Ultrasound-targeted transfection of tissue-type plasminogen activator gene carried by albumin nanoparticles to dog myocardium to prevent thrombosis after heart mechanical valve replacement.

BACKGROUND: There are more than 300,000 prosthetic heart valve replacements each year worldwide. These patients are faced with a higher risk of thromboembolic events after heart valve surgery and long-term or even life-long anticoagulative and antiplatelet therapies are necessary. Some severe complications such as hemorrhaging or rebound thrombosis can occur when the therapy ceases. Tissue-type plasminogen activator (t-PA) is a thrombolytic agent. One of the best strategies is gene therapy, which offers a local high expression of t-PA over a prolonged time period to avoid both systemic hemorrhaging and local rebound thrombosis. There are some issues with t-PA that need to be addressed: currently, there is no up-to-date report on how the t-PA gene targets the heart in vivo and the gene vector for t-PA needs to be determined. AIMS: To fabricate an albumin nano-t-PA gene ultrasound-targeted agent and investigate its targeting effect on prevention of thrombosis after heart mechanic valve replacement under therapeutic ultrasound. METHODS: A dog model of mechanical tricuspid valve replacement was constructed. A highly expressive t-PA gene plasmid was constructed and packaged by nanoparticles prepared with bovine serum albumin. This nanopackaged t-PA gene plasmid was further cross-linked to ultrasonic microbubbles prepared with sucrose and bovine serum albumin to form the ultrasonic-targeted agent for t-PA gene transfection. The agent was given intravenously followed by a therapeutic ultrasound treatment (1 MHz, 1.5 w/cm(2), 10 minutes) of the heart soon after valve replacement had been performed. The expression of t-PA in myocardium was detected with multiclonal antibodies to t-PA by the indirect immunohistochemical method. Venous blood t-PA and D-dimer contents were tested before and 1, 2, 4, and 8 weeks after the operation. RESULTS: The high expression of t-PA could be seen in myocardium with increases in blood t-PA and D-dimer contents and thrombosis was prevented 8 weeks after operation. CONCLUSION: We successfully fabricated an albumin nano-t-PA gene ultrasound-targeted agent that could prevent dog thrombosis after mechanical heart valve replacement. Our study provides an experimental basis for prevention of human thrombosis-related diseases.

[Predictive value of human fatty acid binding protein for myocardial ischemia and injury in perioperative period of cardiac surgery].

OBJECTIVE: To evaluate the value of human fatty acid binding protein (h-FABP) in predicting myocardial ischemia and injury in the perioperative period of cardiac surgery, we observed the dynamic changes of h-FABP in perioperative period of patients underwent coronary artery bypass grafting and ventricular septal defects repairing surgery, and evaluated the relationship of h-FABP and ischemia modified albumin (IMA), CK-MB, cTnI. METHODS: Patients underwent coronary artery bypass grafting (n=30) and ventricular septal defect repairing (n=30) surgery between February 2008 and December 2008 were included in this study. Venous blood sample was obtained at preoperative, aortic clamping, aortic unclamping of 10 min, 2 h, 6 h, 12 h, 24 h for the measurements of h-FABP, IMA, cTnI and CK-MB. RESULTS: h-FABP and IMA changed in the same way at various examined time points, h-FABP changes also paralleled cTnI and CK-MB changes, h-FABP peaked early during myocardial ischemia and injury and returned to baseline level at 2 h post myocardial ischemia and injury. Linear correlation analysis showed that the peak value of h-FABP was positively correlated with IMA, CK-MB and cTnI in both CABG group (r = 0.948, 0.964 and 0.961, P < 0.05) and in the VSD group (r = 0.986, 0.978 and 0.957). CONCLUSIONS: h-FABP is an early diagnostic parameter reflecting perioperative myocardial ischemia and injury in cardiac surgery. Quantitative h-FABP monitoring could predict the severity of myocardial ischemia and injury early during cardiac surgery.

The short-term pulsatile ventricular assist device for postcardiotomy cardiogenic shock: a clinical trial in China.

Despite the recent advances in myocardial protection, surgical techniques, intra-aortic balloon therapy, and maximal pharmacological support, postoperative ventricular dysfunction continues to occur in 0.5-1.0% of all patients undergoing cardiac surgery. Ventricular assist device (VAD) is an important therapeutic adjunct in treating patients with profound ventricular dysfunction with postcardiotomy cardiogenic shock. The purpose of this report was to describe the clinical results with the China-made Luo-Ye VAD as a short-term circulatory support. From May 1998 to December 2006, 17 patients with postcardiotomy cardiogenic shock were supported by the Luo-Ye VAD. Of these patients, 10 were males and seven were females with a mean age of 49.6 years (range 36-68 years). All cases were supported by left VAD (LVAD). Mean duration of support was 46.3 h (range 13-113 h). A criteria of insertion was established to standardize implantation criteria. Among the 17 patients treated with LVAD, eight (47.1%) patients were weaned from support and seven (41.2%) patients were discharged from hospital. Ten (58.8%) patients died while on LVAD support (nine cases) or shortly after weaning (one case). The causes of death in the entire group were cardiac (40%), renal failure (20%), neurologic (10%), sepsis (10%), and multiple organ system failure (20%). The complications were represented by bleeding, renal failure, neurologic event, infection, ventricular arrhythmias, etc. The Luo-Ye VAD functioned well and proved to be useful in patients with postcardiotomy cardiogenic shock. It carries a less-postoperative anticoagulant and a low incidence of VAD-related complications. The survival rate was encouraging in our small cohort of patients.

[Comparison of perioperative myocardial enzyme changes among congenital, rheumatic and coronary artery diseases].

OBJECTIVE: To observe and compare perioperative myocardial enzyme changes in 107 patients with congenital (CHD, n = 53), rheumatic (RHD, n = 40) and coronary artery (CAD, n = 14) diseases, and to find whether different diseases can affect the release and recovery of myocardial enzymes after heart operations. METHODS: On the day before operation and the 1st, 3rd, 5th and the 8th day after operation, the venous blood was taken to measure the release of myocardial enzymes: aspartate aminotransferase (AST), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and LDH-1. RESULTS: All the enzymes measured before operation in three groups were in the normal range; their release increased abruptly on the 1st day postoperatively to 2 - 15 times of those before operation; on the 3rd day, they recovered to some degrees, and on the 8th day they recovered to normal in all groups except LDH and LDH-1 in rh and CAD groups. Because the aortic cross-clamp time (CCT) had a good positive correlation to the release of myocardial enzymes, those patients whose CCT was over 60 minutes in three groups were compared revealing that the CCT was not different between three groups (P < 0.05). The release of CK, CK-MB and AST was significantly higher in CHD60 group than those in CHD60 and CAD60 groups, they recovered afterwards; while the release of DH and LDH-1 was higher in CAD60 group than those in CAD60 and in CHD60 groups from the 1st day to the 8th day postoperatively. CONCLUSIONS: The release of all the 5 enzymes measured before operation was in normal range in selected CHD, RHD and CAD patients. The release peak and the recovery order of all enzymes were the same in three groups. The release of CK, CK-MB and AST was higher in CHD60 group than those in RHD60 and CAD60 groups on the 1st day. The release of LDH and LDH-1 was higher in RHD60 group than those in CHD60 and CAD60 groups from the 1st day to the 8th day postoperatively. The shorter the CCT is, the less the release of myocardial enzymes. Using the release of LDH and LDH-1 to evaluate the recovery of myocardial injury after open-heart operations was recommended.