Marius Grossmann

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.

A Three-Group Model to Predict Mortality in Emergent Coronary Artery Bypass Graft Surgery

BACKGROUND Emergent coronary artery bypass graft surgery (CABG) for acute myocardial infarction is associated with an increased operative risk. For estimation of mortality risk, the European System for Cardiac Operative Risk Evaluation (EuroSCORE) is appropriate up to a medium risk score (<6 points). To predict mortality risk more accurately in cases of higher EuroSCORE, additional cardiac data can be helpful. METHODS Over a 3-year period, patient data including acute myocardial infarction and emergent CABG were retrospectively reviewed. Univariate and multivariate analysis for in-hospital mortality was performed. The EuroSCORE analysis and follow-up was investigated. RESULTS Overall in-hospital mortality was 18.3%. Preoperative cardiac related predictors for in-hospital mortality were cardiogenic shock (p < 0.001), very poor left ventricular function (p = 0.001), and ST-segment elevation (p = 0.012). In multivariate regression analysis, age, cardiogenic shock, and pulmonary hypertension were independent preoperative risk factors. According to the EuroSCORE, we could define three statistically different groups: intermediate-risk, high-risk, and very high risk, with an observed mortality of 3.3%, 20.0%, and 63.2%, respectively. The EuroSCORE correlates with but overestimates the mortality risk. In subgroup analysis, the creatine kinase-myocardial band/hour ratio for the intermediate-risk group and ST-segment elevation for the high-risk group were additional cardiac risk factors. CONCLUSIONS Patients with an acute myocardial infarction and emergency aortocoronary CABG have an elevated operative risk. Logistic EuroSCORE overestimates the mortality rate. Three different risk groups can be defined, in which creatine kinase-MB/h-ratio and ST-segment elevation can more accurately predict operative risk.

Miniaturized HIA microdiagonal pump as left ventricular assist device in a sheep model.

We evaluated the newly developed miniaturized HIA microdiagonal blood pump (MDP) as a continuous flow left ventricular assist device. In a sheep model (n = 6), the MDP was implanted through left lateral thoracotomy and placed paracorporeally with inflow conduit to left atrium and outflow conduit to descending aorta. The sheep were pumped at a mean flow rate of 2.5 L/min for 7 days. Anticoagulation was applied by intravenous heparin administration. Postoperatively, activated clotting time was held stable with values of 200 seconds. During follow-up, blood samples (creatinine kinase, creatinine, glutamic-oxaloacetic transaminase (aspartate aminotransferase) (GOT), glutamate dehydrogenase (GLDH), gamma-GT, plasma-free hemoglobin, and hemoglobine) were taken daily. After 7 days, the sheep were killed for macroscopic examination. Systemic artery pressures remained stable during the whole test period. Because of operative reasons, the hemoglobin value (7.5 ± 0.61 g/dl) decreased perioperatively, but recovered within the test period, whereas creatinine kinase increased initially after thoracotomy, but decreased to normal within days. Renal and liver functions were slightly impaired perioperatively, indicated by temporarily enhanced values of GOT, gamma-GT, GLDH, and creatinine. The MDP did not produce significant hemolysis as measured by plasma-free hemoglobin levels. Wound infections did not occur. We conclude that the MDP ran successfully as an left ventricular assist device for 7 days in sheep has potential for long-term support, and may serve as an alternative to current technologies. Presented data were not obtained in a clinical trial; however, the results are promising enough to proceed with longer duration animal studies.

Norman Edward Shumway – Pionier der Herzchirurgie (9. Februar 1923 bis 10. Februar 2006)

ZusammenfassungAm 10. Februar 2006 verstarb der amerikanische Herzchirurg Norman Edward Shumway 1 Tag nach seinem 83. Geburtstag in Palo Alto, Kalifornien, USA, an den Folgen eines Lungenkrebsleidens.Norman E. Shumway, Pionier der Herzchirurgie, trug maßgeblich dazu bei, Herztransplantationen von Mensch zu Mensch zu ermöglichen. Bereits Anfang der 60er Jahre führte er bahnbrechende experimentelle Arbeiten zur Entwicklung einer Transplantationstechnik an Hunden durch, die er in Zusammenarbeit mit seinem Team, allen voran mit dem Kollegen Richard R. Lower, in den folgenden Jahren Schritt für Schritt kontinuierlich weiterentwickelte. Nach diesen umfangreichen tierexperimentellen Vorarbeiten stand er im Jahre 1967 mit seinem herzchirurgischen Team der Stanford University an der Schwelle, die weltweit erste Herztransplantation von Mensch zu Mensch durchzuführen, allerdings kamen ihm der Südafrikaner Christiaan Neethling Barnard sowie sein New Yorker Kollege Adrian Kantrowitz zuvor.AbstractAfter a fulfilled life, Norman E. Shumway, the great pioneer of cardiac transplantation, died of lung cancer 1 day after his 83rd birthday in Palo Alto, California, USA.Already at the beginning of the 1960s, he and his colleague Richard R. Lower did revolutionary experimental work on developing and establishing the technique of orthotopic cardiac transplantation in dogs. Several studies on cardiac transplantation were carried out in his department and a few years later, Shumway and his team were on their way to perform the worldwide first human-to-human cardiac transplantation. On December 3, 1967, Christiaan Neethling Barnard, a cardiac surgeon from South Africa, forestalled Shumway and performed this operation in Cape Town, South Africa. This event initiated a global boom of cardiac transplantations in the following years.” Many heart centers started their own cardiac transplant programs but high mortality rates led again to stagnancy of transplant activities. Shumway remained stable in believing in good results of cardiac transplantation and continued his program steadily. At the beginning of the 1970s, he and his group were responsible for most cardiac transplantations worldwide.

