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Biomedical subjects

B Rajagopalan

Publications and source records attributed to B Rajagopalan.

At least 19 recordsLinked to original sources
PubMed1998

Mitral regurgitation: impaired systolic function, eccentric hypertrophy, and increased severity are linked to lower phosphocreatine/ATP ratios in humans.

BACKGROUND: A number of phosphorus (31P) magnetic resonance spectroscopy (MRS) studies link alterations of high-energy phosphate metabolism in valvular disease and cardiomyopathy to the clinical severity of heart failure. However, correlations between MRS and indexes of ventricular dysfunction are inconclusive to date. We examined whether changes in 31P MRS are associated with the impaired contractility, which predisposes to chronic congestive heart failure in patients with mitral regurgitation. METHODS AND RESULTS: Thirteen normal control subjects and 22 patients with echocardiographically characterized chronic mitral regurgitation were studied by 31P MRS. The apical phosphocreatine-to-ATP ratio (PCr/ATP) was lower in severe disease (P<.02) and those on therapy (n=13, 1.29+/-0.29, P<.01) in contrast to control subjects (n=13, 1.61+/-0.3). Compared to those with mild mitral regurgitation, patients with more severe incompetence had lower mean myocardial PCr/ATP ratios (mild, n=6, 1.73 [0.17], P<.05 and P<.01; moderate, n=5, 1.49 [0.18], P<.05; and severe, n=1, 1.29 [0.32], P<.01). PCr/ATP in those referred for mitral valve replacement was lower (n=8, 1.17+/-0.23) although not significantly decreased compared with the ratio among subjects on medical therapy alone (n=5, 1.48+/-0.29). PCr/ATP correlated with the end-systolic diameter (r2=.7, P<.001), end-diastolic diameter (r2=.32, P<.05), left ventricular wall thickness (r2=.38, P<.01), left atrial dimension (r2=.36, P<.05), and derived measurements such as the percent fractional shortening (2=.5, P<.01), and left ventricular mass/body surface area (r2=.5, P<.001) but not with wall stress. CONCLUSIONS: These results demonstrate that abnormalities of PCr/ATP in mitral regurgitation are related to disease severity as measured by dimensional indexes of left ventricular dilatation. They suggest that impaired high-energy phosphate metabolism is a marker of hypertrophy and heart failure.

Adenosine Triphosphate↗
PubMed1997

Abnormal skeletal muscle bioenergetics in familial hypertrophic cardiomyopathy.

OBJECTIVE: To determine the skeletal muscle metabolic manifestations of familial hypertrophic cardiomyopathy. DESIGN: A case-control study. SETTING: 31P magnetic resonance spectroscopy of the calf muscle was performed on volunteers from a centre specialising in familial hypertrophic cardiomyopathy. PATIENTS: Five patients with abnormal beta myosin heavy chain protein in cardiac and skeletal muscle and five patients with a troponin T abnormality in cardiac muscle were compared with healthy controls. RESULTS: High energy phosphate metabolism in vivo was examined in a non-invasive manner. In resting muscle, the beta myosin heavy chain group had a higher ratio of phosphocreatine to ATP concentration (4.51 (SD 0.17)) than either the troponin T group (3.88 (0.42)) or controls (n = 16; 4.04 (0.40)). Exercise duration was reduced compared to controls, and during the fourth minute of exercise phosphocreatine depletion and muscle acidification were greater in both patient groups. After exercise, the recovery of phosphocreatine-an index of oxidative metabolic capacity of the muscle-was slower in the beta myosin heavy chain group (mean half time 0.65 (0.08) minutes) than in the troponin T group (0.60 (0.17) minutes) or controls (0.48 (0.14) minutes). CONCLUSIONS: Exercise metabolism was abnormal in both groups of subjects, and the affected contractile protein determined the metabolic changes in muscle at rest and during recovery. In patients with abnormal beta myosin heavy chain protein, there was a decrease in oxidative capacity consistent with the reduction in mitochondria reported in muscle biopsy studies of similar patients.

Adenosine Triphosphate↗
PubMed1997

Hypomelanosis of Ito with unusual associations.

