Clinical Cardiopulmonary Bypass Research Articles

The Influence of Heparin-Coated and Uncoated Extracorporeal Circuits on Blood Rheology During Cardiac Surgery

The effect of heparin-coated perfusion circuits on blood trauma during clinical cardiopulmonary bypass (CPB) was studied in order to find out if traumatic changes in the blood could be minimized. Twenty-four patients undergoing coronary artery bypass surgery were randomized prospectively to CPB with heparin-coated circuits (HCC) or non-coated circuits (NCC). The trauma to blood was assessed by measuring damage to blood cells by estimating red and white cell rheology changes. These were measured as red cell filtration rate (RFR) and white cell filtration rate (WFR) using standard microfiltration methods. Furthermore, changes in plasma hemoglobin (P-Hb), whole blood and plasma viscosity were simultaneously assessed. The RFR was significantly reduced in both groups during CPB by 10% in the HCC and 32% in the NCC groups (p<0.01). When comparing the HCC and NCC groups, a significant difference was first seen after 30 minutes ofbypass (p<0.05) and increased at the end ofCPB (p<0.01). Similar results were seen regarding WFR (15% and 36%, p<0.01). After 30 minutes ofbypass, a significant difference was seen between HCC and NCC groups (p<0.05). Furthermore, a significant increase in P-Hb levels were seen during CPB in both patient groups. At the end of CPB, there was a significant difference in P-Hb levels (HCC 305±90 mg/L; NCC 455±78 mg/L, p<0.01) when comparing the two groups. When comparing HCC and NCC regarding corrected blood viscosity at shear rate 92 s-1, there were significantly higher viscosity values in the NCC group starting at 30 minutes of bypass (p<0.05). Plasma viscosity (PV) at shear rate 583 s-1 , showed similar results (p<0.05). This study suggests that heparin-coated extracorporeal circuits are less damaging to the rheological properties of blood and would therefore be better suited for clinical use during cardiac surgery using CPB.

Heparin surface treatment does not impair gas and heat transfer of an extracorporeal circuit

Surface treatment of a cardiopulmonary bypass circuit with heparin improves its haemocompatibility. However, potential side effects of this layer of heparin are impairment of O2 transfer and CO2 transfer in the oxygenator and heat transfer in the heat exchanger. Therefore we studied these side effects during extracorporeal circulation with moderate hypothermia in 30 patients who underwent elective coronary artery bypass grafting surgery. All patients were heparinized systemically. In 15 patients (Duraflo II-group) we used an extracorporeal circuit (including a Bentley Bos-CM50 membrane oxygenator) which was treated with heparin. The results of this group were compared with those obtained from another group of 15 patients (control-group), who were operated upon with an identical extracorporeal circuit but without heparin surface treatment. We found no significant differences between the two groups in O2 transfer, CO2 transfer or heat transfer during normothermia or hypothermia. We concluded that neither O2 transfer and CO2 transfer of the oxygenator nor heat transfer of the heat exchanger were impaired by Duraflo II heparin surface treatment during clinical cardiopulmonary bypass with moderate hypothermia.

Reduction and elimination of systemic heparinization during cardiopulmonary bypass

