Milrinone Modulates Endotoxemia, Systemic Inflammation, and Subsequent Acute Phase Response after Cardiopulmonary Bypass (CPB)

Background: Compromised splanchnic perfusion and the resulting intestinal mucosal injury leads to a decreased mucosal barrier function, which allows translocation of intestinal flora and endotoxemia. The authors evaluated the effects of milrinone on splanchnic oxygenation, systemic inflammation, and the subsequent acute-phase response in patients undergoing coronary artery bypass grafting.

Methods: This open, placebo-controlled randomized clinical study enrolled 22 adult patients in two groups. Before induction of anesthesia, baseline values were obtained and patients were randomized to receive milrinone (30 [micro sign]g/kg bolus administered progressively in 10 min, followed by a continuous infusion of 0.5 [micro sign]g [middle dot] kg-1 [middle dot] min-1) or saline. The following parameters were determined: hemodynamics; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; intramucosal pH (pHi); and mixed and hepatic venous plasma concentrations of endotoxin, interleukin 6, serum amyloid A, and C-reactive protein.

Results: Milrinone did not prevent gastrointestinal acidosis as measured by pHi, but its perioperative administration resulted in significantly higher pHi levels compared with control. Venous and hepatic venous endotoxin and the interleukin 6 concentration were reduced significantly in the milrinone group. Serum amyloid A values were attenuated in the milrinone group 24 h after surgery. No significant differences could be seen in routinely measured oxygen transport-derived variables.     

Effect of low-dose milrinone on gastric intramucosal pH and systemic inflammation after hypothermic cardiopulmonary bypass

OBJECTIVE: To investigate the usefulness of low-dose milrinone on gastric intramucosal pH (pHi) and systemic inflammation in patients undergoing hypothermic cardiopulmonary bypass (CPB). DESIGN: Prospective randomized study. SETTING: University hospital. PARTICIPANTS: Twenty patients scheduled for cardiac surgery. INTERVENTIONS: Ten patients were administered a low dose of milrinone, 0.25 microg/kg/min, from the initiation of CPB to 1 hour after admission to the intensive care unit. The other patients were administered saline. Supplemental inotropes and intravenous fluid were given to obtain adequate mean arterial blood pressure and pulmonary artery occlusion pressure. MEASUREMENTS AND RESULTS: Gastric pHi and carbon dioxide pressure (PCO2) were assessed by capnometric air tonometry. The difference between PCO2 and arterial carbon dioxide pressure (PaCO2), PCO2-gap, was also examined. Systemic inflammatory responses were evaluated by serum interleukin-6 and leukocyte counts. Hemodynamics, oxygen delivery index, and oxygen uptake index were monitored with catheters in the radial and pulmonary arteries (thermodilution). The hepatic venous blood flow and left ventricular flow were measured using transesophageal echocardiography. Milrinone prevented gastric intramucosal acidosis, detected as a decrease in pHi or an increase in PCO2-gap, without affecting hepatic venous blood flow. Increases in interleukin-6, leukocyte count, and oxygen uptake index, all of which developed after CPB, were significantly less in the milrinone group than in the control group. CONCLUSION: These results suggest that in patients undergoing hypothermic CPB, supplemental low-dose milrinone prevents gastric intramucosal acidosis and increases in some markers of systemic inflammation.     

Hemodynamic effects of milrinone during weaning from cardiopulmonary bypass: comparison of patients with a low and high prebypass cardiac index

