Effects of cyclic AMP and dibutyryl cyclic AMP on cerebral hemodynamics and metabolism in the baboon.

Adenosine 3',5'-cycle monophosphate (cyclic AMP) (0.5 mg/kg) was infused into the carotid artery of baboons anesthesized with sodium pentobarbital, causing a biphasic increase in cerebral blood flow (CBF) and reduction in cerebrovascular resistance (CVR) associated in each phase with stimulation of cerebral metabolism evidenced by increased cerebral oxygen consumption (COMRO2) and cerebral glucose consumption (CMRG1). Intracarotid dibutyryl cyclic AMP (0.5 mg/kg) caused a monophasic increase in CBF and reduction of CVR but failed to alter cerebral metabolism. This may be due to its rapid removal from the circulation with ineffective passage across the blood-brain barrier since intracisternal infusion of dibutyryl cyclic AMP caused sustained increase in CBF, CMRO2 and CMRG1 and reduction in CVR. Intracarotid AMP (0.4 mg/kg) and adenosine (0.3 mg/kg) caused an immediate and more marked increase in CBF and decrease in CVR unassociated with cerebral metabolic change making it unlikely that the observed effects of cyclic AMP can be attributed to its breakdown products. Cyclic AMP or its dibutyryl derivative may alter cerebral metabolism secondary to neuronal activation but increase in glucose/oxygen utilization ratio after intracarotid cyclic AMP and intracisternal dibutytyl cyclic AMP also suggests an influence on enzymatic regulation of glucose metabolism.     

Effects of prostaglandin E1 infusion during cardiopulmonary bypass

Effects of continuous prostaglandin E1 (PGE1) infusion 0.03 micrograms.kg-1.min-1 on hemodynamics, body temperature and urine output during cardiopulmonary bypass (CPB) were studied. Systemic vascular resistance was kept significantly lower in PGE1 administration group than control group. Differences between core and peripheral temperature decreased faster in the PGE1 administration group than the control group. Mean arterial pressure was stable at 40mmHg during CPB in the PGE1 group and 60mmHg in the control group. However, there were no significant differences in urine output between the PGE1 administration group (10.8ml.kg-1.h-1) and the control group (9.4ml.kg-1.h-1). This study indicates that continuous PGE1 infusion (0.03 micrograms.kg-1.min-1) is a method of choice for vasodilation and improvement of peripheral perfusion during hypothermia of CPB.     

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.     

Effects and arterial concentration of prostaglandin E1 during cardiopulmonary bypass

The effects an infusion prostaglandin E1 (PGE1) on both haemodynamics and PGE1 arterial blood concentration during and after cardiopulmonary bypass (CPB) were studied in 15 patients (eight patients received PGE1 30 ng kg-1 min-1; seven served as controls and did not receive PGE1 administration). Mean arterial blood pressure and systemic vascular resistance were significantly lower in the PGE1 group than in the control group during CPB. There were no statistically significant differences between the two groups with regard to mean pulmonary-artery pressure, central venous pressure, and cardiac or perfusion index. The arterial blood concentration of PGE1 in the control group during CPB was about 50 pg ml-1. In the PGE1 group it increased rapidly after the beginning of CPB and reached a level of 1500 pg ml-1 at 60 min of CPB. After weaning off CPB, PGE1 concentration decreased rapidly to 70 pg ml-1 in spite of the continuous PGE1 infusion. It is concluded that the metabolism of PGE1 is strongly inhibited during CPB and the effects of PGE1 may be unexpectedly heightened. Therefore, the infusion rate of PGE1 during CPB should be 30 ng kg-1 min-1 or less in order to avoid severe hypotension.     