After extensive experimental evaluation, heparin-coated perfusion equipment was clinically evaluated with low or no systemic heparinization in three different groups of patients (n = 47). In group 1, resection of descending thoracic aortic aneurysms (n = 24) was performed with heparin-coated equipment used for left heart bypass (n = 12) or partial cardiopulmonary bypass (n = 12) for proximal unloading and distal protection (heparin 5000 IU, autotransfusion). All devices remained functional throughout the procedures and no systemic emboli were detected. The sole death (1 of 24, 4%) occurred in a patient with ruptured thoracoabdominal aortic aneurysm requiring operation in extremis. Paraparesis with spontaneous recovery occurred in one patient (1 of 24, 4%). In group 2, coronary artery revascularization randomized for low (activated clotting time greater than 180 seconds) versus full (activated clotting time greater than 480 seconds) systemic heparinization was prospectively analyzed in 22 patients. All patients recovered without sequelae, and no myocardial infarction was diagnosed. Low dose of heparin (8041 +/- 1270 IU versus 52,500 +/- 17,100 IU; p less than 0.0005) resulted in reduced protamine requirements (7875 +/- 1918 IU versus 31,400 +/- 14,000 IU; p less than 0.0005), reduced blood loss (831 +/- 373 ml versus 2345 +/- 1815 ml; p less than 0.01), reduced transfusion requirements of homologous blood products (281 +/- 415 ml versus 2731 +/- 2258 ml; p less than 0.001), and less patients transfused (5 of 12 versus 10 of 10; p less than 0.05). Lower D-dimer levels in the group perfused with low systemic heparinization (0.50 +/- 0.43 mg/L versus 1.08 +/- 0.59 mg/L; p less than 0.05) were attributed to the absence of cardiotomy suction in this group. In group 3, rewarming in accidental hypothermia by cardiopulmonary bypass was successfully performed without systemic heparinization in a patient with hypothermic cardiac arrest (23.3 degrees C) and intracranial trauma. We conclude that systemic heparinization for clinical cardiopulmonary bypass can be reduced and eliminated in selected patients if perfusion equipment with improved biocompatibility is used. Bypass-induced morbidity can be reduced.

Report on the Clinical Trials of the Plexus Membrane Blood Oxygenator

Twenty adult patients gave informed consent to clinical cardiopulmonary bypass (CPB) trials with a new adult hollow fiber membrane oxygenator. Clinical CPB trials averaged 88 ± 25 min (mean ± 1 SD) for these patients that weighed 78 ± 13 Kg and had BSA's = 1.9 ± 0.2 m2. Blood flow averaged 4.0 ± 0.8 L/min, and hypothermia was employed at 26.5 ± 2.4°C. FiO2's = 0.59 ± 0.15, and gas to blood flow ratios= 0.64 ± 0.18 were required to maintain the PaO2>100 mmHg and to accomplish alpha-stat. The oxygenator exhibited a pressure drop of 50-60 mmHg at 5.09 1/min and a heat exchanger performance factor over .55 during most of CPB. Multiple regression analysis of the clinical database demonstrated that the FiO2 required to achieve a desired PaO2 was dependent on the blood flow, gas flow, and SvO2 (r2 = 0.83, standard error = 0.09). The gas flow required to accomplish alpha-stat was dependent on patient age, weight, blood flow, arterial blood temperature, and desired PaCO2 (r2 = 0.71, standard error= 0.6). The Plexus blood oxygenator is safe for adult cardiopulmonary bypass and its clinical performance is statistically predictable.

Platelet and neutrophil activation in cardiopulmonary bypass

My colleagues and I have employed a simulated extracorporeal circuit to help define blood cell changes during clinical cardiopulmonary bypass. Platelet count decreases sharply due to temporary adhesion to the circuit. Platelets degranulate, synthesize and release thromboxane A 2, and lose the ability to aggregate with adenosine diphosphate and epinephrine. These changes are also due to the loss of α 2-adrenergic and fibrinogen receptors. The neutrophil count decreases to a lesser extent, but neutrophils also are stimulated to secrete latoferrin and elastase concomitant with activation of plasma kallikrein. Although lidocaine can inhibit the neutrophil activation and prostacyclin can inhibit the platelet stimulation, prostaglandin E 1 appears to prevent both neutrophil and platelet alterations.

