scholarly journals Impact of Anesthetics on Cardioprotection Induced by Pharmacological Preconditioning

2019 ◽  
Vol 8 (3) ◽  
pp. 396 ◽  
Author(s):  
Sebastian Bunte ◽  
Tobias Lill ◽  
Maximilian Falk ◽  
Martin Stroethoff ◽  
Annika Raupach ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Wistar Rats ◽  
Constant Pressure ◽  
Size Reduction ◽  
Control Groups ◽  
Infarct Size Reduction ◽  
Male Wistar Rats ◽  
Pharmacological Preconditioning ◽  
Krebs Henseleit Buffer

Anesthetics, especially propofol, are discussed to influence ischemic preconditioning. We investigated whether cardioprotection by milrinone or levosimendan is influenced by the clinically used anesthetics propofol, sevoflurane or dexmedetomidine. Hearts of male Wistar rats were randomised, placed on a Langendorff system and perfused with Krebs–Henseleit buffer (KHB) at a constant pressure of 80 mmHg. All hearts underwent 33 min of global ischemia and 60 min of reperfusion. Three different anesthetic regimens were conducted throughout the experiments: propofol (11 μM), sevoflurane (2.5 Vol%) and dexmedetomidine (1.5 nM). Under each anesthetic regimen, pharmacological preconditioning was induced by administration of milrinone (1 μM) or levosimendan (0.3 μM) 10 min before ischemia. Infarct size was determined by TTC staining. Infarct sizes in control groups were comparable (KHB-Con: 53 ± 9%, Prop-Con: 56 ± 9%, Sevo-Con: 56 ± 8%, Dex-Con: 53 ± 9%; ns). Propofol completely abolished preconditioning by milrinone and levosimendan (Prop-Mil: 52 ± 8%, Prop-Lev: 52 ± 8%; ns versus Prop-Con), while sevoflurane did not (Sevo-Mil: 31 ± 9%, Sevo-Lev: 33 ± 7%; p < 0.05 versus Sevo-Con). Under dexmedetomidine, results were inconsistent; levosimendan induced infarct size reduction (Dex-Lev: 36 ± 6%; p < 0.05 versus Dex-Con) but not milrinone (Dex-Mil: 51 ± 8%; ns versus Dex-Con). The choice of the anesthetic regimen has an impact on infarct size reduction by pharmacological preconditioning.

scholarly journals Effluent from ischemic preconditioned hearts confers cardioprotection independent of the number of preconditioning cycles

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243220
Author(s):  
Katharina Feige ◽  
Annika Raupach ◽  
Carolin Torregroza ◽  
Jan Muehlenbernd ◽  
Martin Stroethoff ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Rat Heart ◽  
Myocardial Protection ◽  
Wistar Rats ◽  
Isolated Hearts ◽  
Infarct Size Reduction ◽  
Male Wistar Rats ◽  
Krebs Henseleit Buffer

Coronary effluent collected from ischemic preconditioning (IPC) treated hearts induces myocardial protection in non-ischemic-preconditioned hearts. So far, little is known about the number of IPC cycles required for the release of cardioprotective factors into the coronary effluent to successfully induce cardioprotection. This study investigated the cardioprotective potency of effluent obtained after various IPC cycles in the rat heart. Experiments were performed on isolated hearts of male Wistar rats, mounted onto a Langendorff system and perfused with Krebs-Henseleit buffer. In a first part, effluent was taken before (Con) and after each IPC cycle (Eff 1, Eff 2, Eff 3). IPC was induced by 3 cycles of 5 min of global myocardial ischemia followed by 5 minutes of reperfusion. In a second part, hearts of male Wistar rats were randomized to four groups (each group n = 4–5) and underwent 33 min of global ischemia followed by 60 min of reperfusion. The previously obtained coronary effluent was administered for 10 minutes before ischemia as a preconditioning stimulus. Infarct size was determined at the end of reperfusion by triphenyltetrazoliumchloride (TTC) staining. Infarct size with control effluent was 54±12%. Effluent obtained after IPC confers a strong infarct size reduction independent of the number of IPC cycles (Eff 1: 27±5%; Eff 2: 35±7%; Eff 3: 35±8%, each P<0.05 vs. Con). Effluent extracted after one cycle IPC is comparably protective as after two or three cycles IPC.

