Both in human and in experimental heart failure, creatine transporter protein content is reduced. This mechanism may contribute to the depletion of creatine compounds and thus to the reduced energy reserve in failing myocardium. This finding may have therapeutic implications, suggesting a search for treatment strategies targeted toward creatine transport.

MRI of total sodium (Na) content may allow assessment of myocardial viability, but information on Na content in normal myocardium, necrotic/scar tissue, and stunned or hibernating myocardium is lacking. Thus, the aims of the study were to: 1) quantify the temporal changes in myocardial Na content postmyocardial infarction (MI) in a rat model (Protocol 1); 2) compare Na in normally perfused, hibernating, and stunned canine myocardium (Protocol 2); and 3) determine whether, in bufferperfused rat hearts, infarct scar can be differentiated from intact myocardium by 23 Na-MRI (Protocol 3). In Protocol 1, rats were subjected to LAD ligation. Infarct/scar tissue was excised at control and 1, 3, 7, 28, 56, and 128 days post-MI (N ‫؍‬ 6 -8 each), Na content was determined by 23 Na-NMR spectroscopy (MRS) and ion chromatography. Na content was persistently increased at all time points post-MI averaging 306*-160*% of control values (*P < 0.0083 vs. control). In Protocol 2, 23 Na-MRS of control (baseline), stunned and hibernating samples revealed no difference in Na. In Protocol 3, 23 Key words: 23 Na NMR; viability; myocardial infarction; hibernating; stunning; 3D-CSI In patients with a large akinetic myocardial region, assessment of myocardial viability is frequently required to decide on further therapy. Specifically, while scarred tissue cannot recover function and does not need revascularization, viable but hibernating myocardium will usually resume contractile function after revascularization with percutaneous transluminal coronary angiography (PTCA) or bypass surgery, whereas viable but stunned myocardium will recover spontaneously over time. Although it is well recognized that preoperative viability assessment is predictive of postoperative prognosis (1), all current methods to assess myocardial viability have intrinsic problems, such as patient discomfort and procedural risk (stress testing with inotropic agents using echocardiography (2) or MRI (3)), dependence on acoustic window (echocardiography), low specificity ( 201 T1-scintigraphy) or limited availability (PET) (4).Experimental 23 Na-MRI was first reported by DeLayre et al. (5) in the isolated heart, and applied in vivo by Ra et al. (6) in humans. 23 Na is among the nuclei offering the potential for the highest spatial MRI resolution due to its high NMR sensitivity and short T 1 , thereby allowing for short pulse repetition times. Considerable evidence indicates that ionic homeostasis is perturbed and tissue Na content is substantially increased during the initial hours, days after myocardial infarction (7-9). However, long-term changes in tissue Na content during postinfarction healing and scar formation have not been reported.We propose that if Na content is persistently and selectively increased in nonviable (i.e., necrotic or scarred) regions of the heart, 23 Na-MRI could provide the basis for distinguishing necrotic/scarred vs. viable myocardium and delineating infarct size. Thus, the purpose of our study was threefold: 1) to quantify temporal chang...

Background-The failing myocardium is characterized by reductions of phosphocreatine (PCr) and free creatine content and by decreases of energy reserve via creatine kinase (CK), ie, CK reaction velocity (Flux CK ). It has remained unclear whether these changes contribute directly to contractile dysfunction. In the present study, myocardial PCr stores in a heart failure model were further depleted by feeding of the PCr analogue ␤-guanidinopropionate (GP). Functional and metabolic consequences were studied. Methods and Results-Rats were subjected to sham operation or left coronary artery ligation (MI). Surviving rats were assigned to 4 groups and fed with 0% (nϭ7, Sham; nϭ5, MI) or 1% (nϭ7 ShamϩGP, nϭ8 MIϩGP) GP. Two additional groups were fed GP for 2 or 4 weeks before MI. After 8 weeks, hearts were isolated and perfused, and left ventricular pressure-volume curves were obtained. High-energy phosphate metabolism was determined with 31 P NMR spectroscopy. After GP feeding or MI, left ventricular pressure-volume curves were depressed by 33% and 32%, respectively, but GP feeding in MI hearts did not further impair mechanical function. Both MI and GP feeding reduced PCr content and Flux CK , but here, effects were additive. In MIϩGP rats, PCr levels and Flux CK were reduced by 87% and 94%, respectively. Although ATP levels were maintained in the GP and MI groups, ATP content was reduced by 18% in MIϩGP hearts. Furthermore, 24-hour mortality in GP-prefed rats was 100%. Conclusions-Rats with an 87% predepletion of myocardial PCr content cannot survive an acute MI. Chronically infarcted hearts subjected to additional PCr depletion cannot maintain ATP homeostasis.

Chronic treatment with beta-receptor blockers or angiotensin-converting enzyme (ACE) inhibitors in heart failure can reduce mortality and improve left ventricular function, but the mechanisms involved in their beneficial action remain to be fully defined. Our hypothesis was that these agents prevent the derangement of cardiac energy metabolism. Rats were subjected to myocardial infarction (MI) or sham operation. Thereafter, animals were treated with bisoprolol, captopril, or remained untreated. Two months later, cardiac function was measured in the isolated heart by a left ventricular balloon (pressure-volume curves), and energy metabolism of residual intact myocardium was analyzed in terms of total and isoenzyme creatine kinase (CK) activity, steady-state levels (ATP, phosphocreatine), and turnover rates (CK reaction velocity) of high-energy phosphates (31P nuclear magnetic resonance) and total creatine content (HPLC). Bisoprolol and partially captopril prevented post-MI hypertrophy and partially prevented left ventricular contractile dysfunction. Residual intact failing myocardium in untreated, infarcted hearts showed a 25% decrease of the total, a 26% decrease of MM-, and a 37% decrease of the mitochondrial CK activity. Total creatine was reduced by 15%, phosphocreatine by 21%, and CK reaction velocity by 41%. Treatment with bisoprolol or captopril largely prevented all of these changes in infarcted hearts. Thus the favorable functional effects of beta-receptor blockers and ACE inhibitors post-MI are accompanied by substantial beneficial effects on cardiac energy metabolism.