Con: The EEG should not be monitored during cardiopulmonary bypass

N EUROPSYCHIATRIC complications continue to be one of the major problems following open heart surgery, despite great improvements in operative and extracorporeal perfusion techniques.‘T2 There are wide variations in the reported incidence of cerebral dysfunction, ranging from 1% to 53%~.~-~ This variation may be related to the criteria selected and indicates that there is room for improvement in the monitoring methods used. Various types of EEG monitoring have been advocated and applied to monitor brain function in the operating room (OR), and particularly to assess the adequacy of cerebral function during clinical cardiopulmonary bypass (CPB) procedures. ‘-lo There is no available means of noninvasive monitoring other than the EEG for detection of cerebral dysfunction during general anesthesia and CPB. Therefore, instead of debating whether we should use EEG monitoring during open heart surgery, we should ask, “Does this type of monitoring provide sufficient warning of inadequate cerebral circulation or of focal embolic phenomena to allow corrective measures that can result in prevention of postoperative cerebral dysfunction ?” Following careful review of published data and of our experience with the EEG, I am forced to conclude that the answer is “no.” Recent literature supporting the usefulness of intraoperative monitoring of the EEG during CPB has usually been anecdotal. In accordance with their observations and bias, the authors generally express a degree of enthusiasm, and there are only occasional notes of caution. If intraoperative monitoring of the EEG is to be of value in the OR for detection of cerebral dysfunction during CPB, however, several criteria must be satisfied. First, the entire brain is at risk and must be amenable to monitoring. Second, personnel and equipment must be available for correct recording and interpretation of the EEGs. Third, it is necessary to monitor brain dysfunction under hypothermia, anesthesia, and various forms of pharmacologic intervention. Fourth, corrective measures must be possible if and when changes in the EEG are found; and when corrective steps are taken, the benefit should outweigh the risk to patients whose EEGs indicate (correctly or falsely) that they will suffer deficits. Let us examine the first criterion, which concerns the relationship between electroencephalography and regional brain function. The EEG can record only the electrical activity arising from the cerebral cortex, thus limiting anatomic resolution of the EEG to the superficial brain structures. Deeper brain structures, including the brain stem, have little effect on the recorded EEG. Still, some authors go so far as to state that EEG activity correlates well with cerebral metabolism and regional cerebral blood flow (CBF), even when CBF and cerebral metabolic rate for oxygen (CMROJ measurements reflect total brain blood flow and oxygen consumption of the entire brain.” However, these relationships are not valid when the patient is experiencing hypoxic brain injury, has a tumor, is receiving certain anesthetics, or is asleep.12*i3 This clearly casts doubt on the value of intraoperative EEG monitoring. Most authorities would agree that the principal causes of diffuse cerebral damage are altered characteristics of CPB perfusion or the occurrence of a microembolism. However, there is no evidence that EEG monitoring is capable of differentiating between these problems. If a patient has a microembolism in some part of the brain, can the simplified EEG detect this problem, or is a more sophisticated EEG program required? How many leads are needed to pick up the microembolism? These questions are still unanswered. The second criterion concerns the availability of qualified personnel and equipment for

Formation of C1s-C1-inhibitor, kallikrein-C1-inhibitor, and plasmin- alpha 2-plasmin-inhibitor complexes during cardiopulmonary bypass

Stimulation of platelets and neutrophils occurs during clinical cardiopulmonary bypass. We investigated whether the classical complement, contact, or fibrinolytic pathways are activated as potential sources of neutrophil agonists. Using enzyme-linked immunosorbent “sandwich” assays specific for C1s-C1-and kallikrein-C1- inhibitor complexes respectively, we found that there was a modest increase in plasma levels of each complex after clinical cardiopulmonary bypass was completed. The increased concentration of enzyme-inhibitor complexes reverted to baseline within 24 hours. Since these complexes are cleared in vivo, we measured their formation by assaying their plasma levels during in vitro simulated extracorporeal circulation. Over a period of two hours, C1s-C1-inhibitor complexes rose from a baseline of 2 +/- 1 nmol/L to 21 +/- 2 nmol/L, and kallikrein-C1-inhibitor complexes rose from 2 +/- 1 nmol/L to 25 +/- 5 nmol/L. However, there was no evidence of either in vivo or in vitro plasmin-alpha 2-plasmin-inhibitor complex formation. These results indicate that the pathways of classical complement and contact activation, but probably not fibrinolysis, may be associated with neutrophil activation seen during clinical cardiopulmonary bypass.

