Termination Of Extracorporeal Circulation Research Articles

Results of flowmetric assessment of composite Y-grafts and autovenous coronary artery bypass grafts.

The purpose of the study was to perform intraoperative assessment of blood flow in coronary bypass grafts of the 'first' and 'third' order according to Calafiore A.M. with the help of the TTFM technique and to compare the obtained results. This retrospective, single-centre study enrolled a total of 222 patients subjected to coronary artery bypass grafting (CABG) from January to November 2017. Depending on the type of bypass grafting of the posterior interventricular artery (PIVA), the patients were divided into 2 groups. Group One consisted of 108 patients undergoing bypass grafting of the PIVA with the help of combined Y-grafts from the right internal thoracic artery (RTIA). Group Two was composed of 114 patients subjected to autovenous coronary artery bypass grafting of the PIVA. Blood flow was assessed with the help of the VeriQ MediStim® flowmeter after termination of extracorporeal circulation (ECC), at systolic pressure of 100-110 mm Hg. The parameters of blood flow were assessed using the 1.5- and 2-mm probes. In a specially designed protocol we registered the type of the shunt, the bypassed artery, and values of flowmetry parameters. We also evaluated the pattern of the flowmetric curve according to Takemi Handa et al. RESULTS: The obtained findings revealed a statistically significant difference in the values of Qmean (p=0.001), with the PI values in the groups not statistically differing (p=0.14). Thus, in patients with similar parameters influencing the volumetric velocity of blood flow (the degree of proximal stenosis, diameter of the bypassed artery, mean systolic AP and HR) the value of Qmean was higher in the group with coronary artery bypass grafting (CABG), i. e., in the group of the 'first-order' conduits. Therefore, an autovein directly anastomosed to the aorta experiences grater haemodynamic overload, which completely confirms the theory of Calafiore A.M. First-order conduits (CABG) appear to experience greater wall strain because of greater haemodynamic overload as compared with third-order conduits (Y-grafts). A composite Y-graft may be an alternative technique of bypass grafting of the basin of the right coronary artery (RCA). A composite Y-graft has greater resistance to wall shear stress than an autovein anastomosed to the aorta.

Early Diagnosis of Acute Kidney Injury during Open Heart Surgery under Extracorporeal Circulation

Objective: to analyze the informative value of new methods for the early diagnosis of acute kidney injury (AKI) to determine treatment policy after heart surgery under extracorporeal circulation (EC). Subjects and methods. Patients of both sexes were examined before and after heart surgery under EC. A perfusion index of 2.5±0.4 l/min/m2, moderate hypothermia, and a mean blood pressure of 60—100 mm Hg were maintained throughout EC. Urine samples were taken 4—6 and 16—18 hours after termination of EC and centrifuged. Urinary neutrophil gelatinase associated lipocalin (NGAL) was determined using an Abbott Architect i1000sr analyzer. The cutoff level proposed by the Abbott Diagnostics was 132 ng/ml. NonResults. Two groups were formed. Group 1 included 14 patients with AKI according to the 2004 RIFLE classification. Stage 1 AKI was seen in 5 cases; there was no disease progression or urinary NGAL elevation. Four to six hours after EC, 8 of 9 patients with Stages 2—3 AKI had a urinary NGAL level of 200 ng/ml. Two patients required renal replacement therapy (RRT), their renal function recovery was observed. Other two patients died from respiratory and cardiac failure. Group 2 comprised 61 patients without AKI: in 59 and 2 patients, urinary NGAL levels were lower and higher than the accepted cutoff levels, respectively. No deaths were observed. AKI developed in patients who had more prolonged EC, transverse aortic ligation, low hemoglobin levels and received more doses of donor blood. In Stages 1—3 AKI, the sensitivity was 57.1% (95% confidence interval (CI), 28.9—82.2) and specificity was 96.7% (95% CI, 88.6—99.5); in Stages 2—3 AKI, these were 88.9% (95% CI, 51.7—98.2) and 97% (95% CI, 89.5—99.5), respectively. Conclusion. Urinary NGAL levels should be determined by using the laboratory platforms 4—6 hours after long EC, as well as aortic ligation, and transfusion of two or more blood doses. Elevated urinary NGAL levels are highly sensitive to Stages 2—3 AKI and useful in assessing indications by the beginning of RRT. Key words: cardiac surgery under extracorporeal circulation, acute kidney injury, urinary NGAL, urinary albumin to creatinine ratio.

