Prevention of TNFalpha-associated myocardial dysfunction resulting from cardiopulmonary bypass and cardioplegic arrest by glucocorticoid treatment.

OBJECTIVE: Cardiac surgery on cardiopulmonary bypass (CPB) results in progressive myocardial dysfunction, despite unimpaired coronary blood flow, and is associated with increased myocardial tumor necrosis factor-alpha (TNFalpha) expression. We investigated whether anti-inflammatory treatment prevents increased TNFalpha expression and myocardial dysfunction after CPB. METHODS AND RESULTS: Baseline systemic hemodynamics, myocardial contractile function, aortic and coronary blood flow were measured in anesthetized pigs. Then, placebo (PLA; saline; n=7) or methylprednisolone (MP; 30 mg/kg; n=6) was infused intravenously and CPB was instituted. Global ischemia was induced for 10 min by aortic cross-clamping, followed by 1 h of cardioplegic cardiac arrest. After declamping and reperfusion, CPB was terminated after a total of 3 h. Measurements were repeated at 15 min, 4 h, and 8 h following termination of CPB. Systemic TNFalpha-plasma concentrations and left ventricular TNFalpha expression were analyzed. With unchanged coronary blood flow in both groups, a progressive loss of myocardial contractile function to 38+/-2% of baseline (p<0.01) and cardiac index to 48+/-6% of baseline (p<0.01) at 8 h after CPB in PLA was attenuated in MP (myocardial function: 72+/-3%, p<0.01 vs PLA; cardiac index: 78+/-6%, p<0.05 vs PLA). Systemic TNFalpha was increased at 8 h in PLA compared to MP (243+/-34 vs 90+/-34 pg/ml, p<0.05). Myocardial TNFalpha was increased at 8 h after CPB compared to baseline and MP (p<0.05). Myocardial TNFalpha immunostaining was more pronounced in PLA than in MP (p<0.05), with TNFalpha-mRNA localization predominantly to cardiomyocytes. CONCLUSIONS: Methylprednisolone attenuates both systemic and myocardial TNFalpha increases and progressive myocardial dysfunction induced by cardiac surgery, suggesting a key role for TNFalpha.     

Prophylactic use of pentoxifylline on inflammation in elderly cardiac surgery patients

BACKGROUND: Inflammation plays a pivotal role in the pathogenesis of organ injury after cardiopulmonary bypass (CPB). Elderly patients appear to be especially prone to develop general inflammation. Use of pentoxifylline (PTX) before surgery may be a promising approach to minimize the negative effects of CPB in these patients. METHODS: In a prospective, randomized study, patients more than 80 years old undergoing aortocoronary artery bypass grafting received either PTX (n = 15) after induction of anesthesia (initial bolus of 300 mg followed by a continuous infusion of 1.5 mg.kg(-1).h(-1) during the next 2 days) or saline as placebo (control group; n = 15). Polymorphonuclear neutrophil (PMN) elastase, C-reactive protein (CRP), and interleukins (IL-6, IL-8, IL-10) were measured from arterial blood samples before surgery (T0), at the end of surgery (T1), 5 hours after surgery (T2), and at the morning of the first (T3) and second (T4) postoperative day. RESULTS: Postoperatively, PTX-treated patients less often needed catecholamines and were extubated earlier than the control patients (p < 0.05). On the intensive care unit, cardiac index inceased more in the PTX-treated (from 1.95 +/- 0.3 to 3.26 +/- 0.4 L.min(-1).m(-2)) than in the control patients (from 1.89 +/- 0.2 to 2.78 +/- 0.3 L.min(-1).m(-2)). Increase in CRP and PMN-elastase was significantly higher in the untreated control than in the PTX patients. After CPB, IL-6, IL-8, and IL-10 increased in both groups showing a significantly higher increase in the untreated control patients (IL-8 control: from 11.3 +/- 2.6 to 154.4 +/- 57 pg/mL [T1]); IL-8 PTX: from 10.9 +/- 2.7 to 71.8 +/- 23 pg/mL [T1]). CONCLUSIONS: In elderly cardiac surgery patients, use of PTX before surgery and continued after CPB resulted in less inflammatory response than in an untreated control group. The value of attenuating the inflammatory process by PTX on outcome in this patient population needs to be evaluated in further controlled studies.     

Impact of acute myocardial edema on left ventricular function.

