Ischemia time impacts on respiratory chain functions and Ca2+-handling of cardiac subsarcolemmal mitochondria subjected to ischemia reperfusion injury.

BACKGROUND: Mitochondrial impairment can result from myocardial ischemia reperfusion injury (IR). Despite cardioplegic arrest, IR-associated cardiodepression is a major problem in heart surgery. We determined the effect of increasing ischemia time on the respiratory chain (RC) function, the inner membrane polarization and Ca2+ homeostasis of rat cardiac subsarcolemmal mitochondria (SSM). METHODS: Wistar rat hearts were divided into 4 groups of stop-flow induced warm global IR using a pressure-controlled Langendorff system: 0, 15, 30 and 40 min of ischemia with 30 min of reperfusion, respectively. Myocardial contractility was determined from left ventricular pressure records (dP/dt, dPmax) with an intraventricular balloon. Following reperfusion, SSM were isolated and analyzed regarding electron transport chain (ETC) coupling by polarography (Clark-Type electrode), membrane polarization (JC1 fluorescence) and Ca2+-handling in terms of Ca2+-induced swelling and Ca2+-uptake/release (Calcium Green-5 N® fluorescence). RESULTS: LV contractility and systolic pressure during reperfusion were impaired by increasing ischemic times. Ischemia reduced ETC oxygen consumption in IR40/30 compared to IR0/30 at complex I-V (8.1 ± 1.2 vs. 18.2 ± 2.0 nmol/min) and II-IV/V (16.4 ± 2.6/14.8 ± 2.3 vs. 2.3 ± 0.6 nmol/min) in state 3 respiration (p < 0.01). Relative membrane potential revealed a distinct hyperpolarization in IR30/30 and IR40/30 (171.5 ± 17.4% and 170.9 ± 13.5%) compared to IR0/30 (p < 0.01), wearing off swiftly after CCCP-induced uncoupling. Excess mitochondrial permeability transition pore (mPTP)-gated Ca2+-induced swelling was recorded in all groups and was most pronounced in IR40/30. Pyruvate addition for mPTP blocking strongly reduced SSM swelling in IR40/30 (relative AUC, ± pyruvate; IR0/30: 1.00 vs. 0.61, IR15/30: 1.68 vs. 1.00, IR30/30: 1.42 vs. 0.75, IR40/30: 1.97 vs. 0.85; p < 0.01). Ca2+-uptake remained unaffected by previous IR. Though Ca2+-release was delayed for ≥30 min of ischemia (p < 0.01), Ca2+ retention was highest in IR15/30 (RFU; IR0/30: 6.3 ± 3.6, IR 15/30 42.9 ± 5.0, IR30/30 15.9 ± 3.8, IR40/30 11.5 ± 6.6; p ≤ 0.01 for IR15/30 against all other groups). CONCLUSIONS: Ischemia prolongation in IR injury gradually impaired SSM in terms of respiratory chain function and Ca2+-homeostasis. Membrane hyperpolarization appears to be responsible for impaired Ca2+-cycling and ETC function. Ischemia time should be considered an important factor influencing IR experimental data on subsarcolemmal mitochondria. Periods of warm global ischemia should be minimized during cardiac surgery to avoid excessive damage to SSMs.

A new technique to implant a transcatheter inflatable, fully repositionable prosthesis in aortic stenosis with severe asymmetric calcification.

OBJECTIVES: In contrast to stented transcatheter aortic valves, the Direct Flow Medical (DFM) valve is a stentless bovine aortic bioprosthesis mounted in a non-metallic inflatable frame. Hence, severe asymmetric annular calcification may result in residually elevated transaortic pressure gradients after DFM implantation. We present a novel intraprocedural dilatation (IDIL) technique for successful implantation of the DFM valve in the presence of complex annular calcification. METHODS: Between January 2014 and May 2015, 55 patients underwent DFM valve-based transcatheter aortic valve implantation at our institution. Of these, 5 patients required an IDIL technique due to a residual intraoperative transaortic pressure mean gradient above 15 mmHg. The mean patient age was 73 ± 8.2 years; the mean logistic EuroSCORE was 24.5 ± 8.2% and the mean Society of Thoracic Surgeons score was 6.3 ± 4.3%. RESULTS: The IDIL technique immediately attenuated transvalvular mean pressure gradients from 20 ± 2 mmHg to 6 ± 1 mmHg. The results remained stable during the 30-day observation period at 10 ± 3 mmHg. Minimal paravalvular aortic regurgitation (trace) was detected in 2 patients. No in-hospital deaths were observed. CONCLUSIONS: The IDIL technique facilitates safe DFM valve implantation in patients with complex asymmetric annular calcification without adverse side effects on valve structure or performance in short-term follow-up.