Hypomelanosis of Ito (HOI) is a neurocutaneous disorder which clinically is a well-characterised disease, in which chromosomal instability may be a component. Various neurological and other non-cutaneous malformations have been reported in association with the characteristic swirling pattern of hypopigmentation. We report two cases of this rare condition, one with hitherto unreported associations.

Abnormalities, Multiple↗
PubMed1996

Skin lesions in HIV-positive and HIV-negative patients in south India.

BACKGROUND: Various dermatologic conditions have been reported to occur with increased frequency in human immunodeficiency virus (HIV)-positive individuals, but there are only a few studies comparing the prevalences of skin diseases in HIV-positive patients with those in matched HIV-negative controls. METHODS: Skin lesions in 129 HIV-positive patients and 258 HIV-negative controls were studied prospectively over an 18-month period from October 1991 to March 1993. RESULTS: Oral candida, tinea cruris, and ichthyosis were significantly more common in HIV-positive patients compared to controls. Several other dermatologic conditions were found only in the HIV-positive group. CONCLUSIONS: The pattern of skin lesions in Indian patients with HIV infection may be different from that in the West.

Adult↗
PubMed1996

Magnetic resonance spectroscopy in congenital heart disease.

OBJECTIVE: To determine the feasibility of studying myocardial and skeletal muscle bioenergetics using 31P magnetic resonance spectroscopy (MRS) in babies and young children with congenital heart disease. SUBJECTS: 16 control subjects aged 5 months to 24 years and 18 patients with CHD, aged 7 months to 23 years, of whom 11 had cyanotic CHD, five had cardiac failure, and two had had a Senning procedure. DESIGN: 31P MRS was carried out using a 1.9 Tesla horizontal 65 cm bore whole body magnet to study the myocardium in 10 patients and skeletal muscle (gastrocnemius) in 14 patients, eight of whom were exercised, together with appropriate controls. RESULTS: In hypoxaemic patients, in skeletal muscle at rest intracellular pH (pHi) was abnormally high [7.06 (SEM 0.04) v 7.04 (0.05), P < 0.01] and showed a positive correlation with haemoglobin (P < 0.03). On exercise, hypoxaemic patients fatigued more quickly but end-exercise pHi and phosphocreatine recovery were normal, implying that an equivalent but smaller amount of work had been performed. End-exercise ADP concentration was lower. On recovery, the initial rate of phosphocreatine resynthesis was low. Skeletal muscle bioenergetics were within normal limits in those in heart failure. In the myocardium, the phosphocreatine/ATP ratio was similar in controls and hypoxaemic subjects, but low in those in heart failure. CONCLUSIONS: In heart failure, the myocardial phosphocreatine/ATP ratio was reduced, as in adults, while resting skeletal muscle studies were normal. By contrast, hypoxaemic children had normal myocardial bioenergetics, but showed skeletal muscle alkalinity, and energy reserves were more readily depleted on exercise. On recovery, the initially slow phosphocreatine resynthesis rate reflects a low rate of mitochondrial ATP synthesis, probably due to an inadequate oxygen supply. 31P MRS offers a safe, non-invasive method of studying myocardial and skeletal muscle bioenergetics in children as young as 5 months.

Adenosine Triphosphate↗
PubMed1996

Abnormalities in exercising skeletal muscle in congestive heart failure can be explained in terms of decreased mitochondrial ATP synthesis, reduced metabolic efficiency, and increased glycogenolysis.

OBJECTIVE: To distinguish between the effects of reduced oxidative capacity and reduced metabolic efficiency on skeletal muscle bioenergetics during exercise in patients with congestive heart failure. DESIGN AND PATIENTS: Patients were studied by 31P magnetic resonance spectroscopy during aerobic exercise and recovery, and results compared with controls. RESULTS: In flexor digitorum superficialis muscle (26 patients) there was a 30% decrease in oxidative capacity compared with control (mean (SE) 36 (2) v 51 (4) mM/min) and also a 40% decrease in "effective muscle mass" (5 (1) v 9 (1) arbitrary units), probably at least partly the result of reduced metabolic efficiency. Both contribute to increased phosphocreatine depletion and intracellular acidosis during exercise. However, an increased concentration of ADP (an important mitochondrial regulator) during exercise permitted near-normal rates of oxidative ATP synthesis. Results were similar in gastrocnemius muscle (20 patients), with a 30% decrease in maximum oxidative capacity (29 (4) v 39 (3) mM/min) and a 65% decrease in effective muscle mass (5 (1) v 13 (2) arbitrary units). Exercise training improved maximum oxidative capacity in both muscles, and in gastrocnemius effective muscle mass also. CONCLUSIONS: Skeletal muscle exercise abnormalities in patients with congestive heart failure results more from decreased metabolic efficiency than from the abnormalities in mitochondrial oxidation. Both decreased efficiency and defective mitochondrial oxidation result in an increased activation of glycogen phosphorylase, and may be improved by exercise training.

