Biomedical subjects

Andreas Skyschally

Publications and source records attributed to Andreas Skyschally.

4 recordsLinked to original sources

PubMed2003

Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo.

During myocardial ischemia, connexin 43 (Cx43) is dephosphorylated in vitro, and the subsequent opening of gap junctions formed by two opposing Cx43 hexamers was suggested to propagate ischemia/reperfusion injury. Reduction of infarct size (IS) by ischemic preconditioning (IP) involves activation of protein kinase C (PKC) and p38 mitogen activated protein kinase (MAPK), both of which can phosphorylate Cx43. We now studied in anesthetized pigs whether IP impacts on Cx43 phosphorylation by measuring the density of non-phosphorylated and total Cx43 (confocal laser) during normoperfusion and 90-min ischemia in non-preconditioned and preconditioned hearts. Co-localization of PKCalpha, p38MAPKalpha, and p38MAPKbeta with Cx43 and the activity of p38MAPK were assessed. IP by 10 min ischemia and 15 min reperfusion reduced IS. Non-phosphorylated Cx43 remained unchanged during ischemia in preconditioned hearts, while it increased from 35+/-3 to 75+/-8 AU (P<0.05) in non-preconditioned hearts. Co-localization of PKCalpha, p38MAPKalpha, and p38MAPKbeta with Cx43 during ischemia increased only in preconditioned hearts. While the ischemia-induced increase in p38MAPKalpha activity was comparable in preconditioned and non-preconditioned hearts, p38MAPKbeta activity was increased only in preconditioned hearts. Blockade of p38MAPK by SB203580 attenuated the IS-reduction and the increased p38MAPK-Cx43 co-localization by IP. We conclude that IP increases co-localization of protein kinases with Cx43 and preserves phosphorylation of Cx43 during ischemia.

Animals↗

PubMed2003

Coronary microembolization.

Atherosclerotic plaque rupture is a key event in the pathogenesis of acute coronary syndromes and during coronary interventions. However, it does not always result in complete thrombotic occlusion of the entire epicardial coronary artery with subsequent acute myocardial infarction; in milder forms the result can be embolization of atherosclerotic and thrombotic debris into the coronary microcirculation. This review summarizes the available morphological evidence for coronary microembolization in patients who died from coronary artery disease, most notably from sudden death, and then goes on to address the experimental pathophysiology of coronary microembolization in animal models of acute coronary syndromes and heart failure. Finally, the review presents the available clinical evidence for coronary microembolization in patients, highlights its key features (ie, arrhythmias, contractile dysfunction, infarctlets and reduced coronary reserve) and addresses its prevention by mechanical protection devices and glycoprotein IIb/IIIa antagonism.

Angina, Unstable↗

PubMed2002

Attenuation of ischemic preconditioning in pigs by scavenging of free oxyradicals with ascorbic acid.

Free oxyradicals are involved in the signal transduction of ischemic preconditioning in rats and rabbits. Data from larger mammals in which the infarct development is closer to that in humans are lacking. We have therefore investigated the impact of the radical scavenger ascorbic acid on ischemic preconditioning in pigs. In 33 anesthetized pigs, the left anterior descending coronary artery was perfused from an extracorporeal circuit. Infarct size (measured as percent area at risk) was determined by triphenyltetrazolium chloride staining. In placebo-treated animals undergoing 90 min of severe ischemia and 120 min of reperfusion, infarct size averaged 26.9 +/- 3.9% (mean +/- SE; n = 9). Ischemic preconditioning by 10 min of ischemia and 15 min of reperfusion reduced infarct size to 6.4 +/- 2.4% (P < 0.05 vs. placebo; n = 9). Intravenous infusion of ascorbic acid (30 min before ischemic preconditioning or ischemia; 2-g bolus followed by 25 mg/min until the end of ischemia) had no effect on infarct size per se (22.6 +/- 6.5%; n = 6), but largely abolished the infarct size reduction by ischemic preconditioning (19.1 +/- 5.4%; n = 9). Scavenging of free oxyradicals with ascorbic acid largely attenuates the beneficial effect of ischemic preconditioning in pigs.

Animals↗

PubMed2002

Reduced coronary and inotropic reserves with coronary microembolization.

Microembolized myocardium is characterized by perfusion-contraction mismatch with reduced contractile function and unchanged or even elevated blood flow. The present study investigated the consequences of microembolization on coronary and inotropic reserves. In eight anesthetized dogs, left circumflex coronary blood flow (CBF), regional blood flow (RBF), and posterior systolic wall thickening were measured. Repetitive injection of 42-microm microspheres into the left circumflex coronary artery decreased systolic wall thickening by 50% (17.2 +/- 2.4% vs. 8.0 +/- 1.4%; means +/- SD). Coronary reserve was determined by either intracoronary infusion of adenosine (n = 4) or the reactive hyperemia response following 15 s of coronary occlusion (n = 4); inotropic reserve was recruited by intracoronary infusion of dobutamine. The amount of injected microspheres was 158,000 +/- 48,000. CBF (45.5 +/- 16.5 vs. 47.8 +/- 14.4 ml/min) and RBF (1.15 +/- 0.18 vs. 1.33 +/- 0.39 ml x min(-1) x g(-1)) remained unchanged. Coronary reserve in response to intracoronary infusion of adenosine (410 +/- 94% vs. 290 +/- 77%; P < 0.05) and reactive hyperemia repayment (360 +/- 174% vs. 155 +/- 66%; P < 0.05) were blunted after microembolization. Inotropic reserve, i.e., the increment in systolic wall thickening with dobutamine, was decreased from 12.4 +/- 3.9% to 8.0 +/- 3.3% (P < 0.05). We conclude that coronary microembolization reduces coronary and inotropic reserves.

Adenosine↗