Effect of cardiopulmonary bypass on pulmonary clearance of adrenomedullin in humans.

BACKGROUND: Adrenomedullin is a potent vasodilatory peptide and its plasma concentration increases after cardiopulmonary bypass. We analyzed the contribution of the lung to the disposition of adrenomedullin before and after cardiopulmonary bypass in humans. METHODS: Thirty-five patients undergoing cardiac surgery with cardiopulmonary bypass were studied. Bloods were sampled from the pulmonary artery and left atrium at the following times: prior to systemic heparinization, during pulmonary reperfusion and after cardiopulmonary bypass. Plasma concentrations of total and mature adrenomedullin were measured using an immunoradiometric assay kit specific for human adrenomedullin. Intermediate adrenomedullin was calculated as the difference between total adrenomedullin and mature adrenomedullin. RESULTS: Before cardiopulmonary bypass, mature and intermediate adrenomedullin concentrations were reduced by the pulmonary circulation by approximately 30% and 20%, respectively. However, these effects were not observed during pulmonary reperfusion. Mature, but not intermediate, adrenomedullin was reduced after cardiopulmonary bypass. Furthermore, pulmonary clearance quantity of mature adrenomedullin was significantly enhanced after cardiopulmonary bypass. CONCLUSION: These results indicate that cardiopulmonary bypass temporally impairs the pulmonary clearance of mature and intermediate adrenomedullin, but clearance of mature, not intermediate adrenomedullin is enhanced after cardiopulmonary bypass.

Prospective analysis of percutaneous central venous catheterization in infants <4.0 kg undergoing cardiac surgery.

Our previous study showed that the success rate of cannulation of the internal jugular vein (IJV) was significantly decreased in infants weighing less than 4.0 kg. We prospectively evaluated results of central venous catheterization in 101 infants weighing less than 4.0 kg undergoing cardiac surgery. The first attempt was routinely performed on the right IJV. If the first attempt failed, the anesthesiologist was free to choose the cannulation site. We examined the effects of patient weight and the experience of the anesthesiologist on successful central catheterization and efficacy of the external jugular vein (EJV) if the first attempt failed. The first right IJV cannulation was successful in 53 infants (52.5%) and the overall successful catheterization rate was 82.2%. Success rates of cannulation of the right IJV, left IJV, and EJV were 64, 13, and 6%, respectively. Body weight contributed significantly to successful catheterization, but the experience of the anesthesiologist did not. These results suggest that EJV cannulation improves the successful central catheterization in infants weighing less than 4.0 kg if IJV cannulation fails. Body weight of an infant, but not the experience of the anesthesiologist, contributed to successful catheterization in this patient population.

What factors are associated with hyperlactatemia after cardiac surgery characterized by well-maintained oxygen delivery and a normal postoperative course? A retrospective study.

BACKGROUND: and objective The purpose of this study was to investigate retrospectively what factors contribute to the development of the type of hyperlactatemia which may follow cardiopulmonary bypass despite well-maintained oxygen delivery and a normal perioperative course. METHODS: The medical records of 124 patients undergoing elective cardiac surgery using cardiopulmonary bypass were reviewed. The patients were divided into a hyperlactatemia group (n=34), where the serum lactate concentration was > 5.0 mmol L(-1) perioperatively, and a normal lactatemia group (n=90), which comprised the remaining patients. RESULTS: The duration of cardiopulmonary bypass in the hyperlactatemia group was significantly longer than for the normal lactatemia group. Significant differences of lactate concentrations between the groups, and significant elevations of serum lactate had been observed after the start of cardiopulmonary bypass. Oxygen extraction rates were significantly reduced during the period of cardiopulmonary bypass but, on the contrary, increased in the hyperlactatemia group after surgery. The area under the curve of mean arterial pressure consisted of 5-min interval plots during the initial period of cardiopulmonary bypass in the hyperlactatemia group. This was significantly smaller than for the normal lactatemia group. Weakly significant correlations between maximal lactate and duration of cardiopulmonary bypass, and especially the area under the curve, were observed. CONCLUSIONS: It is suggested that the pathophysiology observed is based on impairment of tissue oxygen utilization. The duration of cardiopulmonary bypass and especially the occurrence of hypotension at the start of the bypass period appears to be related to the development of lactic acidosis.