前列腺素E1脂微球载体制剂对体外循环患者肾功能的影响

目的 探讨前列腺素E1脂微球载体制剂(Lipo-PGE1)对体外循环(CPB)患者肾功能的影响.方法 择期拟行心脏瓣膜置换术患者20例,ASAⅡ或Ⅲ级,年龄34～56岁,性别不限,体重48～81 kg,随机分为生理盐水对照组(NS组)和前列腺素E1脂微球载体制剂组(Lipo-PGE1组),每组10例.Lipo-PGE1组于CPB开始至结束持续泵注Lipo-PGE13 ng·kg-1·min-1,预充液Lipo-PGE1浓度为5 ng/ml;NS组给予等容量生理盐水.于肝素化后CPB开始前(T1)、CPB开始30 min(T2)及CPB结束即刻、1、24 h(T3-5)时测定血浆血栓素B2(TXB3)、6-酮-前列腺素F1α(6-Keto-PGF1α)、游离血红蛋白(F-Hb)浓度及血清α1-微球蛋白(α1-MG)、β2-微球蛋白(β2-MG)及半胱氨酸蛋白酶抑制剂C(Cys C)的浓度.结果 与T1时比较,两组T2-4时,TXB2、6-Keto-PG F1α及TXB2/6-Keto-PGF1α、α1-MG、β2-MG浓度升高,T2-5时F-Hb及Cys C浓度明显升高(P<0.05);与NS组比较,Lipo-PGE1组T2～4时6-Keto-PGF1α浓度升高,TXB2、TXB2/6-Keto-PGF1α、α1-MG、β2-MG浓度降低,T2-5时F-Hb及Cys C浓度明显降低(P<0.05).结论 Lipo-PGE1可明显改善体外循环患者的肾功能.     

Effects of small doses of prostaglandin E(1) on systemic hemodynamics and jugular venous oxygen saturation during cardiopulmonary bypass

STUDY OBJECTIVE: To examine the effects of small doses of prostaglandin E(1) (PGE(1)) on systemic hemodynamics and cerebral oxygenation during cardiopulmonary bypass(CPB). DESIGN: Randomized, prospective study. SETTING: Cardiac surgery at Saitama Cardiovascular and Pulmonary Center. PATIENTS: Forty patients who underwent elective coronary artery bypass surgery. INTERVENTIONS: The study was performed at the stable CPB period. Patients were randomly divided into four groups: control group (n = 10) received an infusion of saline, PGE(1) 10 group (n = 10) received an infusion of PGE(1) 10 ng/kg/min, PGE(1) 25 group (n = 10) received an infusion of PGE(1) 25 ng/kg/min, and the PGE(1) 50 group (n = 10) received an infusion of PGE(1) 50 ng/kg/min. MEASUREMENTS: After measuring the baseline partial pressure of the arterial oxygen saturation (SpO(2)), mixed venous oxygen saturation (SvO(2)), and jugular venous oxygen saturation (SjvO(2)), blood gases, and cardiovascular hemodynamic values, PGE(1) was infused intravenously at rate of between 10 and 50 ng/kg/min. PGE(1) infusion continued 30 minutes after the start of drug infusion, and the blood gas analysis and cardiovascular hemodynamic values were simultaneously determined together with the hemodynamic values at 2, 5, 10, 20, and 30 minutes during drug infusion. At 30 minutes after discontinuation of the drug infusion, the blood gas analyses were simultaneously determined together with the hemodynamic values. MAIN RESULTS: Mean arterial pressure (MAP) in PGE(1) 25 and 50 groups was decreased 20 and 30 minutes after the start of PGE(1) infusion compared with the baseline value (p < 0.05). In contrast, SvOm(2) in PGE(1) 25 and 50 groups was increased 20 and 30 minutes after the start of PGE(1) infusion compared with the baseline value (p < 0.05). There was no change in SjO(2) value despite a decrease in MAP during the study. CONCLUSIONS: Cerebral oxygenation estimated by SjvO(2) was maintained despite a decrease in MAP during the administration rate of PGE(1) between 10 and 50 ng/kg/min.     

