[Pathogenesis of coronary disease]. / Zur Pathogenese der koronaren Herzerkrankung.

Being overweight (OW) was recognized very early as a risk factor for coronary heart disease (CHD). Its significance in the pathogenesis of CHD has been strengthened by observations showing that OW is responsible for the development of diabetes, hypertension and lipid disorders due to its induction of insulin resistance (IR). Its key role has been underlined further by recent studies indicating that OW causes endothelial dysfunction via elevated serum fatty acids, which initiates the molecular events that further the process of CHD. It is, therefore, of the utmost importance to determine its roots. The most probable reason for its high incidence is due to the genetic outfit of most people which does not permit adequate adaptation of the cerebral cortex according to the environmental changes which have occurred since the early days.

[On pathogenesis of coronary heart disease]. / Zur Pathogenese der koronaren Herzerkrankung.

Being overweight (OW) was recognized very early as a risk factor for coronary heart disease (CHD). Its significance in the pathogenesis of CHD has been strengthened by observations showing that OW is responsible for the development of diabetes, hypertension and lipid disorders due to its induction of insulin resistance (IR). Its key role has been underlined further by recent studies indicating that OW causes endothelial dysfunction via elevated serum fatty acids, which initiates the molecular events that further the process of CHD. It is, therefore, of the utmost importance to determine its roots. The most probable reason for its high incidence is due to the genetic outfit of most people which does not permit adequate adaptation of the cerebral cortex according to the environmental changes which have occured since the early days.

Detection of phosphomonoester signals in proton-decoupled 31P NMR spectra of the myocardium of patients with myocardial hypertrophy.

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.

31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) often causes sudden, unexpected death in adolescents and young adults. Alterations in myocardial metabolism are considered to be causes for contractile dysfunction. We examined the question of whether metabolic abnormalities antedate the manifestation of symptoms in patients with HCM. METHODS AND RESULTS: Proton-decoupled 31P NMR spectroscopy of the anterior left ventricular wall of the heart of 14 young, asymptomatic patients with HCM was performed with a 1.5-T whole-body imager. Spectra of the phosphate metabolites were compared with those of normal control subjects. The patients exhibited a significantly reduced (P<0.02) ratio of phosphocreatine (PCr) to ATP of 1.98+/-0.37 (mean+/-SD), compared with 2.46+/-0.53 obtained in 11 normal control subjects. In addition, the group of patients with severe hypertrophy of the interventricular septum (n=8) showed a significantly increased (P<0.05) Pi-to-PCr ratio, with a Pi x 100/PCr of 20.0+/-8.3 versus 9.7+/-7.2 in control subjects. Both abnormalities are similar to those found in ischemic myocardium. This view is also supported by a significantly increased (P<0.01) phosphomonoester (PME)-to-PCr ratio, with a PME x 100/PCr of 20.7+/-11.2 compared with 8.4+/-6.7 in control subjects, indicating altered glucose metabolism. CONCLUSIONS: 31P NMR spectroscopy detects alterations of myocardial metabolism in asymptomatic patients with HCM. These alterations may contribute to the understanding of the pathophysiology and natural history of the disease.

Proton-decoupled myocardial 31P NMR spectroscopy reveals decreased PCr/Pi in patients with severe hypertrophic cardiomyopathy.

Disturbed myocardial energy metabolism may occur in patients with primary hypertrophic cardiomyopathy (HCM). A noninvasive way to gain insight into cardiac energy metabolism is provided by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. 31P NMR spectroscopy with proton decoupling was performed in 13 patients aged 13-36 years with HCM on a 1.5 T Magnetom with a double resonant surface coil. A 2D chemical shift imaging (CSI) sequence in combination with slice selective excitation was used to acquire spectra of the anteroseptal region of the left ventricle (volume element: 38 mL). The chemical shifts of the phosphorus metabolites, intracellular pHi, and coupling constants J(alphabeta) and J(gammabeta) were calculated. Peak areas of 2,3-diphosphoglycerate (DPG), Pi, and adenosine triphosphate (ATP) were determined and corrected for blood contamination, saturation, and differences in nuclear Overhauser enhancements (NOE). The maximum thickness of the interventricular septum (IVSmax) was determined from tomographic long-axis images and expressed as number of standard deviations above the mean of the normal population (Z score). The patients were then divided into 2 groups: 6 patients with moderate HCM (HCMm, Z score < or = 5) and 7 patients with severe HCM (HCMs, Z score > 5). No differences between both groups and a control group of healthy volunteers (n = 16) were found with respect to phosphocreatine (PCr)/gamma-ATP ratio, pHi, or the coupling constants. Only the PCr/Pi ratio differed significantly from the control group (HCM(all), alpha < 0.05, HCMs, alpha < 0.02, 2-sided U test). The decrease of the PCr/Pi ratio in patients with HCM is probably caused by ischemically decreased oxygen supply in the severely hypertrophied myocardium.

Phosphorus J-coupling constants of ATP in human brain.

