Effect of prostaglandin E1 on peripheral body temperature in pediatric patients after open heart surgery]

The effect of prostaglandin E1 was studied to examine if it works favorably for peripheral circulation in pediatric patients after cardiac surgery. Dose of 0.1 mcg.kg-1.min-1 increased temperature of dorsal pedis significantly. Difference of temperature of dorsalis pedis and that of rectum was significantly smaller than that in control group. A significant increase in heart rate and a decrease in systolic arterial pressure produced no clinical side effects. We conclude that prostaglandin E1 is a useful and safe vasodilator for circulatory management of pediatric patients after cardiac surgery.     

Recovery from cardiac arrest by prostaglandin E1 infusion during emergency open heart surgery

A 21 day old infant, diagnosed as ASD, VSD, and PDA, was scheduled for an emergency radical operation. After admission, she fell into cardiac failure and was treated with artificial ventilation and infusion of inotropic agents. Anesthesia was induced with fentanyl and maintained with continuous fentanyl infusion and chlorpromazine. Dopamine and dobutamine were administered before she underwent a cor-pulmonary by-pass. At the time of release of aortic clamping, her blood pressure went down and dopamine, dobutamine and isoproterenol were administered. After completion of the cor-pulmonary by-pass, tachy-arrhythmia and hypotension occurred. Digitalis and calcium did not reverse the condition. The thorax was reopened and BP rose. After 15 min, ventricular fibrillation occurred. Defibrillation was carried out, but the heart was arrested. Even with pacing and cardiac massage, cardiac contraction did not resume. However immediately on intravenous administration of PGE1, 40 ng.kg-1.min-1, the heart started to beat. The cause of recovery from cardiac arrest was speculated to be due to reuptake of intracellular Ca2+ by PGE1. We stress therefore, that during and after cor-pulmonary by-pass procedures, PGE1 infusion may be beneficial.     

Reduction of neutrophil activation by vitamin E modified dialyzer membranes

BACKGROUND/AIM: Transient leukopenia during hemodialysis due to neutrophil activation is attributed to bioincompatibility of the dialysis membrane, but the mechanism remains unclear. We studied the mechanism of neutrophilic activation by comparing a vitamin E modified membrane (CLEE) and a regular cellulose membrane (CLSS). METHODS: (1) CLSS and CLEE membranes were used in a crossover clinical study in 7 chronic hemodialysis patients. Neutropenia, CD11b expression, and plasma C3a and myeloperoxidase concentrations were compared between the two dialyzer membranes. (2) Normal blood was circulated through CLEE and CLSS minimodels, and the same parameters were compared. (3) Blood samples with modified complement activities (EDTA: both classical and alternative pathways inactivated; EGTA+Mg: classical pathway inactivated; heating: alternative pathway inactivated; control: no modification) were incubated in the CLSS minimodel, and the neutrophilic activation was compared. RESULTS: In clinical hemodialysis, neutropenia, CD11b expression, and C3a and myeloperoxidase levels were significantly lower when CLEE membranes were used. The same tendency was observed in minimodels. However, the degrees of inhibition in clinical dialysis, especially at the venous line, were significantly higher than in minimodels. As compared with controls, CD11b expression and myeloperoxidase level were significantly lower when both classical and alternative pathways were inactivated or when the classical pathway alone was inactivated, but were not significantly different when the alternative pathway alone was inactivated. CONCLUSIONS: Vitamin E modification of the dialyzer reduces some reactions of neutrophilic activation, such as CD11b expression and myeloperoxidase release, more effectively in the clinical situation than in ex vivo models, suggesting a possible effect of vitamin E in inhibiting bioreactions due to pyrogen in the dialysate. The classical complement pathway is required in membrane-induced neutrophilic activation, at least during the initial stage.     

