Effect of adenosine and AICAR on ATP content and regional contractile function in reperfused canine myocardium

Hoffmeister, Hans Martin; Mauser, M.; Schäper, Wolfgang

doi:10.1007/bf01908189

Cited by 94 publications

(21 citation statements)

References 44 publications

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“…This metabolic difference between adenosine-pretreated and control hearts did not appear to influence functional recovery ( Figure 5). This agrees with the observations of other investigators (17,29), who also were unable to demonstrate an influence of cardiac ATP on functional recovery from ischaemia. In spite of this, ATP has beenwidely and successfully used as an indicator of the extent of ischaemic changes in the heart.…”

Section: Discussionsupporting

confidence: 93%

“…Even in the presence of adenosine no increase of ATP during recovery was observed, which is in contrast to an enhanced adenosine uptake and increase of ATP in the reperfused, regionally ischaemic dog heart (28). In the rat, there seems to be a failure of the energy producing or distributing processes rather than a failure of energy utilisation (17) reported in dogs.…”

Section: Discussionmentioning

confidence: 95%

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Adenosine-induced increase in myocardinal ATP: Are there beneficial effects for the ischaemic myocardium?

et al. 1989

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The adenosine triphosphate (ATP) content of isolated Langendorff-perfused rat hearts may be increased by more than 40% above the normal value by a 2-h perfusion with adenosine (15 mumol/l). This metabolic manipulation was used to investigate the hypothetical relationship between total tissue ATP content and ischaemia-induced contractile failure, ischaemic contracture and post-ischaemic functional recovery. Adenosine perfused hearts were submitted to 20 min of normothermic ischaemia and reperfused for 45 min with or without adenosine. Control experiments were performed with adenosine-free preischaemic perfusion. In identically designed experiments the tissue-protective effect of diltiazem (0.5 mumol/l) was determined and compared with the experiments with adenosine. At the end of 120 min of preischaemic perfusion, the ATP content of the adenosine treated hearts was 34.3 +/- 1.8 mumol/g dry weight (control = 23.6 +/- 1.9 mumol/g, p less than 0.01). After a period of 20 min of normothermic ischaemia, the ATP content of the adenosine hearts decreased to 13.3 +/- .4 mumol/g, whereas ATP fell to 8.3 +/- 1.6 mumol/g in the control hearts. The creatine phosphate (CP) levels of adenosine hearts were significantly lower than those of the control group before ischaemia, but did not show major differences following ischaemia. During ischaemia, the contractile activity measured via an intraventricular balloon catheter, as well as ischaemic contracture did not differ between the adenosine and control hearts. The inclusion of diltiazem into the perfusate significantly delayed the onset of contracture. After 45 min of reperfusion, ATP contents of adenosine and control hearts reached similar values (8.4 +/- 2.3 and 8.3 +/- 2.9 mumol/g, respectively). Inclusion of adenosine (15 mumol/l in the reperfusion perfusate of the adenosine experiments prevented a further decrease, but did not increase tissue ATP content. CP values of all groups showed a partial recovery upon reperfusion, they did not differ significantly. Contractile recovery was equal in all experimental groups except for the diltiazem treated hearts, which showed during the first 10 min of reperfusion an improved mechanical performance. It is concluded that total tissue ATP is not necessarily a good indicator of functional capabilities under conditions of normothermic ischaemia and reperfusion in the isolated rat heart.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 95%

Adenosine-induced increase in myocardinal ATP: Are there beneficial effects for the ischaemic myocardium?

et al. 1989

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“…Glower et al reported 24 hours of recovery following 15 minutes of ischemia in the conscious dog (9). Kloner et al (18) found long lasting dysfunction after a short period of regional ischemia, and Vial et al (36) as well as a recent paper from our laboratory showed a regional dysfunction for several hours in open-chest dog preparations (13). It was demonstrated by Heyndrickx et al (12) that 5 minutes of ischemia are long enough to produce a prolonged postischemic dysfunction.…”

Section: Regional Functionmentioning

confidence: 89%

“…Regional sonomierometry was performed according to Hagl (10) as previously described (13). Two pairs of small ultrasound transducers (1.5 mm diameter approximately) were implanted in a subendocardial position oriented to the minor axis of the left ventricle (about 13 mm distance each pair).…”