Adenosine Diphosphate↗
PubMed1995

Haemodynamic consequences of embolizing aneurysms: a transcranial Doppler study.

Twenty patients with aneurysms were studied with transcranial Doppler before, during and after endovascular treatment with Guglielmi detachable coils. Catheterization of the anterior circulation decreased middle cerebral artery velocities by 15-20%. Inserting coils into the aneurysms increased pulsatility indices modestly, reflecting a stiffening of the cerebral circulation. Pre- and posttreatment velocities were not significantly different, and there was no evidence of coil embolization precipitating vasospasm. The haemodynamic stability, seen during and after therapy, suggests that coil embolization may prove a safe alternative way of treating acutely ruptured aneurysms.

Adult↗
PubMed1995

Rat skeletal muscle metabolism in experimental heart failure: effects of physical training.

Skeletal muscle metabolic abnormalities exist in chronic heart failure. The influence of physical training on muscle metabolism after myocardial infarction was studied in a rat model. 31P magnetic resonance spectroscopy and enzyme assays were performed in Wistar rats 12 weeks after coronary artery ligation. Infarcted rats were allocated randomly to either 6 weeks of training or non-training. Spectra were collected from the calf muscles during sciatic nerve stimulation at 2 Hz. Fibre typing and enzymatic assays were performed on the muscles of the contralateral non stimulated leg. Post-mortem rats were also divided into severe and moderate heart failure according to the lung weight per body weight. At 200 g twitch tension, phosphocreatine and pH were found to be significantly lower in the non-trained severe heart failure group compared with the other groups. Phosphocreatine recovery half-time was significantly longer in the non-trained group with severe heart failure and correlated with the citrate synthase activity in the muscle. The training did not induce a change in the enzyme activities in the infarcted animals with moderate heart failure but did correct the lower citrate synthase activity in the non-trained severe heart failure animals. This normalization of muscle metabolism was achieved by training without any change in calf muscle mass, making atrophy unlikely to be the sole cause of the metabolic changes in heart failure. Training in rats with severe heart failure can reverse the abnormalities of skeletal muscle metabolism, implicating decreased physical activity in the aetiology of these changes.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1995

Abnormal ATP turnover in rat leg muscle during exercise and recovery following myocardial infarction.

OBJECTIVE: Clinical and animal studies show increased acidification of skeletal muscle during exercise in heart failure, implying increased anaerobic metabolism, and impaired recovery from exercise, implying defective oxidative function. This study aimed to define the quantitative relationship between these changes in exercise and recovery and relate skeletal muscle bioenergetics to cardiovascular function. METHODS: Wistar rats were studied four weeks after myocardial infarction or a sham operation. 31P magnetic resonance spectroscopy of the hind leg muscle was used to estimate rates of oxidative and non-oxidative ATP synthesis from changes in pH and phosphocreatine concentration during sciatic nerve stimulation and to estimate the maximum rate of mitochondrial ATP synthesis from the kinetics of phosphocreatine recovery after stimulation. RESULTS: Following myocardial infarction, cardiac function was abnormal, with evidence of left ventricular hypertrophy, failure, and diminished arterial pressure. There was impaired phosphocreatine recovery, suggesting an approximate halving of the maximum rate of mitochondrial ATP synthesis. CONCLUSIONS: The response to exercise of the infarct group was abnormal and was quantitatively consistent with the reduced maximum rate of mitochondrial ATP synthesis inferred from recovery, the oxidative deficit during exercise being made up by increased glycogenolysis, causing sufficient acidification to prevent an appropriate increase in [ADP].

