0000000000292787
AUTHOR
Uwe Mehlhorn
Pneumocyte Apoptosis Induction during Cardiopulmonary Bypass: Effective Prevention by Radical Scavenging UsingN-Acetylcysteine
Cardiopulmonary bypass (CPB) and cardioplegic arrest are associated with pulmonary dysfunction. We sought to investigate whether pulmonary ischemia/reperfusion during standard CPB and cardioplegic arrest is associated with reactive oxygen species (ROS)-mediated pulmonary tissue injury and pneumocyte apoptosis induction, and whether ROS scavenging using N-acetylcysteine (NAC) attenuates these alterations. Twelve pigs (41 +/- 8 kg) were randomized to receive either NAC (100 mg/kg prior to CPB; n = 7) or placebo (n = 5) and subjected to CPB and 60 min of cold (4 degrees C) crystalloid cardioplegic arrest. We collected lung biopsies prior to CPB, at 60 min CPB, as well as at 30, 60, and 120 min…
Transmurality of scar influences the effect of a hybrid-intervention with autologous bone marrow cell injection and aortocoronary bypass surgery (MNC/CABG) in patients after myocardial infarction
Abstract Background Cell therapy (CTx) is a strategy to support cardiac regeneration after myocardial infarction (MI). Thus far, clinical studies provided mixed results. Here, we investigated whether transmurality of the infarct may play a relevant role. Methods 18 patients (63±3years, 15 male) undergoing elective coronary artery bypass graft (CABG) surgery 2.2±0.7months post MI participated. 10 had transmural and 8 non-transmural infarct scars assessed by Tc-99m-MIBI Single-Photon Emission Computed Tomography (SPECT) and F18-FDG-Positron-Emission-Tomography (PET). During surgery, 10ml of sternal bone marrow were obtained, mononuclear cells (MNC) were isolated. At the end of surgery MNC wer…
Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase α1β1, α2β1 and α3β1
Abstract Cardiac glycosides inhibit the Na + ,K + -ATPase and are used for the treatment of symptomatic heart failure and atrial fibrillation. In human heart three isoforms of Na + ,K + -ATPase are expressed: α 1 β 1 , α 2 β 1 and α 3 β 1 . It is unknown, if clinically used cardiac glycosides differ in isoform specific affinities, and if the isoforms have specific subcellular localization in human cardiac myocytes. Human Na + ,K + -ATPase isoforms α 1 β 1 , α 2 β 1 and α 3 β 1 were expressed in yeast which has no endogenous Na + ,K + -ATPase. Isoform specific affinities of digoxin, digitoxin, β-acetyldigoxin, methyldigoxin and ouabain were assessed in [³H]-ouabain binding assays in the abse…
Successful Management of Fulminant Pulmonary Embolism Using a Novel Portable Extracorporeal Life Support System
A 46-year-old man presented to the emergency room with pain in his left leg, dyspnea, and general cyanosis. During examination he collapsed and required resuscitation. Under suspicion of pulmonary embolism, a new portable "click 'n run" extracorporeal life support system (LIFEBRIDGE-B(2)T [Medizintechnik AG, Ampfing, Germany]) was implanted by the femoral vessels under resuscitation within 15 minutes of presentation. The patient was stabilized, despite severe decompensation (pH, 6.8), and could be transferred for a computed tomographic scan, which confirmed massive pulmonary embolism. Still connected to the life support system, the patient was transferred to the operating room. After a pulm…
Regulation of endothelial nitric oxide synthase (eNOS) in myocardium subjected to cardioplegic arrest.
BACKGROUND: Nitric oxide (NO) production by both coronary endothelial cells and cardiomyocytes is thought to play a significant role in myocardial pathophysiology following ischemia/reperfusion (I/R). METHODS: In thirteen pigs subjected to 1 hour cardioplegic arrest (CA) on CPB, left ventricular (LV) biopsies were collected prior to CPB (baseline), at 60 min CPA, at 15 and 30 min reperfusion on CPB, and at 120 min post CPB. LV specimens were immunocytochemically stained against phospho-eNOS Ser1177 , phospho-eNOS Thr495 , phosphorylated ERK1/2, and AKT/PKB. Four additional pigs without CA served as controls. Cardiomyocytes were quantitatively investigated using TV densitometry (gray units: …
Composite risk scores and depression as predictors of competing waiting-list outcomes: the Waiting for a New Heart Study
We evaluated two composite risk scores, (Heart Failure Survival Score, HFSS; German Transplant Society Score, GTSS), and depression as predictors of mortality and competing waiting-list outcomes [high-urgency transplantation (HU-HTx), elective transplantation, delisting because of clinical improvement] in 318 heart transplant (HTx) candidates (18% women; aged 53 ± 11 years) from 17 hospitals and newly registered with Eurotransplant. Demographic variables and depression (Hospital Anxiety and Depression Scale, HADS) were assessed using questionnaires. Variables to compute HFSS and GTSS, age, medications, and outcomes were provided by Eurotransplant. At 12 months, 33 patients died, 83 received…
Extracorporeal circulation activates endothelial nitric oxide synthase in erythrocytes.