OBJECTIVE: To compare the hemodynamic effects of milrinone during weaning from cardiopulmonary bypass (CPB) in patients with a low pre-CPB cardiac index (CI) <2.5 L/min/m2) and in patients with a high pre-CPB CI (> or =2.5 L/min/m2). DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PARTICIPANTS: Forty-eight patients scheduled for elective coronary artery bypass graft surgery. INTERVENTION: Patients were divided into 4 groups: (1) low pre-CPB CI/placebo, (2) low pre-CPB CI/milrinone, (3) high pre-CPB CI/placebo, and (4) high pre-CPB CI/milrinone. Patients received a loading dose of 20 microg/kg of milrinone followed by an infusion of 0.2 microg/kg/min or placebo 15 minutes before the anticipated weaning time. MEASUREMENTS AND MAIN RESULTS: In the low pre-CPB CI/ placebo group, low CIs and high systemic vascular resistances (SVRs) were observed after CPB. High doses of dopamine and dobutamine were needed, and infusion of epinephrine was used in 5 of the 12 patients for hemodynamic support. Milrinone improved CI and reduced SVR in the low pre-CPB CI/milrinone group. Norepinephrine was needed to maintain an adequate systemic blood pressure in 6 of the 12 patients, however. In the high pre-CPB CI/placebo group, satisfactory CIs and SVRs were observed during weaning from CPB with low doses of dopamine and dobutamine. Milrinone significantly increased CI and decreased SVR in the high pre-CPB CI/milrinone group: 10 of the 12 patients had CIs above the upper limit of normal, and 7 patients had SVRs below the lower limit of normal. CONCLUSION: Milrinone was effective during weaning from CPB in patients with a low pre-CPB CI. Milrinone in combination with norepinephrine was a good alternative to epinephrine for the treatment of myocardial dysfunction after CPB.     

Influence of Enteral Nutrition-induced Splanchnic Hyperemia on the Septic Origin of Splanchnic Ischemia

Escherichia coli endotoxin via portal vein administration were grouped according to whether they were fed enterally via a jejunostomy or given a placebo. Systemic hemodynamics; portal vein, hepatic, and superior mesenteric artery blood flow; hepatic and intestinal microcirculation; hepatic tissue PO ₂ ; intestinal pHi; and hepatic energy charge were assessed before, during, and after endotoxin infusion as well as during and after enteral or placebo feeding. All splanchnic hemodynamic parameters revealed a statistically significant decline ( p = 0.001) during the endotoxin shock period relative to the baseline. After enteral feeding all parameters exhibited a statistically significant increase ( p = 0.001) relative to the placebo group. The results of this study led us to suggest that enteral nutrition reverses the lipopolysaccharide infusion-induced splanchnic ischemia.     

Milrinone enhances systolic, but not diastolic function during coronary artery bypass grafting surgery

PURPOSE: To evaluate the effect of milrinone on diastolic function during coronary artery bypass grafting surgery (CABG). METHODS: Fifty patients undergoing CABG were randomized to receive a bolus and infusion of milrinone or placebo before cardiopulmonary bypass (CPB) until skin closure. Hemodynamic and transesophageal echocardiographic measurements of systolic and diastolic function were obtained. Pulsed wave Doppler measurements of the early (E wave) and atrial components (A wave) of the transmitral (TMF) and transtricuspid (TTF) flows, and systolic (S wave), diastolic (D wave) and atrial components (Ar) of the pulmonary (PVF) and hepatic venous blood flow (HVF) velocities were performed. Early and atrial components of the mitral (Em and Am waves) and tricuspid annulus velocities (Et and At waves) were assessed by tissue Doppler imaging (TDI). Assessment of diastolic dysfunction was graded from normal to severe using a scale score. RESULTS: Cardiac index and heart rate were higher in the milrinone group compared to placebo after the administration of study drug (2.8 +/- 0.6 vs 2.1 +/- 0.5 L.min(-1)m(-2)) (P < 0.0001) and (67 +/- 8 vs 60 +/- 12 beats.min(-1)) (P < 0.05) respectively. There were no changes in left and right ventricular diastolic dysfunction scores between study groups. Higher PVF S wave, HVF S wave, TTF A wave and At measured by TDI in the milrinone group compared with placebo suggested an improvement in ventricular systolic and atrial contraction. CONCLUSION: Distinct from its effects on systolic function, milrinone administered before CPB is not with associated improved biventricular diastolic function in patients undergoing CABG.     