[Intraoperative assessment of cardiac function with transesophageal echocardiography during the Batista operation].

We experienced anesthetic management for six cases of the Batista operation and measured cardiac function before and after cardiopulmonary bypass (CPB) with transesophageal echocardiography. In the successful three patients, left ventricle ejection fraction and ejection time were maintained over 25% and 200 msec after CPB, respectively. In the other three resulting in implantation of left ventricular assist device, ejection fraction remained below 20% and ejection time under 200 msec after CPB. Intraoperative transesophageal echocardiography may be useful not only for monitoring of cardiac function but also for the prediction of prognosis.

Effects of autologous fresh platelet concentrate on haemostasis in cardiac reoperations.

The aim of this study was to determine whether autologous fresh platelet concentrate (PC) significantly improves haemostasis in cardiac reoperations compared with autologous fresh whole blood (WB). Forty-eight patients who had elective cardiac reoperations with a low-dose aprotinin priming regimen were divided into two groups. The amount of allogeneic blood transfusion was less in patients who were harvested 15 units of PC (Group PC; n = 24) before cardiopulmonary bypass (CPB) than patients who were harvested 400 ml of WB (Group WB; n = 24). The amount of mediastinal drainage for 12 h in intensive care units were significantly reduced in Group PC compared with Group WB (435 +/- 273 ml in Group PC versus 909 +/- 209 ml in Group WB; P < 0.001). Platelet count and collagen-induced whole blood platelet aggregation increased significantly higher in Group PC than Group WB after reinfusion. In conclusion, autologous fresh PC improved haemostasis compared with autologous fresh whole blood in cardiac reoperations with a low-dose aprotinin priming regimen.

[Anesthetic management of parturients with Marfan syndrome].

Ten pregnancies and 7 deliveries in 5 patients of Marfan syndrome were managed at our institution. Three patients were delivered with a cesarean section under general anesthesia, and one was delivered under epidural anesthesia. Three underwent vaginal delivery with epidural anesthesia. Two patients selected induced abortion, and one had a spontaneous abortion. Six of 7 neonates and all 5 mothers survived without any sequela. One had intrauterine fetal death due to dissection of aortic aneurysm. Simultaneous cesarean section and cardiovascular operation under cardiopulmonary bypass were performed in one case. In the parturient without progress of cardiovascular complication during pregnancy, painless labor under epidural anesthesia is our first choice to minimize hemodynamic derangement. Invasive arterial blood pressure and central venous pressure were monitored in all cases of vaginal delivery for tight hemodynamic control. Epidural anesthesia is also preferred in cases of elective cesarean section for obstetric indication. Emergency cesarean sections are performed in the cases of progressive dissection and urgent obstetric indication. General anesthesia was induced with fentanyl and midazolam to minimize cardiovascular response to tracheal intubation. We emphasize that evaluation of cardiovascular status and multidisciplinary approach are the key in the anesthetic management of parturients with Marfan syndrome.

Propofol as a continuous infusion during cardiopulmonary bypass does not affect changes in serum free fatty acids.

Perioperative myocardial infarction or ischaemia is a potential consequence of cardiac surgery and elevated free fatty acids can increase the severity of myocardial ischaemic damage. We investigated perioperative changes in serum free fatty acids, and other serum lipids, as a consequence of using propofol infusions for cardiac surgery during cardiopulmonary bypass. Twenty-five patients undergoing elective coronary artery bypass grafting were allocated to two groups. One group of 12 patients was given a continuous infusion of propofol and the other group of nine patients received intermittent boluses of midazolam as a hypnotic agent. Serum lipid concentrations were measured at four periods perioperatively. Changes in free fatty acid concentrations were similar between the two groups. Lipid concentrations related to triglyceride in the propofol group decreased on one occasion but subsequently returned to control value. On the other hand, such values in the midazolam group remained lower than control values. Propofol is not a contraindication as an anaesthetic for cardiac surgery in respect of concern regarding the effects of free fatty acids.