Formation of Cls-Cl-Inhibitor, Kallikrein-Cl-Inhibitor, and Plasmin-α2-PIasmin-Inhibitor Complexes During Cardiopulmonary Bypass

Stimulation of platelets and neutrophils occurs during clinical cardiopulmonary bypass. We investigated whether the classical complement, contact, or fibrinolytic pathways are activated as potential sources of neutrophil agonists. Using enzyme-linked immunosorbent "sandwich" assays specific for C1s-C1-and kallikrein-C1-inhibitor complexes respectively, we found that there was a modest increase in plasma levels of each complex after clinical cardiopulmonary bypass was completed. The increased concentration of enzyme-inhibitor complexes reverted to baseline within 24 hours. Since these complexes are cleared in vivo, we measured their formation by assaying their plasma levels during in vitro simulated extracorporeal circulation. Over a period of two hours, C1s-C1-inhibitor complexes rose from a baseline of 2 +/- 1 nmol/L to 21 +/- 2 nmol/L, and kallikrein-C1-inhibitor complexes rose from 2 +/- 1 nmol/L to 25 +/- 5 nmol/L. However, there was no evidence of either in vivo or in vitro plasmin-alpha 2-plasmin-inhibitor complex formation. These results indicate that the pathways of classical complement and contact activation, but probably not fibrinolysis, may be associated with neutrophil activation seen during clinical cardiopulmonary bypass.

Loss of platelet fibrinogen receptors during clinical cardiopulmonary bypass

In 10 patients, cardiopulmonary bypass decreased the number of fibrinogen binding sites from 31,730 +/- 12,802 per platelet to 18,590 +/- 9,644 per platelet. Bypass also decreased the amount of the platelet membrane glycoprotein IIIa, which is part of the fibrinogen receptor complex, from 17.1 +/- 3.6 ng/10(9) platelets to 12.9 +/- 4.7. The fibrinogen binding constant did not change. Platelet sensitivity to adenosine diphosphate did not change; however, template bleeding times increased from 5.2 +/- 1.5 minutes before bypass to 8.5 +/- 2.3 minutes after bypass. Analysis of detergent washings from the perfusion circuit after bypass in five patients indicated that platelet material remains attached to the surface as membrane fragments and degranulated platelets. These data further elucidate the mechanism of platelet loss and dysfunction during cardiopulmonary bypass and highlight the importance of platelet membrane fibrinogen receptors and surface adsorbed fibrinogen in this process.

Retinal microembolism and neuropsychological deficit following clinical cardiopulmonary bypass: comparison of a membrane and a bubble oxygenator *1A preliminary communication

To observe and quantify cerebrovascular microembolic events in the central nervous system during cardiopulmonary bypass, 40 patients having elective uncomplicated coronary surgery had retinal fluorescein angiograms 5 min before bypass was discontinued. Each patient also had 10 neuropsychological tests before and after surgery. A Harvey H1700 bubble oxygenator was used for 23 patients and a Cobe CML sheet membrane oxygenator was used for 17 patients. All 23 (100%) of patients in the bubble oxygenator group had retinal microvascular occlusions consistent with microembolism compared to 8/17 (47%) in the membrane oxygenator group (P less than 0.001). In those retinas with occlusions, the mean resultant area of non-perfusion was less in the membrane oxygenator group (0.11 mm2; n = 8) than in the bubble oxygenator group (0.29 mm2; P less than 0.01). Arterial PO2 levels during bypass were similar in both groups at moderate hypothermia, but the mean PaO2 during rewarming was higher in the bubble oxygenator group (27 kPa) than in the membrane group (13 kPa; P less than 0.001). Neuropsychological deficits were more common and more severe after bubble oxygenation than after membrane oxygenation, but in this small patient group, the difference was not statistically significant. We conclude that flat sheet membrane oxygenation during cardiopulmonary bypass may confer significant protection against cerebrovascular microembolism.