Studies of the impact of myocardial edema on left ventricular (LV) systolic function show conflicting results. We sought to evaluate the impact of increased myocardial water content (MWC) on LV systolic and diastolic function. Anesthetized dogs (n = 12) were instrumented with myocardial ultrasonic crystals and an LV micromanometer. Systolic function was measured by preload recruitable stroke work (PRSW) and dP/dt(max). Diastolic function was measured by -dP/dt(max) and the isovolumic relaxation constant tau (t). Myocardial water content (MWC) was determined using microgravimetry. In six dogs (coronary sinus hypertension, CSH group) we produced myocardial edema by inflating a coronary sinus balloon for 2 h (30-40 mm Hg). In six other dogs (Plegisol, PLEG group) cardiopulmonary bypass (CPB) was initiated (12.3 +/- 0.8 min), the aorta was cross-clamped (117 +/- 19 s), and 700 mL 4 degrees C crystalloid, hyperkalemic cardioplegic solution (Plegisol) was administered into the aortic root (62 +/- 4 mm Hg). After declamping and reperfusion (7.2 +/- 1.0 min), the dogs were separated from CPB. Myocardial function parameters and MWC were measured for 2 h after edema generation. In the CSH group, MWC significantly increased from 75.9 +/- 0.3% to 77.6 +/- 0.3% (p < .05). In the PLEG group, MWC increased from 75.8 +/- 0.3% to 77.7 +/- 0.3% (p < .05). PRSW and dP/dt(max) did not decrease in either group. Diastolic parameters did not change significantly. We conclude that acute myocardial edema without myocardial injury does not impair LV function.     

Left ventricular function and chronotropic responses after normothermic cardiopulmonary bypass with intermittent antegrade warm blood cardioplegia in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Recent studies indicate that normothermic cardiopulmonary bypass (CPB) with intermittent antegrade warm blood cardioplegia (IAWBC) may have metabolic and clinical advantages, but limited data exist on its effects on myocardial function. Therefore, we investigated the acute effects of this approach on systolic and diastolic left ventricular function and on chronotropic responses. METHODS: In 10 patients undergoing isolated CABG we obtained on-line left ventricular pressure-volume loops using the conductance catheter before and after normothermic CPB with IAWBC. Steady state and load-independent indices of left ventricular function derived from pressure-volume relations were obtained during right atrial pacing (80-100-120 beats/min) to determine baseline systolic and diastolic function and chronotropic responses. RESULTS: The mean time of CPB was 105+/-36 min (median 103, range 60-167 min) with a mean aortic cross-clamp time of 75+/-27 min (median 69, range 43-129 min). Baseline (80 beats/min) end-systolic elastance (E(ES)) did not change after CPB (1.22+/-0.53 to 1.12+/-0.28 mm Hg/ml, P>0.2), while the diastolic chamber stiffness constant (k(ED)) significantly increased (0.014+/-0.005 to 0.040+/-0.007 ml-1, P=0.018) and relaxation time constant (tau) significantly decreased (61+/-3 to 49+/-2 ms, P=0.004). Before CPB, incremental atrial pacing had no significant effects on E(ES) and tau but significant negative effects on kED (0.014+/-0.005 to 0.045+/-0.012 ml-1, P=0.013). After CPB, atrial pacing had significant positive effects on E(ES), tau and kED (E(ES): 1.12+/-0.28 to 2.60+/-1.54 mm Hg/ml, P=0.021; tau: 49+/-2 to 45+/-2 ms, P=0.009; kED: 0.040+/-0.007 to 0.026+/-0.005 mm Hg, P=0.010), indicating improved systolic and diastolic chronotropic responses. CONCLUSION: On-pump normothermic CABG with IAWBC preserved systolic function, increased diastolic stiffness, and improved systolic and diastolic chronotropic responses. Normalization of the chronotropic responses post-CPB is likely due to effects of successful revascularization and subsequent relief of ischemia.     

A double-blind randomized trial: prophylactic vasopressin reduces hypotension after cardiopulmonary bypass

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) predisposes patients to vasodilatory hypotension after cardiopulmonary bypass (CPB). This hypotension has been correlated with arginine vasopressin deficiency and can be corrected by its replacement. In patients receiving ACE inhibition, we investigated whether initiation of vasopressin before CPB would diminish post-CPB hypotension and catecholamine use by avoiding vasopressin deficiency. METHODS: Cardiac surgical patients on ACE inhibitor therapy were randomized to receive vasopressin (0.03 U/min) (n = 13) or an equal volume of normal saline (n = 14) starting 20 minutes before CPB. RESULTS: Vasopressin did not change pre-CPB mean arterial pressure or pulmonary artery pressure. After CPB, the vasopressin group had a lower peak norepinephrine dose than the placebo group (4.6 +/- 2.5 versus 7.3 +/- 3.5 microg/min, p = 0.03), a shorter period on catecholamines (5 +/- 6 versus 11 +/- 7 hours, p = 0.03), fewer hypotensive episodes (1 +/- 1 versus 4 +/- 2, p < 0.01), and a shorter intensive care unit length of stay (1.2 +/- 0.4 versus 2.1 +/- 1.4 days, p = 0.03). CONCLUSIONS: In this cohort, prophylactic administration of vasopressin, at a dose without a vasopressor effect pre-CPB, reduced post-CPB hypotension and vasoconstrictor requirements, and was associated with a shorter intensive care unit stay.     

