Period Of Extracorporeal Circulation Research Articles

Comparison of the Use of Desflurane vs. Propofol in Aortic Valve Replacement Surgery: Differences in Nephroprotection: An Explorative and Hypothesis-Generating Study.

Introduction: The cardioprotective effect of halogenated drugs in cardiac surgery has been the subject of several studies. However, there is scarcity of data on their potential nephroprotective effects. Aortic valve replacement and coronary revascularization are the most frequent cardiac surgery procedures. The objective of this explorative study was to examine the effect of desflurane vs. propofol on renal function, when administered in aortic valve replacement surgery, including the extracorporeal circulation period. Method: A quasi-experimental prospective study was performed in 60 patients, who were allocated to receive either desflurane or propofol intraoperatively during aortic valve replacement surgery. As a hypnotic, group 1 received propofol, whereas group 2 received desflurane. Markers of renal function and level of cardiac preservation were determined based on biochemical parameters (troponin I, NTProBNP). Results: In the propofol group, there were significant variations between postoperative values of urinary NGAL and creatinine and baseline values. In contrast, no variations were found in the desflurane group in terms of hemodynamic parameters and myocardial damage. Conclusions: The use of propofol vs. desflurane during aortic valve replacement surgery is associated with a decrease in renal function.

The frozen elephant trunk technique: impact of proximalization and the four-sites perfusion technique.

OBJECTIVESTo improve organ protection with the frozen elephant trunk (FET) procedure, a so-called four-sites perfusion in combination with proximalization for the distal aortic anastomosis was performed. The impact of these techniques on patient outcome is reported.METHODSBetween February 2005 and April 2020, a total of 357 patients underwent the FET procedure for acute (54%) or chronic (22%) aortic dissection or aneurysmal disease (24%). The level of the distal FET anastomosis was defined according to aortic arch zones 0–3. Patients were divided into 3 groups according to the intraoperative perfusion strategy: (i) selective antegrade cerebral perfusion (SACP) alone (N = 96, 2 sites); (ii) SACP plus left subclavian artery or distal aorta (N = 84, 3 sites) and (iii) SACP plus left subclavian artery plus distal aorta (N = 177, 4 sites). Early outcome was addressed by a composite end point: occurrence of either a disabling stroke, a disabling spinal cord injury, extracorporeal circulatory support, kidney dialysis or death within 90 days.RESULTSPreoperative characteristics were similar among the groups. Surgery in group C was characterized by FET proximalization in arch zone ≤2, moderate hypothermia at 28°C and shorter periods of extracorporeal circulation, SACP, hypothermic circulatory arrest and cardioplegic arrest (P < 0.001, respectively). Occurrence of the composite end point was reduced in group C (P = 0.008). The combination of FET proximalization and four-sites perfusion was a protective factor for the composite outcome in multivariable analysis (P = 0.009). The 5-year survival was improved in patients who underwent FET proximalization in zone ≤2 (hazard ratio 0.7, 95% confidence interval 0.4–1.0; P = 0.036).CONCLUSIONSFET proximalization in combination with four-sites perfusion has the potential to improve patient outcomes in terms of survival and major events.Subject collection120; 161.

Euthyroid sick syndrome in paediatric and adult patients requiring extracorporeal circulatory support and the role of thyroid hormone supplementation: a review.

Non-thyroid disorders may modify thyroid hormone metabolism, resulting in an 'euthyroid sick syndrome'. Studies determining the association of cardiopulmonary bypass to thyroid function showed changes in line with this euthyroid sick syndrome. In some cases, cardiovascular dysfunction after cardiac surgery with cardiopulmonary bypass is comparable to that noticed in hypothyroidism associated with low cardiac output and elevated systemic vascular resistance. Numerous lines of research have proposed that triiodothyronine can behave acutely as a positive inotropic and vasodilator agent. The aim of this review is to present an update on the current literature about in what clinical situations the use of thyroid supplementation during the perioperative period of extracorporeal circulation in the adult and paediatric populations may impact outcome to any appreciable degree. The contribution of thyroid function in patients undergoing a ventricular assist device implantation is additionally reviewed and future study directions are proposed. This is a narrative review, where the search strategy consisted on retrieving the articles through an extensive literature search performed using electronic databases from January 1978 up to September 2019. All controlled trials randomly allocating to perioperative thyroid hormone administration in children and adults undergoing extracorporeal circulation for cardiac surgery were considered. Thyroid hormone supplementation may be recommended particularly in selected paediatric sub-populations. There is currently no firm evidence regarding the benefits of routine use of thyroid hormone administration in cardiac adult patients. Further studies are required to assess the beneficial effect of thyroid hormone on patients with end-stage heart failure supported by ventricular assist devices.

