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To investigate the drive condition of the artificial heart from a neurophysiological point of view, the dynamic transduction characteristics of the baroreflex system were analyzed by means of sympathetic neurograms. Two pneumatically actuated ventricular assist devices were implanted as biventricular bypasses (BVBs) in adult mongrel dogs to compare the natural heart circulation and prosthetic circulation. After BVB pumping was initiated, the natural heart was electrically fibrillated. Renal sympathetic nerve activity (RSNA) was recorded to analyze sympathetic outflow. Coherence function between the arterial pressure and RSNA was calculated to evaluate the linearity of the baroreflex system. The largest peak coherency was observed when BVB was driven at the frequency of natural heart beat prior to electrical fibrillation, which suggests that the baroreflex system shows the largest linearity at this frequency. These results suggest the possibility that the natural heart heat frequency is the setting frequency at which the baroreflex system transfers the hemodynamic rhythm to the sympathetic outflow.

Intellectual function was evaluated by Gesell's developmental quotient (DQ) and Binet's intelligence quotient (IQ) in 161 infants and children (61 ventricular septal defects, 49 tetralogies of Fallot, 15 transpositions of the great arteries, seven atrial septal defects, five complete atrioventricular canals, five double outlet right ventricles and 19 shunt cases; average age 3.6 years) before and after cardiac surgery. There were no significant differences in preoperative DQs and IQs among the patient groups. Although average DQ scores in 21 infants with hypothermic (13–24 °C) total circulatory arrest (36–70 min) were not significantly different from the preoperative values, 13 patients with an arrest time >50 min showed a significant decrease in DQ scores. The postoperative DQ and IQ scores in patients without circulatory arrest or in shunt cases were not significantly impaired after surgery. It was concluded that cardiac surgery did not impair intellectual function in infants and children, although cerebral dysfunction might occur if circulatory arrest was >50 min.

Twenty-four adult mongrel dogs were divided into four equal groups according to the following method of cardiopulmonary bypass: normothermic continuous (so-called nonpulsatile) perfusion, normothermic pulsatile perfusion, hypothermic continuous perfusion, and hypothermic pulsatile perfusion. Cerebral blood flow was determined by measuring the volume of sagittal sinus venous blood outflow with a transit-time ultrasonic flowmeter. Cardiopulmonary bypass was initiated at a flow rate of 80 ml/kg per minute. Cerebral temperature was maintained at 37 degrees C in the normothermic groups and at 25 degrees C in the hypothermic groups. Arterial pH and carbon dioxide were maintained within the physiologic range by alpha-stat acid-base regulation. Mean cerebral perfusion pressure and blood flow were not affected during 90 minutes of the bypass. The respective values were 67.1 mm Hg and 37.1 ml/100 gm brain per minute with normothermic continuous perfusion, 72.8 mm Hg and 39.0 ml/100 gm per minute with nonpulsatile perfusion, 98.0 mm Hg and 23.0 ml/gm per minute with hypothermic continuous perfusion, and 86.8 mm Hg and 22.3 ml/100 gm per minute with hypothermic pulsatile perfusion. Pump flow rates were altered from 10 to 120 ml/kg per minute in a stepwise fashion to obtain graded changes of perfusion pressure. Cerebral blood flow, however, was not changed significantly by cerebral perfusion pressure so long as perfusion pressure was greater than 50 mm Hg. Conversely, cerebral blood flow changed proportionally with cerebral perfusion pressure at a pressure less than 50 mm Hg. The correlation between cerebral blood flow and perfusion pressure was described as two separate lines determined by linear regression. The slope of the regression line relating cerebral blood flow to perfusion pressure was 0.16 +/- 0.08 for a cerebral perfusion pressure above 50 mm Hg and 0.68 +/- 0.11 below 50 mm Hg in the normothermic continuous perfusion group; 0.14 +/- 0.09 and 0.32 +/- 0.09 with normothermic pulsatile perfusion; 0.10 +/- 0.04 and 0.62 +/- 0.18 with hypothermic continuous perfusion; 0.09 +/- 0.08 and 0.39 +/- 0.04 in the hypothermic pulsatile perfusion group. The slope above 50 mm Hg was significantly smaller and closer to zero in all groups than it was at a perfusion pressure below 50 mm Hg (p0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Seventy-seven patients underwent aortic arch aneuxysm repair using selective cerebral perfusion from January 1987 to August 1992. Early and long-term results and preoperative and postoperative cerebral function were evaluated. Cerebral function was assessed by the mini mental state-Himeji test and the Wechsler adult intelligence scale. Thirty-six patients had true aneurysms, and 41 had dissection. Hospital mortality for true and dissecting aneurysms was 19.4% and 7.3%, respectively. The 5-year actuarial survival rates for true and dissecting aneurysms were 59.0% and 65.3%, respectively (not significant). There were no significant differences in test scores before or after operation. Repair or replacement of the aortic arch using selective cerebral perfusion is a safe procedure with acceptable hospital mortality.

