A Pilot Study of Age-Related Changes in the Sphingolipid Composition of the Rat Sarcoplasmic Reticulum.

BACKGROUND: Muscle strength declines more rapidly than muscle size, manifesting as a loss of muscle quality. One putative contributor to this impairment of muscle quality is impaired sarcoplasmic reticulum (SR) function. OBJECTIVES: The principal objective of this study was to characterize the sphingolipid composition of the SR in adult and aging rat muscles. A secondary, exploratory objective was to test for associations between SR sphingolipids and SR function (i.e., Ca2+ release). DESIGN: Using an animal model, the objectives were evaluated in a pre-clinical, cross-sectional study. SETTING: Data were collected in an academic research laboratory. PARTICIPANTS: Medial gastrocnemius muscles of adult (n=8; 7-8 months) and aged (n=8; 24-25 months), male F344/BN hybrid rats were processed to extract SR. MEASUREMENTS: Sphingolipids in the SR were measured using tandem mass spectrometry. Fatty acid concentrations within the major sphingolipid classes were evaluated via Principal Component Analysis (PCA). In a subset of samples, SR Ca2+ release rates were determined using fluorometric methods, and associations with specific (based on results of PCA) fatty acid concentrations were evaluated. RESULTS: Aging SR showed an overall decline in the ratio of unsaturated to saturated fatty acids. Age-specific differences were observed for hexosylceramide and ceramide-1-phosphate. Within subset of samples with SR Ca2+ release data, a significant negative association between Ca2+ release and C1P18:0 and trends for positive associations with hexCER24:0 and 24:1 were observed. CONCLUSIONS: These preliminary, pre-clinical data suggest that changes in SR sphingolipids may play a role in age-related impairment of muscle function. Further work is needed to explore this hypothesis, as SR sphingolipids may prove a fruitful target for interventions, be they physical (i.e., exercise), nutritional or pharmacological.

Audit of paediatric cardiopulmonary resuscitation.

The causes and outcome of cardiopulmonary arrests were studied in a paediatric hospital over a 12 month period. Forty five resuscitation attempts were made involving 41 children and one adult. Twenty eight (68%) of the children were under 1 year of age and 10 (24%) were neonates. Twenty one (47%) arrests were primarily respiratory and 11 (24%) primarily cardiac in origin. Eighty two per cent of the respiratory arrests had an initially successful outcome, compared with 36% of the cardiac arrests. Overall 70% of cardiopulmonary resuscitation attempts were initially successful. There were no survivors from resuscitation attempts longer than 30 minutes. At 12 months after cardiopulmonary resuscitation 15 (37%) of the children were still alive. The 11 children who had been neurologically normal before the arrest showed no evidence of neurological damage after successful cardiopulmonary resuscitation.

Cavopulmonary connection in repair of atrioventricular septal defect with small right ventricle.

Between February 1991 and May 1992, 9 patients with a nonrestrictive inlet ventricular septal defect or complete atrioventricular septal defect and hypoplasia of the right ventricle underwent successful two-ventricle correction incorporating a bidirectional cavopulmonary anastomosis. Despite a satisfactory early postoperative course, large serous pleural effusions developed in 5 of them between 2 and 6 weeks after operation. Serial echocardiography showed an evolution of flow patterns in the superior vena cava from marked systolic reversal immediately after operation to nearly continuous forward flow into both pulmonary arteries about 6 weeks later. This pattern was consistent with the transition from cardiac-dependent to respiratory-dependent caval flow. The development of pleural effusions appeared to coincide with the loss of systolic caval flow reversal and resolved after establishment of a predominantly respiratory-dependent flow pattern.