General anesthesia with thoracic epidural anesthesia in the cardiopulmonary bypass surgery reduces apoptosis by upregulating antiapoptotic protein Bcl-2

AIM: The aim of the paper was to investigate whether thoracic epidural anesthesia (TEA) together with general anaesthesia (GA) play a role on apoptosis in humans before cardiopulmonary bypass (CPB), before aortic cross clamp (ACC) and at 15 min after ACC release (after ischemia and reperfusion). METHODS: Eighty patients scheduled for elective CABG were randomized to receive either GA group (n: 40) or TEA+GA group (n: 40). The right atrial biopsy samples were taken before CPB, before ACC and at 15 min after ACC release from all patients. Human heart tissues were obtained from patients of TEA+GA group and GA group. The number of Bcl-2 positive cardiomyocytes was counted in multiple tissue sections of biopsies of 80 patients using light microscopy (magnification x 40) with an ocular micrometer system (Olympus). RESULTS: In the TEA+GA group, the Bcl-2 positive cardiomyocytes were distinctly statistically increased compared to the GA group (P<0.001). In addition, the intensity of the immunostaining was also increased in the TEA+GA compared with the GA group. The number of immunoreactive cardiomyocytes is as follows: before CPB, TEA+GA group 396+/-61, GA group 92+/-41, before ACC, TEA+GA group 333+/-47, GA group 94+/-18, at 15 min after ACC release, TEA+GA group 346+/-68.8, GA group 85+/-9.5. There were statistically significant differences between groups, (P<0.001). Between groups, at 4 h and at 24 h after the end of CPB, in the TEA+GA group, the CI was significantly higher than GA group respectively; (3.4+/-0.8 L/min/m(2) vs 2.5+/-0.8 L/min/m(2); P<0.001), (3.8+/-1.1 L/min/m(2) vs 3.1+/-1.1 L/min/m(2); P<0.008). Within groups, at 4 and 24 h after the end of CPB, in the TEA+GA group, the CI was significantly higher than baseline values, respectively, (3.4+/-0.8 L/min/m(2) vs 2.4+/-0.7 L/min/m(2); P<0.001), (3.8+/-1.1 L/min/m(2) vs 2.4+/-0.7 L/min/m(2); P<0.001). Whereas no difference was found in the GA group respectively, (2.6+/-0.8 L/min/m(2) vs. 2.5+/-0.8 L/min/m(2); P>0.05), (2.6+/-0.8 L/min/m(2) vs. 3.1+/-1.1 L/min/m(2); P>0.05). The number of patients showing ventricular fibrillation (VF), atrial fibrillation or heart block after release of the ACC was 11 of 40 (27.5%) in the TEA+GA group versus 25 of 40 (62.5%) in the GA group. The number of patients showing VF after release of ACC was 9 out of 20 patients (22.5%) in the TEA+GA group which was significantly lower than in the GA group (21 of 40 patients 52.5%); (P<0.006). Sinus rhythm after release of ACC, in the TEA+GA group was observed in 29 of 40 patients (72.5%) and was significantly higher than in the GA group (15 of 40 patients 37.5%); (P<0.002). CONCLUSION: The result of the present study indicate that TEA plus GA in coronary surgery had preserved cardiac function during intraoperative and postoperative period by means of reduced apoptosis, improved hemodynamic function and reduced arrhythmias after release of the ACC.     

The effect of combined preinduction thoracic epidural anaesthesia and glucocorticoid administration on perioperative interleukin-10 levels and hyperglycemia. A randomized controlled trial

AIM: Anti-inflammatory cytokines such as interleukin-10 (IL-10) play a key role in the anti-inflammatory cascade after cardiopulmonary bypass (CPB). Even moderate hyperglycemia can increase mortality/morbidity, stroke, and myocardial infarction after coronary artery bypass grafting (CABG). The purpose of our study was to investigate whether preinduction thoracic epidural anesthesia (TEA) and preinduction glucocorticoid have an effect on perioperative anti-inflammatory and perioperative hyperglycemia in patients undergoing CABG with CPB. METHODS: Sixty low-risk patients (n=60) undergoing elective CABG were randomly allocated into 4 groups: Group corticosteroid (Group S) (n=15) received 6-methylprednisolone 15 mg/kg IV 60 min before induction; Group TEA+corticosteroid (Group TEA+S) (n=15) received 20 mg bupivacaine in bolus 60 min before induction followed by 20 mg/h bupivacaine infusion intraoperatively and postoperatively via epidural catheter. Group TEA (n=15) received 20 mg bupivacaine in bolus 60 min before induction followed by 20 mg/h bupivacaine infusion intraoperatively and postoperatively via epidural catheter. Group control (Group C) (n=15) received neither preinduction TEA nor a preinduction steroid. Blood samples were sequentially taken before surgery (baseline), before CPB, 1 h after CPB, in the intensive care unit (ICU) and 24 h after surgery from an indwelling radial arterial catheter. RESULTS: Before CPB, circulating IL-10 levels were higher in groups TEA+S and S than in group C (P<0.05). At 1 h after CPB, IL-10 levels were higher in groups TEA+S and S than in group C (P<0.001). Before CPB and at 1 h after CPB, IL-10 levels were lower in group TEA than in group C (P<0.05). Before CPB, glucose levels were higher in group S than in groups TEA, C or TEA+S (P<0.001; P<0.05). There was no significant difference in glucose levels between groups TEA, TEA+S and C. At 1 hour after CPB, glucose levels were significantly lower in groups TEA and TEA+S than in groups S and C (P<0.001; P<0.05). At 1 hour after CPB, glucose levels were significantly higher in group S than in group C (P<0.05). At ICU, glucose levels were significantly lower in group TEA than in groups S, C and TEA+S (P<0.001; P<0.05). CONCLUSION: The study results show that preinduction TEA improves glucose homeostasis during the perioperative 24-h period in CABG surgery. In addition, we found that while preinduction TEA reduced blood IL-10 levels, preinduction glucocorticoid and TEA+S increased the circulating levels of IL-10.     

