Novel concept of less invasive concomitant surgical aortic valve replacement and coronary artery bypass grafting avoiding full median sternotomy.

In the last decades, minimally invasive procedures have been developed in the therapy of aortic valve disorders. Recently, a novel concept of minimally invasive coronary revascularization in multivessel disease via left anterior mini-thoracotomy demonstrated promising results. Full median sternotomy, as a very invasive procedure, is the standard approach in concomitant surgical aortic valve replacement (sAVR) and coronary bypass grafting (CABG). The aim of our study was to show that the combination of minimal invasive aortic valve replacement via upper mini-sternotomy and coronary artery bypass grafting via left anterior mini-thoracotomy is feasible to avoid full median sternotomy. From 07/2022 to 09/2022, concomitant sAVR via upper partial sternotomy and CABG via left anterior mini-thoractomy on cardiopulmonary bypass and cardioplegic arrest was successfully performed in six consecutive patients (6 males; 69.8 ± 7.4 [60-79] years). All patients had severe aortic stenosis (MPG 45.5 ± 17.3 mmHg) and a significant coronary artery disease (three-vessel: 33%, two-vessel: 33%, one-vessel: 33%) with indication to cardiac surgery. Mean EuroScore2 was 3.2. All patients underwent successful less invasive concomitant biological sAVR and CABG. 67% of patients received a 25 mm, 33% received a 23 mm biological aortic valve replacement (Edwards Lifesciences Perimount). A total of 11 distal anastomoses (1.8 ± 1.0 [1-3] per patient) were performed by using left internal artery mammary (50%), radial artery (17%) and saphenous venous graft (67%) for grafting the left anterior descending (83%), circumflex (67%) and right (33%) coronary artery. Hospital mortality was 0%, stroke rate was 0%, myocardial infarction was 0% and repeat revascularization rate was 0%, ICU stay was 1 day in 83% of all patients and 50% left hospital within 8 days after surgery. Less invasive concomitant surgical aortic valve replacement and coronary artery bypass grafting using upper mini-sternotomy and left anterior mini-thoracotomy is feasible without compromises in surgical principles and complete coronary revascularization while maintaining thoracic stability by avoiding full median sternotomy.

Development of In-Hospital Outcomes in Patients undergoing Transcatheter Aortic Valve Implantation (TAVI) at an Interdisciplinary Heart Center: A Single-Center Experience of 489 Consecutive Cases.

Background: Transcatheter Aortic Valve Implantation (TAVI) has emerged over time, reflected in appropriate adjustments in the European Society of Cardiology (ESC) guidelines in 2007, 2012 and 2017. Objective: The aim of this study was to analyze in-hospital outcomes after TAVI in the development within a single heart center over a period of 10 years depending on adjustments in the guidelines, infrastructural and procedural determinants. Methods: 489 consecutive patients who underwent TAVI from 2010 and 2019 at our center were analyzed retrospectively. Patients were divided into 3 groups of different treatment circumstances depending on guidelines adjustments and local infrastructural progress (group 1: 2010-2015 (n = 132), group 2: 2016-2017 (n = 155), group 3: 2018-2019 (n = 202). The primary endpoint was defined as all-cause in-hospital mortality. Secondary endpoints were selected according to the Valve Academic Research Consortium (VARC)-2 definitions. Multivariate logistic regression analysis was performed to determine predictors of in-hospital mortality. Statistical significance was assumed for p < 0.05. Results: 489 patients (346 (70.8 %) transfemoral and 143 (29.2 %) transapical) underwent TAVI. Comparing periods (group 1 vs. 2 vs. 3) age (82.1 ± 6.2 vs. 82.5 ± 4.8 vs. 81.1 ± 5.1 years, p = 0.012) and EuroSCORE II (8.4 ± 6.0 vs. 5.8 ± 4.9 vs. 5.5 ± 5.0 %, p < 0.001) declined over time. Rates of in-hospital mortality decreased significantly (9.1 % vs. 5.8 % vs. 2.5 %, p = 0.029), especially with observed-to-expected mortality ratios indicating a disproportionate decline of in-hospital mortality (1.08 vs. 1.00 vs. 0.45). Furthermore, post-procedural complications, such as acute kidney injury stage 3 (10.6 % vs. 3.2 % vs. 4.5 %, p = 0.016) and bleeding complications (14.4 % vs. 11.6 % vs 7.9 %, p = 0.165) decreased from group 1 to 3. However, rates of permanent pacemaker implantations (7.6 % vs. 11.0 % vs. 22.8 %, p < 0.001) increased, associated with a switch towards self-expanding valves (0.0 % vs. 61.3 % vs. 76.7 %, p < 0.001). Length of hospitalization as well as stay at intensive care and intermediate care unit could be reduced significantly during the observation period. In multivariate analysis age (OR: 1.103; 95 % CI: 1.013 - 1.202; p = 0.025), creatinine level before TAVI (OR: 1.497; 95 % CI: 1.013 - 2.212; p = 0.043), atrial fibrillation (OR: 2.956; 95 % CI: 1.127 - 7.749; p = 0.028) and procedure duration (OR: 1.017; 95 % CI: 1.009 - 1.025; p < 0.001) could be identified as independent predictors of in-hospital mortality. Conclusion: This study identified age, creatinine level before TAVI, the presence of atrial fibrillation and procedure duration as independent predictors for in-hospital mortality. Although these predictors decreased during the observation period, the decline in hospital-mortality was disproportionate, which was indicated by an observed-to-expected mortality ratio of 0.45 for the last observation period. However, it can be assumed that apart from patient-related factors, there were further institutional, technical and procedural developments, which ran in parallel and affected in-hospital mortality rates after TAVI.

