Terence Gourlay

Neurological injury during cardiopulmonary bypass in the rat

Cerebral injury is a well-known complication of cardiac surgery. Investigations of both injury mechanisms and neuroprotective strategies have partially been limited by the lack of an adequate preclinical model of small animal cardiopulmonary bypass (CPB). We sought to determine if neurological injury could be demonstrated in a recovery model of complete CPB in the rat. Rats (n = 5) underwent 45 min of normothermic CPB followed by 24 h of recovery. Compared to sham-operated rats (n = 5), the CPB group showed a worse neurological outcome score (median, 25-75th percentile) compared to controls (5, 4-7 vs 9, 8-9, p = 0.016). This rat model of CPB may allow for the study of CPB-associated neurological injury.Cerebral injury is a well-known complication of cardiac surgery. Investigations of both injury mechanisms and neuroprotective strategies have partially been limited by the lack of an adequate preclinical model of small animal cardiopulmonary bypass (CPB). We sought to determine if neurological injury could be demonstrated in a recovery model of complete CPB in the rat. Rats (n = 5) underwent 45 min of normothermic CPB followed by 24 h of recovery. Compared to sham-operated rats (n = 5), the CPB group showed a worse neurological outcome score (median, 25-75th percentile) compared to controls (5, 4-7 vs 9, 8-9, p = 0.016). This rat model of CPB may allow for the study of CPB-associated neurological injury.

A literature review of cardiopulmonary bypass models for rats.

Cardiopulmonary bypass (CPB) has improved a great deal since its first applications in the early 1950s. If improvements are to be continued, a preclinical model of CPB for small animals is desirable, mainly because of convenience of equipment and low costs. We review the different models of CPB for rats that have been designed, discuss their characteristics and points where improvements may be made. We give suggestions and requirements for a new up-to-date model that could be a useful tool in continued research on the pathophysiology and therapeutic strategies of CPB.

Biomaterial development for cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is dependent on materials foreign to the patient for its successful application. When blood comes into contact with these so-called biomaterials, an inappropriate inflammatory response, which can be life-threatening in some patients, may develop. The reason for this inappropriate activation of host defence mechanisms is not entirely clear, however a number of strategies have evolved over the years to minimize this unwanted sequelae of CPB. These strategies include surface coating of the materials of the circuit, using new materials thought to improve biocompatibility, and using a number of pharmacological interventions designed to suppress the inflammatory response. Recently, there has been some evidence which indicates that the plasticizer employed in the polyvinyl chloride (PVC) tubing of the CPB circuit may play a part in the development of the inflammatory response. The work described in this paper tends to support this thesis. These studies showed that by washing the plasticizer from the surface of the PVC tubing, the biocompatibility, as reflected in the upregulation of CD11b on the surface of neutrophils, was enhanced. Furthermore, the use of non-plasticized substitutes for PVC had a similar effect. The benefit from removing the plasticizer was similar to that gained from surface coating with heparin, one of the conventional approaches to reducing the inflammatory response to CPB.

Assessment of the risk of systemic fat mobilization and fat embolism as a consequence of liposuction: ex vivo study

Background: Adverse consequences of liposuction, including those associated with fat embolism, have been reported in the literature. Fat embolism syndrome after liposuction may be underestimated because of the unspecific nature of the symptoms. The aim of this study was to determine whether there is a generic risk of the generation of intravascular fat emboli as a consequence of liposuction. Methods: An animal study was conducted in which liposuction was performed on 10 Sprague-Dawley rats. The procedure was conducted with the animals under general anesthesia for 60 minutes, in a similar manner to that practiced clinically. Three blood samples were taken from each animal through a central line (one before liposuction and two at 30 and 60 minutes into liposuction) and examined for the presence of fat particles. The animals were then euthanized and the lungs and brain were removed for histological examination. In the control group, liposuction was not performed, but similar blood and histological samples were taken. Results: In the study group, stained fat particles were seen in all blood samples taken during liposuction but not in those taken before liposuction. The difference between the 30- and 60-minute samples and the preliposuction control ones was statistically significant (p < 0.001 minimum). The differences between the 30-minute and 60-minute samples were also statistically significant (p = 0.017), demonstrating that fat mobilization during liposuction is a cumulative process. Nothing of significance was seen in the blood samples of the control group. Lipid deposits were seen in the lungs of all study group animals but not in the control group. With one possible exception, no lipid deposits were confirmed in brain specimens. Conclusions: The authors’ experiments have demonstrated a significant risk of systemic fat mobilization and fat embolism after liposuction in the animal model. Further clinical investigation is required to evaluate the real clinical risk of this procedure from this perspective.