Methane inhalation reduces the systemic inflammatory response in a large animal model of extracorporeal circulation.

Extracorporeal circulation induces cellular and humoral inflammatory reactions, thus possibly leading to detrimental secondary inflammatory responses. Previous data have demonstrated the bioactive potential of methane and confirmed its anti-inflammatory effects in model experiments. Our goal was to investigate the in vivo consequences of exogenous methane administration on extracorporeal circulation-induced inflammation. Two groups of anaesthetized Vietnamese minipigs (non-treated and methane treated, n = 5 each) were included. Standard central cannulation was performed, and extracorporeal circulation was maintained for 120 min without cardiac arrest or ischaemia, followed by an additional 120-min observation period with haemodynamic monitoring. In the methane-treated group, 2.5% v/v methane-normoxic air mixture was added to the oxygenator sweep gas. Blood samples through the central venous line and tissue biopsies from the heart, ileum and kidney were taken at the end point to determine the whole blood superoxide production (chemiluminometry) and the activity of xanthine-oxidoreductase and myeloperoxidase, with substrate-specific reactions. Methane treatment resulted in significantly higher renal blood flow during the extracorporeal circulation period compared to the non-treated group (63.9 ± 16.4 vs 29.0 ± 9.3 ml/min). Whole blood superoxide production (548 ± 179 vs 1283 ± 193 Relative Light Unit (RLU)), ileal myeloperoxidase (2.23 ± 0.2 vs 3.26 ± 0.6 mU/(mg protein)) and cardiac (1.5 ± 0.6 vs 4.7 ± 2.5 pmol/min/mg), ileal (2.2 ± 0.6 vs 7.0 ± 3.4 pmol/min/mg) and renal (1.2 ± 0.8 vs 13.3 ± 8.0 pmol/min/mg) xanthine-oxidoreductase activity were significantly lower in the treated group. The addition of bioactive gases, such as methane, through the oxygenator of the extracorporeal circuit represents a novel strategy to influence the inflammatory effects of extracorporeal perfusion in cardiac surgical procedures.

Do we need sutureless or self-anchoring aortic valve prostheses?

Surgical aortic valve replacement (AVR) is the 'gold standard' for the treatment of aortic valve stenosis. Due to the increasing age of the patient population (reflecting the demographic changes), the use of biological valves has increased over the past years. At the same time, a large proportion of these patients require concomitant surgical procedures in addition to AVR. Although trans-apical or trans-femoral aortic valve implantations (TAVI) have been introduced for high risk patients, they are limited to patients with isolated aortic valve pathology. Therefore, strategies for avoiding long ischemia times, as well as long periods of extra-corporeal circulation (ECC) resulting in reduced peri-operative risks should be welcomed among the surgical community. Modern 'sutureless valves' with reduced cross-clamp and cardio-pulmonary bypass times as a result of the absence of sutures, combined with excellent hemodynamics in the short and mid-term, may be an ideal solution for geriatric patients. Additionally, 'self-anchoring' valves will increase the armament of surgeons in treating 'technically difficult' group of patients needing AVR who have small calcified aortic roots and those coming back after aortic root replacement with homografts. These valves should also expand the application of minimally access AVR. Therefore, the question of whether we need 'self-anchoring valves' is not only redundant, but the time may have come for these type of valves to be considered as the 'valve of choice' for higher risk geriatric patients who may be 'high risk' for conventional valves but not ineligible for TAVIs.