Thoracic epidural anesthesia preserves myocardial function during intraoperative and postoperative period in coronary artery bypass grafting operation

AIM: The purpose of this study was to investigate the effect of thoracic epidural anesthesia (TEA) in patients with poor ventricular function undergoing conventional coronary artery bypass graft surgery (CABG) during the intraoperative and the postoperative period. METHODS: Eighty patients (n = 80) undergoing elective CABG surgery with cardiopulmobary bypass (CPB) were divided into 4 groups: 1) General anesthesia (GA) plus poor ventricular (PV) function patients (Group GA plus PV) (n = 20), ejection fraction (EF) = or <40%; 2) GA plus good ventricular (GV) function patients (Group GA plus GV) (n = 20), EF >40%; 3) Thoracic epidural anaesthesia (TEA)+GA, poor ventricular function patients (Group TEA+GA plus PV) (n = 20), EF = or <40%; 4) TEA+GA, good ventricular function patients (Group TEA+GA plus GV) (n = 20), EF >40%. RESULTS: Within groups, at 4 h after the end of CPB, in the Group TEA+GA plus PV and Group TEA+GA plus GV, the cardiac index values were significantly higher than baseline values; P < 0.05, whereas no difference was found in the Group GA plus PV and Group GA plus GV. According to Tukey test, using repeated measures, between trend of groups, the cardiac index values were significantly different P < 0.05. In the Group TEA+GA plus PV, cardiac index values were significantly higher than the Group GA plus PV, P < 0.05. But in the Group GA plus GV, cardiac index values were not significantly different than the Group TEA+GA plus GV. The incidence of reperfusion ventricular fibrillation (VF) after release of aortic cross-clamp, in the Group TEA+GA plus PV (4 of 20 patients: 20%) was significantly lower than in the Group GA plus PV (11 of 20 patients: 55%); P < 0.05. The incidence of reperfusion VF after release of aortic cross-clamp, in the Group TEA+GA plus GV (5 of 20 patients: 25%) was not significantly different than in the Group GA plus GV (10 of 20 patients: 50%); NS. CONCLUSIONS: TEA seems to be effective in patients with poor left ventricular function. Our results (improved cardiac index, reduced arrhythmias after release of aortic clamp and decreased inotropic requirement) are better with TEA, particularly in patients with poor left ventricular function.     

Conversion from azathioprine [correction of azathioprina] to mycophenolate mofetil in pediatric renal transplant recipients with chronic rejection

BACKGROUND: Chronic rejection is the leading cause of graft failure. Both nonimmunological and immunological mechanisms contribute to this pathology. METHODS: We studied changes in kidney function, mixed lymphocyte culture, cell-mediated lympholysis, serum HLA class I antigens, cytotoxic antibodies, and lymphocyte population before and after 6 months of follow-up in 22 pediatric renal transplanted patients. The immunosuppressive protocol used was: cyclosporine, azathioprine, and corticosteroids. Eight patients demonstrated chronic graft rejection (by biopsy), group I; and eight patients had no clinical evidence of chronic and/or acute rejection, group II. Substitution of mycophenolate mofetil (MMF) (600 mg/m2 bid for azathioprine was done in patients of groups I and II. Another six patients with chronic rejection, did not receive MMF, group III. RESULTS: Creatinine clearance increased in group I (44+/-5 vs. 51.1+/- ml/min/1.73 m2, P<0.03) but it decreased in group III (30+/-3 vs. 25+/-2, P<0.01). Urinary protein excretion decreased only in group I (0.3+/-0.03 to 0.06+/-0.03 g/24 hr, P<0.03). During MMF therapy antidonor mixed lymphocyte culture decreased 62 and 70% (P<0.05) in group I and II. Cell-mediated lympholysis against lymphocyte of the donor decreased 65% (P<0.05) in group I. Cell-mediated lympholysis toward control cells decreased 54% (P<0.01) in group II. Serum HLA class I antigens, only decreased from 0.7+/-0.1 to 0.5+/-0.1 microl/ml, P<0.05, in group I. CD19+ decreased from 7.9+/-1.1 to 5.6+/-0.8%, P<0.05, and 7.8+/-1.2 to 5.5+/-0.9%, P<0.05, in groups I and II, respectively. CD16+ increased from 5.7+/-1.1 to 8.6+/-1.3 (P<0.05) only in group I. CONCLUSIONS: Our data suggest that substituting MMF for azathioprine therapy leads to an improvement in the immunosuppression and renal function in children with on-going chronic rejection.     