Differential role of sarcolemmal and mitochondrial KATP channels in adenosine-enhanced ischemic preconditioning

2000 ◽  
Vol 279 (6) ◽  
pp. H2694-H2703 ◽  
Author(s):  
Yoshiya Toyoda ◽  
Ingeborg Friehs ◽  
Robert A. Parker ◽  
Sidney Levitsky ◽  
James D. McCully
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Channel Blocker ◽  
Katp Channels ◽  
Size Reduction ◽  
Ischemia And Reperfusion ◽  
Infarct Size Reduction ◽  
Mitochondrial Katp Channels

Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery. The purpose of this study was to determine whether APC is modulated by ATP-sensitive potassium (KATP) channels and to determine whether this modulation occurs before ischemia or during reperfusion. The role of KATP channels before ischemia (I), during reperfusion (R), or during ischemia and reperfusion (IR) was investigated using the nonspecific KATP blocker glibenclamide (Glb), the mitochondrial (mito) KATP channel blocker 5-hydroxydecanoate (5-HD), and the sarcolemmal (sarc) KATPchannel blocker HMR-1883 (HMR). Infarct size was significantly increased ( P < 0.05) in APC hearts with Glb-I, Glb-R, and 5-HD-I treatment and partially with 5-HD-R. Glb-I and Glb-R treatment significantly decreased APC functional recovery ( P < 0.05 vs. APC), whereas 5-HD-I and 5-HD-R had no effect on APC functional recovery. HMR-IR significantly decreased postischemic functional recovery ( P < 0.05 vs. APC) but had no effect on infarct size. These data indicate that APC infarct size reduction is modulated by mitoKATP channels primarily during ischemia and suggest that functional recovery is modulated by sarcKATP channels during ischemia and reperfusion.

Sarcolemmal KATP channel triggers delayed ischemic preconditioning in rats

2005 ◽  
Vol 288 (1) ◽  
pp. H445-H447 ◽  
Author(s):  
Hemal H. Patel ◽  
Eric R. Gross ◽  
Jason N. Peart ◽  
Anna K. Hsu ◽  
Garrett J. Gross
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Size Reduction ◽  
Sprague Dawley ◽  
Area At Risk ◽  
Sprague Dawley Rats ◽  
Rat Hearts ◽  
Opioid Administration ◽  
Infarct Size Reduction ◽  
Prior Administration

Previous work from our laboratory has shown that the sarcolemmal KATP channel (sKATP) is required as a trigger for delayed cardioprotection upon exogenous opioid administration. We also established that the mitochondrial KATP (mKATP) channel is not required for triggering delayed δ-opioid-induced infarct size reduction. Because mechanistic differences have been found among δ-opioids and that due to ischemic preconditioning (IPC), we determined whether the triggering mechanism of delayed IPC-induced infarct size reduction involves either the sKATP or mKATP. Male Sprague-Dawley rats received either sham surgery or IPC (3- to 5-min cycles of ischemia and reperfusion) 24 h before being subjected to 30 min of ischemia and 2 h of reperfusion. Infarct size was determined and expressed as a percentage of the area at risk, with significance compared with sham reported at P ≤ 0.001. A subset of both sham and IPC-treated rats received either the selective sKATP channel antagonist, HMR-1098 (6 mg/kg), or the selective mKATP channel antagonist, 5-hydroxydeconoic acid (5-HD; 10 mg/kg), given 5 min before IPC. Rats subjected to IPC demonstrated a significant reduction in infarct size compared with sham (29.2 ± 4.7 vs. 59.3 ± 2.5%, respectively; P ≤ 0.001). Prior administration of HMR-1098, but not 5-HD, abolished IPC-induced infarct size reduction (48.8 ± 2.9 and 28.8 ± 4.0%, respectively; P ≤ 0.001). Furthermore, administration of HMR 24 h after IPC, before index ischemia, did not abrogate IPC-induced infarct size reduction (33.0 ± 5.0 vs. 29.2 ± 4.7%, respectively; P ≤ 0.001). These data suggest that the sKATP channel is required as a trigger but not a mediator for delayed IPC-induced infarct size reduction in rat hearts.

scholarly journals Mechanisms of myocardial ischemic preconditioning are age related: PKC-ϵ does not play a requisite role in old rabbits

2003 ◽  
Vol 95 (6) ◽  
pp. 2563-2569 ◽  
Author(s):  
Karin Przyklenk ◽  
Guohu Li ◽  
Boris Z. Simkhovich ◽  
Robert A. Kloner
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Myocardial Infarct ◽  
Control Period ◽  
Size Reduction ◽  
Myocardial Infarct Size ◽  
Age Related ◽  
Specific Subset ◽  
Infarct Size Reduction

