.4-16) for new-onset TAPSE ≤16 mm, but no significant change in TAPSE was observed at 10 years. Tricuspid regurgitation was associated with increased risk of annual progression (P < 0.001), but not clinically relevant at 10 years. Actuarial 10-year survival was 91.1%., Conclusions: In Marfan patients with a history of cardiac surgery and subsequent reoperations, the right ventricular function remains stable. The incidence of severe tricuspid regurgitation and tricuspid repair remain low., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: For patients with type A aortic dissection complicated by mesenteric malperfusion syndrome, some centers advocate a nontraditional approach based on up-front endovascular intervention and delayed open repair. However, the efficacy of this strategy cannot be understood without first understanding outcomes of the traditional open-first strategy in the same select patient population eligible for delayed repair, applying modern techniques of hybrid aortic surgery., Methods: Patients with acute type A aortic dissection and mesenteric malperfusion syndrome were queried from a single institution. Those presenting with aortic rupture, tamponade, or cardiogenic shock (ineligible for delayed repair) were excluded. Patients were managed with immediate open aortic repair. Short-term and long-term outcomes are reported., Results: A total of 1228 patients were treated for acute type A dissection in the study period, of whom 77 were included in the mesenteric malperfusion syndrome cohort. In-hospital mortality was 29% compared with 39% in an identically selected mesenteric malperfusion syndrome population undergoing delayed repair reported previously. Among patients with mesenteric malperfusion syndrome, 32% underwent additional procedures addressing distal malperfusion in a hybrid operating room during or after open repair. Concomitant proximal malperfusion (coronary, cerebral, or upper extremity) was common in the mesenteric malperfusion syndrome cohort, present in 35% of cases. Although early mortality was greater in the mesenteric malperfusion syndrome cohort compared with all acute type A dissections, 10-year survival among those discharged alive was similar (65% vs 59%, P = .18)., Conclusions: The traditional open-first repair strategy performs equal to or better than the delayed repair strategy for patients with mesenteric malperfusion syndrome eligible for delayed repair., Competing Interests: Conflict of Interest Statement J.E.B. and N.D.D.: consultants for Gore Medical and Terumo Aortic. W.Y.S.: speaker, investigator, and advisory board member for Edwards Lifesciences, Medtronic, Abbott Laboratories, Terumo Aortic, and Artivion Inc. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to report on mid-term outcomes after endovascular aortic repair (EVAR) in patients with Marfan (MFS) or Loeys-Dietz (LDS) syndrome., Methods: We analysed data from 2 European centres of patients with MFS and LDS undergoing EVAR. Patients were analysed based on (i) timing of the procedure (planned versus emergency procedure) and (ii) the nature of the landing zone (safe versus non-safe). The primary end-point was freedom from reintervention. Secondary end-points were freedom from stroke, bleeding and death., Results: A population of 419 patients with MFS (n = 352) or LDS (n = 67) was analysed for the purpose of this study. Thirty-nine patients (9%) underwent EVAR. Indications for thoracic endovascular aortic repair or EVAR were aortic dissection in 13 (33%) patients, aortic aneurysm in 22 (57%) patients and others (intercostal patch aneurysm, penetrating atherosclerotic ulcer, pseudoaneurysm, kinking of frozen elephant trunk (FET)) in 4 (10%) patients. Thoracic endovascular repair was performed in 34 patients, and abdominal endovascular aortic repair was performed in 5 patients. Mean age at 1st thoracic endovascular aortic repair/EVAR was 48.5 ± 15.4 years. Mean follow-up after 1st thoracic endovascular aortic repair/EVAR was 5.9 ± 4.4 years. There was no statistically significant difference in the rate of reinterventions between patients with non-safe landing zone and the patients with safe proximal landing zone (P = 0.609). Furthermore, there was no increased probability for reintervention after planned endovascular intervention compared to emergency procedures (P = 0.916). Mean time to reintervention, either open surgical or endovascular, after planned endovascular intervention was in median 3.9 years (95% confidence interval 2.0-5.9 years) and 2.0 years (95% confidence interval -1.1 to 5.1 years) (P = 0.23) after emergency procedures., Conclusions: EVAR in patients with MFS and LDS and a safe landing zone is feasible and safe. Endovascular treatment is a viable option when employed by a multi-disciplinary aortic team even if the landing zone is in native tissue., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Implantation of radiopaque markers during aortic root surgery might possibly facilitate upcoming coronary angiography or transcatheter aortic valve implantation. Aim of this study was to report the impact of surgically placed radiopaque markers on procedural characteristics and on angiographic outcomes., Methods: We retrospectively analyzed baseline characteristics, preoperative and postoperative data as well as procedural findings. In addition, a subgroup analysis of all patients who underwent coronary angiography after aortic root surgery was performed to report radiation time and contrast media used., Results: A total of 469 patients underwent aortic root surgery between January 2008 and April 2020. Patients were divided into two groups: group w/ markers (n = 182) and group w/o markers (n = 287). A propensity score matching was performed resulting in a total of 28 patients w/ markers and 28 patients w/o markers. Aortic cross-clamp time did not differ statistically significantly between the group w/o markers and the group w/ markers (124.0 [96.0-150.0] versus 123.0 [110.0-149.0] min, p = 0.09). There was no increased probability for requirement of postoperative angiography in the group w/o markers compared to the group w/ markers (11.8% versus 15.4%, p = 0.27). There was no statistically significant difference in the radiation time 5.5 [3-6.5] versus 5 [2.5-7.5] min, p = 0.62) nor in the amount of contrast media used (85 [77.5-100] versus 80 [60-90] ml, p = 0.07)., Conclusions: Surgically placed radiopaque markers during aortic root surgery do not increase operative risk and have the potential for facilitating secondary diagnostic and therapeutic interventions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: The aim of this study was to determine the outcome of Stanford type B aortic dissection in patients with Marfan syndrome (MFS) and to evaluate aortic diameters at time of dissection as well as the impact of previous aortic root replacement., Methods: Analysis of all patients with MFS fulfilling Ghent criteria seen at this institution since 1995 until 2022., Results: Thirty-six (19%) out of 188 patients with MFS suffered from Stanford type B aortic dissection during the study period. The Mean aortic diameter at the time of dissection was 39.0 mm [95% confidence interval (CI): 35.6-42.3]. The mean pre-dissection diameter (available in 25% of patients) was 32.1 mm (95% CI: 28.0-36.3) and the mean expansion was 19% (95% CI: 11.9-26.2). There was no correlation between age and diameter at the time of dissection (<20, 21-30, 31-40, 41-50, 51-60, <61 years; P = 0.78). Freedom from intervention after dissection was 53%, 44% and 33% at 1, 5 and 10 years. Aortic growth rate in those patients that had to undergo intervention within the 1st year after dissection was 10.2 mm/year (95% CI: 4.4-15.9) compared to 5.8 mm/year (95% CI: 3.3-8.3, P = 0.109) in those thereafter. The mean time between dissection and intervention was 1.8 years (95% CI: 0.6-3.0). While type B dissection seems more frequent after previous elective aortic repair (58% vs 42%), there was no difference between valve-sparing root replacement (VSRR) compared to Bentall procedures [Hazard ratio (HR) for VSRR 0.78, 95% CI: 0.31-2.0, P-value = 0.61]. The mean age of the entire population at the end of follow-up was 42 years (95% CI: 39.2-44.7). The mean follow-up time was 9 years (95% CI: 7.8-10.4)., Conclusions: Stanford type B dissection in patients with MFS occurs far below accepted thresholds for intervention. Risk for type B dissection is present throughout lifetime and two-thirds of patients need an intervention after dissection. There is no difference in freedom from type B dissection between a Bentall procedure and a VSRR., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The prevalence and aetiology of acute aortic dissection type A (AADA) in patients ≤30 years is unknown. The aims of this clinical study were to determine the prevalence and potential aetiology of AADA in surgically treated patients ≤30 years and to evaluate the respective postoperative outcomes in this selective group of patients in a large multicentre study., Methods: Retrospective data collection was performed at 16 participating international aortic institutions. All