Effect of hypothermia on cellular membrane function during low-flow extracorporeal circulation

The use of systemic hypothermia is known to allow recovery from potentially lethal states of profound hypoperfusion or total circulatory arrest. While the cellular alterations accompanying states of decreased perfusion in skeletal muscle are well defined, little is known regarding the impact of coexistent hypothermia. To investigate this issue, nine dogs were placed on total cardiopulmonary bypass (CPB) and perfused in nonpulsatile fashion. The following flow and temperature parameters were used in three different perfusion models: 3.5 L/min/m2 at 23 degrees C (group A, n = 3), 1.6 L/min/m2 at 37 degrees C (group B, n = 3), and 1.6 L/min/m2 at 23 degrees C (group C, n = 3). Assessment of cellular function in a hind limb adductor muscle by measurement of resting transmembrane potential difference (Em) and determination of tissue electrolyte distribution in a biopsy specimen was performed in the control state and again after 60 minutes of total CPB. Low-flow/hypothermic CPB (group C) was associated with depolarization of resting Em to -63.3 +/- 3.2 mV from a control value of -87.0 +/- 1.3 mV (p less than 0.05), an increase in the calculated intracellular Na ([Na]i) to 16.4 +/- 4.0 mEq/L from a control value of 7.6 +/- 1.4 mEq/L (p less than 0.05), and an increase in the ratio of the selective membrane permeabilities of Na+ to K+ (pNa/pK), to 0.067 +/- 0.013 from a control value of 0.013 +/- 0.002 (p less than 0.05). In contrast, resting Em was maintained at -86.4 +/- 6.1 mv during normal-flow/hypothermic CPB (group A), while low-flow/normothermic CPB (group B) produced an intermediate depolarization to -75.2 +/- 3.0 mV (p less than 0.05). Neither [Na]i or pNa/pK was altered significantly in group A or group B dogs. These data characterize a physiologic alteration in the cellular membrane function of skeletal muscle during low-flow/hypothermic CPB, which is similar in many respects to that accompanying hemorrhagic shock. This suggests that during periods of profound hypothermia certain flow-related derangements in skeletal muscle are not obviated and may be exacerbated.     

Sodium-lithium countertransport activity and insulin resistance in normotensive IDDM patients.

In insulin-dependent diabetes (IDDM), an overactivity of sodium-lithium countertransport (Na+/Li+ CT) has been associated with the risk of nephropathy and hypertension, two conditions of insulin resistance. We investigated the sensitivity to insulin with a hyperinsulinemic (approximately 719 pM [approximately 100 microU/ml]) euglycemic clamp in two groups of normotensive nonproteinuric IDDM patients; 12 (10 men, 2 women) had high Na+/Li+ CT activity (mean 0.47, range 0.42-0.68 mmol/L red blood cells [RBC]/h, group 1) and 12 (9 men, 3 women) had normal Na+/Li+ CT activity (mean 0.24, range 0.12-0.31 mmol/L RBC/h, group 2). The two groups were similar in age (mean +/- SE 36 +/- 2 vs. 33 +/- 1 yr), duration of diabetes (19 +/- 3 vs. 18 +/- 2 yr), body mass index (26 +/- 0.8 vs. 24 +/- 0.6 kg/m2), arterial blood pressure (systolic/diastolic 121 +/- 4/79 +/- 2 vs. 122 +/- 3/77 +/- 2 mmHg), and glycemic control (HbA1 8.5 +/- 0.4 vs. 8.0 +/- 0.4%). Albumin excretion rate (AER) ranged between 4.7 and 148 (geometric mean 14) micrograms/min in group 1 and between 2.7 and 93 (geometric mean 11) micrograms/min in group 2. There were four microalbuminuric patients (AER greater than 30 micrograms/min) in each group. Whole-body glucose uptake was significantly reduced on average in group 1 compared with group 2 (41.6 +/- 2.2 mumol.kg-1.min-1 [7.48 +/- 0.4 mg.kg-1.min-1] vs. 49.6 +/- 2.2 mumol.kg-1.min-1 [8.93 +/- 0.4 mg.kg-1.min-1, P = 0.03), but some overlap existed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of pH-state and Alpha-stat Cardiopulmonary Bypass on Cerebral Oxygenation and Blood Flow in Relation to Hypothermic Circulatory Arrest in Piglets

