Anaesthetic considerations for a child with combined Prader-Willi syndrome and mitochondrial myopathy.

We report the anaesthetic management of a child with Prader-Willi syndrome and mitochondrial myopathy for open heart surgery. We used ketamine, fentanyl, rocuronium and caudal morphine together with a propofol infusion with no untoward effects. The implications of both conditions for anaesthesia are discussed.

Reversible shear-mediated platelet dysfunction during cardiac surgery as assessed by the PFA-100 platelet function analyzer.

We undertook this investigation to assess alterations in shear-mediated platelet function during cardiac surgery and to determine the potential for the PFA-100 to predict post-operative bleeding. Platelet aggregation and PFA-100 closure times were determined in 18 adult patients at five intervals during cardiac surgery. Associations between post-operative bleeding and closure times were examined in an additional 58 patients. Statistical analysis consisted of Student's t, Wilcoxon signed rank, and Spearman correlation tests. All results are reported as mean +/- SEM. Collagen/epinephrine closure times were prolonged prior to and throughout surgery. Collagen/adenosine-5'-diphosphate (ADP) closure times were significantly prolonged by heparin administration, 141 +/- 15 s versus 115 +/- 10 s (P = 0.01), and subsequent initiation of cardiopulmonary bypass (CPB), 203 +/- 12 s (P= 0.0001); however, 15 min after protamine administration, closure times returned to near pre-operative values, 138 +/- 12 s (P = not significant). In contrast, platelet aggregation in response to ADP remained impaired in 17 of 19 patients after CPB. Neither ex vivo correction of sample hematocrits nor supplementation with Humate P affected closure times. Positive and negative predictive values for post-CPB collagen/ADP closure times to predict bleeding were 18 and 96%, respectively. These results suggest that factors both intrinsic and extrinsic to the platelet contribute to reversible shear-mediated platelet dysfunction during CPB, and that the PFA-100 may prove useful after CPB to identify patients unlikely to benefit from platelet transfusions.

Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).

Cardiac G protein-coupled receptors that couple to Galpha(s) and stimulate cAMP formation (eg, beta-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have revealed that one of these receptors, the beta(2)-adrenergic receptor (AR), also couples to the inhibitory G protein Galpha(i) (activation of which inhibits cAMP formation). If beta(2)ARs could be shown to couple to Galpha(i) in the human heart, it would have important ramifications, because levels of Galpha(i) increase with age and in failing human heart. Therefore, we investigated whether beta(2)ARs in the human heart activate Galpha(i). By photoaffinity labeling human atrial membranes with [(32)P]azidoanilido-GTP, followed by immunoprecipitation with antibodies specific for Galpha(i), we found that Galpha(i) is activated by stimulation of beta(2)ARs but not of beta(1)ARs. In addition, we found that other Galpha(s)-coupled receptors also couple to Galpha(i), including histamine, serotonin, and glucagon. When coupling of these receptors to Galpha(i) is disrupted by pertussis toxin, their ability to stimulate adenylyl cyclase is enhanced. These data provide the first evidence that beta(2)AR and many other Galpha(s)-coupled receptors in human atrium also couple to Galpha(i) and that abolishing the coupling of these receptors to Galpha(i) increases the receptor-mediated adenylyl cyclase activity.