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Higher morbidity and mortality rates are seen after the use of cardiopulmonary bypass in infants and elderly patients. Clinical procedures acceptable for adult patients may not be acceptable for them. Infants require more effective tissue gas exchange or tissue perfusion because of their active metabolic status. On the other hand, vascular systems of elderly patients are more rigid and do not have enough reserve capacity for nonpulsatile perfusion compared to young adults. More effective tissue perfusion is needed for them during cardiopulmonary bypass. Traditionally, we utilize a nonphysiological, non-pulsatile pump and perfuse the patients with bypass flows below their resting cardiac outputs (70–80%). In our experience, in general, it is necessary to have approximately 20% higher cardiac output in cases where we use a nonpulsatile mode of total body perfusion compared with a pulsatile mode of perfusion. In addition, higher bypass flow is expected to be required for infants because of their higher metabolic rate and for elderly patients because of their more rigid vascular structure.

Sergei S. Brukhonenko designed and constructed one of the earliest heart-lung machines. He was the first to experimentally perform a total body perfusion with the heart of the animal isolated from the circulation. His work paved the way to the first experimental operations on heart valves. Although Brukhoneko's pioneering contributions have not received the recognition they deserve, his work represents an important landmark in cardiac surgery.

Mechanical systems to oxygenate blood outside of the body were first employed in clinical medicine as a component of the «heart-lung machine». The artificial lung has been an essential component of the technology underlying the progress of cardiovascular surgery since 1950. Its impact on clinical medicine can be measured by the widespread acceptance of cardiac surgery for the treatment first of congenital malformations, then valvular lesions, and more recently, coronary artery disease. Whereas the use of the artificial lung during temporary exclusion of the pulmonary circulation for surgical purposes is now well established, the chronic application of extracorporeal membrane oxygenation in end-stage respiratory failure is still controversial. Internally implantable lung prostheses are still at the conceptual or developmental stage, and are unlikely to impact on clinical medicine for another decade.

Cardiopulmonary bypass with 17 to 57 per cent dilution of hemoglobin for repair of ventricular septal defect (VSD) was applied to 26 infants weighing less than 10 kg at normal temperature. The higher flow rate was required to compensate the reduced oxygen carrying capacity and to maintain an adequate arterial pressure in proportion to a decrease of hemoglobin value. Perfusion index resulted in 3.0 to 6.5 L/m2/min in this series. When the dilution ratio of hemoglobin became more than 50 per cent and high flow rate was required, however, oxygen transfer ratio decreased remarkably on account of inadequate oxygen delivery and imparied venous return. In these cases, it was difficult to remove the diluent immediately after the operation in spite of powerful diuretic therapy. The results of the present study indicate that the safe limits of hemodilution is 50 per cent in cardiopulmonary bypass at normal temperature in infants.

An analysis of 541 patients having total body perfusion under hypothermia (30°–33°C) showed that the use of pulsatile as against constant flow perfusion was not associated with a reduction in bicarbonate requirement, though the use of a vasodilator was. The implications of this are discussed.

A survey of the present status of extracorporeal circulation in open heart surgery revealed that the pump oxygenator has been widely accepted around the world, and various kinds of heart disease, especially congenital, have been cured surgically with a reasonable degree of safety. The film-type oxygenator, either disc or screen, is the one most commonly used. High flow rate, nearly equivalent to cardiac output in the normal circulation, is considered advantageous in total body perfusion. The combination of hypothermia with the pump oxygenator is still a debatable issue.

As considerable and widespread interest in open cardiac surgery has developed, many papers have appeared describing the various techniques and results with use of extracorporeal circulatory systems. However, the important aspects of pre and postoperative care of the open heart patients have received much less attention. This omission is indeed significant for given a group of cardiac patients with a good total body perfusion and a good surgical repair of their cardiac lesions, the difference between a very low operative risk and a higher mortality is often made by the attention given to details of management in the immediate pre and postoperative intervals. Therefore, it may be of value to others to examine suggestions based on experiences gained at the University of Minnesota Hospitals during the past five years in which period more than 700 open cardiac operations were performed.