Preservation of collagen-induced whole blood platelet aggregation by tranexamic acid therapy in primary cardiac valve surgery.

Haemostatic disorder is one of the most common complications following cardiac surgery with cardiopulmonary bypass (CPB). Tranexamic acid reduces blood loss and allogeneic blood transfusion requirement in cardiac surgery. It had been thought that tranexamic acid inhibited fibrinolysis alone following CPB. In the present study, the haemostatic effects of tranexamic acid (20 mg/kg body weight bolus after induction of anaesthesia followed by continuous infusion at 2 mg/kg/h), including fibrinolysis and platelet function, were investigated in 22 patients (tranexamic acid group n = 12; control group n = 10) undergoing primary cardiac valve surgery. Fibrinolysis following CPB was reduced significantly in the tranexamic acid group. Following protamine administration, the reduction of collagen-induced whole blood platelet aggregation was mitigated significantly in the tranexamic acid group compared with the control group (36% reduction in the tranexamic acid group vs 58% in the control group; p = 0.011), although platelet counts did not differ between the two groups. In conclusion, tranexamic acid not only inhibits fibrinolysis directly, but also may preserve platelet function following CPB.

An analysis of risk factors of perioperative bleeding in surgical repair of abdominal aortic aneurysm.

BACKGROUND: In surgical repair of abdominal aortic aneurysm (AAA), excessive bleeding which causes postoperative complications is sometimes observed. To determine the risk factors of perioperative excessive blood loss, this retrospective study was performed. METHODS: Design. A retrospective study. Setting. An academic medical center. Participants. One hundred and forty patients underwent elective surgical repair of an abdominal aortic aneurysm (AAA) at our institution from 1995 through 1997. Measurements. The present study includes critical review of 140 consecutive charts of patients undergoing elective surgical repair of AAA. Preoperative laboratory data, intraoperative data and amount of blood loss to identify risk factors of perioperative blood loss. Factors which were found to be significantly associated with the amount of perioperative blood loss were preoperative plasma fibrin degradation product (FDP) level (r=0.445), amount of immediate re-infusion of shed blood (r=0.438), and duration of operation (r=0.411). RESULTS: Preoperative fibrinogen level correlated with perioperative blood loss little (r=-0.187). Preoperative platelet count or the other coagulation profile did not affect the amount of perioperative blood loss. The patients whose preoperative FDP were more than 40 microg x ml(-1) significantly increased the risk of excessive blood loss compared with less than 40 microg x ml(-1). CONCLUSIONS: The significant preoperative risk factor of perioperative blood loss was only FDP level in present study. Especially, the patients whose preoperative FDP were more than 40 microg x ml(-1) increased the risk of excessive blood loss.

[Anesthetic management of heart transplantation].

We anesthetized a 47-yr-old man with end-stage hypertrophic cardiomyopathy for heart transplantation. This is the first case of heart transplantation from a patient with brain death, since the organ transplantation law had become valid in Japan. Anesthesia was induced and maintained with fentanyl and diazepam. Aseptic technique was used in inserting and securing all catheters. The patient was assisted by left ventricular assist system, and hemodynamic suppression at anesthetic induction was trivial. Since complete AV block was present at the termination of cardiopulmonary bypass (CPB), VVI pacing and infusion of isoproterenol were started. In addition, nitroglycerin was given for pulmonary vasodilation. The cardiovascular support used for weaning from CPB included dobutamine, isoprote-renol, dopamine and milrinone. Following weaning from CPB sinus rhythm appeared spontaneously and function of the transplanted heart was satisfactory. When the patient was transported to ICU reduction in doses of catecholamines was possible, and dopamine and milrinone were infused. The patient was extubated 10 hours after admission to ICU.

Cardiac transplantation under new legislation for organ transplantation in Japan: report of two cases.

