Biomedical subjects

Stephen C Lenhard

Publications and source records attributed to Stephen C Lenhard.

4 recordsLinked to original sources

PubMed2005

Differential uptake of ferumoxtran-10 and ferumoxytol, ultrasmall superparamagnetic iron oxide contrast agents in rabbit: critical determinants of atherosclerotic plaque labeling.

PURPOSE: To compare atherosclerotic plaque uptake of a first (ferumoxtran-10) and second generation (ferumoxytol) ultrasmall superparamagnetic iron oxide (USPIO) contrast agent with different pharmacokinetic/pharmacodynamic properties. MATERIALS AND METHODS: New Zealand White rabbits maintained on a high cholesterol/fat diet were subjected to balloon injury to the abdominal aorta. Ferumoxtran-10 or ferumoxytol (500 micromol/kg) was administered at 2, 4, and 8 weeks following injury. In vivo magnetic resonance imaging (MRI) was performed immediately prior to, immediately after, and 6 days post-contrast administration. Ex vivo MRI, histologic, and inductively coupled plasma-mass spectrometry (ICP-MS) iron analyses were performed on the excised vessels. RESULTS: The blood pool clearance of ferumoxytol (t(1/2) < or = 6 hours) was more rapid than that of ferumoxtran-10 (t(1/2) < or = 48 hours). Decreased in vivo MRI signal intensity in the abdominal aorta was observed at 2, 4, and 8 weeks following injury with ferumoxtran-10, but not with ferumoxytol. Consistent with these observations, ex vivo MRI signal intensity was decreased in the ferumoxtran-10 vessels, and to a lesser degree in the ferumoxytol vs. control vessels (- contrast agent). In contrast, in vitro macrophage phagocytosis of USPIO was four to six fold greater with ferumoxytol than with ferumoxtran-10. Additionally, the absolute iron content correlated with ex vivo MRI signal intensity in all vessels (r = -0.86, P < 0.0001). CONCLUSIONS: These data suggest that the exposure period of atherosclerotic plaque to USPIO rather than the kinetics of the USPIO uptake by plaque alone is a critical criterion for experimental design of in vivo studies.

Animals↗

PubMed2004

Simultaneous assessment of left-ventricular infarction size, function and tissue viability in a murine model of myocardial infarction by cardiac manganese-enhanced magnetic resonance imaging (MEMRI).

Owing to its signal-enhancing characteristics in viable well-perfused tissue, divalent manganese (Mn2+) has been used as a myocardial imaging contrast agent. Because Mn2+ can enter excitable cells through the voltage-gated L-type calcium channels, manganese-enhanced MRI (MEMRI) has been used to determine the viability and the inotropic state of the heart. In this study, we examined the correlation between left ventricular infarction zone as assessed by cardiac MEMRI and function in mice with permanent coronary artery occlusion. At an Mn2+ infusion dose of 1.72+/-0.47 nmol/min/g body weight, the steady-state signal intensity (SI) enhancement 20-26 min post-Mn2+ infusion of the normal septum and left-ventricular wall during diastole was 128.2+/-14.4 and 127.9+/-26.5%, respectively, whereas the infarction zone was 56.0+/-7.1%. During systole, the SI enhancement was 144.6+/-33.0, 116.0+/-18.7 and 48.3+/-20.0% for the normal septum, left-ventricular wall and infarction zone, respectively. A good correlation was obtained between the MEMRI determined infarction volume and conventional histological TTC staining (r = 0.9582, p<0.01). There was also a strong negative correlation between MEMRI determined infarction percentage (compared with whole left ventricle) and ejection fraction (r = -0.94, p<0.05). These data suggest that the Mn2+ concentration at steady state in the heart may reflect altered tissue viability in the infarcted tissue as well as surrounding region following myocardial infarction. In conclusion, in vivo cardiac MEMRI offers a manner in which functional, pathologic and viability data may be obtained simultaneously in myocardial tissue.

Animals↗

PubMed2003

p38 MAPK inhibitors ameliorate target organ damage in hypertension: Part 2. Improved renal function as assessed by dynamic contrast-enhanced magnetic resonance imaging.

Recent evidence suggests p38 mitogen-activated protein kinase (MAPK) signal transduction plays an important role in the pathogenesis of progressive renal disease. Using dynamic contrast enhanced magnetic resonance imaging (MRI), we evaluated chronic treatment with a p38 MAPK inhibitor, trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl-methoxypyridimidin-4-yl)imidazole (SB-239063), on renal function in a hypertension model of progressing renal dysfunction. Spontaneously hypertensive-stroke prone rats were placed on a high salt/fat diet (SFD) or maintained on normal chow diet (ND). SFD animals with albuminuria at 4 to 8 weeks (> or =10 mg/day inclusion criteria), were randomized into p38 MAPK inhibitor treatment (SB-239063, 1200 ppm in diet) or vehicle groups. The progression of blood pressure and albuminuria during the treatment period (approximately 6 weeks) was decreased by 12 and 60%, respectively, in the SFD + SB-239063 versus SFD control group. Renal perfusion and filtration were assessed by in vivo MRI at the end of the study. Relative cortical perfusion was increased in the SFD + SB-239063 group compared with the SFD control group as reflected by a 29% decrease in time to peak of contrast agent in the cortex. Additionally, the regional renal glomerular filtration rate index (Kcl) was increased by 39% in the SFD + SB-239063 versus SFD control group and was normalized to the ND control group. Greater functional heterogeneity was observed in the SFD control versus SFD + SB-239063 or ND control group. All alterations of renal function were supported by histopathological findings. In conclusion, chronic treatment with a p38 MAPK inhibitor, SB-239063, attenuates functional and structural renal degeneration in a hypertensive model of established renal dysfunction.

Albuminuria↗

PubMed2003

Strain-dependent response to cerebral ischemic preconditioning: differences between spontaneously hypertensive and stroke prone spontaneously hypertensive rats.

Ischemic preconditioning (PC) is a phenomenon whereby a brief exposure to ischemia renders a tissue more tolerant to a subsequent sustained ischemic insult. Animals of the Spontaneously Hypertensive (SHR) and the Spontaneously Hypertensive Stroke-Prone (SHR-SP) rat strains produce cerebral infarcts that are larger and more reproducible in size than infarcts of normotensive rats. This study compared the effects of PC in SHR and SHR-SP rats, under the hypothesis that PC may not be as effective in the SHR-SP, a strain genetically predisposed to stroke. There were two groups per strain, with between eight and ten animals each. The Precondition group (PC) had a 10 min occlusion of the middle cerebral artery on day -1. On the same day the Sham group (Sham) received sham surgery. On day 0, both groups underwent permanent occlusion of the middle cerebral artery. The ischemic lesion was measured on day 1 using T(2)-weighted magnetic resonance imaging. Percent hemispheric infarct was significantly reduced in SHR PC vs. SHR Sham, SHR-SP PC vs. SHR-SP Sham, and SHR PC vs. SHR-SP PC. Thus, rats of the SHR-SP strain respond to PC less markedly than SHR animals. Both models may now be used to elucidate the mechanisms underlying PC.

Animals↗