Secondary sclerosing cholangitis in cardiac surgical patients: A complication with a dismal prognosis.

OBJECTIVES: Secondary sclerosing cholangitis in critically ill patients is a rapidly progressing disease leading to biliary fibrosis and cirrhosis. We describe the course of sclerosing cholangitis in critically ill patients after cardiac surgery and compare this with matched patients. METHODS: A retrospective search for "secondary sclerosing cholangitis" and "liver and/or hepatic failure" in all adult patients (aged 18-93 years) who underwent cardiac surgery from April 2007 to March 2016 identified 192 of 8625 patients. Of those, 12 were diagnosed with sclerosing cholangitis in critically ill patients (incidence, 0.14%). A 3:1 matching was performed. Laboratory values, pharmacologic requirements, ventilation times, mechanical circulatory support, and endoscopic retrograde cholangiopancreatography studies were extracted from the hospital database. RESULTS: A total of 9 men and 3 women were affected (age 71 years; range, 59.8-75.5 years). Critically ill patients with sclerosing cholangitis required vasoconstrictors and inotropes longer than control patients (norepinephrine 356.5 hours [264.5-621] vs 68 hours [15-132.5], P = .003; enoximone 177 hours [124.3-249.5] vs 48.5 hours [12-81 hours], P < .001, respectively). Critically ill patients with sclerosing cholangitis had longer intubation time (628.5 hours [377.3-883] vs 25 hours [9.8-117.5]; P < .001) and more surgical revisions (3 [2.5-6] vs 1 [0-2], P = .003) than the matching group. Bilirubin (23.3 mg/dL [14.4-32.9] vs 1 mg/dL [0.6-2.7]; P < .001), gamma-glutamyltransferase (1082.3 U/L [259.5-2265.7] vs 53.8 U/L [35.1-146]; P < .001), and alkaline phosphatase (751.5 U/L [372-1722.3] vs 80.5 U/L [53.3-122]; P < .001) were higher in critically ill patients with sclerosing cholangitis. One critically ill patient with sclerosing cholangitis underwent successful liver transplantation. A total of 11 patients sclerosing cholangitis died (92%) versus 12 patients (33%, P < .001) in the control group. CONCLUSIONS: Sclerosing cholangitis in critically ill patients is a fatal complication in patients undergoing cardiac surgery who have a complicated postoperative course with prolonged vasoconstrictor, inotropic, and respiratory therapy, or who require frequent surgical revisions. Liver transplantation remains the only curative option but is often precluded by the age and critical state of patients undergoing cardiac surgery.

Cardiac Surgery is Safe in Female Patients with a History of Breast Cancer.

PURPOSE: In cardiac surgery candidates, a concomitant history of breast cancer suggests adverse outcomes. The possibility of internal mammary artery (IMA) utilization and its patency rate is frequently discussed. Secondary, blood loss and wound related infections might be important issues. However, publications focusing on these issues are limited. METHODS: We analyzed 32 patients with previously treated breast cancer undergoing cardiac bypass (CABG) and combined CABG surgery matched to 99 control subjects in a retrospective cohort study. Patients were analyzed regarding IMA utilization, blood loss and substitution and frequent perioperative complications as well as long-term mortality. RESULTS: No significant differences between groups were observed regarding duration of surgery, IMA-utilization, incidence of infections and postoperative complications or mortality. A pronounced decline of hemoglobin/hematocrit was evident within the first 6 postoperative hours (3.3 ± 1.8 vs. 2.5 ± 1.8 mg/dl; p = 0.03) in breast cancer patients not related to an increased drainage loss but associated with an increase of international normalized ratio (INR) (0.39 ± 0.16 vs. 0.29 ± 0.24; p <0.01). CONCLUSION: In breast cancer patients, CABG and combined CABG procedures can safely be performed with comparable short- and long-term results.

Impact of levosimendan and ischaemia-reperfusion injury on myocardial subsarcolemmal mitochondrial respiratory chain, mitochondrial membrane potential, Ca2+ cycling and ATP synthesis.