Haemocompatibility of membrane and bubble oxygenators

During clinical hypothermic cardiopulmonary bypass (CPB), the haemocompatibility of six groups of membrane oxygenators (Cobe CML2, Shiley M2000, Maxima, Bard HF4000, Bard HF5000, Capiox E has been studied in 60 patients having open-heart surgery. A standardized anaesthetic and perfusion protocol was used, during which the abilityof the perfusionist to achieve target blood gas values (PaO2 20kPa and PaCO2 5.3kPa: alpha-stat) using inline electrodes was assessed. Haemocompatibility was evaluated by measurement of platelet numbers and function, betathromboglobulin (BTG), plasma haemoglobin, complement (C3a des Arg) and white blood cell (WBC) count pre- and post-CPB. Platelet and WBC numbers were also measured every five minutes throughout CPB. All oxygenators allowed the perfusionist to control blood gases adequately to prescribed levels. There were only minor differences in the degree and pattern of platelet depletion, reduction in platelet aggregation, elevation of BTG and C3a des Arg observed between oxygenator groups, which did not appear to be influenced by membrane type (flat plate versus hollow fibre). The membrane oxygenator haematological data was amalgamated with that obtained in previous clinical studies using membrane and bubble oxygenators (Cobe CML, Polystan Venotherm, Harvey H 1700, Bentley BIO-10, Bentley 1 0B, Bentley 1 OPlus, Gambro 10 and Shiley S100A HED) in which a similar evaluation protocol was employed. Comparison of the percentage change in platelet count when the pre- and post-CPB values were compared, demonstrated statistically significantly less platelet depletion (p <0.001 ) in the membrane oxygenator groups (-0.2 ± 8.3%) when compared to the bubble oxygenator groups (-21.7 ± 8.7%). A significantly lower percentage rise in BTG was also observed in the membrane oxygenator group when compared to the bubble oxygenator groups (p <0.001 ). All oxygenator groups showed elevation of both WBC count and plasma haemoglobin with a nonspecific fall in platelet aggregation over the period of bypass but no significant differences could be found between the two types of oxygenator. Membrane oxygenators, when compared to bubble oxygenators, exhibit lower GME production and improved haemocompatibility and allow superior blood gas control. Membrane oxygenators manifestly must be the oxygenator type of choice for clinical CPB.

A clinical evaluation of the Bentley 10B and Bentley 10Plus bubble oxygenators

During clinical hypothermic cardiopulmonary bypass (CPB) in 20 adult patients, the ability of the perfusionist, using an alphastat acid-base blood gas management technique, to control blood gas values has been evaluated in the Bentley 10B and Bentley 10Plus bubble oxygenators. Superior flexibility in control of the blood gas values to within a defined target range (PaO220 ± 3.3 kPa, PaCO25.3 ± 0.6 kPa) with significantly improved control of PaO2was demonstrated in the Bentley 10Plus when compared with the Bentley 1 0B. The percentage of values when both PaCO2and PaO2were within the target range was higher in the Bentley 10Plus (14%) than in the Bentley 10B (11 %). The incorporation of an Integral gas proportioning valve in the Bentley 10Plus oxygenator offers a degree of independence of control of PaO2and PaCO2which is unique in a bubble oxygenator. When the two oxygenator groups were compared, the rise in plasma haemoglobin was significantly less (p<0.005) in the Bentley 10Plus but no significant differences could be demonstrated between the two groups with respect to alteration in other formed blood elements (platelets or white blood cells) or in gaseous microemboli production.

