An object-oriented modelling framework for the arterial wall.

An object-oriented modelling framework for the arterial wall is presented. The novelty of the framework is the possibility to generate customizable artery models, taking advantage of imaging technology. In our knowledge, this is the first object-oriented modelling framework for the arterial wall. Existing models do not allow close structural mapping with arterial microstructure as in the object-oriented framework. In the implemented model, passive behaviour of the arterial wall was considered and the tunica adventitia was the objective system. As verification, a model of an arterial segment was generated. In order to simulate its deformation, a matrix structural mechanics simulator was implemented. Two simulations were conducted, one for an axial loading test and other for a pressure-volume test. Each simulation began with a sensitivity analysis in order to determinate the best parameter combination and to compare the results with analogue controls. In both cases, the simulated results closely reproduced qualitatively and quantitatively the analogue control plots.

Oxygen transport and consumption during experimental cardiopulmonary bypass using oxyfluor.

To evaluate a perfluorocarbon based oxygen carrier (Oxyfluor), a porcine model of cardiopulmonary bypass (CPB) was implemented. Swine (30 kg) were subjected to 2 h of normothermic CPB using Oxyfluor (OF group, n = 8) or Ringer's lactate (RL group, n = 13) as the prime. Mean arterial pressure (MAP) was kept at 50 mm Hg, flow rate at 80 ml x min(-1) x kg(-1), and PaCO2 at 35 mm Hg. Hemodynamic, hematologic, fluid balance, and blood gasimetry variables were measured. Total body oxygen delivery (DO2), consumption (VO2), and the fractional contribution to delivery (FCD) and to consumption (FCC) of the red blood cells (RBC), PFC, and plasma phases were calculated. Mixed venous PO2 (PvO2) was significantly higher at 30 min and 1 h on CPB in the OF group than in the RL group. FCCRBC was significantly lower at 30 min, 1 h, and 90 min on CPB in the OF group than in the RL group. PvjO2, Ca-vO2, Ca-vj O2, and VO2 were slightly higher in the OF group than in the RL group. Tissue fluid accumulation was not alleviated with Oxyfluor, and tissue and brain acidosis were significantly increased in the OF group. This study presented evidence that Oxyfluor improved tissue oxygenation and total body oxygen consumption during experimental CPB. In addition, Oxyfluor reduced FCCRBC, increasing oxygen transport reserve of the RBC phase, which can be useful to reduce hypoxic events during CPB. Further research should be conducted to optimize PFC-OCs for use in CPB and to reduce secondary effects.

Description of a project for the production and evaluation of oxygen-carrying hemosubstitutes.

Scarce availability and risk of transmission of infections and diseases (HIV, hepatitis B, Chagas' disease) limit the use and benefits of homologous blood transfusions for surgical purposes. Recent trials of perfluorocarbon-based hemosubstitutes (PFC-HSs) in experimental cardiopulmonary bypass (CPB) have demonstrated their ability to improve brain oxygenation, as compared with conventional crystalloid priming solutions. The objective of the project described here is to test different formulations of PFC-HSs and optimize their formulation and dosage for use in CPB. The project includes: (1) study the feasibility of implementing a laboratory for small scale production of PFC-HSs; (2) evaluate the efficacy of use of PFC-HSs in an animal model of CPB; and (3) evaluate the safety of use of PFC-HSs in an animal model of hemorrhagic shock. Several in-house PFC-HSs and outside PFC-HSs are being evaluated. The current state of the project is: (1) the feasibility study has been completed and several PFCs, emulsifiers and surfactants are being tested; (2) and (3) the animal models have been implemented are being used to test in-house and outside PFC-HSs as priming solutions in CPB and reinfusion fluids in hemorrhagic shock respectively. Some preliminary results are presented.

Enhancement of brain p0(2) during cardiopulmonary bypass using a hyperosmolar oxygen carrying solution.

During the past decade a new syndrome has been recognized: cerebral hypoxia secondary to cardiopulmonary bypass, resulting in impairment of cognitive memory. The incidence of the syndrome appears to be no less that 30% in patients over 65 years of age undergoing cardiac surgery. There are several factors contributing to hypoxia produced by cardiopulmonary bypass. One of these factors is crystalloid pump prime and replacement solutions devoid of (1) oxygen carrying capacity and (2) devoid of protein and its colloid osmotic pressure. This shortcoming of cardiopulmonary crystalloid solutions is partially responsible for two of the three major pathologic effects of cardiopulmonary bypass: (1) hypoxia (2) interstitial fluid accumulation (anasarca, water-logging, edema). This report describes an oxygen carrying hyperosmolar solution which enhances brain p0(2) and diminishes interstitial fluid accumulation. This blood substitute consists of perfluorcarbons and saccharides, but could consist of a hemoglobin variant plus hyperosmolar ingredients other than saccharides. The advantage of a perfluorochemical is its ability to access small channels and to be centrifuged off the patient post-operatively with a cell saver. The advantage of saccharides is that they can be metabolized by the patient for energy, and they produce a moderate diuresis coming off bypass.

Changes in brain pH, PO2, PCO2, cerebral blood flow, and blood gases induced by a hyperosmolar oxyreplete hemosubstitute during cardiopulmonary bypass.