OBJECTIVES: Levosimendan (LS) is increasingly used in case of myocardial failure after cardiac surgery. The impact of LS on myocardial mitochondrial functions, such as respiratory chain function (RCF), mitochondrial membrane potential (ΔΨm), Ca(2+) handling, mitochondrial permeability transition pore (mPTP) opening and ATP during ongoing ischaemia/reperfusion (IR) injury, is not well understood. Depending on LS, I/R injury or the combination of both, we analysed myocardial functions in a retrograde Langendorff-model followed by the analysis of subsarcolemmal mitochondrial (SSM) functions. METHODS: Rat hearts were divided into four study groups; two were subjected to 30 min of perfusion without (control) or with the application of 1.4 µmol/20 min LS (Levo). Experiments were repeated with hearts being subjected to 40 min of normothermic stop-flow ischaemia and 30 min of reperfusion without (IR) or with LS application (Levo-IR). Systolic left ventricular pressure (LVPsys), left ventricular contractility (LVdp/dtmax) and coronary flow were determined. SSM were analysed regarding RCF, ΔΨm, ATP, and Ca(2+) retention capacity (CRC), Ca(2+)-induced swelling and Ca(2+) fluxes after (re)perfusion. RESULTS: I/R injury suppressed LVdp/dtmax (1381 ± 927 vs 2464 ± 913 mmHg/s; P = 0.01 at 30 min (re-)perfusion time). IR revealed complex I-V state3 (19.1 ± 7.4 vs 27.6 ± 11.0 nmolO2/min; P < 0.044) and II-V state3 (20.6 ± 6.8 vs 37.3 ± 9.10 molO2/min; P < 0.0001) suppression and Levo limited I-V (14.8 ± 11.1 vs 27.6 ± 11.0 nmolO2/min; P < 0.001) and II-V (24.1 ± 6.4 vs 37.3 ± 9.10 molO2/min; P < 0.0001) function. After energizing, ΔΨm hypopolarization was observed in Levo (0.76 ± 0.04 vs 0.84 ± 0.04; P = 0.02), IR (0.75 ± 0.06 vs 0.84 ± 0.04; P = 0.007) and Levo-IR (0.75 ± 0.06 vs 0.06 ± 0.04; P = 0.01). IR (AUC: 626 vs 292; P = 0.023) and Levo-IR (AUC: 683 vs 292, P = 0.003) increased Ca(2+)-induced mPTP-opening susceptibility. CRC declined in IR (6.4 ± 2.1 vs 10.5 ± 2.6; P = 0.04) or Levo (6.5 ± 2.0 vs 10.5 ± 2.6; P = 0.023). Ca(2+) uptake was delayed in IR and Levo-IR without LS impact (P < 0.0001). Ca(2+) liberation was increased in Levo-IR. ATP synthesis was reduced in Levo (0.49 ± 0.14 vs 0.74 ± 0.14; P = 0.002) and Levo-I/R (0.34 ± 0.18 vs 0.74 ± 0.14; P < 0.002). CONCLUSION: LS limited RCF at complex IV and V with ΔΨm hypopolarization suggesting a specific [Formula: see text]-dependent pathway. Ca(2+) redistribution from SSM by LS during I/R injury possibly prevents from Ca(2+) overload due to mPTP flickering. LS-induced mPTP flickering did not promote permanent Ca(2+)-induced mPTP opening. LS-dependent inhibition of ATP generation presumably resulted from complex IV and V limitations and lowered ΔΨm. However, a resulting impact of limited ATP synthesis on myocardial recovery remains arguable.

Cardiac surgery antibiotic prophylaxis and calculated empiric antibiotic therapy.

BACKGROUND: Ongoing debate exists concerning the optimal choice and duration of antibiotic prophylaxis as well as the reasonable calculated empiric antibiotic therapy for hospital-acquired infections in critically ill cardiac surgery patients. METHODS: A nationwide questionnaire was distributed to all German heart surgery centers concerning antibiotic prophylaxis and the calculated empiric antibiotic therapy. RESULTS: The response to the questionnaire was 87.3%. All clinics that responded use antibiotic prophylaxis, 79% perform it not longer than 24 h (single-shot: 23%; 2 doses: 29%; 3 doses: 27%; 4 doses: 13%; and >5 doses: 8%). Cephalosporin was used in 89% of clinics (46% second-generation, 43% first-generation cephalosporin). If sepsis is suspected, the following diagnostics are performed routinely: wound inspection 100%; white blood cell count 100%; radiography 99%; C-reactive protein 97%; microbiological testing of urine 91%, blood 81%, and bronchial secretion 81%; procalcitonin 74%; and echocardiography 75%. The calculated empiric antibiotic therapy (depending on the suspected focus) consists of a multidrug combination with broad-spectrum agents. CONCLUSION: This survey shows that existing national guidelines and recommendations concerning perioperative antibiotic prophylaxis and calculated empiric antibiotic therapy are well applied in almost all German heart centers.