Disadvantages of prostacyclin infusion during cardiopulmonary bypass: a double-blind study of 50 patients having coronary revascularization

Prostacyclin (PGI2) has been suggested for use in cardiopulmonary bypass (CPB) because of its positive effects on platelet number and function. Fifty patients who underwent coronary artery bypass grafting using a bubble oxygenator received heparin, 3 mg per kilogram of body weight, and then were randomly assigned to receive PGI2, 25 ng/kg/min, beginning 5 minutes before and until the end of CPB (26 patients) or a placebo (24 patients). Both groups were similar in sex, age, heparin dose, protamine dose, and CPB time. During CPB, mean arterial pressure fell significantly with PGI2 (76 +/- 2 mm Hg to 53 +/- 2 mm Hg; p less than 0.05) and necessitated pressor substances. Platelet counts fell significantly in both groups with the start of CPB, but after 60 minutes were similar in both groups (118 +/- 9 X 10(3) versus 130 +/- 8 X 10(3); not significant [NS]) and were unchanged 3 hours after CPB. Total chest tube output was 647 +/- 51 ml (placebo group) versus 576 +/- 34 ml (PGI2 group) (NS); 18 of the patients given PGI2 required 26 transfusions compared with 16 transfusions in 8 of the patients given a placebo (p less than 0.05). In PGI2 patients, arterial oxygen tension on 100% oxygen fell from 281 +/- 18 mm Hg before CPB to 223 +/- 17 mm Hg immediately after CPB (p less than 0.05). The placebo patients did not show a change in this variable.(ABSTRACT TRUNCATED AT 250 WORDS)     

A novel technique using echocardiography to evaluate venous cannula performance perioperatively in CPB cardiac surgery.

OBJECTIVE: Transthoracic echocardiography (TTE) has been used clinically to disobstruct venous drainage cannula and to optimise placement of venous cannulae in the vena cava but it has never been used to evaluate performance capabilities. Also, little progress has been made in venous cannula design in order to optimise venous return to the heart lung machine. We designed a self-expandable Smartcanula (SC) and analysed its performance capability using echocardiography. METHODS: An epicardial echocardiography probe was placed over the SC or control cannula (CTRL) and a Doppler image was obtained. Mean (V(m)) and maximum (V(max)) velocities, flow and diameter were obtained. Also, pressure drop (DeltaP(CPB)) was obtained between the central venous pressure and inlet to venous reservoir. LDH and Free Hb were also compared in 30 patients. Comparison was made between the two groups using the student's t-test with statistical significance established when p<0.05. RESULTS: Age for the SC and CC groups were 61.6+/-17.6 years and 64.6+/-13.1 years, respectively. Weight was 70.3+/-11.6 kg and 72.8+/-14.4 kg, respectively. BSA was 1.80+/-0.2 m(2) and 1.82+/-0.2 m(2), respectively. CPB times were 114+/-53 min and 108+/-44 min, respectively. Cross-clamp time was 59+/-15 min and 76+/-29 min, respectively (p=NS). Free-Hb was 568+/-142 U/l versus 549+/-271 U/l post-CPB for the SC and CC, respectively (p=NS). LDH was 335+/-73 mg/l versus 354+/-116 mg/l for the SC and CC, respectively (p=NS). V(m) was 89+/-10 cm/s (SC) versus 63+/-3 cm/s (CC), V(max) was 139+/-23 cm/s (SC) versus 93+/-11 cm/s (CC) (both p<0.01). DeltaP(CPB) was 30+/-10 mmHg (SC) versus 43+/-13 mmHg (CC) (p<0.05). A Bland-Altman test showed good agreement between the two devices used concerning flow rate calculations between CPB and TTE (bias 300 ml+/-700 ml standard deviation). CONCLUSIONS: This novel Smartcanula design, due to its self-expanding principle, provides superior flow characteristics compared to classic two stage venous cannula used for adult CPB surgery. No detrimental effects were observed concerning blood damage. Echocardiography was effective in analysing venous cannula performance and velocity patterns.     

