Biomedical subjects

Stephanie Aker

Publications and source records attributed to Stephanie Aker.

10 recordsLinked to original sources

PubMed2006

Feasibility of real-time magnetic resonance-guided stent-graft placement in a swine model of descending aortic dissection.

AIMS: To evaluate the pre-clinical feasibility of real-time magnetic resonance imaging (rtMRI) to guide stent-graft placement for experimental aortic dissection (AD) and to alleviate disadvantages of ionising radiation and nephrotoxic contrast media. Endovascular stent-graft placement for thoracic aortic disease is usually performed under X-ray guidance. The feasibility of rtMRI-guided stent-graft placement is currently not known. METHODS AND RESULTS: By using a catheter-based technique, dissections of the descending thoracic aorta were successfully created in eight domestic pigs. Subsequent implantation of commercially available, nitinol-based stent-grafts was performed entirely under rtMRI guidance. By pre-interventional MRI, the mean minimal true-lumen diameter was 0.9 (0.825-0.975) cm. rtMRI permitted not only the successful and safe device navigation within the true lumen from the iliac arteries to the thoracic aorta, but also the precise positioning and deployment of the stent-graft and safe withdrawal of the delivery catheter in seven of eight pigs. This was achieved without any other complications. After the stent-graft placement, MRI demonstrated complete obliteration of the false lumen, which was confirmed at autopsy. All stent-grafts were well expanded resulting in an increase in the size of the true-lumen diameter to 2.05 (1.925-2.1) cm (P=0.066 vs. baseline). CONCLUSION: In experimental AD, rtMRI-guided endovascular stent-graft placement is feasible and safe and has the potential for mitigating radiation and contrast-related side effects. Additionally, it allows not only pre-interventional diagnosis and detailed anatomic diagnosis, but also permits immediate post-interventional, anatomical, and functional delineation of procedure success that may serve as a baseline for future comparison during follow-up.

Aortic Dissection↗

PubMed2006

Inhibition of Na+/H+-exchanger with sabiporide attenuates the downregulation and uncoupling of the myocardial beta-adrenoceptor system in failing rabbit hearts.

Chronic heart failure (HF) is characterized by left ventricular (LV) structural remodeling, impaired function, increased circulating noradrenaline (NA) levels and impaired responsiveness of the myocardial beta-adrenoceptor (betaAR)-adenylyl cyclase (AC) system. In failing hearts, inhibition of the sodium/proton-exchanger (NHE)-1 attenuates LV remodeling and improves LV function. The mechanism(s) involved in these cardioprotective effects remain(s) unclear, but might involve effects on the impaired betaAR-AC system. Therefore, we investigated whether NHE-1 inhibition with sabiporide (SABI; 30 mg kg(-1) day(-1) p.o.) might affect myocardial betaAR density and AC activity in relation to changes in LV end-diastolic diameter (LVEDD) and LV systolic fractional shortening (LVS-FS) after 3 weeks of rapid LV pacing in rabbits. After 3 weeks of rapid LV pacing LVEDD was significantly increased (Shams 17+/-0.2 mm, n=9 vs 3 wksHF 20+/-0.5 mm, n=8; P<0.05) and LVS-FS decreased (Shams 31+/-1%, n=9 vs 3 wksHF 10+/-1%, n=8; P<0.05). SABI treatment significantly improved LV function independent of whether rabbits were treated after 1 week of pacing (3 wksHF+2 wksSABI (n=7): LVEDD 18+/-1 mm; LVS-FS 16+/-4%) or before pacing (3 wksHF+3wksSABI (n=9): LVEDD 18+/-1 mm; LVS-FS 18+/-6%). After 3 weeks of rapid LV pacing, SABI treatment significantly attenuated increases in serum NA content (Shams 0.83+/-0.19, 3 wksHF 2.68+/-0.38, 3 wksHF+2 wksSABI 1.22+/-0.32, 3 wksHF+3wksSABI 1.38+/-0.33 ng ml(-1)). Moreover, betaAR density (Shams 64+/-5, 3 wksHF 38+/-3, 3 wksHF+2 wksSABI 48+/-4, 3 wksHF+3 wksSABI 55+/-3 fmol mg(-1) protein) and responsiveness (isoprenaline-stimulated AC activity. (Shams 57.6+/-4.9, 3 wksHF 36.3+/-6.0, 3 wksHF+2 wksSABI 56.9+/-6.0, 3 wksHF+3 wksSABI 54.5+/-4.8 pmol cyclic AMP mg(-1) protein(-1) min(-1)) were significantly improved in SABI-treated rabbits. From the present data we cannot address whether the improved betaAR-AC system permitted improved LV function and/or whether the improved LV function resulted in less activation of the sympathetic nervous system and by this in a reduced stimulation of the betaAR-AC system. Accordingly, additional studies are needed to fully establish the cause-and-effect relationship between NHE-1 inhibition and the restoration of the myocardial betaAR system.