Early Results of Total Coronary Revascularization via Left Anterior Thoracotomy.

BACKGROUND: Avoidance of sternotomy while preserving complete revascularization remains challenging in multivessel coronary disease. Technical issues and in-hospital outcomes of total coronary revascularization via a small left anterior thoracotomy (TCRAT) in nonselected patients with multivessel disease are reported. METHODS: From November 2019 to September 2021, coronary artery bypass grafting via left anterior minithoracotomy on cardiopulmonary bypass and cardioplegic cardiac arrest was performed in 102 patients (92 males; 67 ± 10 [42-87] years). Slings were placed around ascending aorta, left pulmonary veins, and inferior vena cava for exposure of lateral and inferior ventricular wall. All patients had multivessel coronary disease (three-vessel disease: n = 72; two-vessel disease: n = 30; left main stenosis: n = 44). We included patients at old age (> 80 years, 14.7%), with severe left ventricular dysfunction (ejection fraction < 30%, 6.9%), massive obesity (body mass index > 35, 11.6%), and at increased risk (EuroSCORE II > 4, 15.7%). RESULTS: Left internal thoracic artery (n = 101), radial artery (n = 83), and saphenous vein (n = 39) grafts were used for total (61.8%) or multiple (19.6%) arterial grafting. A total of 323 distal anastomoses (3.2 ± 0.7 [2-5] per patient) were performed to revascularize left anterior descending (100%), circumflex (91.2%), and right coronary artery (67.7%). Complete revascularization was achieved in 95.1%. In-hospital mortality was 2.9%, stroke rate was 1.0%, myocardial infarction rate was 2.9%, and repeat revascularization rate was 2.0%. CONCLUSION: This novel surgical technique allows complete coronary revascularization in the broad majority of multivessel disease patients without sternotomy. TCRAT can be introduced into clinical routine safely. Long-term results remain to be investigated.

[Impact of the COVID-19 pandemic on cardiac surgery]. / Auswirkungen der COVID-19-Pandemie auf die Herzchirurgie.

Since the beginning of 2020, the coronavirus disease 2019 (COVID-19) pandemic had a massive impact on and also changed life worldwide and serious consequences have naturally been observed particularly in the healthcare sector. These affect patients as well as medical personnel of all professional groups, both in the outpatient and inpatient areas. As expected, cardiac surgery as a discipline that is more dependent than any other on available capacity in intensive care units, was severely affected by the impact of the pandemic. This article provides an overview of the consequences for clinical care, research and teaching as well as for continuing education in cardiac surgery.

Transcatheter mitral valve implantation versus conventional redo surgery for degenerated mitral valve prostheses and rings in a multicenter registry.