Transposition of greater omentum in deep sternal wound infection caused by methicillin-resistant Staphylococci, with differing clinical course for MRSA and MRSE.

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) are an increasing problem in deep sternal wound infections (DSWI) after cardiac surgery. METHODS Between 2005 and 2009, recalcitrant methicillin-resistant Staphylococcus was found in 21 patients with complicated DSWI, and a transposition of the greater omentum (TGO) was finally performed. A positive microbial culture at the time of procedure was present in all patients. The hospital course was reviewed discretely for MRSA and MRSE. RESULTS Median patient age was 72.3 years (range 60.8-79.7); 76 % of patients were male. Time from the first sternal revision until consecutive open wound therapy due to re-infection and total hospital stay was longer for MRSA compared to MRSE (38 vs. 14 days, P = 0.003, and 141 vs. 91 days, P = 0.007, respectively). The period from cardiac surgery to TGO was likewise prolonged for MRSA (78 vs. 55 days, P = 0.045), whereas in-hospital mortality and one-year mortality rate did not differ. CONCLUSION TGO remains a good treatment option for DSWI type IV. Microbial findings determine the clinical course; nevertheless in-hospital mortality remains low for both MRSA and MRSE infection.

[Norman Edward Shumway - pioneer of cardiac surgery (February 9, 1923 to February 10, 2006)].

ZusammenfassungAm 10. Februar 2006 verstarb der amerikanische Herzchirurg Norman Edward Shumway 1 Tag nach seinem 83. Geburtstag in Palo Alto, Kalifornien, USA, an den Folgen eines Lungenkrebsleidens.Norman E. Shumway, Pionier der Herzchirurgie, trug maßgeblich dazu bei, Herztransplantationen von Mensch zu Mensch zu ermöglichen. Bereits Anfang der 60er Jahre führte er bahnbrechende experimentelle Arbeiten zur Entwicklung einer Transplantationstechnik an Hunden durch, die er in Zusammenarbeit mit seinem Team, allen voran mit dem Kollegen Richard R. Lower, in den folgenden Jahren Schritt für Schritt kontinuierlich weiterentwickelte. Nach diesen umfangreichen tierexperimentellen Vorarbeiten stand er im Jahre 1967 mit seinem herzchirurgischen Team der Stanford University an der Schwelle, die weltweit erste Herztransplantation von Mensch zu Mensch durchzuführen, allerdings kamen ihm der Südafrikaner Christiaan Neethling Barnard sowie sein New Yorker Kollege Adrian Kantrowitz zuvor.AbstractAfter a fulfilled life, Norman E. Shumway, the great pioneer of cardiac transplantation, died of lung cancer 1 day after his 83rd birthday in Palo Alto, California, USA.Already at the beginning of the 1960s, he and his colleague Richard R. Lower did revolutionary experimental work on developing and establishing the technique of orthotopic cardiac transplantation in dogs. Several studies on cardiac transplantation were carried out in his department and a few years later, Shumway and his team were on their way to perform the worldwide first human-to-human cardiac transplantation. On December 3, 1967, Christiaan Neethling Barnard, a cardiac surgeon from South Africa, forestalled Shumway and performed this operation in Cape Town, South Africa. This event initiated a global boom of cardiac transplantations in the following years.” Many heart centers started their own cardiac transplant programs but high mortality rates led again to stagnancy of transplant activities. Shumway remained stable in believing in good results of cardiac transplantation and continued his program steadily. At the beginning of the 1970s, he and his group were responsible for most cardiac transplantations worldwide.