Background: Deep hypothermic circulatory arrest is used in neonatal cardiac surgery. Recent work has suggested improved neurologic recovery after deep hypothermic arrest with pH-stat cardiopulmonary bypass (CPB) compared with alpha-stat CPB. This study examined cortical oxygen saturation (ScO(2)), cortical blood flow (CBF), and cortical physiologic recovery in relation to deep hypothermic arrest with alpha-stat or pH-stat CPB.

Methods: Sixteen piglets were cooled with pH-stat or alpha-stat CPB to 19 [degree sign]C (cortex) and subjected to 60 min of circulatory arrest, followed by CPB reperfusion and rewarming and separation from CPB. Near infrared spectroscopy and laser Doppler flowmetry were used to monitor ScO(2) and CBF. Cortical physiologic recovery was assessed 2 h after the piglets were separated from CPB by cortical adenosine triphosphate concentrations, cortical water content, CBF, and ScO(2).

Results: During CPB cooling, ScO(2) increased more with pH-stat than with alpha-stat bypass (123 +/- 33% vs. 80 +/- 25%); superficial and deep CBF were also greater with pH-stat than with alpha-stat bypass (22 +/- 25% vs. -56 +/- 22%, 3 +/- 19% vs. -29 +/- 28%). During arrest, ScO(2) half-life was greater with pH-stat than with alpha-stat bypass (10 +/- 2 min vs. 7 +/- 2 min), and cortical oxygen consumption lasted longer with pH-stat than with alpha-stat bypass (36 +/- 8 min vs. 25 +/- 8 min). During CPB reperfusion, superficial and deep CBF were less with alpha-stat than with pH-stat bypass (-40 +/- 22% vs. 10 +/- 39%, -38 +/- 28% vs. 5 +/- 28%). After CPB, deep cortical adenosine triphosphate and CBF were less with alpha-stat than with pH-stat bypass (11 +/- 6 pmole/mg vs. 17 +/- 8 pmole/mg, -24 +/- 16% vs. 16 +/- 32%); cortical water content was greater with alpha-stat than with pH-stat bypass (superficial: 82.4 +/- 0.3% vs. 81.8 +/- 1%, deep: 79.1 +/- 2% vs. 78 +/- 1.6%).     

Kombinierte Anästhesie mit Epiduralkatheter Eine retrospektive Analyse des perioperativen Verlaufs bei Patienten mit radikalen Prostatektomien

Patients requiring radical prostatectomy (rPE), including retroperitoneal lymphadenectomy are often aged and have coexisting cardiopulmonary diseases, increasing the risk of perioperative complications. The aim of the present study was to evaluate our perioperative anaesthesiologic regimen over the last five years, in terms of safety and patients comfort. Records of 433 patients who underwent rPE between 1994 and 1999 in our hospital were retrospectively reviewed. Patients were divided in those who received: 1. general anaesthesia (GA) alone, 2. a combination of lumbar epidural anaesthesia (LEA) + GA or, 3. thoracic epidural anaesthesia (TEA) + GA. General anaesthesia was performed as balanced anaesthesia, and epidural administered local anaesthetics were bupivacaine 0.25% or ropivacaine 0.2%, 8-12 ml/h. In terms of intra- and postoperative numbers of tachycardiac and hypertensive episodes, a reduced stress response was observed under epidural anaesthesia (EA). Moreover, the weaning duration was shorter under EA and onset of gastrointestinal motility was found earlier ([h] GA: 50.6 +/- 11.1/LEA: 39.3 +/- 13.6/TEA: 33.8 +/- 13.0). Furthermore, a trend to rarer phases of postoperative vomiting and a significant decrease of in hospital stay of about one day ([d] GA: 12.4 +/- 5.8/LEA: 11.1 +/- 3.1/TEA: 11.5 +/- 3.8) was observed. The duration of personnel binding in the OR did not differ significantly between GA and TEA ([min] GA: 222.9 +/- 43.5/LEA: 238.2 +/- 41.8/TEA: 227.0 +/- 46.2), but ICU stay was shortened under TEA. Besides this, TEA reduced the number of pathologic postoperative thorax-x-rays. Senso-motor blockades, decreases of SaO2 and cardiac complications were experienced more frequent under LEA as compared with TEA. Combination of GA and EA, especially TEA, appears to improve perioperative care of patients undergoing rPE, in terms of patients safety and comfort.     