Intraoperative echocardiographic assessment of left ventricular muscle volume changes after intracardiac operation under cardiopulmonary bypass

Cardiopulmonary bypass (CPB) and concomitant cardioplegic arrest (CA) may cause impairment of cardiac function with development of myocardial edema. There are few reports of intraoperative assessment of LV mass or muscle volume (MV) in patients, Fifteen patients (age; 0.5-68), 10 with congenital and 5 with valvular diseases, were studied by epicardial 2-dimensional and M-mode echocardiography. LVMV was obtained from M-mode study at pre- and post-CPB during surgery. Pre and post CPB LVMV-index (ml/m2) and percent change of LVMV were compared. CPB-time was 170 +/- 78 min (mean +/- SD), and CA time was 97 +/- 49 min. LVMV index increased significantly from 89 +/- 35 to 103 +/- 43 ml/m2 after CPB (p less than 0.01). Percent change ranging from -3 to +37% (14 +/- 12) correlated to CPB time (r = .81, p less than .01) and also to CA time (r = .62, p less than .05). These results indicated that CPB with CA caused acute increase in LVMV with a positive relation to its duration.     

Myocardial protective effect of FR167653; a novel cytokine inhibitor in ischemic-reperfused rat heart.

OBJECTIVES: In this study, a newly synthesized cytokine inhibitor FR167653 was investigated using a rat heart ischemia-reperfusion model to prove its myocardial protective effect and its role in the inhibition of cytokine production in ischemic myocardium. METHODS: Studies were performed with isolated, Langendorff-perfused Lewis rat hearts (n=80) which were either treated with FR167653 or untreated, as the control group, and subjected to ischemia-reperfusion. RESULTS: Reperfusion followed by 30min of 37 degrees C ischemia induced marked myocardial cytokine expression and activated p38MAPK. FR167653 administered before ischemia and during reperfusion significantly reduced ischemia-activated myocardial TNFalpha mRNA expression (190+/-97 vs. 4805+/-3017, P=0.024) as well as TNFalpha production (0 vs. 9.6+/-2.5 ng/ml, P<0.05) and also inhibited p38 MAPK activation. Its administration improved recovery of cardiac contractile function during reperfusion: LVDP (130+/-18 vs. 82+/-21 mmHg (P=0.002)), max/min dP/dt (2812+/-328/-2283+/-216 vs. 1520+/-424/-1325+/-237 mmHg/s, P=0.003). CPK leakage was significantly reduced in FR167653 treated hearts versus untreated hearts (54+/-6 vs. 0.5+/-0.1, P<0.05) and reduction of coronary flow was improved (110+/-13 vs. 77+/-11%) 1h after beginning of reperfusion (P<0.05). Moreover, FR administration attenuated the number of TUNEL positive cardiomyocytes (3+/-1 vs. 9+/-2%). CONCLUSION: These data demonstrated positive inotropic and antiapoptotic effects of a newly synthesized compound (FR167653) of cytokine inhibitors and its inhibitory effect on myocardial TNFalpha production and p38 MAPK activation in ischemic-reperfused rat heart. This suggested that cytokine inhibition is significant as a method for myocardial protection against ischemia-reperfusion injury.     

Moderate versus deep hypothermia for the arterial switch operation--experience with 100 consecutive patients.

OBJECTIVES: To evaluate the impact of moderate versus deep perioperative hypothermia on postoperative morbidity in patients receiving the arterial switch operation (ASO). METHODS: One hundred consecutive patients received the ASO from 9/98 to 4/06 using temperature-corrected full-flow moderate (M>24 degrees C, n=51) or deep hypothermic cardiopulmonary bypass (CPB) (D <20 degrees C, n=49). Complex TGA morphology was present in 33 patients (M: 27.4%, D: 38.8%, n.s.). Median age was 9 days (M) versus 10 days (D) and body weight was 3.5+/-0.7 kg (M) versus 3.6+/-0.9 kg (D) (both p=n.s.). Follow-up was 3.7+/-2.1 years. RESULTS: Lowest perioperative rectal temperature was 25.3+/-1.1 degrees C (M) versus 19.0+/-0.8 degrees C (D), p<0.001. Intraoperative blood transfusion (M: 231+/-47 ml, D: 252+/-112 ml, p=0.04) and postoperative lactate level (M: 3.2+/-1.3 mmol/l, D: 3.8+/-2.4 mmol/l, p=0.02) were lower under moderate hypothermia. One patient (D) suffered myocardial ischemia, required ECMO support and died. All other patients were safely weaned from CPB using dopamine (M: 3.0 microg/kg min, D: 3.4 microg/kg min, n.s.) and dobutamine (M: 5.6 microg/kg min, D: 6.7 microg/kg min, p=0.048). Secondary chest closure was performed in 41% (M) versus 59% (D) (p=0.04). Patients were extubated after 89 h (M) versus 126 h (D) (p=0.03). Under moderate hypothermia ICU stay (M: 8.4+/-4.7 days, D: 12.0+/-13.8 days, p=0.03) and hospital stay (M: 12.8+/-6.8 days, D: 20.7+/-15.5 days, p=0.001) were shorter. Five-year freedom from reoperation was 97.0% for simple and 85.2% for complex TGA with RVOT reconstruction in 4/6 patients. CONCLUSIONS: The ASO under full-flow moderate compared to deep hypothermia was advantageous regarding length of procedure and primary chest closure rate. Moderate hypothermia seemed to be beneficial for pulmonary recovery, length of chest tube drainage treatment and inotropic support. No worse early or long-term effects of moderate hypothermia were found.     

Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures?

OBJECTIVE: To discover the possible effects of methylprednisolone on the systemic inflammatory response during aprotinin treatment. DESIGN: Randomized, double-blinded study. SETTING: University-affiliated heart center. PARTICIPANTS: Fifty-two patients scheduled for elective coronary artery bypass grafting. INTERVENTIONS: In the methylprednisolone group (n = 26), 1 g of methylprednisolone was administered 30 minutes before cardiopulmonary bypass (CPB). The 26 control patients received a placebo instead. High-dose aprotinin was administered to all participants. MEASUREMENTS AND MAIN RESULTS: After CPB, the concentration of the proinflammatory cytokines, interleukin-6 and interleukin-8, was significantly less in the methylprednisolone group. The anti-inflammatory interleukin-10 concentration was, in contrast, greater. After CPB, PaO2 was greater in the methylprednisolone group (245+/-17 v 195+/-16 mmHg). Dynamic pulmonary compliance was also greater, whereas the alveolar-arterial oxygen difference was less (376+/-17 v 428+/-16 mmHg). On arrival in the intensive care unit, the oxygen delivery index was greater in the methylprednisolone group (62+/-2.7 v 54+/-2.3 mL/min/m2) and the oxygen extraction rate was less (25%+/-0.02% v 30%+/-0.02%). After CPB, the cardiac index was significantly greater in the methylprednisolone group (4.1+/-0.2 v 3.6+/-0.2 L/min/m2). These patients had less blood loss postoperatively (616+/-52 v 833+/-71 mL; p = 0.017) and a greater urine output (8,015+/-542 v 6,417+/-423 mL/24 h; p = 0.024). CONCLUSION: The use of methylprednisolone attenuates the systemic inflammatory response during aprotinin treatment and improves clinical outcome parameters.     

Perioperative assessment of left ventricular function by pressure-volume loops using the conductance catheter method

Interpretation of perioperative measurements of cardiac function during cardiac surgery is complicated by changes in loading conditions induced by anesthesia, cardiopulmonary bypass (CPB), and the surgical procedure itself. Quantification of left ventricular (LV) function by pressure-volume relations as obtained by the conductance catheter would be advantageous because load-independent indices can be determined. Accordingly, we evaluated methodological aspects of the conductance-catheter technique and documented LV function before and after CPB in eight patients undergoing coronary artery bypass grafting. LV pressure-volume loops by transesophageal echocardiography-guided transaortic application of the conductance catheter were obtained at steady-state and during preload reduction by temporary occlusion of the inferior cava. All patients remained hemodynamically stable, and no complications occurred. Complete data were acquired within 15 min before and after CPB. Cardiac output (5.2 +/- 1.3 L/min to 6.0 +/- 1.4 L/min) and LV ejection fraction (46% +/- 17% to 48% +/- 19%) did not change, but end-diastolic pressure increased significantly after CPB (8 +/- 2 mm Hg to 16 +/- 7 mm Hg; P < 0.05). Load-independent systolic indices remained constant (end-systolic elastance: 1.31 +/- 1.20 mm Hg/mL to 1.13 +/- 0.59 mm Hg/mL). Diastolic function changed significantly after CPB, as the relaxation time constant decreased from 64 +/- 6 ms to 52 +/- 5 ms (P < 0.05) and the chamber stiffness constant increased from 0.016 +/- 0.014/mL to 0.038 +/- 0.016/mL (P < 0.05). We conclude that the conductance catheter method provides detailed data on perioperative myocardial function and may be useful for evaluating the effects of new surgical and anesthetic procedures. IMPLICATIONS: Pressure-volume loops provide on-line quantification of intrinsic systolic and diastolic myocardial function in a load-independent fashion. This study shows the feasibility of perioperative pressure-volume analysis by use of the conductance-catheter method. This method provides detailed data about the immediate effects of surgery and may be used to evaluate complex cardiac procedures.     