Jejunal mucosal perfusion is well maintained during mild hypothermic cardiopulmonary bypass in humans

In the present study, the effects of mild hypothermic (34 degrees C) cardiopulmonary bypass (CPB) on jejunal mucosal perfusion (JMP), gastric tonometry, splanchnic lactate, and oxygen extraction were studied in low-risk cardiac surgical patients (n = 10), anesthetized and managed according to clinical routine. JMP was assessed by endoluminal laser Doppler flowmetry. Patients were studied during seven 10-min measurement periods before, during, and 1 h after the end of CPB. Splanchnic oxygen extraction increased during hypothermia and particularly during rewarming and warm CPB. JMP increased during hypothermia (26%), rewarming (31%), and warm CPB (38%) and was higher 1 h after CPB (42%), compared with pre-CPB control. The gastric-arterial PCO(2) difference was slightly increased (range 0.04-2.26 kPa) during rewarming and warm CPB as well as 1 h after CPB, indicating a mismatch between gastric mucosal oxygen delivery and demand. None of the patients produced lactate during CPB. We conclude that jejunal mucosal perfusion appears well preserved during CPB and moderate (34 degrees C) hypothermia; this finding is in contrast to previous studies showing gastric mucosal hypoperfusion during CPB. Implications: Jejunal mucosal perfusion increases during mild hypothermic cardiopulmonary bypass (CPB). Intestinal laser Doppler flowmetry, gastric tonometry, and measurements of splanchnic lactate extraction could not reveal a local or global splanchnic ischemia during or after CPB. A mismatch between splanchnic oxygen delivery and demand was seen, particularly during rewarming and warm CPB.     

异丙酚对体外循环中脑氧代谢的影响

目的：探讨异丙酚对体外循环（ＣＰＢ）各阶段脑氧及乳酸代谢的影响。方法：选择心内直视手术病人３１例，随机分为异现酚组（Ａ组）１６例，对照组（Ｂ组）１５例。分别于ＣＰＢ前、降温及３３℃和３０℃，低温期，复温至３０℃和３３℃以及ＣＰＢ后１５分钟七个时点动脉，颈内静脉血气及乳酸值（ＬＡ）并计算脑摄氧率（Ｏ２Ｅｘｔ）及动脉－颈内静脉乳酸差值。     

异丙酚在心脏瓣膜置换术中对氧供、氧耗、氧摄取率及氧合状态的影响

目的：观察异丙酚在心脏瓣膜置换术中对氧供（ＤＯ２）,氧耗（ＶＯ２）,氧摄取率（ＥＲＯ２）及氧合状态的影响。方法：２０例心脏瓣膜置换术病人随机分为两组。组麻醉诱导与维持用异丙酚,对照组用咪唑安定。观察体外循环（ＣＰＢ）期间ＤＯ２,ＶＯ２,ＥＲＯ２,混合静脉血氧饱和度（ＳＶＯ２）及动脉血乳酸（ＡＢＬ０的变化。结果：（１）组内各时点ＤＯ２无明显变化,复温后观察组ＥＲＯ２增加非常显著;降温开始及复温后观察     

Insulin (GIK) improves central mixed and hepatic venous oxygenation in clinical cardiac surgery.

OBJECTIVE: Insulin is a vasodilating agent and it was hypothesized that insulin (GIK) could improve systemic and regional oxygenation in cardiac surgery with cardiopulmonary bypass (CPB). Two questions were addressed: 1) Does insulin improve central mixed and hepatic venous oxygenation during CPB? and 2) Does this treatment reduce systemic levels of the proinflammatory mediators C3a and IL-6? DESIGN: Prospective, randomized, controlled study at a university hospital. Thirty patients were included and 16 of these received an infusion of insulin, glucose and potassium (GIK) using an euglycemic clamp technique. The insulin infusion was started during hypothermia, 15 min before rewarming. Blood gases and hemodynamic parameters were measured during hypothermia (before the insulin infusion was started), during rewarming at 35 degrees C, and 30 min after CPB was discontinued. Inflammatory markers were measured: preoperatively, during hypothermia and 2 h after CPB. RESULTS: GIK was associated with reduced systemic vascular resistance (p = 0.02 vs the control group), higher bypass pump flow (p = 0.001). higher central mixed oxygen saturation (p = 0.036) and oxygen tension (p = 0.001) and higher hepatic venous oxygen saturation (p = 0.04) and oxygen tension (p = 0.006). C3a and IL-6 increased during surgery in both groups but there were no differences between the groups. CONCLUSION: 1) GIK infusion improved central mixed and hepatic venous oxygenation in patients undergoing heart surgery. 2) During the conditions of this study, this had no effect on the proinflammatory mediators C3a and IL-6.     

