H Reichenspurner

Individually Optimized Hemodynamic Therapy Reduces Complications and Length of Stay in the Intensive Care Unit A Prospective, Randomized Controlled Trial

Background:The authors hypothesized that goal-directed hemodynamic therapy, based on the combination of functional and volumetric hemodynamic parameters, improves outcome in patients with cardiac surgery. Therefore, a therapy guided by stroke volume variation, individually optimized global end-diastolic volume index, cardiac index, and mean arterial pressure was compared with an algorithm based on mean arterial pressure and central venous pressure. Methods:This prospective, controlled, parallel-arm, open-label trial randomized 100 coronary artery bypass grafting and/or aortic valve replacement patients to a study group (SG; n = 50) or a control group (CG; n = 50). In the SG, hemodynamic therapy was guided by stroke volume variation, optimized global end-diastolic volume index, mean arterial pressure, and cardiac index. Optimized global end-diastolic volume index was defined before and after weaning from cardiopulmonary bypass and at intensive care unit (ICU) admission. Mean arterial pressure and central venous pressure served as hemodynamic goals in the CG. Therapy was started immediately after induction of anesthesia and continued until ICU discharge criteria, serving as primary outcome parameter, were fulfilled. Results:Intraoperative need for norepinephrine was decreased in the SG with a mean (±SD) of 9.0 ± 7.6 versus 14.9 ± 11.1 µg/kg (P = 0.002). Postoperative complications (SG, 40 vs. CG, 63; P = 0.004), time to reach ICU discharge criteria (SG, 15 ± 6 h; CG, 24 ± 29 h; P < 0.001), and length of ICU stay (SG, 42 ± 19 h; CG, 62 ± 58 h; P = 0.018) were reduced in the SG. Conclusion:Early goal-directed hemodynamic therapy based on cardiac index, stroke volume variation, and optimized global end-diastolic volume index reduces complications and length of ICU stay after cardiac surgery.

Radial Artery Applanation Tonometry for Continuous Noninvasive Cardiac Output Measurement: A Comparison With Intermittent Pulmonary Artery Thermodilution in Patients After Cardiothoracic Surgery.

Objectives:Radial artery applanation tonometry allows completely noninvasive continuous cardiac output estimation. The aim of the present study was to compare cardiac output measurements obtained with applanation tonometry (AT-CO) using the T-Line system (Tensys Medical, San Diego, CA) with cardiac output measured by intermittent pulmonary artery thermodilution using a pulmonary artery catheter (PAC-CO) with regard to accuracy, precision of agreement, and trending ability. Design:A prospective method comparison study. Setting:The study was conducted in a cardiosurgical ICU of a German university hospital. Patients:We performed cardiac output measurements in 50 patients after cardiothoracic surgery. Interventions:None. Measurements and Main Results:Three independent sets of three consecutive thermodilution measurements (i.e., PAC-CO) each were performed per patient, and AT-CO was measured simultaneously. The average of the three thermodilution cardiac output measurements was compared with the average of the corresponding three AT-CO values resulting in 150 paired cardiac output measurements. In 13 patients, cardiac output–modifying maneuvers performed for clinical reasons additionally allowed to evaluate trending ability. For statistical analysis, we used Bland-Altman analysis, the percentage error, four-quadrant plot, and concordance analysis. Mean PAC-CO was 4.7 ± 1.2 L/min and mean AT-CO was 4.9 ± 1.1 L/min. The mean of differences was –0.2 L/min with 95% limits of agreement of –1.8 to + 1.4 L/min. The percentage error was 34%. The concordance rate was 95%. Conclusions:Continuous cardiac output measurement using the noninvasive applanation tonometry technology is basically feasible in ICU patients after cardiothoracic surgery. The applanation tonometry technology provides cardiac output values with reasonable accuracy and precision of agreement compared with intermittent pulmonary artery thermodilution measurements in a clinical study setting and is able to reliably track cardiac output changes induced by cardiac output–modifying maneuvers.