Tumor Necrosis Factor-α Plays an Initiating Role in Extracorporeal Circulation-induced Acute Lung Injury

Despite advances in critical care, the mortality rate for patients with acute lung injury (ALI) remains high. The aim of this study was to test the hypothesis that tumor necrosis factor-α (TNF-α) plays an initiating role in the onset of extracorporeal circulation (ECC)-induced ALI. Eight New Zealand rabbits subjected to 1h of ECC and 40min of observation after termination of ECC were used for monitoring pulmonary nociceptor activity. Fifty Sprague-Dawley (SD) rats that received 2h of ECC and 4h of rest were used to measure the pulmonary function and inflammatory cytokines release, including total cells, neutrophils, and TNF-α in bronchoalveolar lavage (BAL) and white blood cell (WBC) and neutrophils in blood. An additional 40 SD rats were randomized to pretreatment with inhalation of phosphate buffer solution (control group), IgG (IgG inh group), or TNF-α antibody (anti-TNF-α inh group) and venous injection of TNF-α antibody (anti-TNF-α iv group). After 2h of ECC and 4h of rest, the arterial blood and BAL fluid were collected for measurement of arterial oxygen pressure (PaO2) and inflammatory cytokines release. The left-lower-lung tissues of animals were stained with hematoxylin & eosin (H&E). The results demonstrated that the activities of airway nociceptor and TNF-α release were similarly upregulated at the early stage and in a time-related manner in ECC-induced ALI. Pretreatment with TNF-α antibody inhalation, but not venous injection, improved pulmonary function, inhibited pulmonary inflammation, and attenuated pulmonary histopathological changes after ECC. We concluded that TNF-α played an important role in the pathogenesis of ALI and acted as an initiating cytokine at the early stage of ECC-induced ALI.

Comparing microvascular alterations during minimal extracorporeal circulation and conventional cardiopulmonary bypass in coronary artery bypass graft surgery: A prospective, randomized study

Minimal extracorporeal circulation (MECC) has been introduced in coronary artery bypass graft (CABG) surgery, offering clinical benefits owing to reduced hemodilution and no blood-air interface. Yet, the effects of MECC on the intraoperative microvascular perfusion in comparison with conventional extracorporeal circulation (CECC) have not been studied so far. The current study aimed to analyze alterations in microvascular perfusion at 4 predefined time points (T1-T4) during on-pump CABG using orthogonal polarization spectral imaging. Forty patients were randomized for being operated on with either MECC or CECC. Changes in functional capillary density (FCD), blood flow velocity, and vessel diameter were analyzed by a blinded investigator. After start of extracorporeal circulation (ECC) and aortic crossclamping (T2), both groups showed a significant drop of FCD, with a significantly higher FCD in the MECC group (206.8 ± 33.6 cm/cm² in CECC group versus 217.8 ± 35.3 cm/cm² in MECC group; P = .034). In the late phase of the ECC (T3), FCD in the MECC group was already recovered, whereas FCD in the CECC group was still significantly depressed (223.1 ± 35.6 cm/cm² in MECC group; P = .100 vs T1; 211.1 ± 36.9 cm/cm² in CECC group; P = .017 vs T1). After termination of ECC (T4), FCD recovered in both groups to baseline. Blood flow velocity tended to be higher in the MECC group, with a significant intergroup difference after aortic crossclamping (T2). Orthogonal polarization spectral imaging data reveal an impairment of microvascular perfusion during on-pump CABG. Changes in FCD indicate a faster recovery of the microvascular perfusion in MECC during the reperfusion period. Beneficial recovery of microvascular organ perfusion could partly explain the perioperative advantages reported for MECC.

