Ischemic preconditioning protects against infarction in rat heart

1992 ◽  
Vol 263 (4) ◽  
pp. H1107-H1112 ◽  
Author(s):  
Y. Liu ◽  
J. M. Downey
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Rat Heart ◽  
Channel Blocker ◽  
Isolated Rat Heart ◽  
Control Group ◽  
Risk Zone ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Coronary Ischemia

We examined the anti-infarct effect of ischemic preconditioning in the rat heart. All hearts were subjected to 30 min of regional coronary ischemia and 2 h of reperfusion. Infarct size was determined by tetrazolium. The control group had an average infarct size of 31% of the risk zone. Three 5-min cycles of preconditioning ischemia limited the infarct size to 3.7%. Neither the adenosine receptor blocker PD 115,199 nor the ATP-sensitive potassium channel blocker, glibenclamide, could block this protection. Intracoronary adenosine A1-receptor agonist 2-chloro-N6-cyclopentyladenosine offered a significant anti-infarct protection to the isolated rat heart, however. Although one 5-min cycle of preconditioning did not protect the rat heart from infarction (31% infarction in risk zone), it did attenuate arrhythmias. We conclude that 1) the rat heart can be preconditioned, which argues against mitochondrial adenosinetriphosphatase being the mechanism of preconditioning; 2) the threshold for preconditioning is higher in rat than rabbit or dog; 3) a role for adenosine in preconditioning was only partially supported; and 4) a role for ATP-sensitive potassium channels was not supported.

scholarly journals Cramming the causative mechanism of glycogen synthase kinase-3β mediated by ischemic preconditioning against ovariectomy challenged rat heart

2021 ◽  
Vol 12 (1) ◽  
pp. 669-675
Author(s):  
Vishal Kumar Vishwakarma ◽  
Tarique Mahmood Ansari ◽  
Prabhat Kumar Upadhyay ◽  
Ritesh Kumar Srivastav ◽  
Farogh Ahsan ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Rat Heart ◽  
Glycogen Synthase ◽  
Protective Action ◽  
Isolated Rat Heart ◽  
Glycogen Synthase Kinase ◽  
Control Group ◽  
Glycogen Synthase Kinase 3Β ◽  
Mptp Opening ◽  
Gsk 3Β

High risks of cardiovascular diseases in women are associated with low estrogen levels. Ischemic preconditioning (IPC) exhibits protection in the heart by Glycogen synthase kinase-3β (GSK-3β) phosphorylation that inhibits the mPTP opening, and this protective action of IPC is attenuated by estrogen deficiency. An experiment was performed on female Wistar rats with/without ovariectomy (OVX). Isolated rat heart was attached with perfusion assembly. Infract size, coronary flow, LDH, CKMB and histopathology were estimated. Sham control group decreased the LDH, CKMB and infract size in normal rat heart. The IPC mediated protection of heart was attenuated in OVX rat heart. Inhibition of GSK-3β is found to enhance the threshold of mPTP opening during reperfusion. The treatment with atractyloside stuck significantly the protection of heart of IPC in normal and OVX rat heart. These observations show that downregulation of GSK-3β through an impaired opening of mPTP during reperfusion and GSK-3β might be potential adjuvant to IPC against cardiac injury in OVX challenged rats.  

scholarly journals Role of mitochondrial and sarcolemmal KATPchannels in ischemic preconditioning of the canine heart

2001 ◽  
Vol 280 (1) ◽  
pp. H256-H263 ◽  
Author(s):  
Shoji Sanada ◽  
Masafumi Kitakaze ◽  
Hiroshi Asanuma ◽  
Kengo Harada ◽  
Hisakazu Ogita ◽  
...  
Keyword(s):  
Infarct Size ◽  
Intravenous Administration ◽  
Ischemic Preconditioning ◽  
Channel Blocker ◽  
Control Group ◽  
Canine Heart ◽  
Beagle Dogs ◽  
Left Anterior Descending Artery ◽  
Channel Opener

We tested whether mitochondrial or sarcolemmal ATP-sensitive K+(KATP) channels play a key role in ischemic preconditioning (IP) in canine hearts. In open-chest beagle dogs, the left anterior descending artery was occluded four times for 5 min each with 5-min intervals of reperfusion (IP), occluded for 90 min, and reperfused for 6 h. IP as well as cromakalim and nicorandil (nonspecific KATP channel openers) markedly limited infarct size (6.3 ± 1.2, 8.9 ± 1.9, and 7.2 ± 1.6%, respectively) compared with the control group (40.9 ± 4.1%). A selective mitochondrial KATP channel blocker, 5-hydroxydecanoate, partially blunted the limitation of infarct size in the animals subjected to IP and those treated with cromakalim and nicorandil (21.6 ± 3.8, 25.1 ± 4.6, and 19.8 ± 5.2%, respectively). A nonspecific KATP channel blocker, glibenclamide, completely abolished the effect of IP (38.5 ± 6.2%). Intracoronary or intravenous administration of a mitochondria-selective KATP channel opener, diazoxide, at >100 μmol/l could only partially decrease infarct size (19.5 ± 4.3 and 20.1 ± 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal KATP channels independently play an important role in the limitation of infarct size by IP in the canine heart.

