Xenon Administration During Early Reperfusion Reduces Infarct Size After Regional Ischemia in the Rabbit Heart In Vivo

2000 ◽  
Vol 91 (6) ◽  
pp. 1327-1332 ◽  
Author(s):  
Benedikt Preckel ◽  
Jost Müllenheim ◽  
Andrej Moloschavij ◽  
Volker Thämer ◽  
Wolfgang Schlack
Keyword(s):  
Infarct Size ◽  
Rabbit Heart ◽  
Early Reperfusion ◽  
Regional Ischemia

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.

Delayed ischemic preconditioning is mediated by opening of ATP-sensitive potassium channels in the rabbit heart

1999 ◽  
Vol 276 (4) ◽  
pp. H1323-H1330 ◽  
Author(s):  
Nelson L. Bernardo ◽  
Michael D’Angelo ◽  
Shinji Okubo ◽  
Archi Joy ◽  
Rakesh C. Kukreja
Keyword(s):  
Protective Effect ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Action Potential Duration ◽  
Rabbit Heart ◽  
Monophasic Action Potential ◽  
Initial Stimulus ◽  
Selective Blocker ◽  
Second Window Of Protection

Cardioprotection from preconditioning reappears 24 h after the initial stimulus. This phenomenon is called the second window of protection (SWOP). We hypothesized that opening of the ATP-sensitive potassium (KATP) channel mediates the protective effect of SWOP. Rabbits were preconditioned (PC) with four cycles of 5-min regional ischemia each followed by 10 min of reperfusion. Twenty-four hours later, the animals were subjected to sustained ischemia for 30 min followed by 180 min of reperfusion (I/R). Glibenclamide (Glib, 0.3 mg/kg ip) or 5-hydroxydecanoate (5-HD, 5 mg/kg iv) was used to block the KATP channel function. Infarct size was reduced from 41.2 ± 2.6% in sham-operated rabbits to 11.6 ± 1.0% in PC rabbits, a 71% reduction ( n = 11, P < 0.01). Treatment with Glib or 5-HD before I/R increased the infarct size to 43.4 ± 2.6 and 37.8 ± 1.9%, respectively ( P < 0.01 vs. PC group, n = 12/group). Sham animals treated with either Glib or 5-HD had an infarct size of 39.0 ± 3.4 and 37.8 ± 1.5%, respectively, which was not different from control (40.0 ± 3.8%) or sham (41.2 ± 2.6%) I/R hearts. Monophasic action potential duration (APD) at 50% repolarization significantly shortened by 28.7, 26.6, and 23.3% in sham animals during 10, 20, and 30 min of ischemia. However, no further augmentation in the shortening of APD was observed in PC hearts. Glib and 5-HD significantly suppressed ischemia-induced epicardial APD shortening, suggesting that 5-HD may not be a selective blocker of the mitochondrial KATP channel in vivo. We conclude that SWOP is mediated by a KATP channel-sensitive mechanism that may have occurred because of the opening of the sarcolemmal KATP channel in vivo.

Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat

2004 ◽  
Vol 287 (3) ◽  
pp. H1286-H1295 ◽  
Author(s):  
Sarah J. Canyon ◽  
Geoffrey P. Dobson
Keyword(s):  
Infarct Size ◽  
Rat Model ◽  
Cardiac Death ◽  
Constant Infusion ◽  
Therapeutic Window ◽  
High Dose ◽  
Sprague Dawley ◽  
Myocardial Ischemia And Reperfusion ◽  
Regional Ischemia

Despite decades of research, there are few effective ways to treat ventricular fibrillation (VF), ventricular tachycardia (VT), or cardiac ischemia that show a significant survival benefit. Our aim was to investigate the combined therapeutic effect of two common antiarrhythmic compounds, adenosine and lidocaine (AL), on mortality, arrhythmia frequency and duration, and infarct size in the rat model of regional ischemia. Sprague-Dawley rats ( n = 49) were anesthetized with pentobarbital sodium (60 mg·ml−1·kg−1 ip) and instrumented for regional coronary occlusion (30 min) and reperfusion (120 min). Heart rate, blood pressure, and a lead II electrocardiogram were recorded. Intravenous pretreatment began 5 min before ischemia and extended throughout ischemia, terminating at the start of reperfusion. After 120 min, hearts were removed for infarct size measurement. Mortality occurred in 58% of saline controls ( n = 12), 50% of adenosine only (305 μg·kg−1·min−1, n = 8), 0% in lidocaine only (608 μg·kg−1·min−1, n = 8), and 0% in AL at any dose (152, 305, or 407 μg·kg−1·min−1 adenosine plus 608 μg·kg−1·min−1 lidocaine, n = 7, 8, and 6). VT occurred in 100% of saline controls (18 ± 9 episodes), 50% of adenosine-only (11 ± 7 episodes), 83% of lidocaine-only (23 ± 11 episodes), 60% of low-dose AL (2 ± 1 episodes, P < 0.05), 57% of mid-dose AL (2 ± 1 episodes, P < 0.05), and 67% of high-dose AL rats (6 ± 3 episodes). VF occurred in 75% of saline controls (4 ± 3 episodes), 100% of adenosine-only-treated rats (3 ± 2 episodes), and 33% lidocaine-only-treated rats (2 ± 1 episodes) of the rats tested. There was no deaths and no VF in the low- and mid-dose AL-treated rats during ischemia, and only one high-dose AL-treated rat experienced VF (25.5 sec). Infarct size was lower in all AL-treated rats but only reached significance with the mid-dose treatment (saline controls 61 ± 5% vs. 38 ± 6%, P < 0.05). We conclude that a constant infusion of a solution containing AL virtually abolished severe arrhythmias and prevented cardiac death in an in vivo rat model of acute myocardial ischemia and reperfusion. AL combinational therapy may provide a primary prevention therapeutic window in ischemic and nonischemic regions of the heart.

