Comparison of various methods for assessing infarctsize in the dog

Martorana, P. A.; Göbel, Helmut; Kettenbach, B.; Nitz, Rolf-Eberhard

doi:10.1007/bf01908045

Cited by 16 publications

(4 citation statements)

References 13 publications

(11 reference statements)

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“…This protective effect could be the result of the shorter period of ischemia in these groups (coronary occlusion occurred later than in controls) and/ or of the hemodynamic effects of M (29). M, in fact, has been found to reduce infarct-size following ligation of coronary artery in dogs (17,18). ISDN and NTG did not significantly affect infarct size in the present study.…”

Section: Discussioncontrasting

confidence: 78%

“…Infarct size, assessed by weighing the mass of the infarcted myocard, a reliable methodology when used in animals of similar weight and size (17), was reduced in the M groups as compared to the controls. This protective effect could be the result of the shorter period of ischemia in these groups (coronary occlusion occurred later than in controls) and/ or of the hemodynamic effects of M (29).…”

Section: Discussionmentioning

confidence: 99%

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Comparison of the effects of molsidomine, nitroglycerin and isosorbide dinitrate on experimentally induced coronary artery thrombosis in the dog

Martorana¹,

Kettenbach²,

Göbel³

et al. 1984

Basic Res Cardiol

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Platelet activation and aggregation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Molsidomine (M), isosorbide dinitrate (ISDN) and nitroglycerin (NTG) have been found to inhibit platelet aggregation in vitro. In the present study, the activity of these compounds was investigated in a model of coronary artery thrombosis in vivo. Dogs were anesthetized, thoracotomized, and their heart was exposed. An electrode was inserted into the left circumflex coronary artery and set to rest on the intima. Electrical stimulation (9 V, 150 microA) lasted for 6 h. Compounds (each in 2 dose levels) were given as an i.v. infusion starting 30 min after the beginning of the stimulation and lasting for the duration of the experiment. All control (saline-treated) animals underwent thrombotic occlusion of the coronary artery as assessed by flow measurement. On the other hand, 2/8 dogs treated with the lower M dose and 4/8 dogs treated with the higher M dose did not have a coronary occlusion. Neither ISDN nor NTG, at both doses, prevented the coronary occlusion. In control animals thrombus wet weight was 74.43 +/- 11.25 mg. M reduced the thrombus weight in a dose-related manner, while ISDN (marginally) and NTG (significantly at the higher dose) increased this parameter. Following the coronary thrombosis, all control animals developed myocardial infarcts as assessed by the tetrazolium technique. Similarly all animals treated with ISDN and with NTG (at both doses) showed infarcts. However, 3/8 M-dogs did not have a myocardial infarction in the lower as well as in the higher dose groups. The hemodynamic changes induced by the 3 compounds were similar in magnitude. Thus M but not ISDN or NTG showed in this in-vivo study antithrombotic and consequently antiischemic activity.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of molsidomine, nitroglycerin and isosorbide dinitrate on experimentally induced coronary artery thrombosis in the dog

Martorana¹,

Kettenbach²,

Göbel³

et al. 1984

Basic Res Cardiol

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“…In four animals, the chest was reopened, the coronary occluder was inflated, the ascending aorta was clamped and 10 ml of 1% methylene blue was injected into the coronary tree through the aortic wall, as previously described [11]. Then the heart was excised, and 10 mm thick slices were cut and photographed.…”

Section: Mri Scanningmentioning

confidence: 99%

“…[1-13C]pyruvate polarization was performed using Dynamic Nuclear Polarization (Hypersense, Oxford Instruments, Oxford, UK) [11]. The injection solution contained 230 mM of sodium [1-13C]pyruvate, 100 mM TRIS buffer, 0.27 mM Na 2EDTA and 20 microM Gd 3+ -complex (Dotarem-Guerbet-France).…”

Section: Hyperpolarization and Image Acquisitionmentioning

confidence: 99%

Cardiac Metabolism in a Pig Model of Ischemia–Reperfusion by Cardiac Magnetic Resonance with Hyperpolarized 13C-Pyruvate

