[Influence of ECMO and IABP on coronary blood flow. Valuable combination or waste of resources?]. / Einfluss von ECMO und IABP auf die Koronardurchblutung. Sinnvolle Kombination oder Ressourcenverschwendung?

BACKGROUND: The treatment of patients in severe cardiogenic shock with an intra-aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO) is a common procedure to achieve stabilization. Only limited data are available on the simultaneous use of both systems. The aim of the present study was to assess the effect of the concomitant use of IABP and ECMO on coronary blood flow. In addition, the influence of antegrade and retrograde perfusion was evaluated. METHODS: A median sternotomy was performed in adult pigs under general anesthesia. Arterial ECMO perfusion was realized through the ascending aorta or the femoral artery, and the IABP was implanted via the second femoral artery. Six measurements of arterial pressure in the left anterior descending artery (LAD) and in the left atrium were made at intervals of 2 min. In addition, lactate concentration and oxygen saturation in the coronary sinus were recorded. The ECMO support was either 100 or 50 % of cardiac output. Each experiment was carried out first without and then with additional IABP support. RESULTS: The simultaneous use of ECMO and IABP is feasible for antegrade perfusion, where the IABP leads to an increase of blood pressure in the coronary arteries. In addition, the myocardial oxygen supply improves. By contrast, the use of an IABP in retrograde perfusion leads to a reduction of blood pressure in the LAD and to a reduced oxygen supply. A comparison between antegrade and retrograde perfusion with IABP support showed significantly better mean arterial pressure in the LAD for antegrade perfusion. Without IABP, blood pressure in the LAD was better in retrograde perfusion. CONCLUSION: In antegrade perfusion the simultaneous use of IABP and ECMO is useful. In retrograde perfusion IABP impairs the mean arterial pressure and consequently the perfusion of the coronary arteries.

Target promiscuity and physicochemical properties contribute to pharmacologically induced ER-stress.

In vivo toxicity of drug candidates remains a major problem in the pharmaceutical industry, and is a significant cause of late stage attrition. As a consequence predictive in vitro assays are developed and put in place early in the discovery pipeline to aid compound selection. Endoplasmic reticulum stress (ER-stress) has been implicated in many disease states, as well as compound-induced organ toxicities. We explored the role of ER-stress as a general mechanism of toxicity by utilizing a high-throughput in vitro assay to screen 316 chemically diverse Pfizer proprietary compounds with known in vivo toxicity outcome for nuclear accumulation of spliced x-box binding protein 1 (XBP1s), a key transcription factor of the unfolded protein response (UPR). We examined the correlation between physicochemical properties, such as molecular weight, pKA, lipophilicity, topological polar surface area, and passive permeability, as well as target promiscuity, between XBP1s hits and non-hits and found that lipophilicity, target promiscuity and low passive permeability significantly contributed to ER-stress. In addition, we have shown that compounds which cause ER-stress in the form of XBP1s activation at concentrations below 40 µM have a more than four times greater chance of causing in vivo toxicity at 10 µM plasma exposure.

Patent foramen ovale. Correct route for implantation of a biventricular permanent pacemaker?

INTRODUCTION: Intentional or unintentional placement of a pacemaker lead into the left ventricle is an uncommon clinical entity that is associated with a high risk for systemic embolization and enormous difficulties in case of explantation. Unintentional implantation through a patent foramen ovale via the mitral valve is the usual pathway for this malposition. METHODS: We report a case where a pacemaker lead was placed intentionally into the left ventricle via a patent foramen ovale for biventricular pacing for resynchronization therapy. Later, the patient developed life-threatening pacemaker lead-associated endocarditis with sepsis. Emergency open heart surgery for lead removal was necessary in the form of a reoperation after bypass graft surgery a number of years earlier. CONCLUSION: Although it is technically feasible to implant the pacemaker lead into the left ventricle via a patent foramen ovale, we consider this option to be obsolete for use with a biventricular pacemaker, due to the multitude of risks, which can, in part, be life-threatening for the patient.

[Right heart failure resulting from pacemaker lead-induced tricuspid valve regurgitation]. / Rechtsherzversagen durch schrittmachersondeninduzierte Trikuspidalklappeninsuffizienz.

Pacemaker lead-induced tricuspid valve regurgitation is a severe and often underdiagnosed complication due to the widely variable time interval between implantation and the development of severe tricuspid valve insufficiency with ensuing right heart failure. Complete explantation of inactive pacemaker leads is necessary to avoid permanent damage to right heart structures. If performed in a timely fashion, regression of tricuspid insufficiency can be achieved without additional cardiac procedures.

