Markus Hoenicka

Anticoagulation management during multivessel coronary artery bypass grafting: a randomized trial comparing individualized heparin management and conventional hemostasis management.

Individualized heparin management (IHM) uses heparin dose–response curves to improve hemostasis management during cardiac surgery as compared with activated clotting time‐based methods.

Similarity of coagulation and inflammation despite different surgical revascularization strategies – a prospective randomized trial

Background: Supposedly, minimized extracorporeal circulation or off-pump revascularization as alternatives to conventional extracorporeal circulation (ONCAB) reduce inflammation and coagulation disturbances. Methods: One hundred and twenty coronary artery bypass graft (CABG) patients were prospectively randomized for three surgical techniques. Coagulation and inflammation markers were measured up to 72 hours postoperatively. Results: Coagulation factors I, II, V, X, antithrombin III and C-reactive protein did not differ perioperatively between the groups and increased, as did several other markers, 12 to 72 hours postoperatively. Compared to its alternatives, ONCAB showed the most obvious transient increase in thrombin-antithrombin complexes (p<0.0001), D-dimers (p=0.0059), tissue factor pathway inhibitor (p=0.0005), factor VIII (p=0.0041) and tumor necrosis factor α (p=0.0300) during the operation and up to 12 hours postoperatively. Furthermore, ONCAB generated lower leukocyte and platelet counts and higher values of soluble P-selectin and soluble intercellular adhesion molecule 1 at some time points. Conclusions: With similarity in pivot coagulation factors, a specific detrimental influence of ONCAB on common coagulation pathways was excluded. Higher perioperative concentrations of products from the coagulation cascade most likely indicate activation of pericardial blood – recirculated only in ONCAB. Furthermore, with only temporary differences in markers of inflammation, the alternatives to ONCAB altogether were without advantage at 72 hours postoperatively. In the general answer to surgical trauma, the part of modern extracorporeal circulation is possibly overestimated. The study is registered at the German Clinical Trial Registry. Registration number DRKS00007580. URL: https://drks-neu.uniklinik-freiburg.de/drks_web/ URL: http://apps.who.int/trialsearch/

Contact-free monitoring of vessel graft stiffness – proof of concept as a tool for vascular tissue engineering

Tissue‐engineered vessel grafts have to mimic the biomechanical properties of native blood vessels. Manufacturing processes often condition grafts to adapt them to the target flow conditions. Graft stiffness is influenced by material properties and dimensions and determines graft compliance. This proof‐of‐concept study evaluated a contact‐free method to monitor biomechanical properties without compromising sterility. Forced vibration response analysis was performed on human umbilical vein (HUV) segments mounted in a buffer‐filled tubing system. A linear motor and a dynamic signal analyser were used to excite the fluid by white noise (0–200 Hz). Vein responses were read out by laser triangulation and analysed by fast Fourier transformation. Modal analysis was performed by monitoring multiple positions of the vessel surface. As an inverse model of graft stiffening during conditioning, HUV were digested proteolytically, and the course of natural frequencies (NFs) was monitored over 120 min. Human umbilical vein showed up to five modes with NFs in the range of 5–100 Hz. The first natural frequencies of HUV did not alter over time while incubated in buffer (p = 0.555), whereas both collagenase (−35%, p = 0.0061) and elastase (−45%, p < 0.001) treatments caused significant decreases of NF within 120 min. Decellularized HUV showed similar results, indicating that changes of the extracellular matrix were responsible for the observed shift in NF. Performing vibration response analysis on vessel grafts is feasible without compromising sterility or integrity of the samples. This technique allows direct measurement of stiffness as an important biomechanical property, obviating the need to monitor surrogate parameters. Copyright

Superior vasodilation of human pulmonary vessels by vardenafil compared with tadalafil and sildenafil: additive effects of bosentan†.

