A genome-wide search for synaptic vesicle cycle proteins in Drosophila.

The recent completion of the Drosophila genome sequence opens new avenues for neurobiology research. We screened the fly genome sequence for homologs of mammalian genes implicated directly or indirectly in exocytosis and endocytosis of synaptic vesicles. We identified fly homologs for 93% of the vertebrate genes that were screened. These are on average 60% identical and 74% similar to their vertebrate counterparts. This high degree of conservation suggests that little protein diversification has been tolerated in the evolution of synaptic transmission. Finally, and perhaps most exciting for Drosophila neurobiologists, the genomic sequence allows us to identify P element transposon insertions in or near genes, thereby allowing rapid isolation of mutations in genes of interest. Analysis of the phenotypes of these mutants should accelerate our understanding of the role of numerous proteins implicated in synaptic transmission.

Myocardial protection with high-dose beta-blockade in acute myocardial ischemia.

OBJECTIVE: The risk of postoperative cardiac dysfunction is markedly increased by emergency coronary artery bypass grafting in the presence of acute myocardial ischemia. High dose beta-blockade during continuous coronary perfusion has been suggested as an alternative to conventional cardioplegia and this technique has been applied successfully in high risk patients for coronary artery bypass grafting (CABG) surgery. This study compared high dose beta-blockade with esmolol to continuous warm blood cardioplegia in a clinically oriented model of acute left ventricular (LV) ischemia and reperfusion. METHODS: Twelve dogs were subjected to 60 min of regional LV ischemia by left anterior descending branch (LAD) ligation. Cardiopulmonary bypass (CPB) and aortic crossclamp were applied after 45 min of ischemia. Thereafter, high dose beta-blockade during continuous coronary perfusion (ESMO, n = 6) or antegrade continuous warm blood cardioplegia (WBC, n = 6) were maintained for 60 min. Myocardial water content (measured from endomyocardial biopsies using a microgravimetric technique), global LV function (preload recruitable stroke work: PRSW), and regional LV function (echocardiographic wall motion score) were determined at baseline and after weaning from CPB. RESULTS: During aortic crossclamp interstitial edema formation was significantly higher in the WBC group with an average water gain of 2.2 +/- 0.49 vs. 0.76 +/- 0.12% in the ESMO group. Thereafter, edema resolved in both groups, but myocardial water gain remained significantly higher in the WBC group at 60 and 120 min post CPB (0.98 +/- 0.19 and 1.13 +/- 0.32% vs. 0.07 +/- 0.25 and 0.04 +/- 0.08%). Global LV function was significantly higher in the ESMO group at 60 and 120 min post CPB (PRSW 103 +/- 6 and 94.7 +/- 4.6% of baseline vs. 85.3 +/- 4.9 and 74.7 +/- 7.6% of baseline). However, regional LV function showed no significant difference between groups. CONCLUSIONS: High-dose beta-blockade during continuous coronary perfusion may allow the surgeon to utilize the advantages of warm heart surgery, while avoiding the interstitial edema formation and temporary cardiac dysfunction associated with continuous warm blood cardioplegia. In high risk patients such as patients with unstable angina or after failed PTCA, high-dose beta-blockade may be an applicable alternative to cardioplegic arrest.