No ischemic preconditioning in heterozygous connexin 43-deficient mice--a further in vivo study.
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Biomedical subjects
Uwe Schwanke
Publications and source records attributed to Uwe Schwanke.
Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosine.
Coronary microembolization results in progressive myocardial dysfunction, with causal involvement of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha uses a signal transduction involving nitric oxide (NO) and/or sphingosine. Therefore, we induced coronary microembolization in anesthetized dogs and studied the role and sequence of NO, TNF-alpha, and sphingosine for the evolving contractile dysfunction. Four sham-operated dogs served as controls (group 1). Eleven dogs received placebo (group 2), 6 dogs received the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, group 3), and 6 dogs received the ceramidase inhibitor N-oleoylethanolamine (NOE, group 4) before microembolization was induced by infusion of 3000 microspheres (42-microm diameter) per milliliter inflow into the left circumflex coronary artery. Posterior systolic wall thickening (PWT) remained unchanged in group 1 but decreased progressively in group 2 from 20.6+/-4.9% (mean+/-SD) at baseline to 4.1+/-3.7% at 8 hours after microembolization. Leukocyte count, TNF-alpha, and sphingosine contents were increased in the microembolized posterior myocardium. In group 3, PWT remained unchanged (20.3+/-2.6% at baseline) with intracoronary administration of L-NAME (20.8+/-3.4%) and 17.7+/-2.3% at 8 hours after microembolization; TNF-alpha and sphingosine contents were not increased. In group 4, PWT also remained unchanged (20.7+/-4.6% at baseline) with intravenous administration of NOE (19.5+/-5.7%) and 16.4+/-6.3% at 8 hours after microembolization; TNF-alpha, but not sphingosine content, was increased. In all groups, systemic hemodynamics, anterior systolic wall thickening, and regional myocardial blood flow remained unchanged throughout the protocols. A signal transduction cascade of NO, TNF-alpha, and sphingosine is causally involved in the coronary microembolization-induced progressive contractile dysfunction.
Amidohydrolases↗
[The isolated rabbit heart: comparison between five different modifications].
BACKGROUND: The isolated heart as an experimental model has been firmly established for more than 100 years. MATERIAL AND METHODS: In this study, five modifications are compared: 1. modified Langendorff apparatus (LA) with modified Krebs-Henseleit (KH) solution a) not containing bovine serum albumin (BSA; n = 13) and b) containing BSA (n = 16), 2. LA with KH solution containing BSH and bovine erythrocytes (n = 14), 3. LA with support rabbit (n = 6), and 4. "working heart" preparation with KH solution, BSA and bovine erythrocytes (n = 16). In the latter modification, no balloon was inserted into the left ventricular cavity, i. e., systemic and coronary circuits were not separated from each other. After completion of the preparation and 20-min stabilization, hemodynamic and metabolic data were assessed while the hearts were contracting in the ejecting mode. Thereafter, protocols for different studies were performed that are not presented here. However, the stability of the modifications within their individual protocols is reported. RESULTS: The results suggest that hearts perfused with KH solution are well suited for short protocols. In spite of the additional costs and time, blood perfusion is required for long-lasting protocols or if changes in coronary flow are to be investigated. CONCLUSIONS: The working heart exhibits both the best function and stability at a relatively low experimental expenditure. Yet, it is not suited for studies where perfusion pressure needs to be changed independent of arterial pressure.
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No ischemic preconditioning in heterozygous connexin43-deficient mice.
Protein kinase Cepsilon (PKCepsilon) plays a central role in ischemic preconditioning (IP) in mice and rabbits, and activated PKCepsilon colocalizes with and phosphorylates connexin43 (Cx43) in rats and humans. Whether or not Cx43 contributes to the mechanism(s) of IP in vivo is yet unknown. Therefore, wild-type (n = 8) and heterozygous Cx43-deficient mice (n = 8) were subjected to 30 min occlusion and 120 min reperfusion of the left anterior descending coronary artery. IP was induced by one cycle of 5 min occlusion and 10 min reperfusion (n = 8/8 mice) before the sustained occlusion. Infarct size was reduced by IP in wild-type mice [11.3 +/- 3.4% vs. 23.7 +/- 7.2% of the left ventricle (LV), P < 0.05] but not in Cx43-deficient mice (26.0 +/- 6.0% vs. 25.1 +/- 3.8% of LV). Also, three cycles of 5 min occlusion and 10 min reperfusion (n = 5) did not induce protection in Cx43-deficient mice (27.6 +/- 5.5 % of LV). Thus Cx43 contributes to the protection of IP in mice in vivo.
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