scholarly journals Ischemic preconditioning limits infarct size following regional ischemia–reperfusion in in situ mouse hearts

1999 ◽  
Vol 42 (3) ◽  
pp. 680-684 ◽  
Author(s):  
D Miller
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Regional Ischemia

Anti-Stunning and Anti-Infarct Effects of Adenosine-Enhanced Ischemic Preconditioning

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Yoshiya Toyoda ◽  
Vincenzo Di Gregorio ◽  
Robert A. Parker ◽  
Sidney Levitsky ◽  
James D. McCully
Keyword(s):  
At Risk ◽  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Bolus Injection ◽  
Ischemia Reperfusion ◽  
Area At Risk ◽  
Regional Ischemia ◽  
Infarct Size Reduction ◽  
Tetrazolium Staining

Background —Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing post-ischemic functional recovery. In this study, the anti-infarct effects and the anti-stunning effects of APC in contributing to enhanced post-ischemic functional recovery were determined and compared with IPC. Methods and Results —Sheep (n=96) were subjected to 15, 30, 45, or 60 minutes of regional ischemia and 120 minutes of reperfusion. IPC hearts received 5 minutes of regional ischemia and 5 minutes of reperfusion before ischemia/reperfusion. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine hearts (ADO) received a bolus injection of adenosine before ischemia/reperfusion. Regional ischemia (RI) hearts received no pretreatment. Infarct size/area at risk was determined by tetrazolium staining. Regional myocardial function was determined by sonomicrometry. Segment shortening after 15 minutes of ischemia in which no infarct was incurred was 32.1±10.6% in RI, 70.6±8.5% in IPC, and 77.4±6.0% in APC hearts. Segment shortening after 30 minutes of ischemia was 60.7±6.3% in APC hearts ( P <0.05 versus RI, ADO, IPC) but was <37% in all other groups. Infarct size/area at risk after 30 and 60 minutes of ischemia was, respectively, 25.8±5.7% and 49.8±6.0% in RI, 12.9±3.0% and 29.2±5.0% in ADO, 11.6±2.4% and 24.6±2.7% in IPC, and 5.1±1.6% and 12.4±2.0% in APC hearts ( P <0.05 versus RI, ADO, IPC). Conclusions —APC and IPC exhibit anti-infarct and anti-stunning effects in the ovine heart, but these effects are rapidly diminished with IPC. APC significantly extends these effects, providing for significantly enhanced infarct size reduction and post-ischemic functional recovery ( P <0.05 versus IPC).

Modification of ischemia/reperfusion induced infarct size by ischemic preconditioning in hypertrophied hearts

2021 ◽  
Vol 99 (2) ◽  
pp. 218-223
Author(s):  
Mohamad Nusier ◽  
Mohammad Alqudah ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Protein Kinase ◽  
Cardiac Hypertrophy ◽  
Infarct Size ◽  
P38 Mapk ◽  
Ischemic Preconditioning ◽  
Creatine Phosphokinase ◽  
Ischemia Reperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Normal Heart ◽  
Mitogen Activated Protein

This study examined the effects of ischemic preconditioning (IP) on the ischemia/reperfusion (I/R) induced injury in normal and hypertrophied hearts. Cardiac hypertrophy in rabbits was induced by L-thyroxine (0.5 mg/kg/day for 16 days). Hearts with or without IP (3 cycles of 5 min ischemia and 10 min reperfusion) were subjected to I/R (60 min ischemia followed by 60 min reperfusion). IP reduced the I/R-induced infarct size from 68% to 24% and 57% to 33% in the normal and hypertrophied hearts, respectively. Leakage of creatine phosphokinase in the perfusate from the hypertrophied hearts due to I/R was markedly less than that form the normal hearts; IP prevented these changes. Although IP augmented the increase in phosphorylated p38-mitogen-activated protein kinase (p38-MAPK) content due to I/R, this effect was less in the hypertrophied than in the normal heart. These results suggest that reduced cardioprotection by IP of the I/R-induced injury in hypertrophied hearts may be due to reduced activation of p38-MAPK in comparison with normal hearts.