Proton decoupled 31P NMR spectroscopy of the occipital brain of healthy volunteers was performed with a 1.5 T whole-body imager. By use of two-dimensional chemical-shift imaging in combination with slice-selective excitation well resolved localized spectra (38 ml) were obtained within 34 min from which the homonuclear 31P-31P J-coupling constants of ATP could be determined: J(gammabeta) = 16.1 Hz +/- 0.2 Hz and J(alphabeta) = 16.3 Hz +/- 0.1 Hz (mean +/- SEM, n = 14). Both, the J-coupling constants and the chemical-shift difference between alpha- and beta-ATP (delta(alphabeta) = 8.61 ppm +/- 0.01 ppm) were used to calculate the concentration of intracellular free magnesium. The concentrations are 0.39 mM +/- 0.09 mM by using the average of both coupling constants of each spectrum, which is in fair agreement with 0.32 mM +/- 0.01 mM obtained from the chemical shift of alpha and beta phosphate resonances, which is the more accurate result.

Change in chemical shift and splitting of 31P gamma-ATP signal in human skeletal muscle during exercise and recovery.

Proton decoupled 31P in vivo NMR spectroscopy of the human finger flexor muscles was performed during exercise and recovery using a 1.5 T whole-body imager. Predominantly the gamma-ATP signal shows a splitting caused by different signal contributions with chemical shifts that vary independently. Studies on the human gastrocnemius and biceps femoris muscle were undertaken to investigate the appearance of the splitting in these muscles as well. In all cases more than one signal contribution was found which might represent the different muscle fibre types and their recruitment pattern following exercise. An analysis of the chemical shifts (delta) of ATP results in changes of up to 0.4 ppm and 0.1 ppm for delta gamma- and delta beta-ATP, respectively. Based solely on the chemical shifts of the ATP 31P signals the tissue pH value following exercise was determined. The result was in good agreement with the value derived from delta Pi.

Phosphorus J coupling constants of ATP in human myocardium and calf muscle.

Proton-decoupled 31P NMR spectroscopy of the heart and calf muscle of healthy volunteers was performed with a 1.5 T whole-body imager. By use of two-dimensional chemical-shift imaging in combination with slice-selective excitation, well-resolved localized spectra (elements of 38 ml) were obtained within 20 to 35 min from which the homonuclear J coupling constants of ATP could be determined. In myocardium, J gamma beta = 16.03 +/- 0.17 Hz and J alpha beta = 15.82 +/- 0.23 Hz were obtained, while the values in calf muscle were J gamma beta = 17.16 +/- 0.12 Hz and J alpha beta = 16.04 +/- 0.09 Hz. The difference in J gamma beta was significant. According to the literature, a possible reason for greater ATP J coupling constants is a smaller fraction of ATP complexed to magnesium. However, the chemical-shift difference between alpha- and beta-ATP, which is also a measure for the fraction of ATP complexed to magnesium, showed only a small difference in ATP complexation: 88% in myocardium and 90% in calf muscle. This small difference cannot account for the observed difference in J gamma beta.

[Ergospirometric findings in respiration- and QT-controlled pacemakers]. / Spiroergometrische Befunde bei atmungs- und QT-gesteuerten Schrittmachern.

This study used ergospirometry with quantification of gas exchange parameters to analyze the beneficial effects of two sensors for rate responsive pacing: QT-interval and minute ventilation (MV). Bicycle exercise testing was performed with modulating VVIR pacing modes in random sequence. Rate responsiveness effected a mean increase of exercise tolerance of 31.1% in the QT group and 22.6% in the MV group. With both systems maximal oxygen uptake increased by 29.4% (QT) and 28.3% (MV). Oxygen consumption at the anaerobic threshold was improved by 28.3% (QT) and 32.1% (MV). The increase of cardiopulmonary parameters achieved by rate responsiveness was significant (p < 0.05) without significant difference in comparison between both groups. Despite the initially delayed rate increase at the onset of exercise mediated by the QT-interval, the programmed upper rate limit was satisfactorily attained by both principles. Thus, both sensors--minute ventilation and QT-interval--provide an adequate rate modulation in response to exercise and a marked improvement of cardiopulmonary work capacity.

Asymptomatic left ventricular malposition of a transvenous pacemaker lead through a sinus venosus defect: follow-up over 17 years.

The case of a woman with an asymptomatic transvenous left ventricular endocardial pacemaker lead is presented. The chest X ray and the electrocardiogram suggested pacemaker catheter malposition. By two-dimensional echocardiography, the pacemaker lead was shown to cross from the left atrium through the mitral valve and implant in the left ventricular endocardium. The underlying sinus venosus defect and the passage of the electrode through this interatrial communication were directly visualized by transesophageal echocardiography. No thrombotic material attached to the lead was detected corresponding to the patient's uneventful course for surprisingly more than 17 years without evidence of past or present neurological deficiencies or of peripheral embolic phenomena. Thus, no operative correction was performed. Warfarin sodium therapy, however, was initiated.