Aortic root replacement with a stentless bioprosthesis in osteogenesis imperfecta.

Herein is reported a successful surgical case of aortic root replacement for aortic regurgitation in a patient with osteogenesis imperfecta. A 37-year-old male, who had been diagnosed as osteogenesis imperfecta of type IA, underwent mitral valve repair for mitral regurgitation. Severe aortic regurgitation developed four years after surgery. A stentless bioprosthesis was implanted using the full root technique for fear of progressive dilatation of the sinus of Valsalva or aortic dissection, which is well documented in osteogenesis imperfecta. Aortic root replacement with a stentless bioprosthesis for aortic regurgitation represents an alternative procedure of choice for a patient with osteogenesis imperfecta.

Two surgical cases of acute aortic dissection in pregnancy with marfan syndrome.

We describe 2 surgical cases of acute aortic type A dissection during pregnancy in women with Marfan syndrome. Both of them underwent emergency aortic root replacement under deep hypothermia; one patient was in her 21(st) week of pregnancy and the other was treated 1 day after a normal delivery. The patients experienced fair postoperative courses, but intrauterine fetus death was confirmed in the first case.

Cardioplegia and diazoxide modulate STAT3 activation and DNA binding.

BACKGROUND: Previously, we have shown that magnesium supplemented potassium (DSA) cardioplegia and DSA containing diazoxide (DSA+DZX) significantly decrease apoptosis after ischemia. The mechanism for this enhanced cardioprotection was unknown, but we believed that alterations in signal transducers and activators of transcription (STATs) may play a role. To investigate this hypothesis, we examined the effects of DSA and DSA+DZX cardioplegia on STAT1/3 phosphorylation and DNA binding in the in situ blood perfused pig heart model. METHODS: Pigs (32 to 42 kg) undergoing total cardiopulmonary bypass underwent left anterior descending coronary artery occlusion for 30 minutes. The aorta was crossclamped and DSA (n = 6) or DSA+DZX (n = 6) cardioplegia was administered, followed by 30 minutes of global ischemia and 120 minutes of reperfusion. Control hearts (n = 3) received cardiopulmonary bypass and sham reperfusion only. Tissue samples from regional and global ischemia zones were harvested and used for Western blot and electrophoretic mobility shift assay. RESULTS: Regional and global ischemia significantly increase proapoptotic STAT1 tyrosine phosphorylation. This increase is significantly greater in the regional as compared with the global ischemia zone. Tyrosine phosphorylation of antiapoptotic STAT3 is increased in the global ischemic zone but is significantly decreased in the regional ischemic zone and is associated with increased apoptosis. The DSA+DZX significantly increases tyrosine phosphorylation of antiapoptotic STAT3 and DNA binding in the regional ischemia zone and significantly decreases apoptosis. CONCLUSIONS: The addition of diazoxide to DSA cardioplegia significantly decreases apoptosis by significantly increasing tyrosine phosphorylation of STAT3 and its DNA binding and represents an additional modality for enhancing myocardial protection.

Reoperation for early failure of a freestyle bioprosthesis using a full root technique.

The case is reported of a 65-year-old male who required reoperation for early failure of a Freestyle stentless valve aortic root bioprosthesis implanted using the full root technique. The bioprosthesis had been implanted to treat annuloaortic ectasia associated with severe aortic regurgitation (AR). At 18 months postoperatively, a new diastolic murmur developed, though without complaint by the patient. Transthoracic echocardiography demonstrated severe AR with aneurysmal dilatation of the non-coronary porcine sinus of Valsalva. Pseudoaneurysm formation, associated with perforation of the non-coronary sinus of Valsalva of the bioprosthesis, was observed at surgery. On inspection, the pseudoaneurysm had pushed the commissures inward, and had created severe aortic valve regurgitation. No infection or calcification was detected on the Freestyle valve, and the aortic root was successfully reconstructed using a composite graft.

Age- and gender-related differences in ischemia/reperfusion injury and cardioprotection: effects of diazoxide.

BACKGROUND: Recent studies have demonstrated that aging is associated with reduced tolerance to ischemia and that the aged (not senescent) female heart has greater susceptibility to ischemia as compared with the aged male heart. Previously, we have shown that ischemia can be modulated with cardioplegia in the male heart; however, efficacy in the female heart was unknown. METHODS: In this study, male and female mature (15 to 20 weeks) aged (>32 months) rabbit hearts (n = 134) were subjected to Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia hearts received 30 minutes of equilibrium, 30 minutes of global ischemia, and 120 minutes of reperfusion. Cardioplegia +/- diazoxide was infused separately, 5 minutes before global ischemia. RESULTS: Global ischemia significantly decreased postischemic functional recovery and significantly increased infarct size in the mature and aged male and female heart (p < 0.05 versus control). The effects of global ischemia were significantly exacerbated (p < 0.05) in the aged heart as compared with the mature heart. Cardioplegia +/- diazoxide significantly increased postischemic functional recovery and significantly decreased infarct size in mature male and female hearts, but these effects were significantly decreased in the aged heart (p < 0.05) and in the aged female as compared with the aged male heart. CONCLUSIONS: Postischemic functional recovery and infarct size are affected by age but not by gender. The cardioprotection afforded by cardioplegia is affected by age and gender with a strong age-by-gender interaction for end-diastolic pressure and infarct size. Our results indicate that currently optimized cardioplegia protocols effective in the male heart are not as efficacious in the aged female heart.