Cardiac output determination by thermodilution and arterial pulse waveform analysis in patients undergoing aortic valve replacement

To compare the accuracy of cardiac output (CO) measurement by arterial pulse waveform analysis (CO(PW)) to thermodilution assessments in patients with aortic stenosis, a high-risk patient group who may benefit from extended hemodynamic monitoring. In 30 patients with aortic stenosis, CO was assessed in triplicate by thermodilution via pulmonary artery catheterization (CO(PAC)), and by arterial pulse waveform analysis (CO(PW)), before and after valve replacement. The techniques were compared by assessing the repeatability coefficient of each method and by calculating the percentage error, bias, and the limits of agreement between methods. The repeatability coefficients of CO(PAC) and CO(PW) were 0.89 L.min(-1) and 1.04 L.min(-1) respectively after induction of anesthesia, which corresponded to 24% of CO(PAC) and 26% of CO(PW), and increased to 33% of CO(PAC) and 32% of CO(PW) immediately after extracorporeal circulation. A systematic error between methods was not observed. The limits of agreement were bias +/- 1.42 L.min(-1) after anesthesia induction, corresponding to a 36% percentage error. The scattering of differences between methods increased markedly after termination of extracorporeal circulation (percentage error 56%). The repeatability of CO(PAC), as well as of CO(PW), is reduced in patients with aortic stenosis. The repeatability of both methods, as well as the agreement between methods, decreased markedly immediately after termination of cardiopulmonary bypass.

Perfusing and ventilating the patient’s lungs during bypass ameliorates the increase in extravascular thermal volume after coronary bypass grafting

Background To test the hypothesis that bilateral extracorporeal circulation (ECC) (Drew technique) ameliorates the increase in extravascular thermal volume (ETV) observed after conventional cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting. Methods Thirty-four consecutive patients underwent either bilateral ECC (n = 24, additional cannulation of pulmonary artery and left atrium and lungs perfused and ventilated during bypass) or conventional CPB (n = 10, right atrial and aortic cannulation, lungs statically inflated to 4 mbar (0.41 cm H 2O) with oxygen, 500 mL/min). Determinations of ETV (thermodye dilution technique) and intraoperative fluid balance were made before surgery, at the end of surgery, and 4 hours thereafter. In addition, interleukin (IL)-8, thromboxane B2 (TxB 2), and endothelin (ET)-1 concentrations were measured in the right atrium and pulmonary vein at specified time points. Results Comparisons of ETV made at the start of surgery, after aortic declamping, and after termination of ECC, respectively, revealed an increase from 4.8 ± 0.2 mL/kg (mean ± SEM) to 6.7 ± 0.4 mL/kg, and 6.3 ± 0.3 mL/kg with conventional CPB but ETV remained unchanged at 5.2 ± 0.3 mL/kg, 5.1 ± 0.2 mL/kg, and 4.9 ± 0.3 mL/kg with bilateral ECC. Priming volume (1,580 ± 10 mL versus 2,213 ± 77 mL, p < 0.001) and intraoperative fluid balance (+1,955 ± 233 mL versus +2,654 ± 210 mL, p < 0.05) were less with conventional CPB. Concentrations of IL-8, TxB 2, and ET-1 were not different between groups. Conclusions Despite a significantly greater prime volume and a more positive intraoperative fluid balance, ETV did not change with bilateral ECC but increased with conventional CPB. Thus, using the patient’s lungs as an oxygenator during bypass mitigates the increase in extravascular pulmonary fluid.