Adenosine Triphosphate↗
PubMed1994

Phosphorus-31 magnetic resonance spectra reveal prolonged intracellular acidosis in the brain following subarachnoid hemorrhage.

Subarachnoid hemorrhage may be complicated by cerebral ischemia which, though reversible initially, can progress to an irreversible neurological deficit. 31P magnetic resonance spectroscopy, which can determine intracellular pH and thus detect areas of ischemia noninvasively, was applied to 10 patients on 30 occasions, at various times after subarachnoid hemorrhage. In 5 of them, there were focal areas of the brain in which the intracellular pH was reduced to < 6.8 compared with the normal range of 7.05 +/- 0.05. Consciousness was impaired in 4 of these patients. Repeat studies in these 4 patients showed that intracellular pH remained abnormally low for several days but eventually returned toward normal. The return of intracellular pH to normal paralleled an improvement in clinical condition in each case. In the fifth patient with lowered regions of intracellular pH, there had been an impaired level of consciousness and a transient focal deficit prior to the single study. In the other 5 patients there were no areas of reduced pHi even though in 3 of them there was intraventricular or cisternal blood shown on brain computerized tomography. In 2 of these 3 patients there were no abnormal neurological signs at the time of the magnetic resonance study. The third patient had a dense and persistent hemiparesis. The remaining two patients had no abnormal neurological signs at any stage. We suggest that the areas of acidosis may reflect ischemia which is potentially reversible. Since the technique is noninvasive, sequential 31P magnetic resonance spectroscopy of the brain offers a method of detecting cerebral ischemia and, more importantly, of assessing methods of treatment.

Acidosis↗
PubMed1994

Metabolic abnormalities in skeletal muscle after myocardial infarction in the rat.

1. The effect of experimental myocardial infarction on exercise and recovery of rat skeletal muscle was studied using 31P n.m.r. 4 weeks post-operatively. 2. Myocardial infarction (12 +/- 3% of left ventricular volume), insufficient to produce haemodynamic manifestations of heart failure, was without significant effect on exercise bioenergetics of skeletal muscle. 3. Citrate synthase activity was reduced by 17% in the infarcted animals and there was a marked slowing of the rate of phosphocreatine recovery after infarction (half-time 0.7 +/- 0.1 min to 1.6 +/- 0.2 min) in the absence of evidence of left ventricular failure or hypertrophy. 4. The study of recovery bioenergetics could provide a more sensitive measure of mitochondrial function than exercise, where no bioenergetic abnormality was detected. 5. Myocardial infarction can produce evidence of mitochondrial abnormality in skeletal muscle in the absence of haemodynamic compromise.

Adenosine Diphosphate↗
PubMed1994

Training partially reverses skeletal muscle metabolic abnormalities during exercise in heart failure.

Using 31P-magnetic resonance spectroscopy during and after exercise, we studied whether forearm metabolic responses to exercise were improved by 1 mo of training in 10 males with heart failure. In the control (untrained) arm, there were no changes in any of the measured variables. In the trained arm, maximal voluntary contraction increased 6% (P = 0.05). During incremental exercise, duration increased 19% (P < 0.05) and submaximal responses improved for pH (6.78 +/- 0.13 pretraining vs. 6.85 +/- 0.17 posttraining; P < 0.01) and PCr/(PCr+Pi) (where PCr is phosphocreatine; 0.48 +/- 0.09 pretraining vs. 0.52 +/- 0.07 posttraining; P < 0.01). The PCr resynthesis rate increased by 48% (P < 0.01), and estimated effective maximal rate of mitochondrial ATP synthesis increased by 37% (P < 0.05). Endurance exercise duration increased by 67% (P < 0.01), and submaximal levels of PCr/(PCr+Pi) (P < 0.05) and pH (P = 0.07) improved. The PCr resynthesis rate (P < 0.01) and the effective maximal rate of mitochondrial ATP synthesis (P < 0.05) also improved. These findings document that impaired oxidative capacity of skeletal muscle can be improved by local muscle training in heart failure, which is compatible with the hypothesis that a part of the abnormality present in heart failure may be due to inactivity.

