phosphocreatine and Aortic-Valve-Insufficiency

Topics: Adenosine Triphosphate; Angina Pectoris; Animals; Aortic Valve Insufficiency; Cricetinae; Dilatation; Dogs; Endoplasmic Reticulum; Golgi Apparatus; Heart Failure; Humans; Hypoxia; Lactates; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Myofibrils; Necrosis; Oxygen Consumption; Papillary Muscles; Phosphates; Phosphocreatine; Polyribosomes; Rabbits; Rats

Uncoupling proteins, inner mitochondrial membrane proton transporters, are important for regulating myocardial energy efficiency. We investigated the effects of the ACE inhibitor perindopril on cardiac performance, myocardial energy efficiency, and uncoupling protein expression in an aortic regurgitation rat model. Twenty male Sprague-Dawley rats, in which aortic regurgitation was produced, were divided into untreated and perindopril-treated (5 mg x kg(-1) x d(-1)) rats. The treatments were initiated 3 days after operation. Ten control rats were sham-operated. Measurements of blood pressure and echocardiography were repeated before and 100 days after operation (endpoint). Left ventricular uncoupling protein-2 expression, creatine phosphate, and adenosine triphosphate were measured at endpoint. In perindopril-treated rats, systolic and diastolic blood pressure decreased after treatment (92+/-4/65+/-2 mm Hg). At endpoint, left ventricular end-diastolic dimension in untreated (10.7+/-0.2 mm) and treated rats (9.2+/-0.2 mm) was increased, and fractional shortening was reduced in untreated rats (28+/-1%) but did not change in treated rats (36+/-2%). Uncoupling protein-2 mRNA expression increased in untreated rats (3.7-fold) and was suppressed by perindopril (1.5-fold). The creatine phosphate was reduced in untreated rats (10.6+/-0.7 micro mol/g) but not in treated rats (15.9+/-2.0 micro mol/g). In the chronic stage of aortic regurgitation, perindopril improved cardiac performance and myocardial energy efficiency, in which the suppression of uncoupling protein-2 may play an important role.

Topics: Adenosine Triphosphate; Angiotensin-Converting Enzyme Inhibitors; Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Blood Pressure; Echocardiography, Doppler; Energy Metabolism; Heart; Heart Failure; Heart Rate; Ion Channels; Male; Membrane Transport Proteins; Mitochondrial Proteins; Myocardium; Organ Size; Perindopril; Phosphocreatine; Protein Biosynthesis; Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Uncoupling Protein 2

Topics: Adenosine Triphosphate; Animals; Aortic Valve Insufficiency; Atrial Natriuretic Factor; Blotting, Northern; Cardiac Output, Low; Disease Models, Animal; Humans; Ion Channels; Male; Membrane Transport Proteins; Mitochondria, Heart; Mitochondrial Proteins; Muscle, Skeletal; Myocardium; Phosphocreatine; Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tumor Necrosis Factor-alpha; Uncoupling Agents; Uncoupling Protein 2

Topics: Adenosine Triphosphate; Aortic Valve Insufficiency; Aortic Valve Stenosis; Diastole; Heart; Humans; Hypertension; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Myocardium; Nuclear Magnetic Resonance, Biomolecular; Phosphocreatine; Phosphorus; Physical Fitness; Systole; Ventricular Function, Left

The purpose of this work was to determine the clinical and hemodynamic correlates of alterations in cardiac high-energy phosphate metabolism in patients with aortic stenosis and with aortic incompetence.. Fourteen volunteers, 13 patients with aortic stenosis, and 9 patients with aortic incompetence were included. Patients underwent echocardiography and left and right heart catheterization. 31P-MR spectra from the anterior myocardium were obtained with a 1.5 Tesla clinical MR system.. Aortic stenosis and aortic incompetence patients had similar New York Heart Association (NYHA) classes (2.77 +/- 0.12 vs 2.44 +/- 0.18), ejection fractions (normal), left ventricular (LV) end-diastolic pressures, and LV wall thickness. In volunteers, phosphocreatine/adenosine triphosphate (ATP) ratios were 2.02 +/- 0.11. For all patients, phosphocreatine/ATP was significantly reduced (1.64 +/- 0.09; *p = 0.011 vs volunteers). Phosphocreatine/ATP decreased to 1.55 +/- 0.12 (*p = 0.008) in aortic stenosis, while in aortic incompetence, phosphocreatine/ATP only showed a trend for a reduction (1.77 +/- 0.12; p = 0.148). For all patients, phosphocreatine/ATP decreased significantly only with NYHA class III (1.51 +/- 0.09; *p = 0.001), but not with NYHA classes I and II (phosphocreatine/ATP 1.86 +/- 0.18). In aortic stenosis, phosphocreatine/ATP ratios decreased (1.13 +/- 0.03; *p = 0.019) only when LV end-diastolic pressures were > 15 mm Hg or when LV diastolic wall stress was > 20 kdyne cm-2 (1.13 +/- 0.03; *p = 0.024).. For a similar clinical degree of heart failure in human myocardium, volume overload hypertrophy does not, but pressure overload does, induce significant impairment of cardiac high-energy phosphate metabolism. In aortic valve disease, alterations of high-energy phosphate metabolism are related to the degree of heart failure.