Retrograde autologous priming: is it useful in elective on-pump coronary artery bypass surgery?

BACKGROUND: The effect of reduced cardiopulmonary bypass (CPB) prime volume by retrograde autologous priming (RAP) was studied. METHODS: Twenty patients undergoing elective coronary artery bypass grafting were randomized to either standard prime (SP) volume (1,602 +/- 202 mL crystalloid prime, n = 10) or RAP (395 +/- 150 mL). RAP was performed by draining crystalloid prime from the arterial and venous lines into a recirculation bag before CPB. Cardiac index, pulmonary vascular resistance index, systemic vascular resistance index, alveolar-arterial oxygen tension difference, pulmonary shunt fraction, extravascular lung water (EVLW), plasma colloid osmotic pressure (COP), crystalloid fluid balance, body weight, and clinical parameters were evaluated perioperatively. RESULTS: Demographic data and operative parameters were equal for patients in both groups. During CPB, COP was reduced by 55% in the SP group (9.8 +/- 2.0 vs 21.4 +/- 2.1 mm Hg) and by 41% in the RAP group (12.4 +/- 1.1 vs 20.9 +/- 1.8 mm Hg) (p = 0.008, SP vs RAP group). Compared with preoperatively, EVLW was unchanged in the RAP group 2 hours post-CPB, but it was elevated by 21% in the SP group (p = 0.002, SP vs RAP group). End-CPB crystalloid fluid balance was significantly reduced in the RAP group (1,857 +/- 521 vs 2,831 +/- 637 mL). Postoperative (day 2) weight gain in the SP group (1.5 +/- 1.2 kg, p = 0.021) was absent in the RAP group (0.1 +/- 0.9, NS). Postoperative time to full mobilization was shorter in the RAP group. Postpump cardio-respiratory function did not differ among groups. CONCLUSIONS: This small-scale pilot study indicates that by reducing crystalloid fluid administration and fall of COP during CPB, RAP reduces postpump EVLW accumulation and weight gain in uncomplicated coronary artery bypass graft patients with no associated effects on cardio-respiratory function.     

Milrinone, not epinephrine, improves left ventricular compliance after cardiopulmonary bypass

OBJECTIVE: To compare the effects of milrinone versus epinephrine administered after cardiopulmonary bypass (CPB) on left ventricular compliance. DESIGN: Prospective and randomized. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty consenting adult patients. INTERVENTIONS: Patients undergoing aortocoronary bypass surgery were randomized to receive 50 microg/kg of milrinone (group M; n = 10) or 0.03 microg/kg/min of epinephrine (group E; n = 10) shortly after separation from CPB. Left ventricular compliance was assessed by observing changes in left ventricular end-diastolic area (LVEDA) in the short-axis view with transesophageal echocardiography, while maintaining a constant left atrial pressure. Measurements were performed (1) before CPB, (2) after separation from CPB, and (3) after either milrinone or epinephrine. MEASUREMENTS AND MAIN RESULTS: Baseline LVEDA decreased by 20% after CPB in the milrinone group (from 16.6 +/- 3.1 cm2 to 14.3 +/- 2.4 cm2; p < 0.05) and by 22% in the epinephrine group (from 19.4 +/- 4.1 cm2 to 17.2 +/- 3.8 cm2; p < 0.05). LVEDA increased by 15% after milrinone (from 14.3 +/- 2.4 cm2 to 15.6 +/- 2.8 cm2; p < 0.05) but remained unchanged after epinephrine (from 17.2 +/- 3.8 cm2 to 17.1 +/- 4.2 cm2; p = ns). CONCLUSIONS: Left ventricular compliance was decreased after CPB. The administration of milrinone, but not epinephrine, was associated with a partial return to prebypass values. The exact mechanism of action remains to be determined.     