OBJECTIVES: Degeneration of mitral prostheses/rings may be treated by redo surgery, and, recently, by transcatheter valve-in-valve/ring implantation. This multicenter registry presents results of transcatheter valve-in-valve and repeat surgery for prostheses/rings degeneration. METHODS: Data provided by 10 German heart centers underwent propensity score-matched retrospective analysis. The primary endpoint was 30-day/midterm mortality. Perioperative outcome was assessed according to the Mitral Valve Academic Research Consortium criteria. Further, the influence of moderate or greater tricuspid regurgitation (TR) on 30-day/midterm mortality was analyzed. RESULTS: Between 2014 and 2019, 273 patients (79 transcatheter mitral valve-in-valve [TM-ViV] and 194 redo mitral valve replacement [Re-MVR]) underwent repeat procedure for mitral prosthesis/ring degeneration. Propensity score matching distinguished 79 patient pairs. European System for Cardiac Operative Risk Evaluation (EuroSCORE) II-predicted risk was 15.7 ± 13.7% in the TM-ViV group and 15.0% ± 12.7% in the Re-MVR group (P = .5336). TM-ViV patients were older (74.73 vs 72.2 years; P = .0030) and had higher incidence of atrial fibrillation (54 vs 40 patients; P = .0233). Severe TR incidence was similar (17.95% in TM-ViV vs 14.10%; P = .1741). Sixty-eight TM-ViV patients previously underwent mitral valve replacement, whereas 41 Re-MVR patients underwent valve repair (P < .0001). Stenosis was the leading degeneration mechanism in 42 TM-ViV versus 22 Re-MVR patients (P < .0005). The 30-day/midterm mortality did not differ between groups. Moderate or greater TR was a predictor of total (odds ratio [OR], 4.36; P = .0011), 30-day (OR, 3.76; P = .0180), and midterm mortality (OR, 4.30; P = .0378), irrespective of group. CONCLUSIONS: In both groups, observed mortality was less than predicted. Redo surgery enabled treatment of concomitant conditions, such as atrial fibrillation or TR. TR was shown to be a predictor of total, 30-day, and midterm mortality in both groups.

Novel concept of routine total arterial coronary bypass grafting through a left anterior approach avoiding sternotomy.

Coronary artery bypass grafting (CABG) via full sternotomy remains a very invasive procedure, often requiring prolonged recovery of the patient. We describe a novel, less invasive approach for totally arterial CABG via a small left anterior thoracotomy in a pilot series of 20 unselected patients. From January to March 2020, 20 consecutive patients (mean age 65.9 ± 9.2 years, 100% male, STS-score: 1.6 ± 2) underwent CABG using only arterial conduits via a small left anterior thoracotomy. Patients were operated on cardiopulmonary bypass with peripheral cannulation and transthoracic aortic cross-clamping. Pulling tapes encircling the great vessels, the arrested empty heart was rotated and moved within the pericardium to enable conventional anastomotic techniques especially on lateral and inferior wall coronary targets. In all patients, left internal mammary artery and radial artery were utilized for bypass with 3.3 ± 0.7 distal coronary anastomoses per patient. Anterior, lateral, and inferior wall territories were revascularized in 100%, 85%, and 70% of patients, respectively. Complete anatomical revascularization was achieved in 95% of patients. ICU stay was 1 day in 17 patients, and 14 of patients left the hospital within 8 days. There was no hospital death, no stroke, no myocardial infarction, and no repeat revascularization. In this pilot series of 20 patients, minimally invasive, totally arterial CABG with avoidance of sternotomy was technically feasible with favorable patient outcomes.

Description of a Heart Team approach to coronary revascularization and its beneficial long-term effect on clinical events after PCI.

