[Therapeutic strategies for postinfarction left ventricular free wall rupture].

We treated 93 patients who developed left ventricular free wall rupture after acute myocardial infarction. Medical management including pericardial drainage was performed in 78 patients (84%), but 67 of them died. All 11 surviving patients showed an oozing type rupture. Surgical repair was performed in 15 patients (16%). As a result, 9 patients died and 6 survived. All but 1 of the patients who died presented with a blow-out rupture. Blow-out type rupture occurred in 3 and oozing type rupture in 3 of the surviving patients. One patient with blow-out type rupture underwent implantation of a left ventricular assist device following percutaneous cardiopulmonary support (PCPS), because of low output syndrome after the operation. The device was successfully removed 7 days after implantation. In all of the 3 patients with oozing type rupture, sutureless technique was successfully performed using fibrin-glue or fibrin-glue sheet fixation. After a mean follow-up period of 7 years after operation, 5 of 6 are still alive. To improve the clinical outcome of left ventricular free wall rupture, it is important for surgeons to closely liaise with physicians, to perform surgical repair as soon as possible, and to utilize a circulatory support system after operation. Therefore, we developed a new PCPS system compatible with emergency cardiac surgery and a new left ventricular assist system draining via the left ventricle.

Changes in expression of the DNA repair protein complex DNA-dependent protein kinase after ischemia and reperfusion.

Reperfusion of ischemic tissue causes an immediate increase in DNA damage, including base lesions and strand breaks. Damage is reversible in surviving regions indicating that repair mechanisms are operable. DNA strand breaks are repaired by nonhomologous end joining in mammalian cells. This process requires DNA-dependent protein kinase (DNA-PK), composed of heterodimeric Ku antigen and a 460,000 Da catalytic subunit (DNA-PKcs). In this study, a rabbit spinal cord model of reversible ischemia was used to demonstrate the effect of acute CNS injury on the activity and expression of DNA-dependent protein kinase. The DNA-binding activity of Ku antigen, analyzed by an electrophoretic mobility shift assay, increased during reperfusion after a short ischemic insult (15 min of occlusion), from which the animals recover neurological function. After severe ischemic injury (60 min of occlusion) and reperfusion that results in permanent paraplegia, Ku DNA binding was reduced. Protein levels of the DNA-PK components-Ku70, Ku80, and DNA-PKcs-were monitored by immunoblotting. After 60 min of occlusion, the amount of DNA-PKcs and the enzyme poly(ADP-ribose) polymerase (PARP) decreased with the same time course during reperfusion. Concurrently 150 and 120 kDa fragments were immunostained by an anti-DNA-PKcs monoclonal antibody. This antibody was shown to cross-react with alpha-fodrin breakdown products. The 120 kDa fodrin peptide is associated with caspase-3 activation during apoptosis. Both DNA-PKcs and PARP are also substrates for caspase-3-like activities. The results are consistent with a model in which after a short ischemic insult, DNA repair proteins such as DNA-PK are activated. After severe ischemic injury, DNA damage overwhelms repair capabilities, and cell death programs are initiated.

Activation of nuclear factor-kappaB in the rabbit spinal cord following ischemia and reperfusion.

The transcription factor NF-kappaB is a ubiquitously expressed inducible regulator of a broad range of genes. Recent studies have shown that activation of NF-kappaB predominantly is associated with protecting cells from apoptosis, but in some cell models, it is associated with promoting cell death. We used a rabbit spinal cord model of reversible ischemia to determine whether NF-kappaB was activated by ischemic and reperfusion injury. DNA binding activity of NF-kappaB was analyzed by an electrophoretic mobility shift assay in animals subjected to varying durations of ischemia and reperfusion. A low level of constitutive NF-kappaB DNA binding was detected in normal lumbar spinal cord extracts. Animals subjected to a short ischemic insult of 15 min, from which they usually recover neurologic function, had a significant increase in the amount of active NF-kappaB in nuclear extracts after 18 h reperfusion. There was no change in nuclear NF-kappaB DNA binding in animals occluded for 60 min that are permanently paraplegic and exhibit extensive neuropathological damage. The amount of deoxycholate-releasable NF-kappaB sequestered in the cytosol, however, decreased after 18 h reperfusion in rabbits occluded for 60 min. This correlated with a decrease in the amount of RelA(p65) NF-kappaB subunit. The results suggest that activation of NF-kappaB after a limited ischemic injury may participate in a neuroprotective response and not in cell death.

[Pitfalls in echocardiographic diagnosis of mitral bileaflet prolapse].

Preoperative echocardiography provides good planning information for successful repair of mitral valve regurgitation, but identifying the prolapse of both the anterior and posterior leaflets is sometimes difficult. To clarify the cause of this problem, preoperative echocardiographic findings and intraoperative observations of the prolapse were analyzed in 124 patients with non-rheumatic pure mitral regurgitation. In 48 patients with final diagnoses of bileaflet prolapse, 16 (33%) were considered to have only single leaflet prolapse before the operation. Anterior leaflet prolapse was overlooked in 14, and prolapse of either of its commissural segments was the least detectable by echocardiography. Chordal rupture was seen more in the posterior leaflet than in the anterior leaflet. Movement of the anterior leaflet may be influenced by a prolapsed and hypermobile posterior leaflet and/or regurgitant jet flow caused by the posterior leaflet prolapse.

Identification of proximal sequence element nucleotides contributing to the differential expression of variant U4 small nuclear RNA genes.

The two U4 genes in the chicken genome code for distinct sequence variants of U4 small nuclear RNA that are differentially expressed during development. Whereas U4B RNA is constitutively expressed, U4X RNA is specifically down-regulated relative to U4B in a tissue-specific manner during development. To investigate mechanisms controlling the differential expression of the U4B and U4X genes, chimeric U4 genes were constructed and their transcriptional activities assayed by injection into Xenopus oocytes or by transfection of CV-1 cells. The proximal regulatory region of the U4B gene and the enhancers of both the U4B and U4X genes functioned efficiently in each expression system. However, the proximal region of the U4X gene was inactive. To localize and identify the responsible nucleotides, reciprocal point mutations were introduced into the U4X and U4B proximal regulatory regions. The results indicate that the U4X gene contains a suboptimal proximal sequence element, and that this results primarily from the identities of the nucleotides at positions -61 and -57 relative to the transcription start site.