Catheter-Induced Left Ventricular Perforation and Cardiac Tamponade During Left Heart Catheterization.

Iatrogenic ventricular perforation of the myocardial wall is a rare but life-threatening complication. It has been described using pulmonary artery catheter, pigtail catheter, and Judkins catheter. Straight wires and catheters can be used to cross the aortic valve for left ventriculogram; however, the risk of perforation is higher compared with J-tip wires. Prompt recognition of cardiac tamponade and pericardial drain insertion is vital, but surgical patch repair may be required for definitive treatment. This case highlights the importance of increased vigilance and prompt management of cardiac tamponade with the use of high-risk equipment during cardiac catheterization.

Caspase-2 modulates osteoclastogenesis through down-regulating oxidative stress.

The loss of caspase-2 (Casp-2) in mice results in an osteopenic phenotype associated with increased numbers of osteoclasts in vivo. In this study, we show that Casp-2 is involved in osteoclastogenesis. Protein levels of Casp-2 decrease during the differentiation of macrophages to osteoclasts. Furthermore, siRNA-mediated Casp-2 knockdown in osteoclast precursors or differentiation of bone marrow macrophage (BMM) precursors from Casp2(-/-) mice results in increased osteoclast numbers and tartrate-resistant acid phosphatase (TRAP) activity. Casp2(-/-) osteoclasts are larger in size compared to wild-type osteoclasts and exhibited increased numbers of nuclei, perhaps due to increased precursor fusion. The loss of Casp-2 did not alter earlier stages of differentiation, but had a greater consequence on later stages involving NFATc1 auto-amplification and pre-osteoclast fusion. We have previously shown that the loss of Casp-2 results in increased oxidative stress in the bone. Reactive oxygen species (ROS) is known to play a critical role in late osteoclast differentiation and we show that total ROS and specifically, mitochondrial ROS, significantly increased in Casp2(-/-) BMM precursors after RANKL administration, with a concomitant reduction in FoxO3a and its target antioxidant enzymes, catalase and superoxide 2 (SOD2). Because mitochondrial ROS has been identified as a putative regulator of the later stages of differentiation, the heightened ROS levels in Casp2(-/-) cells likely promote precursor fusion and increased osteoclast numbers. In conclusion, our results indicate a novel role of Casp-2 in the osteoclast as a modulator of total and mitochondrial ROS and osteoclast differentiation.

Safety of same day discharge following percutaneous coronary intervention.

BACKGROUND: There is a body of literature reporting the safety of discharging patients the same day as percutaneous coronary revascularisation. Nevertheless, overnight stay continues to be the general standard of care. METHODS: Over a single calendar year, 130 patients having elective, percutaneous coronary revascularisation were discharged home the day of the procedure with the majority of procedures using radial access. Patients were observed post procedure for six hours and if no problems occurred, discharge was undertaken. The purpose of the study was to assess complications in the 24 hours following discharge. RESULTS: Within the following 24 hours post discharge, there were no complications reported including bleeding, recurrent ischaemia, or hospitalisation. CONCLUSION: Same day discharge following elective percutaneous revascularisation appears both efficacious and safe with a low risk of post discharge complications.

Safety and efficacy of offsite percutaneous coronary interventions in 1,348 consecutive patients in rural Tasmania.

Despite controversy, a growing body of data exists suggesting that percutaneous coronary intervention (PCI) with no surgical onsite availability is safe and efficacious. Over a period of 3 years all patients requiring PCI had their intervention performed at the Launceston General Hospital, a regional hospital serving rural Tasmania, Australia. There were no exclusion criteria uniformly adopted. Primary end points included angiographic success and major procedure-related complications. A total cohort of 1,348 consecutive patients underwent PCI during the calendar years of 2005 through 2007, including patients with ST-elevation myocardial infarction. Angiographic success for all patients was >98%. In-hospital mortality was 0.8% overall. Only 1 patient required urgent transfer to a cardiac surgical center. Bleeding rates requiring transfusion were approximately 1%. Excellent clinical outcomes have been achieved in a relatively remote PCI center in rural, northern Tasmania, where there is no emergency cardiac surgical availability. Angiographic success was high and complication rates were low, consistent with worldwide standards. In conclusion, PCI without onsite surgery appears safe and efficacious when well-trained staffing is available.

Very late stent thrombosis after discontinuation of clopidogrel therapy.

Stent thrombosis is an infrequent but severe complication after coronary stent implantation. Dual antiplatelet therapy has markedly reduced the occurrence of this potentially catastrophic event. The optimal duration of clopidogrel therapy in patients with drug-eluting stents is unknown. We describe a case of stent thrombosis 9 days after discontinuation of clopidogrel therapy, more than 3 years after placement of drug-eluting stents.