During the past 2 years since new legislation for organ transplantation from brain-dead donors came into effect in Japan, 3 cardiac transplants have been carried out, 2 of which were performed at the National Cardiovascular Center (NCVC). The recipient cases were 46- and 25-year-old male patients who suffered from end-stage dilated cardiomyopathy and had been listed for cardiac transplantation in the Japan Organ Transplantation Network as status I candidates. The first patient was supported by the use of a paracorporeal air-driven left ventricular assist device of the NCVC type, and had a moderate degree of renal and hepatic dysfunction at the time of transplantation. Donor hearts were transported from distant hospitals (Tokyo and Miyagi prefecture) and the transportation time was 1 h 33 min and 2h 4 min, respectively. The operation was performed by the standard technique (Lower-Shumway) in the first patient and by the bicaval anastomosis technique in the second patient. Reperfusion of the transplanted heart was performed retrogradely through the coronary sinus utilizing leukocyte-depleted blood with a gradual increase in temperature. Total ischemic time was 3 h 34 min and 3 h 35 min, respectively. Weaning from the cardiopulmonary bypass was easy and uneventful in each patient. Immunosuppressive therapy was conducted with OKT-3 induction in the first patient because of the coexisting renal dysfunction and with a triple immunosuppressive regimen for both patients. Routine endomyocardial biopsy showed acute rejection of less than grade Ib, and the patients were discharged on the 65th and 46th postoperative day, respectively. At present, both patients are in the NYHA class I state and are ready to return to work. The uneventful recovery seen in these patients shows the advances made in transplant medicine, including the progress and improvement of immunosuppressive therapy, surgical techniques, myocardial protection, and detection and treatment of infection. Further efforts are required to fully establish the cardiac transplantation program in Japan.

Cytogenetic studies of Hynobiidae (Urodela) XVI. Comparative C-banded karyotype analysis of Pseudohynobius flavomaculatus (Fei et Ye), Ranodon shihi (Liu) and Batrachuperus pinchonii (David).

Initial analysis of Pseudohynobius flavomaculatus chromosomes determined the chromosome number of this species to be 2n = 52. A re-examination of Ranodon shihi chromosomes detected 2n = 66 chromosomes, in contrast with a previous finding of 2n = 64. The C-banding patterns of these two species and that of Batrachuperus pinchonii were compared with each other. Regions of homoeology in the C-banding pattern among these three species represented 33.51-48.30% of the total length of their chromosomes. We also detected two types of chromosome rearrangement in hynobiid species based on the results of the present and previous cytogenetic studies.

[Intraoperative management of heart transplantation in Japan--report of two cases].

We experienced intraoperative anesthetic management of two cases of heart transplantation in Japan. Both patients were in the end stage of cardiac failure due to dilated cardiomyopathy. One patient had had implantation of left ventricular assist system, and another patient had had implantation of automated cardioveter defibrillator. Transesophageal echocardiography was useful for the monitoring of cardiac function during the operation. Anti-arrythmic therapy including heart pacing and protection of right heart failure are important for the circulatory management of heart transplantation. The anesthesiologist is needed not only for the management of respiration and circulation but also for the prevention of infection and control of the time schedule.

Hemostatic effects of low-dose protamine following cardiopulmonary bypass.

Twenty-eight patients undergoing cardiac surgery were prospectively studied and were assigned to two groups. The patients received 0.8- (Group L) or 2.0-fold (Group H) dose of protamine for the neutralization after cardiopulmonary bypass (CPB) which was determined by Hepcon HMS(R) assay system in which the reagent chamber containing the concentration of protamine that completely neutralized the heparin had the shortest clotting time. Mean dose of protamine was 1.60 +/- 0.50 mg kg(-1) in Group L, and 3.56 +/- 1.48 mg kg(-1), respectively. Activated clotting times (ACT) were comparable between the two groups through this study period. In Group H, platelet counts significantly decreased to 69% of that before protamine administration, and plasma platelet factor 4 level significantly increased to approximate 2-fold of that before protamine administration just after protamine administration, respectively. However, these phenomena were not observed in Group L. In addition, these hemostatic changes occurred transiently just after protamine administration. We conclude that the low-dose protamine may prevent transient platelet depletion following CPB. Low-dose protamine can neutralize anticoagulation effect of heparin sufficiently and may mitigate protamine-induced platelet dysfunction.