Initial topical cooling followed by backtable Celsior flush perfusion provides excellent early graft function in porcine single lung transplantation after 24 hours of cold ischemia.

BACKGROUND: Topical in situ cooling of the donor lungs is a prerequisite for procurement of non-heart-beating donor lungs and may be of interest for living related lung donation. METHODS: Twenty-four single lung transplants were performed in 4 groups of Landrace pigs (6 per group). Control LPD, control Celsior and topical cooling in situ, followed by LPD (exLPD) or Celsior (exCel) ex situ flush, were employed. All lungs were perfused antegrade with 1 liter of solution at 4°C. Lungs were stored immersed in preservation solution for 24 hours at 4°C. After transplantation of the left lung, the right recipient bronchus and pulmonary artery were clamped. RESULTS: Four of 6 animals each in the LPD and Celsior groups and all 6 animals in both the exLPD and the exCel groups survived the 7-hour reperfusion. The mean oxygenation index was favorably preserved in the exCel group at 7 hours after reperfusion (417 ± 81) over all other groups (LPD 341 ± 133, Celsior 387 ± 86, exLPD 327 ± 76; p < 0.0001). Pulmonary vascular resistance showed significantly lower values in the Celsior and exCel groups (LPD 1,310 ± 620, Celsior 584 ± 194, exLPD 1,035 ± 361, exCel 650 ± 116 dyn/s/cm(5) at 7 hours after reperfusion; p < 0.0001). Consistently, the wet-to-dry lung weight ratio also indicated beneficial graft protection in the exCel group (LPD 8.1 ± 0.8, Celsior 8.4 ± 0.8, exLPD 7.5 ± 1.0, exCel 3.1 ± 0.9; p < 0.0001). CONCLUSION: Initial topical cooling followed by backtable perfusion is a sufficient technique for pulmonary graft preservation providing excellent post-transplant function. Celsior subsequent to in-situ topical cooling revealed the most beneficial results in this setting. This combined technique could advance non-heart-beating, living related lung lobe donation and, potentially, regular heart-beating lung donation.

The predictive value of multiple electrode platelet aggregometry (multiplate) in adult cardiac surgery.

BACKGROUND: The purpose of this retrospective observational study is to analyze the value of multiple electrode platelet aggregometry (Multiplate analyzer, Verum Diagnostica, Munich) as a point-of-care (POC) device in adult cardiac surgical patients. METHODS: Two hundred and twenty-three cardiac surgical patients were analyzed preoperatively and postoperatively with multiple electrode platelet aggregometry by stimulation ADPtest, ASPItest, and TRAPtest. End points were postoperative bleeding, need for reexploration, and perioperative transfusions requirements. Furthermore, a literature survey using the key phrases "platelet function" and "cardiac surgery" was performed. RESULTS: When comparing patients with normal Multiplate test results concerning end points, patients with pathological ADPtest (n = 140) needed significant more platelet concentrates (PCs) (p = 0.009), patients with pathological ASPItest (n = 175) did not show any significant differences, and patients with pathological TRAPtest (n = 139) needed more red blood cells (p = 0.008) and PCs (p = 0.02). The literature survey showed 208 hits, spanning the publication years 2002 to 2012 resulted in 123 hits. CONCLUSIONS: The ADPtest and the TRAPtest significantly predict the requirement of perioperative blood transfusion. Therefore, multiple electrode platelet aggregometry is beneficial for POC testing in cardiac surgical patients. Prospective, randomized, and controlled clinical studies are rare.

Cardiac surgery in cases of myeloproliferative neoplasm: risk factor for stroke.

