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GATA-4 is a novel transcription factor expressed in endocardium of the developing heart.

We have isolated and characterized Xenopus cDNA clones for a new transcription factor that represents an early marker for the developing heart. The cDNAs encode a protein that we have designated GATA-4; it contains the highly conserved DNA-binding domain that characterizes this family of cell-type restricted transcriptional activators. Whole-embryo in situ analysis of Xenopus embryos demonstrates that the GATA-4 gene is transcribed in presumptive cardiac ventral mesoderm at the time that bilateral progenitors fuse and form the cardiac tube. GATA-4 is therefore the earliest molecular marker of cardiogenesis yet characterized. By stage 30, the GATA-4 mRNA is expressed in the developing atria and ventricles; at stage 38, cross-sections reveal that the gene is active in the endocardial layer, but not in myocardium. By stage 40, GATA-4 message is detected in the great vessels. In the adult frog, the GATA-4 gene is highly transcribed in heart and gut; lower levels of message are detected in various endoderm-derived tissues and gonads. Expression in the stomach is largely confined to the epithelium. The GATA-4 gene is first activated at stage 11; mRNA is initially present throughout the marginal zone of explants and later partially localized to the ventral marginal zone. GATA-4 mRNA is also detected at high levels in cultured endodermal explants derived from the vegetal region of early embryos. In mesoderm induction experiments, GATA-4 transcription is not induced in animal caps treated with activin or bFGF. The GATA-4 gene may provide a new early marker for studying the inductive processes that lead to the formation of the cardiovascular system and for the specification of the endocardial lineage.

Amino Acid Sequence↗

Epicardial ablation with cooled tip catheter close to the coronary arteries is effective and safe in the porcine heart if the ventricular potential is being monitored in the epicardium and endocardium.

BACKGROUND: Transthoracic epicardial ablation can be an alternative to conventional treatment for critical pathways of ventricular tachycardia located in the epicardium. However, the usefulness and safety of epicardial ablation close to the coronary arteries (CA) is not clear. The purpose of the present experimental animal study was to analyze the efficacy and safety of epicardial radiofrequency (RF) ablation close to the CA. METHODS AND RESULTS: Of the left ventricle-epicardium ablated sites, 35 lesions (20 with cooling and 15 without cooling) were close to the CA (left anterior descending artery < or = 15 mm) and 33 lesions (23 with cooling and 10 without cooling) were further from the CA. For sites close to the CA, epicardial ablation was effective in 77% (15/20) with cooling and in 40% (6/15) without cooling. There was a significant difference of effective ablation between with cooling and without cooling (p < 0.05). For cooling, epicardial lesion size could be predicted by the change of endocardial ventricular potential using a basket catheter. No damage to major epicardial arteries was detected when the catheter tip was positioned 5 mm away from the CA. CONCLUSIONS: Close to the CA, RF ablation with cooling is more effective than RF without cooling and is safe if the ablation sites are located 5 mm away from the major CA.

Animals↗

Is communication to endocardium necessary for angiogenesis in transmyocardial laser revascularization?

There is evidence of angiogenesis being induced after transmyocardial laser revascularization (TMLR), although the precise mechanism has not been fully elucidated. This study was designed to examine whether or not blood flow from the left ventricle through the channels is essential for angiogenesis following TMLR. Ten dogs underwent the creation of two types of laser channels in the left ventricle: 1) a transmural channel (TMC), which penetrates the myocardium, and 2) a non-transmural channel (NTMC), which does not open to the epicardium. The animals were sacrificed on the 28th postoperative day and the vascular density was examined. Vessels with smooth muscle media were seen within or around the channel remnant. The vessel density was compared between TMC and NTMC. The outer and inner halves of the myocardium in the TMC region were compared in the same way. The density of vessels within and around the channel remnants was significantly higher in TMC than in NTMC (1.439 versus 0.685 vessels/microscopic visual field (mvf=40X); p=0.0025). The vascular density was significantly higher in the region adjacent to TMC than in a distant region (>3 mm from the channel center). The vascular density was significantly higher in the outer half than in the inner half of the myocardium (1.730 versus 1.180 vessels/mvf: p=0.0459). These findings demonstrate that communication to the left ventricular lumen enhances angiogenesis of TMLR, although blood flow in the channel did not exist 4 weeks after TMLR and angiogenesis tended to be more highly enhanced in the outer half than in the inner half of the myocardium.

Animals↗