The effects of cardiopulmonary bypass and deep hypothermic circulatory arrest on blood viscoelasticity and cerebral blood flow in a neonatal piglet model.

The purpose of this study is to determine the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on the viscoelasticity (viscosity and elasticity) of blood and global and regional cerebral blood flow (CBF) in a neonatal piglet model. After initiation of CPB, all animals (n = 3) were subjected to core cooling for 20 min to reduce the piglets' nasopharyngeal temperatures to 18 degrees C. This was followed by 60 min of DHCA, then 45 min of rewarming. During cooling and rewarming, the alpha-stat technique was used. Arterial blood samples were taken for viscoelasticity measurements and differently labeled microspheres were injected at pre-CPB, pre- and post-DHCA, 30 and 60 min after CPB for global and regional cerebral blood flow calculations. Viscosity and elasticity were measured at 2 Hz, 22 degrees C and at a strain of 0.2, 1, and 5 using a Vilastic-3 Viscoelasticity Analyzer. Elasticity of blood at a strain = 1 decreased to 32%, 83%, 57%, and 61% (p = 0.01, ANOVA) while the viscosity diminished 8.4%, 38%, 22%, 26% compared to the baseline values (p = 0.01, ANOVA) at pre-DHCA, post-DHCA, 30 and 60 min after CPB, respectively. The viscoelasticity of blood at a strain of 0.2 and 5 also had similar statistically significant drops (p < 0.05). Global and regional cerebral blood flow were also decreased 30%, 66%, 64% and 63% at the same experimental stages (p < 0.05, ANOVA). CPB procedure with 60 min of DHCA significantly alters the blood viscoelasticity, global and regional cerebral blood flow. These large changes in viscoelasticity may have a significant impact on organ blood flow, particularly in the brain.

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients.

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991-92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community-acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre-intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high-risk solid organ transplant patients.

Decrease in red blood cell deformability caused by hypothermia, hemodilution, and mechanical stress: factors related to cardiopulmonary bypass.

During extracorporeal circulation in cardiopulmonary bypass (CPB) surgery, blood is exposed to anomalous mechanical and environmental factors, such as high shear stress, turbulence, decreased oncotic pressure caused by dilution of plasma, and moderate and especially deep hypothermia widely applied during CPB in infants. These factors cause damage to the red blood cells (RBCs), which is manifest by immediate and delayed hemolysis and by changes in the mechanical properties of RBCs. These changes include, in particular, decrease in RBC deformability impeding the passage of RBCs through the microvessels and may contribute to the complications associated with CPB surgery. We investigated in vitro the independent and combined effects of hypothermia, plasma dilution, and mechanical stress on deformability of bovine RBCs. Our studies showed each of these factors to cause a significant decrease in the deformability of RBCs, especially acting synergistically. The impairment of RBC deformability caused by hypothermia was found to be more pronounced for RBCs suspended in phosphate buffered saline (PBS) than for RBCs suspended in plasma. The decrease in RBC deformability caused by mechanical stress was significantly exacerbated by dilution of plasma with PBS. In summary, results of our in vitro study strongly point to a possible detrimental consequence of conventional CPB arising from increased RBC rigidity, which may lead to impaired microcirculation and tissue oxygen supply.

Testing neonate-infant membrane oxygenators with the University of Texas neonatal pulsatile cardiopulmonary bypass system in vitro.

Neurologic complications are already well documented after cardiopulmonary bypass (CPB) procedures in neonates and infants. Physiologic pulsatile flow CPB systems may be the alternative to the currently used steady-flow CPB circuits. In addition to the pulsatile pump, a membrane oxygenator should be chosen carefully, because only a few membrane oxygenators are suitable for physiologic pulsatile flow. We have tested four different types of neonate-infant membrane oxygenators for physiologic pulsatility with The University of Texas neonate-infant pulsatile CPB system in vitro. Evaluation criteria were based on mean ejection time, extracorporeal circuit (ECC) pressure, and upstroke of dp/dt. The results suggested that the Capiox 308 hollow-fibre membrane oxygenator produced the best physiologic pulsatile waveform according to the ejection time, ECC pressure, and the upstroke of dp/dt. The Minimax Plus and Masterflo Infant hollow-fibre membrane oxygenators also produced adequate pulsatile flow. Only the Variable Prime Cobe Membrane Lung (VPCML) Plus flat-sheet membrane oxygenator failed to reach the criteria for physiologic pulsatility. Depending on the oxygenator used, the lowest priming volume of the infant CPB circuit was 415 ml and the highest 520 ml.