[Chordal cutting for the treatment of ischemic mitral regurgitation: two case reports].

The surgical treatment for ischemic mitral regurgitation remains controversal. Ring annuloplasty results in recurrent mitral regurgitation in some cases. Strut chordal cutting is a new surgical procedure in addition to ring annuloplasty for ischemic mitral regurgitation. Two patients (63-year-old woman, 53-year-old man) with severe ischemic mitral regurgitation were treated with this procedure. The patients had congestive heart failure due to mitral regurgitation, associated with inferior myocardial infarction. Regurgitant fraction of mitral regurgitation was 70% and 52% before surgery. Mitral leaflet tethering caused by apical displacement of the papillary muscle was observed. Mitral valve repair was performed by ring annuloplasty and chordal cutting. Intraoperative echocardiography showed that chordal cutting improved the configuration of the anterior leaflet, resulting in good mitral valve coaptation without regurgitation.

Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury.

Necrosis and apoptosis differentially contribute to myocardial injury. Determination of the contribution of these processes in ischemia-reperfusion injury would allow for the preservation of myocardial tissue. Necrosis and apoptosis were investigated in Langendorff-perfused rabbit hearts (n = 47) subjected to 0 (Control group), 5 (GI-5), 10 (GI-10), 15 (GI-15), 20 (GI-20), 25 (GI-25), and 30 min (GI-30) of global ischemia (GI) and 120 min of reperfusion. Myocardial injury was determined by triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), bax, bcl2, poly(ADP)ribose polymerase (PARP) cleavage, caspase-3, -8, and -9 cleavage and activity, Fas ligand (FasL), and Fas-activated death domain (FADD). The contribution of apoptosis was determined separately (n = 42) using irreversible caspase-3, -8, and -9 inhibitors. Left ventricular peak developed pressure (LVPDP) and systolic shortening (SS) were significantly decreased and infarct size and TUNEL-positive cells were significantly increased (P < 0.05 vs. Control group) at GI-20, GI-25, and GI-30. Proapoptotic bax, PARP cleavage, and caspase-3 and -9 cleavage and activity were apparent at GI-5 to GI-30. Fas, FADD, and caspase-8 cleavage and activity were unaltered. Irreversible inhibition of caspase-3 and -9 activity significantly decreased (P < 0.05) infarct size at GI-25 and GI-30 but had no effect on LVPDP or SS. Myocardial injury results from a significant increase in both necrosis and apoptosis (P < 0.05 vs. Control group) evident by TUNEL, TTC staining, and caspase activity at GI-20. Intrinsic proapoptotic activation is evident early during ischemia but does not significantly contribute to infarct size before GI-25. The contribution of necrosis to infarct size at GI-20, GI-25, and GI-30 is significantly greater than that of apoptosis. Apoptosis is significantly decreased by caspase inhibition during early reperfusion, but this protection does not improve immediate postischemic functional recovery.

Late results of mitral valve repair for mitral regurgitation.

OBJECTIVE: This study was undertaken to evaluate the long-term results of mitral valve repair for mitral regurgitation. METHODS: Between 1991 and 2000, 301 patients with mitral regurgitation underwent mitral valve repair. There were 167 men and 134 women whose mean age was 56 +/- 14 years. The patients were comprised of 7 patients in Carpentier's type I, 277 patients in type II, and 17 patients in type III. Chordal replacement with expanded polytetrafluoroethylene sutures had been prospectively applied to repair the anterior mitral leaflet prolapse. Ring annuloplasty was performed in 230 patients (76%). The follow-up was complete and mean follow-up was 67 +/- 33 months, for a cumulative follow-up of 1,624 patient-years. RESULTS: There were 5 hospital deaths and 11 late deaths (2 cardiac and 9 noncardiac). All survivors except those with stroke were in the New York Heart Association (NYHA) functional class I or II. At 10 years, the actuarial survival was 90 +/- 3%, the freedom from embolism was 86 +/- 4%, the freedom from reoperation was 96 +/- 2%, and the freedom from valve-related events was 77 +/- 4%. At 10 years, the freedom from reoperation in the patients with anterior leaflet prolapse was 90 +/- 5%. CONCLUSIONS: Mitral valve repair is feasible in most patients with mitral regurgitation and is associated with low mortality and low rates of valve related events. Chordal replacement with expanded polytetrafluoroethylene sutures is effective, safe, and durable at long-term follow-up for patients with anterior leaflet prolapse.

A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs.