Ischemic preconditioning in rats: role of mitochondrial KATP channel in preservation of mitochondrial function

2000 ◽  
Vol 278 (1) ◽  
pp. H305-H312 ◽  
Author(s):  
Ryan M. Fryer ◽  
Janis T. Eells ◽  
Anna K. Hsu ◽  
Michele M. Henry ◽  
Garrett J. Gross
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion ◽  
Mitochondrial Protein ◽  
Atp Synthesis ◽  
Area At Risk ◽  
Selective Antagonist ◽  
Mitochondrial Katp Channel

We examined the role of the sarcolemmal and mitochondrial KATPchannels in a rat model of ischemic preconditioning (IPC). Infarct size was expressed as a percentage of the area at risk (IS/AAR). IPC significantly reduced infarct size (7 ± 1%) versus control (56 ± 1%). The sarcolemmal KATP channel-selective antagonist HMR-1098 administered before IPC did not significantly attenuate cardioprotection. However, pretreatment with the mitochondrial KATP channel-selective antagonist 5-hydroxydecanoic acid (5-HD) 5 min before IPC partially abolished cardioprotection (40 ± 1%). Diazoxide (10 mg/kg iv) also reduced IS/AAR (36.2 ± 4.8%), but this effect was abolished by 5-HD. As an index of mitochondrial bioenergetic function, the rate of ATP synthesis in the AAR was examined. Untreated animals synthesized ATP at 2.12 ± 0.30 μmol ⋅ min−1 ⋅ mg mitochondrial protein−1. Rats subjected to ischemia-reperfusion synthesized ATP at 0.67 ± 0.06 μmol ⋅ min−1 ⋅ mg mitochondrial protein−1. IPC significantly increased ATP synthesis to 1.86 ± 0.23 μmol ⋅ min−1 ⋅ mg mitochondrial protein−1. However, when 5-HD was administered before IPC, the preservation of ATP synthesis was attenuated (1.18 ± 0.15 μmol ⋅ min−1 ⋅ mg mitochondrial protein−1). These data are consistent with the notion that inhibition of mitochondrial KATPchannels attenuates IPC by reducing IPC-induced protection of mitochondrial function.

Endogenous myocardial norepinephrine is not essential for ischemic preconditioning in rabbit heart

1996 ◽  
Vol 270 (3) ◽  
pp. H1078-H1084 ◽  
Author(s):  
J. L. Ardell ◽  
X. M. Yang ◽  
B. A. Barron ◽  
J. M. Downey ◽  
M. V. Cohen
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Rabbit Heart ◽  
Chemical Sympathectomy ◽  
Single Cycle ◽  
Risk Zone ◽  
Regional Ischemia ◽  
Norepinephrine Content ◽  
Ischemic Period

To determine whether endogenous cardiac catecholamines mediate ischemic preconditioning (PC) in the rabbit heart, myocardial catecholamines were depleted by reserpine (5 mg/kg, 18-24 h pre-PC) or surgical sympathectomy (2 wk pre-PC). In vivo hearts were subjected to 30 min of regional ischemia and 3 h of reperfusion. PC involved either one or four cycles of 5-min ischemia and 10-min reperfusion before the 30-min ischemic period. Right ventricular norepinephrine content (pmol/mg protein), 51.4 +/- 11.1 in untreated rabbits, was reduced to 0.6 +/- 0.2 and 1.8 +/- 0.5 by surgical sympathectomy and reserpine, respectively. Infarct size (IS) was measured by tetrazolium and expressed as percentage of the risk zone. In untreated animals exposed solely to 30 min of regional ischemia IS was 35.5 +/- 1.6% and was unchanged by reserpine (43.3 +/- 5.4%) or surgical sympathectomy (33.4 +/- 3.5%). compared with infarction in the respective non-PC controls, IS in untreated (7.4 +/- 1.5%, P < 0.0001) and surgically sympathectomized (11.2 +/- 1.5%, P < 0.0001) animals was significantly diminished by a single cycle of PC, but the latter exerted less protection in reserpinized animals (27.6 +/- 3.5%, P < 0.0025). Four cycles of PC, however, reduced IS to 10.3 +/- 1.2% in reserpinized animals. Therefore, despite comparable depression of myocardial norepinephrine content, surgical and chemical sympathectomy had different effects on the level of protection afforded by ischemic PC. These data demonstrate that endogenous myocardial catecholamines are not essential for protection from PC in the rabbit.

Ischemic preconditioning and morphine attenuate myocardial apoptosis and infarction after ischemia-reperfusion in rabbits: role of δ-opioid receptor

2004 ◽  
Vol 287 (4) ◽  
pp. H1786-H1791 ◽  
Author(s):  
Shinji Okubo ◽  
Yujirou Tanabe ◽  
Kenji Takeda ◽  
Michihiko Kitayama ◽  
Seiyu Kanemitsu ◽  
...  
Keyword(s):  
Infarct Size ◽  
Opioid Receptor ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Apoptotic Cells ◽  
Protective Effects ◽  
Δ Opioid Receptor