Eleven goats (mean weight, 69 +/- 16 kg) underwent 5 hrs of normothermic nonpulsatile cardiopulmonary bypass (CPB) using as priming fluid either a Ringer's based crystalloid priming solution (CP, n = 5) of a hyperosmolar oxyreplete hemosubstitute (HS, n = 6). The HS contained 20% w/v perfluorocarbon (perfluorodecalin), its osmolarity was 800-900 mOsm/1, and the administered dose of perfluorocarbon was 30-50 ml/kg. Otherwise, the experimental procedure was identical for both groups. PaCO2 was maintained above 35 mmHg and blood flow rate at 65 ml/kg. Brain tissue pH, PO2, and PCO2, cerebral blood flow (CBF), arterial and venous blood gases, and other systemic variables were monitored. During CPB, PVO2 and brain tissue PO2 were increased significantly in the HS group. The CBF per kilogram of weight also was significantly higher in the HS group. Metabolic acidosis developed in both groups and, surprisingly, brain tissue pH and pHV were lower in the HS group. The mean values of PVCO2 and brain tissue PCO2 indicate that brain tissue hypercapnia also occurred in both groups. The HS provided long-term stability and compatibility with electrolytes, and did not cause major complications or allergic reactions during CPB. Perfluorocarbon based HSs improve tissue oxygenation, eliminate the risk of infection due to homologous transfusions, do not require blood type matching, have a shelf life longer than that of blood, and, therefore, they can be an important factor in diminishing the incidence of complications after CPB.

Monitoring of blood gases during prolonged experimental cardiopulmonary bypass and their relationship to brain pH, PO2, and PCO2.

Eight adult goats under went 5 hr of normothermic cardiopulmonary bypass (CPB) with pulsatile (n = 3) and nonpulsatile flow (n = 5). PaCO2 was maintained at 30-40 mmHg and blood flow rate at 50 ml/min/kg. Brain tissue pH, PO2, and PCO2, arterial and venous blood gases, and other systemic variables were monitored. No significant differences in brain electrochemistry between pulsatile and nonpulsatile perfusion were observed owing to the large variability of the results and the small number of experiments. The overall data for brain tissue pH, PO2, and PCO2 were analyzed and compared to the results of arterial and venous pH, PO2, and PCO2. Brain acidosis developed at the onset of bypass, and the values for brain tissue pH dissociated from those of blood pH, suggesting that hemodilution and the initial body response to CPB are involved in its development. Brain hypercapnia also developed during CPB, the values of brain tissue PCO2 dissociated from those of blood PCO2, and brain hypercapnia appears to be secondary to brain acidosis. Brain tissue PO2 closely followed the values of PvO2, suggesting that PvO2 can be an indicator of brain tissue PO2 during normothermic CPB and must be monitored during the procedure. Brain tissue acidosis is evidently related to neurologic dysfunction after CPB, and must be addressed. Replacement of the priming solution with whole blood or artificial blood, reduction of the priming volume, and application of vigorous pulsatile flow appear feasible interventions to mitigate brain tissue acidosis during CPB.

Hemodialysis: evidence of enhanced molecular clearance and ultrafiltration volume by using pulsatile flow.

We describe several in vitro experiments showing evidence that pulsatile flow hemodialysis enhances ultrafiltration volume and molecular clearance as compared with steady flow hemodialysis. A new pulsatile pump and a conventional roller pump were compared using different hollow fiber dialyzers and a simulated blood solution containing urea, aspartame and vitamin B-12 at different flow rates and configurations. Ultrafiltration volume and concentration of urea, aspartame and B-12 were measured and molecular clearance (K) calculated. Ultrafiltration volume markedly increased with pulsatile flow. After 10 min K for urea with pulsatile flow was higher in all experiments even when ultrafiltration was prevented. Clearance of aspartame and B-12 also increased with pulsatile flow. We propose three mechanisms by which pulsatile flow is more efficient than steady flow hemodialysis: greater fluid energy, avoidance of molecular channeling and avoidance of membrane layering. We hypothesize that using pulsatile flow in hemodialysis can significantly shorten the duration of dialysis sessions for most of the patients, and consequently reduce the duration of the procedure and its cost.

Achievement of physiologic pulsatile flow on cardiopulmonary bypass with a 24 French cannula.

In 1990, the NIH formally recognized the need for investigation of the problem of damaging the effects of cardiopulmonary bypass, issuing RFA HL-90-12-H, which emphasized production of neurologic defects in the very young and the elderly. The authors were at that time involved in comparison of pulsatile flow to steady flow cardiopulmonary bypass in large ungulates. The world literature recognizes five damaging effects of steady flow cardiopulmonary bypass that can be mitigated by pulsatile flow: metabolic acidosis, interstitial fluid accumulation, elevated systemic vascular resistance, arteriovenous shunting, and impaired brain oxygenation. To maximize the beneficial effect of pulsatile flow, however, it is necessary that its morphology be physiologic. It has been stated in the past that this goal may not be possible using standard size aortic cannulas. The purpose of this publication is to describe a method by which this feat has been achieved in 150 pound ungulates undergoing prolonged cardiopulmonary bypass.

Tubing spallation in extracorporeal circuits. An in vitro study using an electronic particle counter.

The roller pump is the most common pumping device used in extracorporeal circulation (ECC). The interaction between the roller and tubing causes tubing spallation. Spallation has been associated with complications in ECC. Previous spallation studies present mixed results, including a decrease in the number of circulating particles. The objective of this work is to perform an in vitro study of tubing spallation which elucidates the causes of the particle sequestration, and the effect of tubing material, blood flow rate and duration of the procedure upon spallation. A sampling method minimizing background counts was devised. Silicone and PVC tubing were tested under normal and tight occlusion pressure at typical cardiopulmonary bypass and hemodialysis flow rates, for circulating times up to 4 h. Occlusion pressure and flow rate highly influenced the amount of spallation produced. Particle sequestration was noted and aggregation of the plastic particles was demonstrated. We conclude that, at least in vitro, aggregation causes the decrease in the particle counts and the misleading results obtained in most spallation studies using a Coulter counter.