Clinical and biomaterial evaluation of a new condensed dual-function extracorporeal circuit in reoperation for coronary artery bypass surgery.

PURPOSE: This prospective, randomized study compared the clinical performance of three types of circuits: a newly introduced, fully-coated, interchangeable open-closed circuit with a dual configuration (hard shell with a bypass shunt), reduced length, and reduced prime of less than 800 cc (CondECC); a completely coated circuit (ECC); and a similar uncoated, open circuit with standard length and prime (CONT). METHODS: 75 patients undergoing reoperation for coronary revascularization were randomly allocated into three groups (N=25): Group 1: CondECC with shortened tubing, components and an open-closed configuration of low priming volume with a centrifugal pump and a shunt which bypassed the reservoir for closed configuration; Group 2: ECC with a roller pump and hard-shell reservoir; Group 3: CONT. Blood samples for CBC, inflammatory mediators [Interleukin-2 (IL-2), Complement-3a (C3a)] and flow cytometry (CD11b/CD18) were collected after induction (T1) and heparin administration (T2), 15 min after cardiopulmonary bypass (CPB) (T3), before cessation of CPB (T4), 15 min after reversal (T5), and the first postoperative day (T6). RESULTS: Leukocyte counts demonstrated significant increases at T4, T5 in CONT but remained stable in ECC and CondECC (p<0.05). Platelets were preserved better at T4, T5 in both ECC and CondECC study groups (p<0.05). IL-2 and C3a levels were significantly lower at T3, T4, T5 in CondECC and T4, T5 in ECC (p<0.05). Blood protein adsorption analysis demonstrated increased amount of microalbumin on CONT fibers (p<0.05). CONCLUSIONS: The CondECC is a flexible, dual-function, open/closed configuration system that was easy to use, safe and achieved better biocompatibility when compared to coated and uncoated conventional circuits.

Clinical and biomaterial evaluation of hyaluronan-based heparin-bonded extracorporeal circuits with reduced versus full systemic anticoagulation in reoperation for coronary revascularization.

OBJECTIVE: This prospective randomized study compares full and reduced heparinization on novel hyaluronan-based heparin-bonded circuits vs. uncoated controls under challenging clinical setting including biomaterial evaluation. METHODS: 100 patients undergoing reoperation for coronary artery bypass grafting were allocated into two equal groups (n = 50): Group one was treated with hyaluronan-based heparin bonded preconnected circuits (Vision HFOGBS, Gish, California, USA) and Group two with identical uncoated controls (Vision HFO, Gish, USA). In the study group, half of the patients (n = 25) received low-systemic heparin (125 IU/kg, ACT >250 s) or full dose like control group. Blood samples were collected after induction of anesthesia (T1) and heparin administration before cardiopulmonary bypass (CPB) (T2), 15 min after initiation of CPB (T3), before cessation of CPB (T4), 15 min after reversal with protamine (T5), and the first postoperative day at 08: 00 h (T6). RESULTS: Platelet counts were preserved significantly better at T5, T6 in hyaluronan groups (P < 0.05 vs. control). Serum IL-2 levels were significantly lower at T4, T5 in both hyaluronan groups and C3a levels at T4 and T5 only in low-dose group (P < 0.05). Troponin-T levels in coronary sinus blood demonstrated well preserved myocardium in hyaluronan groups. No significant differences in thrombin-antithrombin levels were observed between full and low-dose heparin groups at any time point. Amount of desorbed protein was 1.41 +/- 0.01 in full and 1.43 +/- 0.01 in low dose vs. 1.78 +/- 0.01 mg/dl in control (P < 0.05). CONCLUSION: Hyaluronan-based heparin-bonded circuits provided better clinical outcome and less inflammatory response compared with uncoated surfaces. Reduced systemic heparinization combined with hyaluronan-based heparin-bonded circuits is feasible and clinically well tolerated.

Upregulation of glucose-6-phosphate dehydrogenase and NAD(P)H oxidase activity increases oxidative stress in failing human heart.