A review of anti-inflammatory strategies in cardiac surgery

It is generally accepted that cardiac surgery is frequently associated with the development of systemic inflammatory response. This phenomenon is very variable clinically, and can be detected by measuring plasma concentrations of certain inflammatory markers. Complement component, cytokines and adhesion molecules are examples of these markers. Systemic inflammation can be potentially damaging to major organs. Several anti-inflammatory strategies have been used in recent years, aiming to attenuate the development of systemic inflammatory response. This article summarizes recently published literature concerning the use of anti-inflammatory techniques and pharmacological agents in cardiac surgery. In particular, the anti-inflammatory effects of off-pump surgery, leukocyte filtration, corticosteroids, aprotinin, phosphodiesterase inhibitors, dpoexamine, H2 antagonists and ACE inhibitors are reviewed. The overall conclusion is that although certain strategies reduce plasma levels of inflammatory mediators, convincing evidence of significant clinical benefits is yet to come.

Leucodepletion during cardiopulmonary bypass reduces blood transfusion and crystalloid requirements

Cardiopulmonary bypass (CPB) is associated with the production of inflammatory responses, which can have significant influence on prognosis. We studied the effects of leucocyte-depletion filters on inflammatory parameters and early postoperative prognosis during coronary revascularization. Twenty patients undergoing elective coronary revascularization were randomly divided into two groups. Ten patients had leucocyte-depletion filters added to the CPB circuit (treatment group) and 10 were used as control cases (control group). Expression of CD11 b on neutrophils, and production of myeloperoxidase and lactoferrin, were measured in arterial samples between induction and 3 h postbypass. In addition, clinical parameters were measured during inpatient recovery. CD11b neutrophil expression, and myeloperoxidase and lactoferrin production, were found to be upregulated during CPB and then to decline to preoperative levels by the third postoperative hour. Blood transfusion requirements were reduced in the treatment group, equalling 1.5 ± 1.2 units, compared to 2.7 ± 1.1 units for the control group (p value = 0.034) and so were the volumes of crystalloid infused during the first 24 h postoperatively, equalling 3.9 ± 1.2 I in the treatment group and 3.3 ± 0.7 I in the control group (p value = 0.021). Overall, the application of leucocyte depletion produced an early clinical advantage, underlining the need for an improved understanding and manipulation of the inflammatory response to CPB.

Early experience with a new technique and technology designed for the study of pulsatile cardiopulmonary bypass in the rat

The benefits of pulsatile flow during the period of cardiopulmonary bypass (CPB) applied during open-heart surgery remains controversial. We have developed a rodent (rat) model of CBP that has been designed to functionally mimic the clinical setting, principally, but not solely, for the study of pulsatile CPB. The successful development of this model centres on the design of the bypass circuitry and the surgical approach employed. The entire circuit is similar to clinical equipment in terms of its construction, configuration, performance, material surface area to blood volume ratio, and priming volume to blood volume ratio. The overall priming volume of the perfusion circuitry is less than 12 ml. Early studies confirm that the pumping technology functions well, gas exchange was adequate at all times, and blood pressure exhibited a normal CPB profile and haemodynamic response to pulsatile blood flow. We conclude that this is an effective tool for investigating the pathophysiology of pulsatile blood flow during CPB.

Leucocyte depletion in cardiopulmonary bypass: a comparison of four strategies

Leucocytes have been shown to play a fundamental role in the pathophysiology of inflammation. This prospective, randomized, controlled study was designed to identify the most advantageous leucocyte depletion technique in terms of reduction in systemic inflammatory response syndrome and myocardial ischaemia reperfusion injury associated with cardiopulmonary bypass (CPB). Forty consecutive patients undergoing elective coronary artery bypass graft (CABG) surgery were randomly allocated to one of four groups. The four groups consisted of a control group, a systemic leucocyte depletion (SLD) group, a cardioplegic leucocyte depletion (CLD) group and a total leucocyte depletion (TLD) group. There were 10 patients in each group. Lactoferrin (marker of neutrophil activation) and troponin-I (marker of myocardial ischaemia reperfusion injury) were measured at six time points: post induction, 5 min on CPB, 5 min before releasing the aortic crossclamp, 15 min after releasing the clamp and 1 and 24 hours after the discontinuation of CPB. Plasma lactoferrin levels increased rapidly in every group after the commencement of CPB, subsequently reached a peak after releasing the aortic crossclamp and gradually declined after the discontinuation of CPB. The lowest lactoferrin concentration was observed in the TLD (range 2.15-141.9 ng/mL) and CLD groups (7.469-114.6 ng/mL). Regarding myocardial injury, plasma cardiac troponin-I levels did not differ significantly between groups; but troponin-I concentrations rose dramatically after releasing the aortic crossclamp in all groups. Nevertheless, the CLD group had the lowest troponin-I level (1.37-5.55 ng/mL). In conclusion, it is believed that myocardial ischaemia is probably a major contributor to the inflammatory response. Although there is no clear statistical significance shown in this pilot study, the data tend to support the cardioplegic leucocyte depletion strategy as the optimal method for attenuating neutrophil activation and myocardial ischaemia reperfusion injury.