Effects of thiopental, ketamine, etomidate, propofol and midazolam on the production of adrenomedullin and endothelin-1 in vascular smooth muscle cells.

Endothelin-1 (ET-1) and adrenomedullin (AM) are potent vasoconstrictive and vasodilative peptides. Vascular smooth muscle cells are one of the major producing tissues of these peptides. We investigated effect of thiopental, ketamine, etomidate, midazolam and propofol on the production of ET-1 and AM in cultured rat aorta vascular smooth muscle cells. Rat cultured vascular smooth muscle cells are used and the dose-dependent effect (10(-8)-10(-4) M) of thiopental, ketamine, etomidate, midazolam, and propofol on the production of ET-1 and AM was examined. The concentration of these peptides in the culture medium were measured by radioimmunoassay. Ketamine, etomidate, propofol and midazolam, but not thiopental, decreased the production of ET-1 at a concentration of 10(-4) M and the effect of midazolam is the most potent. Thiopental and etomidate produced small but significant increases in the production of AM at a concentration of 10(-4) M. Ketamine did not affect the production, but propofol and midazolam decreased the production at 10(-4) M and 10(-5) M, respectively. These results suggest that thiopental, ketamine, etomidate, propofol and midazolam differentially affect the production of ET-1 and AM in rat vascular smooth muscle cells.

[Anesthetic management for carotid and coronary artery surgery--concomitant versus two stage operation].

We reviewed the anesthetic management of 16 patients with concomitant severe coronary and carotid artery diseases. Eight patients underwent concomitant operations of coronary artery bypass graft and carotid endarterectomy, while the other 8 patients underwent two stage operation. Candidates for concomitant operations had unstable angina or serious coronary disease such as three vessel disease or severe stenosis of LMT. In comparison, most of patients undergoing two stage operation had symptomatic or occlusive carotid disease. In all cases, anesthesia was maintained with fentanyl and midazolam and the perfusion pressure during cardiopulmonary bypass was maintained above 70 mmHg. Some patients received thiopental or propofol for brain protection. The concomitant operations required much more transfusion and longer operation time than two stage operation. In addition, several cases of the concomitant operation needed intra-aortic balloon pumping or high dose of catecholamines. Indications for concomitant operation or two stage operation have to be determined through discussion among anesthesiologist, neurovascular as well as cardiovascular surgeons.

[Anesthetic management for implantation of implantable cardioverter-defibrillators].

Implantable cardioverter-defibrillators (ICDs) were implanted in 44 patients at the authors' institution. The anesthetic management was reviewed retrospectively. Ten of the 44 patients received the third generation ICD devices, while the rest received the fourth generation devices. For thirteen patients receiving the fourth generation devices, implantation was performed under local anesthesia with monitored care of anesthesiologists. Propofol was infused to achieve deep sedation during induced ventricular fibrillation and later cardioversion for testing the devices. Implantation was performed under general anesthesia with combination of fentanyl and volatile anesthetics for the remaining 31 patients. Patients who received ICDs under local anesthesia had significantly greater values of ejection fraction in preoperative examination than values in patients who received ICDs under general anesthesia. Operation time of the implantation under local anesthesia was significantly shorter than that under general anesthesia. Though infusion of propofol produced a moderate decrease of blood pressure in patients who received ICDs under local anesthesia, no patient showed major complication. Local anesthesia with sedation with propofol can be an option in anesthetic management for implantation of an ICD if an anesthesiologist cares the patient whose cardiac function is not compromised.

[Anesthetic management of patients undergoing implantation of left ventricular assist system].