Continuous measurement of blood Po2, Pco2, and pH can be made either with intravascular electrodes or with electrodes placed in a flow cuvette. The two methods are reviewed. In this study a system based on the Radiometer flow cuvette was used. The continuous recording was checked at intervals against results obtained by conventional electrode analyses of individual blood samples. The continuous recording and individual checks were virtually identical. Checks on electrode calibration were made after 4–5 hours use, and no significant electrode drift was noted. During perfusion with Rygg-Kyvsgaard bubble-oxygenator, variations in Po2, Pco2 and pH were measured continuously in dogs to register any changes, which might occur in the transition to and from perfusion, and which would be too rapid for measurement by the single sample technique. Apart from catheterization of the venae cavae through the right atrium the heart was undisturbed. In the first minutes of perfusion marked falls in all three parameters wer...

The technic of total body perfusion with a pump oxygenator system has been used to extend pressure flow studies to the circulation as a whole. The effect of alterations in vasomotor tone on both total peripheral resistance and pressure flow relationships has been investigated by surgical ablation of the central nervous system or administration of vasoactive drugs. Certain aspects of the results obtained are discussed in relation to the concept of critical closing pressures.

SUMMARY Blood which is spilled into the pericardial cavity is rapidly hemolyzed. The return of this blood to the pump oxygenator is the major source of free plasma hemoglobin in total body perfusion.

Summary A preliminary study of the suspension of animation incorporating a modified model of Neely's indicates that survival may be possible in a reasonable number of experimental animals after a period of 60 min of asanguineous perfusion. Although all measurable parameters of biological activity appear to be considerably reduced, initial studies suggest that some metabolic processes continue, even at markedly reduced temperatures. There is no evident neurological damage in the surviving dog. However, electrocardiography demonstrates changes that may prove to be associated with permanent morphological changes as well. The latter aspect is still under investigation. The potential use of the Neely model for studying complex questions of physiology in the intact organism is tenable, and further exploration of the technique is justified.

A disposable blood oxygenator with built-in temperature controlling element is described. It is made with a semirigid housing of a clear polycarbonate plastic (Lexan). Within the housing is a bubble oxygenating system incorporating within its reservoir a canister providing 270 square inches of temperature exchanging surface.

Acute viral hepatitis complicated by coma carries an extremely poor prognosis. If coma supervenes, it is rare that more than 2o% of patients survive. Exchange transfusions increase the incidence of patients' survival to no more than 35%, and other generally known treatments have less effect. It was found that asanguineous hypothermic total body perfusion (total body wash-out) increased the incidence of the patients' survival to almost 70%. The treatment of acute infectious hepatitis with coma is assisted by the use of total body wash-out. The criteria for patient selection and the optimum timing of the procedure are defined and the method is described in detail.

Use of a commercially available disposable membrane oxygenator for total body perfusion and open heart surgery has been evaluated in clinical cases. Preliminary data indicate excellent oxygenation and minimal trauma to blood under conditions requiring prolonged perfusion. Two perfusion circuits are described. One has an intrinsic recirculating circuit to minimize pressure exerted on the membrane and multiple oxygenator units combined in series. The other utilizes gravity venous drainage directly into the multiple oxygenator units which are arranged in parallel to decrease resistance to gravity flow. Eighteen patients were perfused with the first method. Three have been perfused with the second. Physiologic data from both groups are presented. The technical advantages and disadvantages of each of the methods are described. Both methods are adequate for perfusion. The latter method of perfusion seems more desirable because the technicians have 1 less pump to operate and therefore can be more accurate in their control of total body perfusion.

Oozing of blood from wound tissues after some time of total body perfusion and the demonstration of microemboli have brought into focus the inevitable disappearance of platelets from the blood during extracorporeal circulation. Recirculation experiments using dog blood are reported. The effect of a bubble oxygenator and a membrane oxygenator is compared. It is concluded that in principle they both contribute to the removal of functionally active platelets.

The success of Alexis Carrel with innovative vascular surgical techniques added a great deal of stimulus to the previously rather mild efforts of developing a pump suitable to perfuse organs or the entire body. The noted aviator Charles Lindberg joined Dr. Carrel in a dedicated effort to develop a blood pump suitable for total body perfusion. Their device was intended to facilitate the surgery necessary to correct myocardial defects which had been identified at that time. It is obvious that their progress would have been far greater had suitable anticoagulants been available. This concentrated program, along with other gallant efforts in attempting to perfect a blood pump that could be used for cardiopulmonary bypass (CPB), was fraught with many difficulties, not the least of which was the lack of a suitable anticoagulant. Some early pioneers had even speculated on the development of a total artificial heart [1]. Numerous accomplishments combined to bring a mechanical blood pump to the clinical theater in the early 1950s [2].