Background Extracorporeal circulation used in cardiopulmonary bypass and hemodialysis is often associated with severe hypotension, which is an important predictor for mortality and morbidity. One pathophysiological hypothesis includes nitric oxide (NO) generation. Recently, a functional NO synthase (endothelial type NO synthase [eNOS]), was found to be expressed in human red blood cells. However, to date, activation of red blood cell eNOS has not been shown. We hypothesized that eNOS in circulating red blood cells might be activated during extracorporeal circulation and thus contribute to hypotension through vasodilation upon NO release. Methods We collected blood samples from 28 patients e…
Reevaluation of direct true lumen cannulation in surgery for acute type A aortic dissection.
Background The optimal mode of arterial cannulation in acute type A aortic dissection is controversial. We retrospectively investigated our experience with direct true lumen cannulation as an alternative to standard cannulation procedures. Methods From April 2004 to August 2007, 29 patients (20 men, 9 women; mean age of 63.2 ± 12.6 years) underwent emergency operation for acute type A aortic dissection with direct true lumen cannulation. After venous drainage into the venous reservoir, the ascending aorta was completely transected in the region between the sinotubular junction and innominate artery. After visual and digital identification of the true lumen, the arterial cannula was directly…
Cross-clamping a porcelain aorta: an alternative technique for high-risk patients
Background Aortic cross-clamping in patients with porcelain aorta is associated with high mortality and morbidity rates. The aim is to establish a new approach to improve the outcome in this high-risk population. Methods Between September 2007 and November 2012, 42 patients with an aortic (N.=33; 81.3±6.4 years) or mitral valve disease (N.=9; 80.3±5.7) combined with a porcelain aorta underwent aortic (AVR) or mitral valve replacement (MVR). After arterial cannulation via distal aortic arch or femoral artery, longitudinal aortotomy under total cardiopulmonary bypass (CPB) was performed. The aorta was slowly clamped, thus mobilized atherosclerotic material could leave the aorta through the op…
Mortality in patients with acute aortic dissection type A: analysis of pre- and intraoperative risk factors from the German Registry for Acute Aortic Dissection Type A (GERAADA)
Acute aortic dissection type A (AADA) is an emergency with excessive mortality if surgery is delayed. Knowledge about independent predictors of mortality on surgically treated AADA patients is scarce. Therefore, this study was conducted to identify pre- and intraoperative risk factors for death.Between July 2006 and June 2010, 2137 surgically treated patients with AADA were enrolled in a multicentre, prospective German Registry for Acute Aortic Dissection type A (GERAADA), presenting perioperative status, operative strategies, postoperative outcomes and AADA-related risk factors for death. Multiple logistic regression analysis was performed to identify the influence of different parameters …
How to do it: direct true lumen cannulation technique of the ascending aorta in acute aortic dissection type A†
In acute aortic dissection type A (AADA), direct true lumen cannulation (DTLC) of the ascending aorta is a fast and safe cannulation site providing antegrade perfusion of the supraaortic and visceral vessels. An Overholt clamp is passed around the ascending aorta to place a Mersilene tape for later securing of the arterial cannula. After draining venous blood into the cardiopulmonary bypass system (CPB), the ascending aorta is transected and the aortic lumen inspected. The true lumen is identified and an arterial cannula inserted directly. Finally, the cannula is secured with the previously placed tape and CPB is initiated. DTLC can be used as arterial cannulation standard technique in oper…
Feasibility of transcatheter aortic valve implantation in patients with coronary heights ≤7 mm: insights from the transcatheter aortic valve implantation Karlsruhe (TAVIK) registry.
OBJECTIVES Transcatheter aortic valve implantation (TAVI) in patients with low coronary heights is generally denied but is not impossible. Information about these high-risk procedures is sparse. METHODS Since May 2008, data of more than 3000 patients who had TAVI were prospectively collected in the institutional TAVI Karlsruhe registry. Characteristics, peri- and postoperative outcome of patients with low coronary heights of ≤7 mm were analysed according to the Valve Academic Research Consortium-2. RESULTS Eighty-six patients with an average coronary height of 6.4 ± 1.1 mm (mean age 81.0 ± 5.3 years, logistic EuroSCORE I 19.6 ± 13.3%) were treated. TAVI was performed in 72 transfemoral (83.…
Role of balloon occlusion for mononuclear bone marrow cell deposition after intracoronary injection in pigs with reperfused myocardial infarction
Aims In clinical studies on cell therapy for acute myocardial infarction (MI), cells are usually applied by intracoronary infusion with balloon (IC/B). To test the utility of balloon occlusion, mononuclear bone marrow cell (MNC) retention after intracoronary infusion without balloon (IC/noB) was compared with IC/B and intramyocardial (IM) injection. Methods and results Four hours after LAD ligation in male pigs, reperfusion was allowed (confirmed by coronary angiography). Five days later, 1 × 108 autologous 111Indium-labelled MNC were injected IC/noB ( n = 4), IC/B ( n = 4), or IM ( n = 4). At 1 h the fraction of injected MNC that was detected in the heart was 4.1 ± 1.1% after IC/noB inject…
Oxygen Radical Scavengers
The myocardium can tolerate only relatively short periods of total myocardial ischemia without myocardial cell death. Following short ischemic periods, ischemic damage is reversible by reperfusion. However, with increasing duration and severity of ischemia, the damage inflicted to cardiomyocytes following reperfusion becomes irreversible. The combined pathologic events in the myocardium that follow a critical period of ischemia and leading to either reversible or irreversible damage to both cardiomyocytes and cardiac microvasculature is known as ischemia-reperfusion injury (Goldhaber and Weiss 1992).