A Gorski

Interference with ERK(Thr188) phosphorylation impairs pathological but not physiological cardiac hypertrophy.

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are central mediators of cardiac hypertrophy and are discussed as potential therapeutic targets. However, direct inhibition of ERK1/2 leads to exacerbated cardiomyocyte death and impaired heart function. We have previously identified ERKThr188 autophosphorylation as a regulatory phosphorylation of ERK1/2 that is a key factor in cardiac hypertrophy. Here, we investigated whether interference with ERKThr188 phosphorylation permits the impairment of ERK1/2-mediated cardiac hypertrophy without increasing cardiomyocyte death. The impact of ERKThr188 phosphorylation on cardiomyocyte hypertrophy and cell survival was analyzed in isolated cells and in mice using the mutant ERK2T188A, which is dominant-negative for ERKThr188 signaling. ERK2T188A efficiently attenuated cardiomyocyte hypertrophic responses to phenylephrine and to chronic pressure overload, but it affected neither antiapoptotic ERK1/2 signaling nor overall physiological cardiac function. In contrast to its inhibition of pathological hypertrophy, ERK2T188A did not interfere with physiological cardiac growth occurring with age or upon voluntary exercise. A preferential role of ERKThr188 phosphorylation in pathological types of hypertrophy was also seen in patients with aortic valve stenosis: ERKThr188 phosphorylation was increased 8.5 ± 1.3-fold in high-gradient, rapidly progressing cases (≥40 mmHg gradient), whereas in low-gradient, slowly progressing cases, the increase was not significant. Because interference with ERKThr188 phosphorylation (i) inhibits pathological hypertrophy and (ii) does not impair antiapoptotic ERK1/2 signaling and because ERKThr188 phosphorylation shows strong prevalence for aortic stenosis patients with rapidly progressing course, we conclude that interference with ERKThr188 phosphorylation offers the possibility to selectively address pathological types of cardiac hypertrophy.

Preoperative serum h-FABP concentration is associated with postoperative incidence of acute kidney injury in patients undergoing cardiac surgery

BackgroundFatty acid binding protein (FABP) is an intracellular transport protein associated with myocardial damage size in patients undergoing cardiac surgery. Furthermore, elevated FABP serum concentrations are related to a number of common comorbidities, such as heart failure, chronic kidney disease, diabetes mellitus, and metabolic syndrome, which represent important risk factors for postoperative acute kidney injury (AKI). Data are lacking on the association between preoperative FABP serum level and postoperative incidence of AKI.MethodsThis prospective cohort study investigated the association between preoperative h-FABP serum concentrations and postoperative incidence of AKI, hospitalization time and length of ICU treatment. Blood samples were collected according to a predefined schedule. The AKI Network definition of AKI was used as primary endpoint. All associations were analysed using descriptive and univariate analyses.ResultsBetween 05/2009 and 09/2009, 70 patients undergoing cardiac surgery were investigated. AKI was observed in 45 patients (64%). Preoperative median (IQR) h-FABP differed between the AKI group (2.9 [1.7–4.1] ng/ml) and patients without AKI (1.7 [1.1–3.3] ng/ml; pu2009=u20090.04), respectively. Patients with AKI were significantly older. No statistically significant differences were found for gender, type of surgery, operation duration, CPB-, or X-Clamp time, preoperative cardiac enzymes, HbA1c, or CRP between the two groups. Preoperative h-FABP was also correlated with the length of ICU stay (rsu2009=u20090.32, pu2009=u20090.007).ConclusionsWe found a correlation between preoperative serum h-FABP and the postoperative incidence of AKI. Our results suggest a potential role for h-FABP as a biomarker for AKI in cardiac surgery.

Cardiac Operations in the Presence of Meningioma

BACKGROUNDnWe 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.nnnMETHODSnWe 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.nnnRESULTSnFive 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.nnnCONCLUSIONSnThe 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.

Rapid deployment valve system shortens operative times for aortic valve replacement through right anterior minithoracotomy

BackgroundThere is growing evidence from the literature that right anterior minithoracotomy aortic valve replacement (RAT-AVR) improves clinical outcome. However, increased cross clamp time is the strongest argument for surgeons not performing RAT-AVR. Rapid deployment aortic valve systems have the potential to decrease cross-clamp time and ease this procedure. We assessed clinical outcome of rapid deployment and conventional valves through RAT.MethodsSixty-eight patients (mean age 76u2009±u20096xa0years, 32% females) underwent RAT-AVR between 9/2013 and 7/2015. According to the valve type implanted the patients were divided into two groups. In 43 patients (R-group; mean age 74.1u2009±u20096.6xa0years) a rapid deployment valve system (Edwards Intuity, Edwards Lifesciences Corp; Irvine, Calif) and in 25 patients (C-group; mean age 74.2u2009±u20096.6xa0years) a conventional stented biological aortic valve was implanted.ResultsAortic cross-clamp (42.1u2009±u200912xa0min vs. 68.3u2009±u200920.3xa0min; pu2009<u20090.001) and bypass time (80.4u2009±u200939.3xa0min vs. 106.6u2009±u200923.2xa0min; pu2009=u20090.001) were shorter in the rapid deployment group (R-group). We observed no differences in clinical outcome. Postoperative gradients (R-group: max gradient, 14.3u2009±u20098xa0mmHg vs. 15.5u2009±u20095xa0mmHg (C-group), mean gradient, 9.2u2009±u20091.7xa0mmHg (R-group) vs. 9.1u2009±u20092.3xa0mmHg (C-group) revealed no differences. However, larger prostheses were implanted in C-group (25xa0mm; IQR 23–27xa0mm vs. 23xa0mm; IQR 21–25; pu2009=u20090.009).ConclusionsOur data suggest that the rapid deployment aortic valve system reduced cross clamp and bypass time in patients undergoing RAT-AVR with similar hemodynamics as with larger size stented prosthesis. However, larger studies and long-term follow-up are mandatory to confirm our findings.

No touch technique and hypothermic circulatory arrest for porcelain aorta in combined valve surgery

Cardiac surgery in patients scheduled for combined single or multiple valve and CABG surgery with preoperatively undetected porcelain aorta is challenging. Different surgical strategies may address this problem. Abortion of the initial operation with subsequent interventional therapy and hypothermic circulatory arrest offer clampless treatment options in these patients.