Nonlinear scaling analysis of glucose metabolism in normal and cancer cells.

Cancer progression is commonly accompanied by an altered glucose metabolism. In general, spatially resolved imaging of glucose metabolism and its subtle alterations might provide valuable diagnostic information in vivo. A classical example is positron emission tomography that exploits this feature in obtaining preferential accumulation of fluorescent analog of glucose in tumors, thereby achieving an imaging contrast. We report a novel scaling analysis of glucose metabolism in mammary epithelial (NMuMG) cells by detrended fluctuation analysis of Cerulean (cyan fluorescent protein variant) fluorescence. Fluorescence fluctuations of Cerulean are reasoned to be indicative of dynamic pH changes associated with glucose metabolism. Normal parental cells and the spontaneously transformed (cancerous) NMuMG cells displayed robust scaling exponent that reflects nonrandom fluctuations in Cerulean fluorescence. Acute dependence of cancer cells on glycolysis as compared with normal cells is exploited to yield a statistically significant difference in scaling exponent, thereby providing discrimination between normal and cancer cells in vitro. By careful design of experiments in vivo, the proposed scaling approach might even have diagnostic potential for early detection of cancer lesions in small animal models.

Aging process modulates nonlinear dynamics in liver cell metabolism.

Regulatory dynamics of energy metabolism in living cells entails a coordinated response of multiple enzyme networks that operate under non-equilibrium conditions. Here we show that mitochondrial dysfunctions associated with the aging process significantly modify nonlinear dynamical signatures in free radical generation/removal, thereby altering energy metabolism in liver cells. We support our data with a plausible biochemical mechanism for modified bioenergetics that involves uncoupling protein-2 that is up-regulated in aged cells as an adaptive response to mitigate increased oxidative stress. Combining high spatial and temporal resolution imaging and bio-energetic measurements, our work provides experimental support to the hypothesis that mitochondria manifest nonlinear dynamical behavior for efficiently regulating energy metabolism in intact cells, and any partial or complete reduction in this behavior would contribute to organ dysfunctions including the aging process and other disease processes.

Spectral kinetics ratiometry: a simple approach for real-time monitoring of fluorophore distributions in living cells.

BACKGROUND: Spectral Imaging Microscopy is gaining attention in biological research. Most of the commercial systems in vogue employ linear spectral un-mixing algorithms and/or spectral profile matching algorithms to extract the component spectral information from the measured specimen spectra. The need to accurately deconvolve multiple spectra with minimal cross-contamination is always accompanied by an increase in system complexity and cost. METHODS: We describe here a variant of the spectral waveform cross-correlation analysis (SWCCA) method where the master reference spectral library is constructed by composite spectra with varying ratios of component spectra, unlike the conventional spectral library where pure spectra form the components. We demonstrate that this spectral kinetics ratiometric approach gives realistic estimates of fluorophore distribution in living cells with a better spectral correlation as compared with pure component spectral libraries. RESULTS: Biological applications demonstrated in this article include acceptor photobleaching FRET, caspase activity during cell death and mitochondrial membrane polarization kinetics during substrate metabolism. CONCLUSIONS: Beyond the representative applications presented in this article, we think the proposed approach can be valuable in dynamic studies of a variety of other cellular processes such as pH oscillations, photobleaching and quenching kinetics. Besides giving better spectral correlation and real-time monitoring of biophysical processes in living cells, this method can serve as an economical solution for high-throughput spectral classification requirements.

Scaling behavior in mitochondrial redox fluctuations.

Scale-invariant long-range correlations have been reported in fluctuations of time-series signals originating from diverse processes such as heart beat dynamics, earthquakes, and stock market data. The common denominator of these apparently different processes is a highly nonlinear dynamics with competing forces and distinct feedback species. We report for the first time an experimental evidence for scaling behavior in NAD(P)H signal fluctuations in isolated mitochondria and intact cells isolated from the liver of a young (5-month-old) mouse. Time-series data were collected by two-photon imaging of mitochondrial NAD(P)H fluorescence and signal fluctuations were quantitatively analyzed for statistical correlations by detrended fluctuation analysis and spectral power analysis. Redox [NAD(P)H / NAD(P)(+)] fluctuations in isolated mitochondria and intact liver cells were found to display nonrandom, long-range correlations. These correlations are interpreted as arising due to the regulatory dynamics operative in Krebs' cycle enzyme network and electron transport chain in the mitochondria. This finding may provide a novel basis for understanding similar regulatory networks that govern the nonequilibrium properties of living cells.