In patients undergoing open cardiac surgery there are substantial differences in acidbase balance, preoperatively, between acyanotic and cyanotic patients. Metabolic studies on patients undergoing total body perfusion by means of a bubble oxygenator show the arterial pH values for all 84 acyanotic patients were within the range of normal at the termination of the bypass, and in 31 cyanotic patients the arterial pH remained at the control level—somewhat acidotic. Other physiological responses have been measured to achieve the goal of providing for the patient an optimum perfusion volume plus a margin of safety to allow for biological variations. This goal is obtained by monitoring each bypass procedure by means of a continuous recording of the patient's electroencephalogram and systemic blood pressure, and adjusting thereafter the perfusion rate to keep these variables normal or near normal.

SUMMARY 1.The effect of total body perfusion on digitalis tolerance was studied clinically in 84 infants and children undergoing open heart surgery and experimentally in eight mongrel dogs subjected to total body perfusion. 2.The clinical studies consisted of comparison of immediate postperfusion electrocardiograms to preperfusion electrocardiograms. There was no statistically significant difference between the incidence of postperfusion electrocardiographic arrhythmias in patients who had been digitalized prior to perfusion and in patients who had not received digitalis. Additionally there was no correlation between the incidence of postperfusion arrhythmias and the degree of the preperfusion electrocardiographic evidence of digitalis effect. 3.Studies of the effect of perfusion on digitalis tolerance in the dog were performed both for digitalis administered prior to perfusion ("tissue fixed") and for digitalis administered following perfusion. Perfusion was associated with no significant change in sensitivity to "tissue fixed" digitalis; however, all of the animals tested showed a decreased tolerance to digitalis administered one hour following perfusion. Decreased tolerance to digitalis persisted at four hours in 80 per cent of animals and at seven hours in 40 per cent of animals. 4.The application of this information to the administration of digitalis to patients undergoing open heart surgery is discussed.

Six dogs were subjected to asanguineous total body perfusion, hypothermia, and hyperbaric oxygenation for periods up to 2 hrs. After a brief recovery of, vital functions all dogs died. Pancreatitis was a consistent finding at autopsy.

In the period immediately following total body perfusion for open cardiotomy, careful evaluation and management of the patient is required. While physiologic studies carried out during this period are designed principally to give proper direction to the postoperative care of the patient, they may also be used as a measure of the adequacy of perfusion and the functional state of the cardiopulmonary systems. Materials and Methods The data to be presented were obtained during perfusion and in the immediate postoperative period in a group of 10 consecutive patients operated upon for a variety of congenital cardiac defects. One of the patients was mildly cyanotic; the other nine were acyanotic. The patients ranged in age from 1 to 15 years and in weight from 6 to 43 kg. With all patients the Clark oxygenator pump 1 was used. The period of total body perfusion varied from 15½ to 59 minutes. Seven of

SUMMARY In eight out of eleven patients investigated, the arterial carbon dioxide tension was higher in the period immediately after total cardiopulmonary bypass than before, although the minute volume delivered from the ventilator was unchanged. It was concluded that the increased carbon dioxide tension was due to an increase in physiological deadspace. Possible causes are discussed.

Calculations of arterial elastic coefficients of dogs under conditions of total body perfusion have been made by utilizing the pressure data obtained from steady state perfusion and inflow stoppage. This was done by finding the first derivative of the pressure-time curve after inflow stoppage and evaluating this at the starting time of the transient. This "zero" time slope gave the value of the elastic coefficient divided by the resistance at the instant of inflow stoppage, and multiplying this ratio by the resistance evaluated from the immediately preceding steady state conditions gave an estimate of the elastic coefficient, E, of the arterial tree. Drugs were used to alter the resistance, and this permitted an estimate of E under various conditions. The value of E appeared to be a function of arterial pressure, and the value at a pressure of 124 mm Hg was 4,080 dynes/cm5.