Aquaro¹,

Frijia²,

Positano³

et al. 2015

IJC Metabolic & Endocrine

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Background: Magnetic resonance (MRI) with hyperpolarized 13 C-pyruvate is a new technique for the assessment of myocardial metabolism. Aims: The aim of this study is to assess the effectiveness of MRI with hyperpolarized 13 C-pyruvate to detect cardiac metabolic changes in a model of ischemia/reperfusion. Methods: A pneumatic occluder was placed around the left anterior descending artery in 7 pigs. A 3 T scanner with a 13 C quadrature birdcage coil was used. Hyperpolarized 13 C-pyruvate was injected intravenously at rest, during coronary occlusion and 5 min after reperfusion. Metabolic images were acquired using a 3D-IDEAL spiral CSI during the injection of 13 C-pyruvate and 3D-parametric maps of 13 C-pyruvate, 13 C-lactate and 13 Cbicarbonate were generated. Metabolic Activity Mismatch (MAM) was defined as the relative change between a) resting state and coronary occlusion or b) resting and reperfusion in all the myocardial segments. Results: During occlusion, a decrease in 13 C-lactate (− 21 ± 26% vs baseline 3 ± 16%, P b 0.0001) and 13 Cbicarbonate (− 29 ± 34% vs 33 ± 52%, P b 0.0001) was found in myocardial segments at risk, as compared with remote segments. In ischemic segments, the 13 C-lactate signal increased during reperfusion (20 ± 42% vs −7 ± 22%, P = 0.0007), while 13 C-bicarbonate was persistently reduced (−38 ± 27% vs 36 ± 51%, p b 0.0001).Conclusions: 13 C-pyruvate MRI is able to detect transient changes in regional metabolism in an in-vivo model of myocardial ischemia-reperfusion.Magnetic resonance (MRI) with hyperpolarized 13C-labeled tracers is an emerging imaging technique for the evaluation of coronary artery anatomy, quantification of myocardial perfusion and a direct assessment of myocardial viability [1]. In particular, MRI with hyperpolarized 13C-pyruvate has allowed, for the first time, to evaluate cardiac metabolism in real time and in vivo [2][3][4]. Relative changes of pyruvate and of its metabolites lactate, alanine and bicarbonate can be monitored under normal conditions, during either acute ischemia or reperfusion, following short-or long-lasting coronary occlusion [5]. Differently from PET where FDG is not metabolized by myocites, the main advantage of hyperpolarized 13C-pyruvate MRI is that the metabolic fate of 13C-pyruvate and its metabolites is directly assessed. A recent study using hyperpolarized 13C-pyruvate showed increased levels of 13C-lactate after 10 min of global ischemia in isolated hearts [6]. Golman et al. combined conventional MRI scan and H13C by a single short-axis slice of chemical shift images (CSI) in a pig model of ischemia-reperfusion, demonstrating decreased 13C-bicarbonate production in stunned viable myocardial segments, after 15-minute coronary occlusion, and decreased 13C-bicarbonate and 13C-alanine production after 45-minute occlusion [7]. Recently, Lau et al. proposed a three-dimensional multislice cardiac-gated spiral 13C imaging approach, permitting wholeheart coverage [8]. A novel fast three-dimensional acquisition (3D IDEAL, Iterative DEcompositio...

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Molsidomine: Alternative Approaches To Treat Myocardial Ischemia

Nitz¹,

Fiedler²

1987

Pharmacotherapy

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The long-acting antianginal drug molsidomine has been shown experimentally to reduce myocardial infarct size when administered prior to or after cardiac insult. This is due to several drug actions. Dilation of postcapillary capacitance vessels diminishes venous return, preload, heart dimensions, and myocardial oxygen consumption. Relaxation of stenosed conductive coronary arteries increases the perfusion of myocardial areas at risk of infarction due to enhanced collateral circulation. Increased regional blood supply nourishes predominantly subendocardial cardiac muscles as a result of reduction of extravascular coronary pressure, and resistance. The stable heart rate and cardiac contractility favor improved heart performance. The inhibition of platelet aggregation in vivo by molsidomine or its active metabolites, SIN-1 and SIN-1A, is linked to the stimulation of prostacyclin synthesis, inhibition of thromboxane release with induction of thrombosis and vasoconstriction, and enhanced concentrations of cyclic guanosine monophosphate. Dilation of coronary arteries after intracoronary administration of SIN-1, with inhibition of platelet aggregation by restrained release of adenosine diphosphate and stabilization of platelet membranes, facilitates the recanalization of stenosed arteries and reduces coronary muscle tone at the site of thrombosis. Activation of the human fibrinolytic system and drug-induced release of a plasminogen activator favor dysaggregatory effects. The drug's inhibiting actions on lipoxygenase products of arachidonate (e.g., 12-hydroperoxy-eicosatetraenoic acid and leukotrienes) may shift prostaglandin catabolism to cyclooxygenase products (e.g., prostacyclin) that protect against the expansion of ischemia and the induction of coronary spasm. Experimentally, the hemodynamic effectiveness of molsidomine can be antagonized by catecholamines (afterload effects) and dihydroergotamine (preload and afterload effects) respectively. Further clinical investigations will clarify the application of these mechanisms for the therapeutic success of the drug in human myocardial infarction.

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Comparison of various methods for assessing infarctsize in the dog

Cited by 16 publications

References 13 publications

Comparison of the effects of molsidomine, nitroglycerin and isosorbide dinitrate on experimentally induced coronary artery thrombosis in the dog

Comparison of the effects of molsidomine, nitroglycerin and isosorbide dinitrate on experimentally induced coronary artery thrombosis in the dog

Cardiac Metabolism in a Pig Model of Ischemia–Reperfusion by Cardiac Magnetic Resonance with Hyperpolarized 13C-Pyruvate

Molsidomine: Alternative Approaches To Treat Myocardial Ischemia

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