OBJECTIVE AND BACKGROUND: We present a first description of a Heart Team (HT)-guided approach to coronary revascularization and its long-term effect on clinical events after percutaneous coronary intervention (PCI). The HT approach is a structured process to decide for coronary bypass grafting (CABG), PCI or conservative therapy in ad hoc situations as well as in HT conferences. As a hypothesis, during the long-term course after a PCI performed according to HT rules, a low number of late revascularizations, especially CABGs, are expected (F-PCI study). METHODS: In this monocentric study, the HT approach to an all-comer population was first analyzed and described in general with the help of a database. Next the use of a HT approach was described for a more homogeneous subgroup with newly detected CAD (1.CAD). Those patients in whom the HT decision was PCI (which was a 1.PCI) were then studied with the help of questionnaires for clinical events during a very long-term follow-up. Events were CABG, PCI, diagnostic catheterization (DCath) and death. RESULTS: A significant number of patients were presented to HT conferences: 22 % out of all 11,174 catheterizations, 24 % out of all 7867 CAD cases and 35 % out of 3408 1.CAD cases. Most of these patients had multi-vessel disease (MVD). Conference decisions were isolated CABG in 46-66 %, PCI in 10-14 %, valvular surgery in 9-16 %, HTx in 10-21 % (Endstage heart failure candidates for surgery) and conservative therapy (Medical or no therapy, additional diagnostic procedures or no adherence to recommended therapy) in 2-3 %. However, most PCIs, ad hoc and elective, were performed under Heart Team rules, but without conference. During follow-up of 1.PCI patients (Kaplan-Meier analysis), CABG occurred in only 15 % of patients, PCI in 37 % and DCath in 65 %; mortality of any course was 51 %. Mortalities were similar in one-vessel disease and in a population of the same year, matched for age and sex (p < 0.057), but mortality was higher in 1.PCI patients with MVD (p < 0.001). Beyond 2 years, Kaplan-Meier curves were linear. CONCLUSION: The structured Heart Team approach is an effective tool for ad hoc and conference-based clinical decision-making with a sustained clinical benefit. This is demonstrated in low late CABG (and PCI) rates after a 1.PCI, without elevated mortality. The all-comer population supports the universal value of these data. Stable annual event rates late after PCI suggest a conversion to stable CAD. Heart Team conferences are also important tools in cases of valvular and end-stage heart disease.

Incidence of deep sternal wound infection is not reduced with autologous platelet rich plasma in high-risk cardiac surgery patients.

BACKGROUND: Deep sternal wound infections (DSWI) remain a devastating complication in cardiac surgery applying full sternotomy. As the risk profile in cardiac surgery changed toward an older and sicker population, the incidence of DSWI increases. Platelet rich plasma (PRP) holds promise in tissue regeneration with respect to bone regeneration, reduction of bleeding, and accelerated wound healing. The effect of PRP on DSWI was investigated in high-risk patients undergoing cardiac surgery with full sternotomy. METHODS: 196 consecutive patients at risk of DSWI were randomized to application of autologous PRP before sternal wiring (n = 97) or control (n = 99). All patients underwent cardiac surgery on cardiopulmonary bypass with cardioplegic cardiac arrest. Endpoint was occurrence of DSWI requiring revision surgery. RESULTS: Demographic, intraoperative, and perioperative variables as well as risk factors were comparable between groups. Incidence of DSWI was not different between the PRP-group and the control-group (6/97 (6.2%) vs. 3/99 (3.0%); n.s.). CONCLUSIONS: Local application of autologous PRP in cardiac surgery patients with full sternotomy at high risk for sternal complications did not reduce the incidence of DSWI.

Extravascular perivenous fibrin support leads to aneurysmal degeneration and intimal hyperplasia in arterialized vein grafts in the rat.

BACKGROUND AND AIMS: External support of vein grafts by fibrin glue possibly prevents overdistension, vascular remodeling, and neointimal hyperplasia. Previous animal models of neointimal hyperplasia showed conflicting results. Here, long-term effects of external fibrin glue support were studied in a new rat model of jugular vein to abdominal aorta transposition. MATERIALS AND METHODS AND METHODS: In male Wistar rats (250-300 g) right jugular vein (1.0-1.5 cm) was transposed to the infrarenal aorta. Fibrin glue (0.25 ml) covered the vein before releasing the vascular clamps (n = 6). Control vein grafts were exposed directly to blood pressure. After 16 weeks vein grafts were pressure-fixed for histology. Intima thickness, luminal and intimal area were measured by planimetry and elastic fibers demonstrated by Elastica van Giesson staining. RESULTS: Intimal thickness (74.04 +/- 6.7 microm vs 1245 +/- 187 microm, control vs fibrin treatment; p < 0.001), intimal area (2517.16 +/- 355 mm(2) vs 18424 +/- 4927 mm(2), control vs fibrin treatment; p < 0.05) and luminal area (2184.75 +/- 347 mm(2) vs 7231.85 +/- 1782 mm(2), control vs fibrin treatment; p < 0.05) were significantly increased, elastic fibers in the vessel wall were diminished and the vessel wall infiltrated by mononuclear cells in fibrin glue supported veins. CONCLUSION: External support of vein grafts by fibrin glue leads to aneurysmal degeneration and intimal hyperplasia, thereby possibly jeopardizing long-term graft patency.