Right ventricular function after coronary artery bypass grafting in patients with and without revascularization of the right coronary artery

To evaluate the influence of revascularization of a stenosis of the right coronary artery on right ventricular function. Prospective study. Single institutional study in a university hospital. 20 patients with different degrees of stenosis of the right coronary artery undergoing elective coronary artery bypass grafting. In 10 patients, bypass surgery included revascularization of a significant stenosis of the right coronary artery (group 1). In 10 other patients, the pathology of the right coronary artery was judged to be not significant, without indication for revascularization (group 2). Using the fast-response thermodilution pulmonary artery catheter, right ventricular function was estimated perioperatively. After termination of extracorporeal circulation, there was an increase in right ventricular volumes in group 2 (p < 0.05) and an initial decrease in group 1 (p < 0.05), with higher volumes in group 2 compared with group 1 (p < 0.05). The ejection fraction increased in group 1 (p < 0.05) and decreased in group 2 after operation (p < 0.05), with higher values in group 1 compared with group 2 (p < 0.05). In addition to these findings, the pressure-volume relationship showed a leftward and upward shift in group 1 and a rightward shift in group 2 postoperatively. These results indicate that right ventricular depression can occur after bypass grafting in patients with a moderate stenosis of the right coronary artery that is not revascularized. Revascularization of more severe stenosis of the right coronary artery appears to preserve postoperative right ventricular function.

Effects of desmopressin acetate on platelet aggregation, von Willebrand factor, and blood loss after cardiac surgery with extracorporeal circulation.

The effects of desmopressin acetate (DDAVP) on platelet aggregation and the von Willebrand factor antigen (vWF:Ag) were studied in 19 patients undergoing cardiac surgery with extracorporeal circulation. The patients represented one of five blocks in a randomized double-blind placebo-controlled parallel group trial on the effects of DDAVP on postoperative bleeding after uncomplicated coronary artery bypass operations. After termination of extra-corporeal circulation, DDAVP (0.3 microgram/kg body wt) or its vehicle was infused into a peripheral vein throughout 15 minutes. The increase in factor VIII coagulant activity after infusion did not differ between the groups but there was a significantly larger increase in vWF:Ag levels in DDAVP-treated patients. The aggregatory response to adenosine-diphosphate (ADP) and ristocetin showed a normal pattern and was not significantly different between the two groups. As compared with placebo, DDAVP did not decrease the bleeding time or the postoperative blood loss. We conclude that DDAVP causes an increase in vWF:Ag levels but does not alter platelet aggregation, bleeding time, or blood loss in uncomplicated coronary artery bypass patients.

Reduction of blood utilization during myocardial revascularization

The efficacy of four different blood conservation techniques in decreasing the homologous blood requirement in cardiac operations was studied prospectively in 100 patients undergoing myocardial revascularization. The patients were randomly assigned to four groups of 25 each as follows: group I, retransfusion of oxygenator blood after termination of extracorporeal circulation; group II, processing of oxygenator content by means of a cell separator; group III, predonation of autologous blood and isovolumetric substitution of hydroxyethyl starch (10 ml/kg bodyweight) after the induction of anesthesia in addition to the use of a cell separator; and group IV, predonation and the use of a cell separator plus postoperative retransfusion of shed mediastinal blood. To form homologous groups, we accepted only male patients without impairment of left ventricular function for the study. In addition, patients with internal mammary artery grafts and a duration of extracorporeal circulation less than 45 minutes or more than 90 minutes were excluded. The bank blood requirement during hospitalization was 2132 +/- 824 ml in group I, 1371 +/- 928 ml in group II, 833 +/- 599 ml in group III, and 408 +/- 559 ml in group IV. The use of blood conservation techniques resulted in reductions of homologous blood requirements of 34%, 60%, and 80%, respectively, in groups II to IV as compared with the requirement in group I. There were no complications related to autologous blood transfusion. We conclude that the use of blood conservation techniques can considerably reduce the homologous blood requirement in cardiac operations and therefore decrease transfusion-related risks.

An evaluation of the perioperative efficacy of selective beta 1-blockade in coronary surgery. Studies with a late preoperative dose of metoprolol.