BACKGROUND: Reactive oxygen and nitrogen species generated after reperfusion injury result in organ dysfunction. Peroxynitrite, a reactive nitrogen molecule produced from the reaction of superoxide anions and nitric oxide, is thought to be a causative agent in oxidative reperfusion injury. The aim of this study was to investigate the effects of a novel peroxynitrite decomposition catalyst (FP-15) in an acute myocardial ischemia/reperfusion model. METHODS: Pigs were subjected to 60 minutes of regional ischemia by reversibly ligating the left anterior descending coronary artery followed by 180 minutes of reperfusion. In the treatment group (n = 6), an FP-15 (1 mg/kg) bolus was infused through the jugular vein after 30 minutes of ischemia followed by a continuous infusion (1 mg x kg(-1) x h(-1)) during reperfusion. Vehicle was infused in the control group (n = 6). Coronary flow was recorded by an ultrasonic flow probe and infarct size determined by tetrazolium staining. Arterial and left ventricular pressures were monitored continuously and regional myocardial function determined by sonomicrometry. RESULTS: No significant differences were observed in either hemodynamics or ischemic area at risk. However, the infarct size was significantly reduced (35.3% +/- 3.5% versus 21.6% +/- 2.6% of the ischemic area, control versus FP-15-treated groups, respectively, p < 0.05). +dP/dt was transiently improved in the FP-15-treated groups while during most of the reperfusion period coronary flow, and was significantly lower in the FP-15-treated group as compared to the control group (p < 0.01). CONCLUSIONS: FP-15 administration reduces myocardial infarct size and reactive hyperemia. These data support the pathogenic role of endogenously produced peroxynitrite and that FP-15 is effective in preventing myocardial reperfusion injury.

Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis.

OBJECTIVE: Mitochondrial ATP-sensitive potassium channels have been proposed to be myoprotective. The relevance and specificity of this mechanism in cardiac surgery was unknown. The purpose of this study was to examine the effects of the mitochondrial potassium ATP-sensitive channel opener diazoxide on regional and global myocardial protection using a model of acute myocardial infarction. METHODS: Pigs (n=19) were placed on total cardiopulmonary bypass and then subjected to 30 min normothermic regional ischemia by snaring the left anterior descending coronary artery (LAD). The aorta was then crossclamped and cold blood Deaconess Surgical Associates cardioplegia (DSA; n=6) or DSA containing 50 microM diazoxide (DZX; n=6) was delivered via the aortic root and the hearts subjected to 30 min hypothermic global ischemia. The crossclamp and snare were removed and the hearts reperfused for 120 min. RESULTS: No significant differences in preload recruitable stroke work relationship, Tau, proximal, distal or proximal/distal coronary flow, regional or global segmental shortening, systolic bulging or post-systolic shortening were observed within or between DSA and DZX hearts during reperfusion. Infarct was present only in the region of LAD occlusion in both DSA and DZX hearts. Infarct size (% of area at risk) was 33.6+/-2.9% in DSA and was 16.8+/-2.4% in DZX hearts (P<0.01 versus DSA). Apoptosis as estimated by TUNEL positive nuclei was 120.3+/-48.8 in DSA and was significantly decreased to 21.4+/-5.3 in DZX hearts. Myocardial infarct was located centrally within the area at risk in both DSA and DZX hearts but was significantly increased at borderline zones within the area at risk in DSA hearts. CONCLUSIONS: The addition of diazoxide to cardioplegia significantly decreases regional myocardial cell necrosis and apoptosis in a model of acute myocardial infarction and represents an additional modality for achieving myocardial protection.

Diazoxide amelioration of myocardial injury and mitochondrial damage during cardiac surgery.

BACKGROUND: Recently, we have shown that the selective opening of mitochondrial ATP-sensitive potassium channels with diazoxide significantly decreases myocardial injury. The purpose of this study was to determine the effects of diazoxide on apoptosis and the mechanisms modulating apoptosis and myocardial injury in a blood-perfused model of acute myocardial infarction. METHODS: Pigs (32 to 42 kg) undergoing total cardiopulmonary bypass underwent left anterior descending coronary artery occlusion for 30 minutes. The aorta was cross-clamped and magnesium-supplemented potassium cold-blood cardioplegia (DSA; n = 6) or magnesium-supplemented potassium cardioplegia containing 50 micromol/L diazoxide (DZX; n = 6) was administered, followed by 30 minutes of global ischemia and 120 minutes of reperfusion. Left ventricular tissue samples from DSA and DZX hearts were obtained after reperfusion. Apoptosis was determined by TUNEL, caspase-3 and PARP cleavage, and caspase-3 activity. Bax and bcl-2 levels were determined and tissue morphology was examined by light and transmission electron microscopy. RESULTS: Apoptosis, as estimated by TUNEL-positive nuclei/3,000 myocardial cells, was 120.3 +/- 48.8 in DSA hearts and was significantly decreased to 21.4 +/- 5.3 in DZX hearts (p < 0.05 vs control). Caspase-3 and poly-ADP-ribose polymerase cleavage and pro-apoptotic bax protein levels were significantly decreased with diazoxide (p < 0.05 vs DSA). Light and transmission electron microscopy indicated severe disruption of tissue with capillary dilatation, mitochondrial cristae damage, and evidence of increased presence of mitochondrial granules in DSA as compared with DZX hearts. CONCLUSIONS: The addition of diazoxide (50 micromol/L) to cardioplegia significantly decreases regional myocardial apoptosis and mitochondrial damage, and provides an additional modality for achieving myocardial protection.