Mesenteric complications after hypothermic cardiopulmonary bypass with cardiac arrest: underlying mechanisms

The aim of this study was to determine the pathophysiological mechanisms of postcardiopulmonary bypass (CPB) intestinal dysfunction using an in vivo canine model of extracorporeal circulation. Six dogs underwent a 90 min hypothermic CPB with continuous monitoring of mean arterial blood pressure (MAP) and mesenteric blood flow (MBF). Reactive hyperemia and vasodilator responses of the superior mesenteric artery to acetylcholine and sodium nitroprusside were determined before and after CPB. Mesenteric lactate production, glucose consumption, creatine kinase (CK) release and venous free radicals were determined. CPB induced a significant fall (p < 0.05) in MAP and MBF. After CPB, reactive hyperemia (-26 +/- 15% versus -53 +/- 2%, p < 0.05) and the response to acetylcholine (-42 +/- 9 versus -55 +/- 6%, p < 0.05) were significantly decreased. Reperfusion increased lactate production (0.8 +/- 0.09 mmol/L versus 0.4 +/- 0.18, p < 0.05) and the CK release (446 +/- 98 U/L versus 5 +/- 19 U/L, p < 0.01). Endothelial dysfunction, conversion from aerobic to anaerobic metabolism, and intestinal cell necrosis seem to be responsible for intestinal complications associated with CPB.     

Effects of phospholipase D on cardiopulmonary bypassinduced neutrophil priming

To investigate the relationship betweenphospholipase D (PLD) activation and neutrophil priminginduced by cardiopulmonary bypass (CPB), and try toclarify whether CPB-induced systemic inflammatoryresponse can be attenuated by inhibiting neutrophilic PLDactivation.     

The efficacy of low prime volume completely closed cardiopulmonary bypass in coronary artery revascularization.

PURPOSE: This study was conducted to evaluate and demonstrate the efficacy of low prime volume completely closed cardiopulmonary bypass (LPVP) in arrested coronary artery bypass grafting (CABG). We improved the percutaneous cardiopulmonary support (PCPS) circuit to reduce the deleterious effects of cardiopulmonary bypass (CPB). METHODS: Between April 1999 and May 2003, among 228 isolated CABG procedures, 47 procedures using LPVP (group L) and 86 procedures using standard prime volume open CPB (group S) were compared. The LPVP priming volume was 590 mL; the circuit was completely closed with a soft reservoir. Cardiac arrest was obtained by warm blood cardioplegia. RESULTS: The following average values were obtained: packed red blood cell transfusions, 0.88 +/- 1.4 U (group L) vs. 2.1 +/- 2.5 U (group S); intraoperative lowest hematocrit value, 28.7 +/- 4.6% (group L) vs. 22.4 +/- 3.3% (group S); blood loss over first 24 hours, 439 +/- 242 mL (group L) vs. 599 +/- 409 mL (group S); ventilation time, 5.1 +/- 3.1 hours (group L) vs. 10.4 +/- 14.9 hours (group S). CONCLUSION: Compared to standard prime volume open CPB, LPVP resulted in fewer deleterious operative effects. Less blood loss, fewer blood transfusions, and earlier patient recovery was noted with LPVP. Thus, LPVP is a very efficient form of CPB.     

Cold continuous antegrade blood cardioplegia: high versus low hematocrit.

OBJECTIVE: Cold continuous antegrade blood cardioplegia (CCABCP) is used with different hematocrit values. We investigated the consequences of CCABCP with low hematocrit (LH: 20-25%) versus high hematocrit (HH: 40-45%). METHODS: Anesthetized open chest pigs (25 kg) were placed on cardiopulmonary bypass (CPB). The hearts were arrested for 30 min by 6 degrees C CCABCP with either LH or HH (n=8, each): After an initial 3 min application of high potassium (20 mEq) BCP the hearts were arrested for subsequent 27 min by normokalemic 6 degrees C cold blood delivered continuously antegradely. Thereafter the hearts underwent perfusion with warm systemic blood for an additional 30 min on CPB. Biochemical cardiac data (MVO(2) (ml min(-1)100 g(-1)), release of creatine kinase (CK; units min(-1)100 g(-1))) and lactate (mg min(-1)100 g(-1))) and the coronary vascular resistance index (CVRI (mmHg ml(-1)ming)) were measured during CPB. Total tissue water content (%) and left and right ventricular stroke work indices (LV-and RV-SWI (g m kg(-1))) were assessed 30 min after discontinuation of CPB and compared to pre-CPB controls. RESULTS: The hearts of the LH group had no biochemical or functional disturbance. The HH group showed marked CK leakage (0.6+/-0.2* vs. 0.1+/-0.1, *P<0.05 for comparison of LH vs. HH with Student's t-test for unpaired data), impaired initial oxygen consumption (4+/-1* vs. 7+/-1) after cardiac arrest, an increased CVRI (82+/-12* vs. 50+/-8), the formation of myocardial edema (81.0+/-1.3* vs. 77.5+/-1.2), and poor functional recovery (LVSWI 0.2+/-0.1* vs. 1.0+/-0.1; RVSWI 0.1+/-0.1* vs. 0.5+/-0.1). The absence of lactate production in both groups was in accord with the non-ischemic protocol. CONCLUSIONS: CCABCP with a low hematocrit of 20-25% is cardioprotective. In contrast, CCABCP with a high hematocrit of 40-45% jeopardizes the heart despite avoiding ischemic periods, and should be avoided.     