Human Induced Pluripotent Stem Cells for Tissue Engineered Cardiac Repair

Objectives: Myocardial infarction causes unrecoverable loss of cardiomyocytes. Engineered heart tissue (EHT) is an in vitro model of three-dimensional cardiomyocyte network with morphological and functional similarity to native heart tissue. We transplanted EHTs from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) on cryo-injured guinea pig hearts and investigated whether hiPSC-CM-EHTs support left ventricular function. Methods: Human iPSC were generated by retroviral reprogramming of dermal fibroblasts. Cardiac differentiation of hiPSC was performed by an embryoid body-based three-stage differentiation protocol. EHTs were created from hiPS-CM (5*10^6 cardiomyocytes and 2*10^6 GFP+-HUVECs per EHT) and cultivated for 3 weeks. Development of contractile force was monitored prior to transplantation. Left ventricular myocardial cryo-injury was induced in adult guinea pigs (n = 21). 7 days after injury EHTs (2 per animal, n = 12) or cell-free constructs (n = 9) were implanted. Animals received ciclosporin and methylprednisolon for immunosuppression. Functional parameters were examined by echocardiography and histology at baseline, before and 28 days after transplantation. Results: The cardiac differentiation protocol resulted in a cell population with ∼50% cardiomyocytes, which was further enriched by lactate-based selection to > 90% purity and directly used for EHT generation. HiPSC-CM-EHTs developed contractile force and displayed morphological properties of native heart tissue. Cryo-injury of the guineea pigs resulted in large transmural scars (∼30% of ventricular wall), which were verified histologically. Immunohistochemical staining for dystrophin and MLC2v showed the formation of large islets of cross-striated muscle tissue in the scar. The human origin was demonstrated by fluorescent-in-situ-hybridization. The new myocardium was vascularized with endothelium partly being of human origin. Animals receiving cell-free constructs showed left ventricular dilatation 28 days after transplantation. The EHT-group showed less dilatation (LV end-diastolic diameter 8.9 ± 0.4 mm versus 9.7 ± 0.7 mm in 28d control [basal 8.1 ± 0.2 mm, 7d post cryo-injury 8.2 ± 0.2 mm]) and significantly better fractional area shortening (42.0 ± 4.5% versus 23.0 ± 3.2% in 28d control [basal 42.2 ± 1.9%, 7d post cryo-injury 26.1 ± 2.1%]). Conclusion: Transplantation of hiPSC-derived EHTs in a guinea pig cryo-injury model under generates new myocardium and improves cardiac function.

Tissue-Engineered Cardiovascular Products

Abstract Tissue engineering of heart valves, small-diameter blood vessels, and myocardial patches is an exciting field with great clinical potential. The concerted research activity of several disciplines in the biomedical and engineering fields has yielded significant progress. It is still a major challenge to reproduce the exquisite natural design of any of the cardiovascular structures, but the first truly tissue-engineered vascular grafts have been implanted as AV-shunts in patients with diabetes and showed very good performance. Thus, cardiovascular tissue engineering entered the clinical arena. Current attempts to make the techniques simpler and provide readily available and cost-effective products look promising. Myocardial tissue engineering is less advanced yet, but the dramatic progress in stem cell technologies made cardiac repair with engineered heart grafts a realistic option for patients with malformations and heart failure in a foreseeable future.

Central venous-arterial carbon dioxide gradient is a prognostic factor of mortality in patients admitted to intensive care unit after cardiac surgery