OBJECTIVES: a history of myeloproliferative neoplasms is considered to increase the risks in cardiac surgery. In patients with myeloproliferative neoplasms, increased rates of perioperative infections and thromboembolic complications are suspected, but studies analyzing the impact of myeloproliferative neoplasms on results after cardiac surgery are lacking. METHODS: 13 patients with the diagnosis of myeloproliferative neoplasm underwent cardiac surgery. These patients were matched to 36 controls. Matching criteria consisted of sex, age, diagnosis, and comorbidities. Patients were analyzed regarding laboratory parameters, blood transfusion demands, morbidity, and mortality. RESULTS: compared to controls, patients with myeloproliferative neoplasms demonstrated a significantly lower body-mass index (p<0.01), creatinine (p=0.024), prothrombin time (p=0.001), and urea level (p=0.012). The perioperative leukocyte response (p=0.03) was ameliorated, and platelet counts (p<0.02) increased. Patients with myeloproliferative neoplasms had a reduced need for erythrocyte concentrates (54% vs. 86%, p=0.047) but increased need for plasma and thrombocytes (15% vs. 0%, p=0.07). Patients with myeloproliferative neoplasms had a significantly increased incidence of thromboembolic events compared to controls (31% vs. 3%, p=0.014). Hospital mortality remained at zero, but mid-term survival was lower in patients with myeloproliferative neoplasms (p=0.078). CONCLUSIONS: myeloproliferative neoplasm as a concomitant diagnosis increases the risk of thromboembolic complications during cardiac surgery. Plasma and platelet substitutions have to be administered, although strokes were not associated with hemostatic treatment.

Glycine preconditioning to ameliorate pulmonary ischemia reperfusion injury in rats.

This study examines the impact of glycine (Gly) preconditioning on ischemia reperfusion (IR)-induced pulmonary mitochondrial injury to research the previously, in pig lungs, demonstrated Gly-dependent amelioration of pulmonary IR injury. IR injury was induced in rat lungs by 30 min pulmonary hilum clamping followed by 60 min reperfusion time. Rats were subjected to controls, shams and two study groups (IR30/60, Gly-IR30/60) receiving 37.5 mg Gly i.v. or not before IR induction. The wet/dry-weight ratio, mitochondria viability (MV), membrane integrity (MI), respiratory chain complex (RCC) activities, mitochondrial membrane potential (ΔΨm) and cytochrome C (Cyt C) content were analysed. In IR30/60, RCC and MV were impaired; Cyt C loss and MI combined with matrix metalloproteinase-9 (MMP-9) activation and ΔΨm alteration were observed when compared with controls. In Gly-IR30/60, complex II function and mitochondrial viability were protected during IR, and MMP-9 activation combined with tissue-water content accumulation and ΔΨm alteration were ameliorated. Cyt C loss, mitochondrial membranes damage, tissue GSH oxidation or neutrophil sequestration was not extenuated in Gly-IR30/60. Gly ameliorates IR-associated mitochondrial dysfunction and decay of viability and normalizes ΔΨm but does not protect from Cyt C liberation and mitochondrial membrane damage. Our data suggest that the previously described effect of Gly preconditioning results at least partially from mitochondrial protection. A dose-finding study is necessary to improve results of Gly preconditioning.

Glutathione preconditioning ameliorates mitochondria dysfunction during warm pulmonary ischemia-reperfusion injury.

OBJECTIVES: Reduced glutathione (GSH) has been shown to improve pulmonary graft preservation. Mitochondrial dysfunction is regarded to be the motor of ischemia-reperfusion injury (IR) in solid organs. We have shown previously that IR induces pulmonary mitochondrial damage. This study elucidates the impact of GSH preconditioning on the integrity and function of pulmonary mitochondria in the setting of warm pulmonary IR. METHODS: Wistar rats were subjected to control, sham, and to two-study-group conditions (IR30/60 and GSH-IR30/60) receiving IR with or without GSH preconditioning. Rats were anesthetized and received mechanical ventilation. Pulmonary in situ clamping followed by reperfusion generated IR. Mitochondria were isolated from pulmonary tissue. Respiratory chain complexes activities (I-IV) were analyzed by polarography. Mitochondrial viability (Ca2+-induced swelling) and membrane integrity (citrate synthase assay) were determined. Subcellular-fractional cytochrome C-content (Cyt C) was quantified by enzyme-linked immunosorbent assay (ELISA). Mitochondrial membrane potential (ΔΨm) was analyzed by fluorescence-activated cell sorting (FACS) after energizing and uncoupling. Inflammatory activation was determined by myeloperoxidase activity (MPO), matrix-metalloproteinase 9 (MMP-9) activity by gel zymography. RESULTS: Pulmonary IR significantly reduced mitochondrial viability in combination with ΔΨm hyper-polarization. GSH preconditioning improved mitochondrial viability and normalized ΔΨm. Cyt C was reduced after IR; GSH protected from Cyt C liberation. Respiratory chain complex activities (I, II, III) declined during IR; GSH protected complex II function. GSH also protected from MMP-9 and neutrophil sequestration (P>.05). CONCLUSIONS: GSH preconditioning is effective to prevent mitochondrial death and improves complex II function during IR, but not mitochondrial membrane stability. GSH-mediated amelioration of ΔΨm hyper-polarization appears to be the key factor of mitochondrial protection.