前列腺素E1不同给药时机治疗围术期先天性心脏病肺动脉高压的观察

目的　观察先天性心脏病合并重度肺动脉高压（ＰＨ）患者围术期血液动力学的变化。方法　２０ 例先天性心脏病合并重度肺动脉高压患者以前列腺素Ｅ１ 应用不同时机分对照组和试验组,每组１０例。试验组在体外循环开始后从中心静脉持续泵注前列腺素Ｅ１２０ｎｇ·ｋｇ－ １ ·ｍ ｉｎ－ １;对照组在体外循环中,开放升主动脉后开始用前列腺素Ｅ１ 。观察围术期平均动脉压（ＭＡＰ）、平均肺动脉压（ＰＡＰ）、动脉压与肺动脉压之比（ＰＰ／ＰＳ）、心脏指数（ＣＩ）、肺阻力指数（ＰＶＲＩ）、体循环阻力指数（ＳＶＲＩ）的动态变化。结果　体外循环后各时点的肺动脉压力与主动脉压力之比较术前显著降低,（Ｐ＜ ０．０１）。肺阻力指数和体循环阻力指数在体外循环后逐渐升高,试验组肺阻力指数在升主动脉开放后６ 小时显著低于对照组,（Ｐ＜ ０．０１）。试验组心指数在开放循环后２～４ 小时高于对照组,（Ｐ＜０．０５）。结论　重度肺动脉高压心内畸形矫正手术中,体外循环开始即应用前列泉素Ｅ１ 的效果优于传统的开放升主动脉后给药的效果。     

Nitecapone reduces cardiac neutrophil accumulation in clinical open heart surgery.

BACKGROUND: To study the effect of nitecapone, a novel antioxidant, on cardiac neutrophil activation during cardiopulmonary bypass in patients. METHODS: In a double-blind, placebo controlled trial, 30 male patients undergoing coronary artery bypass grafting were randomly assigned to control (crystalloid cardioplegia, n = 15) and nitecapone groups (cardioplegia supplemented with nitecapone, n = 15). Leukocyte differential counts, neutrophil and monocyte CD11b and L-selectin expressions and neutrophil hydrogen peroxide production were measured in blood samples parallelly obtained from the coronary sinus and aorta before cardiopulmonary bypass and at 1, 5, and 10 min after aortic declamping. Myocardial myeloperoxidase activity was analyzed in biopsies taken at 1, 5, and 10 min after declamping. RESULTS: Transcoronary neutrophil difference (i.e., aorta--sinus coronarius) at 1 min after aortic declamping was significantly lower in nitecapone-treated patients (0.41 [-0.42-0.98] x 10(9) cells/l) than in controls (0.68 [-0.28-2.47] x 10(9) cells/l; P = 0.032). At 5 min after aortic declamping, significant transcoronary reduction of neutrophil hydrogen peroxide production and CD11b expression were observed in controls but not in nitecapone patients. At 24 h postoperatively, left ventricular stroke volume was better in nitecapone-treated patients (94 [51-118] ml) than controls (66 [40-104] ml; P= 0.018). Data are median [range]. CONCLUSION: Nitecapone added to cardioplegia solution reduces cardiac neutrophil accumulation and transcoronary neutrophil activation during clinical cardiopulmonary bypass. Reflected by better left ventricular stroke volume, nitecapone treatment may be an additional way of reducing the deleterious effects of neutrophil activation during cardiopulmonary bypass.     

Recommendation for open heart surgery in infancy]

Progress in infant open-heart surgery last 10 years was reviewed mainly based on the surgical experiences in Fukuoka Children's Hospital. Recent advances and present problems in patient's care, cardiopulmonary bypass methods and cardioplegia were discussed. Low surgical mortality of 4.8% in 245 infant open-heart repairs between 1988 and 1990 in Fukuoka is highly suggestive of early primary repair for most of congenital heart diseases.     

Predonation and transfusion in open heart surgery]

The efficacy of predonation of autologous blood in reducing the use homologous blood during open heart surgery was investigated. Between January 1997, and February 1998, predonation and transfusion was studied in 100 consecutive open heart operations (CABG, 77; valve surgery, 17; ASD, 5; myxoma, 1). The guidelines for autologous predonation were as follows: an age < 70 years, a weight > 40 kg and a hemoglobin > 12 g/dl. Patients in NYHA class IV or undergoing emergency operation were excluded. The blood loss during operation ranged from 195 to 1,850 ml (mean; 670 ml), being from 305 to 1,850 ml (723 ml) for CABG, from 260 to 1,020 ml (493.5 ml) for valve surgery and from 195 to 570 ml (342 ml) for ASD. The blood loss was not significantly dependent on sex or age and did not differ elective and emergent operations. Only 36.6% of patients with autologous predonation needed homologous transfusion versus 63.4% of those without predonation. Homologous transfusion was done in only 5% of the those with predonation of 800 ml versus 69% at 400 ml and 71% at 200 ml. In conclusion, autologous blood transfusion is effective for reducing the homologous blood requirement. It also seems that predonation of 800 ml may be sufficient to allow open heart surgery without blood transfusion.     

