phosphocreatine and Aortic-Valve-Stenosis

During myocardial ischemia there is a drop in high-energy phosphates in the myocardium. Cold potassium cardioplegia decreases but does not altogether prevent this reduction. Supplementation of cardioplegic solutions with the high-energy compound creatine phosphate (10 mmol/L) compared to plain cardioplegic solutions was investigated in this study. Thirty patients scheduled for aortic valve replacement were included. The patients were randomized to group I (creatine phosphate) or group II (control). Postoperative hemodynamic evaluation revealed no significant differences between the groups. However, group I exhibited a tendency toward a better stroke-work index (135 +/- 18% vs. 102 +/- 5% recovery 15 minutes after bypass and 145 +/- 16% vs. 119 +/- 11% recovery 105 min after bypass). There were fewer patients in group I (5/15) needing inotropic support compared to group II (9/14). The myocardial content of ATP and creatine phosphate showed no significant differences during ischemia and reperfusion. It is concluded that the myocardial protection during ischemia was sufficient to prevent significant reductions of myocardial ATP and creatine phosphate irrespective of supplementation with CP.

Topics: Adenosine Triphosphate; Aged; Aortic Valve Stenosis; Cardioplegic Solutions; Creatine Kinase; Female; Heart Ventricles; Hemodynamics; Humans; Isoenzymes; Male; Middle Aged; Phosphocreatine

Left ventricular (LV) hypertrophy in aortic stenosis (AS) is characterized by reduced myocardial perfusion reserve due to coronary microvascular dysfunction. However, whether this hypoperfusion leads to tissue deoxygenation is unknown. We aimed to assess myocardial oxygenation in severe AS without obstructive coronary artery disease, and to investigate its association with myocardial energetics and function.. Twenty-eight patients with isolated severe AS and 15 controls underwent cardiovascular magnetic resonance (CMR) for assessment of perfusion (myocardial perfusion reserve index-MPRI) and oxygenation (blood-oxygen level dependent-BOLD signal intensity-SI change) during adenosine stress. LV circumferential strain and phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were assessed using tagging CMR and 31P MR spectroscopy, respectively.. AS patients had reduced MPRI (1.1 ± 0.3 vs. controls 1.7 ± 0.3, p < 0.001) and BOLD SI change during stress (5.1 ± 8.9% vs. controls 18.2 ± 10.1%, p = 0.001), as well as reduced PCr/ATP (1.45 ± 0.21 vs. 2.00 ± 0.25, p < 0.001) and LV strain (-16.4 ± 2.7% vs. controls -21.3 ± 1.9%, p < 0.001). Both perfusion reserve and oxygenation showed positive correlations with energetics and LV strain. Furthermore, impaired energetics correlated with reduced strain. Eight months post aortic valve replacement (AVR) (n = 14), perfusion (MPRI 1.6 ± 0.5), oxygenation (BOLD SI change 15.6 ± 7.0%), energetics (PCr/ATP 1.86 ± 0.48) and circumferential strain (-19.4 ± 2.5%) improved significantly.. Severe AS is characterized by impaired perfusion reserve and oxygenation which are related to the degree of derangement in energetics and associated LV dysfunction. These changes are reversible on relief of pressure overload and hypertrophy regression. Strategies aimed at improving oxygen demand-supply balance to preserve myocardial energetics and LV function are promising future therapies.

Topics: Adenosine; Adenosine Triphosphate; Aged; Aortic Valve Stenosis; Biomarkers; Case-Control Studies; Coronary Circulation; Energy Metabolism; Female; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging, Cine; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardial Perfusion Imaging; Myocardium; Oxygen Consumption; Phosphocreatine; Predictive Value of Tests; Severity of Illness Index; Vasodilator Agents; Ventricular Dysfunction, Left; Ventricular Function, Left