patients ≤30 years at the time of dissection onset were included. The postoperative results were analysed with regard to connective tissue disease (CTD)., Results: The overall prevalence of AADA ≤30 years was 1.8% (139 out of 7914 patients), including 51 (36.7%) patients who were retrospectively diagnosed with CTD. Cumulative postoperative mortality was 8.6%, 2.2% and 1.4%. Actuarial survival was 80% at 10 years postoperatively. Non-CTD patients (n = 88) had a significantly higher incidence of arterial hypertension (46.6% vs 9.8%; P < 0.001) while AADA affected the aortic root (P < 0.001) and arch (P = 0.029) significantly more often in the CTD group. A positive family history of aortic disease was present in 9.4% of the study cohort (n = 13)., Conclusions: The prevalence of AADA in surgically treated patients ≤30 years is <2% with CTD and arterial hypertension as the 2 most prevalent triggers of AADA. Open surgery may be performed with good early results and excellent mid- to long-term outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Neuroprotection during aortic arch surgery involves selective antegrade cerebral perfusion. The parameters of cerebral perfusion, e.g. flow rate, are inconsistent across centres and are subject of debate. The aim of this study was to determine the cerebral perfusion flow rate during hypothermic circulatory arrest required to meet preoperative awake baseline regional cerebral oxygen saturation (rSO2)., Methods: Patients scheduled for aortic arch surgery with hypothermic circulatory arrest were enrolled in this prospective observational study. After initiation of hypothermic circulatory arrest, bilateral selective antegrade cerebral perfusion was established and cerebral flow rate was continuously increased. The primary end point was the difference of cerebral saturation from baseline during cerebral perfusion flow rates of 6, 8 and 10 ml/kg/min., Results: A total of 40 patients were included. During antegrade cerebral perfusion, rSO2 was significantly lower than the baseline at 6 ml/kg/min [-7.3, 95% confidence interval (CI): -1.7, -12.9; P = 0.0015]. In contrast, flow rates of 8 and 10 ml/kg/min resulted in rSO2 that did not significantly differ from the baseline (-2; 95% CI: -4.3, 8.3; P > 0.99 and 1.8; 95% CI: -8.5%, 4.8%; P > 0.99). Cerebral saturation was significantly more likely to meet baseline values during selective antegrade cerebral perfusion with 8 ml/kg/min than at 6 ml/kg/min (44.1%; 95% CI: 27.4%, 60.8% vs 11.8%; 95% CI: 0.9%, 22.6%; P = 0.0001)., Conclusions: At 8 ml/kg/min cerebral flow rate during selective antegrade cerebral perfusion, regional cerebral oximetry baseline values are significantly more likely to be achieved than at 6 ml/kg/min. Further increasing the cerebral flow rate to 10 ml/kg/min does not significantly improve rSO2., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The aim of this study was to explore sex and gender differences regarding aortic events in Marfan patients., Methods: We analysed all data from our connective tissue disorder database. Only patients with Marfan syndrome were included. For analysis, patients were divided by sex. Female patients were further divided into 2 subgroups: with versus without children. Aortic events were defined as Stanford type A aortic dissection (TAAD) or type B aortic dissection (TBAD) or any aortic intervention., Results: A population of 183 Marfan patients was analysed for the purpose of this study. One hundred four (57%) were male and 79 (43%) were female patients. Thirty-seven (47%) of the 79 female patients had at least 1 child. Male patients had a significantly higher probability of experiencing an aortic event (P = 0.015) compared to female patients. However, there was no increased probability for recurrent events in male patients compared to female patients (P = 0.063). Follow-up revealed no sex and gender differences in the occurrence of Stanford TAAD or TBAD between male and female patients (P = 0.324/P = 0.534). While 11% of women with children suffered from peripartum aortic events, 24% experienced Stanford TAAD unrelated to pregnancy., Conclusions: Male patients have a higher risk of aortic events than female patients. The majority of women were not aware of their Marfan syndrome diagnosis before conceiving. One out of 10 women suffered from peripartum Stanford TAAD or TBAD. Twice as many female patients with children suffered from aortic dissection unrelated to childbirth. There were no sex and gender differences affecting mortality in Marfan patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Abstract: We aimed to determine the parameters that affect mortality in pulmonary intensive care units that are faster and inexpensive to determine than existing scoring systems. The relationship between serum osmolarity and prognosis was demonstrated for predialysis patients, in acute pulmonary embolism, heart failure, acute coronary syndrome, myocardial infarction, and acute spontaneous intracerebral hemorrhage in the literature. We hypothesized that serum osmolarity, which is routinely evaluated, may have prognostic significance in patients with respiratory failure.This study comprised 449 patients treated in the Pulmonary Intensive Care Clinic (PICU) of our hospital between January 1, 2020, and December 31, 2020. The modified Charlson Comorbidity Index (mCCI), Acute Physiology and Chronic Health Assessment (APACHE II), Sequential Organ Failure Evaluation Score (SOFA), Nutrition Risk Screening 2002 (NRS-2002), and hospitalization serum osmolarity levels were measured.Of the 449 patients included in the study, 65% (n = 292) were female and the mean age of all patients was 69.86 ± 1.72 years. About 83.1% (n = 373) of the patients included in the study were discharged with good recovery. About 4.9% (n = 22) were transferred to the ward because their intensive care needs were over. About 6.9% (n = 31) were transferred to the tertiary intensive care unit after their status deteriorated. About 5.1% (n = 23) died in the PICU. In the mortality group, APACHE II (P = .005), mCCI (P < .001), NRS-2002 total score (P < .001), and SOFA score (P < .001) were significantly higher. There was no statistically significant difference between the groups in terms of serum osmolarity levels.Although we could not determine serum osmolarity as a practical method to predict patient prognosis in this study, we assume that our results will guide future studies on this subject., Competing Interests: No conflict of interest was declared by the authors., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Magnesium deficiency is defined as a pathophysiologic factor in numerous illnesses. This study aims to define the effects of magnesium levels on patients in the intensive care unit (ICU) regarding length of stay in the ICU, length of mechanical ventilation (MV), and 28-day mortality.The following data were collected during initial assessment of patients admitted to the ICU with acute respiratory failure (ARF). Demographic data, magnesium and potassium levels, Charlson's Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, length of MV, length of hospital stay in the ICU, 28-day mortality, and ICU discharge status.In the initial serum analysis prior to treatment of patients in the ICU, the mortality rate of the patient group with hypermagnesemia was found to be statistically significant when compared with other magnesium levels (P = .018). Apart from renal failure, ICU mortality is higher in the hypermagnesemia group than other groups.Hypermagnesemia is an electrolyte abnormality that is generally seen in older individuals and those with serious comorbidity and it can be used in mortality prediction., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The goal of this study was to report the long-term outcomes of patients with Marfan syndrome who had aortic surgery on any aortic segment except for the replacement of the aortic root itself., Methods: An observational retrospective single-centre study was conducted with 115 Marfan syndrome patients who underwent 189 major aortic interventions from 1995 until 2018. Patients without aortic root replacement were identified and aortic root growth was analysed over time., Results: Eleven of 115 patients (9.5%) did not have aortic root replacement during a follow-up of 10.5 [standard deviation (SD) 5.7] years and a mean age at last follow-up of 53.9 (SD 13.4) years. Patients without root replacement did not suffer less frequently from any type of acute aortic dissection (type A 27% vs 25%, P = 0.999; type B 36% vs 25%, P = 0.474). Patients with native aortic roots did not undergo fewer aortic interventions than those with aortic root replacement [12/11, mean 1.09 (SD 0.54) operations/patient vs 177/104, mean 1.7 (SD 1.3); P = 0.128]. Progression of the aortic root dimension was 0.5 (SD 0.3) mm/year in the group of patients with native aortic roots., Conclusions: Current data suggest that 10% of patients with Marfan syndrome with previous aortic surgery will be free from aortic root replacement until the sixth decade of life., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