Adenylyl Cyclases↗

PubMed2005

Interventional magnetic resonance angiography with no strings attached: wireless active catheter visualization.

Active instrument visualization strategies for interventional MR angiography (MRA) require vascular instruments to be equipped with some type of radiofrequency (RF) coil or dipole RF antenna for MR signal detection. Such visualization strategies traditionally necessitate a connection to the scanner with either coaxial cable or laser fibers. In order to eliminate any wire connection, RF resonators that inductively couple their signal to MR surface coils were implemented into catheters to enable wireless active instrument visualization. Instrument background to contrast-to-noise ratio was systematically investigated as a function of the excitation flip angle. Signal coupling between the catheter RF coil and surface RF coils was evaluated qualitatively and quantitatively as a function of the catheter position and orientation with regard to the static magnetic field B0 and to the surface coils. In vivo evaluation of the instruments was performed in interventional MRA procedures on five pigs under MR guidance. Cartesian and projection reconstruction TrueFISP imaging enabled simultaneous visualization of the instruments and vascular morphology in real time. The implementation of RF resonators enabled robust visualization of the catheter curvature to the very tip. Additionally, the active visualization strategy does not require any wire connection to the scanner and thus does not hamper the interventionalist during the course of an intervention.

Animals↗

PubMed2004

Inhibition of the Na+/H+ exchanger attenuates the deterioration of ventricular function during pacing-induced heart failure in rabbits.

AIMS: Inhibition of the Na+/H+-exchanger (NHE) preserves myocardial morphology and function in rat and mouse models of hypertrophy and failure. The mechanism(s) involved in such cardioprotective effects remain(s) unclear, but might involve blockade of increased protein kinase activity as observed in untreated hearts. METHODS AND RESULTS: We investigated the functional, morphological and biochemical consequences of NHE-inhibition with BIIB722 in rabbits with pacing-induced heart failure (HF). In sham rabbits treated with placebo (n = 9) or BIIB722 (30 mg/kg/day po, n = 9), LV end-diastolic diameter (LVEDD) and systolic fractional shortening (FS, %) remained unchanged. In HF rabbits (n = 9), LVEDD increased and FS decreased from 31.5 +/- 1.4 to 8.1 +/- 0.9 (p < 0.05) at 3 weeks of LV pacing (400 bpm). Apoptosis, fibrosis and myocyte cross-sectional area as well as p38MAPK phosphorylation and iNOS protein expression were significantly increased in HF compared to sham rabbits. The activity of the 90 kDa NHE-kinase was greater in HF than in sham rabbits. In HF rabbits receiving BIIB722 prior to (18.1 +/- 2.2, n = 9) or following 1 week (15.5 +/- 1.6, n = 7) of pacing, FS at 3 weeks was better preserved than in untreated HF rabbits (p < 0.05). Apoptosis, fibrosis, myocyte cross-sectional area, p38MAPK phosphorylation and iNOS protein expression were significantly reduced in HF rabbits receiving BIIB722. CONCLUSION: NHE-inhibition attenuates the functional, morphological and biochemical derangements of pacing-induced HF in rabbits.

Animals↗

PubMed2004

Glucocorticoid treatment prevents progressive myocardial dysfunction resulting from experimental coronary microembolization.