Policies of withholding and withdrawal of life-sustaining treatment in critically ill patients on cardiac intensive care units in Germany: a national survey.

OBJECTIVE: To determine the decision-making process of withholding and/or withdrawal (WH/WD) of life-sustaining treatment in cardiac intensive care units (ICUs) in Germany. METHODS: A questionnaire regarding 16 medical and 6 ethical questions of WH/WD of life-sustaining treatment was distributed to the clinical director, senior ICU physician and head nurses of all German heart surgery centres (n = 237 questionnaires). Furthermore, we present a literature survey using the key words 'End-of-life care AND withholding/withdrawal of life support therapy AND intensive care unit'. RESULTS: We received replies from 86 of 237 (36.3%) contacted persons. Concerning medical reasons, cranial computed tomography (CCT) with poor prognosis (91.9%), multi-organ failure (70.9%) and failure of assist device therapy (69.8%) were the three most frequently cited medical reasons for WH/WD life-sustaining treatment. Overall, 32.6% of persons answered that ethical aspects influence their decision-making processes. Poor expected quality of life (48.8%), the patient's willingness to limit medical care (40.7%) and the families' choice (27.9%) were the top three reported ethical reasons. There was a significant difference regarding the perception of the three involved professional groups concerning the decision-making parameters: multi-organ failure (P = 0.018), failure of assist device therapy (P = 0.001), cardiac index (P = 0.009), poor expected quality of life (P = 0.009), the patient's willingness to limit medical care (P = 0.002), intraoperative course (P = 0.054), opinion of family members (P = 0.032) and whether decision-making process are done collaboratively (clinical director, 45.7%; ICU physician, 52%; and head of nursing staff, 26.9%). Palliation medication in patients after WH/WD of life-support consisted of morphine (92%) and benzodiazepines (88%). CONCLUSIONS: This survey is a step towards creating standards of end-of-life care in cardiac ICUs, which may contribute to build consensus and avoid conflicts among caregivers, patients and families at each step of the decision-making process.

Ischemia-reperfusion injury-induced pulmonary mitochondrial damage.

BACKGROUND: Mitochondrial dysfunction is a key factor in solid organ ischemia-reperfusion (IR) injury. Impaired mitochondrial integrity predisposes to cellular energy depletion, free radical generation, and cell death. This study analyzed mitochondrial damage induced by warm pulmonary IR. METHODS: Anesthetized Wistar rats received mechanical ventilation. Pulmonary clamping was followed by reperfusion to generate IR injury. Rats were subjected to control, sham, and to 2 study group conditions: 30 minutes of ischemia without reperfusion (IR30/0), or ischemia followed by 60 minutes of reperfusion (IR30/60). Pulmonary edema was quantified by wet/dry-weight ratio. Polarography determined activities of respiratory chain complexes. Mitochondrial viability was detected by using Ca(2+)-induced swelling, and integrity by citrate synthase assay. Enzyme-linked immunosorbent assay determined cytochrome C content. Mitochondrial membrane potential (ΔΨm) stability was analyzed by flow cytometry using JC1, inflammation by myeloperoxidase (MPO) activity, and matrix-metalloproteinase-9 (MMP-9) activity by gel zymography, respectively. RESULTS: In IR30/60 rats, tissue water content was elevated from 80.6 % (sham) to 86.9%. After ischemia, ΔΨm showed hyperpolarization and rapid decline after uncoupling compared with controls. IR, but not ischemia alone, impaired respiratory chain function complexes I, II and III (p < 0.05). Mitochondrial viability (p < 0.001) and integrity (p < 0.01) was impaired after ischemia and IR, followed by mitochondrial cytochrome C loss (p < 0.05). Increased activation of MPO (p < 0.01) and MMP-9 (p < 0.001) was induced by reperfusion after ischemia. CONCLUSIONS: Ischemia-related ΔΨm hyper-polarization induces reperfusion-associated mitochondrial respiratory chain dysfunction in parallel with tissue inflammation and degradation. Controlling ΔΨm during ischemia might reduce IR injury.