Insulin (GIK) Improves Central Mixed and Hepatic Venous Oxygenation in Clinical Cardiac Surgery

Objective - Insulin is a vasodilating agent and it was hypothesized that insulin (GIK) could improve systemic and regional oxygenation in cardiac surgery with cardiopulmonary bypass (CPB). Two questions were addressed: 1) Does insulin improve central mixed and hepatic venous oxygenation during CPB? and 2) Does this treatment reduce systemic levels of the proinflammatory mediators C3a and IL-6? Design - Prospective, randomized, controlled study at a university hospital. Thirty patients were included and 16 of these received an infusion of insulin, glucose and potassium (GIK) using an euglycemic clamp technique. The insulin infusion was started during hypothermia, 15 min before rewarming. Blood gases and hemodynamic parameters were measured during hypothermia (before the insulin infusion was started), during rewarming at 35°C, and 30 min after CPB was discontinued. Inflammatory markers were measured: preoperatively, during hypothermia and 2 h after CPB. Results - GIK was associated with reduced systemic vascular resistance ( p = 0.02 vs the control group), higher bypass pump flow ( p = 0.001), higher central mixed oxygen saturation ( p = 0.036) and oxygen tension ( p = 0.001) and higher hepatic venous oxygen saturation ( p = 0.04) and oxygen tension ( p = 0.006). C3a and IL-6 increased during surgery in both groups but there were no differences between the groups. Conclusion - 1) GIK infusion improved central mixed and hepatic venous oxygenation in patients undergoing heart surgery. 2) During the conditions of this study, this had no effect on the proinflammatory mediators C3a and IL-6.     

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.     

Small-dose epoprostenol decreases systemic oxygen consumption and splanchnic oxygen extraction during normothermic cardiopulmonary bypass

Normothermic, nonpulsatile cardiopulmonary bypass (CPB) impairs systemic and splanchnic oxygen transport and increases gastrointestinal permeability. It is an important therapeutic goal to avoid splanchnic dysoxia during CPB. Small-dose prostacyclin therapy improves splanchnic oxygen transport and microcirculation in septic patients. In this study, we sought to determine if during cardiac surgery, the prostacyclin analog epoprostenol improves the balance of systemic and splanchnic oxygen transport. Eighteen patients undergoing cardiac valve replacement were randomized to receive either epoprostenol (3 ng x kg(-1) x min(-1)) or placebo during, and for 1 hour after, surgery. Systemic and splanchnic oxygen delivery, consumption, and extraction and arterial, mixed venous, and hepato-venous lactate concentrations were measured before, during, and after CPB. Gastrointestinal permeability was measured 1 day before and 1 day after surgery using the triple sugar permeability test. During CPB, the epoprostenol group had decreased systemic oxygen consumption and splanchnic oxygen extraction (P = 0.024). These effects were not present 1 hour after the end of epoprostenol infusion. The study was not adequately powered to determine whether epoprostenol altered the trend towards increased lactate metabolism and increased postoperative gastrointestinal permeability, nor could we demonstrate any differences between groups in clinically relevant end-points. In conclusion, these findings suggest that during normothermic CPB, small-dose epoprostenol therapy may reduce systemic oxygen consumption and splanchnic oxygen extraction.     