BACKGROUND: The frequency and importance of microembolization in patients with acute coronary syndromes and during coronary interventions have recently been appreciated. Experimental microembolization induces immediate ischemic dysfunction, which recovers within minutes. Subsequently, progressive contractile dysfunction develops over several hours and is not associated with reduced regional myocardial blood flow (perfusion-contraction mismatch) but rather with a local inflammatory reaction. We have now studied the effect of antiinflammatory glucocorticoid treatment on this progressive contractile dysfunction. METHODS AND RESULTS: Microembolization was induced by injecting microspheres (42-microm diameter) into the left circumflex coronary artery. Anesthetized dogs were followed up for 8 hours and received placebo (n=7) or methylprednisolone 30 mg/kg IV either 30 minutes before (n=7) or 30 minutes after (n=5) microembolization. In addition, chronically instrumented dogs received either placebo (n=4) or methylprednisolone (n=4) 30 minutes after microembolization and were followed up for 1 week. In acute placebo dogs, posterior systolic wall thickening was decreased from 20.0+/-2.1% (mean+/-SEM) at baseline to 5.8+/-0.6% at 8 hours after microembolization. Methylprednisolone prevented the progressive myocardial dysfunction. Increased leukocyte infiltration in the embolized myocardium was prevented only when methylprednisolone was given before microembolization. In chronic placebo dogs, progressive dysfunction recovered from 5.0+/-0.7% at 4 to 6 hours after microembolization back to baseline (19.1+/-1.6%) within 5 days. Again, methylprednisolone prevented the progressive myocardial dysfunction. CONCLUSIONS: Methylprednisolone, even when given after microembolization, prevents progressive contractile dysfunction.

Animals↗

PubMed2003

Interventional MR angiography with a floating table.

A floating table was integrated into a setup for performance of interventional magnetic resonance (MR) angiography procedures with actively visualized catheters and biplanar real-time image fusion. The setup was evaluated by performing catheterizations in eight pigs. The floating table enabled the authors to follow actively visualized instruments in the pigs' vasculature during MR imaging-guided interventional angiography procedures while performing real-time biplanar MR imaging. Interventional MR angiography with a floating table enables the field of view to be moved along with the instrument tip to the region of interest and thus enhances the usability and flexibility of the interventional MR imaging setup.

Animals↗

PubMed2003

TNFalpha in ischemia/reperfusion injury and heart failure.

During myocardial ischemia, both the myocardial and serum TNFalpha concentrations are rapidly increased within the area at risk. With prolongation of ischemia and development of cardiomyocyte necrosis, the TNFalpha concentration increases also in the surrounding viable portions of the myocardium. Indeed, in the scenario of myocardial ischemia/reperfusion, treatment with TNFalpha antibodies reduced the extent of myocardial infarction in rabbits and attenuated the contractile dysfunction following microembolization in dogs. In the latter studies, the serum TNFalpha concentration remained unaltered thereby supporting the notion of a direct action of TNFalpha at the level of cardiomyocytes during ischemia/reperfusion. In heart failure, the serum TNFalpha concentration is also increased, and in patients with advanced heart failure the serum TNFalpha concentration is an independent predictor of mortality. The origin of the increased serum TNFalpha concentration is not clearly identified yet, but TNFalpha derived from the heart and peripheral organs contributes to the increased serum TNFalpha concentration. Treatment with TNFalpha antibodies in the clinical scenario, however, did not improve the prognosis of heart failure patients.

Animals↗

PubMed2003

Stress kinase phosphorylation is increased in pacing-induced heart failure in rabbits.

