Start Of Bypass Research Articles

Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass

A placebo-controlled double-blind study of patients undergoing cardiopulmonary bypass was conducted, comparing the effects of dexamethasone and a placebo on the activation of the plasmatic systems and blood cells and on the postoperative course after cardiopulmonary bypass. In the placebo group two patterns of blood activation could be distinguished. From the start of bypass, blood-material interaction caused an increase in complement C3a and elastase concentration. After release of the aortic crossclamp, a statistically significant increase was observed in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity (p <0.01, p <0.05, p <0.05, respectively). Dexamethasone treatment was not able to inhibit complement activation and elastase release during cardiopulmonary bypass. However, dexamethasone treatment effectively inhibited the increase in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity after release of the crossclamp (p <0.01 compared with the placebo group). In the postoperative period the patients in the placebo group had hyperthermia and hypotension and required considerable intravenous fluid administration and cardiotonic treatment. The dexamethasone-treated patients, however, showed normothermia (p <0.01), had significantly higher blood pressures (p <0.01) without supportive treatment, and consequently were in the intensive care unit for a shorter period of time. We conclude that dexamethasone prevents the hemodynamic instability after cardiopulmonary bypass and thus improves the postoperative course by inhibition of the leukocyte and tissue plasminogen activator activity generated after release of the aortic crossclamp.

Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass

A placebo-controlled double-blind study of patients undergoing cardiopulmonary bypass was conducted, comparing the effects of dexamethasone and a placebo on the activation of the plasmatic systems and blood cells and on the postoperative course after cardiopulmonary bypass. In the placebo group two patterns of blood activation could be distinguished. From the start of bypass, blood-material interaction caused an increase in complement C3a and elastase concentration. After release of the aortic cross-clamp, a statistically significant increase was observed in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity (p less than 0.01, p less than 0.05, p less than 0.05, respectively). Dexamethasone treatment was not able to inhibit complement activation and elastase release during cardiopulmonary bypass. However, dexamethasone treatment effectively inhibited the increase in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity after release of the crossclamp (p less than 0.01 compared with the placebo group). In the postoperative period the patients in the placebo group had hyperthermia and hypotension and required considerable intravenous fluid administration and cardiotonic treatment. The dexamethasone-treated patients, however, showed normothermia (p less than 0.01), had significantly higher blood pressures (p less than 0.01) without supportive treatment, and consequently were in the intensive care unit for a shorter period of time. We conclude that dexamethasone prevents the hemodynamic instability after cardiopulmonary bypass and thus improves the postoperative course by inhibition of the leukocyte and tissue plasminogen activator activity generated after release of the aortic crossclamp.

Creatine phosphate (Neoton) as an additive to St. Thomas' Hospital cardioplegic solution (Plegisol) *1, *2Results of a clinical study

Experimentally, creatine phosphate (CP) added to St. Thomas' Hospital cardioplegic solution (STH) improved post-ischaemic recovery of cardiac function in the rat heart. We investigated the effect of adding CP (10.0 mmol/l) to STH. Fifty open-heart surgery patients were randomized into control (STH) and treated (STH + CP) groups (25 per group). Patients underwent (a) monitoring for peri- and postoperative arrhythmias (48-h Holter monitoring). (b) quantitative birefringence assessment of intraoperative myocardial protection in left and right ventricular biopsies sampled at start of bypass (pre-isch.), end of bypass (end-isch.) and after 10 min reperfusion (post-isch.), and (c) measurement of serum creatine kinase-MB isozyme (CK-MB) values for up to 4 days postoperatively; results were assessed with respect to (d) haemodynamics and postoperative clinical outcome. Inotropic support (adrenaline) was required in three patients (12%) from each group; no patient died. All patients required defibrillation, and the number of direct current shocks required for sinus rhythm was the same in each group. The occurrence and incidence of reperfusion-induced arrhythmias were the same in both groups. Serum CK and CK-MB values were similar throughout the sampling period in both groups of patients; one patient in the control group had raised CK-MB levels postoperatively, but perioperative infarction was not indicated by the electrocardiogram.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin protects platelets against the initial effect of cardiopulmonary bypass