The purpose of the present study was to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in normal, hypertrophied, and failing human heart.. Conflicting evidence exists on the extent of changes of high-energy phosphate metabolites in hypertrophied and failing human heart. Previous reports using phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) have quantified metabolites in relative terms only. However, this analysis cannot detect simultaneous reductions.. Four groups of subjects (n = 10 each), were studied: volunteers and patients with hypertensive heart disease (HHD), aortic stenosis, and dilated cardiomyopathy (DCM). Left ventricular (LV) function and mass were measured by cine magnetic resonance imaging. Absolute and relative concentrations of PCr and ATP were determined by (31)P-MRS with spatial localization with optimum point spread function.. Left ventricular ejection fraction remained normal in HHD and aortic stenosis, but was severely reduced to 18% in DCM; LV mass was increased by 55%, 79%, and 68% respectively. In volunteers, PCr and ATP concentrations were 8.82 +/- 1.30 mmol/kg wet weight and 5.69 +/- 1.02 mmol/kg wet weight, and the PCr/ATP ratio was 1.59 +/- 0.33. High-energy phosphate levels were unaltered in HHD. In aortic stenosis, PCr was decreased by 28%, whereas ATP remained constant. In DCM, PCr was reduced by 51%, ATP by 35%, and reduction of the PCr/ATP ratio by 25% was of borderline significance (p = 0.06). Significant correlations were observed among energetic and functional variables, with the closest relations for PCr.. In human heart failure due to DCM, both PCr and ATP are significantly reduced. Ratios of PCr to ATP underestimate changes of high-energy phosphate levels.

Topics: Adenosine Triphosphate; Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Bias; Cardiomyopathy, Dilated; Case-Control Studies; Energy Metabolism; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardium; Phosphocreatine; Phosphorus Isotopes; Stroke Volume; Ventricular Function, Left

To evaluate whether functional and metabolic changes recover after aortic valve replacement (AVR).. Eighteen men with aortic valve stenosis (mean pressure gradient +/- SD, 79.9 mm Hg +/- 15.1) underwent magnetic resonance (MR) imaging and phosphorus 31 MR spectroscopy. In nine patients who underwent AVR, MR imaging and spectroscopy were repeated 40 weeks +/- 12 after AVR. Ten age-matched healthy men were control subjects.. Before AVR, the myocardial phosphocreatine (PCr)-to-adenosine triphosphate (ATP) ratio in the 18 patients was 1.24 +/- 0.17 and 1.43 +/- 0.14 in the control group (P <.01). In nine patients who underwent follow-up MR spectroscopy, the ratio increased from 1.28 +/- 0.17 to 1.47 +/- 0.14 (P <.05) following AVR. Before AVR, early acceleration peak corrected for cardiac output was (0.043 +/- 0.008) x 10(-3) sec(-1) in patients and (0.081 +/- 0.033) x 10(-3) sec(-1) in the control group (P <.05). After 40 weeks +/- 12, the mean early acceleration peak corrected for cardiac output in the nine patients increased significantly to (0.055 +/- 0.006) x 10(-3) sec(-1) (P <.05), although it was still significantly lower than that of the control group (P <.05). Before AVR, a significant correlation was found between the myocardial PCr-ATP ratio and left ventricular diastolic function (n = 18; P <.05).. Severe aortic valve stenosis leads to a decreased myocardial PCr-ATP ratio and impairment of left ventricular diastolic function; following AVR, the ratio normalizes completely, whereas function improves significantly. There is an association between altered myocardial high-energy phosphate metabolism and impaired left ventricular diastolic function.

Topics: Adenosine Triphosphate; Aortic Valve; Aortic Valve Stenosis; Blood Vessel Prosthesis Implantation; Case-Control Studies; Diastole; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardial Contraction; Myocardium; Phosphocreatine; Ventricular Function, Left

Topics: Adenosine Triphosphate; Aortic Valve Stenosis; Cardiomyopathy, Dilated; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardium; Phosphates; Phosphocreatine

Topics: Adenosine Triphosphate; Aortic Valve Stenosis; Case-Control Studies; Heart Valve Prosthesis; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Ventricular Dysfunction, Left

Proton-decoupled 31P NMR spectroscopy at 1.5 T of the anterior left ventricular myocardium was used to monitor myocardial phosphate metabolism in asymptomatic patients with hypertrophic cardiomyopathy (HCM, n = 14) and aortic stenosis (AS, n = 12). In addition to the well-known phosphorus signals a phosphomonoester (PME) signal was detected at about 6.9 ppm in 7 HCM and 2 AS patients. This signal was not observed in the spectra of normal controls (n = 11). We suggest that in spectra of patients with myocardial hypertrophy the presence of a PME signal reflects alterations in myocardial glucose metabolism.