Delayed preconditioning with adenosine is mediated by opening of ATP-sensitive K+ channels in rabbit heart

1999 ◽  
Vol 277 (1) ◽  
pp. H128-H135 ◽  
Author(s):  
Nelson L. Bernardo ◽  
Shinji Okubo ◽  
Mohammed M. Maaieh ◽  
Mark A. Wood ◽  
Rakesh C. Kukreja
Keyword(s):  
Infarct Size ◽  
Coronary Artery Occlusion ◽  
Rabbit Heart ◽  
Blue Dye ◽  
Channel Blockers ◽  
Area At Risk ◽  
Risk Area ◽  
Group I ◽  
Ischemia Group

The adenosine agonist 2-chloro- N 6-cyclopentyladenosine (CCPA) induces delayed ischemic protection in vivo. We hypothesized that this protection is mediated by opening of ATP-sensitive K+(KATP) channels and increased synthesis of 72-kDa heat shock protein (HSP 72). Six groups ( n = 9–13 animals/group) of animals were studied: group I, control rabbits that received no treatment; group II, animals given glibenclamide (0.3 mg/kg iv) 30 min before ischemia; group III, animals given 5-hydroxydecanoate (5-HD; 5 mg/kg iv) 15 min before ischemia; group IV, rabbits treated with CCPA (0.1 mg/kg iv) 24 h before ischemia; and groups V and VI, CCPA-treated animals that received the KATP-channel blockers glibenclamide or 5-HD, respectively, 30 or 15 min before ischemia. All animals were subjected to ischemia by 30 min of coronary artery occlusion followed by 3 h of reperfusion. Risk area was delineated by injection of 10% Evans blue dye, and infarct size was determined by triphenyltetrazolium staining. Action potential duration (APD) was measured with an epicardial electrode. HSP 72 was measured by Western blotting. CCPA caused a significant reduction in infarct size [12.02 ± 1.0 vs. 40.0 ± 3.8% (%area at risk) in controls, P < 0.01] that was blocked by glibenclamide (36.2 ± 3.1%, P < 0.01) and 5-HD (35.0 ± 2.9%, P < 0.01). Glibenclamide and 5-HD did not change infarct size in control rabbits. These blockers significantly suppressed ischemia-induced APD shortening in control and CCPA-treated animals. CCPA treatment did not induce HSP 72 in hearts. These data suggest that adenosine-initiated delayed protection is mediated via opening of KATP channels but does not involve the synthesis of HSP 72.

Pretreatment with a Nitric Oxide Inhibitor Reduces Infarct size in both the in vivo and the in vitro Rabbit Heart

1993 ◽  
Vol 84 (s28) ◽  
pp. 30P-30P
Author(s):  
VC Patel ◽  
RG Woolfson ◽  
M Singer ◽  
GH Neild ◽  
DM Yellon
Keyword(s):  
Nitric Oxide ◽  
Infarct Size ◽  
Rabbit Heart ◽  
Nitric Oxide Inhibitor

scholarly journals Treatment With 1-cis Diltiazem Before Reperfusion Reduces Infarct Size in the Ischemic Rabbit Heart In Vivo

1999 ◽  
Vol 80 (4) ◽  
pp. 319-326 ◽  
Author(s):  
Motohiro Nishida ◽  
Kenji Sakamoto ◽  
Tetsuro Urushidani ◽  
Taku Nagao
Keyword(s):  
Infarct Size ◽  
Rabbit Heart

scholarly journals Ecto-5′-nucleotidase is not required for ischemic preconditioning in rabbit myocardium in situ

1998 ◽  
Vol 275 (4) ◽  
pp. H1329-H1337 ◽  
Author(s):  
Takayuki Miki ◽  
Tetsuji Miura ◽  
Rolf Bünger ◽  
Katsuo Suzuki ◽  
Jun Sakamoto ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Cardiovascular Responses ◽  
Adenosine Diphosphate ◽  
Rabbit Heart ◽  
Area At Risk ◽  
Inotropic Effects ◽  
And Control