Activator protein 1 activation following hypoosmotic stress in HepG2 cells is actin cytoskeleton dependent

BACKGROUND: An appropriate animal model of cardiopulmonary bypass (CPB) is critical in order to study the morbidity and mortality in newborn children undergoing long-term cardiac surgery. Since this has been reported to be technically difficult, this paper describes a neonatal porcine CPB model (3 days old, n = 18) for up to 8 h to study long-term bypass. METHODS: After anesthesia, neonates had arterial/venous monitoring lines inserted, they were heparinized (300 IU/kg), the aorta was cannulated for arterial retroperfusion, and a two-stage venous drainage catheter was placed in the right atrium. A Medtronic Minimax Plus oxygenator and the bypass circuit were primed with donor blood and CPB was instituted. RESULTS: Line and mean arterial pressures were kept at 147.7 +/- 73 and 62.7 +/- 9 mm Hg, respectively. Myocardial (38.1 +/- 1.0 degrees C) and rectal temperatures (37.7 +/- 1.0 degrees C) were maintained. Heart rate was 184.8 +/- 34.5 bpm. Hematocrits were 29.6 +/- 6.0%, activated clotting time was sustained above 400 s throughout bypass, blood gas parameters were maintained in the normal range (pH, 7.39 +/- 0.1; PO(2), 123.1 +/- 65.2 mm Hg; PCO(2), 37.2 +/- 8.5 mm Hg; and HCO(3)(-), 21.5 +/- 3.6 mmol/L). CPB was terminated after 8 h and no visceral edema or other imbalances normally associated with swine on bypass were observed. CONCLUSIONS: Results demonstrate a model of stable long-term bypass in neonatal swine which can be used to study issues critical to children requiring surgical correction and CPB at a young age. Overall effects of surgery and bypass on these younger patients have yet to be explored and therefore a stable long-term normothermic model of CPB would allow the study of numerous parameters associated with this complicated procedure.     

Normothermic cardiopulmonary bypass and myocardial cardioplegic protection for neonatal arterial switch operation.

OBJECTIVE: Hypothermic cardiopulmonary bypass (CPB) associated with cold myocardial protection is commonly used to perform neonatal cardiac surgery. Hypothermia is usually chosen to preserve the brain in case of failure of oxygen delivery whatever it may result from. Nowadays, there is a growing number of evidence demonstrating that hypothermia induces deleterious effects, which may culminate in organ dysfunctions. In 2001, we started a protocol where the heart and the body were no longer cooled, in all the procedures, including the arterial switch operation (ASO), except those with aortic arch reconstruction. METHODS: Because data on the neonatal arterial switch operation were prospectively gathered in our unit (and included fine biochemical analysis of myocardial damage), we have compared two consecutive populations of arterial switch operation to sort out the impact of normothermic CPB and normothermic cardioplegia. RESULTS: The results show that warm cardiopulmonary bypass associated with warm cardioplegia is feasible for ASO, and that most of the operative data are similar to hypothermic bypass, none are worse. Among the postoperative data, the cardiac troponin I (cTnI) time course showed significantly lower values in the normothermic group after 24 h (4.46 ng ml(-1) vs 6.17 ng ml(-1) (p = 0.027)), time to extubation is improved (32+/-26 h vs 70+/-69 h (p = 0.02)) and there is a trend to reduce the ICU length of stay (3.5+/-1.5 days vs 5.6+/-3.9 days (p = 0.08)), and consequently the cost of surgery. CONCLUSION: Normothermic cardiopulmonary bypass is feasible for ASO and seems to allow a faster recovery time.     

The synergistic effects of pentoxifylline on systemic and regional perfusion after hemorrhage and hypertonic resuscitation

Small volumes of hypertonic saline solution ([HS] 7.5% NaCl) produce systemic and microcirculatory benefits in hemorrhaged animals. Pentoxifylline (PTX) has beneficial effects when administrated after hemorrhagic shock. We tested the hypothesis that the combination of HS and PTX in the initial treatment of hemorrhagic shock provides synergistic hemodynamic benefits. Twenty-four dogs were bled to a target arterial blood pressure of 40 mm Hg and randomized into 3 groups: lactated Ringer's solution (33 mL/kg; n = 6); HS (7.5% NaCl 4 mL/kg; n = 9); and HS+PTX (7.5% NaCl 4 mL/kg + PTX 15 mg/kg; n = 9). Systemic hemodynamics were measured by Swan-Ganz and arterial catheters. Gastric mucosal-arterial Pco2 gradient (D(g-a)Pco2; gas tonometry), portal vein blood flow (ultrasonic flowprobe), and systemic and regional O2-derived variables were also evaluated. HS induced a partial increase in mean arterial blood pressure, cardiac output, and portal vein blood flow. In the HS+PTX group, we observed a significant, but transitory, increase in systemic oxygen delivery (180 +/- 17 versus 141 +/- 13 mL/min) in comparison to HS alone. PTX infusion during hypertonic resuscitation promoted a significant reduction in D(g-a)Pco2 (41.8 +/- 4.8 to 25.7 +/- 3.9 mm Hg) when compared with isolated HS infusion (48.2 +/- 6.4 to 39.4 +/- 5.5 mm Hg). We conclude that PTX as an adjunct drug during hypertonic resuscitation improves cardiovascular performance and gastric mucosal oxygenation.     