Differences in hemodynamic effects of amrinone, milrinone and olprinon after cardiopulmonary bypass in valvular cardiac surgery

The differences in hemodynamic effects of amrinone, milrinone and olprinone were evaluated in 46 patients for valvular cardiac surgery after cardiopulmonary bypass (CPB). Patients were randomly allocated to three groups; group A with amrinone infusion (17 patients); group M with milrinone infusion (15 patients); and group O with olprinone infusion (14 patients). Each drug was administrated as a single dose into the venous reservoir of the CPB circuit 15 min prior to the end of emergence from CPB, followed by continuous infusion. Hemodynamic parameters were measured at the time of preCPB (C0), just after the end of CPB (C1), one hour after the termination of CPB (C2) and after the chest closure (C3). Catecholamines were used in order of dopamine, norepinephrine and dobutamine. These doses were modulated to maintain the cardiac index > 3.0 l.min-1.m-2 by each anesthesiologist. Hemodynamic parameters (at C0, C1, C2 and C3) and the doses of cathecholamine (at C1, C2 and C3) were compared among the 3 drugs. The systolic blood pressure in group M was significantly higher than that of group A and group O after chest closure. In group M and A, the systolic blood pressure showed a significant increase after CPB. On the other hand, the systolic blood pressure showed no significant change in group O after CPB. Three drugs showed no significant difference in the dosages of catecholamines used.     

Effect of Cardiopulmonary Bypass and Calcium Administration on the Splanchnic Circulation

Gastrointestinal complications following cardiopulmonary bypass (CPB) are associated with high mortality rates. The identification of prolonged CPB time and calcium administration as independent predictors of gastrointestinal complications suggests decreased splanchnic perfusion as a possible mechanism. To test this hypothesis, we evaluated splanchnic organ perfusion during CPB and after calcium chloride administration. Mongrel dogs were studied under anesthesia and were cannulated for bypass. CPB was begun at 37°C, and the heart was fibrillated and vented. After 30 min, CPB temperature was reduced to 25°C for 1 h with the heart arrested through cold crystalloid cardioplegia. After rewarming to 37°C for 30 min, the heart was cardioverted, and CPB was weaned off. Calcium chloride (10 mg/kg) or saline was administered. Organ blood flow was determined with radiolabeled microspheres at baseline, during CPB, and after weaning from CPB. Splanchnic organ blood flow did not decrease during any phase of CPB. Calcium chloride administration after CPB had no effect on splanchnic organ blood flow. While gastrointestinal injury may result from CPB, this study suggests that the mechanism of injury is not decreased by splanchnic organ perfusion during bypass. While calcium chloride can cause pancreatic injury, the responsible mechanism is not calcium-induced hypoperfusion.     

雾化吸入与静脉输注米力农治疗先天性心脏病患儿术后肺动脉高压效果的比较

目的 比较雾化吸入与静脉输注米力农治疗先天性心脏病患儿术后肺动脉压的效果.方法 先天性心脏病患儿40名,年龄5～14岁,体重15～38 kg,肺动脉压(PAP)30～90mm Hg,随机分为2组(n=20):雾化吸入组和静脉输注组.体外循环结束即刻,雾化吸入组每隔30 min吸入米力农1 mg/ml 10 min,共吸入12 h;静脉输注组先静脉注射米力农负荷剂量10μg/kg,然后以0.5μg·kg-1·min-1的速率静脉辅注12 h.于给药12 h时行血气分析,记录混合静脉血氧饱和度(S(-v)O2);于术前(基础状态)、给药12 h内每隔2 h记录MAP、PAP、肺血管阻力指数(PVRI)和体血管阻力指数(SVRI);记录带管时间和给药12 h内肺动脉高压、肺部感染以及术后低氧血症的发生情况.结果 与静脉输注组比较,雾化吸入组PAP和PVRI降低,S(-v)O2、MAP和SVRI升高,肺动脉高压和肺部感染发生率降低(P＜0.05),低氧血症发生率和带管时间差异无统计学意义(P＞0.05).结论 雾化吸入米力农治疗先天性心脏病患儿术后肺动脉高压的效果优于静脉输注,提示先天性心脏病患儿更宜选择雾化吸入的方法给予米力农.     