In this study, we carried out with the DTP (dithieno(3,2-b:2,3-d) pyrrole) molecule which is a member of the conductive polymer class that is one of the topics that have been studied prevalently in recent times, and the density functional theory's (DFT) calculation methods were used to shed light on the sensor mechanisms of its interactions with SOx (SO 2 and SO 3 ) sulfur oxides. The changes in the geometric and electronic characteristics of a sensor mechanism designed with the DTP molecule when it encountered sulfur oxides were examined. With these changes, the usability of DTP as a sensor material was proven. DTP sensor applications using this method were not investigated in previous studies. The B3LYP 6-31 G(d) levels of DFT were used in the calculations. In the calculations, during the interaction between analyte (SO 2 -SO 3 ) and the conductive polymer DTP (dithieno(3,2-b:2,3-d) pyrrole), especially, the changes in its geometric and electronic structures were observed. With these changes that were observed in the geometric structure, as a result of the interaction between the conductive polymer and gas molecules, the resistance on the polymer's main chain decreased, and conductivity increased. Calculations on the bandgap on HOMO-LUMO energy levels were observed to decrease. Thus, the structural conductivity of the molecule increased. Additionally, the experiments showed that, as a result of interaction with gas molecules, the bandgap in the ionization potential, electron affinity, and HOMO-LUMO energy levels varied. These variations showed the detection mechanisms for sulfur oxides by the DTP (dithieno(3,2-b:2,3-d) pyrrole) molecule that may be used to design sensors.