Remarkable improvement in hemostasis after cardiopulmonary bypass has been achieved by treatment with the proteinase inhibitor aprotinin, but the mechanism is still unclear. The present study is designed to elucidate the importance of platelet adhesive (glycoprotein Ib) or aggregatory (glycoprotein IIbIIIa) receptors on this hemostatic function in cardiopulmonary bypass and its improvement by aprotinin treatment. To determine whether the first pass of blood through the circuit or a continuous proteolytic attack is the main cause of platelet damage, we gave two different dose regimens of aprotinin treatment to patients undergoing coronary artery bypass grafting. Part I of the study consisted of a double-blind trial on 60 patients. Patients received placebo or aprotinin infusion (total 6.10(6) KIU) before and during bypass. A consecutive group of 22 matching patients received one single bolus of aprotinin in the pump prime (2.10(6) KIU). Blood samples were collected before and during operation to assess the effect of bypass and aprotinin on platelets and the activation of the various proteases in relation to hemostasis expressed in blood loss and blood requirements. The adhesive platelet membrane Ib glycoproteins were decreased by 50% in the untreated patients within 5 minutes of cardiopulmonary bypass and remained low during bypass, whereas glycoprotein Ib did not decrease in either group of aprotinin-treated patients. The platelet membrane IIbIIIa glycoproteins did not significantly change during bypass in either group, but fibrinogen binding to these receptors improved significantly in the 6.10(6) KIU aprotinin-treated group at the end of bypass as compared with initial values. The high continuous dose of 6.10(6) KIU aprotinin inhibited the clotting and kallikrein/kinin system throughout the operation; the pump prime dose of 2.10(6) KIU inhibited these systems only initially. Although the fibrinolytic activity was effectively inhibited in both aprotinin groups, fibrinolytic activity became apparent only at the end phase of bypass in the placebo group. However, improved hemostasis was observed intraoperatively from the start of bypass and resulted in a 40% lower blood loss intraoperatively and postoperatively and consequently a 40% lower total blood requirement in the aprotinin-treated patients than in the untreated patients. Our results therefore demonstrate that the improved hemostasis during and after bypass in patients treated with aprotinin has specifically to be attributed to a preserved adhesive capacity of platelets that was affected in the first pass of blood through the cardiopulmonary bypass circuit.

Alteration of red cell deformability during extracorporeal bypass: membrane ν bubble oxygenator

Red cell deformability is essential for normal microcirculation, since the red cell is greater in diameter than the caliber of small capillaries. Red cell filtration rate (RFR) was measured using a 5 microns nucleopore polycarbonate filter as an index of red cell deformability before, during, and after two hours of extracorporeal circulation for coronary artery bypass surgery, with a bubble oxygenator (eight patients) or a hollow fiber membrane oxygenator (14 patients). RFR decreased steadily and significantly during bypass in the bubble oxygenator group. After the start of bypass, RFR was significantly higher at all measurement intervals in the membrane oxygenator group as compared with the bubble oxygenator group. It can be postulated that significantly impaired red cell deformability caused by the bubble oxygenator is attributed to mechanical damage secondary to a huge blood-gas interface, and possibly to neutrophil-mediated oxygen free radical formation due to complement activation. Results indicate that the hollow fiber membrane oxygenator is superior to the bubble oxygenator in maintaining red cell deformability.