A double blind clinical trial of Iloprost during cardiopulmonary bypass

Twenty patients undergoing elective coronary surgery were randomized to receive either the prostacyclin analogue Iloprost (Zk 36374) 5 ng/kg/min for 30 minutes before cardiopulmonary bypass (CPB) increasing to 10 ng/kg/min during CPB, or placebo, to investigate any beneficial effect on platelet preservation, or protection of the central nervous system during clinical CPB. Originally 50 patients were to have entered the trial, but unacceptable hypotensive effects occu rred in five patients who received Iloprost, lead i ng to early data analysis. No significant improvement in platelet number, volume or function; bleeding time; arterial line filter δ dry weight; retinal microembolism; or neuropsychological function, attributable to Iloprost, could be identified. The role and optimal dose of Iloprost in clinical CPB remains to be established.

Human neutrophil degranulation during extracorporeal circulation

Cardiopulmonary bypass, especially when prolonged, may result in hemostatic failure and pulmonary dysfunction, which has been attributed to changes in platelets and leukocytes, respectively. It has been well documented that contact of blood with synthetic surfaces causes platelet activation. In this report, we explore mechanisms of the activation of neutrophils during simulated in vitro extracorporeal circulation and document the release of neutrophil lactoferrin and elastase during clinical cardiopulmonary bypass (CCB). Inhibition in the simulated circuit by prostaglandin E1 (PGE1) and lidocaine suggests different mechanisms for release of neutrophil-specific proteins. During CCB with a bubble oxygenator it was observed that platelet counts fell to 42% +/- 2% of baseline. In addition, beta-thromboglobulin antigen (beta TG), a platelet-specific, alpha-granule protein marker reflecting the release reaction, increased from 0.15 +/- 0.05 to 0.84 +/- 0.11 microgram/mL. Neutrophil counts decreased to 67% +/- 7% of prebypass levels but then gradually rose as bypass continued. Both lactoferrin, a neutrophil-specific granule marker, and neutrophil elastase, an azurophilic granule marker, increased in plasma threefold to 1.66 +/- 0.33 micrograms/mL and 1.65 +/- 0.68 microgram/mL, respectively, just before bypass was stopped. When fresh heparinized human blood was recirculated within an extracorporeal membrane oxygenator bypass circuit for 120 minutes, plasma beta-TG rose to 5.13 micrograms/mL, lactoferrin increased from 0.13 +/- 0.04 to 1.62 +/- 0.22 micrograms/mL, and neutrophil elastase rose from 0.05 +/- 0.02 to 1.86 +/- 0.41 micrograms/mL. At 120 minutes, lidocaine (100 mumol/L), which inhibits neutrophil activation, delayed release of lactoferrin (1.33 +/- 0.26 micrograms/mL) and markedly inhibited release of elastase (0.24 +/- 0.05 microgram/mL) but did not inhibit release of beta-TG antigen (5.66 micrograms/mL at 120 minutes). PGE1 (0.3 mumol/L) inhibited significantly the release of beta-TG (0.31 microgram/mL) and elastase (0.52 +/- 0.11 microgram/mL) and attenuated the release of lactoferrin (1.57 +/- 0.45 micrograms/mL).