Dislocation of a transapically implanted aortic valve prosthesis with a functionally bicuspid aortic valve and ascending aortic aneurysm.

In recent years, catheter-based aortic valve interventions have become established procedures for the treatment of high-risk and advanced age patients with aortic valve pathologies. One of the limitations of the widespread applicability of this procedure is the annulus size. Until recently, no prosthesis was available to treat patients with a large annulus. We report on a patient with high-grade aortic stenosis (AS) and a 27-mm annulus, who underwent transapical implantation (TAP) of an Edwards SAPIEN® 29-mm prosthesis (Edwards LifeScience, Irvine, CA, USA). Due to insufficient dilation of his heavily calcified, functionally bicuspid aortic valve leaflets during balloon aortic valvuloplasty (BAV), the TAP prosthesis did not anchor adequately. This was determined during follow-up as he developed progressive aortic insufficiency and orthopnea, and an echocardiography revealed that the valve had been displaced into the LVOT. A conventional aortic valve replacement and ascending aorta replacement were performed, at which time the TAP prosthesis was removed. The patient recovered uneventfully, and was discharged with a well-functioning aortic bioprosthetic valve and in good general condition.

Life-threatening hemothorax resulting from lung hernia after minimally invasive mitral valve surgery.

Lung hernia following minimally invasive mitral valve surgery is an uncommen entity. We report the case of a male patient who developed a lung hernia as a sequela to limited access mitral valve surgery. Two months after discharge, the patient presented with a bulge in the region of the lateral thoracotomy related to respiration which could be provoked by a Valsalva maneuver. In the night following admission the patient had acute cardiovascular decompensation with worsening dyspnea, pallor and hypotension. The patient was quickly transferred to the ICU, where a chest X-ray revealed the presence of a large hemothorax with compression of the entire right lung. We transferred the patient to the operation room, evacuated the hemothorax and reconstructed the 15-cm long and 3-cm wide dehiscence using a GoreTex patch adapted in a special technique.

Pacemaker-associated thrombotic occlusion of the inferior vena cava causing liver failure.

Pacemaker implantation using endocardial leads can give rise to thrombotic venous occlusion. We report the case of a 23-year-old male with transposition of the great arteries, who had previously undergone a Senning repair at the age of one year. A sick sinus syndrome required pacemaker implantation with subsequent multiple lead revisions. Following the implantation of the last lead, the patient developed complete occlusion of the inferior vena cava (IVC) with stenosis of the superior vena cava (SVC) with pacemaker leads in both lesions. Liver failure, ascites and esophageal varices developed. Thrombolytic treatment was ineffective; finally the patient was listed for liver transplantation. We explanted the lead embedding the thrombosis, together with some lead remnants. The stenosis of the SVC and the occlusion of the IVC were dilatated and stabilized with four stents. Over a follow-up period of 4 months, NYHA class improved from NYHA III to NYHA I-II, the hepatic function showed complete remission, and a liver transplantation was not necessary.

Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity.

The emerging critical implications of Rho/Rho-kinase (ROCK) signaling in neurodegenerative diseases, glaucoma, renoprotection, diabetes and cancer have sparked growing interest in the pharmacological potential of ROCK inhibitors beyond their current application in cardiovascular disease. This article discusses the therapeutic benefits of novel ROCK inhibitors in development, and highlights the recent advances in the current understanding of disease-dependent and isoform-specific functions of ROCK and their potential impact on future therapeutic strategies.

Tobramycin once- vs thrice-daily for elective intravenous antipseudomonal therapy in pediatric cystic fibrosis patients.