Cardiac surgery and hematologic malignancies: a retrospective single-center analysis of 56 consecutive patients.

OBJECTIVE: Patients with a history of hematologic malignancies (HMs) are considered high-risk candidates for cardiac surgery. Increased perioperative rates of infections, thrombo-embolic complications, and bleeding disorders are reported. However, low patient numbers and lack of control groups limit all published studies. METHODS: A total of 56 patients with a history of HM underwent cardiac surgery. As many as 29 patients suffered from non-Hodgkin lymphoma, five from Hodgkin disease, and 12 from myeloproliferative disorders, one from acute lymphatic leukemia, and nine from monoclonal gammopathy. Surgery consisted of coronary artery bypass grafting, valvular surgery or combination procedures. HM patients were matched to 142 controls. Matching criteria applied consisted of sex, age, main diagnosis, and co-morbidities. RESULTS: In-hospital mortality was elevated in HM patients though not reaching significance (P = 0.7). HM patients demonstrated increased rates of vascular, pulmonary, infectious complications (P > 0.1), and transfusion requirements (P = 0.077). The long-term survival of HM patients was significantly impaired (P = 0.043). A history of irradiation or chemotherapy predisposed to postoperative respiratory insufficiency, acute renal failure, and an impaired long-term survival (P > 0.065). CONCLUSIONS: Cardiac surgery in patients with a history of a malignant hematologic disorder might achieve acceptable results. However, a higher complication and mortality rate have to be anticipated. Patients with hematologic disorders and a history of either irradiation or chemotherapy appear to be at an increased risk to develop postoperative end-organ failure.

Heartmate II implantation with right coronary bypass grafting in ischemic cardiomyopathy with "fixed" pulmonary hypertension: treatment strategy to protect right ventricular function.

A 49-year-old male patient suffering from end-stage ischemic cardiomyopathy with a left ventricular ejection fraction below 15% was presented to redo coronary artery bypass grafting (CABG). Coronary angiogram demonstrated an occluded left anterior descending artery and occluded right coronary artery, perfused retrogradely from the circumflex artery. Since positron emission tomography did not demonstrate viable left ventricular myocardium except for the basis of the left ventricle, CABG was considered futile. Cardiac transplantation was contra-indicated due to pharmacologically unresponsive pulmonary artery hypertension. The patient successfully underwent left ventricular assist device implantation in combination with right coronary artery revascularization. The article reflects the regimen of right ventricular preservation in this patient.

Cardiac operations in the presence of meningioma.

BACKGROUND: We investigated the effect of concomitant intracranial meningiomas on perioperative and postoperative complications after cardiac operations. Also studied was the intraoperative and perioperative management and long-term outcome of such patients. METHODS: We retrospectively evaluated 16 cardiac surgical patients with intracranial meningiomas between January 1996 and July 2007. Neurologic outcome, incidence of transient neurologic deficits, and long-term follow-up focusing on freedom from any cardiac or neurosurgical intervention were assessed. RESULTS: Five men and 11 women with a concomitant diagnosis of intracranial meningioma underwent cardiac operations using extracorporeal circulation. One patient received additional edema prophylaxis by intravenous dexamethasone. All patients were discharged home in good physical condition. Data on long-term survival were available on 14 patients, with 12 alive. Postoperatively, 2 patients died from myocardial infarction at 26.8 months and 2 from metastatic colon cancer at 57.9 months. Perioperative neurologic disorders were observed in 2 patients, comprising one stroke after intervention for aortic dissection and one thromboembolic event 2 weeks after biologic mitral valve replacement due to anticoagulation disorders. No meningioma-related adverse event was observed. CONCLUSIONS: The presence of intracranial meningioma does not appear to be a risk factor for patients undergoing cardiac operations. No meningioma-related neurologic sequelae were documented postoperatively. Neurosurgical consultation should be obtained in all patients preoperatively.

