Intra-individual head-to-head comparison of Sirolimus®- and Paclitaxel®-eluting stents for coronary revascularization. A randomized, multi-center trial.

BACKGROUND: Despite the known effects of drug-eluting stents (DES), other cofactors attributed to patient characteristics affect their success. Interest focused on designing a study minimizing these factors to answer continuing concerns on the heterogeneity of response to different DESs. The study's aim was to investigate the feasibility and impact of an intra-individual comparison design in patients (pts) with two coronary artery stenosis treated with a Sirolimus- (SES) and a Paclitaxel- (PES) eluting stent. METHODS AND RESULTS: The study was conducted as a prospective, randomized, multi-center trial in 112 pts who consented to treatment with a SES and a PES. Pts were eligible if they suffered from the presence of two single primary target lesions in two different native coronary arteries. Lesions were randomized to either SES or PES treatment. The primary endpoint was in-stent luminal late loss (LLL), as determined by quantitative angiography at 8 months; clinical follow up was obtained at 1, 8, and 12 months additionally. The LLL (0.13 ± 0.28 mm SES vs. 0.26 ± 0.35 mm PES, p=0.011) showed less neointima in SES. With a predefined cut-off criterion of 0.2mm difference in LLL, 53/87 pts SES and PES were similar effective. 34/87 pts had a divergent result, 26 pts had greater benefit from SES while 8 pts had greater benefit from PES. Overall, MACE (MI, TLR, and death) occurred in 19 (17%) pts. Based on lesion analysis of 108 lesions treated with SES and 110 lesions treated with PES, 5 (4.6%) lesions with SES and 3 (2.7%) lesions with PES required repeated TLR. CONCLUSION: An intra-individual comparison design to assess differences in efficacy of different DESs is feasible, safe and achieves similar results to inter-individual studies. This study is among the first to show that failure of one DES does not necessarily implicate failure of another DES and vice versa.

Magnetic resonance tissue phase mapping: analysis of age-related and pathologically altered left ventricular radial and long-axis dyssynchrony.

PURPOSE: To employ magnetic resonance tissue phase mapping (TPM) for the assessment of age-related left ventricular (LV) synchrony of radial and long-axis motion in healthy volunteers and in hypertensive heart disease, dilated cardiomyopathy (DCM), and left bundle branch block (LBBB). MATERIALS AND METHODS: TPM (spatial/temporal resolution = 1.3 × 2.6 mm(2)/13.8 msec) was employed to measure radial and long-axis myocardial velocities in 58 healthy volunteers of three age groups and 37 patients (hypertensive, n = 18; DCM, n = 12; DCM and LBBB n = 7). Regional times-to-peak velocities (TTP) in systole and diastole were derived for all LV segments. Four measures of dyssynchrony were defined as the standard deviation of systolic and diastolic TTP for radial and long-axis motion. RESULTS: Systolic radial and diastolic long-axis dyssynchrony was increased (P < 0.01) in all patient groups compared to controls. Multiple regressions revealed a significant relationship of dyssynchrony with LV ejection fraction and mass for systolic radial (P < 0.001 resp. P = 0.02), diastolic radial (P < 0.001 resp. P < 0.05), and long-axis (P < 0.001 resp. P = 0.001) motion. Diastolic dyssynchrony correlated with the LV remodeling index (P < 0.05) and increased with age (P < 0.03). Systolic long-axis dyssynchrony was not influenced by disease or LV function. CONCLUSION: Radial systolic and long-axis diastolic dyssynchrony were the most sensitive markers for altered dyssynchrony in hypertensive heart disease or DCM. Future studies are needed to evaluate the diagnostic value of TPM-derived dyssynchrony parameters.

Safety and feasibility of nasopharyngeal evaporative cooling in the emergency department setting in survivors of cardiac arrest.

AIM: Mild therapeutic hypothermia improves survival and neurologic recovery in primary comatose survivors of cardiac arrest. Cooling effectivity, safety and feasibility of nasopharyngeal cooling with the RhinoChill device (BeneChill Inc., San Diego, USA) were determined for induction of therapeutic hypothermia. METHODS: Eleven emergency departments and intensive care units participated in this multi-centre, single-arm descriptive study. Eighty-four patients after successful resuscitation from cardiac arrest were cooled with nasopharyngeal delivery of an evaporative coolant for 1h. Subsequently, temperature was controlled with systemic cooling at 33 degrees C. Cooling rates, adverse events and neurologic outcome at hospital discharge using cerebral performance categories (CPC; CPC 1=normal to CPC 5=dead) were documented. Temperatures are presented as median and the range from the first to the third quartile. RESULTS: Nasopharyngeal cooling for 1h reduced tympanic temperature by median 2.3 (1.6; 3.0) degrees C, core temperature by 1.1 (0.7; 1.5) degrees C. Nasal discoloration occurred during the procedure in 10 (12%) patients, resolved in 9, and was persistent in 1 (1%). Epistaxis was observed in 2 (2%) patients. Periorbital gas emphysema occurred in 1 (1%) patient and resolved spontaneously. Thirty-four of 84 patients (40%) patients survived, 26/34 with favorable neurological outcome (CPC of 1-2) at discharge. CONCLUSIONS: Nasopharyngeal evaporative cooling used for 1h in primary cardiac arrest survivors is feasible and safe at flow rates of 40-50L/min in a hospital setting.

