Autumn Schumacher

Temporal and Noninvasive Monitoring of Inflammatory-Cell Infiltration to Myocardial Infarction Sites Using Micrometer-Sized Iron Oxide Particles

Micrometer‐sized iron oxide particles (MPIO) are a more sensitive MRI contrast agent for tracking cell migration compared to ultrasmall iron oxide particles. This study investigated the temporal relationship between inflammation and tissue remodeling due to myocardial infarction (MI) using MPIO‐enhanced MRI. C57Bl/6 mice received an intravenous MPIO injection for cell labeling, followed by a surgically induced MI seven days later (n = 7). For controls, two groups underwent either sham‐operated surgery without inducing an MI post‐MPIO injection (n = 7) or MI surgery without MPIO injection (n = 6). The MRIs performed post‐MI showed significant signal attenuation around the MI site for the mice that received an intravenous MPIO injection for cell labeling, followed by a surgically induced MI seven days later, compared to the two control groups (P < 0.01). The findings suggested that the prelabeled inflammatory cells mobilized and infiltrated into the MI site. Furthermore, the linear regression of contrast‐to‐noise ratio at the MI site and left ventricular ejection function suggested a positive correlation between the labeled inflammatory cell infiltration and cardiac function attenuation during post‐MI remodeling (r2 = 0.98). In conclusion, this study demonstrated an MRI technique for noninvasively and temporally monitoring inflammatory cell migration into the myocardium while potentially providing additional insight concerning the pathologic progression of a myocardial infarction. Magn Reson Med, 2010.

Assessing manganese efflux using SEA0400 and cardiac T1-mapping manganese-enhanced MRI in a murine model

The sodium–calcium exchanger (NCX) is one of the transporters contributing to the control of intracellular calcium (Ca2+) concentration by normally mediating net Ca2+ efflux. However, the reverse mode of the NCX can cause intracellular Ca2+ concentration overload, which exacerbates the myocardial tissue injury resulting from ischemia. Although the NCX inhibitor SEA0400 has been shown to therapeutically reduce myocardial injury, no in vivo technique exists to monitor intracellular Ca2+ fluctuations produced by this drug. Cardiac manganese‐enhanced MRI (MEMRI) may indirectly assess Ca2+ efflux by estimating changes in manganese (Mn2+) content in vivo, since Mn2+ has been suggested as a surrogate marker for Ca2+. This study used the MEMRI technique to examine the temporal features of cardiac Mn2+ efflux by implementing a T1‐mapping method and inhibiting the NCX with SEA0400. The change in 1H2O longitudinal relaxation rate, ΔR1, in the left ventricular free wall, was calculated at different time points following infusion of 190 nmol/g manganese chloride (MnCl2) in healthy adult male mice. The results showed 50% MEMRI signal attenuation at 3.4 ± 0.6 h post‐MnCl2 infusion without drug intervention. Furthermore, treatment with 50 ± 0.2 mg/kg of SEA0400 significantly reduced the rate of decrease in ΔR1. At 4.9–5.9 h post‐MnCl2 infusion, the average ΔR1 values for the two groups treated with SEA0400 were 2.46 ± 0.29 and 1.72 ± 0.24 s−1 for 50 and 20 mg/kg doses, respectively, as compared to the value of 1.27 ± 0.28 s−1 for the control group. When this in vivo data were compared to ex vivo absolute manganese content data, the MEMRI T1‐mapping technique was shown to effectively quantify Mn2+ efflux rates in the myocardium. Therefore, combining an NCX inhibitor with MEMRI may be a useful technique for assessing Mn2+ transport mechanisms and rates in vivo, which may reflect changes in Ca2+ transport. Copyright

Indirectly probing Ca(2+) handling alterations following myocardial infarction in a murine model using T(1)-mapping manganese-enhanced magnetic resonance imaging.

Prolonged ischemia causes cellular necrosis and myocardial infarction (MI) via intracellular calcium (Ca2+) overload. Manganese‐enhanced MRI indirectly assesses Ca2+ influx movement in vivo as manganese (Mn2+) is a Ca2+ analog. To characterize myocardial Mn2+ efflux properties, T1‐mapping manganese‐enhanced MRI studies were performed on adult male C57Bl/6 mice in which Ca2+ efflux was altered using pharmacological intervention agents or MI‐inducing surgery. Results showed that ( 1 ) Mn2+ efflux rate increased exponentially with increasing Mn2+ doses; ( 2 ) SEA0400 (a sodium–calcium exchanger inhibitor) decreased the rate of Mn2+ efflux; and ( 3 ) dobutamine (a positive inotropic agent) increased the Mn2+ efflux rate. A novel analysis technique also delineated regional features in the MI mice, which showed an increased Mn2+ efflux rate in the necrosed and peri‐infarcted tissue zones. The T1‐mapping manganese‐enhanced MRI technique characterized alterations in myocardial Mn2+ efflux rates following both pharmacologic intervention and an acute MI. The Mn2+ efflux results were consistent with those in ex vivo studies showing an increased Ca2+ concentration under similar conditions. Thus, T1‐mapping manganese‐enhanced MRI has the potential to indirectly identify and quantify intracellular Ca2+ handling in the peri‐infarcted tissue zones, which may reveal salvageable tissue in the post‐MI myocardium. Magn Reson Med, 2010.

Integrating animal model research into perianesthesia nursing practice.

IN THIS ISSUE of the Journal of PeriAnesthesia Nursing (JoPAN), Corbett and colleagues investigated the anti-inflammatory effects of ellagic acid using an established rodent animal model. Ellagic acid is a major component of pomegranate juice, an increasingly popular dietary supplement used by the American adult population. How pomegranate juice and other over-the-counter dietary supplements interactwith anesthesia and affect a patient’s recovery from surgery is largely unknown. Although it is rare for JoPAN to publish nursing research involving animal (ie, preclinical) models, such studies may significantly influence the clinical practice of perianesthesia nurses. For example, Pierce and Clancy found that hypoxia-induced diaphragm fatigue was not caused by a decrease in neuromuscular excitation of the diaphragm in anesthetized rats, but rather by decreased oxygen availability caused by low arterial blood oxygen content. These authors concluded that tidal volume might not be a reliable index of diaphragm fatigue, because a patient could be using their accessory muscles to maintain adequate tidal volume.