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Biomedical subjects

J Ledingham

Publications and source records attributed to J Ledingham.

28 records · Page 2Linked to original sources
PubMed1988

Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow.

Previous studies with 31P nuclear magnetic resonance have demonstrated that patients with chronic congestive heart failure often exhibit increased glycolytic metabolism and impaired oxidative phosphorylation in exercising skeletal muscle, but the mechanism for these changes remains unresolved. This study was conducted to determine whether these abnormalities result from impaired blood flow or oxygen delivery. Nine patients with mild-to-moderate congestive heart failure and nine age- and size-matched, healthy control volunteers were studied during repetitive submaximal finger flexion exercise under aerobic and ischemic conditions. Skeletal muscle metabolism was assessed by 31P nuclear magnetic resonance of the flexor digitorum superficialis muscle. During steady-state aerobic exercise at 33% of each subject's predetermined maximum workload, the patients with congestive heart failure exhibited significantly lower pH values (6.65 +/- 0.22 vs. 6.97 +/- 0.09, p less than 0.002) and phosphocreatine concentrations, expressed as [phosphocreatine]/([phosphocreatine] + [inorganic phosphate]) (0.59 +/- 0.14 vs. 0.79 +/- 0.08, p less than 0.002). Similar differences were also present throughout ischemic exercise at the same workload. Based upon these measurements, calculated lactate production and adenosine 5'-triphosphate consumption rates were significantly higher in the patients with congestive heart failure. These results indicate that in many patients with congestive heart failure exercising muscle exhibits increased glycolytic metabolism and appears to be metabolically less efficient in relation to external work performed. These changes cannot be explained by impaired blood flow or oxygen delivery alone.

Adult↗
PubMed1987

31P nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with congestive heart failure.

In patients with congestive heart failure (CHF), exercise limitation correlates poorly with central hemodynamic abnormalities, suggesting that additional abnormalities in skeletal muscle blood flow or metabolism play an important pathophysiologic role. Therefore, muscle metabolism was examined by 31P nuclear magnetic resonance (NMR) at rest and during repetitive bulb squeeze exercise in 11 patients with New York Heart Association class II to IV CHF and 7 age-matched control subjects. Serial spectra were obtained at rest, at 2 levels of exercise and during recovery. At rest, the only abnormal finding was an elevated inorganic phosphate (Pi) concentration (5.0 +/- 1.5 vs 3.6 +/- 0.4 mM, p less than 0.01). At the lower exercise level, phosphocreatine (PCr) utilization, which was followed as the ratio of [PCr]/[( PCr] + [Pi]), was greater (0.36 +/- 0.16 vs 0.53 +/- 0.10, p less than 0.02), and pH fell more rapidly and to a lower value (6.38 +/- 0.25 vs 6.85 +/- 0.17, p less than 0.001). At the higher level of exercise, the patients could not work effectively and the group differences narrowed. Compared with control subjects, acidification was disproportionately greater in relation to PCr depletion in patients, further suggesting excessive dependence on glycolytic metabolism. The Pi peak was prominently double in 5 patients, indicating presence of a population of muscle fibers undergoing unusually active glycolysis. PCr resynthesis, a reflection of oxidative phosphorylation, was delayed in 4 patients. These findings indicate that in many patients with CHF, exercising muscle has marked metabolic changes consistent with impaired substrate availability and altered biochemistry.

Adenosine Triphosphate↗
PubMed1987

Skeletal muscle metabolism in patients with congestive heart failure: relation to clinical severity and blood flow.

We and others have previously demonstrated excessive phosphocreatine (PCr) depletion and acidosis in skeletal muscle during exercise in patients with congestive heart failure (CHF). In the present study, we performed serial measurements of PCr and pH during gradually incremental flexor digitorum superficialis exercise in 22 patients with CHF and 11 age-matched controls to determine: (1) whether abnormalities were present at the same relative workloads (a comparison that would at least partially compensate for differences in muscle mass), (2) the temporable course of the metabolic changes, (3) the relationship of the metabolic findings to clinical variables, and (4) the relationship of the metabolic abnormalities to forearm blood flow. The patients with CHF had significantly lower [PCr] and pH at all submaximal levels of exercise, and these abnormalities were apparent from the onset of low-level exercise. There was considerable heterogeneity among the patients with CHF with respect to the metabolic findings, with 14 of 22 exhibiting either PCr or pH values more than 2 SDs below normal. Patients whose capacity was more limited during the protocol had lower [PCr], and especially pH, at low loads than did other patients with CHF or the control subjects. The more symptomatic patients and those with more limited bicycle exercise tolerance also had lower pH values. In contrast, there were no significant differences in forearm blood flow between the patients and controls and no relationship between forearm blood and either clinical variables or the metabolic findings. These results indicate that skeletal muscle metabolic abnormalities are present in many patients with CHF and that they are not primarily due to either muscle atrophy or impaired blood flow. These changes may explain in part the marked heterogeneity of symptom status and exercise capacity of patients with similar degrees of cardiac dysfunction.