Biologically variable pulsation improves jugular venous oxygen saturation during rewarming

BACKGROUND: Conventional pulsatile (CP) roller pump cardiopulmonary bypass (CPB) was compared to computer controlled biologically variable pulsatile (BVP) bypass designed to return beat-to-beat variability in rate and pressure with superimposed respiratory rhythms. Jugular venous O2 saturation (SjvO2) below 50% during rewarming from hypothermia was compared for the two bypass techniques. A SjvO2 less than 50% during rewarming is correlated with cognitive dysfunction in humans. METHODS: Pigs were placed on CPB for 3 hours using a membrane oxygenator with alpha-stat acid base management and arterial filtration. After apulsatile normothermic CPB was initiated, animals were randomized to CP (n = 8) or BVP (roller pump speed adjusted by an average of 2.9 voltage output modulations/second; n = 8), then cooled to a nasopharyngeal temperature of 28 degrees C. During rewarming to stable normothermia, SjvO2 was measured at 5 minute intervals. The mean and cumulative area for SjvO2 less than 50% was determined. RESULTS: No between group difference in temperature existed during hypothermic CPB or during rewarming. Mean arterial pressure, arterial partial pressure O2, and arterial partial pressure CO2 did not differ between groups. The hemoglobin concentration was within 0.4 g/dL between groups at all time periods. The range of systolic pressure was greater with BVP (41 +/- 18 mm Hg) than with CP (12 +/- 4 mm Hg). A greater mean and cumulative area under the curve for SjvO2 less than 50% was seen with CP (82 +/- 96 versus 3.6% +/- 7.3% x min, p = 0.004; and 983 +/- 1158 versus 42% +/- 87% x min; p = 0.004, Wilcoxon 2-sample test). CONCLUSIONS: Computer-controlled BVP resulted in significantly greater SjvO2 during rewarming from hypothermic CPB. Both mean and cumulative area under the curve for SjvO2 less than 50% exceeded a ratio of 20 to 1 for CP versus BVP. Cerebral oxygenation is better preserved during rewarming from moderate hypothermia with bypass that returns biological variability to the flow pattern.     

High-dose aprotinin reduces activation of hemostasis,allogeneic blood requirement,and duration of postoperative ventilation in pediatric cardiac surgery

BACKGROUND: Though multiple studies have affirmed the effectiveness of aprotinin in reducing blood loss in adult cardiac surgery, the possible benefit in pediatric cardiac surgery is controversial. METHODS: In a double-blind, randomized, and placebo-controlled study, the efficacy of aprotinin in attenuating the hemostatic and inflammatory activation during cardiopulmonary bypass in 60 patients weighing less than 10 kg was investigated. Secondary endpoints were the influence of aprotinin on the reduction of blood loss and allogeneic blood requirement, as well as postoperative oxygenation and length of mechanical ventilation. Aprotinin was administered in a high-dose of 3 x 10(4) KIU/kg plus a bolus of 5 x 10(5) KIU (not weight adjusted) added to the pump prime. RESULTS: Aprotinin plasma concentration at the end of cardiopulmonary bypass (CPB) was with 184 +/- 45 KIU/mL, within the targeted range of 200 KIU/mL. Coagulation and fibrinolysis were suppressed (F1.2 1 hour after CPB: 5.35 +/- 2.9 nmol/L vs 14.5 +/- 23.1 nmol/L; D-dimer 1 hour after CPB: 0.63 +/- 0.6 ng/mL vs 2.3 +/- 3.1 ng/mL; p < 0.05), inflammatory markers (interleukin [IL]-6, IL-8, IL-10) increased over time without significant differences between the groups, and only complement C3a activation was significantly attenuated at the end of CPB in the aprotinin group. Chest tube drainage was significantly reduced (24 hours: median 13.5 [IQR 12.2] mL/kg vs 19.4 [8.2] mL/kg; p < 0.05). All patients received one unit of packed cells to prime the heart lung machine. A second unit was needed significantly less often in the aprotinin group (13% vs 47%; p < 0.05). Postoperative oxygenation (pO2/FIO2 172 [IQR 128] mm Hg vs 127 [74]; p < 0.05) improved, and the time on ventilator was shorter in the aprotinin group (median 45 hours [IQR 94] vs 101 [IQR 74]; p < 0.05). No side effects were attributable to the use of aprotinin. CONCLUSIONS: High-dose aprotinin effectively attenuated hemostatic activation and reduced blood loss and transfusion requirement in pediatric cardiac surgery. Postoperative ventilation was also shortened in the aprotinin group.