Surgical treatment of pulmonary aspergillosis/mycosis in immunocompromised patients.

Invasive pulmonary aspergillosis is a severe complication in immunosuppressed patients. Surgical resection can be curative in certain patients after antifungal treatment. Over a 7-year period, ten patients with suspected invasive pulmonary aspergillosis of two university hospitals were retrospectively reviewed. A literature review was undertaken. Patient's age was 48.1 years (mean); the cause of immunosuppression was a hematological disease with consecutive therapy in seven patients and chronically corticoid therapy in three patients. After an antifungal therapy, surgical resection was performed with lobectomy/segmentectomy in 60% and with wedge-resection in 40%. Postoperative course were uneventful in seven patients, two patients died due to infectional circumstances, and one patient was reoperated because of empyema. The underlying disease marked long-term follow-up. Resection of focal pulmonary invasive aspergillosis can be curative. Clinical circumstances and dissemination must be taken into consideration to indicate surgery. To point out the best pathway randomised prospective studies are necessary.

Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing cardiac surgery: a meta-analysis of over 30,000 patients.

AIMS: To determine the strength of evidence for preoperative statin use for prevention of adverse postoperative outcomes in patients undergoing cardiac surgery. METHODS AND RESULTS: After literature search in major databases, 19 studies were identified [three RCT (randomized prospective clinical trials), 16 observational] that reported outcomes of 31 725 cardiac surgery patients with (n = 17 201; 54%) or without (n = 14 524; 46%) preoperative statin therapy. Outcomes that were analysed included early all-cause mortality (30-day mortality), myocardial infarction (MI), atrial fibrillation (AF), stroke and renal failure. Odds ratio (OR) with 95% confidence intervals (95%CI) were reported using fixed or random effect models and publication bias was assessed. Preoperative statin therapy resulted in a 1.5% absolute risk reduction (2.2 vs. 3.7%; P < 0.0001) and 43% odds reduction for early all-cause mortality (OR 0.57; 95%CI: 0.49-0.67). A significant reduction (P < 0.01) in statin pretreated patients was also observed for AF (24.9 vs. 29.3%; OR 0.67, 95%CI: 0.51-0.88), stroke (2.1 vs. 2.9%, OR 0.74, 95%CI: 0.60-0.91), but not for MI (OR 1.11; 95%CI: 0.93-1.33) or renal failure (OR 0.78, 95%CI: 0.46-1.31). Funnel plot and Egger's regression analysis (P = 0.60) excluded relevant publication bias. CONCLUSION: Our meta-analysis provides evidence that preoperative statin therapy exerts substantial clinical benefit on early postoperative adverse outcomes in cardiac surgery patients, but underscores the need for RCT trials.

Angiotensin II and myosin light-chain phosphorylation contribute to the stretch-induced slow force response in human atrial myocardium.

AIMS: Stretch is an important regulator of atrial function. The functional effects of stretch on human atrium, however, are poorly understood. Thus, we characterized the stretch-induced force response in human atrium and evaluated the underlying cellular mechanisms. METHODS AND RESULTS: Isometric twitch force of human atrial trabeculae (n = 252) was recorded (37 degrees C, 1 Hz stimulation) following stretch from 88 (L88) to 98% (L98) of optimal length. [Na(+)](i) and pH(i) were measured using SBFI and BCECF epifluorescence, respectively. Stretch induced a biphasic force increase: an immediate increase [first-phase, Frank-Starling mechanism (FSM)] to approximately 190% of force at L88 followed by an additional slower increase [5-10 min; slow force response (SFR)] to approximately 120% of the FSM. FSM and SFR were unaffected by gender, age, ejection fraction, and pre-medication with major cardiovascular drugs. There was a positive correlation between the amplitude of the FSM and the SFR. [Na(+)](i) rose by approximately 1 mmol/L and pH(i) remained unchanged during the SFR. Inhibition of Na(+)/H(+)-exchange (3 microM HOE642), Na(+)/Ca(2+)-exchange (5 microM KB-R7943), or stretch-activated channels (0.5 microM GsMtx-4 and 80 microM streptomycin) did not reduce the SFR. Inhibition of angiotensin-II (AngII) receptors (5 microM saralasin and 0.5 microM PD123319) or pre-application of 0.5 microM AngII, however, reduced the SFR by approximately 40-60%. Moreover, stretch increased phosphorylation of myosin light chain 2 (MLC2a) and inhibition of MLC kinase (10 microM ML-7 and 5 microM wortmannin) decreased the SFR by approximately 40-85%. CONCLUSION: Stretch elicits a SFR in human atrium. The atrial SFR is mediated by stretch-induced release and autocrine/paracrine actions of AngII and increased myofilament Ca(2+) responsiveness via phosphorylation of MLC2a by MLC kinase.