The perfusion rates of the brain, intestine and heart ventricle were studied under conditions of total body perfusion. The perfusion rates were estimated by using antipyrine and D2O as reference substances. Local flow was determined from arterial curves and tissue analysis. When the total body perfusion rate was varied between 20 and 80 cc/kg/min., it was found at each rate that the perfusion rate of these organs was over three times that of the body as a whole. At the lowest flows these three organs were favored even more. Tables of perfusion rates at various sites in the brain and intestine are given. Pressure-flow curves for the brain, intestine and heart are given.

A membrane-covered silver-lead fuel cell is desceibed which gives an output voltage proportional to the oxygen partial pressure in the environment to which the membrane is exposed. The device produces a constant output voltage in the temperature range 10° to 40° C when used in conjunction with a temperature compensation circuit. The fuel cell is used to monitor continuously the arterial oxygen partial pressure during whole body perfusion.

IN THE PAST 6½ years nearly 1,500 total body perfusions have been performed at this center and many thousands elsewhere. "Things are never so good that they might not be better" and this philosophy has stimulated us to reexamine our techniques for total body perfusion for open cardiotomy in light of our own experience and that of others. Promoters of the maximum flow techniques have not provided any convincing evidence that their more complicated methods have superiority, nor have the "deep coolers" in their efforts to achieve technical simplicity provided results, at least to date, that are likely to warm the hearts of their confreres. From the time open heart surgical procedures began there has been a trend towards increasingly complex pump-oxygenators, heating exchange units, numbers of personnel required, more complicated ancillary monitoring devices, and greater blood priming requirements, without any corresponding decrease in patient morbidity and mortality. It has

NOT since the time of Hippocrates has the diagnostic value of the arterial pulse been disputed. Yet its role in physiology is considered of little, if any, consequence. Typical of this attitude was Wesolowski's1 statement that "the presence of the pulse may represent nothing more in physiological terms than an expression of the limitations of the organic heart design." Indeed, this concept is reflected by clinicians using "nonpulsatile"† delivery of blood during partial and total body perfusion. We should like to propose that a review of the physiologic disturbances encountered in "nonpulsatile" perfusion and a consideration of the progressive phylogenetic . . .

To the Editor.— Recently we published an article citing our initial experience with asanguineous hypothermic total body perfusion (total body washout or TBW) in the resuscitation of a patient dying of stage IV hepatic coma. 1 The patient went on to die of Pseudomonas pneumonia which was present prior to the performance of the TBW. That partial success served to teach us to be more selective of future candidates and to make certain adjustments in our perfusate. These were done in our latest attempt to use the procedure in the care of a young airman dying of acute Australia antigen hepatitis. The airman had been ill and hospitalized for four weeks prior to transfer to our hospital. In the fifth week of his illness and in spite of intensive therapy with bowel antisepsis, steroids, and modified diet, he lapsed into a deepening coma. When received at our hospital, the patient

Fifty dogs have been perfused at flow rates of between 5 and 100 cc/kg/min. with complete cardio-pulmonary bypass for up to three hours using a pump-oxygenator. There was an approximately linear relationship between pressure and flow. Extrapolation to zero flow produced an intercept on the pressure axis of approximately 20 mm Hg. Calculated total systemic resistance was more uniformly related to flow than to pressure. Coronary blood flow did not correlate with perfusion pressure. There was, however, an inverse relationship between perfusion rate and the percentage of total flow passing through the coronary bed. Coronary resistance decreased with perfusion time whereas total systemic resistance rose initially and then declined. Total peripheral resistance in these open chest perfused animals was one to two times the accepted normal for the intact dog. The actual value varied with the anesthetic agent used.

A paracorporeal left ventricular assist device (LVAD) with a capacity to pump 8 L/min of blood was employed in a clinical trial, and this report details the first survivor. A 60-year-old man could not be separated from the pump oxygenator following coronary artery bypass grafting, and, therefore, an LVAD was employed. Almost the entire left ventricular workload was assumed by the mechanical pump so that the myocardium was allowed to rest and recover. The LVAD support was continued for 105 hours. It provided satisfactory total body perfusion with maintenance of good hemodynamics—without serious deleterious effects on hematologic factors. The patient is alive and active without cardiac symptoms 16 months after his operation. The total experience with 13 LVAD implantations warrants continuation of the clinical trials in selected patients. (JAMA243:46-49, 1980)