Objectives: The aim of this study was to investigate the fate of nonaortic arterial segments in patients with Marfan syndrome (MFS)., Methods: This was a retrospective analysis of 100 consecutive patients with MFS fulfilling Ghent criteria who underwent 192 interventions on any segment of the arterial tree and were followed over the past 20 years. A review of the available imaging regarding 9 defined regions of interest of the carotid, innominate, subclavian, iliac, and femoral arteries was performed., Results: Mean follow-up interval was 11.6 ± 7.7 years. Of 600 measurements that were performed, 414 (69%) arterial segments showed dilatation above the upper range of normal. There were no significant sex differences. In 100 patients, 66 dissections in nonaortic arterial segments in 33 patients were identified. Nineteen patients with or without previous dissection underwent 34 interventions. Most interventions were performed on the iliac arteries (56%), followed by the subclavian arteries (21%), the intercostal arteries (9%), the carotid arteries (6%), the visceral arteries (6%), and the innominate artery (3%). Most iliac artery interventions (88%) were caused by dilatations due to previous dissections, whereas this was only the case in 17% of interventions on the subclavian arteries., Conclusions: Most patients with MFS presented with at least 2 dilated nonaortic arterial segments. The current data suggest that 20% of MFS patients will need some form of intervention on nonaortic arterial segments 5 to 6 years after their first aortic intervention, referring to the first aortic dissection of the patient if the patient had a history of dissection. Routine long-term follow-up imaging should include the iliac arteries as well as the supra-aortic branches., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Ischemia-modified albumin (IMA) is a marker which can be associated with oxidative stress in various ischemic and non-ischemic processes. Oxidative stress plays roles in diabetes mellitus, its complications and pathogenesis. Serum IMA levels are examined in various clinical events. However, urine IMA levels have not yet been evaluated in diabetic patients. In this study, we aim to examine the relationship between metabolic features and urine microalbuminuria levels of diabetic patients and their urine IMA levels., Materials and Methods: There were totally 50 type 2 diabetic patients in the study at the Mevlana University Hospital. Patients with cerebrovascular disease, acute myocardial infarction, hemodialysis patients with end stage chronic renal failure, pulmonary embolism, and malignant disease were excluded from the study. Metabolic features, urine IMA levels and cardiological parameters of patients were evaluated., Results: Mean age of patients was 59 ± 9 years, 20 of them (40%) were male and 30 of them (60%) were female. There were six patients with albuminuria value of <0.03 mg/g (normal), there were 39 patients with microalbuminuria value of 0.03-0.3 mg/g and there were five patients with macroalbuminuria of >0.3 mg/g. According to the analysis of patients with microalbuminuria (n = 39), there was no correlation between IMA levels and numerical demographic data, albuminuria, glucose, HbA1c, lipid profile, creatinine, uric acid, hematological parameters., Discussion: Conclusively, there was no relationship between urine IMA levels and microalbuminuria related to the diabetic nephropathy. These findings can be associated with urinary excretion mechanisms of IMA., (© 2016 The Authors Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