The type of aortic cannula and membrane oxygenator affect the pulsatile waveform morphology produced by a neonate-infant cardiopulmonary bypass system in vivo.

Although the debate still continues over the effectiveness of pulsatile versus nonpulsatile perfusion, it has been clearly proven that there are several significant physiological benefits of pulsatile perfusion during cardiopulmonary bypass (CPB) compared to nonpulsatile perfusion. However, the components of the extracorporeal circuit have not been fully investigated regarding the quality of the pulsatility. In addition, most of these results have been gathered from adult patients, not from neonates and infants. We have designed and tested a neonate-infant pulsatile CPB system using 2 different types of 10 Fr aortic cannulas and membrane oxygenators in 3 kg piglets to evaluate the effects of these components on the pulsatile waveform produced by the system. In terms of the methods, Group 1 (Capiox 308 hollow-fiber membrane oxygenator and DLP aortic cannula with a very short 10 Fr tip [n = 2]) was subjected to a 2 h period of normothermic pulsatile CPB with a pump flow rate of 150 ml/kg/min. Data were obtained at 5, 30, 60, 90, and 120 min of CPB. In Group 2 (Capiox 308 hollow-fiber membrane oxygenator and Elecath aortic cannula with a very long 10 Fr tip [n = 7]) and Group 3 (cobe VPCML Plus flat sheet membrane oxygenator and DLP aortic cannula with a very short 10 Fr tip [n = 7]), the subjects' nasopharyngeal temperatures were reduced to 18 degrees C followed by 1 h of deep hypothermic circulatory arrest (DHCA) and then 40 min rewarming. Data were obtained during normothermic CPB in the pre- and post-DHCA periods. The criteria of pulsatility evaluations were based upon pulse pressure (between 30 and 40 mm Hg), aortic dp/dt (greater than 1000 mm Hg/s), and ejection time (less than 250 ms). The results showed that Group 1 produced flow which was significantly more pulsatile than that of the other 2 groups. Although the same oxygenator was used for Group 2, the quality of the pulsatile flow decreased when using a different aortic cannula. Group 3 did not meet any of the criteria for physiologic pulsatility. In conclusion these data suggest that in addition to a pulsatile pump, the aortic cannula and the membrane oxygenator must be chosen carefully to achieve physiologic pulsatile flow during CPB.

Management of major tracheobronchial injuries: a 28-year experience.

BACKGROUND: Tracheobronchial injuries are rare but potentially life threatening. Their successful diagnosis and treatment often require a high level of suspicion and surgical repairs unique to the given injury. METHODS: We reviewed our experience with 32 patients with tracheobronchial injuries treated over the past 28 years. RESULTS: Forty-one percent (13/32) of the injuries were due to blunt trauma and 59% (19/32), to penetrating trauma. Most penetrating injuries were located in the cervical trachea (74%), whereas blunt injuries were more commonly located close to the carina (62%). Fifty-nine percent of the patients required urgent measures to secure the airway. Penetrating injuries were usually diagnosed by clinical findings or at surgical exploration. The diagnosis of blunt injuries was more difficult and required a high index of suspicion and the liberal use of bronchoscopy. The majority of the injuries were repaired primarily using techniques specific to the injury, and most patients returned to their normal activity soon after discharge. CONCLUSIONS: A high level of suspicion and the liberal use of bronchoscopy are important in the diagnosis of tracheobronchial injury. A tailored surgical approach is often necessary for definitive repair.

Error associated with the choice of an aortic cannula in measuring regional cerebral blood flow with microspheres during pulsatile CPB in a neonatal piglet model.