Myocardial revascularization with and without cardiopulmonary bypass in multivessel disease: impact of strategy on midterm outcome

BACKGROUND: In a previous study, we demonstrated that patients with multivessel disease benefit during the first postoperative month from elimination of cardiopulmonary bypass (CPB). We evaluated the midterm results of the same patients excluding the first postoperative month from the analysis. METHODS: From May 1997 to November 2000, 1,802 patients with multivessel disease survived the first postoperative month; 906 were operated on without (group A) and 896 with (group B) CPB. Follow-up ranged from 23 to 65 months (mean, 42 +/- 12 months). Four-year actuarial freedom from the following events was evaluated: death from any cause; cardiac death; acute myocardial infarction (AMI) in any territory; AMI in a grafted area; redo percutaneous transluminal coronary angioplasty (PTCA); redo PTCA in a target vessel; cardiac events (death from a cardiac cause, acute myocardial infarction on grafted vessel, redo PTCA on target vessel); and any event. RESULTS: No statistical difference was found between groups A and B with regard to freedom from any death (95.3 +/- 0.8 vs 95.7 +/- 0.7, p = 0.5160); from cardiac death (97.3 +/- 0.6 vs 97.5 +/- 0.6, p = 0.5345); from AMI (98.4 +/- 0.4 vs 98.7 +/- 0.4, p = 0.4655); from AMI in a grafted area (98.9 +/- 0.4 vs 98.7 +/- 0.4, p = 0.9374); from redo PTCA (97.9 +/- 0.5 vs 97.7 +/- 0.6, p = 0.8485); from redo PTCA in a grafted area (98.7 +/- 0.4 vs 98.5 +/- 0.5, p = 0.8774); from target cardiac events (95.8 +/- 0.7 vs 95.9 +/- 0.8, p = 0.6070); and from any event (92.9 +/- 0.9 vs 93.4 +/- 1.0, p = 0.3721). CONCLUSIONS: After exclusion of the first postoperative month, myocardial revascularization without CPB has midterm results similar to myocardial revascularization with CPB. In particular, failure of revascularization does not depend on intraoperative strategy.     

Changes of microvascular vasomotion and oxygen metabolism during cooling and rewarming period of cardiopulmonary bypass

Microcirculation plays an important role in keeping a stable tissue metabolism during cardiopulmonary bypass (CPB). The relationship between microvascular vasomotion (MV) and total body's oxygen metabolism with temperature alteration during CPB remains unclear. Is there a relationship, or is the autoregulation a consequence of CO2, pressure and/or blood flow? The purpose of this study was to investigate the effect of temperature alteration on cutaneous MV and the total body's oxygen metabolism during CPB. Sixteen consecutive patients scheduled for elective cardiac valve replacement surgery were included in this study. The pump flow varied from 1.8-3.0 L/m(-2)min(-1) to maintain venous oxygen saturation above 65% and mean arterial blood pressure above 60 mmHg. At a nasopharyngeal temperature of 30 degrees C, oxygen consumption (VO2) and oxygen extraction (O2 ext) were measured during the cooling and rewarming periods. MV and skin microcircular flow (SMF) were monitored dynamically at the middle of two sides of the eyebrow with a laser Doppler flowmeter simultaneously VO2 and O2 ext at 30 degrees C were significantly lower during the cooling period (VO2, 49.9 +/- 17.7 mL/m(-2)/min(-1); O2 ext, 19.3 +/- 6.2%) than that during the rewarming period (VO2, 133.3 +/- 40.0 mL/m(-2)/min(-1); O2 ext, 35.2 +/- 9.2%) (p < .05). SMF was significantly depressed during CPB (p < .05). SMF during the cooling period (50.2% +/- 10.1%) was significantly less than that during the rewarming period (79.5% +/- 12.3%) (p < .05). MV was significantly less active during CPB than that before CPB (5.8 +/- 1.2 cyc/min) (p < .05), whereas there was no significant difference in MV between the cooling (3.7 +/- 1.8 cyc/min) and the rewarming period (4.1 +/- 1.5 cyc/min) and (p > .05). SMF and MV were depressed during hypothermic CPB, and there was some recovery during the rewarming period. Compared to baseline, SMF and MV were still significantly reduced during the warming period, indicating microvascular function was abnormal. Some measures should be taken for improvement of microvascular function during CPB.     