Concentrations sériques et tissulaires du céfamandole pendant la chirurgie cardiaque

This study aimed to determine plasma (CPC) and tissue concentrations of cefamandole during cardiac surgery, so as to compare them with the minimal inhibitory concentration (MIC) for staphylococci (0.25 – 1 μg · ml −1 for S. aureus ; 2 μg · ml −1 for S. epididermis). Cefamandole was given prophylactically to 8 consecutive patients as a single intravenous dose of 60 mg · kg −1. Tissue concentrations were measured in presternal subcutaneous loose tissue and sternal marrow. Average CPC was 233.75 ± 58 μg · ml −1, 15 min after drug administration, 187 ± 6.4 μg · ml −1 at the time of sternotomy, 57.9 ± 36.5 μg · ml −1 10 min after the start of bypass and 36.4 ± 18.4 μg · ml −1 at its end, and 15.5 ± 5.9 μg · ml −1 at the end of the procedure. Sternal subcutaneous tissue and marrow concentrations were respectively 24.4 ± 13.3 μg · g −1 and 31 ± 5.6 μg · g −1 at the time of sternotomy, and 9.4 ± 5.5 μg · g −1 and 9.2 ± 3.5 μg · g −1 at the end of the procedure. Giving a high dose of cefamandole preoperatively appeared to have an effective prophylactic antibiotic action, as the plasma and tissue concentrations were always higher than the MIC for staphylococci.

Hemodynamic variables and the incidence of prebypass ischemia during sufentanil/O 2/pancuronium anesthesia in patients undergoing coronary artery surgery

It has been suggested that sufentanil is a superior anesthetic to fentanyl for patients undergoing myocardial revascularization. This study was performed to determine the incidence of prebypass myocardial ischemia using sufentanil, 20 micrograms/kg for patients undergoing coronary artery bypass grafting (CABG). Twenty-seven patients with normal left ventricular function, scheduled for elective CABG, were studied. Anesthesia was induced with sufentanil, 10 micrograms/kg; and pancuronium, 0.1 mg/kg, was given for muscle relaxation. Further increments of sufentanil, 5 micrograms/kg, were given before skin incision and sternotomy. All patients had ECG leads V6 and V9 recorded continuously with a Holter monitor from arrival in the operating room until the start of bypass. Hemodynamic profiles were recorded at specific intervals in the prebypass period. Seven patients (25.9%) developed prebypass myocardial ischemia, three at intubation, and three at aortic dissection. Fourteen patients developed hypertension and 14 had hypotension, defined as increases or decreases greater than 20% from baseline values, respectively. Only five patients had neither hypotension nor hypertension. Three patients (11.1%) had perioperative myocardial infarctions, two of whom had prebypass myocardial ischemia. It is concluded that the incidence of prebypass ischemia with sufentanil anesthesia approximates 26%, which is similar to other studies using sensitive ECG monitoring techniques for the detection of ST segment changes. Hemodynamic instability, in the form of bradycardia, hypertension and hypotension, but not tachycardia, may have contributed to the incidence of prebypass ischemia.

A Qualitative Analysis of Pulsatile Perfusion: Effects on Cortisol Response to Cardiopulmonary Bypass Surgery

Continuous analysis of pressure waveform has enabled quantitative assessment of pulsatile perfusion in a series of 51 patients randomly allocated to "pulsatile" (N = 37) and "non-pulsatile" (N = 14) groups. Cortisol and hematocrit (PCV) were measured preoperatively, at 2 minutes and 30 minutes after the start of bypass and just prior to the end of bypass. Radial artery pressure, pulse pressure and dp/dt were recorded continuously on a specially constructed device. Though there was significant difference between the pulsatile and non-pulsatile groups in terms of pulse pressure (P less than 0.001) and dp/dt (P less than 0.01), no difference was demonstrated in terms of mean arterial pressure (P greater than 0.4), total plasma cortisol (P greater than 0.9) and PCV corrected plasma cortisol (P greater than 0.8). Multiple regression analysis of cortisol and change in cortisol with pulse pressure dp/dt and mean arterial pressure failed to show any correlation. We found a normal cortisol response to surgery irrespective of the quality of pulsation.

Quantitative analysis of EEG changes during hypothermia.