The effectiveness of an infant pulsatile cardiopulmonary bypass (CPB) system on maintaining regional cerebral blood flow (CBF) using two different types of aortic cannulae in 3 kg piglets has been investigated. The University of Texas Neonatal Pulsatile Pump was used with either a DLP (Group I, n = 6) or an Elecath (Group II, n = 7) 10Fr aortic cannula. In all the subjects, nasopharyngeal temperature was reduced to 18 degrees C, followed by 1 hr of deep hypothermic circulatory arrest (DHCA), then 45 min of rewarming. During cooling and rewarming, alpha-stat blood gas management was used. The radionuclide labeled microsphere technique was used to determine blood flows in the cerebellum, basal ganglia, brainstem, right and left hemispheres, as well as global CBF (ml/100 g/min). When the DLP aortic cannula was used, regional and global CBF appeared to be higher pre- and post DHCA. In both groups regional CBF was significantly decreased following DHCA. Although better pulsatile flow was attained using the DLP cannula and this may have resulted in higher regional CBF, these results must be interpreted in light of the large standard deviations noted when this cannula was chosen for the studies. These results demonstrate the importance of choosing an appropriate aortic cannula for measuring regional CBF with a pulsatile neonate-infant CPB system.

Pathophysiology of chest trauma.

Recent information indicates that there is a complex cellular and molecular generic response to injury that can lead to multi-organ failure. For many years, basic physiology and biochemistry were considered to be the systemic mechanisms to injury, but now it is known that subcellular and molecular events are the keys to unlocking the secrets of the body's response to trauma. The interaction of the endothelial cell with neutrophils and platelets to produce cytokines, free radicals, and upregulating adhesion molecules is especially significant.

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.

Regional blood flow during pulsatile cardiopulmonary bypass and after circulatory arrest in an infant model.

BACKGROUND: Pulsatile perfusion systems have been proposed as a means of improving end-organ perfusion during and after cardiopulmonary bypass. Few attempts have been made to study this issue in an infant model. METHODS: Neonatal piglets were subjected to nonpulsatile (n = 6) or pulsatile (n = 7) cardiopulmonary bypass and 60 minutes of circulatory arrest. Cerebral, renal, and myocardial blood flow measurements were obtained at baseline, on bypass before and after circulatory arrest, and after bypass. RESULTS: Cerebral blood flow did not differ between groups at any time and was diminished equally in both groups after circulatory arrest. Renal blood flow was diminished in both groups during bypass but was significantly better in the pulsatile group than in the nonpulsatile group prior to, but not after, circulatory arrest. Myocardial blood flow was maintained at or above baseline in the pulsatile group throughout the study, but in the nonpulsatile group, it was significantly lower than baseline during CPB prior to circulatory arrest and lower compared with baseline and with the pulsatile group 60 minutes after CPB. CONCLUSIONS: Pulsatile bypass does not improve recovery of cerebral blood flow after circulatory arrest, may improve renal perfusion during bypass but does not improve its recovery after ischemia, and may have beneficial effects on myocardial blood flow during bypass and after ischemia compared with nonpulsatile bypass in this infant model.

Dual-inflow great vessel aneurysm: delayed presentation after penetrating trauma.

Aneurysms constitute uncommon sequelae of injuries to the thoracic outlet. Most such aneurysms are secondary to blunt trauma and usually involve the great vessels at their take-off from the aortic arch. Penetrating injuries are more often identified in the more distal vessels and only very rarely present as pseudoaneurysms. Reported here is a single case of a chronic posttraumatic pseudoaneurysm arising from both the right common carotid artery and the right subclavian artery. The workup and surgical approach provide practical lessons, complemented with illustrations that aid in the understanding of the case. It is an unusual case because of the dual-inflow nature of the aneurysm.

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.

Systemic availability of itraconazole in lung transplantation.

Systemic availability of itraconazole in lung transplantation was evaluated by serially measuring the bioactivity of itraconazole in lung transplant patients who received itraconazole for prophylaxis (n = 12) or therapy (n = 5). These patients also received concomitant antacid and H2 blocker therapy. In patients receiving itraconazole at 200 and 400 mg/day, the median concentrations in serum were 0.5 microgram/ml (range, < 0.05 to 2.7) and 3.5 micrograms/ml (< 0.5 to 14), respectively. The concentration following administration of 400 mg/day was > 2.5 micrograms/ml in 56% of samples, while only 4% of samples from patients who were administered 200 mg/day had levels over 2.5 micrograms/ml. This study documents that itraconazole can be absorbed in patients receiving concomitant antacid and H2 blocker therapy. However, the reduced and variable absorption suggests the importance of confirming drug delivery by measurement of concentrations in serum.