Section: Methodsmentioning

confidence: 99%

Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels

1986

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The effect of recurrent periods of ischemia on the myocardium was investigated in 15 open-chest dogs. Ischemia was produced by 3 minutes of proximal occlusion of the left anterior descending coronary artery. Each occlusion was followed by reperfusion of 3 minutes duration. Forty occlusions with a total of 120 minutes of ischemia were performed, and regional function (sonomicrometry) as well as high energy phosphates (needle biopsies) were determined at the end of the 5th, 20th, and 40th period of ischemia and reperfusion. The first periods of ischemia had a cumulative effect both on regional postischemic function (44% and 59% respectively of preischemic control after 20 occlusions) and on the ATP content, but with increasing number of occlusions the additive effects became smaller (ATP reduction/mumol/g w w/per occlusion). The ATP breakdown per occlusion was diminished with increasing number of periods of ischemia, and no significant adenosine was measured in the ischemic myocardium. Higher than normal postischemic creatine phosphate levels (9.1 mumol/g w w at the 40th reperfusion vs. 6.7 mumol/g w w control) indicated a functioning oxidative phosphorylation in the presence of an ATP utilization problem at the sarcomere level, because indicators of the cellular energy level (energy charge, free energy change of ATP hydrolysis) quickly normalized during reperfusion. Stunned myocardium is therefore not a problem of energy supply but rather of energy utilization. Reduced ATP utilization and regional dysfunction are the expressions of the same cellular defect which resides either in the ATP-splitting contractile apparatus or in the electromechanical coupling. Contractile dysfunction during reperfusion protects the heart against subsequent periods of ischemia because ATP turnover is reduced.

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“…On this subject, Hoffmeister et al reported that an experimental promotion of recovery of ATP content in the myocardium did not produce any improvement in contractility. 13 It seems that there may be a greater delay in the recovery of contraction compared with ATP content, even though CV-11974 improves myocardial energy metabolism during reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Role of Cardiac ATP-Sensitive K+ Channels Induced by Angiotensin II Type 1 Receptor Antagonist on Metabolism, Contraction and Relaxation in Ischemia-Reperfused Rabbit Heart.

2001

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he renin-angiotensin system (RAS) plays an important role in the regulation of the cardiovascular system in various physiological or pathological conditions 1 and is activated on acute myocardial infarction both in humans 2 and in experimental animals. 3,4 Angiotensin II (Ang II) increases myocardial necrosis. 5 The localized Ang II exerts some deleterious effects on the myocardium of ischemia-reperfused heart. 6 Angiotensin II type 1 (AT1) receptor antagonists have the cardioprotective effect on ischemia-reperfusion injury. 7,8 And also, AT1 receptor antagonists have been shown to involve AT2 receptor activation and the subsequent action of bradykinin. 9 Recent evidence suggests that the adenosine triphosphate-sensitive K + (KATP) channels are mainly involved in effectors of cardioprotection against ischemia-reperfusion. 10,11 A reducJapanese Circulation Journal Vol.65, May 2001 tion in myocardial damage, reduced formation of Ang II, preservation of bradykinin, or opening of KATP channels could all play the role. The effect of AT1 receptor antagonists against the KATP channels in myocardial ischemiareperfusion injury is not clearly identified.The purpose of the present study was to test the hypothesis that AT1 receptor antagonist contributes to the cardioprotective effect in the ischemia-reperfused heart by acting against KATP channels through the bradykinin B2 receptor or not. We measured the effects of AT1 receptor antagonist on myocardial energy metabolism by using phosphorus 31-nuclear magnetic resonance ( 31 P-NMR spectrometer) and assessed cardiac function in isolated rabbit heart. The administration of this agent was found to improve abnormal myocardial energy metabolism and relaxation by acting against KATP channels through the bradykinin B2 receptor. Methods Isolated Heart PreparationMale, Japanese white rabbits weighing 1.6-1.7 kg were anesthetized by intravenous injection of sodium pentobar- . Group II showed a significant inhibition of the decrease in ATP during ischemia and reperfusion compared with Group I (p<0.01), being 42±3% and 19±4% at ischemia, 69±3% and 47±4% at reperfusion in Group II and Group I, respectively. Group II also showed a significant inhibition of the increase in LVEDP during ischemia and reperfusion compared with Group I (p<0.01), being 13±4 mmHg and 52±8 mmHg at ischemia, 8±2 mmHg and 26±5 mmHg at reperfusion in Group II and Group I, respectively. However, Group III did not inhibit the decrease in ATP and the increase in LVEDP during ischemia and reperfusion. Group IV also showed no inhibition of the aforementioned parameters during the same period. These results suggest that CV-11974 has a significant beneficial effect for improving myocardial energy metabolism and relaxation during both myocardial ischemia and reperfusion, which is provided by KATP channels and bradykinin B2 receptor. The cardioprotective quality of the AT1 receptor antagonist is caused by the KATP channels that are mediated by the bradykinin B2 receptor. (Jpn Circ J 2001; 65: 451 -456)

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Effect of adenosine and AICAR on ATP content and regional contractile function in reperfused canine myocardium

Cited by 94 publications

References 44 publications

Adenosine-induced increase in myocardinal ATP: Are there beneficial effects for the ischaemic myocardium?

Adenosine-induced increase in myocardinal ATP: Are there beneficial effects for the ischaemic myocardium?

Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels

Role of Cardiac ATP-Sensitive K+ Channels Induced by Angiotensin II Type 1 Receptor Antagonist on Metabolism, Contraction and Relaxation in Ischemia-Reperfused Rabbit Heart.

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