Accelerated intimal hyperplasia in aortocoronary internal mammary vein grafts in minipigs.

BACKGROUND: More than 50% of aortocoronary saphenous vein grafts are occluded 10 years after surgery. Intimal hyperplasia is the initial critical step in the progression toward occlusion. Internal mammary veins, which are physiologically prone to less hydrostatic pressure, may undergo an accelerated progression to intimal hyperplasia and thus be suitable for investigation of the mechanisms of aortocoronary vein graft disease. METHODS: Six minipigs underwent aortocoronary bypass grafting using standard cardiopulmonary bypass and cardioplegic arrest. Mammary vein were grafted in a reversed manner from ascending aorta to left anterior descending coronary artery (LAD). The proximal LAD was ligated, rendering the anterior left ventricle vein graft-dependent. Minipigs were killed after 4 weeks, and vein grafts were harvested. Histological and immunohistological investigation were performed with respect to morphometric analysis, endothelial damage/dysfunction (v-Willebrand-factor (vWF)), smooth muscle cells (alpha-smooth actin) and proliferation rate (proliferation marker Ki 67). RESULTS: Mean intimal area of vein grafts was increased compared to ungrafted mammary veins. Intimal hyperplasia in vein grafts was characterized by massive accumulation of smooth muscle cells with a high proliferation rate and endothelial perturbation. Significant (p = 0.001) intimal hyperplasia of the grafted mammary vein compared to the ungrafted mammary vein was found. These changes were absent in ungrafted mammary veins. CONCLUSION: The present study demonstrates a pig model of aortocoronary vein graft intimal hyperplasia which is characterized by an accelerated progression within internal mammary veins. The model is suitable to investigate the pathophysiology of aortocoronary vein graft intimal hyperplasia as well as therapeutic approaches.

Methylprednisolone fails to preserve pulmonary surfactant and blood-air barrier integrity in a porcine cardiopulmonary bypass model.

BACKGROUND: Pulmonary inflammation after cardiac surgery with cardiopulmonary bypass (CPB) has been linked to respiratory dysfunction and ultrastructural injury. Whether pretreatment with methylprednisolone (MP) can preserve pulmonary surfactant and blood-air barrier, thereby improving pulmonary function, was tested in a porcine CPB-model. MATERIALS AND METHODS: After randomizing pigs to placebo (PLA; n = 5) or MP (30 mg/kg, MP; n = 5), animals were subjected to 3 h of CPB with 1 h of cardioplegic cardiac arrest. Hemodynamic data, plasma tumor necrosis factor-alpha (TNF-alpha, ELISA), and pulmonary function parameters were assessed before, 15 min after CPB, and 8 h after CPB. Lung biopsies were analyzed for TNF-alpha (Western blot) or blood-air barrier and surfactant morphology (electron microscopy, stereology). RESULTS: Systemic TNF-alpha increased and cardiac index decreased at 8 h after CPB in PLA (P < 0.05 versus pre-CPB), but not in MP (P < 0.05 versus PLA). In both groups, at 8 h after CPB, PaO2 and PaO2/FiO2 were decreased and arterio-alveolar oxygen difference and pulmonary vascular resistance were increased (P < 0.05 versus baseline). Postoperative pulmonary TNF-alpha remained unchanged in both groups, but tended to be higher in PLA (P = 0.06 versus MP). The volume fraction of inactivated intra-alveolar surfactant was increased in PLA (58 +/- 17% versus 83 +/- 6%) and MP (55 +/- 18% versus 80 +/- 17%) after CPB (P < 0.05 versus baseline for both groups). Profound blood-air barrier injury was present in both groups at 8 h as indicated by an increased blood-air barrier integrity score (PLA: 1.28 +/- 0.03 versus 1.70 +/- 0.1; MP: 1.27 +/- 0.08 versus 1.81 +/- 0.1; P < 0.05). CONCLUSION: Despite reduction of the systemic inflammatory response and pulmonary TNF-alpha generation, methylprednisolone fails to decrease pulmonary TNF-alpha and to preserve pulmonary surfactant morphology, blood-air barrier integrity, and pulmonary function after CPB.