Supra-aortic interventions for endovascular exclusion of the entire aortic arch

Objective: Our aim was to analyze the outcomes of endovascular exclusion of the entire aortic arch (proximal landing in zone 0, distal landing in zone III or beyond, after Ishimaru) in which complete surgical debranching of the supra‐aortic vessels (I), endovascular supra‐aortic revascularization (chimney, fenestrated, or branched grafts) with partial surgical debranching (II), or total endovascular supra‐aortic revascularization (III) was additionally performed. Methods: Publications describing endovascular repair of the aortic arch (2000‐2016) were systematically searched and reviewed. Results: From a total of 53 relevant studies including 1853 patients, only 1021 patients undergoing 35 different total aortic arch procedures were found eligible for further evaluation and included in group I, II, or III (429, 190, and 402 patients, respectively). Overall early mortality was higher in group I vs groups II and III (P = .001; 1 − &bgr; = 95.6%) but exceeded in group III (18.6%) and group II (14.0%) vs group I (8.0%; P = .044; 1 − &bgr; = 57.4%) for diseases involving zone 0. Mortality was higher in all subgroups treated for zone 0 disease compared with corresponding subgroups treated for zone I to zone III disease. The incidence of cerebral ischemic events was increased in groups I and II vs group III (7.5% and 11% vs 1.7%; P = .0001) and correlated with early mortality (R2 = .20; P = .033). The incidence of type II endoleaks and endovascular reintervention was similar between groups and correlated with each other (R2 = .37; P = .004). Type Ia endoleak occurred more often in groups II and III than in group I (7.1% and 12.1% vs 5.8%; P = .023) and correlated with midterm mortality (R2 = .53; P = .005). Retrograde type A dissection was low in all groups, whereas aneurysm growth was higher in group III (2.6%, 4.2%, 10.7%; P = .002), correlating with midterm mortality (R2 = .311; P = .009). Surgical revision slightly correlated with surgical complications (R2 = .18; P = .044) but not with mortality (R2 = .10; P = .214). Conclusions: Because early mortality was significantly higher in patients receiving endovascular treatment for proximal aortic disease, endovascular‐based approaches proved to be feasible alternatives to hybrid surgical procedures, especially when they were performed for aneurysms located in the distal aortic arch. Whereas cerebral ischemia accompanies both surgical and endovascular involvement of the supra‐aortic vessels, endoleaks and aneurysm growth remain hallmarks of endovascular supra‐aortic repair. Because surgical revision had no impact on mortality, complete surgical debranching may become the option of choice for patients with good life expectancy suffering from proximal aortic arch disease, whereas total endovascular procedures could be particularly advantageous in patients with short life expectancy and distal aortic arch disease.

Is there a correlation between late re-exploration after cardiac surgery and removal of epicardial pacemaker wires?

BackgroundRe-exploration for bleeding accounts for increased morbidity and mortality after major cardiac operations. The use of temporary epicardial pacemaker wires is a common procedure at many departments. The removal of these wires postoperatively can potentially lead to a serious bleeding necessitating intervention.MethodsFrom Jan 2011 till Dec 2015 a total of 4244 major cardiac procedures were carried out at our department. We used temporary epicardial pacemaker wires in all cases. We collected all re-explorations for bleeding and pericardial tamponade from our surgical database and then we focused on the late re-explorations, meaning on the 4th postoperative day and thereafter, trying to identify the removal of the temporary pacemaker wires as the definite cause of bleeding. Patients’ records and medication were examined.ResultsThirty-nine late re-explorations for bleeding, consisting of repeat sternotomies, thoracotomies and subxiphoid pericardial drainages, were gathered. Eight patients had an acute bleeding incidence after removal of the temporary wires (0.18%). In four of these patients, a pericardial drainage was inserted, whereas the remaining patients were re-explorated through a repeat sternotomy. Two patients died of the acute pericardial tamponade, three had a blood transfusion and one had a wound infection. Seven out of eight patients were either on dual antiplatelet therapy or on combination of aspirin and vitamin K antagonist.ConclusionsA need for re-exploration due to removal of the temporary pacemaker wires is a very rare complication, which however increases morbidity and mortality. Adjustment of the postoperative anticoagulation therapy at the time of removal of the wires could further minimize or even prevent this serious complication.

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.

Heart Transplantation in a Toddler with Cardiac Kawasaki Disease

Kawasaki disease is very rare in Western Europe. The disease may involve coronary arteries. A 2-year-old boy diagnosed with Kawasaki disease had had seizure-like symptoms. Further evaluation revealed recurrent myocardial ischemia and myocardial infarction. Due to extraordinary extension of the coronary disease, myocardial revascularization was not feasible and the toddler underwent successful heart transplantation after 97 days on waiting list.