Distinct effects of surgical denervation on hepatic perfusion, bowel ischemia, and oxidative stress in brain dead and living donor porcine models.

The liver function and perfusion following brain death is mainly influenced by the sympathetic nerves and hormones. We examined the specific influence of surgical liver denervation on systemic and hepatic perfusion parameters, bowel ischemia and oxidative stress in hemodynamically stable BD and control (living donor [LD]) pigs. Brain death was induced in 8 pigs via saline infusion into the balloon of an epidural Tieman-catheter (1 mL/15 minutes) and compared to the control group (n = 6) over 4 hours. At 2 hours postoperatively, complete liver denervation was initiated. We analyzed systemic cardiocirculatory parameters (mean arterial pressure, aortic flow, bowel ischemia (endotoxin, and endotoxin-neutralizing capacity) and oxidative stress (total glutathione in erythrocytes [tGSH(E)]) and compared them to local/hepatic perfusion parameters (hepatic artery and portal venous flow, liver blood flow index, and microperfusion), local bowel ischemia (intramucosal pH [pHi] of stomach [pHi(S)]/colon[pHi(C)]), and liver oxidative stress (glutathione [rGSH(L), GSSG(L)]). Following brain death, the parameters including mean arterial pressure, aortic flow, pHi, endotoxin, and tGSH(E) showed no significant changes at 2 hours. Portal venous flow and microperfusion were decreased significantly and hepatic arterial buffer response was ineffective. Hepatic oxidative stress was increased in BD animals (decrease rGSH(L), increase GSSG(L)). Surgical denervation/manipulation increased portal venous flow significantly, hepatic arterial buffer response became effective, and stomach pHi decreased (BD and LD groups). Hepatic oxidative stress was reduced in the BD group (increase rGSH(L)/GSSG(L); P < 0.001) while it was increased in the LD group (decrease rGSH(L)/GSSG(L); P < 0.001). In conclusion, denervation reduces hepatic oxidative stress in BD only in contrast to the LD. The reciprocal effect of denervation depends on the state of neural activation and postulates a potential benefit of surgical denervation before organ harvesting in brain death.     

Milrinone improves intestinal villus blood flow during endotoxemia

PURPOSE: To determine whether the compromised intestinal villus blood flow in a rat model of endotoxemia could be improved by continuous infusion of the phosphodiesterase (PDE) inhibitor milrinone. METHODS: Twenty-four anesthetized and ventilated rats were laparotomized and an ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides without phosphodiesterase inhibitor pretreatment (=LPS group); or infusion of LPS with milrinone pretreatment (= milrinone group), or without infusion of LPS or milrinone (=control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = D(A) and mean erythrocyte velocity within the arterioles= V(E)) were measured 30 min before and at 0, 60, and 120 min after induction of endotoxemia. Mucosal villus blood flow was calculated from D(A) and V(E). RESULTS: In the milrinone group MAP decreased 60 min after induction of endotoxemia whereas it remained stable in the control and the LPS group. In both groups given endotoxin V(E) decreased after start of LPS infusion. In contrast, D(A) decreased in the LPS group, but increased in the milrinone group after 120 min of endotoxemia. Thus, the endotoxin-induced decrease of intestinal villus blood flow was diminished but not fully restored by milrinone infusion. CONCLUSION: Our results indicate that milrinone has some beneficial microcirculatory effects during endotoxemia. Although it contributed to systemic hypotension, it attenuated intestinal mucosal hypoperfusion.     

