Browsing by Subject "Cellular and Integrative Physiology"

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    The effects of temperature on cardiac paging thresholds.
    (2010-05) Marshall, Mark Thomas
    Background: Concerns exist that ventricular pacing capture thresholds (VPCT) are modified by changing cardiac temperatures due to fluctuations in core body temperature or as caused by interactions between implantable pacing systems and heating caused by MRI scans. This project was designed to assess the effects of temperature on VPCT of the mammalian heart. Methods: Fresh ventricular specimens were obtained from healthy canine, healthy swine, and diseased human hearts. Isolated trabecula were suspended in temperature-controlled tissue baths containing oxygenated Krebs buffer. Small active fixation pacing leads delivered pacing pulses to each specimen. Baseline strength-duration curves were determined at Background: Concerns exist that ventricular pacing capture thresholds (VPCT) are modified by changing cardiac temperatures due to fluctuations in core body temperature or as caused by interactions between implantable pacing systems and heating caused by MRI scans. This project was designed to assess the effects of temperature on VPCT of the mammalian heart. Methods: Fresh ventricular specimens were obtained from healthy canine, healthy swine, and diseased human hearts. Isolated trabecula were suspended in temperature-controlled tissue baths containing oxygenated Krebs buffer. Small active fixation pacing leads delivered pacing pulses to each specimen. Baseline strength-duration curves were determined atBackground: Concerns exist that ventricular pacing capture thresholds (VPCT) are modified by changing cardiac temperatures due to fluctuations in core body temperature or as caused by interactions between implantable pacing systems and heating caused by MRI scans. This project was designed to assess the effects of temperature on VPCT of the mammalian heart. Methods: Fresh ventricular specimens were obtained from healthy canine, healthy swine, and diseased human hearts. Isolated trabecula were suspended in temperature-controlled tissue baths containing oxygenated Krebs buffer. Small active fixation pacing leads delivered pacing pulses to each specimen. Baseline strength-duration curves were determined at 37°C, then at randomized temperatures ranging from 35°C to 42°C. Final thresholds were repeated at 37°C to confirm baseline responses. All threshold data were normalized to a baseline average. Results: Both canine and swine trabeculae elicited significant decreases in thresholds (10-14%) at pacing stimulus durations (pulsewidths) of 0.02ms (p<0.01) and 0.10ms (p<0.05) between the temperatures of 38°C and 41°C, compared to baseline. Thresholds at 42°C trended back to baseline for both canine (NS) and swine trabeculae (p<0.05 compared to 38-41°C). Human trabeculae thresholds increased > 35% (p<.05) at 42°C relative to baseline with no significant differences at other temperatures. Conclusions: Temperature is a significant factor on pacing thresholds for mammalian ventricular myocardium. This data for the diseased human trabeculae indicates that cases where cardiac heating may occur (e.g. RF energy due to MRI scans), patients with marginal VPCT may lose proper function of an implanted pacing system.
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    The role of renin in the adipose tissue renin-angiotensin system.
    (2009-07) Fowler, Jason Dean
    The renin angiotensin system (RAS) has been implicated in a variety of adipose tissue functions including tissue growth, differentiation, metabolism, and inflammation. While expression of all components necessary for a locally derived adipose tissue RAS have been demonstrated within adipose tissue, independence of local adipose RAS component concentrations from corresponding plasma RAS fluctuations has not been addressed. To analyze this, we varied in vivo rat plasma concentrations of two RAS components, renin and angiotensinogen (AGT), to determine the influence of their plasma concentrations on adipose and cardiac tissue levels in both perfused (plasma removed) and nonperfused samples. Variation of plasma RAS components was accomplished by 4 treatment groups: Normal, DOCA-salt, Bilateral nephrectomy, and Losartan. Adipose and cardiac tissue AGT concentrations correlated positively with plasma values. Perfusion of adipose tissue decreased AGT concentrations by 11.1% indicating that adipose tissue AGT was in equilibrium with plasma. Cardiac tissue renin levels positively correlated with plasma renin concentration for all treatments. In contrast, adipose tissue renin levels did not correlate with plasma renin, with the exception of extremely high plasma renin concentrations achieved in the Losartan treated group. These results suggest that adipose tissue may control its own local renin concentration independently of plasma renin as a potential mechanism for maintaining a functional local adipose RAS. Whereas adipose tissue possesses a local renin-angiotensin system, the synthesis and regulated release of renin has not been addressed. To that end we utilized differentiating 3T3-L1 cells and analyzed renin expression and secretion. Renin mRNA expression and protein enzymatic activity were not detectable in preadipocytes. However, upon differentiation, renin mRNA and both intracellular and extracellular renin activity were up regulated. In differentiated adipocytes, forskolin treatment resulted in a 28-fold increase in renin mRNA while TNF alpha treatment decreased renin mRNA 4-fold. IL-6, insulin, and angiotensin II (Ang II) were without effect. In contrast, forskolin and TNF alpha each increased renin protein secretion by 12- and 7-fold, respectively. Although both forskolin and TNFalpha induce lipolysis in adipocytes, fatty acids, prostaglandin E2 or lipopolysaccharide had no effect on renin mRNA or secretion. To evaluate mechanism(s) by which forskolin and/or TNF alpha are able to regulate renin secretion, a general lipase inhibitor (E600) and PKA inhibitor (H89) were used. Both inhibitors attenuated forskolin induced renin release while having no effect on TNF alpha regulated secretion. In contrast, E600 potentiated forskolin-stimulated renin mRNA levels while H89 had no effect. Neither inhibitor had any influence on TNFalpha regulation of renin mRNA. Relative to lean controls, renin expression was reduced 78% in the epididymal adipose tissue of obese male C57Bl/6J mice, consistent with TNF alpha-mediated down regulation of renin mRNA in the culture system. In conclusion, the expression and secretion of renin are regulated under a complex series of hormonal and metabolic determinants in mature 3T3-L1 adipocytes.