The compression index and recompression index are one of the important compressibility parameters to determine the settlement calculation for fine-grained soil layers. These parameters can be determined by carrying out laboratory oedometer test on undisturbed samples; however, the test is quite time-consuming and expensive. Therefore, many empirical formulas based on regression analysis have been presented to estimate the compressibility parameters using soil index properties. In this paper, an artificial neural network (ANN) model is suggested for prediction of compressibility parameters from basic soil properties. For this purpose, the input parameters are selected as the natural water content, initial void ratio, liquid limit and plasticity index. In this model, two output parameters, including compression index and recompression index, are predicted in a combined network structure. As the result of the study, proposed ANN model is successful for the prediction of the compression index, however the predicted recompression index values are not satisfying compared to the compression index.

Purpose: To determine the predictability of gestational diabetes mellitus (GDM) during the first trimester using the degree of insulin resistance and anthropometric measurements and to assign the risk of developing GDM by weight gained during pregnancy (WGDP)., Methods: A total of 250 singleton pregnancies at 7-12 gestational weeks were studied. Body mass index (BMI), waist/hip ratio (WHR), quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment-insulin resistance (HOMA-IR) scores and WGDP were determined. The backward stepwise method was applied to estimate possible associations with GDM. Cutoff points were estimated using receiver operating characteristic curve analysis., Results: GDM was found in 20 of 227 singleton pregnancies (8.8 %). The calculated HOMA-IR, QUICKI, BMI, WHR, WGDP, and parity were significantly associated with GDM. Logistic regression analyses showed that three covariates (HOMA-IR, BMI, WGDP) remained independently associated with GDM. It was calculated as OR 1.254 (95 % CI 1.006-1.563), AUC 0.809, sensitivity 90 %, specificity 61 % with cutoff = 2.08 for HOMA-IR; OR 1.157 (CI 1.045-1.281), AUC 0.723, sensitivity 80 %, specificity 58 % with cutoff = 25.95 for BMI; OR 1.221, (CI 1.085-1.374), AUC 0.654, sensitivity 80 %, specificity 46 % with cutoff = 4.7 for WGDP. Despite a HOMA-IR score of >3.1 in pregnant women, GDM was detected in only three of 29 patients (10.3 %) if WGDP was <4.7 kg at weeks 24-28., Conclusions: First trimester screening for GDM can be achieved based on maternal anthropometric measurements and HOMA-IR. In particular, if BMI is >25.95 kg/m(2) and the HOMA-IR score >2.08, controlling weight gain may protect against GDM.

Fibromyalgia syndrome (FMS), usually observed commonly in females over age 30, is a rheumatic disease accompanied by extensive chronic pain. In the diagnosis of the disease non-objective psychological tests and physiological tests and laboratory test results are evaluated and clinical experiences stand out. However, these tests are insufficient in differentiating FMS with similar diseases that demonstrate symptoms of extensive pain. Thus, objective tests that would help the diagnosis are needed. This study analyzes the effect of sympathetic skin response (SSR) parameters on the auxiliary tests used in FMS diagnosis, the laboratory tests and physiological tests. The study was conducted in Suleyman Demirel University, Faculty of Medicine, Physical Medicine and Rehabilitation Clinic in Turkey with 60 patients diagnosed with FMS for the first time and a control group of 30 healthy individuals. In the study all participants underwent laboratory tests (blood tests), certain physiological tests (pulsation, skin temperature, respiration) and SSR measurements. The test data and SSR parameters obtained were classified using artificial neural network (ANN). Finally, in the ANN framework, where only laboratory and physiological test results were used as input, a simulation result of 96.51 % was obtained, which demonstrated diagnostic accuracy. This data, with the addition of SSR parameter values obtained increased to 97.67 %. This result including SSR parameters - meaning a higher diagnostic accuracy - demonstrated that SSR could be a new auxillary diagnostic method that could be used in the diagnosis of FMS.

Objective: To evaluate the thickness of the peripapillary retinal fiber layer (RNFL) and macula ganglion cell-inner plexiform layer (GCL+) using optical coherence tomography (OCT) in patients with iron deficiency (ID) anemia., Methods: This study included 73 eyes of 39 patients with ID anemia and 68 eyes of 34 age- and sex-matched healthy subjects. The measurements included the peripapillary RNFL thicknesses as average, 4 quadrant and 12 clock-hour (CH) based and macula GCL+ thicknesses as average and 6 quadrant based. All measurements were completed with Cirrus HD-OCT and the results were compared between the groups., Results: A total of 73 eyes of 39 patients with ID anemia and 68 eyes of 34 healthy subjects were included to the study. Regarding peripapillary RNFL thicknesses of the study and control patients, the values of average and quadrants revealed no significant differences between the groups. In CH sectors comparison, peripapillary RNFL thicknesses were significantly decreased only in CH4 (68.7 ± 14.5 μm in study versus 72.0 ± 13.4 μm in control patients, p = 0.049) and CH5 (93.4 ± 20.0μm in study versus 102.2 ± 20.1 μm in control patients, p = 0.01) sectors. All measured quadrants were statistically similar, when macula GCL+ thicknesses were compared between the groups. When the correlations between peripapillary RNFL and macula GCL+ thicknesses and serum hemoglobin and ferritin levels of study and control patients were calculated, the only statistically significant parameter was the correlation of peripapillary RNFL thickness in CH10 sector with serum ferritin level (p = 0.032, Spearman correlation coefficient: 0.369)., Conclusion: The study revealed that peripapillary RNFL is thinner in nasal-inferior quadrant in patients with ID anemia. The measurements of macula GCL+ thicknesses were similar between the groups. Analyzing the retinal layers using OCT may provide valuable information in neurodegenerative events.