The effect of haemodilution on blood-biomaterial contact-mediated CD11b expression on neutrophils:ex vivo studies

Modern cardiopulmonary bypass (CPB) systems are getting smaller, both in terms of the exposed surface area of biomaterials and the priming volume. In a series of studies utilizing a rat recirculation model, we demonstrated that the magnitude of the inflammatory response seen under these conditions is proportional to the surface area of exposed material, a finding that supports the use of miniature systems in terms of moderating the inflammatory response. However, the second impact of miniature perfusion systems, the reduced priming volume with concomitant reduction in haemodilution, was not investigated with reference to inflammation. The present study was designed to determine whether this change in CPB haematocrit profile has any effect on the inflammatory response. In common with previous studies by this group, we employed the expression of the integrin CD11b on neutrophils as a marker of neutrophil activation, and hence the inflammatory response, in a rat recirculation biomaterial testing model, containing di-(2-ethyl-hexyl)-phthalate plasticized polyvinyl chloride of the type commonly employed in CPB circuits. The results demonstrated that neutrophil activation is influenced by haemodilution. We studied five groups of animals, each with different mean induced haematocrit: Group 1 (41.39 /1.27%); Group 2 (30.939 /2.85%); Group 3(24.839 /1.36%); Group 4 (20.609 /3.47%); Group 5(20.489 /1.31%). Groups 1 and 5 animals were controls, neither of which underwent the period of recirculation. Rather, these controls were employed to isolate the noncontact effect of haemodilution on CD11b expression. We found that there were differences in per cent change in CD11b expression from start to end of the recirculation period between Group 1 (109.549 /49.53%), Group 2(189.19 /18.68%), Group 3 (224.289 /43.97), Group 4(368.979 /24.28%) and Group 5 (1279 /57.8%). There were intergroup statistically significant differences (p B /0.05). These results confirm that there is a relationship between haematocrit level and biomaterial contact-mediated activation of neutrophils. Furthermore, these studies confirm that haemodilution alone has no effect on neutrophil activation. One possible explanation for this outcome is that with higher levels of haemodilution, neutrophils have a greater opportunity to contact surface ‘receptor’ sites on the biomaterial, resulting in more neutrophil activation. Whatever the mechanism, these data tend to support the modern trend towards lower circuit surface area and higher haematocrit.

A prospective randomized study to evaluate the renal impact of surgical revascularization strategy in diabetic patients

Acute kidney injury (AKI) is a major postoperative complication following cardiac surgery. Diabetes mellitus is a major cause of nephropathy and end-stage renal failure. We aimed to evaluate the occurrence of adverse renal outcomes, in diabetic patients, between on-pump (CPB) and off-pump (OPCAB) coronary artery bypass graft (CABG). Seventy-one diabetic patients (36 and 35 patients in the CPB and OPCAB groups, respectively) were enrolled in a prospective randomized study. Renal tubular and glomerular functions, were monitored preoperatively and over five consecutive days. There was no significant difference between the groups in terms of age, gender, New York Heart Association class, Canadian Cardiovascular Society functional classification of angina grade and number of CABG. Intensive care unit stay, duration of intubation, hospital stay and bleeding were significantly higher in the CPB group. No significant differences in plasmatic creatinine, urinary creatinine, creatinine clearance, proteinuria or osmolality were detected. A significant rise in urinary albumine excretion occurred in both groups peaking on the operative day; for the on-pump CABG group (10±5 vs. 48±57; P=0.015) and for the OPCAB group (11±6 vs. 37±59; P=0.04). Values were less important in the OPCAB group and return to the baseline was faster than in the CPB group. OPCAB attenuates sub-clinical AKI, in diabetic patients.