The plasma concentration of metoprolol was measured hourly following an oral dose on two consecutive days--the day before, and the day of, coronary surgery. No significant difference was found between the two sampling days, though there was a tendency to lower concentrations during and after extracorporeal circulation. After a median dose of 50 mg the peak concentration (reached on average after 1.5 h) was 545 +/- 70 nmol/l on the first day and 388 +/- 57 on the day of surgery. The respective elimination rates from plasma, expressed as half-life, were 3.4 +/- 0.21 and 3.5 +/- 0.19 hours (NS). On the day of surgery the heart rate rose during the second half of the observation period, peaking above 130 beats/min. Heart rate was inversely correlated to metoprolol concentration in plasma with coefficient -0.68 before induction of anesthesia and -0.77 two hours after termination of extracorporeal circulation. The perioperative efficacy of beta-blockade following a late preoperative oral dose of the agent thus appeared to be reduced and inadequate.

Time-related changes in the Starling forces following extracorporeal circulation.

The intra- and postoperative variations of the transcapillary forces [colloid osmotic pressure of plasma (COPpl), colloid osmotic pressure of interstitial fluid (COPif), average hydrostatic pressure in the interstitium (Pif)] were studied in the subcutaneous tissue as a function of time in 13 patients operated on for coronary artery disease using extra-corporeal circulation (ECC). The measurements were performed before operation, during ECC, and during the first 24 hours postoperatively. COPif was measured subcutaneously on the chest both by the wick method and by a noninvasive blister suction method. The latter technique allowed several consecutive measurements in the same individual during the postoperative period. Pif was measured by "wick-in-needle" technique in the same area as the COPif measurements. COPpl was measured in a blood sample collected from a cubital vein. COPpl was reduced about 50% during ECC returned to pre-ECC level within the first 6 hours postoperatively. During ECC COPif was higher than COPpl, reaching its minimum level 4 to 5 hours postoperatively. Measurements performed following ECC showed return of the transcapillary COP-gradient to the normal direction (COPpl greater than COPif). Pre-ECC level of COPif was not entirely obtained during the first postoperative day. Pif increased gradually during ECC and continued to increase the first 2 to 3 hours following ECC. Pre-ECC level was reached within 24 hours postoperatively. The present investigation has demonstrated major dynamic variations in the transcapillary forces in patients undergoing open heart surgery with ECC. There was an increased net capillary filtration (F) intraoperatively predisposing to interstitial edema formation in subcutaneous tissue until several hours following the termination of ECC.

Transcapillary fluid balance in subcutaneous tissue of patients undergoing aortocoronary bypass with extracorporeal circulation.

Colloid osmotic pressure in plasma (COPpl) from a cubital vein and in interstitial fluid (COPif) in the subcutaneous tissue at heart level, and interstitial fluid pressure (Pif) at the same level, were measured in 18 healthy subjects and in 28 patients requiring aortocoronary bypass. Interstitial fluid was collected via subcutaneously implanted double nylon wicks and Pif was measured with the 'wick-in-needle' technique. Measurements were made preoperatively and 1 1/2 to 8 hours (mean 4 hours) after termination of extracorporeal circulation. Pif rose to 2.3 mmHg above the pre-bypass level. COPpl concomitantly fell from 22.2 to 14.4 and COPif from 12.4 to 10.1 mmHg. These changes were statistically significant. Although the relatively large COPpl drop resulted in a net rise of 3.2 mmHg in filtration pressure, the incidence of pulmonary complications was low and no subcutaneous edema was discernible. The fall in COPif and rise in Pif may be regarded as important edema-preventing mechanisms.