[Anticoagulation in atrial fibrillation]. / Antikoagulation bei Vorhofflimmern.

In this overview the actual guideline-recommendations for anticoagulation in atrial fibrillation and the problems of the currently available therapy are discussed. Furthermore an outlook over future developments in this field is given. Effective anticoagulation can prohibit thrombembolic events and is thus essential for the prognosis of patients suffering from atrial fibrillation. Until now vitamin-K-antagonists (VKAs) and acetylsalicylic acid (ASA) are available for oral anticoagulation in these patients. VKAs demonstrate a satisfying efficiency combined with rather high bleeding hazard. ASA on the other hand allows only moderate risk reduction with minimal side effects. Thus the guidelines recommend anticoagulation tailored to the individual risk, which can be evaluated by the CHADS2-Score. New therapeutic strategies, like the factor Xa inhibitor rivaroxaban or the factor II inhibitor dabigatran, are actually evaluated in phase III studies. These drugs bear the hope of higher efficiency combined with improved safety and much more comfortable use in the daily practice (e. g. no need for INR measurement, no dose adaptation).

Effects of local MCP-1 protein therapy on the development of the collateral circulation and atherosclerosis in Watanabe hyperlipidemic rabbits.

OBJECTIVE: The objective of our study was to quantify the arteriogenic potency of Monocyte Chemoattractant Protein-1 (MCP-1) under hyperlipidemic conditions. Additionally, we aimed to determine the effects of locally applied MCP-1 on systemic serum lipid levels as well as on atherosclerosis. METHODS: A total of sixty-four Watanabe rabbits was treated with either low dose MCP-1 (1 microg/kg/week), high dose MCP-1 (3.3 microg/kg/week) or PBS as a control substance. Substances were applied directly into the collateral circulation via an osmotic minipump with the catheter placed in the proximal stump of the ligated femoral artery. Either 1 week or 6 months after initiation of the treatment X-ray angiography was performed as well as measurements of collateral conductance using fluorescent microspheres. The extent of atherosclerosis was quantified in whole aortas using Sudan IV staining. RESULTS: One week after ligation of the femoral artery a significant increase in collateral conductance was observed in animals treated with high dose MCP-1 (control: 2.2+/-0.8 ml/min/100 mmHg vs. MCP-1 high dose: 8.9+/-2.0 ml/min/100 mmHg, P<0.05). Six months after femoral artery ligation no differences were found between the treated and the control group (PBS; 44.9+/-11.6 ml/min/100 mmHg, MCP-1; 47.8+/-11.5 ml/min/100 mmHg, P=NS). No influence was found on serum lipids or on the development of atherosclerosis in the present model. CONCLUSION: MCP-1 accelerates arteriogenesis upon femoral artery ligation under hyperlipidemic conditions. Six months after treatment these pro-arteriogenic effects of MCP-1 can no longer be observed. The present data do not show an effect of local MCP-1 treatment on serum lipids or on atherosclerosis. It should be noted however that a high standard deviation was observed for the data on atherosclerotic surface area, necessitating additional experiments in a different model of atherosclerosis.

[Effect of hydrostatic pressure on quaternary structure on the chaperone function of alpha-crystallin]. / Vplyv hidrostatychnoho tisku na chetvertynnu strukturu ta shaperonovu funktsiiu alpha-krystalinu.

High hydrostatic pressure-induced changes in bovine lens alpha-crystallin oligomers size and chaperone-like function were studied by a static light scattering. Under pressure 1.5 kbar, alpha-crystallin oligomers size is almost unaffected. Increase of the size was observed during several hours of incubation at 3 kbar. Such high-pressure effect on association has been previously revealed for detergent micelles, whereas the "typical" protein oligomers are known to dissociate under high pressure. Our results about pressure influence on alpha-crystallin association supports the previously proposed "protein micelle" model of the protein quaternary structure. Chaperone-like activity of alpha-crystallin is shown to increase after incubation at 3 kbar. After the end of the incubation this activity is slowly decreasing during several hours.

[Management of acute myocardial infarct with ST segment elevation]. / Management des akuten Myokardinfarktes mit ST-Strecken-Hebung.

In the management of acute myocardial infarction with ST segment elevation, the primary goal is rapid reperfusion of the initially occluded infarct-related coronary artery. This may be achieved either by catheter using direct coronary angioplasty or by medical therapy in form of thrombolysis. These two methods, their concomitant treatment strategies as well as most recent results of combination therapy are presented and discussed. This results in recommendations for the management of these patients which have to take into account logistic possibilities and minimize time delays.

[Enzyme levels and morphological picture of normal and cirrhotic rat livers following portal vein ligation and subcutaneous transposition of the spleen]. / Enzymausstattung und morphologisches Bild der normalen und cirrhotischen Rattenleber nach Pfortaderligatur und Subcutantransposition der Milz

The effect of portal vein ligation after subcutaneous transposition of the spleen is investigated on enzyme-activities. and morphological pattern of the normal and cirrhotic rat-liver. The increase of glycolytic enzyme-activities and the decrease of enzyme-activities of oxidative metabolic pathways can be explained by adaptation on throttled blood supply of the liver. Significant decrease of arginase-activity (urea-cycle) can not be explained by reduced protein content of food (pair-fed-animals). Diminished substrate (ammonia)-level (NH3/t/hepatocytes) may be an explanation. Histological pattern of normal and cirrhotic rat liver is nearly unchanged after portal vein ligation.