The impact of subarachnoid hemorrhage on regional cerebral blood flow and large-vessel diameter in the canine model of chronic vasospasm.

OBJECTIVE: The aim of this study was to correlate changes in regional cerebral blood flow (rCBF) to the degree of cerebral vasospasm in the canine two-hemorrhage model of subarachnoid hemorrhage (SAH). METHODS: SAH was induced in 13 adult beagle dogs using the two-hemorrhage model. Eleven beagle dogs served as controls. Angiography of the basilar artery and measurements of rCBF with colored microspheres were performed on days 1 and 8. Diameter of the basilar artery was calculated at equidistant points from the angiogram. RESULTS: In controls, basilar artery diameter (mm) and rCBF (mL/min/g) were equal on days 1 and 8. In the SAH group, basilar artery diameter decreased significantly (1.27 +/- 0.17 [mean +/- SD]-0.84 +/- 0.15 mm). rCBF decreased significantly (P < .05) in the cerebrum (1.69 +/- 0.54 [mean +/- SD]-1.06 +/- 0.45 mL/min/g), cerebellum (1.18 +/- 0.40-0.80 +/- 0.32 mL/min/g), and brain stem (0.81 +/- 0.33-0.51 +/- 0.21 mL/min/g). However, decrements in CBF were not correlated to the reduction in vessel caliber in the corresponding vascular territory. CONCLUSION: Induced SAH in the canine model produces a significant impairment in rCBF irrespective of the degree of vasospasm of large cerebral vessels. The findings support the presumptive role of the microvasculature in regard to delayed cerebral ischemia after SAH.

Cardiopulmonary and systemic effects of methylprednisolone in patients undergoing cardiac surgery.

BACKGROUND: Cardiopulmonary bypass (CPB)-related inflammatory response can be attenuated by glucocorticoid treatment, but its impact on postoperative cardiopulmonary function remains controversial. It was investigated whether the systemic and myocardial antiinflammatory effects of glucocorticoids are associated with improved cardiopulmonary function in cardiac surgery patients. METHODS: Eighty patients undergoing elective coronary artery bypass grafting were randomly assigned to receive a single shot of methylprednisolone (15 mg/kg) or placebo before CPB. Variables of myocardial and pulmonary function and systemic hemodynamics were measured before and 1, 4, 10, and 24 hours after CPB. Blood was sampled for measurement of proinflammatory (tumor necrosis factor-alpha, interleukin 6, interleukin 8) and antiinflammatory (interleukin 10) cytokines (by enzyme-linked immunoassay), troponin T, and C-reactive protein. Phosphorylation of inhibitory kappa-B alpha and p38 mitogen-activated protein kinase was determined in right atrial biopsies before and after CPB (phosphoprotein assay). RESULTS: Preoperative and intraoperative characteristics of patients were not different between groups. Methylprednisolone attenuated postoperative tumor necrosis factor-alpha, interleukin 6, interleukin 8, and C-reactive protein levels while increasing interleukin 10 release. Myocardial inhibitory kappa-B alpha was preserved with methylprednisolone (p < 0.05 versus placebo), but p38 mitogen-activated protein kinase activation occurred in both groups after CPB (p < 0.05 versus before CPB). Methylprednisolone improved postoperative cardiac index and was associated with decreased troponin T when compared with placebo (p < 0.05). Postoperative blood glucose, oxygen delivery index, and pulmonary shunt flow were increased in the methylprednisolone group (p < 0.05). There was no difference in postoperative oxygenation index, ventilation time, and clinical outcome between treatment groups. CONCLUSIONS: Glucocorticoid treatment before CPB attenuates perioperative release of systemic and myocardial inflammatory mediators and improves myocardial function, suggesting potential cardioprotective effects in patients undergoing cardiac surgery.

Three reactive compartments in venous malformations.