Data obtained from adult cohorts have implicated activation/translocation of protein kinase C (PKC)-ϵ as an important cellular mediator of myocardial infarct size reduction with ischemic preconditioning (PC). Age-related alterations in cellular signaling may, however, confound the extrapolation of mechanistic insight derived from adults to the aging population, the specific subset in which cardioprotection is undoubtedly most relevant. Accordingly, our aim was to investigate the role of PKC-ϵ as a mediator of infarct size reduction with PC in old vs. adult rabbits. In protocol 1, we assessed the effect of PKC-ϵ translocation inhibitor peptide (PKC-ϵ-TIP) and the pan-PKC inhibitor chelerythrine on infarct size reduction with PC in adult and ∼4-yr-old rabbits, a population previously shown to exhibit definitive hallmarks of cardiovascular aging. Rabbits received 5 min of PC ischemia or a matched control period followed by 30 min of coronary artery occlusion and 3 h of reperfusion, with infarct size (delineated by tetrazolium staining) serving as the primary endpoint. In protocol 2, we obtained insight (by Western immunoblotting) into the subcellular redistribution of PKC-ϵ in response to the 5-min PC stimulus in adult and old rabbits. In adults, infarct size reduction with PC was abrogated by both PKC-ϵ-TIP and chelerythrine. However, in old rabbits, 1) PC-induced cardioprotection was maintained despite inhibitor treatment and 2) brief PC ischemia was not associated with activation/translocation of PKC-ϵ. Thus the mechanisms responsible for PC are age related in the rabbit heart, with no apparent, requisite role of PKC-ϵ in aging animals.

scholarly journals Hypercholesterolemia Interferes with Induction of miR-125b-1-3p in Preconditioned Hearts

2020 ◽  
Vol 21 (11) ◽  
pp. 3744
Author(s):  
Márton R. Szabó ◽  
Renáta Gáspár ◽  
Márton Pipicz ◽  
Nóra Zsindely ◽  
Petra Diószegi ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Wistar Rats ◽  
Ischemia Reperfusion ◽  
Sodium Cholate ◽  
Blood Cholesterol ◽  
High Blood Cholesterol ◽  
Cholesterol Levels ◽  
Male Wistar Rats ◽  
Underlying Mechanisms

Ischemic preconditioning (IPre) reduces ischemia/reperfusion (I/R) injury in the heart. The non-coding microRNA miR-125b-1-3p has been demonstrated to play a role in the mechanism of IPre. Hypercholesterolemia is known to attenuate the cardioprotective effect of preconditioning; nevertheless, the exact underlying mechanisms are not clear. Here we investigated, whether hypercholesterolemia influences the induction of miR-125b-1-3p by IPre. Male Wistar rats were fed with a rodent chow supplemented with 2% cholesterol and 0.25% sodium-cholate hydrate for 8 weeks to induce high blood cholesterol levels. The hearts of normo- and hypercholesterolemic animals were then isolated and perfused according to Langendorff, and were subjected to 35 min global ischemia and 120 min reperfusion with or without IPre (3 × 5 min I/R cycles applied before index ischemia). IPre significantly reduced infarct size in the hearts of normocholesterolemic rats; however, IPre was ineffective in the hearts of hypercholesterolemic animals. Similarly, miR-125b-1-3p was upregulated by IPre in hearts of normocholesterolemic rats, while in the hearts of hypercholesterolemic animals IPre failed to increase miR-125b-1-3p significantly. Phosphorylation of cardiac Akt, ERK, and STAT3 was not significantly different in any of the groups at the end of reperfusion. Based on these results we propose here that hypercholesterolemia attenuates the upregulation of miR-125b-1-3p by IPre, which seems to be associated with the loss of cardioprotection.

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

TNF-α antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits

2003 ◽  
Vol 284 (3) ◽  
pp. H927-H930 ◽  
Author(s):  
Sergej Belosjorow ◽  
Ines Bolle ◽  
Alexej Duschin ◽  
Gerd Heusch ◽  
Rainer Schulz
Keyword(s):  
At Risk ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Myocardial Infarct ◽  
Size Reduction ◽  
Myocardial Infarct Size ◽  
Area At Risk ◽  
Tnf Α ◽  
Infarct Size Reduction ◽  
Group 1