Topics: Adenosine Triphosphate; Adult; Aged; Aortic Valve Insufficiency; Aortic Valve Stenosis; Female; Hemodynamics; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardium; Phosphates; Phosphocreatine; Phosphorus Radioisotopes

Phosphorus-31 magnetic resonance spectroscopy can be used to study intracellular biochemistry non-invasively by measuring the relative proportions of high energy phosphates. Study of deteriorating cardiac metabolism might be useful in the management of hypertrophy and heart failure. 31P magnetic resonance spectroscopy was carried out in fourteen patients with aortic valve disease (six with aortic stenosis, eight with aortic incompetence). Six patients were receiving treatment for symptoms of heart failure. The phosphocreatine (PCr) to ATP ratio in these patients (1.1 [SD 0.32]) was significantly lower than that in thirteen controls (1.5 [0.2], p less than 0.001) or in the eight patients who did not have symptoms of heart failure (1.56 [0.15], p less than 0.0035). These findings indicate that heart failure in aortic valve disease is associated with low PCr, which could be due to loss of intracellular creatine. The measurement could eventually have a role in helping to determine the optimum timing for aortic valve replacement.

Topics: Adenosine Triphosphate; Adult; Aged; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiomyopathy, Hypertrophic; Humans; Magnetic Resonance Spectroscopy; Middle Aged; Myocardium; Phosphocreatine; Phosphorus

Asymmetric septal hypertrophy is considered by many to be pathologic but its presence in a number of states associated with left ventricular overload indicates that it may develop as an adaptive feature in the overloaded heart. This hypothesis implies that initially in these states a greater systolic stress and thus energy metabolism occurs in the ventricular septum than in the left ventricular free wall. It was previously demonstrated that in the early stages of ischemia regional differences in energy metabolism could be determined by comparisons of tissue high energy phosphate depletion and lactate accumulation. In the present study these measurements were made in an animal model of left ventricular overload. In open chest dogs aortic insufficiency was produced, which served to provide both volume overload to the left ventricle and regional myocardial ischemia. In addition to regional metabolite levels, measurements of regional blood flow were determined using radioactive microspheres. Tissue samples were taken from the left ventricle and interventricular septum, freeze clamped, divided transmurally into thirds and analyzed for creatine phosphate, adenosine triphosphate and lactate. Animals with myocardial ischemia after aortic insufficiency were classified into two groups: those in which ischemia was limited to the inner left ventricle and left side of the septum and those with more extensive ischemia transmurally. In the latter group, creatine phosphate depletion and lactate accumulation were greater in the septum, but myocardial blood flow was also more depressed in the septum than in the left ventricle. In the former group, where ischemia was more restricted, metabolite changes were also more severe in the left septum than in the inner left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Animals; Aortic Valve Insufficiency; Blood Pressure; Cardiomegaly; Dogs; Energy Metabolism; Heart Septum; Lactates; Myocardium; Phosphocreatine

Twenty-five patients undergoing aortic valve replacement were administered two different electrolyte solutions pre- and intraoperatively: patients in group A (n = 9) received a balanced solution of electrolytes and trace metals with aspartate as anion (Inzolen), patients in group B (n = 16) received Ringer's solution with potassium chloride referenced to frequently-measured serum potassium levels. From the left ventricular apex region, needle biopsies were obtained at three points in time: 1. beginning of CPB, 2. end of ischemia, 3. after ten minutes of reperfusion. The tissue samples were enzymatically analyzed for the content of ATP, CP, ADP and lactate. In group A (patients with aspartate) ATP (moderately) and CP (markedly) decreased after ischemia with a marked increase after reperfusion. ADP and lactate in this group (A) increased at the end of ischemia and decreased after reperfusion. ATP and CP in group B (KCl) showed a similar course during the investigation. Lactate (markedly) and ADP (moderately) increased after ischemia without changing after reperfusion. Mean values of ATP and CP in group A were significantly higher than those of group B at all times. Mean values of ADP and lactate, however, in group A were below those of group B. The data indicate an improvement in energetic metabolism of myocardium in man. The results point out the possible importance of aspartates in compound with electrolytes and trace metals in preservation of biochemical energy.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Aortic Valve; Aortic Valve Insufficiency; Aortic Valve Stenosis; Aspartic Acid; Energy Metabolism; Female; Heart; Heart Valve Prosthesis; Humans; Isotonic Solutions; Lactates; Lactic Acid; Male; Middle Aged; Myocardium; Phosphocreatine; Ringer's Solution

Topics: Adenosine Triphosphate; Adult; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiomegaly; Cyclic AMP; DNA; Fatty Acids, Nonesterified; Humans; Lactates; Middle Aged; Myocardium; Phosphocreatine; RNA

Topics: Adaptation, Physiological; Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Aortic Valve Insufficiency; Biopsy; Cardiomegaly; Glycogen; Heart Failure; Heart Ventricles; Lactates; Muscle Proteins; Myocardium; Phosphocreatine; Rabbits