Hypothermia after cardiopulmonary bypass in man: effects of prostaglandin E1 and phentolamine

The "afterdrop" in body temperature (TEMP) following adequate rewarming from hypothermic cardiopulmonary bypass (CPB) is frequently observed. This temperature drop sometimes accompanied by shivering results in increased myocardial oxygen demand. We investigated the relations between the afterdrop and use of vasodilators after CPB. For vasodilator therapy, PGE1 at the rate of 0.025-0.088 microgram.kg-1.min-1 (Prostaglandin Low Doses, PLD; n = 8), 0.107-0.136 microgram.kg-1.min-1 (Prostaglandin High Doses, PHD; n = 7), or phentolamine at 4.1-5.9 micrograms.kg-1.min-1 (PHENT; n = 8) were intravenously infused in 23 adult patients after CPB. During three hour period after CPB, esophageal, rectal, and forehead TEMP are lower in PHENT than in PGE1 groups. There were significant differences between PHD and PHENT group. Finger tip TEMP was lower in PGE1 groups than in PHENT group. There were significant differences between PHD and PHENT group. There were no differences in systemic arterial pressure, cardiac index (CI) and systemic vascular resistance (SVR) at any point between PHD and PHENT groups. It is concluded that PHENT increases the peripheral skin blood flow and TEMP but decreases the visceral TEMP possibly due to vasodilatation of the skin vessels, while PGE1 decreases skin blood flow and TEMP but increases the visceral TEMP, although SVR clearly decreases at the same rate in the two groups.     

Effects of prostaglandin E1 on renal hemodynamics

The glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF), filtration fraction (FF), and the ratio of mean arterial pressure (MAP) to RBF (MAP/RBF), reflecting renal vascular resistance (RVR) were determined to investigate the effects of intravenously administered prostaglandin E₁ (PGE₁) on renal hemodynamics in humans. PGE₁ produced no significant changes in GFR, but did cause significant increases in RPF and RBF and significant decreases in FF and MAP/RBF. The relationships between MAP and GFR, MAP and RBF, and MAP and MAP/RBF were investigated. PGE₁ suppressed the increase of MAP/RBF along with the increase of MAP, increased the RBF along with the increase of MAP, and kept the GFR constant, regardless of MAP. Also, the effects of PGE₁ on renal pericapillary vessels were simulated. According to this simulation, PGE₁ had a vasodilator action on both preglomerular and postglomerular capillaries.     

心肺转流心脏手术用乌司他丁对肾功能的影响

目的研究乌司他丁对心肺转流（CPB）心脏手术患者。肾功能的影响。方法30例拟行心脏瓣膜置换手术患者,分为两组,每组各15例。对照组未用药（C组）,实验组乌司他丁（U组）。实验组（U组）给予乌司他丁2万U／kg,体外循环前静脉滴入1／3量,体外循环机内预充1／3量,开放升主动脉后给予1／3量。术后第1、2、3天分别静脉输注乌司他丁0．5万U/kg,对照组（C组）给予等量生理盐水。分别于术前（T0）、术后1d（T1）、3d（T3）、5d（T5）、7d（T7）检测血清尿素氮（BUN）、血清肌酐（Cr）、血清β2-微球蛋白（β2-MG）、尿视黄醇结合蛋白（RBP）、尿β2-微球蛋白（β2-MG）的含量。结果①BUN、Cr：C组术后T1和T3显著高于术前及U组同一时点值（P〈0．05）;②血清β2-MG：C组术后仅T1、T3明显高于术前及U组同一时点值（P〈0．05）;③尿RBP：C组术后各时点值及U组T1、T3值明显高于术前值（P〈0．01）,两组术后各时点比较,U组明显低于C组（P〈0．01）;④尿β2-MG：C组术后各时点值显著高于术前值（P〈0．01）,U组T1、T3明显高于术前值（P〈0．05）,两组间术后各同一时点值比较有统计学差异（P〈0．01）。结论乌司他丁对心肺转流（CPB）心脏手术后患者。肾功能有一定保护作用。     