Markers for endothelial activation during open heart surgery

BACKGROUND: Reliable markers for endothelial activation are needed when studying biocompatibility of cardiopulmonary bypass. METHODS: Blood samples from 21 patients undergoing combined valve and coronary artery bypass surgery were collected before anesthesia (T1), after re-transfusion of blood from the heart-lung machine (T2), and on the first postoperative morning (T3). Concentrations of soluble markers were determined using sandwich enzyme-linked immunoadsorbent assay for sICAM-1, sVCAM-1, and sE-selectin. The sera were also used to stimulate human umbilical vein endothelial cells (HUVEC) in culture for 6 hours, in which activation was measured using cell enzyme immunoassay for mICAM-1 and mVCAM-1. RESULTS: The concentrations of sICAM-1 and sVCAM-1 increased during both measurement intervals (p < 0.05). The sICAM-1 T1 was 311.0 ng/mL (range, 271.0 to 350.7 ng/mL); the sICAM-1 T2 was 341.6 ng/mL (range, 322.0 to 422.0 ng/mL), and the sICAM-1 T3 was 400.2 ng/mL (range, 348.0 to 556.4 ng/mL; the sVCAM-1 T1 was 607.5 ng/mL (range, 497.8 to 813.8 ng/mL), the sVCAM-1 T2 was 755.3 ng/mL (range, 660.6 to 834.4 ng/mL), and the sVCAM-1 T3 was 1149.0 ng/mL (946.0 to 1406.0 ng/mL); whereas the sE-selectin increased from T1 to T3 (p < 0.01). Both the mICAM-1 (p < 0.002) and the mVCAM-1 (p < 0.005) increased on the human umbilical vein endothelial cells in culture after stimulation with the patient sera. The amounts of soluble markers in vivo were not correlated with the degree of endothelial activation in vitro, but were correlated with various operative variables including age, medication, and time of aortic cross-clamping. CONCLUSIONS: Endothelial cells were activated during cardiopulmonary bypass. The soluble adhesion molecules sICAM-1, sVCAM-1, and sE-selectin displayed different kinetics, rendering it difficult to determine a simple expression for the degree of endothelial cell activation. Clinically, sVCAM-1 seemed to be the best-suited marker for endothelial cell activation, because it was only associated with aortic cross-clamping and heparin and protamine doses, and it also showed the largest numerical changes.     

The factors effecting complement activation in open heart surgery.

The activation of the complement system was investigated in 10 patients with rheumatic valve disease having heart surgery. The C3c, C4, leukocyte count and polymorphonuclear neutrophil count were determined in the blood samples taken before anaesthesia, after anaesthesia, 10 minutes after protamine administration and after the closure of the skin incision. In addition, atrial blood samples were taken after the release of the cross-clamp and pulmonary neutrophil trapping was investigated. In this study C3c and C4 consumption was found to take place after 30 minutes of CPB (cardiopulmonary bypass) and 10 minutes after protamine administration; the affects of anaesthesia and heparin were not significant.     

The effects of prostaglandin E1 on myeloperoxidase and alpha 1-protease inhibitor in head-neck surgery]

To investigate whether prostaglandin E1 (PGE1) 30 ng.kg-1.min-1 inhibits the release of lysosomal enzyme from granulocytes by surgical stimuli, we measured myeloperoxidase and alpha 1-protease inhibitor (alpha 1-PI) in 32 patients for head neck surgery. The patients were divided into two groups; no PGE1 infusion group (C group) and PGE1 30 ng.kg-1.min-1 infusion group (P group). PGE1 was infused intravenously using a syringe pump during operation. MPO and alpha 1-PI were measured at 4 points: before induction of anesthesia, before surgery, 4 hours after the start of surgery or the infusion of PGE1, and on the first postoperative day. MPO was maintained at significantly higher levels during and after surgery in both groups. alpha 1-PI decreased significantly during operation and increased for 10% in the first postoperative day in both groups. There were no significant differences between groups in MPO and alpha 1-PI levels. We conclude that the infusion of PGE1 30 ng.kg-1.min-1 did not completely inhibit the release of lysosomal enzyme from granulocytes by surgical stimuli.     