Surgical Repair of Coronary Artery Fistula Combined with Coronary Artery Ectasia in Adults

Coronary artery fistula (CAF) is rare in patients undergoing coronary angiography. Coronary artery ectasia (CAE) is found in 1.2% to 4.9% of patients at autopsy or during angiographic studies. CAF combined with CAE is a extremely rare clinical condition. This study aimed to summarize a treatment strategy for this complex disorder. Ten consecutive patients who underwent surgical repair of CAF combined with CAE between 2000 and 2012 are reported. The main outcome measure was death. Secondary outcome measures included surgical technique, the extracorporeal circulation time, intubation duration, the intensive care unit stay period and discharge period. The mean extracorporeal circulation period was 103.8 W 25.7 minutes. The mean intubation duration was 10.5 W 3.2 hours. The mean intensive care unit stay period was 2.0 W 0.8 days and the mean discharge period was 11.4 W 2.6 days two patients were lost to follow-up. The other eight patients were asymptomatic and there were no deaths during the follow-up period. Surgical repair for CAF combined with CAE is effective with satisfactory results in adults.

Editorial Comment: Rescue mechanical circulatory support for failing transplanted hearts

It is indeed a rewarding experience for transplant surgeons when the donor heart, after being weaned from the cardiopulmonary bypass, beats in sinus rhythm, with satisfactory haemodynamics, and has excellent biventricular function as assessed by transoesophageal echocardiography, the chest is closed and the patient returns to the intensive care unit for postoperative monitoring and recovery. Conversely, it becomes a humbling and indeed terrifying experience when, while waiting expectantly, we find that the transplanted heart does not contract, but we observe an echocardiogram showing arrhythmias, which herald impending cardiac failure [1]. When this happens, we may have a recipient who cannot be weaned from cardiopulmonary bypass despite maximal medical management, or the donor heart may begin to fail on the intensive care unit, which may end in graft failure during his/her hospital stay. Why does the transplanted heart fail? It is believed to be largely due to the mechanism of ischaemia-reperfusion injury. Graft failure may result from long ischaemic times, inadequate myocardial preservation at the time of procurement, hyperacute rejection, which is extremely rare, or poor adaptation of the graft to the recipient’s haemodynamic environment. It may also be caused by donor heart hypertrophy, coronary artery disease, air embolism and the neural influence of the donor’s brain death. In children, it may be due to increased pulmonary vascular resistance either as a consequence of left ventricular (LV) failure or as a result of single ventricle physiology, resulting in the risk of right ventricular failure after transplantation [2]. Primary graft failure is a severe cardiac dysfunction of the cardiac allograft without obvious anatomical or immunological causes [2], characterized by hypotension, high filling pressures, and refractory low-cardiac output, and mostly right ventricular failure after coming off the cardiopulmonary bypass. Measures aimed at decreasing pulmonary vascular resistance after transplantation include the use of inhaled nitric oxide as well as medications with pulmonary vasodilator effects such as prostacyclin and milrinone. Graft ventricular function is also supported postoperatively with inotropes. However, despite these interventions, ventricular failure may persist, and mechanical circulatory support (MCS) then becomes necessary. Prior to the introduction of MCS, primary graft failure was fatal except in isolated cases where emergency salvage retransplantation, sometimes after prolonged periods of extracorporeal circulation, was attempted, but the outcomes of this strategy were poor [3], and it has, therefore, been seldom applied. With the advent of MCS devices, hopes of rescuing failing transplanted hearts have been resurging. Presently, we offer support either with extracorporeal membrane oxygenation (ECMO) or with ventricular assist devices (VADs), depending on whether recovery can be expected or retransplantation is anticipated.

What is the best predictor of postoperative erectile function in patients who will undergo coronary artery bypass surgery?