双心房输注对二尖瓣置换术患者体外循环后肺动脉压的影响

目的 评价双心房输注对二尖瓣置换术患者体外循环后肺动脉压(PAP)的影响.方法 择期行二尖瓣置换术合并肺动脉高压[平均肺动脉压(MPAP)＞50 mm Hg]的患者20例,年龄22～53岁,体重34～57kg,心功能分级Ⅱ或Ⅲ级,随机分为2组(n=10):右心房输注组(R组)和双心房输注组(B组).麻醉诱导后右颈内静脉穿刺置入Swan-Ganz三腔漂浮导管,监测CVP、PAP、肺毛细血管楔压(PCWP)和CO.R组经中心静脉输注前列腺素E130～150 ng·kg-1·min-1和去氧肾上腺素0.2～0.6μg·kg-1·min-1.B组经中心静脉输注前列腺素E130～150 ng·kg·min-1,经左心房输注去氧肾上腺素0.2～0.6μg·kg-1·min-1.分别于给药前5 min(T0)、给药后5 min(T1)、10 min(T2)、30 min(T3)和60 min(T4)时记录MAP、HR、MPAP、PCWP、CVP和CO,计算肺血管阻力指数(PVRI)、体循环血管阻力指数(SVRI)和CI.结果 与T0时比较,R组T1-4时MAP、MPAP、PCWP和PVRI降低,CI升高(P＜0.05),HR、CVP和SVRI差异无统计学意义(P＞0.05),B组T1-4时MAP、CI和SVRI升高,HR、MPAP、PCWP、CVP和PVRI降低(P＜0.05);与R组比较,B组MAP、CI和SVRI升高,HR、MPAP、PCWP、PVRI和CVP降低(P＜0.05).结论 双心房输注可降低二尖瓣置换术患者体外循环后肺动脉压和肺血管阻力.     

Effects of dibutyryl cyclic AMP and theophylline on biliary cholesterol secretion

Glucagon increases hepatocellular cAMP and decreases biliary cholesterol output. In these experiments, we examined the relation between cAMP and biliary cholesterol secretion. Bile flow and composition were measured in conscious dogs previously prepared by cholecystectomy, ligation of the lesser pancreatic duct, and placement of duodenal and gastric cannulae. Sodium taurocholate (500 mg/hr) was given intravenously to stabilize bile flow. After 2 hr of taurocholate infusion, dibutyryl cyclic AMP (160 mg kg-1 hr-1) or theophylline (20 mg kg-1 hr-1) was administered intravenously. Dibutyryl cAMP caused a decrease in both cholesterol concentration (242 +/- 25 micrograms/ml to 81 +/- 11 micrograms/ml) and cholesterol output (692 +/- 102 micrograms/15 min to 382 +/- 47 micrograms/15 min). Theophylline decreased cholesterol concentration (282 +/- 39 micrograms/ml to 221 +/- 21 micrograms/ml), but there was no significant change in cholesterol output. Bile flow increased significantly with both dibutyryl cAMP (2.8 +/- 0.2 ml/15 min to 4.9 +/- 0.2 ml/15 min) and theophylline (2.6 +/- 0.4 ml/15 min to 4.2 +/- 0.4 ml/15 min). In additional experiments, aminophylline (85% theophylline, 15% ethylenediamine) was administered intravenously (24.7 mg kg-1 hr-1). Aminophylline reduced cholesterol concentration (59 +/- 6 micrograms/ml to 36 +/- 5 micrograms/ml), but cholesterol output was stable. Bile flow increased significantly (3.7 +/- 0.2 ml/15 min to 6.5 +/- 0.4 ml/15 min). The mechanisms of these changes remain unknown. The effect of dibutyryl cAMP on biliary cholesterol secretion supports but does not prove the hypothesis that glucagon decreases biliary cholesterol output via the second messenger, cAMP.     

氨甲环酸对心肺转流患者手术出血量的影响

目的 探讨氨甲环酸(TA)对心肺转流(CPB)术中出血及输血量的影响.方法 择期心脏二尖瓣瓣膜置换术患者100例,随机分为五组:TA100、TA75、TA50、TA25、TAO组,TA剂量分别为100、75、50、25、0 mg/kg,每组20例.除TA0组外,其他四组均于诱导后切皮前静注TA.记录术前、术毕、术后12 h血细胞比容(Hct),记录CPB时间、术中出血量、红细胞用量、术后12 h心包及纵隔引流量、输血量等.结果 与TA0组比较,其他四组术中出血量及红细胞用量、术后12 h心包引流量及红细胞用量、血浆用量显著降低(P＜0.05或P＜0.01);但四组间比较差异无统计学意义.结论 CPB前使用TA 25～100 mg/kg可以减少术中、术后的出血量和输血量.