A clinically relevant extracorporeal circulation model would be a valuable tool for investigating the pathophysiological and therapeutic strategies in whole blood. Previous models were limited by issues such as large circuit area; the inability to achieve full bypass; and donor blood requirement for prime. Here we established a miniature circuit to overcome these limitations consisting of a peristaltic pump, a test cell, a blood reservoir, and an oxygenator connected via polyvinylchloride and porous platinum silicon tubing. A heparinised (10 U/mL) saline solution at pH 7.4 was used to prime the circuit and the test cell was incubated in a water bath to maintain the temperature at 37°C. Blood flow through the circuit was at 5 mL/minute rate. Haemodynamics, haemoglobin concentration, and blood gases were analysed and the circuit performance was optimised according to the levels of haemolysis at three circulation time intervals: before the start, 30 minutes, and 60 minutes. No statistically significant haemodynamics and blood gases differences were observed. We have established a miniature extracorporeal circuit consisting of asanguineous prime for CPB model that maintains clinically acceptable results regarding hemodynamic parameters, blood gases, and haemodilution. This surrogate model would be important for further use in clinically pertinent research.
Cardiopulmonary bypass (CPB) is one of the major technological advances in medicine that allows operating in controlled conditions. Since its introduction in the 1950s, there has been a rapid growth in the number of cardiac surgical operations performed throughout the world. Though the mortality for many of these operations has fallen, CPB is still associated with a significant morbidity [
As shown in Figures
Schematic view of the
Overview of the blood recirculation model.
50 mL heparinised blood was taken from ischaemic heart disease (IHD) patients (
Plasma haemoglobin was used as an index of the level of haemolysis induced by flow conditions of the circuit. This was determined using the plasma haemoglobin assay from Sigma Diagnostics, Poole, UK as described previously [
(a) The effect of flow rate on plasma blood haemoglobin. (b) The effect of flow rate on haematocrit.
10 mL/minute | 5 mL/minute |
| |
---|---|---|---|
0 |
|
|
N/A |
10 |
|
|
<0.05 |
60 |
|
|
<0.05 |
240 |
|
|
<0.05 |
10 mL/minute | 5 mL/minute |
| |
---|---|---|---|
0 |
|
|
N/A |
10 |
|
|
<0.05 |
60 |
|
|
<0.05 |
240 |
|
|
<0.05 |
Changes with time of full blood count and gases for model and CPB samples
Sampling time (minutes) |
| ||||||
---|---|---|---|---|---|---|---|
Model | CPB | ||||||
0 | 30 | 60 | 0 | 30 | 60 | ||
PH |
|
|
|
|
|
|
NS |
pCO2 |
|
|
|
|
|
|
NS |
pO2 |
|
|
|
|
|
|
NS |
Hb (plasma) |
|
|
|
|
|
|
NS |
Hct |
|
|
|
|
|
|
NS |
Platelets counts × 109/L |
|
|
|
|
|
|
NS |
Total WBC × 109/L |
|
|
|
|
|
|
NS |
HB: haemoglobin; Hct: haematocrit; WBC: white blood cells count.
The use of
Some investigators had previously developed similar models as a primary goal without taking the next step of conducting research to simulate clinical CPB. Our model provides a platform for simulating the effect on blood alone when exposed to artificial surfaces of the extracorporeal circuit and of experimental conditions [
The evidence from these studies using this experimental model of blood has limitations which warrant discussion. First the preparation is superfused (surrogate blood circulation) as opposed to being arterially circulated. However, the preclusion of the vasculature as the natural pathway for the provision of substrate may also be advantageous in that confounding effects of the endothelial mediated inflammation and oxidative stress induced by ischaemia and reperfusion are separated. Secondly, although the model can be adapted for use in larger animal studies as it is, it is not appropriate for small animal studies (i.e., mice and rats) without significant modifications in the design.
In conclusion, we have characterised an extracorporeal blood recirculation model that is readily available; the preparation is inexpensive and stable for at least 4 h and above. This permits the researchers to effectively study a host of pathophysiological processes such as the mechanism of generation of oxygen free radicals and their roles in the induction of oxidative stress and proinflammatory factors in a laboratory setup. These types of study could help to establish the identity of the components that play the greatest part in inducing cytokine production and may represent a potential target for the reduction of the inflammatory reaction induced by CPB. In addition, the extended stability of the model may be potentially useful for studying the effect of genetic manipulation on pathophysiological mechanisms underlying injury sustained during ischaemia and reperfusion and developing new therapeutic strategies for combating undesirable effects.
The authors do not have any direct financial relation with the commercial identities mentioned in the paper.