Objectives: Increased venous hypercarbia is related to systemic hypoperfusion in various conditions of reduced hemodynamics. This retrospective investigation was started to evaluate the value of venous-arterial carbon dioxide gradient (dpCO2) measurement after cardiac surgery as predictor of mortality. Methods: 454 patients after cardiac surgery with cardiopulmonary bypass were examined. Admission and perioperative data were recorded. For dpCO2 receiver operating curve was generated. Optimal cut-off-value was calculated to determine the best predictor of mortality. Therefore patients were separated in high-dpCO2 and low-dpCO2. Mann-Whitney-U-test and fischers exact test were used to detect differences between these groups. Results: For dpCO2 area under the curve was 0.717 and the optimal cut-off-value was 9.15mmHg. According to this value sensitivity was 67% and specificity was 80% for mortality. There was a statistically difference detected between low-dpCO2 versus highdpCO2 for mortality (0.84% vs. 3.09%; p=0.004). There were no differences detected for Euro-score (3.91±2.65 vs. 4.01±2.2; p=0.52), cardiopulmonary bypass time (136.23 ±53.98min. vs. 149.33±75.42min., p=0.33), Cross clamp time (85.02±43.26min. vs. 96.12±50.63min.; p=0.14). There were no differences for the admission-values lactate (2.08±1.96mmol/l vs. 2.3±2.92mmol/l, p=0.58), base excess (-2.56±2.26mmol/l vs. -2.87±2.32mmol/l; p=0.25) and pH (7.36±0.07 vs. 7.37±0.08; p=0.07), excepted for ScvO2 (72.86±7.76% vs. 62.49±10.62%; p<0.001). No differences were detected for ICU-stay (2.92±2.12d vs.3.31±2.69d; p=0.32) and morbidity (6.44% vs. 10.31%; p=0.19). Conclusion: These data suggest that increased dpCO2 may be useful to predict outcome in patients admitted after cardiac surgery. Delta-pCO2 above 9.15mmHg is associated with an increased risk of mortality in these patients.

Pharmacokinetics of aerosolized tacrolimus in rats

immunsuppression, to prevent acute rejection after transplantation and to overcome graft vs. host disease or haematological disorders. ATGs induce apoptosis and complement-mediated cell death in peripheral T-lymphocytes having the potential to inhibit leukocyte adhesion by direct binding to adhesion molecules. The aim of our study was to investigate the expression of adhesion and inflammation molecules in an ischemia/reperfusion model after low-dose treatment with ATGs. Methods and Materials: Extremities of cynomolgus monkeys (n 19) were flushed with Ringer’s lactate solution at 4 C° via either the femoral or the brachial artery. After 60 minutes of ischemia the limbs were reperfused with human blood. Three low-dosed ATGs (1.5 mg/kg) were added to the blood 30 min prior to the reperfusion. The limbs (n 60) were assigned to four groups: ATG-1 group (n 16), ATG-2 group (n 16), ATG-3 (n 12) and control group (without ATG; n 16). Biopsies from muscular tissue were obtained. Expression of inflammation (IL-1, IL-6, TNF) and adhesion (ICAM-1, VCAM-1, PECAM, CD62E) molecules was investigated by means of immunhistochemistry. Semi-quantitative analysis was performed by two independent observers. Results: Histological and immunohistochemical analyses showed a decrease in vascular and perivascular infiltration and inflammatory reactions after ATG administration in all ATG-groups. Expression of the inflammatory molecules IL-1 and IL-6 was significantly decreased in the ATG-groups. The adhesion molecules studied (ICAM-1, VCAM-1, PECAM, CD62E), were decreased in the ATG-groups in muscle, endothelium, and in perivascular structures. Conclusions: ATGs demonstrate not only a direct immunosuppressive activity by depleting WBC but also a decrease of the expression of inflammation and adhesion molecules. This fact may be responsible for the reduced leukocyte-endothelium interactions in our ischemia/ reperfusion model.

Pseudoaneurysm Complicating Homograft Aortic Valve Replacement - Two Different - Courses and Strategies

The courses of two patients with pseudoaneurysm formation following aortic valve replacement using homografts are reported. Both patients had aortic valve replacement due to acute infective endocarditis with paravalvular abscess formation. The first case had an uneventful postoperative course; but on routine echocardiography, a pseudoaneurysm located at the left coronary commissure was found at one year follow-up. As the pseudoaneurysm was completely asymptomatic, the patient was followed up carefully at six months intervals. The second patient also had pseudoaneurysm formation postoperatively, but he presented one year after surgery with fever and elevated leucocyte count. He had surgical revision of the pseudoaneurysm because no other reason for an infection could be found. Four months later he presented again with infection signs and pseudoaneurysm formation. This time, the homograft was completely excised and another homograft was implanted. One year after the final operation, he is now free from re-infection. The two presented courses show that pseudoaneurysms complicating aortic valve replacement should be managed according to attendant circumstances and symptoms.