A comparison of haemostatic biomarkers during low-risk patients undergoing cardiopulmonary bypass using either conventional centrifugal cell salvage or the HemoSep device.

BACKGROUND: Cardiac surgery using cardiopulmonary bypass (CPB) is associated with a coagulopathy due to haemodilution, thrombocytopenia and platelet dysfunction and the activation of coagulation and fibrinolysis, despite the use of large doses of unfractionated heparin. Conventional red cell salvage may exacerbate post-operative bleeding as plasma containing haemostatic factors is discarded. We hypothesized that a novel cell salvage device (HemoSep) may attenuate haemostatic changes associated with red cell salvage. We studied haemostatic markers following autologous transfusion from conventional cell salvage or the HemoSep device. METHODS: This randomised, controlled trial compared haemostatic markers in patients undergoing coronary artery bypass grafting or aortic valve replacement who received autologous blood returned from cell salvage (control) or HemoSep (study). Blood samples were taken pre-operatively, end of CPB, post-transfusion of salvaged blood and 3 hours post-operatively and analysed for full blood count (FBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer and endogenous thrombin potential (ETP). RESULTS: Fifty-four patients were recruited (n=28 control, n=26 study). Processed blood volume for transfusion was significantly (p<0.001) higher in the HemoSep group. In the HemoSep group, the PT was shorter (18.7±0.3 vs 19.9±0.3 sec; p<0.05) post-operatively and the aPTT was longer (48.6±3.8 vs 37.3±1.0 sec; p<0.01) following autologous transfusion. In the control group, D-dimer and ETP levels were higher (1903±424 vs.1088±151; p<0.05 and 739±46 vs. 394±60; p<0.001, respectively) following autologous transfusion. CONCLUSIONS: Although centrifuged cell salvage is known to adequately haemoconcentrate and remove unwanted substrates and bacteriological contamination, the process can exacerbate coagulopathy. The HemoSep device demonstrated some increase in haemostatic markers when used in low-risk cardiac surgery patients.

Critical physiological and surgical considerations for hydrodynamic pressurization of individual segments of the pig liver.

Hydrodynamic gene delivery to the liver is a promising approach for liver gene therapy in the clinic, but levels of gene expression in larger species have been much less than in rodents. The development of surgical techniques for pressurizing individual liver segments and the establishment of whether hepatic vascular anatomy in fact permits pressurization of individual segments are critical issues that need to be addressed. We have evaluated these issues using hydrodynamic delivery to individual segments of the pig liver, via branches of both portal and hepatic veins. Our objective was to develop surgical techniques that achieve elevated vascular pressures within individual liver segments with small volumes, but without interruption of portal blood flow or reduction in venous return to the heart. We report that, without specific surgical interventions to obstruct outflow of DNA solution from the targeted liver segment, little or no increase in intrahepatic vascular pressure occurs. We demonstrate, for the first time, that selective pressurization of individual liver segments is possible without compromising portal venous flow or venous return to the heart. Thus, hydrodynamic gene delivery to individual liver segments is technically achievable in a clinical setting, but will require open abdominal surgery rather than minimally invasive techniques.

Low-volume hydrodynamic gene delivery to the rat liver via an isolated segment of the inferior vena cava: efficiency, cardiovascular response and intrahepatic vascular dynamics.

BACKGROUND: Clinical application of hydrodynamic gene delivery to the liver requires the use of small volumes, an evaluation of the cardiovascular consequences of acute volume overload, and a better understanding of the intrahepatic vascular pressures driving gene delivery. Injection of DNA solution into the isolated segment of inferior vena cava (IVC) draining the hepatic veins is a potentially valuable low-volume approach. METHODS: Various volumes of DNA solution (pGL3 plasmid) were injected at 100 ml/min either systemically or into the isolated IVC segment in the DA rat. Arterial pressure, portal venous pressure, heart rate and electrocardiogram, in addition to reporter gene expression in the liver, were monitored. RESULTS: The 2% volume was > 10 000-fold more effective when delivered via the IVC segment than when given systemically, and as effective as 6% systemically. Isolation of the IVC segment caused profound falls in arterial pressure, with electrocardiogram signs of myocardial ischemia. On release of the IVC ties, without DNA infusion (no volume overload), arterial pressure recovered rapidly. However, with DNA infusion (volume overload) there was a brief recovery of arterial pressure, followed by complete heart block and fall in arterial pressure and pulse for several minutes. Portal venous pressure rose steeply to 30-33 mm Hg during the infusion. CONCLUSIONS: The IVC segment approach enables excellent gene delivery to the whole liver with small volumes, but causes severe cardiovascular disturbances in the rat. Portal venous pressures are slightly higher than in the mouse, and suggest functional outflow obstruction by the capillary bed of the intestines.