The aim of this prospective study was to evaluate the impact of extracorporeal circulation and cross clamping period on erectile function in patients undergoing coronary artery bypass surgery (CABS). A total of 50 patients undergoing CABS were evaluated in this prospective study. Before and 6-12 months after the CABS, patients were interviewed for erectile dysfunction (ED) using the International Index of Erectile Function (IIEF). Scoring the IIEF domain of erectile function allowed the classification of each patient as having no (26-30), mild (17-25), moderate (11-16) or severe (0-10) ED. Patients with normal, mild and moderate ED score were designated as group A, B and C, respectively. Patients were classified in 2 groups to evaluate the impact of extracorporeal circulation and cross clamping period on erectile function in patients undergoing CABS. Patients who had no change in ED score in group A and patients who had recovery in group B were included in group1. Patients who had impaired ED score in group A and group B were included in group 2. All patients were also interviewed for sociodemographic and relevant medical history. Sociodemographic data were age, job, marital status, alcohol, narcotic and smoking habit. Medical risk factors were diabetes, hypertension and psychiatric disorders. The mean age of patients included in the study were 46,6 (range 31-55). After the operation, 3 (7.5%) of 41 patients in group A had moderate, 1 (2.5%) had mild and 37 (90%) had no change in ED score. In group B, 2 (28%) of 7 patients had moderate, 4 (57%) had recovery in ED score, 1 had no change in ED score. There were only 2 patients in group C and 1 had severe, the other one had mild ED after the operation. The mean operation period was 234.8 m inutes in group 1 and 280 min in group 2. Cross clamping period and extracorporeal circulation of patients in group 1 and 2 were 33.2, 41.6 min and 54.7, 64.6 min, respectively. The groups were not statistically different with regard to mean operation, cross clamping and extracorporeal circulation period. Preoperative erectile function seems to be the best predictor of postoperative erectile function in patients who will undergo CABS.

Effect of sodium nitroprusside on complement activation induced by cardiopulmonary bypass: A clinical and experimental study

Complement activation and leukocyte stimulation were prospectively studied during and after cardiopulmonary bypass in 16 children receiving sodium nitroprusside—a nitrovasodilator releasing nitric oxide—for vasodilation during the cooling and rewarming periods of extracorporeal circulation. Results were compared with those in 29 patients who were not treated with sodium nitroprusside during the operation. Patients treated with sodium nitroprusside had significantly less C3 conversion during cardiopulmonary bypass as measured by the ratio C3d/C3 (p < 0.05) and significantly less C5a liberation immediately after cardiopulmonary bypass (p < 0.005) than patients not treated with sodium nitroprusside. C4 was not overtly consumed in our series. Leukocyte count during the rewarming period of cardiopulmonary bypass, but not leukocyte elastase release during cardiopulmonary bypass, was significantly reduced in patients treated with sodium nitroprusside (p < 0.05). In vitro experiments were conducted to analyze the effect of sodium nitroprusside on complement hemolytic activity initiated by the classic and the alternate pathways and on zymosan-induced C3 conversion by the activation of the alternate pathway. The in vitro experiments clearly demonstrate inhibition of complement hemolytic activity by sodium nitroprusside in the sera tested. The 50% inhibitory concentration of sodium nitroprusside on the available complement hemolytic activity was less through the alternate pathway than through the classic one (4.2 ± 0.8 mmol/L and 14.0 ± 2.88 mmol/L, respectively). The decrease of complement hemolytic activity measured was dose-dependent and was enhanced by the sodium nitroprusside preincubation of the sera tested. This effect was related to the duration of preincubation. Sodium nitroprusside photodegradation (enhancing nitric oxide release) increased the anticomplementary effect of the drug, reducing the 50% inhibitory concentration on complement hemolytic activity to 0.24 to 0.02 mmol/L for the alternate pathway and 2.74 to 0.3 mmol/L for the classic pathway. The zymosan-induced C3 conversion was inhibited by sodium nitroprusside. Nitroglycerin and isosorbide dinitrate (other nitric oxide donors) had in vitro effects on complement hemolytic activity similar to those of nonphotodegraded sodium nitroprusside at similar concentrations (1 mmol/L). Our results suggest that sodium nitroprusside, both in vitro and in vivo, has an inhibiting effect on complement activation initiated by both classic and alternate pathways and that this effect is mediated by nitric oxide release from sodium nitroprusside. This is the first report on the anticomplementary effect of sodium nitroprusside by nitric oxide release. (J T HORAC C ARDIOVASC S URG 1996;111:882-92)

The Circulatory Effect of Pheniramice Malate at Initial Period of Extracorporeal Circulation in Pediatric Open Heart Surgery

The Circulatory Effect of Pheniramice Malate at Initial Period of Extracorporeal Circulation in Pediatric Open Heart Surgery

Correction of bilirubin conjugation in the Gunn rat using hepatocytes immobilized in alginate gel beads as an extracorporeal bioartificial liver.