This study tested the hypothesis that cardiac ecto-5′-nucleotidase (ecto-5′-NT) activity during ischemic preconditioning (PC) contributes to augmented tolerance against ischemia, thereby reducing infarct size in the rabbit heart in situ. The effects of α,β-methylene-adenosine diphosphate (AOPCP), a selective inhibitor of ecto-5′-NT, on cardiovascular responses to AMP were measured to establish in vivo activities of the enzyme and its inhibitor. Left atrial infusion of AOPCP (0.75 mg ⋅ kg−1⋅ min−1) raised AOPCP plasma levels to 138 μM; under these conditions negative chronotropic and inotropic effects of AMP were blocked, demonstrating essentially full inhibition of ecto-5′-NT in the heart in situ. This AOPCP-blocked heart in situ model was used to examine the proposed contribution of ecto-5′-NT in ischemic PC. Myocardial infarction caused by 30-min ischemia was followed by 3-h reperfusion. Infarct size (IS) was measured and expressed as a percentage of the size of the area at risk (%IS/AR). In untreated controls, %IS/AR was 38.1 ± 3.8%; PC (5-min ischemia, 5-min reperfusion) markedly reduced %IS/AR to 10.0 ± 2.0%. Essentially identical IS reductions by PC were observed in AOPCP-blocked animals (%IS/AR = 13.8 ± 2.2 and 13.3 ± 1.8% in rabbits receiving AOPCP at 0.75 and 1.50 mg ⋅ kg−1⋅ min−1, respectively); here plasma AOPCP levels were established before and during PC but not during the subsequent prolonged ischemia. As expected, AOPCP also did not affect %IS/AR in non-PC controls (%IS/AR = 35.5 ± 3.7%). In contrast but as predicted, adenosine-receptor blockade by 8-phenyltheophylline (10 mg/kg iv) substantially attenuated IS reduction by PC in both AOPCP-blocked and control hearts (%IS/AR = 25.2 ± 4.3 and 21.8 ± 2.2%, respectively; P < 0.05 vs. PC alone). The results demonstrate that cardiac ecto-5′-NT is not required for ischemic PC against infarction in the rabbit.

Cardioprotective effects of ingliforib, a novel glycogen phosphorylase inhibitor

2004 ◽  
Vol 286 (3) ◽  
pp. H1177-H1184 ◽  
Author(s):  
W. Ross Tracey ◽  
Judith L. Treadway ◽  
William P. Magee ◽  
Jill C. Sutt ◽  
R. Kirk McPherson ◽  
...  
Keyword(s):  
Heart Rate ◽  
Infarct Size ◽  
Glycogen Phosphorylase ◽  
Ischemic Injury ◽  
Left Ventricular ◽  
Regional Ischemia ◽  
Myocardial Ischemic Injury ◽  
Glycogen Phosphorylase Inhibitor

Interventions such as glycogen depletion, which limit myocardial anaerobic glycolysis and the associated proton production, can reduce myocardial ischemic injury; thus it follows that inhibition of glycogenolysis should also be cardioprotective. Therefore, we examined whether the novel glycogen phosphorylase inhibitor 5-Chloro- N-{(1 S,2 R)-3-[(3 R,4 S)-3,4-dihydroxy-1-pyrrolidinyl)]-2-hydroxy-3-oxo-1-(phenylmethyl)propyl}-1H-indole-2-carboxamide (ingliforib; CP-368,296) could reduce infarct size in both in vitro and in vivo rabbit models of ischemia-reperfusion injury (30 min of regional ischemia, followed by 120 min of reperfusion). In Langendorff-perfused hearts, constant perfusion of ingliforib started 30 min before regional ischemia and elicited a concentration-dependent reduction in infarct size; infarct size was reduced by 69% with 10 μM ingliforib. No significant drug-induced changes were observed in either cardiac function (heart rate, left ventricular developed pressure) or coronary flow. In open-chest anesthetized rabbits, a dose of ingliforib (15 mg/kg loading dose; 23 mg·kg–1·h–1 infusion) selected to achieve a free plasma concentration equivalent to an estimated EC50 in the isolated hearts (1.2 μM, 0.55 μg/ml) significantly reduced infarct size by 52%, and reduced plasma glucose and lactate concentrations. Furthermore, myocardial glycogen phosphorylase a and total glycogen phosphorylase activity were reduced by 65% and 40%, respectively, and glycogen stores were preserved in ingliforib-treated hearts. No significant change was observed in mean arterial pressure or rate-pressure product in the ingliforib group, although heart rate was modestly decreased postischemia. In conclusion, glycogen phosphorylase inhibition with ingliforib markedly reduces myocardial ischemic injury in vitro and in vivo; this may represent a viable approach for both achieving clinical cardioprotection and treating diabetic patients at increased risk of cardiovascular disease.

Sign in / Sign up

Export Citation Format

Share Document