BACKGROUND: We previously found that higher NADPH levels produced by glucose-6-phosphate dehydrogenase (G6PD) can enhance myocardial superoxide generation by NAD(P)H oxidase in a dog model of dilated cardiomyopathy. Therefore, we tested whether G6PD activity is elevated and enhances NADPH level and increases NAD(P)H oxidase-derived superoxide production in the myocardium from patients with heart failure from ischemic cardiomyopathy. METHODS AND RESULTS: Surgical discards of left ventricle were collected from 8 congestive heart failure patients undergoing surgical ventricular restoration procedures, whereas control left ventricle tissue was obtained from 5 normal donor hearts deemed not suitable for transplantation. Biochemical assays were performed in tissue homogenates. We found that superoxide and hydrogen peroxide were elevated, respectively, by 9- and 3-fold in failing versus normal hearts (P < .05). The NAD(P)H oxidase inhibitors gp91(ds-tat), apocynin, and diphenyleneiodonium, significantly inhibited superoxide generation by approximately 75%, 89%, and 91%, respectively. Superoxide production by NAD(P)H oxidase increased 10- and 3-fold by adding NADPH (100 micromol/L) and NADH (100 micromol/L), respectively, in a DPI- and gp91(ds-tat)-inhibitable manner. Interestingly, chelerythrine, a PKC inhibitor, and PP2, a Src kinase family inhibitor, reduced G6PD activity (0.29 +/- 0.04 nM x min x mg protein) by 50% and 51% and these inhibitors also decreased myocardial superoxide by 99% and 79%, respectively. Furthermore, 6-aminonicotinamide, a G6PD inhibitor, decreased myocardial superoxide production by 71%. CONCLUSIONS: These data suggest that high NAD(P)H oxidase, fueled by G6PD-derived NADPH, generates most of the superoxide in failing hearts of patients with ischemic cardiomyopathy. In addition, PKC-Src kinase signaling pathways seem to coordinate the activation of both G6PD and NAD(P)H oxidase in human cardiac muscle.

Regulation of human internal mammary and radial artery contraction by extracellular and intracellular calcium channels and cyclic adenosine 3', 5' monophosphate.

BACKGROUND: The internal mammary (IMA) and radial arteries (RA), which are routinely used in coronary artery bypass grafting, show a significant incidence of postoperative vasospasm. The present study evaluated the respective roles of calcium (Ca2+)-dependent and cyclic adenosine 3', 5' monophosphate-dependent (cAMP) signaling in mediating contraction and relaxation of the IMA and RA. METHODS: We examined the contractile responses of the IMA and RA to potassium chloride, a depolarizing agent; phenylephrine, an alpha-adrenergic agonist; and U46619, a thromboxane analogue, in the absence and presence (0.045 to 1.500 mM) of extracellular Ca2+. RESULTS: Potassium chloride elicited little or no contraction in the absence of extracellular Ca2+. Contractions elicited by U46619 were similar in the IMA and RA, both in the absence and presence of extracellular Ca2+. By contrast, phenylephrine elicited significantly greater extracellular Ca2+-dependent contraction of the IMA than the RA. Estimation of cyclic guanosine 3', 5' monophosphate (cGMP) and cAMP revealed levels of cAMP to be about fourfold higher than cGMP in both the RA and IMA. Whereas forskolin and milrinone elicited similar relaxation of IMA and RA precontracted with either U46619 or phenylephrine and increased adenylate cyclase-catalyzed cAMP production, isoproterenol-induced relaxation of the arteries precontracted with U46619 was significantly impaired compared with arteries precontracted with phenylephrine. CONCLUSIONS: Our findings suggest that thromboxane A2 receptor-dependent pathways activate contraction of IMA and RA through both extracellular Ca2+-dependent and Ca2+-independent pathways. In addition, adenylate cyclase appears to play a key role in attenuating thromboxane A2 and alpha-adrenergic receptor-mediated contraction through both pathways.

Clinical effects of leukofiltration and surface modification on post-cardiopulmonary bypass atrial fibrillation in different risk cohorts.