Clinical use of prostaglandin E1 during intracranial surgery

Prostaglandin E1 was administered to 19 patients to induce hypotension during intracranial surgery. Urine volume during the operation and after the first day was well maintained, and serum BUN and creatinine were within normal ranges after the surgery. Serum GOT and GPT increased significantly on the 7th and 14th day after the operation compared with the control, but this did not seem to be the results of PGE1 administration. LDH and ALP showed no significant change. Thirty minutes and two hours after the administration of PGE1, arterial blood oxygen tension decreased significantly. These results suggest that PGE1 does not adversely affect the liver and kidneys, and it can be used safely and is useful to control blood pressure during intracranial operation.     

Role of prostaglandin E1 in steroidogenesis by isolated rat adrenal cells]

In order to investigate the effects of prostaglandin E1 (PGE1) used in hypotensive anesthesia on the adrenal endocrine function, aldosterone, corticosterone (Comp B) and cAMP production were measured in isolated glomerulosa (G-c) and fasciculata cells (F-c) of the rats. Rat glomerulosa and fasciculata cells were obtained by enzymatic digestion of the adrenals of male wistar rats. The cell pellet was suspended in Hank's balanced salt solution containing 0.1% BSA and distributed in 900 microliters aliquots to polyethylene tubes. The samples were preincubated for 90 min in a 37 degrees C water bath aerated with 5% CO2/95% O2. PGE1 or ACTH 50 microliters was added and incubated for 4 hr. Total volume of the incubation medium is 1.0 ml. Aldosterone and cAMP were measured by radioimmunoassay and Comp B was determined by fluorimetric method. PGE1 increased significantly the basal secretion of aldosterone and Comp B in G-c and F-c, respectively. The steroidogenic effect of PGE1 was dose dependent in aldosterone production. This aldosterone production was also accompanied with cAMP production. On the other hand, significant increase of cAMP was not observed in comp B production. These results suggest that cAMP may be the second messenger in PGE1-induced aldosterone production in G-c. But PGE1 receptors in F-c seem not to be coupled to the adenylate cyclase system. The addition of ACTH and PGE1 resulted in inhibition of aldosterone secretion when compared with that obtained by ACTH alone. Several researchers have shown that low doses of PGE1 depressed the basal aldosterone secretion. These findings may be contributing to Na-uresis effect during PGE1-induced hypotension.     

Effects of aprotinin on prostaglandin metabolism and platelet function in open heart surgery.

The effects of the protease inhibitor, aprotinin, on plasma prostaglandin levels and platelet function during and after cardiopulmonary bypass (CPB) were studied in a group of 23 patients which consisted of 11 untreated patients (control group) and 12 aprotinin-treated patients (aprotinin group). Thromboxane B2 (TXB2, a stable metabolite of thromboxane A2) and beta-thromboglobulin levels in the control group increased significantly during CPB compared with preoperative values. These increases were significantly suppressed in the aprotinin group. 6-Keto-PGF1 alpha (stable metabolite of prostacyclin) increased significantly during CPB in both groups, and there was no significant difference between the two groups. In the aprotinin group, the TXB2/6-Keto-PGF1 alpha ratio decreased significantly during CPB compared with the preoperative value, whereas no significant decrease was observed in the control group. Platelet counts decreased significantly during and after CPB in both groups. Platelet aggregability decreased significantly during CPB in the control group, whereas no significant decrease was found in the aprotinin group. In conclusion, aprotinin treatment improved prostaglandin metabolism and preserved platelet function during open heart surgery.     

Effects of prostaglandin E1 in the treatment of congestive heart failure after mitral valve replacement]

Prostaglandin E1 (PGE1) was intravenously administrated to 3 patients for treatment of postoperative congestive heart failure. Preoperative diagnoses of these patients were mitral valve stenosis (2 cases) and mitral valve regurgitation (1 case), associated with tricuspid valve regurgitation in every case. Mitral and tricuspid valve replacements was performed in one case, and mitral valve replacement and tricuspid annuloplasty in two cases. After infusion of PGE1, the central venous pressure was decreased rapidly and the patients recovered from congestive heart failure. As minimal doses of PGE1 (0.01-0.03 micrograms/kg/min) was infused, neither remarkable systemic hypotension nor fall of PaO2 were observed. It appears that application of small amount of PGE1 can be a useful mean for the treatment of congestive heart failure after valvular surgery.