Design and performance of a physiologic pulsatile flow neonate-infant cardiopulmonary bypass system.

The authors have designed an alternative infant cardiopulmonary bypass (CPB) system using the University of Texas neonatal pulsatile pump, which produces physiologic pulsatile flow and allows a low priming volume. This system has been tested with normothermic CPB (n = 8), and deep hypothermic circulatory arrest (n = 14) in 3 kg piglets. Data obtained during these studies suggest that this system can produce flow characteristics that approximate normal physiologic values. Unlike other pulsatile pumps, this pump can produce a very small stroke volume, ranging from 0.5 to 7.1 ml with a pump rate of 120 beats/min. These stroke volumes correspond to our target value of 1 ml/kg body weight. This system is designed to cause minimal hemodilution and minimal exposure of blood to foreign surface areas. The pump does not produce negative pressure, and therefore the venous reservoir is not essential, and only a cardiotomy reservoir is required. Conclusions after in vivo testing are, first, that physiologic pulsatile flow can be achieved readily with this system using a 10 Fr aortic cannula in 3 kg piglets; and second, that a significant reduction in priming volume and hemodilution can be obtained using this system.

Twelve-hour canine heart preservation with a simple, portable hypothermic organ perfusion device.

BACKGROUND: Cardiac transplantation is limited to an ischemic time of around 6 hours by available preservation solution and technique. Complex organ preservation devices have been developed that extend this time to 24 hours or more, but are clinically impractical. This study evaluates a portable oxygen-driven organ perfusion device weighing approximately 13.5 kg. METHODS: Organs are perfused with the University of Wisconsin solution at low perfusion pressure using less than 400 L of oxygen per 12 hours. Left ventricular parameters were measured in anesthetized adult beagles to establish control values (n = 5). Hearts were procured after cardioplegia with 4 degrees C University of Wisconsin solution, weighed, then stored for 12 hours in University of Wisconsin solution at 4 degrees C. Hearts were perfused (n = 3) or nonperfused (n = 2) during storage. Organ temperature, partial pressure of oxygen in the aorta and right atrium, perfusion pressure, and aortic flow were recorded hourly in perfused hearts. After 12 hours, hearts were transplanted into littermates and left ventricular parameters measured after stabilization off bypass. RESULTS: Organ weight for both groups was unchanged. Nonperfused hearts required both pump and pharmacologic support with significantly depressed left ventricular function. Perfused hearts needed minimal pharmacologic support, with left ventricular end-diastolic pressure, cardiac output, and rate of change of left ventricular pressure showing no statistical difference from control. CONCLUSIONS: These findings confirm the potential for extended metabolic support for ischemia-intolerant organs in a small, lightweight, easily portable preservation system.

Design of a physiologic pulsatile flow cardiopulmonary bypass system for neonates and infants.

Cardiopulmonary bypass surgical techniques that allow a surgeon to operate on the infant's heart use an extracorporeal circuit consisting of a pump, oxygenator, arterial and venous reservoirs, cannulae, an arterial filter, and tubing. The extracorporeal technique currently used in infants and neonates is sometimes associated with neurologic damage. We are developing a modified cardiopulmonary bypass system for neonates that has been tested in vitro and in one animal in vivo. Unlike other extracorporeal circuits which use steady flow, this system utilizes pulsatile flow, a low prime volume (500 ml) and a closed circuit. During in vitro experiments, the pseudo patient's mean arterial pressure was kept constant at 40 mmHg and the extracorporeal circuit pressure did not exceed a mean pressure of 200 mmHg. In our single in vivo experiment, the primary objective was to determine whether physiologic pulsatility with a 10 F (3.3 mm) aortic cannula could be achieved. The results suggest that this is possible.