Sternal closure techniques and postoperative sternal wound complications in elderly patients.

OBJECTIVE: Postoperative sternal wound complications (PSWC) including deep sternal wound infection (DSWI) and sternal dehiscence (SD) cause significant morbidity and mortality. Elderly patients with several risk factors are particularly prone to suffer PSWC. METHODS: We present (I) a subset of 86 patients, all aged > or =75 years out of 339 cardiac surgery patients prospectively randomised to receive either conventional sternal closure or a Robicsek type closure. Primary end-points were SD and DSWI; secondary end-points included a composite of clinical parameters; (II) we retrospectively assessed data of 54/5273 patients with mediastinitis regarding the influence of advanced age. In addition, we report an epidemiological overview of different sternal closure techniques. RESULTS: (I) The Robicsek technique showed an impact on SD and DSWI, and several secondary end-points: ventilator support (p=0.03), postoperative blood loss (p=0.04), and chest pain >3 days (p=0.04). (II) A total of 54/5273 (1.02%) patients developed postoperative mediastinitis. Twelve out of 54 (22%) patients died within 6 months of the initial operation. Predictors of mortality were insulin-dependent diabetes mellitus (p=0.05), renal insufficiency (p=0.01), delayed sternal closure (p=0.05), ICU-stay >10 days (p=0.01), and methicillin-resistant Staphylococcus aureus (p=0.03) or fungal infection (p=0.02). CONCLUSIONS: No statistical difference in sternal dehiscence or mediastinitis was found irrespective of whether the bilateral and longitudinal parasternal closure or the conventional peri/trans-sternal wiring technique was used, but there was an obvious, positive influence on sternal dehiscence, deep sternal wound infection, and clinical parameters. However, the study population is relatively small.

Primary treatment of deep sternal wound infection after cardiac surgery: a survey of German heart surgery centers.

There are various primary treatment modalities of managing deep sternal wound infection (DSWI) following cardiac surgery, namely surgical debridement with primary reclosure in conjunction with irrigation, Vacuum-assisted closure (V.A.C. therapy, and primary or delayed flap closure. The purpose of this study was to assess whether there is consensus of the primary management of DSWI using one method as a single line therapy or a combination of these procedures. Therefore, a questionnaire with regards to the primary treatment modalities of DSWI was distributed to all 79 German heart surgery centers. All replied to the questionnaire. V.A.C. is used in 28/79 (35%) heart centers as the 'first-line' treatment, 22/79 (28%) perform primary reclosure in conjunction with a double-tube irrigation/suction system, and in 29/79 (37%) clinics both treatment options were used according to intraoperative conditions. Mostly, as a primary management of DSWI two treatment modalities are mainly in use: primary reclosure coupled with a double-tube suction/irrigation system and V.A.C. therapy. The current understanding is based purely on retrospective studies, not evidence-based medicine. Since prospective randomized studies have not yet been performed, controlled clinical trials comparing these treatment modalities are pivotal to define evidence for patients presenting with DSWI.

The innominate vein as alternative venous access for complicated implantable cardioverter defibrillator revisions.

BACKGROUND: Venous complications of implantable cardioverter defibrillator (ICD) systems may cause significant problems when the need for system revision or upgrades arises. Such revisions require venous access close to the site of the previous ICD implantation. The internal and external jugular vein have disadvantages due to a long subcutaneous course crossing the clavicle and problems with lead extraction if infection occurs. METHODS: In seven patients with ICD revisions due to lead dysfunction (n = 4) and upgrade to a biventricular device (n = 2) and status after system removal due to infection with new device implantation (n = 1) conventional venous access could not be obtained. Intraoperative contrast venography demonstrated an occluded left subclavian and/or left innominate vein in all patients. In all patients, we gained venous access through puncture of the right innominate vein and tunneled the new lead subcutaneously to the ICD pocket on the left. RESULTS: No intraoperative complications were observed. All patients are followed in our ICD clinic. Mean follow-up is 16 +/- 4 months now. So far, no clinical or lead complications with this access have been observed. CONCLUSIONS: We have demonstrated that ICD lead placement through puncture of the right innominate vein is feasible. We propose the innominate vein as an alternative route for establishing venous access in patients requiring ICD revisions or upgrades who suffer from venous obstruction. ICD implanting physicians should acquaint themselves with the technique of right innominate vein puncture to use this vein as a bail-out strategy in patients with complicated venous access.