Blood Flow Velocity↗
PubMed1986

The pineal gland is very large and active in newborn antarctic seals.

The pineal gland of newborn elephant seals and Weddell seals is larger than in adult females. The gland is considerably larger at birth in Weddell seals than in elephant seals. The former experience greater extremes of temperature. Plasma melatonin concentrations in excess of 2000 pg/ml were recorded in the first days of life, compared with 20-50 pg/ml in adults.

Animals↗
PubMed1986

Cardiac and renal hyperplasia in newborn genetically hypertensive rats.

Newborn spontaneously hypertensive rats (SHR), compared with Wistar-Kyoto (WKY) controls, usually show cardiac and renal hyperplasia. To determine whether these anomalies are common to genetically hypertensive rats, we examined newborn rats from models of essential hypertension (Kyoto, Montreal, Dunedin and Lyon strains of hypertensive rats), renal hypertension (Milan strain of hypertensive rats) and experimental hypertension [deoxycorticosterone acetate (DOCA)-salt hypertensive Wistar rats]. The hearts, kidneys and livers of these newborns were collected on site at various centres and sent to Montreal for protein and DNA determinations. The results showed that protein and DNA, corrected for body weight in models of essential hypertension, were increased in the heart and kidney, and normal or decreased in the liver at birth. This pattern differed in offspring of the Milan strain (renal hypertension) and of DOCA-salt hypertensive animals (experimental hypertension). Since cardiac and renal hyperplasia associated with the hypertensive trait in four different genetic models of spontaneous hypertension was distinct from that observed in renal and experimental hypertension, it is conceivable that a specific cardiovascular growth pattern is a reflection not of a simple linkage or consequence, but of a causal association with spontaneous hypertension.

Animals↗
PubMed1986

Electrolytes and spontaneous genetic hypertension in rats.

Electrolytes are involved to a greater or lesser extent in the hypertension of probably all the inbred strains but it is difficult to sort out whether the involvement is primary or secondary and the detected abnormalities differ in the various strains. The fundamental faults are still elusive, except perhaps in the Dahl salt-sensitive rats, which appear to have a form of mineralocorticoid hypertension. Sodium and calcium appear to be the electrolytes most closely implicated in the pathogenesis of hypertension but potassium, magnesium and chloride should not be neglected. More data are needed. Knowledge gained from rat studies is useful in the context of both basic physiology and human hypertension.

Animals↗
PubMed1985

Shrinking lungs, diaphragmatic dysfunction, and systemic lupus erythematosus.

One of the more unusual respiratory manifestations of systemic lupus erythematosus is "shrinking lungs." We report a patient with this syndrome and provide evidence for this being due to diaphragm dysfunction. Significant improvement occurred after albuterol therapy, providing new possibilities in the treatment of this syndrome. This is the first report in humans supporting animal work demonstrating that beta-agonists can improve diaphragmatic performance.

Adolescent↗
PubMed1978

Inhibition of active-transport sodium-potassium-A.T.P.ase by myeloma protein.

Patients with multiple myeloma excrete immunoglobulin light chain (Bence-Jones protein) in the urine. Light chain accumulates in the nephron, and this may result in renal disease, which accounts for the death of between 1 in 4 and 1 in 7 patients with multiple myeloma. Myeloma light chain inhibits transport of paraaminohippurate in the kidney. Evidence is presented here that light chain affects renal transport by inhibiting the active-transport enzyme, ouabain-sensitive Na-K-A.T.P.ase. As a direct consequence, renal A.T.P. content and the maximum rate of gluconeogenesis from lactate are enhanced in the presence of light chain.

Adenosine Triphosphatases↗