PURPOSE: We hypothesized that a single intravenous (iv) tobramycine infusion (treatment B) would have equivalent anti-infectious efficacy in chronic Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) as the commonly performed treatment of three doses (treatment A) . Toxicity and practicability may even be improved in the single-dose regimen. METHODS: This was a randomized crossover study comparing outcome after 14 and 35 days. The primary end-point was a decrease in the leukocyte count, and the secondary end-points were clinical and lung function parameters, Pseudomonas quantification in sputum, and inflammation markers (immunoglobulin G, C-reactive protein) in serum. 30 patients (20 female, mean age 11.2 years, mean age range 1.7-18.1 years) received elective 14-day courses of treatments A or B, followed by the alternative treatment after a mean interval of 37 (+/- 21) weeks. RESULTS: With the exception of PA density, there were no significant differences between both treatment strategies after 14 days of treatment. After 35 days of treatment, there were no significant changes in the leukocyte count and inflammation markers. Both treatment strategies reduced the bacterial load in the airways, as reflected by a decreased PA density in sputum. Nephrotoxicity was equal in both groups, with a transient slight elevation of urinary N-acetyl-beta-glucosaminidase concentrations. Standard audiometry tests revealed no evidence of a hearing impairment in any patient following therapy. Mean body weight increased during the study period by 0.5 kg. Forced expiratory volume increased by approximately 5% of the predicted volume, forced vital capacity increased by 2% of predicted capacity, and forced mid expiratory flow rate increased by 7% (A) or 4% (B) of the predicted normal value, although these changes were not statistically significant. CONCLUSION: We conclude that tobramycin given in a daily single dose (with the advantage of being more practical in a home environment) has an efficacy equal to that of three daily doses in terms of elective antipseudomonal therapy in clinically stable patients with CF.

Continuous vs thrice-daily ceftazidime for elective intravenous antipseudomonal therapy in cystic fibrosis.

BACKGROUND/AIM: We hypothesized that a continuous 24-h infusion of 100 mg/kg per day ceftazidime (treatment C) would result in equivalent or even superior anti-infectious efficacy in chronic Pseudomonus aeruginosa (PA) infection in patients with cystic fibrosis (CF) in comparison to the usual application of 200 mg/kg per day ceftazidime in three doses (treatment T). METHODS: This was a randomized crossover study comparing outcome after 14 days and 35 days. Tobramycin administered once daily (10 mg/kg per day) was administered concomitantly in both groups. The primary end-point was a decrease in the leukocyte count, and the secondary endpoints were clinical and lung function parameters, Pseudomonas quantification in sputum, and inflammation markers (immunogloblulin [Ig] G, C-reactive protein [CRP]) in serum. All patients received antibiotics electively as 14-day courses on a regular basis, not for acute exacerbations. RESULTS: Fifty-six patients (29 females, mean patient age 14.4 years, age range 5-37) initially received treatments C or T, followed by the alternative treatment after a mean interval of 37 (+/- 21) weeks. After 2 weeks of antibiotic treatment, the overall study group showed significant improvements compared to baseline for body weight, leukocyte counts, CRP, forced expiratory volume in 1 s (FEV(1)), FVC (forced vital capacity), and bacterial load in the airways, with no significant differences between treatment groups. Both regimens were well tolerated. Three weeks after cessation of antimicrobial therapy, leukocytes and PA density had returned to pre-treatment values. CONCLUSION: We conclude that continuous or thrice-daily dosing of intravenous ceftazidime, both combined with once-daily tobramycin, are equally effective application regimens for elective antipseudomonal therapy in clinically stable patients with CF.

Late perforation of a right ventricular pacing lead: a potentially dangerous complication.

Four days after uncomplicated implantation of a two-chamber pacemaker and a normal postoperative course, a patient was referred to our hospital with left-sided hemothorax and early hemorrhagic shock. Chest X-ray and CT scan were suspicious of a right ventricular lead perforation with additional pericardial and pleural injury. Immediate surgery was performed via a lateral thoracotomy and the perforation was repaired via direct suture. An epimyocardial ventricular lead was implanted simultaneously. The patient made an uneventful recovery.

Brachial artery compression by the lacertus fibrosus.

Five patients presented with classic symptoms diagnostic of intermittent claudication that were exacerbated by strenuous activity. Examination demonstrated localized tenderness over the lacertus fibrosus (bicipital aponeurosis), as well as increased pain and an obliterated radial pulse with forearm pronation and resisted elbow flexion. All 5 were athletes who had hypertrophied forearm muscles. Patients were diagnosed with brachial artery compression by the lacertus fibrosus. Release of the lacertus fibrosus restored normal pulses in all cases. Followup ranged from 6 months to 25 years. Full clinical recovery was achieved in 3 patients. One patient had a good result and 1 a fair result. Although the lacertus fibrosus has been well described as a cause of neural compression and compartment syndrome, it has been reported only once to cause intermittent arterial compromise. Hypertrophy of the muscles and the lacertus fibrosus related to excessive use is an important factor in the development of isolated vascular, neural, or combined neurovascular lesions.