OBJECTIVE: A manifestation of inflammatory injury to the heart, atrial fibrillation (AF), ranks among the most frequent and potentially life-threatening post-operative complications. METHODS: In a prospective randomized study, 120 patients undergoing CABG were allocated into two groups (N = 60): Group 1: Polymethoxyethylacry late-coated circuits + Leukocyte filters (Terumo,USA); Group 2: CONTROL: Uncoated circuits (Terumo,USA). Each group was further divided into three subgroups (N = 20) with respect to low (Euroscore 0-2), medium (3-5) and high (6+) risk patients. RESULTS: Serum IL-2 levels were significantly lower in the study group at T4 and T5 (p < 0.01). C3a levels showed significant differences in the leukofiltrated group at T4 and T5 (p < 0.05). CPKMB levels demonstrated well-preserved myocardium in the leukofiltration group, post-operatively. AF incidence was 10% (2 patients) in the study and 35% (7 patients) in the control cohorts (p < 0.05). Phagocytic capacity on fibers in filtered patients was significantly lower. CONCLUSION: Leukofiltration and coating significantly reduce the incidence, ventricular rate, and duration of AF after CABG via modulation of systemic inflammatory response and platelet preservation in high risk groups.

Influence of hematocrit and pump prime on cerebral oxygen saturation in on-pump coronary revascularization.

BACKGROUND: The couplings between cerebral oxygenation (rSO2), on-pump hematocrit and circuit prime are explored in this study. METHODS: Thirty-eight consecutive patients undergoing coronary revascularization with cardiopulmonary bypass (CPB) were matched on preoperative hematocrit < 40% and > 40% (n = 16). Similarly, six blood prime patients were matched with six crystalloid prime patients. Hematocrit and rSO2 levels were then compared on CPB. RESULTS: The preoperative hematocrit > 40% group retained higher levels on pump run (p < 0.01) and significantly higher rSO2 prior to CPB (64.8 +/- 9.6 versus 73.2 +/- 7.3), and on and off CPB (61.1 +/- 8.8 versus 67.4 +/- 6.4). Blood priming increased absolute rSO2 (2.3 +/- 6.3 versus -10.9 +/- 5.9) and % rSO2 (4.7 +/- 11.8 versus -14.2 +/- 7.4%) in the low hematocrit group. CONCLUSION: Blood primes are instrumental in high-risk and low preoperative hematocrit patients in preventing cerebral oxygen desaturation during initiation and maintenance of CPB.

Thromboxane receptor stimulation suppresses guanylate cyclase-mediated relaxation of radial arteries.

BACKGROUND: The internal mammary artery (IMA) and the radial artery (RA) are routinely used in coronary artery bypass grafting. However, RA grafts have a higher incidence of postoperative vasospasm and comparatively poor patency rates. The present study was undertaken to investigate the signaling pathways mediating contraction and relaxation in the IMA and RA with the aim of better understanding the mechanism underlying the propensity of RA grafts to spasm. METHODS: We examined the contractile responses of the IMA and RA to KCl (a depolarizing agent), phenylephrine (an alpha-adrenergic agonist), and U46619 (a thromboxane analogue). RESULTS: Contractions induced by KCl or U46619 did not significantly differ in IMA and RA. By contrast, phenylephrine evoked significantly greater contraction of the IMA than the RA. Contractions induced by both phenylephrine and U46619 were dose-dependently inhibited by nifedipine (an L-type calcium channel blocker). Estimation of thromboxane A2 (TxA2) and prostacyclin (PGI2) synthesis revealed that the TxA2 to PGI2 ratio in the RA was twice that in the IMA. Moreover, acetylcholine-induced and nitroglycerin-induced relaxation of RA precontracted with U46619 was significantly impaired, as compared with RA precontracted with phenylephrine. These data suggest that inhibition of nitroglycerin-induced soluble guanylate cyclase activity by U46619 was at least partially responsible for the diminished vasodilatory response of RA to nitric oxide. CONCLUSIONS: Our findings suggest that by reducing nitric oxide-stimulated soluble guanylate cyclase activity, the higher TxA2 to PGI2 ratios in RA, and the elevated serum TxA2 levels seen during coronary artery bypass grafting operations, may underlie the vasospasm and poor patency rates seen with the RA.

