Hu S

Strategy for biventricular outflow tract reconstruction: Rastelli, REV, or Nikaidoh procedure?

OBJECTIVEnThree techniques have been developed as the surgical management for patients with anomalies of ventriculoarterial connection, ventricular septal defect, and pulmonary outflow tract obstruction (stenosis): the Rastelli, Lecompte, (REV), and Nikaidoh procedures. This study was designed to compare these procedures in terms of hemodynamics of the reconstructed biventricular outflow tract, early clinical consequences, and follow-up.nnnMETHODSnBetween March 2004 and September 2006, a total of 30 consecutive patients underwent double root translocation procedures (modified Nikaidoh n = 11, REV n = 7, Rastelli n = 12). In the Nikaidoh procedure, both aortic and pulmonary roots were translocated. A single-valved bovine jugular vein patch was used to repair the stenotic pulmonary artery in both Nikaidoh and REV procedures. The Senning procedure was added for those with atrioventricular discordance.nnnRESULTSnThe Nikaidoh procedure was the most time-consuming in terms of mean cardiopulmonary bypass and aortic crossclamp times. The average mechanical ventilation time was significantly shorter in the Rastelli group (63.3 +/- 89 hours) than that in the Nikaidoh group (188.7 +/- 159 hours, P = .016), but not different from that in the REV group (76.4 +/- 112.5 hours, P = .395). Two patients in the REV group and 1 in the Rastelli group died. There were no in-hospital or late deaths in the Nikaidoh group. Postoperative echocardiography demonstrated physiologic hemodynamics in the left ventricular outflow tract and normal heart function in the Nikaidoh group. Abnormal flow pattern in the left ventricular outflow tract was noted in both REV and Rastelli groups. There were no late deaths or reoperations in any group during follow-up.nnnCONCLUSIONnThe modified Nikaidoh procedure is a better surgical option for transposition of the great arteries, ventricular septal defect, and pulmonary stenosis in terms of physiologic cardiac hemodynamics. Its long-term benefits need to be evaluated with a larger number of patients and longer follow-up.

Intramyocardial injection of tannic acid attenuates postinfarction remodeling: A novel approach to stabilize the breaking extracellular matrix

OBJECTIVEnMyocardial infarction is associated with early matrix metalloproteinase activation and extracellular matrix degradation. We tested the hypothesis that stabilizing the original extracellular matrix of the infarcted left ventricle with local injection of tannic acid would preserve cardiac structure and function.nnnMETHODSnIn vitro cytotoxicity of tannic acid was performed first; myocardial infarction model was induced by ligation of the left anterior descending branch in rats. Tannic acid was intramyocardially injected into infarcted site 24 hours after myocardial infarction (n = 30), and saline solution was injected in the same way as in the control (n = 30). The matrix metalloproteinase activity from tannic acid/saline solution-treated tissues was assayed by gelatin zymography 24 hours and 1 week after the treatment. The collagen content in the infarcted area was evaluated by hydroxyproline colorimetry assay 1 and 4 weeks after the treatment. Left ventricular structure and function were also evaluated with echocardiography, hemodynamics, and histologic examination.nnnRESULTSnTannic acid at a concentration of 0.05% had minimal cytotoxic effects on cultured cardiomyocytes and thus was subsequently chosen as the optimal concentration for injection. Compared with the saline solution injection group, tannic acid treatment inhibited the matrix metalloproteinase-2/-9 activity and increased the collagen content at the early post-myocardial infarction stage (48.6 +/- 7.2 vs 37.3 +/- 6 microg/mg dry weight). Tannic acid treatment also significantly reduced infarct expansion (infarct expansion index: 1.04 +/- 0.15 vs 1.42 +/- 0.21) and left ventricular dilatation at 4 weeks after infarction. Although tannic acid treatment improved fractional shortening (26% +/- 2.4% vs 23.3% +/- 3.2%), it failed to alter blood pressure (systolic blood pressure: 93.8 +/- 8.2 vs 90.6 +/- 8.5 mm Hg) and rate of pressure rise.nnnCONCLUSIONSnLocal delivery of tannic acid prevents collagen matrix degradation via cross-linking fibrous collagen and inhibiting matrix metalloproteinase activity but does not improve the intrinsic contractile function of myocardium. This treatment may be helpful to attenuate the adverse topographic remodeling after acute myocardial infarction.