Power spectrum analysis of 4-channel EEGs was performed during cooling and rewarming using cardiopulmonary bypass. During rewarming, linear correlations of temperature with the total power and with peak power frequency of the high-frequency band were observed in a significant number of cases (85%, P less than 0.0001 and 76%, P less than 0.002, respectively). The magnitude of these changes were 1,215 microV2/degrees C (+/- 150 [SEM] ) and 0.39 Hz/degrees C (+/- 0.04 [SEM] ). Two other descriptors of the EEG power spectrum (the spectral edge and average frequencies) did not correlate with the temperature changes in a significant number of cases. Changes during cooling followed a similar trend but were more variable, presumably because of other physiologic changes associated with the start of bypass. Knowledge of the relationship of the EEG to temperature should permit distinguishing EEG changes secondary to hypothermia from those caused by acute hypoxia.

Activated coagulation time method for control of heparin is reliable during cardiopulmonary bypass.

The ability of the heparin dose-activated coagulation time (ACT) response curve to predict doses of heparin during open-heart operations has been debated since its proposal. The dose-response method was examined in a statistically rigorous manner in 23 patients. The ACT response to 3 mg/kg heparin varied among patients from 308 to 520 s. Although at the start of bypass, ACTs often increased beyond the linear part of the dose-response curve (500 s), they returned to 483.7 +/- 176.8 s (SD) within 1 h. After this first hour, one to four additional data points fit the initial two-point dose-response curve closely, and additional points did not significantly change dosage calculations for heparin and protamine. After a dose of protamine calculated to exactly neutralize heparin, the average ACT returned to within 7 +/- 11% (SD) of control values. A two-point dose-response curve, generated for each patient before bypass begins, remains statistically valid and clinically useful throughout open-heart operations as long as the ACT is less than 500 s. The dose-response method is a simple, valid way to control coagulation during open-heart operations.

St. Thomas Cardioplegia Versus Topical Cooling: Ultrastructural and Biochemical Studies in Humans

Transmural left ventricular biopsies were studied from 28 patients undergoing cardiopulmonary bypass with anoxic cardiac arrest. The myocardium was protected by topical cooling (20° C) (Group 1, 15 patients) or by cardioplegia with St. Thomas' solution (Group 2, 13 patients). Biopsies were taken at the start of bypass and 3 to 5 minutes after unclamping of the aorta. Mean cross-clamp time was not significantly different between the groups (50 minutes for Group 1 and 53 minutes for Group 2; p > 0.05). The ultrastructural changes induced by ischemia and subsequent reperfusion were almost exclusively related to the mitochondria. The degree of mitochondrial damage was evaluated by a semiquantitative analysis based on mitochondrial fine structure. The frequency of severe postischemic mitochondrial damage was significantly higher in Group 1 (20.1% verus 2.7% in Group 2; p < 0.05). Biochemical analysis of the biopsies indicates that the myocardial concentration of creatine phosphate decreases by about 50% after topical cooling ( p < 0.05). With St. Thomas cardioplegia, no significant change in the tissue level of this high-energy phosphate takes place. The results show evidence of the superiority of the St. Thomas cardioplegia to topical cooling alone.

Cardiac hypothermia evaluated by ultrastructural studies in man

Transmural left ventricular biopsies from 13 patients undergoing cardiopulmonary bypass were studied. The hypertrophic myocardium was protected by deep hypothermia (15 degrees C.) during ischemic arrest for a maximal period of 96 minutes. Biopsies were taken at the start of bypass, at the end of aortic cross-clamping, and after 20 minutes of reperfusion. The structure of the mitochondria remained normal, whereas cellular alterations in the form of widened intercalated discs, interstitial and intracellular edema, myelin figures, and slight myofibrillar lysis were observed in all stages. As no clear correlation between these structural injuries and aortic cross-clamping time was seen, they are a result of cardiac hypertrophy rather than intraoperative ischemia.

Effects of hemodilution on hypotention during cardiopulmonary bypass.