Comparison of polymethoxyethylacrylate-coated circuits with leukocyte filtration and reduced heparinization protocol on heparin-bonded circuits in different risk cohorts.

OBJECTIVES: The relative benefits of strategic leukofiltration on polymer-coated and low-dose heparin protocol on heparin-coated circuits were studied across EuroSCORE patient risk strata for three different cohorts. METHODS: In a prospective, randomized study, 270 patients undergoing coronary artery bypass grafting were allocated into three groups (n = 90): Group 1 - polymethoxyethylacrylate-coated circuits + leukocyte filters; Group 2 - polypeptide-based heparin-bonded circuits with reduced heparinization; and Group 3--CONTROL: uncoated circuits. Each group was further divided into three subgroups (n = 30), with respect to low- (EuroSCORE 0-2), medium- (3-5), and high- (6+) risk patients. Blood samples were collected at T1: following induction of anesthesia; T2: following heparin administration; T3: 15 min after CPB; T4: before cessation of CPB; T5: 15 min after protamine reversal; and T6: ICU. RESULTS: In high-risk cohorts, leukocyte counts demonstrated significant differences at T4 and T5 in Group 1, and at T4 in Group 2. Platelet counts were preserved significantly better at T4 and T5 in both groups (p < 0.05 versus control). Serum IL-2 and C3a levels were significantly lower at T3, T4 and T5 in Group 1, and T4 and T5 in Group 2 (p < 0.05). Postoperative bleeding, respiratory support time and incidence of atrial fibrillation were lower in the study groups versus control. Cell counts on filter mesh and heparin-coated fibers/ circuits were significantly higher in the high-risk cohorts versus uncoated fibers. Phagocytic capacity increased on filter mesh, especially in high-risk specimens. SEM evaluation demonstrated better preserved coated circuits. CONCLUSION: Leukofiltration and coating reduced platelet adhesion, protein adsorption, atrial fibrillation and reduced heparinization acted via modulation of systemic inflammatory response in high-risk groups.

Clinical performance and biocompatibility of novel hyaluronan-based heparin-bonded extracorporeal circuits.

We tested documented in vitro and ex vivo advantages of novel hyaluronan based heparin bonded extracorporeal circuits in a prospective randomized study. During the period from June until September 2005, 40 patients undergoing reoperation for coronary artery bypass grafting were allocated into two equal groups (n = 20): Group 1 was treated with hyaluronan-based heparin-bonded circuits and group 2 was treated with uncoated control circuits. Complete blood count, fibrinogen, albumin, C3a, interleukin-2 levels, and thromboelastographic data were documented after induction of anesthesia (T1) and heparin administration before cardiopulmonary bypass (CPB) (T2), 15 minutes after initiation of CPB (T3), before cessation of CPB (T4), 15 minutes after reversal with protamine (T5), and the first postoperative day at 8:00 a.m. (T6). Hollow fibers were collected for consecutive biomaterial analysis by optical and scanning electron microscopy (SEM). Desorbed protein deposition on fibers was compared by spectrophotometry. Leukocyte counts were lower in T4-T6 in group 1 (p < .05). Platelet counts demonstrated significant differences at T4 and T5 in coated group (p < .05). Albumin and fibrinogen levels were better preserved in Group 1 at T4, T5 and T4, T6, consecutively (p < .05). C3a and IL-2 levels were lower at T3-T5 and T4-T5 in intervention group (p < .05). Postoperative hemorrhage was 412 +/- 50 mL in group 1 and 684 +/- 50 ml in group 2 (p < .05). Respiratory support time was shorter in group 1 versus control (p < .05). Platelet adhesion was significantly lower in intervention group. Amount of desorbed protein was 1.44 +/- 0.01 mg/dL in group 1 and 1.94 +/- 0.01 mg/dL in control (p < .05). SEM and spectrophotometry demonstrated better surface preservation in the hyaluronan coated group. Novel hyaluronan-based heparin-bonded circuits reduce platelet adhesion-aggregation and protein adsorption and provide better perioperative clinical parameters through platelet, albumin, and fibrinogen-sparing effects.