We examined the anesthetic management of six patients with end-stage dilated and hypertrophic cardiomyopathy for implantation of left ventricular assist system. Although anesthesia was induced only with fentanyl or with combination of fentanyl and diazepam, hemodynamic changes after the anesthetic induction were variable and preoperative evaluation of left ventricular ejection fraction did not predict the hemodynamic changes. After the weaning from cardiopulmonary bypass, the right ventricular support by catecholamines, such as dopamine and dobutamine, and phosphodiesterase III inhibitors, such as amrinone, and pulmonary vasodilation by inhalation of nitric oxide were useful to maintain volume loading to the left ventricular assist system.

Study on the effectiveness of toborinone (OPC-18790) in the treatment of heart failure in patients following cardiac surgery.

Toborinone ((+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-qui nolinone, CAS 128667-95-8, OPC-18790), a novel cardiotonic agent with an inhibitory action on phosphodiesterase, is known to have a potent positive inotropic action with no positive chronotropic effect. The effectiveness of this drug in the treatment of heart failure occurring immediately after extracorporeal circulation (ECC) in cardiac surgery was investigated. The study was conducted in 12 patients with valvular heart disease showing a cardiac index (CI) of below 2.8 l/min/m2 and/or pulmonary capillary wedge pressure (PCWP) or pulmonary arterial diastolic pressure (PAD) of above 8 mmHg immediately after extracorporeal circulation. In group A (n = 6), toborinone was infused at a rate of 40 micrograms/kg/min for the first 5 min and then at 10 micrograms/kg/min for 85 min. In group B (n = 6), the drug was infused at a rate of 10 micrograms/kg/min for the entire 90 min. CI, mean systemic arterial pressure (mSAP), mean pulmonary artery pressure (mPAP), CVP, PCWP, and heart rate were measured at 5, 15, 30, 60, and 90 min after the start of infusion. The infusion volume required to maintain a constant PCWP was also estimated. In group A, CI increased rapidly and significantly from the baseline of 2.48 +/- 0.23 l/min/m2 to 3.57 +/- 1.07 l/min/m2 at 5 min after the start of infusion, and at that time mSAP was slightly decreased. In group B, CI increased gradually from the baseline of 2.53 +/- 0.18 l/min/m2 to 3.08 +/- 0.34 l/min/m2 at 15 min after the start of infusion, but almost no change was seen in mSAP. During the first 30 min, group A required a significantly larger infusion volume (983 +/- 395 ml) than group B (475 +/- 184 ml). From 30 to 90 min after the start of infusion, CI remained increased to similar levels in both groups and mSAP levels were also similar. There were no significant differences between the two groups in any other parameter. Continuous infusion of toborinone appears to be effective for treating heart failure occurring immediately after ECC in cardiac surgery. Initial loading at a rate of 40 micrograms/kg/min rapidly increased CI but was accompanied by mild hypotension. Constant infusion at 10 micrograms/kg/min brought about a more gradual effect that was similar to that of loading at 40 micrograms/kg/min, but without inducing hypotension. Thus, infusion at 10 micrograms/kg/min is considered preferable in order to avoid a larger-than-necessary infusion volume.

Retrospective analysis of effect of low-dose aprotinin priming on allogeneic blood transfusion in repeated cardiac operations.

The objective of this retrospective study was to investigate efficacy of low-dose aprotinin priming therapy on the requirement of allogeneic transfusion and to identify risk factors for allogeneic transfusion in patients undergoing repeated cardiac operations. The present study includes a critical review of 124 consecutive charts of patients undergoing elective repeat cardiac surgery. We examined the effect of low-dose aprotinin priming therapy on blood loss, amounts of mediastinal drainage following intensive care unit (ICU) administration and the number of units of blood products given during the perioperative period. The rate of nonallogeneic transfusion was not affected by low-dose aprotinin priming therapy, although aprotinin reduced the amount of allogeneic transfusion and the amount of mediastinal drainage 12 h following ICU admission. In conclusion, low-dose aprotinin priming therapy is effective in reducing blood loss and the amount of allogeneic transfusion. However, it failed to improve the rate of cardiac reoperations without allogeneic blood transfusion.