The protein C system in patients undergoing cardiopulmonary bypass

Fifteen men undergoing extracorporeal circulation for aorta-coronary bypass grafting were investigated for alterations of the plasma levels of cross-linked fibrin degradation products, protein C, free protein S, coagulation factor II, immunoglobulin G, and albumin. Although all patients were given heparin, a progressive increase of cross-linked fibrin degradation products was recorded during extracorporeal circulation, which indicates an activation of the plasmatic coagulation system. This increase was most pronounced in the late phase of extracorporeal circulation after reperfusion of the lung and in the early postoperative period. The levels of all other investigated plasma proteins decreased drastically after the patient was connected to the bypass circuit, which was primed with saline solution. These levels increased after termination of extracorporeal circulation and administration of fresh-frozen plasma. To study the consumption of protein C, protein S, and factor II during extracorporeal circulation, we formed ratios of the values of these parameters to the value of immunoglobulin G. After this volume correction, protein C was found to decrease significantly in the late phase of extracorporeal circulation, remaining low in the early postoperative period; protein S increased significantly soon after the onset of extracorporeal circulation and decreased after termination of extracorporeal circulation; factor II was unaffected by extracorporeal circulation, showing only a slight, insignificant increase in the postoperative phase. These results suggest a disturbance of the protein C system by extracorporeal circulation, which is possibly linked to the reported high bleeding tendency in patients undergoing operations with extracorporeal circulation.

Interaction of right and left ventricular filling pressures at the termination of cardiopulmonary bypass: Central venous pressure/pulmonary capillary wedge pressure ratio

In 50 patients who underwent coronary bypass grafting, the interaction of left- and right-sided filling pressures were prospectively evaluated to determine whether restoration and/or maintainance of a normal central venous pressure/pulmonary capillary wedge pressure (CVP/PCWP) ratio could improve biventricular performance. In 40 patients, the CVP/PCWP ratio was normal (less than 1) and termination of cardiopulmonary bypass was uneventful. In 10 patients, during loading at the termination of extracorporeal circulation, CVP exceeded PCWP and the ratio was reversed (less than 1). Cardiac index and systolic arterial pressure were low. Restoration of normal ratio by emptying the right heart helped in the improvement of systolic arterial pressure and cardiac index. Thus, in the presence of reversed CVP/PCWP ratio at the termination of cardiopulmonary bypass, restoration of the ratio may prevent unnecessary pharmacologic and/or mechanical intervention, such as inotropic agents, balloon pumps, or assist devices.

Hemodynamic Effects of Calcium Chloride Injection Following Cardiopulmonary Bypass: Response to Bolus Injection and Continuous Infusion

To determine the hemodynamic effects of intravenous injection of calcium chloride, 26 patients were studied immediately after termination of extracorporeal circulation. Eighteen patients (Group A) had injection of a single bolus of CaCl 2; in the other 8 patients (Group B), the bolus injection was followed by infusion of CaCl 2 at a rate of 1.5 mg/kg/min for 10 minutes. Myocardial contractile element velocity (V pm), aortic blood flow, electrocardiograms, and left ventricular, systemic arterial, pulmonary arterial, and left atrial pressures were recorded continuously. The baseline ionized calcium level after bypass was 3.6 ± 0.6 mg/100 ml (normal range, 3.9 to 4.5 mg/100 ml); this increased to 5.4 ± 0.5 mg/100 ml 1 minute after CaCl 2 injection. The ionized calcium level was 4.7 ± 0.6 mg/100 ml 6 minutes after CaCl 2 injection in Group A, and was 5.9 ± 0.2 mg/100 ml and 6.4 ± 0.2 mg/100 ml at 6 and 10 minutes, respectively, in Group B. There was significant early hemodynamic improvement after CaCl 2 injection, including increases in V pm ( p < 0.001), cardiac index ( p < 0.001), mean blood pressure ( p < 0.01), and stroke volume index ( p < 0.001). A similar pattern of hemodynamic response was observed in both groups. Approximately 1 minute after CaCl 2 injection, cardiac index returned to control level, V pm and mean blood pressure remained elevated, and heart rate declined ( p < 0.01). Systemic vascular resistance gradually increased and was significantly elevated ( p < 0.05) in Group B at 3 minutes and in Group A at 6 minutes. We conclude that after cardiopulmonary bypass, injection of CaCl 2 causes both immediate and sustained enhancement of myocardial performance and blood pressure. A transient elevation of cardiac index is followed by a gradual increase in systemic vascular resistance.

