Joseph Sikora

Subchronic In Vivo Effects of a High Static Magnetic Field (9.4 T) in Rats

The potential adverse biologic effects of sub chronic (cumulatively 10 weeks) exposure to a high magnetic field (9.4 T) were evaluated in young adult male and female Fischer rats as well as in their progeny. Biologic end points in adult rats included changes in daily clinical observations; spatial memory tests; weekly heart rates, body weights, food and water consumption, and the feed efficiency ratio; terminal hematologic, blood biochemical and urinary parameter changes; gross pathologic findings; and major organ weights. In offspring, biologic end points included the gestation period, number of live births, number of pups, ratio of male to female pups/litter; postnatal time period of eye opening; birth and weekly body weights, behavorial changes, central nervous system responses, as well as hematologic, blood biochemistry, and urinary parameter changes; and gross pathologic findings. Findings from this study showed that there were no adverse biologic effects in male and female adult rats or their progeny that could be attributed to 10‐week exposure to a 9.4‐T static magnetic field. J. Magn. Reson. Imaging 2000;12:122–139.

Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning

Altered expression of mitochondrial electron transport proteins has been shown in early preconditioned myocardial tissue. We wished to determine whether these alterations persist in the Second Window of Protection (SWOP) and if so, whether a favorable energetic state is facilitated during subsequent ischemia. Fourteen pigs underwent a SWOP protocol with ten 2-minute balloon inflations in the LAD artery, each separated by 2 minutes reperfusion. Twenty-four hours later, mitochondria were isolated from SWOP and SHAM pig hearts and analyzed for uncoupling protein (UCP)-2 content by western blot analysis, proteomic changes by iTRAQ(®) and respiration by an oxygen electrode. In parallel in vivo studies, high-energy nucleotides were obtained by transmural biopsy from anesthetized SWOP and SHAM pigs at baseline and during sustained low-flow ischemia. Compared with SHAM mitochondria, ex vivo SWOP heart tissue demonstrated increased expression of UCP-2, Complex IV (cytochrome c oxidase) and Complex V (ATPase) proteins. In comparison with SHAM pigs during in vivo conditions, transmural energetics in SWOP hearts, as estimated by the free energy of ATP hydrolysis (ΔG(0)), were similar at baseline but had decreased by the end of low-flow ischemia (-57.0 ± 2.1 versus -51.1 ± 1.4 kJ/mol; P < 0.05). In conclusion, within isolated mitochondria from preconditioned SWOP hearts, UCP-2 is increased and in concert with enhanced Complex IV and V proteins, imparts a favorable energetic state during low-flow ischemia. These data support the notion that mitochondrial adaptations that may reduce oxidant damage do not reduce the overall efficiency of energetics during sustained oxygen deprivation.

Myocardial glucose uptake after dobutamine stress in chronic hibernating swine myocardium

BackgroundIn patients with hibernating myocardium, regional uptake of the glucose analog 2-fluorine 18-fluoro-2-deoxy-D-glucose (FDG) is increased under resting conditions. It is unclear whether the degree of increased FDG uptake correlates with the degree of impaired blood flow response and whether chronic changes in the glucose transporters may play a role in the enhanced FDG uptake under fasted conditions.Methods and ResultsTwelve swine were instrumented with a constrictor on the left anterior descending (LAD) artery. Serial echocardiography and positron emission tomography studies were done to assess temporal changes in myocardial function, blood flow, and FDG uptake. One week after surgery (early study), wall thickening, blood flow, and postdobutamine FDG uptake in LAD and remote territories were similar. By approximately 6 weeks (late study), baseline wall thickening in the LAD region was lower than in remote regions (20% ±7% and 36% ± 6%, P < .05), as was dobutamine-stimulated blood flow (0.92 ± 0.16 mL⋅min-1⋅g-1 and 1.17 ± 0.20 mL⋅min-1⋅g-1 in LAD and remote regions, respectively; P < .05). After the dobutamine infusion, FDG uptake in the LAD region during fasted conditions was higher than in remote regions (0.128 ± 0.053 μmol⋅min-1⋅g-1 and 0.098 ± 0.044 μmol⋅min-1⋅g-1, respectively; P < .05), and the increase was proportional to the impairment in dobutamine blood flow (r2 = 0.62, P < .001). After the animals were killed, the LAD region showed a higher content of GLUT4 by immunoblots and a greater degree of translocation as estimated by immunohisto-chemistry. In 5 additional hibernating pigs studied under resting fasted conditions, FDG uptake and GLUT4 translocation were also higher in the LAD region, in the absence of dobutamine stimulation.ConclusionsIn hibernating myocardium, regional FDG uptake under fasting conditions is higher than in remote regions, both at rest and after an infusion of dobutamine. The degree of poststress FDG uptake is proportional to the impaired stress-induced blood flow. Total GLUT4 content as well as membrane-bound protein is higher in the hibernating tissue, and these changes may facilitate the observed increase in FDG uptake.