Topics: 2,3-Diphosphoglycerate; Adenosine Triphosphate; Adolescent; Adult; Aortic Valve Stenosis; Cardiomyopathy, Hypertrophic; Female; Glucose; Heart Ventricles; Humans; Magnetic Resonance Spectroscopy; Male; Myocardium; NAD; Organophosphates; Phosphates; Phosphocreatine; Phosphorus

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

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

Using a canine model of subcoronary valvular aortic stenosis, we determined myocardial blood flow, high-energy phosphate content, and mitochondrial function in eight hearts with chronic left ventricular hypertrophy. Fourteen normal hearts were used for control data. Myocardial blood flow was determined by injection of tracer microspheres. During cardiopulmonary bypass, left ventricular transmural biopsy specimens were taken for metabolic analyses. Subepicardial and subendocardial content of adenosine triphosphate (ATP) and creatine phosphate (CP) were assayed. Respiratory control indices for isolated mitochondria were measured by use of NAD-linked and FAD-linked substrates. Endocardial blood flow, subendocardial high-energy phosphate content, and respiratory control indices for NAD-linked substrate in the hearts with chronic left ventricular hypertrophy were significantly lower than the normal values. These data provide insight into the metabolic and myocardial blood flow abnormalities occurring in cardiac hypertrophy and provide a framework for understanding the altered response of hypertrophied hearts to ischemia.

Topics: Adenosine Triphosphate; Animals; Aortic Valve Stenosis; Cardiomegaly; Coronary Circulation; Dogs; Mitochondria, Heart; Oxygen Consumption; Phosphocreatine

The increased susceptibility of hearts with chronic left ventricular hypertrophy (CLVH) to damage during ischemia has been suggested but not documented. The purpose of this study was to isolate ischemic events in hearts with CLVH from reperfusion events. Using physiological and biochemical parameters, we compared the rate and extent of myocardial injury during ischemic contracture between eight canine hearts with CLVH induced by subcoronary valvular aortic stenosis and 14 normal canine hearts. Preischemic myocardial blood flow was determined by injection of tracer microspheres. During cardiopulmonary bypass, each heart was instrumented with a left ventricular balloon and made globally ischemic. At control, contracture initiation, and contracture completion left ventricular transmural biopsy specimens were assayed for subepicardial and subendocardial adenosine triphosphate (ATP) and creatine phosphate (CP). Mitochondrial respiratory control indices for NAD-linked and FAD-linked substrates were measured. Preischemic endocardial blood flow in hearts with CLVH was significantly lower than in normal hearts. At control, subendocardial ATP and CP and the respiratory control index for NAD-linked substrate were significantly lower in hearts with CLVH than in normal hearts. Hearts with CLVH reached contracture initiation significantly sooner than normal hearts. All hearts demonstrated significant decreases in high-energy phosphate content and mitochondrial function during ischemia. Reperfusion injury notwithstanding, we concluded that hearts wih CLVH are more susceptible to ischemic injury than are normal hearts, perhaps related to lower endocardial blood flow, lower subendocardial high-energy phosphate stores, and depressed mitochondrial function prior to ischemia.

Topics: Adenosine Triphosphate; Animals; Aortic Valve Stenosis; Cardiomegaly; Coronary Circulation; Dogs; Ischemia; Mitochondria, Heart; Myocardial Contraction; Oxygen Consumption; Phosphocreatine

In this paper, an attempt was made to describe the alterations of the myocardial energy metabolism following moderate stenoses of aorta or pulmonary artery. Biochemical investigations regarding the main high energy phosphates and a large series of dehydrogenases in the myocardium of the overloaded ventricles have revealed the following facts: (1) the myocardial CP-CPK system appears to be more labile than the myocardial AMP-ATP system in response to a ventricular overload; (2) the changes in the amounts of myocardial high energy phosphates seem to be more important in the right chronic cardiac overload than in the left one; (3) before the overloaded ventricle becomes insufficient, the myocardial dehydrogenase system elicits no alteration, suggesting that the oxidative phosphorylation is not affected; (4) there is a closer relationship between the coronary flow and pressure and the myocardial energy metabolism than that existing between this metabolism and the tension of the myocardial fibres following a persistent increase in the systemic arterial resistance.

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Aortic Valve Stenosis; Blood Pressure; Coronary Circulation; Creatine Kinase; Dogs; Energy Metabolism; Female; Heart Rate; Male; Myocardial Contraction; Myocardium; Oxidoreductases; Oxygen Consumption; Phosphates; Phosphocreatine; Phosphoric Monoester Hydrolases; Pulmonary Valve Stenosis

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