Peroxynitrite, a product between nitric oxide and superoxide anion, plays a cytotoxic role in the development of post-bypass systemic inflammatory response.

OBJECTIVE: Cardiopulmonary bypass (CPB) is known to induce post-bypass systemic inflammatory response. Peroxynitrite (ONOO-) is a potent oxidant formed by a rapid reaction between nitric oxide (NO) and superoxide anion. We hypothesized that ONOO- plays a role in the development of post-bypass systemic inflammatory response and examined the efficacy of ONOO- scavenger in a rat-CPB model. METHODS: Adult Sprague-Dawley rats underwent 60 min of CPB (100 ml/kg per min, 34 degrees C). Group-P (n = 10) received 50 mg/kg of ONOO- scavenger, quercetin, intraperitoneally 24 h before the initiation of CPB, and Group-C (n = 10) served as controls. RESULTS: There were significant time-dependent changes in plasma nitrate+nitrite (NOx), the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr: an indicator of ONOO- formation), interleukin (IL)-6, IL-8, and respiratory index (RI). There were significant differences in %NO2-Tyr between the groups both at CPB termination (Group-P vs C; 0.26+/-0.07 vs 0.55+/-0.11%, P < 0.01) and 3 h after CPB termination (0.65+/-0.14 vs 1.46+/-0.25%, P < 0.01); whereas there were no significant differences in NOx between the groups at any sampling point ((at CPB termination) Group-P vs C; 31.6+/-4.3 vs 32.7+/-4.1 micromol/l, (3 h after CPB termination) Group-P vs C; 47.8+/-4.9 vs 51.7+/-5.3 micromol/l). Group-P showed significantly lower plasma IL-6 (176.8+/-44.3 vs 302.4+/-78.1 pg/ml, P < 0.01), IL-8 (9.45+/-1.78 vs 16.42+/-2.53 ng/ml, P < 0.01) and RI (1.07+/-0.19 vs 1.54+/-0.25, P < 0.01) 3 h after CPB termination, though there were no significant differences between the groups at CPB termination. CONCLUSIONS: These results suggest that ONOO- plays a crucial role in the development of post-bypass systemic inflammatory response and the pretreatment with quercetin has a potential benefit to avoid deleterious effects of ONOO-.     

超极化停搏对家猫体外循环时心肌细胞膜脂区域流动性的影响

目的 探讨超极化停搏对猫体外循环(CPB)时心肌细胞膜脂区域流动性的影响.方法 家猫75只,体重3～4 kg,随机分为3组(n=25),CPB组:CPB建立后不阻断上腔静脉、下腔静脉和主动脉,仅行CPB 150 min;去极化停搏组:主动脉阻断60 min,再灌注60 min,心脏停搏液使用高钾St Thomas液;超极化停搏组:心脏停搏液使用含吡那地尔的低钾St Thomas液,余处理与去极化停搏组相同.应用自旋标记-电子自旋共振技术测定CPB时心肌细胞膜脂区域流动性.结果 与CPB组比较,去极化停搏组主动脉阻断30 min后心肌细胞膜脂S和τc均升高,超极化停搏组主动脉阻断60 min后心肌细胞膜脂S和τc均升高(P＜0.01);与去极化停搏组比较,超极化停搏组主动脉阻断30 min后心肌细胞膜脂S和τc均降低(P＜0.01).结论 与去极化停搏相比,超极化停搏能够更好地维持家猫CPB时心肌细胞膜脂的区域流动性.     

Vasopressin therapy for vasoplegic syndrome following cardiopulmonary bypass

BACKGROUND: Hypotension refractory to maximal doses of alpha-adrenergic drugs after cardiac operations employing cardiopulmonary bypass (CPB) has been referred as "vasoplegic syndrome." Vasopressin has been used for its therapy with encouraging results. MATERIAL AND METHODS: 16 patients (mean age 71, range 47 to 84 years) were treated with intravenous vasopressin (0.1-1 IU/min) for hypotension refractory to maximal doses (>30 microg/kg/min) of norepinephrine after undergoing complex cardiac operations employing CPB. Preoperative ejection fraction was 40.5% (mean, range 20% to 60%), preoperative NYHA class was 3.5 (mean). Hemodynamic measurements were obtained one hour before and one hour after beginning vasopressin infusion; urine output was measured for the 4 hours before and the 4 hours after beginning the infusion. Duration of vasopressin treatment was 58.8 +/- 37.3 hours (mean +/- SD). RESULTS: Systolic blood pressure increased from 89.6 +/- 7.9 to 119.6 +/- 10.5 mmHg (mean +/- SD) (p < 0.001); systemic vascular resistance increased from 688.0 +/- 261.7 to 1043.3 +/- 337.1 dyne/s/cm2 (mean +/- SD) (p < 0.001); cardiac index decreased from 2.69 +/- 0.8 to 2.2 +/- 0.5 L/min/m2 (mean +/- SD) (p < 0.008); urine output increased from 36.8 +/- 30.4 to 72.8 +/- 38.2 mL/h (mean +/- SD) (p < 0.001). Seven patients (44%) survived the hospital stay. CONCLUSIONS: High-dose vasopressin is effective in the treatment of the vasoplegic syndrome after cardiac operations employing cardiopulmonary bypass.     