We examined whether ischemic preconditioning (IPC) attenuates ischemia-reperfusion injury, in part, by decreasing apoptosis and whether the δ-opioid receptor (DOR) plays a pivotal role in the regulation of apoptosis. Rabbits were subjected to 30-min coronary artery occlusion (CAO) and 180 min of reperfusion. IPC was elicited with four cycles of 5-min ischemia and 10-min reperfusion before CAO. Morphine (0.3 mg/kg iv) was given 15 min before CAO. Naloxone (Nal; 10 mg/kg iv) and naltrindole (Nti; 10 mg/kg iv), the respective nonselective and selective DOR antagonists were given 10 min before either morphine or IPC. Infarct size (%risk area) was reduced from 46 ± 3.8 in control to 11.6 ± 1.0 in IPC and 19.5 ± 3.8 in the morphine group (means ± SE; P < 0.001 vs. control). Nal blocked the protective effects of IPC and morphine, as shown by the increase in infarct size to 38.6 ± 7.2 and 44.5 ± 1.8, respectively. Similarly, Nti blocked IPC and morphine-induced protection. The percentage of apoptotic cells (revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) decreased in IPC (3.6 ± 1.9) and morphine groups (5.2 ± 1.2) compared with control group (12.4 ± 1.6; P < 0.001). Nti pretreatment increased apoptotic cells 11.2 ± 2.2% in IPC and 12.1 ± 0.8% in morphine groups. Nal failed to block inhibition of apoptosis in the IPC group (% of cells: 5.7 ± 1.3 vs. 3.6 ± 1.9 in IPC alone; P > 0.05). These results were also confirmed by nucleosomal DNA laddering pattern. We conclude that IPC reduces lethal injury, in part, by decreasing apoptosis after ischemia-reperfusion and activation of the DOR may play a crucial role in IPC or morphine-induced myocardial protection.

Menadione mimics the infarct-limiting effect of preconditioning in isolated rat hearts

2001 ◽  
Vol 281 (2) ◽  
pp. H590-H595 ◽  
Author(s):  
Yuankun Yue ◽  
Maike Krenz ◽  
Michael V. Cohen ◽  
James M. Downey ◽  
Stuart D. Critz
Keyword(s):  
Free Radicals ◽  
Infarct Size ◽  
P38 Mapk ◽  
Ischemic Preconditioning ◽  
Free Radical Scavenger ◽  
Mitogen Activated Protein Kinase ◽  
Radical Scavenger ◽  
Risk Zone ◽  
Regional Ischemia ◽  
Rat Hearts

The role of mitochondrial free radicals in the cardioprotective effect of ischemic preconditioning was examined in isolated buffer-perfused rat hearts. Infarct size in control rat hearts subjected to 30 min of regional ischemia and 120 min of reperfusion was 32.6 ± 3.4% of the risk zone. Ischemic preconditioning (3 cycles of 5-min global ischemia/5-min reperfusion) before the same regional ischemia and reperfusion protocol significantly reduced infarct size to 2.6 ± 0.8% of the risk zone. Perfusion with menadione (3.0 μM), a generator of mitochondrial free radicals, in lieu of preconditioning ischemia significantly reduced infarction to 10.9 ± 2.7%. N-2-mercaptopropionylglycine (1.0 mM), a free radical scavenger, blocked the protection of menadione, significantly increasing infarction to 23.5 ± 1.1%. Myxothiazol (0.6 μM), a site III mitochondrial inhibitor, blocked the protection of menadione and significantly increased infarction to 25.2 ± 3.8%. The infarct-limiting effect of menadione was attenuated to 19.7 ± 1.5% of the risk zone by 10 μM SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor. Furthermore, menadione significantly increased p38 MAPK phosphorylation to a level 5.6-fold over basal. These results indicate that free radicals that originate within mitochondria can activate p38 MAPK and protect hearts against infarction.

Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion

2001 ◽  
Vol 280 (2) ◽  
pp. H591-H602 ◽  
Author(s):  
James D. McCully ◽  
Yoshiya Toyoda ◽  
Masahisa Uematsu ◽  
Robert D. Stewart ◽  
Sidney Levitsky
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Ischemia And Reperfusion ◽  
Infarct Size Reduction