Human Neutrophil Degranulation During Extracorporeal Circulation

Abstract Cardiopulmonary bypass, especially when prolonged, may result in hemostatic failure and pulmonary dysfunction, which has been attributed to changes in platelets and leukocytes, respectively. It has been well documented that contact of blood with synthetic surfaces causes platelet activation. In this report, we explore mechanisms of the activation of neutrophils during simulated in vitro extracorporeal circulation and document the release of neutrophil lactoferrin and elastase during clinical cardiopulmonary bypass (CCB). Inhibition in the simulated circuit by prostaglandin E1 (PGE1) and lidocaine suggests different mechanisms for release of neutrophil-specific proteins. During CCB with a bubble oxygenator it was observed that platelet counts fell to 42% +/- 2% of baseline. In addition, beta- thromboglobulin antigen (beta TG), a platelet-specific, alpha-granule protein marker reflecting the release reaction, increased from 0.15 +/- 0.05 to 0.84 +/- 0.11 microgram/mL. Neutrophil counts decreased to 67% +/- 7% of prebypass levels but then gradually rose as bypass continued. Both lactoferrin, a neutrophil-specific granule marker, and neutrophil elastase, an azurophilic granule marker, increased in plasma threefold to 1.66 +/- 0.33 micrograms/mL and 1.65 +/- 0.68 microgram/mL, respectively, just before bypass was stopped. When fresh heparinized human blood was recirculated within an extracorporeal membrane oxygenator bypass circuit for 120 minutes, plasma beta-TG rose to 5.13 micrograms/mL, lactoferrin increased from 0.13 +/- 0.04 to 1.62 +/- 0.22 micrograms/mL, and neutrophil elastase rose from 0.05 +/- 0.02 to 1.86 +/- 0.41 micrograms/mL. At 120 minutes, lidocaine (100 mumol/L), which inhibits neutrophil activation, delayed release of lactoferrin (1.33 +/- 0.26 micrograms/mL) and markedly inhibited release of elastase (0.24 +/- 0.05 microgram/mL) but did not inhibit release of beta-TG antigen (5.66 micrograms/mL at 120 minutes). PGE1 (0.3 mumol/L) inhibited significantly the release of beta-TG (0.31 microgram/mL) and elastase (0.52 +/- 0.11 microgram/mL) and attenuated the release of lactoferrin (1.57 +/- 0.45 micrograms/mL).

Early Clinical Experience with Gas-STAT™

The purpose of this study was to evaluate and report on the Gas-STAP™ continuous blood gas and pH monitoring system. This system was tested for accuracy, stability and reproducibility during extracorporeal circulation when compared to intermittent blood gas sampling. The Gas-STAT was used in conjunction with 44 clinical cardiopulmonary bypass procedures. There were 261 arterial and 259 venous blood samples obtained for analysis. Early results comparing Gas-STAT versus intermittent samples analyzed on an IL813 blood gas analyserb showed less than ideal correlation. With continued clinical experience and further system refinements, data agreement improved substantially. This system provides valuable information to the perfusion team. Continuous blood gas and pH readings give the perfusionist immediate visualization of the effects of therapeutic interventions. Changes in gas flows and mixtures, blood flow, perfusate temperatures, hemodilution and the effects of pharmacologic agents all can affect the acid base and blood gas status of the patient. This system can be calibrated and employed without any substantial increase in time required by the perfusionist.

Effects of Simulated Clinical Cardiopulmonary Bypass and Cardioplegia on Mass of the Canine Left Ventricle

Myocardial edema is a well-documented response to ischemia and reperfusion in dogs and can be detected as an increase in left ventricular (LV) mass measured echocardiographically. Investigation in human beings has failed to demonstrate similar increases in LV mass after routine cardiac operations. However, direct comparison of these observations is not possible, because dogs have not been studied under conditions of cardiopulmonary bypass (CPB) and global ischemia that rigorously reproduce those of a clinical operation. Accordingly, clinical CPB and global ischemia were simulated in 8 adult dogs. Multisection two-dimensional echocardiograms and a computerized light pen were used to calculate LV volume and mass. The data were analyzed during four periods: before CPB; CPB before cross-clamping; CPB after cross-clamping, and after CPB. Echocardiographic LV mass increased significantly from 89.5 ± 7.4 gm (before CPB) to 94.6 ± 8.5 gm (CPB before cross-clamping) ( p < 0.05) and from 94.6 ± 8.5 gm to 100.4 ± 8.1 gm (CPB after cross-clamping) ( p < 0.05). Overall, mass increased 13.9% ( p < 0.05). Mean wall thickness increased 0.08 cm ( p < 0.05) overall and correlated with the increase in mass ( r = 0.79). Postmortem mass correlated well with late echocardiographic mass ( r = 0.95). Interobserver correlation of 98 separate mass determinations was high ( r = 0.84) with a coefficient of variation of 10.5%. We conclude that canine LV mass increases significantly with CPB and global ischemia maintained within clinical standards and that human beings and dogs may differ in extent of edema during CPB.