Vascular malformations affect 3% of neonates. Venous malformations (VMs) are the largest group representing more than 50% of cases. In hereditary forms of VMs gene mutations have been identified, but for the large group of spontaneous forms the primary cause and downstream dysregulated genes are unknown. We have performed a global comparison of gene expression in slow-flow VMs and normal saphenous veins using human whole genome micro-arrays. Genes of interest were validated with qRT-PCR. Gene expression in the tunica media was studied after laser micro-dissection of small pieces of tissue. Protein expression in endothelial cells (ECs) was studied with antibodies. We detected 511 genes more than four-fold down- and 112 genes more than four-fold up-regulated. Notably, chemokines, growth factors, transcription factors and regulators of extra-cellular matrix (ECM) turnover were regulated. We observed activation and "arterialization" of ECs of the VM proper, whereas ECs of vasa vasorum exhibited up-regulation of inflammation markers. In the tunica media, an altered ECM turnover and composition was found. Our studies demonstrate dysregulated gene expression in tunica interna, media and externa of VMs, and show that each of the three layers represents a reactive compartment. The dysregulated genes may serve as therapeutic targets.

Large emboli on their way through the heart - first live demonstration of large paradoxical embolisms through a patent foramen ovale.

We report a case of large paradoxical embolisms through a patent foramen ovale in a patient with acquired heparin-induced thrombocytopenia type II (HIT). One large ventricular thrombus embolizing through the aortic valve was documented on videotape for the first time while performing transesophageal echocardiography. A 56-year-old man was admitted with acute respiratory failure initially believed to have an exacerbated chronic obstructive pulmonary disease. Arterial oxygen saturation was only 33%. He received antibiotic and anti-obstructive treatments and was mechanically ventilated for 7 days. Few hours after extubation, he developed recurrent severe dyspnea accompanied by acute pain and pulselessness in his left leg. Transthoracic echocardiography revealed an enlarged right ventricle and suggested the presence of free-floating thrombi both in the right and in the left-heart cavities. During transesophageal echocardiography, a large serpentine left-heart thrombus embolized through the aortic valve and disappeared. The patient developed ventricular fibrillation and underwent successful cardiopulmonary resuscitation including emergency thrombolysis with alteplase. Four hours later, the surgeon retrieved a 20-cm long thrombus from the left femoral artery.

Prevention of TNFalpha-associated myocardial dysfunction resulting from cardiopulmonary bypass and cardioplegic arrest by glucocorticoid treatment.

OBJECTIVE: Cardiac surgery on cardiopulmonary bypass (CPB) results in progressive myocardial dysfunction, despite unimpaired coronary blood flow, and is associated with increased myocardial tumor necrosis factor-alpha (TNFalpha) expression. We investigated whether anti-inflammatory treatment prevents increased TNFalpha expression and myocardial dysfunction after CPB. METHODS AND RESULTS: Baseline systemic hemodynamics, myocardial contractile function, aortic and coronary blood flow were measured in anesthetized pigs. Then, placebo (PLA; saline; n=7) or methylprednisolone (MP; 30 mg/kg; n=6) was infused intravenously and CPB was instituted. Global ischemia was induced for 10 min by aortic cross-clamping, followed by 1 h of cardioplegic cardiac arrest. After declamping and reperfusion, CPB was terminated after a total of 3 h. Measurements were repeated at 15 min, 4 h, and 8 h following termination of CPB. Systemic TNFalpha-plasma concentrations and left ventricular TNFalpha expression were analyzed. With unchanged coronary blood flow in both groups, a progressive loss of myocardial contractile function to 38+/-2% of baseline (p<0.01) and cardiac index to 48+/-6% of baseline (p<0.01) at 8 h after CPB in PLA was attenuated in MP (myocardial function: 72+/-3%, p<0.01 vs PLA; cardiac index: 78+/-6%, p<0.05 vs PLA). Systemic TNFalpha was increased at 8 h in PLA compared to MP (243+/-34 vs 90+/-34 pg/ml, p<0.05). Myocardial TNFalpha was increased at 8 h after CPB compared to baseline and MP (p<0.05). Myocardial TNFalpha immunostaining was more pronounced in PLA than in MP (p<0.05), with TNFalpha-mRNA localization predominantly to cardiomyocytes. CONCLUSIONS: Methylprednisolone attenuates both systemic and myocardial TNFalpha increases and progressive myocardial dysfunction induced by cardiac surgery, suggesting a key role for TNFalpha.