Endotoxemia in coronary artery bypass surgery: a comparison of the off-pump technique and conventional cardiopulmonary bypass

OBJECTIVES: The endotoxemia associated with cardiac surgery is thought to be dominantly influenced by the use of cardiopulmonary bypass. The objectives of this study were to assess the relative contribution of cardiopulmonary bypass on endotoxemia apart from cardiac surgical access and to improve our understanding of the potential benefits of off-pump procedures. METHODS: Thirty patients undergoing coronary artery bypass grafting were followed up prospectively. The patients were divided into 2 equal groups: those who underwent bypass grafting through a sternotomy incision without cardiopulmonary bypass (off-pump group) and those who underwent bypass grafting through a sternotomy incision with cardiopulmonary bypass (CPB group). Blood sampling for endotoxin, lactate, and cardiac index measurements were performed during the following time points: (1) after sternotomy; (2) during the coronary occlusion period in the off-pump group and during aortic clamping in the CPB group; (3) after removal of the coronary occlusion sutures in the off-pump group and after removal of the aortic clamp in the CPB group; (4) 30 minutes after the completion of all distal anastomoses in the off-pump group and immediately after weaning from cardiopulmonary bypass in the CPB group; (5) 1 hour postoperatively; and (6) 12 hours postoperatively. RESULTS: Endotoxin and lactate levels were significantly (P <.05) lower in the off-pump group at all sampling time points, except after sternotomy. CONCLUSIONS: In conclusion, this study has shown that endotoxemia during coronary artery bypass surgery seems mainly to be associated with cardiopulmonary bypass procedure. The relatively lower endotoxin levels observed in off-pump surgery might contribute to improved postoperative recovery.     

The neurologic sequelae of cardiopulmonary bypass-induced cerebral hyperthermia and cerebroprotective strategies

Cerebral hyperthermia during the rewarming phase of cardiopulmonary bypass (CPB) is associated with adverse outcomes. Cerebral hyperthermia can exacerbate a preexisting injury prior to rewarming, and may be damaging in itself. Temperature and cerebral metabolic rate (CMRO2) play a vital role in cerebral autoregulation. Therefore, hyperthermia can have a strong impact on cerebral oxygen transfer, and neurologic outcome. Glutamate levels can increase during cerebral hyperthermia, leading to eventual cell death. Rapid rewarming decreases jugular venous hemoglobin saturation, creating a mismatch between cerebral oxygen consumption and delivery. With these ill effects in mind, cerebral protection during CPB is imperative. Special attention should be given during rewarming to prevent these harmful outcomes. Pharmacologic agents such as sodium nitroprusside can be used to assist the rewarming process. Temperature management is the key component during the rewarming phase of CPB in the prevention of cerebral hyperthermia.     

The effects of olprinone (a phosphodiesterase III inhibitor) on hepatic vascular bed in a porcine model of endotoxemia

Decreased hepatic blood flow, and impaired hepatic oxygen delivery caused by endotoxin, result in hepatic metabolic deterioration followed by liver dysfunction and multiple organ failure. Among phosphodiesterase III inhibitors, only olprinone increases hepatosplanchnic blood flow. We evaluated the effects of olprinone on systemic hemodynamics, hepatic circulation, and hepatic oxygen delivery in a porcine model of endotoxemia. Fifteen pigs received a continuous infusion (1.7 microg. kg(-1). h(-1)) of endotoxin (lipopolysaccharide [LPS]) via the portal vein for 240 min. Seven of these pigs received olprinone infusion (0.3 microg. kg(-1). min(-1)) via a central vein from t = 150 min to t = 240 min, whereas the eight remaining pigs served as LPS controls. Continuous infusion of LPS caused significant reductions in hemodynamic variables and a significant increase in arterial lactate. After the administration of olprinone during the LPS infusion, portal venous flow and hepatic oxygen delivery were increased and were higher than in the LPS group. Furthermore, olprinone prevented any further increase in arterial lactate. We conclude that the administration of olprinone halted the disturbances in the hepatic circulation, especially in portal venous flow and hepatic oxygen delivery, in a porcine model of endotoxemia. IMPLICATIONS: Endotoxin is a causative factor in peripheral vascular failure, resulting in a hemodynamic depression that includes a reduction in liver blood flow. The administration of olprinone (phosphodiesterase III inhibitor) improves the liver blood flow circulation in a porcine model of endotoxemia.