OBJECTIVES Pulmonary arterial hypertension is characterized by pulmonary vascular proliferation and remodelling, leading to a progressive increase in pulmonary arterial resistance. Vasodilator properties of 3 different phosphodiesterase (PDE)-5 inhibitors alone and in combination with an endothelin (ET) receptor antagonist were compared in an ex vivo model. METHODS Segments of human pulmonary arteries (PAs) and pulmonary veins (PVs) were harvested from lobectomy specimens. Contractile forces were determined in an organ bath. Vessels were constricted with norepinephrine (NE) to determine the effects of sildenafil, tadalafil and vardenafil and with ET-1 to assess the effects of bosentan. RESULTS All 3 PDE-5 inhibitors had no relevant effect on the basal tone of the vessels. Both sildenafil and vardenafil significantly (P < 0.0001) reduced the responses of the vessels to NE, whereas tadalafil was effective only in PA (P = 0.0009) but not in PV (P = 0.097). Sildenafil relaxed NE-preconstricted PV (P < 0.0001) but not PA (P = 0.143). Both tadalafil and vardenafil relaxed PA and PV significantly. Vardenafil appears to be the most potent of the PDE-5 inhibitors tested. Furthermore, we analysed the combination of bosentan and vardenafil in PA. Bosentan and vardenafil reduced ET-1 and NE induced vasoconstriction stronger than vardenafil alone (P ≤ 0.049). CONCLUSIONS Vardenafil caused the most consistent antihypertensive response in this ex vivo model. However, ET receptor antagonism appears to be an even more potent mechanism. A combination therapy using vardenafil and bosentan turned out to be an effective combination to lower vessel tension in PA.

Influence of Cannulation Site on Carotid Perfusion During Extracorporeal Membrane Oxygenation in a Compliant Human Aortic Model

Blood oxygenized by veno-arterial extracorporeal membrane oxygenation (ECMO) can be returned to the aorta (central cannulation) or to peripheral arteries (axillar, femoral). Hemodynamic effects of these cannulation types were analyzed in a mock loop with an aortic model representative of normal anatomy and compliance under physiological pressures and flow rates. Pressures, flow rates, and contribution of ECMO flow to total flow as a measure of oxygen supply were monitored in the carotids. Steady or pulsatile ECMO flow, residual or no cardiac output, and intraaortic balloon pump counterpulsation were tested as independent factors. With residual heart function, central cannulation provided the best oxygenated flow and pressure to the carotid arteries (CA). Axillar cannulation preferentially perfused the right CA at the expense of the left CA. Femoral cannulation provided only lower amounts of oxygenated blood to both CA. Pulsation increased the surplus hemodynamic energy. Counterpulsation reduced flow with femoral cannulation but improved flow and pressure with axillar cannulation. Femoral cannulation failed to provide oxygenated blood to coronary and supraaortic arteries with residual heart function. Central cannulation provided the best hemodynamics and oxygen supply to the brain. With a resting heart but not with an ejecting heart, pulsatile ECMO flow enhanced CA hemodynamics.

Postoperative Bleeding after CABG - does Individualized Heparin Management Save Blood?

Objectives: To compare routine activated clotting time (ACT) based hemostasis management to individualized heparin management (IHM) in terms of postoperative bleeding, platelet function, and coagulation markers. Methods: 120 CABG patients (≥ 3 distal anastomoses) were enrolled in a prospective trial and were randomized for hemostasis management (ACT versus IHM). With a target ACT of 400 second conventional hemostasis management antagonized heparin with protamine in a ratio of 1:>0.8, whereas in IHM protamine dosages were calculated from residual heparin concentrations. Hemostasis was analyzed immediately post-OP by thrombelastometry, aPTT, INR, and a range of coagulation markers. Results: A total of 112 patients (ACT: 56, IHM: 56) were included. Median heparin dosages were equivalent in both groups, whereas IHM patients received significantly less protamine. INR did not differ significantly, but aPTT values were significantly higher in HM patients. INTEM clotting times were elevated in IHM patients, whereas HEPTEM clotting times did not differ. Most coagulation markers (antithrombin III, d-dimers, fibrinogen, factors II/V/VIII/X, tissue factor pathway inhibitor, platelet counts) did not differ between groups, whereas thrombin-antithrombin complexes (TATs) were higher in ACT patients (29.69 [15.14–42.19] versus 18.50 [12.14–29.22] µg/l, p = 0.005), indicating recovered coagulation capacities. TATs correlated significantly with protamine doses (p = 0.022). Blood losses were slightly but significantly higher in IHM patients within the first 12 hour which balanced at 24 hour and which did not lead to more blood transfusions (40 PRBC in 15 patients versus 44/17, p = 0.926). Conclusions: IHM patients did not benefit from allegedly reduced coagulation factor activation mainly because heparin dosages were unexpectedly identical in both groups. On the contrary, postoperative parameters indicated an incomplete heparin antagonization in IHM patients.