Adenosine Triphosphate↗
PubMed1994

Effects of cardiac transplantation on bioenergetic abnormalities of skeletal muscle in congestive heart failure.

BACKGROUND: Patients with advanced heart failure have bioenergetic abnormalities of skeletal muscle metabolism during exercise. Using 31P magnetic resonance spectroscopy, we sought to determine whether skeletal metabolic responses to exercise are normalized by orthotopic cardiac transplantation. METHODS AND RESULTS: Four groups were studied: healthy normal volunteers (n = 9), subjects awaiting heart transplantation (n = 10), subjects < 6 months (mean, 4 months) after transplant (n = 9), and subjects > 6 months (mean, 15 months) after transplant (n = 8). None of the posttransplant patients had biopsy evidence of rejection at the time of study. There were no significant differences in age, preoperative functional class, or symptom duration among the three patient groups. Metabolic responses were monitored in the dominant arm during incremental weight pull exercise and 10 minutes of recovery by 31P magnetic resonance spectroscopy, with measurement of pH and the phosphocreatine (PCr)/(PCr + inorganic phosphate [Pi]) ratio, an index of PCr concentration. In addition, based on recovery data, the rate of PCr resynthesis was calculated as a measure of oxidative metabolism that is independent of work level, recruitment, or muscle mass, and the effective maximal rate of mitochondrial ATP synthesis (Vmax) was determined. Analysis was by ANOVA. There were no differences between groups in pH or PCr/(PCr + Pi) at rest. Compared with the normal control group, the pretransplant group had a decreased exercise duration (11.3 +/- 2.5 versus 15.0 +/- 1.3 minutes, P = .02), a lower submaximal exercise PCr/(PCr + Pi) ratio (0.58 +/- 0.11 versus 0.76 +/- 0.08, P < .05), a reduced PCr resynthesis rate (13 +/- 6 versus 22 +/- 9 mmol/L per minute, P < .05), and a lower calculated Vmax (26 +/- 14 versus 53 +/- 26 mmol/L per minute, P < .05). In the group studied early after transplantation, all the changes noted in the pretransplant group persisted and were if anything somewhat worse. In the group studied late after transplantation, there was a significant improvement in the PCr resynthesis rate compared with the early-posttransplant group (27 +/- 6 late versus 15 +/- 6 mmol/L per minute early, P < .05) and statistically nonsignificant trends toward improvements in submaximal exercise pH (6.86 +/- 0.24 late versus 6.72 +/- 0.24 early) and submaximal PCr/(PCr + Pi) ratio (0.56 +/- 0.14 late versus 0.44 +/- 0.15 early) and Vmax (45 +/- 21 late versus 33 +/- 15 mmol/L per minute early). However, compared with normal subjects, exercise duration and submaximal PCr/(PCr + Pi) were still reduced in the late-posttransplant group. CONCLUSIONS: Despite successful heart transplantation, skeletal muscle abnormalities of advanced heart failure persist for indefinite periods, although partial improvement occurred at late times. The persistent abnormalities may contribute to the reduced exercise capacity that is present in most patients after transplantation.

Energy Metabolism↗
PubMed1994

Uraemic muscle metabolism at rest and during exercise.

The effect of chronic renal failure and the accompanying hyperphosphataemia on muscle metabolism at rest and during exercise was examined in a group of undialysed patients suffering from chronic renal failure. 31P magnetic resonance spectroscopy was used to measure intracellular high-energy phosphates in resting muscle as well as changes in the concentrations of these metabolites during exercise and recovery from exercise. In resting muscle, cell [Pi] rose with plasma [Pi], and free [ADP] changed such that the phosphorylation potential ([ATP]/([ADP] x [Pi])), which probably controls mitochondrial oxidation in resting muscle, was preserved despite a wide variation in cell [Pi]. The maximal oxidative capacity of the muscle was calculated from the kinetics of phosphocreatine recovery after exercise. There was no reduction in uraemic muscle oxidative capacity compared to control muscle. This contrasts with our finding of a reduction in the mitochondrial oxidative capacity in the muscle of patients established on dialysis, suggesting that a substance crucial for mitochondrial function or substrate supply to mitochondria is removed by dialysis.

Adenosine Diphosphate↗