A new extracorporeal bioartificial liver using alginate-entrapped hepatocytes was developed and evaluated for its ability to correct the lack of bilirubin conjugation in the Gunn rat. Hepatocytes were harvested from Sprague-Dawley rats by the two-step collagenase perfusion method and then immobilized in Ca(++)-alginate beads. The ability of immobilized hepatocytes to conjugate bilirubin was investigated in vitro by comparison with hepatocyte monolayer cultures. The bioartificial liver consisted of a cylindric bioreactor containing either alginate beads with hepatocytes (test group) or alginate beads alone (control group). Gunn rats were connected to this bioreactor via an extracorporeal circulation and bile fractions were collected at hourly intervals. Both bilirubin monoconjugates and bilirubin diconjugates were measured in the bile by high pressure liquid chromatography. Hepatocyte viability in alginate beads was determined prior to and at the end of each experiment and found to be unchanged (75%). In the test group, the concentration of bilirubin conjugates increase rapidly, attaining median values of 72.26 microM and 92.59 microM for mono and diconjugated bilirubin respectively, during a 3 h period of extracorporeal circulation. In the control group, the levels of either conjugate did not exceed 0.87 microM throughout the experiments. Statistical analysis showed a significant difference between the two groups (p < 0.0023). These results suggest that the bioartificial liver used in this study represents an effective method for the temporary correction of the Gunn rat's genetic defect. Such a system might be of therapeutic interest in acute liver failure.

Histamine and tryptase in serum of patients after coronary surgery: influence of pretreatment with methylprednisolone

The presence of histamine and tryptase in serum during and after coronary artery bypass grafting may be an indication for the induction of inflammation. One group of patients received no glucocorticoids, a second one received methylprednisolone before extracorporeal circulation. In the steroid group, no effects were seen on the basal levels of histamine and tryptase. In the other group, two peak levels of histamine were observed, one peak 10 minutes after starting extracorporeal circulation and another peak 4 hours post-surgery. In this group, tryptase was only elevated during the period of extracorporeal circulation. There were no differences between both groups in complement activation. It was concluded that during surgery mast cells were activated but, since tryptase levels decreased in the post-operative period, the increase in histamine level can only be explained by activation of basophils.

Remoção cirúrgica de trombos em próteses valvulares mecânicas

É relatada a retirada cirúrgica de trombos em próteses mecânicas em dois pacientes, manobra rara e inédita em nossa Instituição. O primeiro paciente, do sexo masculino, de 19 anos de idade, com história de doença reumática na infância, tendo sido submetido a duas duplas trocas mitro-aórticas, com duas próteses metálicas na última operação, realizada em 1988. Tendo descontinuado o uso de anticoagulantes por conta própria, deu entrada no pronto-socorro em edema agudo dos pulmões, com diagnóstico de trombose nas próteses. Foi levado ao centro cirúrgico, optando-se pela limpeza cirúrgica das próteses, diminuindo, desta forma, o tempo de circulação extracorpórea em paciente de extrema gravidade. Outra paciente, de 2 anos e 6 meses de idade, com diagnóstico de insuficiência mitral por degeneração mixomatosa, foi submetida a troca da valva mitral por prótese mecânica em 13/10/92. Apesar de bem anticoagulada, apresentou trombose da prótese e, no dia 12/1/93, foi submetida a trombectomia cirúrgica. Os dois pacientes apresentaram boa evolução pós-operatória, sendo que a segunda paciente, 3 meses após a trombectomia, apresentou nova trombose aguda, sendo administrada estreptoquinase, com sucesso. A trombectomia cirúrgica pode ser uma boa opção em pacientes com alto risco e portadores de trombose de próteses metálicas.

