Cellular Mechanisms of Myocardial Hibernation, Stunning, and Ischemic Preconditioning

2000 ◽  
pp. 106-111
Author(s):  
Herwig Köppel ◽  
Ernst Pilger ◽  
Robert Gasser
Keyword(s):  
Ischemic Preconditioning ◽  
Cellular Mechanisms ◽  
Myocardial Hibernation

scholarly journals Effects of different ischemic preconditioning strategies on physiological and cellular mechanisms of intestinal ischemia/reperfusion injury: Implication from an isolated perfused rat small intestine model

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256957
Author(s):  
Yuk Lung Wong ◽  
Ingmar Lautenschläger ◽  
Lars Hummitzsch ◽  
Karina Zitta ◽  
François Cossais ◽  
...  
Keyword(s):  
Small Intestine ◽  
Ischemic Preconditioning ◽  
Intestinal Ischemia ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Cellular Mechanisms ◽  
Vascular Perfusion ◽  
Group I ◽  
Intestinal Ischemia Reperfusion

Background Intestinal ischemia/reperfusion (I/R)-injury often results in sepsis and organ failure and is of major importance in the clinic. A potential strategy to reduce I/R-injury is the application of ischemic preconditioning (IPC) during which repeated, brief episodes of I/R are applied. The aim of this study was to evaluate physiological and cellular effects of intestinal I/R-injury and to compare the influence of in-vivo IPC (iIPC) with ex-vivo IPC (eIPC), in which blood derived factors and nerval regulations are excluded. Methods Using an established perfused rat intestine model, effects of iIPC and eIPC on physiological as well as cellular mechanisms of I/R-injury (60 min hypoxia, 30 min reperfusion) were investigated. iIPC was applied by three reversible occlusions of the mesenteric artery in-vivo for 5 min followed by 5 min of reperfusion before isolating the small intestine, eIPC was induced by stopping the vascular perfusion ex-vivo 3 times for 5 min followed by 5 min of reperfusion after isolation of the intestine. Study groups (each N = 8–9 animals) were: iIPC, eIPC, I/R (iIPC group), I/R (eIPC group), iIPC+I/R, eIPC+I/R, no intervention/control (iIPC group), no intervention/control (eIPC group). Tissue morphology/damage, metabolic functions, fluid shifts and barrier permeability were evaluated. Cellular mechanisms were investigated using signaling arrays. Results I/R-injury decreased intestinal galactose uptake (iIPC group: p<0.001), increased vascular perfusion pressure (iIPC group: p<0.001; eIPC group: p<0.01) and attenuated venous flow (iIPC group: p<0.05) while lactate-to-pyruvate ratio (iIPC group, eIPC group: p<0.001), luminal flow (iIPC group: p<0.001; eIPC group: p<0.05), goblet cell ratio (iIPC group, eIPC group: p<0.001) and apoptosis (iIPC group, eIPC group: p<0.05) were all increased. Application of iIPC prior to I/R increased vascular galactose uptake (P<0.05) while eIPC had no significant impact on parameters of I/R-injury. On cellular level, I/R-injury resulted in a reduction of the phosphorylation of several MAPK signaling molecules. Application of iIPC prior to I/R increased phosphorylation of JNK2 and p38δ while eIPC enhanced CREB and GSK-3α/β phosphorylation. Conclusion Intestinal I/R-injury is associated with major physiological and cellular changes. However, the overall influence of the two different IPC strategies on the acute phase of intestinal I/R-injury is rather limited.

scholarly journals Demonstration of an early and a late phase of ischemic preconditioning in mice

1998 ◽  
Vol 275 (4) ◽  
pp. H1375-H1387 ◽  
Author(s):  
Yiru Guo ◽  
Wen-Jian Wu ◽  
Yumin Qiu ◽  
Xian-Liang Tang ◽  
Zequan Yang ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Murine Model ◽  
Late Phase ◽  
Genetically Engineered ◽  
Acid Base Balance ◽  
Cellular Mechanisms ◽  
Physiological Variables ◽  
Normal Limits ◽  
Base Balance

It is unknown whether ischemic preconditioning (PC; either early or late) occurs in the mouse. The goal of this study was to answer this question and to develop a reliable and physiologically relevant murine model of both early and late ischemic PC. A total of 201 mice were used. In nonpreconditioned open-chest animals subjected to 30 min of coronary occlusion followed by 24 h of reperfusion, infarct size (tetrazolium staining) averaged 52% of the region at risk. When the 30-min occlusion was performed 10 min after a PC protocol consisting of six cycles of 4-min occlusion and 4-min reperfusion, infarct size was reduced by 75%, indicating an early PC effect. When the 30-min occlusion was performed 24 h after the same PC protocol, infarct size was reduced by 48%, indicating a late PC effect. In mice in which the 30-min occlusion was followed by 4 h of reperfusion, infarct size was similar to that observed after 24 h of reperfusion, indicating that a 4-h reperfusion interval is sufficient to detect the final extent of cell death in this model. Fundamental physiological variables (body temperature, arterial oxygenation, acid-base balance, heart rate, and arterial pressure) were measured and found to be within normal limits. Taken together, these results demonstrate that, in the mouse, a robust infarct-sparing effect occurs during both the early and the late phases of ischemic PC, although the early phase is more powerful. This murine model is physiologically relevant, provides reliable measurements, and should be useful for elucidating the cellular mechanisms of ischemic PC in genetically engineered animals.