Ischemic preconditioning and myocardial hypothermia in rabbits with prolonged coronary artery occlusion

1999 ◽  
Vol 276 (6) ◽  
pp. H2029-H2034 ◽  
Author(s):  
Sharon L. Hale ◽  
Robert A. Kloner
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Regional Myocardial Blood Flow ◽  
Control Group ◽  
Risk Zone ◽  
Ischemic Region ◽  
Regional Myocardial Blood

This study tests whether combining regional hypothermia and ischemic preconditioning (IP) provides greater myocardial protection during prolonged coronary artery occlusion (CAO) than either intervention alone, and whether increasing the duration of IP from 5 to 7 min extends the window of protection to include a 2-h CAO. Anesthetized rabbits were randomized to four groups ( n = 8 rabbits/group): control (C), hypothermia alone (H), IP alone for two 7-min episodes (IP7), and IP plus hypothermia (H + IP7). To compare differences in IP for 5 versus 7 min, additional rabbits ( n = 6) received one 5-min episode of ischemia (IP5). All rabbits got 2 h of CAO and 3 h of reperfusion. In comparison with the infarct size in the control group (72 ± 4% of the risk zone), infarct size was significantly reduced in H (50 ± 7%), IP7 (49 ± 5%), and H + IP7 (42 ± 6%) (all P < 0.05 vs. control group). IP5 failed to confer protection (67 ± 5% of the risk zone). Therefore, IP can protect against a 2-h CAO if the IP regimen is increased from 5 to 7 min. The combination therapy significantly improved regional myocardial blood flow in the previously ischemic region to a greater extent than either treatment alone.

scholarly journals Pharmacological Manipulations of ATP-Dependent Potassium Channels and Adenosine A1 Receptors do not Impact Hippocampal Ischemic Preconditioning in Vivo: Evidence in a Highly Quantitative Gerbil Model

2004 ◽  
Vol 24 (5) ◽  
pp. 556-563 ◽  
Author(s):  
Takatoshi Sorimachi ◽  
Thaddeus S. Nowak
Keyword(s):  
Ischemic Preconditioning ◽  
Intraperitoneal Injection ◽  
Adenosine A1 ◽  
Neuron Damage ◽  
A1 Receptor ◽  
Ischemic Depolarization ◽  
Pharmacological Manipulations ◽  
Dose Dependent ◽  
Ischemic Neuronal Injury

Ischemic preconditioning models have been characterized in brain, heart, and other tissues, and previous pharmacologic studies have suggested an involvement of adenosine and ATP dependent potassium (KATP) channels in such tolerance phenomena. This question was reexamined in a reproducible gerbil model in which the duration of ischemic depolarization defined the severity of preconditioning and test insults. Agents studied were glibenclamide, a blocker of KATP channels; 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A1 receptor antagonist; and N6-cyclopentyladenosine (CPA), an A1 agonist. Intraventricular glibenclamide injections aggravated neuron damage after brief priming insults, in parallel with a dose-dependent prolongation of ischemic depolarization. However, the depolarization thresholds for ischemic neuronal injury were identical in vehicle- and glibenclamide-treated animals, and glibenclamide did not affect preconditioning when equivalent insult severity was maintained during priming insults. Neither DPCPX nor CPA had any effect on the onset or duration of depolarization after intraperitoneal injection in this model, and neither drug affected neuron damage. In the case of CPA, it was necessary to maintain temperature for 4 to 6 hours of recirculation to avoid significant confounding hypothermia. These results fail to support a direct involvement of A1 receptors or KATP channels during early stages in the development of ischemic tolerance in vivo, and emphasize the need for robust, well-controlled, and quantitative models in such studies.

Kolaviron and Garcinia kola Seed Extract Protect Against Ischaemia/Reperfusion Injury on Isolated Rat Heart

Drug Research ◽  
2018 ◽  
Vol 68 (05) ◽  
pp. 286-295
Author(s):  
Ademola Oyagbemi ◽  
Dirk Bester ◽  
Johan Esterhuyse ◽  
Ebenezer Farombi
Keyword(s):  
Reperfusion Injury ◽  
Rat Heart ◽  
Caspase 3 ◽  
Isolated Rat Heart ◽  
Seed Extract ◽  
Parp Cleavage ◽  
Control Group ◽  
Ischaemia Reperfusion Injury ◽  
Garcinia Kola ◽  
Isolated Rat

Abstract Background The incidence of cardiovascular diseases and its associated complications have increased greatly in the past three decades. The purpose of this study was to evaluate the acute cardioprotective effects of Garcinia kola (GK) seed extract and Kolaviron (KV) and determine mechanisms of action involving RISK signalling pathways. Methods Male Wistar rats were used in this study. Hearts were excised and mounted on the Langendorff perfusion system. The control, group 1 was perfused with dimethyl sulfoxide (DMSO), group II with KV and group III with GK respectively. Western blot analyses were performed on frozen heart tissues. Results Isolated rat hearts perfused with KV and GK attenuated apoptotic pathways with significant reduction in p38 MAPK protein phosphorylation, as well as reduction in total caspase 3, cleaved caspase 3 (Asp 175) and PARP cleavage. KV and GK also down-regulated p-JNK1 (Tyr 185) and p-JNK 2 (Thr 183) protein expression at the 10 min reperfusion time ponit. Cardioprotection was achieved in part, by enhancement of the reperfusion injury signalling kinase (RISK) pathway; as evidenced by significant increases in protein expresion of Akt/PKB and p-Akt/PKB (Ser 473) in KV and GK respectively. Conclusions KV and GK supplementation led to significant increases in the expressions of survival proteins. It is noteworthy that both KV and GK supplementation offered cardioprotection in ischaemic/reperfusion injury rat heart model. In all, GK showed better cardioprotective effect that KV.

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