The effects of thoracic epidural analgesia with bupivacaine 0.25% on ventilatory mechanics in patients with severe chronic obstructive pulmonary disease

Optimal analgesia is important after thoracotomy in pulmonary-limited patients to avoid pain-related pulmonary complications. Thoracic epidural anesthesia (TEA) can provide excellent pain relief. However, potential paralysis of respiratory muscles and changes in bronchial tone might be unfavorable in patients with end-stage chronic obstructive pulmonary disease (COPD). Therefore, we evaluated the effect of TEA on maximal inspiratory pressure, pattern of breathing, ventilatory mechanics, and gas exchange in 12 end-stage COPD patients. Pulmonary resistance, work of breathing, dynamic intrinsic positive end-expiratory pressure, and peak inspiratory and expiratory flow rates were evaluated by assessing esophageal pressure and airflow. An increase in minute ventilation (7.50 +/- 2.60 vs 8.70 +/- 2.10 L/min; P = 0.04) by means of increased tidal volume (0.46 +/- 0.16 vs 0.53 +/- 0.14 L/breath; P = 0.003) was detected after TEA. These changes were accompanied by an increase in peak inspiratory flow rate (0.48 +/- 0.17 vs 0.55 +/- 0.14 L/s; P = 0.02) and a decrease in pulmonary resistance (20.7 +/- 9.9 vs 16.6 +/- 8.1 cm H(2)O. L(-1). s(-1); P = 0.02). Peak expiratory flow rate, dynamic intrinsic positive end-expiratory pressure, work of breathing, PaO(2), and maximal inspiratory pressure were unchanged (all P > 0.50). We conclude that TEA with bupivacaine 0.25% can be used safely in end-stage COPD patients. IMPLICATIONS: Thoracic epidural anesthesia with bupivacaine 0.25% does not impair ventilatory mechanics and inspiratory respiratory muscle strength in severely limited chronic obstructive pulmonary disease patients. Thus, thoracic epidural anesthesia can be used safely in patients with end-stage chronic obstructive pulmonary disease.     

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.     

Influence of angiotensin-I-converting-enzyme insertion/deletion gene polymorphism on perioperative hemodynamics after coronary bypass graft surgery

AIM: The angiotensin I-converting enzyme insertion/ deletion polymorphism (ACE-I/D), including three genotypes (II, ID, DD), with a known impact on midterm mortality and morbidity in patients after coronary artery bypass graft surgery (CABG), was studied. Since this polymorphism has been linked with increased vascular response to phenylephrine during cardiopulmonary bypass (CPB), we investigated its possible effect on perioperative hemodynamics in patients undergoing CABG. METHODS: Genotyping for the ACE-I/D was performed by polymerase chain reaction (PRC) amplification in 110 patients who underwent elective CABG with CPB. Patients were assigned to two groups according to their genotype (group II [II genotype] and group ID/DD [ID and DD genotypes]). Systemic hemodynamics were measured directly before and at 4 h, 9 h, and 19 h after CPB. RESULTS: Genotype distribution of ACE-I/D was 18%, 57%, and 25% in genotypes II, ID, and DD, respectively. The two groups were similar in age (group II: 66+/-6 years, group ID/DD: 66+/-8 years), body-mass-index (BMI) (group II: 28+/-2, group ID/DD: 29+/-5 kg/m2), male: female ratio (group II: 16: 4, group ID/DD: 63: 27) and Euroscore (group II: 3.1+/-1.9, group ID/DD: 3.5+/-2.1). There were no differences in mortality rate or perioperative systemic hemodynamics. The pulmonary vascular resistance before cardiopulmonary bypass was higher in the ID/DD genotypes than in the II genotypes (227+/-121 vs 297+/-169 dyn.s(-1).m2.cm(-5)). Four hours after CPB no difference remained; at 9 h after cardiopulmonary bypass there was a slight difference in pulmonary vascular resistance between the two groups (247+/-134 vs 290+/-117 dyn.s(-1).m2.cm(-5)) and a significant difference in pulmonary arterial pressure (19+/-6 vs 23+/-8); at 19 h after CPB the differences were no longer detectable. CONCLUSION: ACE-I/D had no influence on perioperative systemic hemodynamics. However, transitory differences in pulmonary hemodynamic were observed after CPB. These differences may have been due to changes in serum ACE activity during CPB.