Evaluation of antiplatelet effects of a modified protocol by platelet aggregation in patients undergoing “one-stop” hybrid coronary revascularization

“One-stop” hybrid coronary revascularization has emerged to be a reliable and attractive alternative for selected patients with multivessel coronary artery disease. However, the optimal antiplatelet regimen of the one-stop hybrid procedure still remains controversial. We modified the antiplatelet protocol in order to reduce the risk of perioperative bleeding and maximally inhibit platelet activity. This study sought to investigate whether the inhibition of platelet activity by this modified antiplatelet protocol is comparable with the conventional protocol widely used and recommended in percutaneous coronary interventions (PCI). Twenty three patients undergoing one-stop hybrid procedure and 20 patients undergoing conventional PCI were enrolled in this prospective study. The modified antiplatelet protocol included perioperative use of aspirin; clopidogrel was administered immediately before PCI with a 300 mg loading dose, followed by a maintenance dose of 75 mg/day for 12 months. Blood samples were obtained before the operation and 2 hours, day 1 and day 3 after operation. Platelet aggregation was induced with: 1) arachidonic acid (AA) (final concentration 0.5 mmol/L) to assess the efficacy of aspirin; 2) adenosine diphosphate (ADP) (final concentration 10 μmol/L) to assess the specific efficacy of clopidogrel. Platelet counts were statistically lower in the hybrid group than in the PCI control group (p = 0.0018) on day 1 after operation. AA-induced platelet aggregation increased significantly in comparison with the preoperative baseline values (p = 0.0079) and the PCI control group (p = 0.0023) on day 1 after operation. ADP-induced platelet aggregation gradually decreased in the hybrid group, and achieved similar platelet inhibition with the PCI group on 2 hours and day 1 after operation. No major adverse clinical events such as death, perioperative myocardial infarction, stent thrombosis or reoperation for bleeding occurred in both groups within 30 days after procedure. These results demonstrate that our modified antiplatelet therapy can sufficiently inhibit platelet activity similarly as the conventional protocol for PCI early after operation. Thus, this modified protocol, with continuous use of aspirin and intraoperative administration of loading dose clopidogrel, might be a safe and effective antiplatelet strategy for the one-stop hybrid coronary revascularization.

Effect of simvastatin on the expression of farnesoid X receptor in diabetic animal models of altered glucose homeostasis.

Background Statin therapy has affected glucose homoeostasis of type 2 diabetes patients, which could be related with bile acids metabolism. Whether bile acid metabolism and the expression of farnesoid X receptor (FXR), liver X receptor‐&agr; (LXR‐&agr;) and sterol regulatory element‐binding protein (Srebp)‐1c is regulated by hyperglycemia, or whether simvastatin therapy led to higher glucose is related with down‐regulated expression of FXR in diabetic rats remained unclear. Methods Forty male Wistar rats were randomly divided into four groups: normal control rats, insulin resistance rats, diabetic model rats, and the late simvastatin induced diabetic rats. Normal control rats were fed with standard diet, others were fed with high‐fat diet. Diabetic model rats were induced by a single intraperitoneal injection of streptozotocin (STZ). The late simvastatin induced diabetic rats started simvastatin administration after STZ induced diabetic model rats. Characteristics of fasting blood glucose (FPG), lipid files and total bile acids (TBAs) were measured and the oral glucose tolerance test (OGTT) was performed after overnight fasting at the eighth weekend. RNA and protein levels of FXR, LXR‐&agr; and Srebp‐1c were tested by Western blotting and reverse transcription polymerase chain reaction (RT‐PCR). Results The insulin resistance rats showed higher glucose, lipid files and lower expression of FXR compared with normal control rats (P >0.05). The diabetic model rats showed significantly higher glucose, lipid files, TBA and lower expression of FXR compared with insulin resistance rats (P <0.05). The late simvastatin induced diabetic rats displayed higher glucose and TBA and lower expression of FXR compared with diabetic model rats (P <0.05). Conclusions Changes in bile acid homeostasis, including the alterations of bile acid levels and bile acid receptors, are either a cause or a consequence of the metabolic disturbances observed during diabetic models. Statin therapy induced hyperglycemia may be related with FXR, SHP, LXR‐&agr; and Srebp‐1 pathways.

