Control of inflammation decreases the need for subsequent esophageal dilation in patients with eosinophilic esophagitis.

It is unknown if successful control of esophageal inflammation in eosinophilic esophagitis (EoE) decreases the need for subsequent esophageal dilation. We aimed to determine whether histologic response to topical steroid treatment decreases the likelihood and frequency of subsequent esophageal dilation. We conducted a retrospective cohort study. Patients with an incident diagnosis of EoE were included if they had an initial esophageal dilation, received topical steroids, and had a subsequent endoscopy with biopsies. The number of dilations performed in each group was determined, and histologic responders (<15 eos/hpf) were compared to nonresponders. The 55 EoE patients included (27 responders and 28 nonresponders) underwent a mean of 3.0 dilations over a median follow-up of 19 months. Responders required fewer dilations than nonresponders (1.6 vs. 4.6, P = 0.03), after adjusting for potential confounders. Despite undergoing significantly fewer dilations, responders achieved a similar increase in esophageal diameter with dilation (4.9 vs. 5.0 mm; P = 0.92). In EoE patients undergoing esophageal dilation at baseline, control of inflammation with topical steroids was associated with a 65% decrease in the number of subsequent dilations to maintain the same esophageal caliber. This suggests that inflammation control is an important goal in patients with fibrostenotic changes of EoE.

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.

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.

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.

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.

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.

A single pulsatile pump for total biventricular cardiac support using patient lung ventilation.

An extracorporeal pulsatile heart pump has been modified to render biventricular cardiac support while maintaining automatic volume balance between the left and right sides. The device consists of two independent fluid circuits, externally valved and compressed by a common pusher plate configuration. Because the pusher plate compresses both circuits simultaneously, the volume-heavy side is unloaded via larger stroke volumes until the two sides achieve a balanced stroke volume. The process is automatic from beat-to-beat and is not dependent upon external pressure or flow transducers to maintain equilibrium. Two in vivo studies in pigs weighing 25 kg have demonstrated the feasibility of the concept, with physiologic aortic and pulmonary artery flow during 2 hr of ac-induced ventricular fibrillation and oscillatory ventilator support via left atrium-to-aorta and right atrium-to-pulmonary artery cannulation. Efforts to scale up to human adult size requirements have resulted in in vitro outputs of up to 7.0 L/min in each circuit.

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.

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.

Comparison of a steady flow pump to a preload responsive pulsatile pump in left atrial-to-aorta bypass in canines.

A unique preload responsive pulsatile pump was compared to a centrifugal pump in total cardiac support in 25-kg canines (n = 6, each group) in the left atrial-to-aorta mode during 5 h of ventricular fibrillation. With steady flow, there was immediate drop in output from 2.1 +/- 1.0 L/min to 1.4 +/- 0.3 L/min, followed by further reduction to 0.9 +/- 0.2 L/min during 5 h of ventricular fibrillation. With a pulsatile pump, there was no significant reduction from control of 2.4 +/- 0.6 L/min and no decline during 5 h of ventricular fibrillation. With steady flow, systemic vascular resistance (SVR) rose significantly from 1,762 dyne-s-cm-5 immediately on pump to 3,013 dyne-s-cm-5 at 5 h. With physiologic pulsatile flow, significant elevation of SVR did not occur. When stressed, due to diminished left atrial return, the centrifugal pump displayed line chatter and streaks of microbubbles, whereas the pulsatile pump did not. Crystalloid volume replacement with the centrifugal pump was 6.5 +/- 1.9 L, and with the preload responsive pulsatile pump, 5.6 +/- 1.3 L. It is concluded that in the left atrial-to-aorta mode during 5 h of ventricular fibrillation and with comparable volume replacement, total cardiac support of canines is associated with lower SVR with physiologic pulsatile flow and is not accompanied by line chatter and cavitation with this preload responsive pump.

Preload-responsive, pulsatile-flow, externally valved pump: cardiopulmonary bypass.

Currently two pumps are used for cardiopulmonary bypass, the roller pump and the centrifugal or vortex pump. Both are steady-flow pumps. The procedure of cardiopulmonary bypass possesses a finite morbidity and mortality. The degree to which steady flow is responsible for this morbidity and mortality remains to be clarified, but investigators have established the fact that a physiologic degree of pulsatile flow must be achieved before its beneficial results, such as normal systemic resistance and absence of lactate production, can be demonstrated. Availability of a satisfactory pulsatile pump for cardiopulmonary bypass has been a problem in the past but the pump presented here may satisfy this need. It produces physiologic pulsatility with rate dependent ejection time equal to or less than that of humans (413 microseconds minus 1.7 times heart rate), and it is preload-responsive, varying its pumping rate and output with filling pressure. The pump is externally valved to minimize hemolysis, which has been demonstrated in two laboratory studies to be significantly less than with the roller pump. It produces pulsatile flow through membrane oxygenators. The pump is thought to have potential for several clinical applications in addition to (1) pulsatile-flow cardiopulmonary bypass, including (2) left, right, or combined transthoracic QRS synchronized ventricular assist, (3) femoral vein to femoral artery QRS synchronized left ventricular assist, (4) adult or infant ECMO, (5) pulsatile flow hemodialysis. In the latter, spallation and embolization of hemodialysis tubing particles should not be a problem as has proved to be the case with the present hemodialysis pump.