A New Hollow‐Fiber Oxygenator for Clinical Cardiopulmonary Bypass

A new hollow-fiber oxygenator has become available for clinical cardiopulmonary bypass. It is available in three sizes for adult use, ranging from 3.3 to 5.4 m2. The surface area is dependent on the number of fibers, with blood and oxygen effecting very efficient gas transfer throughout the length of each of the fibers. The clinical experience now covers 100 patients, using the 3.3-m2 device in 16 patients, the 4.3-m2 device in 12 patients, and the 5.4-m2 device in 72 patients. In all cases, the oxygenator has proven highly efficient in gas transfer. The addition of an oxygen-blending unit was found to be necessary to prevent overoxygenation. It is a safe and effective device to use in routine clinical practice.

The Effect of Prostaglandin E 1 in Patients Undergoing Clinical Cardiopulmonary Bypass

The effect of prostaglandin E 1 (PGE 1) on protection of platelets during cardiopulmonary bypass (CPB) was evaluated in 9 patients, who were compared with an identical control group of 10 patients undergoing coronary artery bypass grafting. To evaluate the hemodynamic side-effects, PGE 1 (0.05 μg/kg/min) was infused prior to CPB, resulting in a 26% drop in mean systemic arterial pressure. With this dose, no inhibition of the adenosine diphosphate-induced aggregation could be measured in the pulmonary artery sample. During CPB, the same infusion dose resulted in a severe drop in systemic arterial pressure below 50 mm Hg in 7 of the 9 patients. In 5 of these patients, volume load and phenylephrine infusion could not compensate for the pressure drop, and PGE 1 had to be reduced to 0.02 μg/kg/min. Platelet aggregation was reduced significantly in the PGE 1-treated group compared with the control group, but not completely inhibited during CPB. However, in the postbypass period no platelet preservation was seen in the PGE 1 group. In both groups, platelet number and function were equally low. No differences were measured in blood loss or blood transfusion requirements. Except for hypotension, no side-effects of the PGE 1 treatment were seen. It is concluded that the hypotension caused by minimal doses of PGE 1 during CPB precluded using higher doses, which might have had a greater effect on platelet inhibition. These hypotensive side-effects should be reduced or eliminated before PGE 1 can be expected to have the same protective effect on platelet damage that has been demonstrated in animal experiments.

Laboratory and clinical evaluation of a membrane oxygenator with secondary flows in the blood channels.

AbstractA microporous membrane oxygenator which has transverse furrows on the membrane surface has been used in 50 clinical cardiopulmonary bypass procedures for coronary revascularization. The transverse furrows on the membrane, together with intermittent rapid pulsatile reversal of the blood flow in the blood film, produce secondary flows in the film and increase exposure of desaturated blood to the membrane. Venous drainage flows into a plastic reservoir, from which it is pumped through the oxygenator and integral heat exchanger into the aorta of the patient. Perfusions were carried out with hemodilution and moderate hypothermia. The oxygenator was ventilated with oxygen. In experimental perfusions using calves, the oxygen transfer was as high as 371 ml/min. During the clinical perfusions, arterial oxygen saturation was always 98% or higher. The mean arterial carbon dioxide tension was 41 mm Hg at a mean O2 flow of 1.4 L/min. The mean arterial pH was 7.40. The oxygenator puiser which created the secondary flows in the blood film was operated at a rate of between 90 and 255 pulses per minute. Pressure drop across the oxygenator averaged 18 mm Hg. Oxygen tension in the arterial blood could be regulated with the pulser rate, greater pulser rates being associated with larger oxygen transfer. Carbon dioxide transfer was best regulated by changes in gas flow rate. The oxygenator functioned well and was safe and reliable during these 50 perfusions.