Background: This study aimed to compare pantoprazole, a proton-pomp inhibitors (PPIs), and ranitidine, a H2 receptor antagonists (H2RA), in ceasing dyspeptic symptoms in the emergency department (ED)., Methods: This randomized, double-blinded study compared the effectiveness of 50 mg ranitidine (Ulcuran(®)) and 40 mg pantoprazole (Pantpas(®)), given in a 100 mL saline solution by an intravenous rapid infusion within 2-4 minutes in patients with dyspepsia presented to the ED. Pain intensity was measured at baseline, 30 and 60 minutes after the drug administration., Results: A total of 72 patients were eligible for the study. Of these patients, 2 were excluded from the study because the initial visual analogue scale (VAS) scores were under 20 mm and 4 were excluded from the statistical analysis because of being diagnosed as having other causes of epigastric pain despite being allocated to one of the study groups. Thirty-three patients in the pantoprazole group and 33 patients in the ranitidine group were analyzed ultimately. The mean age of the patients was 36.6±15 years, and 26 (39.4%) patients were male. Both of the groups reduced pain effectively at 30 [27.6±28 (18 to 37) vs. 28.3±23 (20 to 37), respectively] and 60 minutes [39.6±39 (26 to 53) vs. 42.3±25 (33 to 51), respectively]. There were 13 (39.4%) patients in the pantoprazole group and 8 (24.2%) patients in the ranitidine group who required additional drug at the end of the study (P=0.186)., Conclusion: Intravenous pantoprazole and ranitidine are not superior to each other in ceasing dyspeptic symptoms at 30 and 60 minutes in the ED.

Unlabelled: Cognitive impairment (CI) can be demonstrated in 40-65% of multiple sclerosis (MS) patients, sometimes starting from the early stages of the disease. The objective of this study was a community-based investigation of FLAIR-hyperintense lesion volumes (LV) and their association with CI in patients with relapsing remitting (RR) MS. The neurocognitive assessment was conducted with the brief cognitive screening instrument, MUSIC. Magnetic resonance imaging (MRI) scans were obtained with a 1.5 Tesla Sigma Magnetom MRI scanner. We conducted a stepwise multiple regression analysis to assess the relative contribution of the main clinical, demographic and MRI-variables in predicting cognitive impairment. We recruited 78 patients with RRMS. The mean MUSIC score was 20.6 ± 5.4. Forty five percent of patients (n = 35, mean score 15.1 ± 3.3) had CI and 55% (n = 43, mean score 24.4 ± 2.5) had no sign of CI. In the correlation analysis of the MUSIC subtests only the interference test correlated negatively with the LV (r = -0.23). Multivariate linear regression analysis using MUSIC as the dependent continuous variable revealed LV and disability severity as independent factors associated with MUSIC (p value of the regression model < 0.001; adjusted R-square = 0.11). The results of the present study suggest an association between white matter damage and CI in MS. We could demonstrate an association between attention difficulties and the LV in MS patients., Trial Registration: ClinicalTrials.gov Identifier: NCT01250665 and NCT01250678., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival., Methods and Findings: We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n = 52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3-123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61-2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCD = 0 (p = 0.04; hazard ratio 1.63, 95% CI 1.02-2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories., Conclusions: Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically.

Fatigue is one of the most debilitating symptoms in multiple sclerosis (MS). The aim of this study was to observe the severity of MS associated fatigue in a community-based sample of natalizumab (ntz) treated patients over one year. In 48 relapsing remitting MS patients (mean age=38.3 years) fatigue was longitudinally measured with the Modified Fatigue Impact Scale (MFIS) at two time points. The primary analysis of differences in MFIS was performed using non-parametric Wilcoxon test for dependent variables. Mean total MFIS Score increased significantly from 32.6±20.9 to 49.1±20.0 over the observation period of 12 months (p<0.001). 83% of patients remained clinically disease activity free (no relapse, no progression in the Expanded Disability Status Scale, EDSS) over the observation period of one year. Age, gender, disease duration, spinal involvement, Gd-enhancement, depressive symptoms and EDSS had no influence on fatigue levels as measured with MFIS. Severity of fatigue symptoms during ntz treatment might increase despite very low disease activity., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Fibromyalgia syndrome (FMS) is a chronic musculoskeletal disease which causes dysfunction of the autonomic nervous system. Sympathetic Skin Response (SSR) is a part of electrical impedance of body which is affected by the autonomic nervous system dysfunctions. In this study, values obtained from the results of the patients diagnosed with fibromyalgia syndrome, and healthy subjects blood samples in the laboratory conditions are recorded in Suleyman Demirel University, Faculty of Medicine, Department of Physical Medicine and Rehabilitation. SSR measurements are recorded from patients and healthy controls. Values of latency time, maximum amplitude and elapsed time between two stimulus parameters are obtained from recorded sympathetic skin response data by using Matlab software. The relationship between SSR parameters and laboratory tests is investigated by using artificial neural networks. As a result SSR seems to be a valid parameter in the classification of FMS.