Arterial pressure, systemic vascular resistance, and viscosity measurements were made on 20 patients, during cardiopulmonary bypass with hemodilution to an average hematocrit reduction of 48 plus or minus 12 percent. The arterial pressure and blood viscosity decreased an average of 56 plus or minus 16 percent and 40 plus or minus 12 percent, respectively. The total peripheral resistance following the start of bypass was significantly below normal (p smaller than 0.005), but not when corrected for the change in viscosity. There was a strong correlation between the extent of pressure reduction and the viscosity decrease with hemodilution (p smaller than 0.01), although not all the changes in pressure could be accounted for in terms of viscosity. There was no apparent correlation between the extent of hypotension as measured by the area of the pressure-time curve below 50 mm. Hg and the presence or absence of postoperative cerebral or cardiac complications, in contrast to other recent reports.

Effects of Hemodilution on Hypotension During Cardiopulmonary Bypass

Arterial pressure, systemic vascular resistance, and viscosity measurements were made on 20 patients during cardiopulmonary bypass with hemodilution to an average hematocrit reduction of 48 ± 12 percent. The arterial pressure and blood viscosity decreased an average of 56 ± 16 percent and 40 ± 12 percent, respectively. The total peripheral resistance following the start of bypass was significantly below normal (p<0.005), but not when corrected for the change in viscosity. There was a strong correlation between the extent of pressure reduction and the viscosity decrease with hemodilution (p<0.01), although not all the changes in pressure could be accounted for in terms of viscosity. There was no apparent correlation between the extent of hypotension as measured by the area of the pressure-time curve below 50 mm. Hg and the presence or absence of postoperative cerebral or cardiac complications, in contrast to other recent reports.

Changes in arterial pressure, viscosity, and resistance during cardiopulmonary bypass

Large changes in arterial pressure and systemic vascular resistance are frequently observed at the onset of and during cardiopulmonary bypass, particularly when hemodilution is employed. In order to assess the extent to which these changes are induced by changes in blood viscosity, we measured viscosity, pressure, and flow in a series of 17 patients. Hemodilution was used in Group A (12 patients) but not in Group B (5 patients). At the beginning of cardiopulmonary bypass, the arteriovenous pressure difference decreased an average of 53.8 per cent in the Group A patients, concomitant with a 41.7 per cent decrease in blood viscosity. The arteriovenous pressure difference in the Group B patients increased an average of 6.4 per cent, while the blood viscosity increased by 8 per cent. A nomogram was theoretically derived for the Group A patients, which allows rapid estimation of the extent of viscosity-induced hypotension for a given volume of priming fluid, initial patient hematocrit, and patient weight. After correction for viscosity changes due to hemodilution, the Group A patients were found to exhibit essentially normal values of systemic vascular resistance at the start of bypass, with a mean of 1,155 dynes-sec./cm.5. On the other hand, the Group B patients had elevated resistance values, with a mean of 1,611 dynes-sec./cm.5. During perfusion, the resistance of both groups tended to increase, sometimes by 100 per cent or more. In some cases, however, the resistance values changed in an erratic fashion. These effects were not due to changes in blood viscosity.

Landé-Edwards membrane oxygenator without pump as total lung prosthesis

Fourteen anesthetized dogs remained in apnea for 1 to 4 hours on total extracorporeal breathing through a Landé-Edwards membrane oxygenator (LEMO). The LEMO was directly perfused by the right heart in total pulmonary bypass, without a pump or reservoir, as an external artificial lung. A 2 sq. M. LEMO proved adequate for a dog weighing 10 kiolgrams. Pulmonary arterial pressure increased 60 per cent of the base-line value at the start of bypass because of transitory LEMO resistance, three times the normal pulmonary resistance; the pressure then returned to the initial value. Systemic arterial pressure dropped to 61 per cent on bypass. The heart did not fail. Cardiac output, central venous pressure, and the electrocardiogram remained unchanged. PO2 at the LEMO outlet was more than 200 mm. Hg. Oxygen transfer was less than 20 ml. per minute per square meter because of hemodilution and hypothermia. Dogs survived if bypass was arrested after 1 hour; if not, they died after an average of 3 hours, 20 minutes on bypass.