In hearts with chronic left ventricular (LV) systolic dysfunction secondary to hypertension or myocardial infarction, MAPK phosphorylation and/or activity are increased. Whether other settings of LV dysfunction not associated with ischemia-reperfusion are also characterized by increased MAPK phosphorylation or activity is unknown. After 3 wk of rapid LV pacing (400 beats/min), eight rabbits displayed clinical signs of heart failure (HF), and echocardiography revealed an increase in LV end-diastolic diameter from 15.6 +/- 0.7 (means +/- SE) to 18.8 +/- 0.7 mm and a reduced shortening fraction from 31 +/- 1to10 +/- 2% (both P < 0.05). Morphological alterations in HF included increased numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cardiomyocytes, extent of fibrosis, and cross-sectional cardiomyocyte area. Total p38 MAPK did not differ between failing and normal hearts (n = 8). However, p38 MAPK phosphorylation [164,488 +/- 29,323 vs. 43,565 +/- 14,817 arbitrary units (AU), P < 0.05, densitometry] and the activities of p38 MAPK-alpha and -beta were increased in failing compared with normal hearts (149,441 +/- 38,381 and 170,430 +/- 32,952 vs. 68,815 +/- 28,984 and 81,788 +/- 22,774 AU, respectively, both P < 0.05). In failing compared with normal hearts, total and phosphorylated JNK46 and JNK54 MAPK were increased, whereas total and phosphorylated ERK MAPK remained unchanged. In pacing-induced HF, p38 and JNK MAPK phosphorylation as well as p38 MAPK activity was increased. Further studies will have to define whether or not chronic specific blockade of MAPK activity can interfere with apoptosis/fibrosis and thereby attenuate the progression of HF.

Animals↗

PubMed2003

Serum but not myocardial TNF-alpha concentration is increased in pacing-induced heart failure in rabbits.

In animals and patients with severe heart failure (HF), the serum tumor necrosis factor-alpha (TNF-alpha) concentration is increased. It is, however, still controversial whether or not such increased serum TNF-alpha originates from the heart itself or is of peripheral origin secondary to gastrointestinal congestion and increased endotoxin concentration. We therefore now examined TNF-alpha in serum, myocardium, and liver of sham-operated and HF rabbits. In nine rabbits in which HF was induced by left ventricular (LV) pacing at 400 beats/min for 3 wk, LV end-diastolic diameter was increased and systolic shortening fraction (9.4 +/- 1.0 vs. 28.5 +/- 1.3%, echocardiography, P < 0.05) was reduced. Serum TNF-alpha was higher in HF than in sham-operated rabbits (240 +/- 24 vs. 150 +/- 22 U/ml, WEHI-cell assay, P < 0.05). In the heart, TNF-alpha was located mainly in the vascular endothelium (immunohistochemistry), and TNF-alpha protein (920 +/- 160 vs. 900 +/- 95 U/g) did not differ between groups. In the liver of HF rabbits, hepatocytes expressed TNF-alpha, and TNF-alpha protein was increased compared with sham-operated rabbits (2,390 +/- 310 vs. 1,220 +/- 135 U/g, P < 0.05) and correlated to the number of hepatic leukocytes (r = 0.85) and serum TNF-alpha (r = 0.69). The intestinal endotoxin concentration was 24.5 +/- 1.2 vs. 17.0 +/- 3.1 endotoxin units/g wet wt (P < 0.05) in HF compared with sham-operated rabbits. In this HF model, serum but not myocardial TNF-alpha is increased. The increased serum TNF-alpha originates from peripheral sources.

Animals↗

PubMed2003

Interventional MRA using actively visualized catheters, TrueFISP, and real-time image fusion.

An integrated system for performing interventional magnetic resonance angiography (MRA) with actively visualized instruments and real-time image fusion was implemented on a 1.5 T scanner. True fast imaging with steady precession (TrueFISP) imaging provided high acquisition speed paired with high signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for the simultaneous visualization of active instruments and arterial morphology. The system enabled simultaneous image reconstruction and image postprocessing of multiple receiver channels, with subsequent image fusion display in real time. Optional interleaved image acquisition in two planes provided additional important information for biplanar instrument guidance. Various vascular interventions, including selective catheterization and subsequent selective MRA of the abdominal aorta, renal arteries, superior mesenteric artery (SMA), hepatic artery, and aortic arch, were performed on 10 pigs under MR guidance. In terms of instrument contrast, image acquisition, reconstruction, and fusion speed, the setup represents a powerful platform for performing interventional MRA procedures.

Animals↗