Estimation of total body fluid shifts between plasma and interstitium in man during extracorporeal circulation.

Fluid transport between plasma and interstitium during extracorporeal circulation was studied in seven patients undergoing aortocoronary bypass grafting. The absolute shifts in plasma volume during hypothermia were determined as the difference between input and loss of fluid and the changes in blood volume. The change in haemoglobin concentration due to acute haemodilution when starting extracorporeal circulation was used to calculate the absolute blood and plasma volume. The Starling equation for exchange across the capillary wall was used to describe fluid shifts. The total fluid filtered during the 60- to 90-min period of extracorporeal circulation averaged 34.1 +/- 11.1 (s.d.) ml/min. The total body filtration coefficient from the Starling relationship averaged 0.046 +/- 0.012 ml/kg.mmHg.min (0.354 +/- 0.092 ml/kg.kPa.min). Haemodilution, reducing colloid osmotic pressure in plasma (COPP) by approximately 10 mmHg (1.3 kPa) will result in a loss of plasma fluid of around 2 1 per hour. When corrected for lower fluid viscosity due to hypothermia during extracorporeal circulation, CFC would be about 40% higher, and a filtered volume of nearly 3 1 in a normothermic 70-kg person would be expected. Crystalloid haemodilution for shorter periods of time does not produce excessive oedema and thus may be well tolerated.

Metabolic gas exchange during aortocoronary bypass surgery using a double pump systemand mechanical ventilation

Oxygen uptake and carbon dioxide excretion during aorto-coronary bypass surgery were studied in seven patients by indirect calorimetry and compared to blood-gas based measurements. Medium-high dose fentanyl, droperidol and midazolam were used for maintaining anaesthesia. During the period of extracorporeal circulation no external oxygenator was used. Circulation was maintained by two pumps by-passing the left and right heart respectively and the patient's lungs were ventilated with O2/N2 using a Servo 900C ventilator. For indirect calorimetric measurements gas concentrations were analysed by Beckman instruments and gas volumes were measured by the Servo 900C ventilator. Oxygen uptake and carbon dioxide excretion decreased by 31% and 39%, respectively. For invasive measurements during extracorporeal circulation, arterial and venous blood gases and pump flow were used. Using pump flow instead of cardiac output when calculating oxygen uptake circumvented errors in thermodilution measurements. There was a good correlation (r = 0.88) between the invasive and the indirect calorimetric measurements. Further, there was a good correlation between naso-pharyngeal temperature and indirect calorimetric measurements of oxygen uptake (r = 0.87).

Enhanced Effective Fibrinolysis following the Neutralization of Heparin in Open Heart Surgery Increases the Risk of Post-Surgical Bleeding

The tissue-type plasminogen activator related fibrinolytic system was studied in 24 patients undergoing cardiopulmonary bypass surgery. The degradation of fibrinogen and fibrin was followed during and after surgery by means of new sensitive and specific assays and the changes were related to the blood loss measured in the chest tube drain during the first 24 postoperative hours. Although tissue-type plasminogen activator was significantly released into the circulation during the period of extracorporeal circulation (p less than 0.01), constantly low levels of fibrinogen degradation products indicated that a systemic generation of plasmin could be controlled by the naturally occurring inhibitors. Following extracorporeal circulation heparin was neutralized by protamine chloride, and in relation to the subsequent generation of fibrin, there was a short period with increased concentrations of fibrinogen degradation products (p less than 0.01) and a prolonged period of degradation of cross-linked fibrin, as detected by increased concentrations of D-Dimer until 24 h after surgery (p less than 0.01). Patients with a higher than the median blood loss (520 ml) in the chest tube drain had a significantly higher increase of D-Dimer than patients with a lower than the median blood loss (p less than 0.05). We conclude that the incorporation of tissue-type plasminogen activator into fibrin and the in situ activation of plasminogen enhance local fibrinolysis, thereby increasing the risk of bleeding in patients undergoing open heart surgery.