Background: Vitamin D levels have not been previously published for Swiss multiple sclerosis (MS) patients. An association between vitamin D status and disease activity in MS has been suggested., Aim: To define 25-hydroxy-vitamin D (25(OH)D) levels in Swiss multiple sclerosis patients., Method: Cross sectional case control study., Results: 25(OH)D levels of 80 patients (76.3% female, mean age 37.9 ± 10.6 years, mean Expanded Disability Status Scale (EDSS) 2.6 ± 1.2) were collected. Mean levels of 25(OH)D were 57.0 ± 29.7 nmol/l (range 18-175 nmol/l) in all patients. A total of 21.3% of patients had levels ≤37 nmol/l and 75% had levels ≤70 nmol/l. 25(OH)D levels in patients with previous high disease activity were 52.8 ± 23.1 nmol/l versus 58.9 ± 32.3 nmol/l in the low disease activity group (p = 0.4)., Conclusion: The prevalence of 25(OH)D deficiency was high in Swiss MS patients.

Objective. Despite observations that abnormal parietal lobe (PL) function is associated with psychotic-like experiences, our knowledge about the nature of PL involvement in schizophrenia is modest. The objective of this paper is to investigate the role of the PL in schizophrenia. Method. Medline databases were searched for English language publications using the following key words: parietal lobe, combined with schizophrenia, lesions, epilepsy, cognition, rare genetic disorders, MRI, fMRI, PET, and SPECT, respectively, followed by cross-checking of references. Results. Imaging studies in childhood onset schizophrenia suggest that grey matter abnormalities start in parietal and occipital lobes and proceed to frontal regions. Although, the findings are inconsistent, several studies with patients at risk to develop schizophrenia indicate early changes in the PL. Conclusions. We want to propose that in a proportion of individuals with emerging schizophrenia structural and functional alterations may start in the PL and progress to frontal regions.

In this study, the points of Sympathetic skin response that can be measured from different zones on body of healthy and patient subjects are determined. The Sympathetic skin responses on these points are obtained using a measurement device that is called Grass Model 7 Polygraph 1. The database is formed in Cerrahpaşa University, Faculty of Medicine and data is taken from healthy and patient subjects who are volunteer. Some parameters of the subjects which are more effective on SSR such as height, weight, age must be chosen between the specific limits to obtain results more clearly. The symmetric points on human body are chosen for the measurement. After that, the Sympathetic skin response values which are measured from a human body are simulated and tested by using artificial neural network toolbox on Matlab software. The structure of the chosen neural network is a multilayer feedforward neural network. According to simulation results, the application method as diagnosis-purposed of the lung cancer patients is explained by using the differences related to these values on the skin.

In this study, a method was proposed in order to determine how well features extracted from the EEG signals for the purpose of sleep stage classification separate the sleep stages. The proposed method is based on the principle component analysis known also as the Karhunen-Loéve transform. Features frequently used in the sleep stage classification studies were divided into three main groups: (i) time-domain features, (ii) frequency-domain features, and (iii) hybrid features. That how well features in each group separate the sleep stages was determined by performing extensive simulations and it was seen that the results obtained are in agreement with those available in the literature. Considering the fact that sleep stage classification algorithms consist of two steps, namely feature extraction and classification, it will be possible to tell a priori whether the classification step will provide successful results or not without carrying out its realization thanks to the proposed method.

For both, cardioplegia (CP) and ischemic preconditioning (IP), increased ischemic tolerance with reduction in infarct size is well documented. These cardioprotective effects are related to a limitation of high energy phosphate (HEP) depletion. As CP and IP have to be assumed to act by different mechanisms, their effects on myocardial HEP metabolism cannot be assumed to be identical. Therefore, a systematic analysis of myocardial HEP metabolism for both procedures and their combination was performed, addressing the question whether there are different effects on myocardial HEP metabolism by IP and CP. In this study, metabolic control analysis was used to analyze the regulation of HEP metabolism. In open chest pigs subjected to 45 min LAD occlusion (index ischemia), CP and IP preserved myocardial ATP (control (C) 0.14 +/- 0.05 micromol/g wwt; CP: 0.95 +/- 0.14, IP: 0.61 +/- 0.12; p<0.05 C vs. CP and IP) and reduced myocardial necrosis (infarct size IA/RA: C: 90.0 +/- 3.0%; CP: 0.0 +/- 0.0% but patchy necroses; IP: 5.05 +/- 2.1%; p<0.05 C vs. CP and IP). The effects on HEP metabolism, however, were different: CP acted predominantly by slowing down the breakdown of phosphocreatine (PCr) during early phases of ischemia (C: DeltaPCr 0-2 min: 5.24 +/- 0.32 micromol/g wwt; CP: DeltaPCr 0-2 min: 3.38 +/- 0.23 micromol/g wwt, p<0.05 vs. C), leaving ATP breakdown during later stages unaffected (C: DeltaATP 5-45 min: 1.77 +/- 0.11 micromol/g wwt CP: DeltaATP 5-45 min: 1.59 +/- 0.28 micromol/g wwt, n.s. vs. C). In contrast to CP, in IP PCr breakdown was even increased (IP: DeltaPCr 0-2 min: 7.06 +/- 0.34 micromol/g wwt, p<0.05 vs. C), but ATP depletion greatly attenuated (IP: DeltaATP 5-45 min: 0.48 +/- 0.10 micromol/g wwt, p<0.05 vs. C and CP). Combining IP and CP yielded an additive effect with slowing down the breakdown of both PCr (IP+CP: DeltaPCr 0-2 min: 5.09+/- 0.35 micromol/g wwt, p<0.05 vs. C and IP) and ATP (IP+CP: DeltaATP 5-45 min: 0.56 +/- 0.48 micromol/g wwt, p<0.05 vs. C and CP), resulting in a higher ATP content at the end of index ischemia (1.86 +/- 0.46 micromol/g wwt, p<0.05 vs. C, CP and IP). Compared to IP, combining IP+CP achieved also a further reduction in infarct size (IA/RA: 0.0 +/- 0.0%, p<0.05 vs IP) and--compared to CP--a disappearance of the patchy necroses. The concept of major differences in myocardial HEP metabolism during CP and IP is further supported at a molecular level by metabolic control analysis. CP but not IP slowed down the CK reaction velocity at high PCr levels. In contrast to CP exerting a continuous decline in vATPase for any given ATP level, in IP myocardium ATPase reaction velocity was even increased at higher ATP contents, whereas a marked decrease in ATPase reaction velocity was found if ATP levels decreased. The equilibrium of the CK-reaction remained unchanged following CP, whereas IP induced a changing CK equilibrium, which was the more shifted towards PCr the more myocardial HEP content decreased. The data demonstrate different effects of CP and IP on myocardial HEP metabolism, i.e. PCr and ATP breakdown as well as the apparent equilibrium of the creatine kinase (CK)-reaction. For these reasons the combination of the two protective interventions has an additive effect.