Adenosine-enhanced ischemic preconditioning (APC) extends the cardioprotection of ischemic preconditioning (IPC) by both significantly decreasing myocardial infarct size and significantly enhancing postischemic functional recovery. In this study, the role of adenosine receptors during ischemia-reperfusion was determined. Rabbit hearts ( n = 92) were used for Langendorff perfusion. Control hearts were perfused for 180 min, global ischemia hearts received 30-min ischemia and 120-min reperfusion, and IPC hearts received 5-min ischemia and 5-min reperfusion before ischemia. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine receptor (A1, A2, and A3) antagonists were used with APC before ischemia and/or during reperfusion. GR-69019X (A1/A3) and MRS-1191/MRS-1220 (A3) significantly increased infarct size in APC hearts when administered before ischemia and significantly decreased functional recovery when administered during both ischemia and reperfusion ( P < 0.05 vs. APC). DPCPX (A1) administered either before ischemia and/or during reperfusion had no effect on APC cardioprotection. APC-enhanced infarct size reduction is modulated by adenosine receptors primarily during ischemia, whereas APC-enhanced postischemic functional recovery is modulated by adenosine receptors during both ischemia and reperfusion.

scholarly journals Ischemic preconditioning protects the heart against ischemia-reperfusion injury in chronic kidney disease in both males and females

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Márta Sárközy ◽  
Fanni Magdolna Márványkövi ◽  
Gergő Szűcs ◽  
Zsuzsanna Z. A. Kovács ◽  
Márton R. Szabó ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Uremic Cardiomyopathy ◽  
Males And Females

Abstract Background Uremic cardiomyopathy is a common cardiovascular complication of chronic kidney disease (CKD) characterized by left ventricular hypertrophy (LVH) and fibrosis enhancing the susceptibility of the heart to acute myocardial infarction. In the early stages of CKD, approximately 60% of patients are women. We aimed to investigate the influence of sex on the severity of uremic cardiomyopathy and the infarct size-limiting effect of ischemic preconditioning (IPRE) in experimental CKD. Methods CKD was induced by 5/6 nephrectomy in 9-week-old male and female Wistar rats. Two months later, serum and urine laboratory parameters were measured to verify the development of CKD. Transthoracic echocardiography was performed to assess cardiac function and morphology. Cardiomyocyte hypertrophy and fibrosis were measured by histology. Left ventricular expression of A- and B-type natriuretic peptides (ANP and BNP) were measured by qRT-PCR and circulating BNP level was measured by ELISA. In a subgroup of animals, hearts were 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). Then infarct size or phosphorylated and total forms of proteins related to the cardioprotective RISK (AKT, ERK1,2) and SAFE (STAT3) pathways were measured by Western blot. Results The severity of CKD was similar in males and females. However, CKD males developed more severe LVH compared to females as assessed by echocardiography. Histology revealed cardiac fibrosis only in males in CKD. LV ANP expression was significantly increased due to CKD in both sexes, however, LV BNP and circulating BNP levels failed to significantly increase in CKD. In both sexes, IPRE significantly decreased the infarct size in both the sham-operated and CKD groups. IPRE significantly increased the phospho-STAT3/STAT3 ratio in sham-operated but not in CKD animals in both sexes. There were no significant differences in phospho-AKT/AKT and phospho-ERK1,2/ERK1,2 ratios between the groups. Conclusion The infarct size-limiting effect of IPRE was preserved in both sexes in CKD despite the more severe uremic cardiomyopathy in male CKD rats. Further research is needed to identify crucial molecular mechanisms in the cardioprotective effect of IPRE in CKD.

Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-reperfusion injury

2001 ◽  
Vol 281 (4) ◽  
pp. H1630-H1636 ◽  
Author(s):  
Daniel Schulman ◽  
David S. Latchman ◽  
Derek M. Yellon
Keyword(s):  
Infarct Size ◽  
Rat Heart ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Middle Aged ◽  
Aged Rat ◽  
Isolated Hearts ◽  
Regional Ischemia ◽  
Kinase C ◽  
Rat Hearts

Ischemic preconditioning (IP) reduces infarct size in young animals; however, its impact on aging is underinvestigated. The effect of variations in IP stimuli was studied in young, middle-aged, and aged rat hearts. Isolated hearts underwent 35 min of regional ischemia and 120 min of reperfusion. Hearts with IP were subjected to either one ischemia-reperfusion cycle (5 min of ischemia and 5 min of reperfusion per cycle) or three successive cycles before 35 min of regional ischemia. Additional studies investigated the effects of pharmacological preconditioning in aged hearts using the adenosine A1 receptor agonist 2-chloro- N 6-cyclopentyladenosine, the protein kinase C analog 1,2-dioctanoyl- sn-glycerol, and the mitochondrial ATP-sensitive potassium (KATP)-channel opener diazoxide. Infarct sizes indicated that the aged rat heart could not be preconditioned via ischemic or pharmacological means. The middle-aged rat heart had a blunted IP response compared with the young adult (only an increased IP stimulus caused a significant reduction in infarct size). These results suggest that there are defects within the IP signaling cascade of the aged heart. Clinical relevance is important if we are to use any IP-like mimetics to the benefit of an aging population.

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