Plasma levels of glucose, insulin and cortisol in children undergoing cardiac surgery: effects of pulsatile and nonpulsatile perfusion

The effects of pulsatile and nonpulsatile perfusion on the plasma glucose, insulin and cortisol levels were studied in 12 children undergoing intracardiac repair of congenital heart defects. Hyperglycaemia was noted in both subgroups during the operation but plasma glucose returned to normal levels at 24 hours. Insulin secretion was suppressed during the period of extracorporeal circulation (ECC) and this was pronounced while the aorta was crossclamped. Cortisol levels were elevated during the whole period of study and remained elevated at 24 hours. In the pulsatile group cortisol levels were higher than the nonpulsatile group. However there was no significant difference between the groups. Like adults, children exhibit a metabolic response during open-heart operations. Pulsatile perfusion delivered by a modified Stöckert roller pump during ECC, did not alter the glucose, insulin and cortisol response to cardiac surgery in this study.

Long-term daily study of blood volume in cardiac autotransplanted dogs.

Cardiac transplantation is followed by the interruption of afferent nerves to the heart. Knowing that some of the afferent nerves are responsible for the homeostasis of the blood volume, we undertook a serial and long-term study of the blood volume in 25 dogs with denervated hearts. The animals were autotransplanted in order to eliminate repercussions linked to rejection and to its treatment. To discern the effects of surgery and of extracorporeal circulation from those of denervation, a group of 11 control dogs was operated upon and subjected to a period of extracorporeal circulation. In both groups, serial and long-term studies of blood volume were carried out daily with 131I-labeled albumin. Analysis of the results demonstrated that in the hours following surgery, blood volume is significantly decreased by 11% in the control group and by 22% in group 2. By the 5th postoperative day, the blood volume had increased gradually to attain normal values in both groups. At the 2nd postoperative week, the total blood volume remained normal in the control group, whereas blood volume had increased by 5.7% in the autotransplanted dogs, this being due to a 38% increase of the plasmatic phase. This increment persisted from the 14th to the 42nd postoperative day and attained 7.4%. Our conclusion is that the variations in blood volume during the 1st postoperative week in the autotransplanted heart are inherent in surgery and in extracorporeal circulation. Afterwards, the hypervolemia shown in the transplanted dogs is secondary to cardiac denervation.

Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation.

The influence of cardiopulmonary bypass on fibrinolytic activity was assessed by a sensitive clot lysis assay in eight patients undergoing coronary artery bypass operations. Fibrinolytic activity increased immediately after cardiopulmonary bypass was begun and remained elevated throughout the period of extracorporeal circulation. At the conclusion of the operative procedure, fibrinolytic activity returned to the normal range in all patients, and no subject had postoperative bleeding.

Anaphylatoxin formation in extracorporeal circuits.

Anaphylatoxin radioimmunoassay techniques have been employed to define both the temporal profile and the amount of complement activation taking place in two different types of extracorporeal circuits. Prospective studies of patients undergoing both maintenance hemodialysis and cardiopulmonary bypass provided essentially similar findings. In both cases, plasma C3a antigen levels proved to be the most accurate and sensitive indicator of intravascular complement activation. By contrast, plasma C5a levels varied little during the period of extracorporeal circulation. Instead, this anaphylatoxin retained considerable biologic activity in vivo as evidenced by its ability to promote granulocyte activation and transient granulocytopenia which was displayed by patients in both groups. Plasma levels of C4a antigen were not elevated during the period of extracorporeal circulation, suggesting that alternative pathway mechanisms were predominantly responsible for the complement activation taking place in both hemodialyzers and bypass oxygenators. However, classical pathway activation events could be documented when protamine sulfate was administered to heparinized patients after cardiopulmonary bypass. In this instance, elevated plasma levels of both C4a and C3a antigens were observed. Prospective studies also suggested that complement activation could be associated with the development of both acute and delayed clinical sequelae. Available data support the hypothesis that C5a anaphylatoxin might be the primary mediator of these undesirable effects of extracorporeal circulation. These types of investigations have contributed significantly to our understanding of the role of the anaphylatoxins in human disease and may be directly applied to facilitate design of more biocompatible medical devices.