Exact adjustment of the Embden-Meyerhof pathway (EMP) is an important issue in ischemic preconditioning (IP) because an attenuated ischemic lactate accumulation contributes to myocardial protection. However, precise mechanisms of glycolytic flux and its regulation in IP remain to be elucidated. In open chest pigs, IP was achieved by two cycles of 10-min coronary artery occlusion and 30-min reperfusion prior to a 45-min index ischemia and 120-min reperfusion. Myocardial contents in glycolytic intermediates were assessed by high performance liquid chromatographic analysis of serial myocardial biopsies under control conditions and IP. Detailed time courses of metabolite contents allow an in-depth description of EMP regulation during index ischemia using metabolic control analysis. IP reduced myocardial infarct size (control, 90.0 +/- 3.1 versus 5.05 +/- 2.1%; p < 0.001) and attenuated myocardial lactate accumulation (end-ischemic contents, 31.9 +/- 4.47 versus 10.3 +/- 1.26 micromol/wet weight, p < 0.0001), whereby a decrease in anaerobic glycolytic flux by at least 70% could constantly be observed throughout index ischemia. By calculation of flux:metabolite co-responses, the mechanisms of glycolytic regulation were investigated. The continuous deceleration of EMP flux in control myocadium could neither be explained on the basis of substrate availability nor be attributed to regulatory "key enzymes," as multisite regulation was employed for flux adjustment. In myocardium subjected to IP, an even pronounced deceleration of EMP flux during index ischemia was observed. Again, the adjustment of EMP flux was because of multisite modulation without any evidence for flux limitation by substrate availability or a key enzyme. However, IP changed the regulatory properties of most EMP enzymes, and some of these patterns could not be explained on the basis of substrate kinetics. Instead, other regulatory mechanisms, which have previously not yet been described for EMP enzymes, must be considered. These altered biochemical properties of the EMP enzymes have not yet been described.

In ischemia, the myocardial metabolic status determines the expansion of necrosis. Decreased ATP levels and increased lactate contents in ischemic myocardium undergoing lethal injury are known to be related to the expansion of irreversible damage. However, their individual contributions have not yet been firmly established. Using two differently effective protocols of ischemic preconditioning (IP short and IP long), ischemic cardioplegic arrest (CP) and their combination (IP+CP) to directly influence the metabolic status of porcine myocardium, graded preservations in ATP content and decreases in lactate accumulation during 45 min ischemia could be achieved (control: ATP, 0.15+/-0.03; lactate, 60.53+/-4.89 micromol/g wet weight; IP short, 0.33+/-0.10/27.42+/-3.90; IP long, 0.60+/-0.10/17.49+/-2.14; CP, 0.98+/-0.12/11.82+/-0.96; IP+CP, 2.24+/-0.28/10.88+/-0.89; all P<0.001 vs. control). At the same time, a graded reduction of myocardial necrosis was observed (90.0+/-3.1 vs. 31.7+/-4.55 vs. 5.05+/-2.1 vs. 0.0 [isolated patchy necroses] vs. none). Regression analysis revealed only a weak correlation of infarct size and ATP preservation (r=0.567). In fact, there was a biphasic relation: with ATP levels above 1 micromol/g wet weight, no infarction occurred. ATP levels below this threshold value were associated with steep increase in infarct size. However, even for this latter range, the regression coefficient remained low (r=0.654). Instead, over the entire range, there was a close, rectilinear correlation of infarct size and lactate accumulation (r=0.939). These data indicate that lactate accumulation rather than ATP depletion determines the development of lethal myocardial injury. However, the biphasic relation between ATP depletion and infarct size suggests the latter to play a permissive role, since above a threshold value of 1 micromol/g wet weight neither substantial lactate accumulation nor infarction was observed. Below this threshold, however, infarct size increased as lactate accumulated.