Brain hyperperfusion during cardiac operations: Cerebral blood flow measured in man by intra-arterial injection of xenon 133: Evidence suggestive of intraoperative microembolism

Cerebral blood flow (CBF) was measured by intra-arterial injection of xenon 133 in 29 patients during cardiac operations. Marked changes occurred in all patients. A normal and significant correlation with temperature and plasma PCO2 (p less than 0.01) support the reliability of the method. Mean CBF measured between sternotomy and the onset of extracorporeal circulation (ECC) was 38 ml/100 gm . min. The first minute of ECC was associated with a decrease in CBF in nine of 12 patients (p less than 0.02). During steady-state hypothermic ECC (temperature 29 degrees C), CBF increased unexpectedly to 64 ml/100 gm . min (p less than 0.01). Following rewarming steady-state normothermic ECC, mean CBF decreased to 42 ml/100 gm . min with signs of impairment of cerebral autoregulation. Ten and 20 minutes after termination of ECC, mean CBF was 40 and 41 ml/100 gm . min, respectively. Arterial PCO2 was found to be important in regulating CBF. The cerebral autoregulation maintained CBF down to arterial pressures of around 55 mm Hg. Below this level, CBF was significantly correlated with perfusion pressure (p less than 0.01). Multiple small emboli with a hyperemic border zone could cause a brain hyperperfusion, as seen in our patients during bypass. Measurements of CBF during ECC hold promise as a guide toward safer cardiac operations.

Heparin administration during extracorporeal circulation: Heparin rebound and postoperative bleeding

The individual variations in heparin dose response and heparin activity decay have indicated limitations of the protocols based on body surface area and weight of the patients. In the present study the heparin levels and simpler clotting tests were monitored in a consecutive series of 71 patients undergoing standard cardiac operations. The clotting tests used were the Celite activated clotting time (Celite ACT) and the whole blood activated recalcification time (BART). Forty-four patients received a loading dose of heparin, 3 mg. per kilogram, a maintenance dose of heparin, 1.5 mg. per kilogram per hour, and 6 mg. of protamine sulfate per kilogram at the termination of extracorporeal circulation (ECC) (Protocol I). Twenty-seven patients received a similar initial dose, but the maintenance dose of heparin and the dosage of protamine sulfate were administered according to the measured heparin levels (Protocol II). A significant difference was seen in the measured heparin levels (p less than 0.01, Celite ACT (p less than 0.01), and BART (p less than 0.01) in patients on Protocols I and II. Ten of the 24 patients on Protocol I and none on Protocol II showed heparin rebound phenomenon, and blood loss in patients on Protocol I was significantly greater than that in patients on Protocol II. The study clearly demonstrates that our protocol of heparin administration and control with simpler tests ensures safe hypocoagulation during ECC and efficient reversal at the end, with minimal postoperative blood loss.

Inhibition of kinin formation by a kallikrein inhibitor during extracorporeal circulation in open-heart surgery.

Involvement of the kinin system was studied in 58 patients during extracorporeal circulation in open heart surgery. At the onset of extracorporeal circulation, there was no increase of free kinin in blood and no reduction of plasma kininogen, when the latter was expressed as mug bradykinin/mg plasma protein. With the lapse of time, kinin in the blood increased significantly, and decrease of kininogen was also significant. The longer the circulation time, the greater the consumption of kininogen. The site of the kinin formation was presumed to be the heart-lung machine since the level of kinin increased slightly and kininogen decreased gradually in the blood leaving the machine, compared with those levels entering the machine. The difference in kininogen was significantly different from zero at termination of extracorporeal circulation. Administration of a kallikrein-trypsin inhibitor, trasylol (A. G. Bayer), infused into the heart-lung machine, prevented the decrease of kininogen. Reduction of the total peripheral resistance during this circulation was also prevented. The hemoconcentration, presumably the result of vascular permeability increase caused by increased kinin, was prevented by trasylol in cases in which extracorporeal circulation lasted over 60 minutes. Trasylol applied thus appears to be an effective counteragent for circulatory disturbances which occur during extracorporeal circulation.