Repair of Anomalous Origin of Right Coronary Artery from the Pulmonary Artery

Anomalous origin of the right coronary artery from the pulmonary artery is a rare cardiac malformation. Between July 2002 and July 2005, we operated on 4 patients with this defect. There were 2 males and 2 females, aged from 18 months to 42 years. Three patients underwent direct re-implantation of the right coronary artery into the aorta, and one had an intrapulmonary tunnel repair (intrapulmonary artery baffle with an autologous pericardial patch for tunneling to the anomalous right coronary ostium). Cardiopulmonary bypass was used in 2 patients, and an off-pump technique in the other 2. One patient had an atrial septal defect that was closed with an Amplatzer septal occluder through the right atrium under transesophageal echocardiography, without cardiopulmonary bypass. All patients survived and recovered uneventfully. Follow-up ranged from 3 to 39 months (mean, 17 months). All patients were doing well and free from symptoms, with normal exercise tolerance. Surgical correction of anomalous right coronary artery shows good early and midterm results.

Repair of Anomalous Origin of Left Coronary Artery from the Pulmonary Artery

Patients with anomalous origin of the left coronary artery from the pulmonary artery often have mitral valve regurgitation. Although establishing dual coronary circulation is the procedure of choice, there remains controversy as to how the mitral valve is handled. Between April 1999 and August 2005, 8 patients underwent surgical correction at our institution. There were 4 males and 4 females, aged from 9 months to 13 years (mean, 6.4 years). Six patients underwent direct aortic reimplantation and 2 had a Takeuchi procedure. Simultaneous mitral annuloplasty was performed in 7 patients with moderate or severe mitral regurgitation. There were no deaths or postoperative complications. Follow-up ranged from 4 to 80 months (mean, 34 ± 26 months). Left ventricular function improved significantly from a preoperative fractional shortening of 0.21 ± 0.09 to 0.35 ± 0.06. Mitral regurgitation decreased on follow-up in the 7 patients who had mitral annuloplasty. We recommend performing mitral annuloplasty at the time of operation in patients with moderate or severe mitral regurgitation and anomalous origin of the left coronary artery from the pulmonary artery.

Association of Carney Complex with an Intronic Splice Site Mutation in the PRKAR1A Gene

This study was aimed to investigate the clinical features and mutations in the PRKAR1A gene of a multigenerational kindred including 17 individuals at risk for Carney complex. Eight patients were diagnosed with Carney complex among the 17 individuals (47.1%). Among the 8 affected patients, 4 had cardiac myxomas, 8 had skin pigmentation, and 3 had diabetes. Genomic DNA sequencing in 14 surviving patients showed 6 had the same germline mutation in the sixth intron and affected the splice site. cDNA sequencing and DNAMAN software showed 159 bases were absent, resulting in the absence of the amino acids 249 to 301 from the protein. All 6 patients with this PRKAR1A gene mutation had skin pigmentation. In conclusion, the present study reported for the first time an intronic splice site mutation in the PRKAR1A gene of a Chinese family with Carney complex, which probably caused skin pigmentation observed in affected family members.