Pretreatment with tumor necrosis factor-α (TNF-α) antibodies abolishes myocardial infarct size reduction by late ischemic preconditioning (IP). Whether or not TNF-α is also important for myocardial infarct size reduction by classic IP is unknown. Anesthetized rabbits were untreated ( group 1, n = 7), classically preconditioned by 5 min left coronary artery occlusion/10 min reperfusion ( group 2, n = 6), or pretreated with TNF-α antibodies without ( group 3, n = 6) or with IP ( group 4, n = 6) before undergoing 30 min of occlusion and 180 min of reperfusion. Infarct size in group 1 was 44 ± 11 (means ± SD)% of the area at risk. With a comparable area at risk, infarct size was reduced to 13 ± 7%, 23 ± 8%, and 19 ± 12% (all P < 0.05) in groups 2, 3, and 4, respectively. The circulating TNF-α concentration was increased during ischemia in group 1 from 752 ± 403 to 1,542 ± 482 U/ml ( P < 0.05) but remained unchanged in all other groups. Circulating TNF-α concentration during ischemia and infarct size correlated in all groups ( r = 0.76). IP, TNF-α antibodies, and the combined approach reduced infarct size to a comparable extent. Therefore, the question of whether or not TNF-α is causally involved in the infarct size reduction by IP in rabbits could not be answered.

scholarly journals Influence of Hyperglycemia on Dexmedetomidine-Induced Cardioprotection in the Isolated Perfused Rat Heart

2020 ◽  
Vol 9 (5) ◽  
pp. 1445 ◽  
Author(s):  
Carolin Torregroza ◽  
Katharina Feige ◽  
Laura Schneider ◽  
Sebastian Bunte ◽  
Martin Stroethoff ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Total Concentration ◽  
Experimental Studies ◽  
Size Reduction ◽  
Control Group ◽  
Pharmacological Agents ◽  
Acute Hyperglycemia ◽  
Infarct Size Reduction ◽  
Krebs Henseleit Buffer

Pharmacological preconditioning (PC) and postconditioning (PoC), for example, by treatment with the α2-adrenoreceptor agonist Dexmedetomidine (Dex), protects hearts from ischemia-reperfusion (I/R) injury in experimental studies, however, translation into the clinical setting has been challenging. Acute hyperglycemia adversely affects the outcome of patients with myocardial infarction. Additionally, it also blocks cardioprotection by multiple pharmacological agents. Therefore, we investigated the possible influence of acute hyperglycemia on Dexmedetomidine-induced pre- and postconditioning. Experiments were performed on the hearts of male Wistar rats, which were randomized into 7 groups, placed in an isolated Langendorff system and perfused with Krebs-Henseleit buffer. All hearts underwent 33 min of global ischemia, followed by 60 min of reperfusion. Control (Con) hearts received Krebs-Henseleit buffer (Con KHB), glucose (Con HG) or mannitol (Con NG) as vehicle only. Hearts exposed to hyperglycemia (HG) received KHB, containing 11 mmol/L glucose (an elevated, but commonly used glucose concentration for Langendorff perfused hearts) resulting in a total concentration of 22 mmol/L glucose throughout the whole experiment. To ensure comparable osmolarity with HG conditions, normoglycemic (NG) hearts received mannitol in addition to KHB. Hearts were treated with 3 nM Dexmedetomidine (Dex) before (DexPC) or after ischemia (DexPoC), under hyperglycemic or normoglycemic conditions. Infarct size was determined by triphenyltetrazoliumchloride staining. Acute hyperglycemia had no impact on infarct size compared to the control group with KHB (Con HG: 56 ± 9% ns vs. Con KHB: 56 ± 7%). DexPC reduced infarct size despite elevated glucose levels (DexPC HG: 35 ± 3%, p < 0.05 vs. Con HG). However, treatment with Dex during reperfusion showed no infarct size reduction under hyperglycemic conditions (DexPoC HG: 57 ± 9%, ns vs. Con HG). In contrast, hearts treated with mannitol demonstrated a significant decrease in infarct size compared to the control group (Con NG: 37 ± 3%, p < 0.05 vs. Con KHB). The combination of Dex and mannitol presents exactly opposite results to hearts treated with hyperglycemia. While DexPC completely abrogates infarct reduction through mannitol treatment (DexPC NG: 55 ± 7%, p < 0.05 vs. Con NG), DexPoC had no impact on mannitol-induced infarct size reduction (DexPoC NG: 38 ± 4%, ns vs. Con NG). Acute hyperglycemia inhibits DexPoC, while it has no impact on DexPC. Treatment with mannitol induces cardioprotection. Application of Dex during reperfusion does not influence mannitol-induced infarct size reduction, however, administering Dex before ischemia interferes with mannitol-induced cardioprotection.

Infarct Size Reduction by Ischemic Preconditioning is a Monophasic, Short-Lived Phenomenon in Anesthetized Pigs

1998 ◽  
Vol 3 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Ernst R. Schwarz ◽  
Jan Fleischhauer ◽  
Holger Montino ◽  
Raj Chakupurakal ◽  
Mike Foresti ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Size Reduction ◽  
Infarct Size Reduction
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