Cardioprotection with ischemic preconditioning and MLA: role of adenosine-regulating enzymes?

1996 ◽  
Vol 271 (3) ◽  
pp. H1004-H1014 ◽  
Author(s):  
K. Przyklenk ◽  
L. Zhao ◽  
R. A. Kloner ◽  
G. T. Elliott
Keyword(s):  
Blood Flow ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Lipid A ◽  
Canine Heart ◽  
Collateral Blood Flow ◽  
Cellular Mechanisms ◽  
Monophosphoryl Lipid A ◽  
Anesthetized Dogs ◽  
Increased Activity

Both ischemic preconditioning and pretreatment with the endotoxin derivative monophosphoryl lipid A (MLA) protect the heart against infarction, yet the cellular mechanisms responsible for the cardioprotection achieved with either intervention are unknown. Using pentobarbital-anesthetized dogs, we tested the hypothesis that increased activity of 5'-nucleotidase (5'-NT), the enzyme that catalyzes the formation of adenosine from AMP, may play a role. Twenty-two dogs underwent 1 h of coronary occlusion and 4 h of reperfusion: eight controls received no intervention, seven animals were preconditioned with four 5-min episodes of brief ischemia, and seven received MLA (35 micrograms/kg iv) 24 h previously. Collateral blood flow was measured by injection of radiolabeled microspheres, infarct size was delineated by tetrazolium staining, and myocardial 5'-NT activities were measured by quantifying the release of adenosine from AMP. Despite comparable values of collateral blood flow in all groups, infarct size was reduced in preconditioned and MLA-treated dogs vs. controls. In addition, 5'-NT activities were increased throughout the heart with preconditioning and MLA treatment. However, single and multivariate regression analyses revealed no correlation between infarct size and 5'-NT activities for either treatment group. In fact, in the preconditioned cohort, animals with the highest enzyme activities developed the largest infarcts. This dissociation between infarct size and 5'-NT suggests that increased activity of 5'-NT is not the mechanism by which preconditioning or MLA treatment protects the canine heart against infarction.

Cellular Mechanisms of Infarct Size Reduction with Ischemic Preconditioning: Role of Calcium?

1999 ◽  
Vol 874 (1 HEART IN STRE) ◽  
pp. 192-210 ◽  
Author(s):  
KARIN PRZYKLENK ◽  
BORIS Z. SIMKHOVICH ◽  
BARBARA BAUER ◽  
KATSUYA HATA ◽  
LIN ZHAO ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Size Reduction ◽  
Cellular Mechanisms ◽  
Infarct Size Reduction

scholarly journals Role of opening of ATP-sensitive K+ channels in cardioprotection afforded by ischemic preconditioning-investigation of cellular mechanisms.

1999 ◽  
Vol 19 (2) ◽  
pp. 161-169
Author(s):  
M Kitakaze ◽  
S Sanada ◽  
H Asanuma ◽  
K Node ◽  
T Minamino ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Cellular Mechanisms ◽  
K Channels

scholarly journals Role of endogenous opioids in ischemic preconditioning but not in short-term hibernation in pigs

2001 ◽  
Vol 280 (5) ◽  
pp. H2175-H2181 ◽  
Author(s):  
Rainer Schulz ◽  
Petra Gres ◽  
Gerd Heusch
Keyword(s):  
Free Energy ◽  
Ischemic Preconditioning ◽  
Atp Hydrolysis ◽  
Endogenous Opioids ◽  
Short Term ◽  
Area At Risk ◽  
Myocardial Hibernation ◽  
Percent Area ◽  
Severe Ischemia

Endogenous opioids are involved in ischemic preconditioning (IP) in several species. Whether or not opioids are important for IP and short-term myocardial hibernation (STMH) in pigs is currently unknown. In 34 enflurane-anesthetized pigs, the left anterior descending coronary artery was flow constantly perfused. Subendocardial blood flow (Endo), infarct size (IS; percent area at risk), and the free energy change of ATP hydrolysis (Δ G) were determined. After 90-min severe ischemia and 120-min reperfusion, IS averaged 28.3 ± 5.4% (means ± SE) ( n = 8; Endo: 0.047 ± 0.009 ml · min−1· g−1). IP by 10-min ischemia and 15-min reperfusion reduced IS to 9.9 ± 3.8% ( P < 0.05, n = 8; Endo: 0.044 ± 0.009 ml · min−1· g−1). After naloxone (1 mg/kg iv followed by 2 μg · kg−1· min−1), IS averaged 25.8 ± 7.0% ( n = 6; Endo: 0.039 ± 0.008 ml · min−1· g−1) without and 24.7 ± 4.7% ( n = 6; Endo: 0.044 ± 0.006 ml · min−1· g−1) with IP. At 5-min moderate ischemia in the presence of naloxone, Endo decreased from 0.90 ± 0.07 to 0.28 ± 0.03 ml · min−1· g−1and Δ G decreased from −58.6 ± 1.0 to −52.6 ± 0.4 kJ/mol. Prolongation of ischemia to 90 min did not alter Endo, but Δ G recovered toward control values (57.7 ± 1.1 kJ/mol), and the myocardium remained viable. These responses are identical to those of nonnaloxone-treated pigs. Endogenous opioids are involved in IP but not in STMH in pigs.

Sign in / Sign up

Export Citation Format

Share Document