In order to analyze the origin of the rhythmical fluctuations in the cardiovascular system, an artificial heart, which does not have rhythmical periodicities such as altering heart rate and cardiac function, was utilized in chronic animal experiments with adult goats. Two pneumatically actuated ventricular assist devices were implanted as a total biventricular bypass under general anesthesia, and then the natural heart was electrically fibrillated to constitute the biventricular bypass type of complete prosthetic circulation model. All hemodynamic data were recorded under awake conditions and were calculated in the computer system by spectral analysis methods. In the power spectrum of the arterial blood pressure of the animal with the artificial heart, the Mayer wave peak and respiratory wave peak were clearly observed, and spectral analysis including the coherence function suggests that the Mayer waves originated from the peripheral vascular resistance and the respiratory waves probably originated from the periodicities of the pulmonary circulation. These fluctuations in the circulatory system influenced the arterial baroreflex system and transfer to the sympathetic outflow through the central baroreflex system, which suggests that rhythmical fluctuations in hemodynamic parameters originate at least in part from these vascular periodicities.

Pulmonary vascular disease was morphometrically analyzed in 67 patients (mean age, 19 months) with isolated complete atrioventricular canal defect. Complete obstruction of the small pulmonary arterial lumen resulting from acute fibrous proliferation and atrophy of the peripheral arterial media, which were considered absolute operative contraindications, were characteristic in six patients with Down's syndrome. Morphometric analysis of medial thickness revealed that thinning of the media of the small pulmonary arteries is generally observed at around 6 months of age in patients with complete atrioventricular canal defect and that the media in patients who have complete atrioventricular canal defect and Down's syndrome was thinner than that in such patients without Down's syndrome. These results suggest that thinning of the media as a result of two factors--Down's syndrome and aging--facilitates the rapid occurrence of fibrous intimal proliferation. Therefore intracardiac repair is desirable within 6 months of life, before medial thinning, in patients with complete atrioventricular canal defect and Down's syndrome. Excluding patients with absolute operative contraindications, the scores of the index of pulmonary vascular disease in operative survivors were below 2.0 and death occurred when scores were more than 2.2. The pulmonary vascular resistances measured in room air and by the oxygen inhalation and tolazoline tests in patients with operative contraindications were more than 7.3, 3.8, and 6.6 units.m2, respectively. We thus conclude that lung biopsy should be undertaken for patients in whom pulmonary vascular resistance is beyond these values to determine the appropriateness of surgical intervention.

Surgical treatment of acute aortic dissection involving the segment of transverse aortic arch is difficult and often associated with a high mortality and morbidity. The high mortality and morbidity are primarily related to anatomic features and techniques of cerebral protection employed during the period of aortic branch occlusion needed for reconstruction. This study reports our experience of 20 consecutive cases of acute type A aortic dissection treated by repair or replacement of the transverse aortic arch during emergency operation. Ages of the patients ranged from 56 to 76 years. All patients were referred to us within 2 weeks of onset (mean time, 58 hours). Selective cerebral perfusion or deep hypothermia with complete circulatory arrest was employed during the period of aortic branch occlusion. Duration of cerebral perfusion, circulatory arrest, myocardial ischemia, and cardiopulmonary bypass averaged 106 minutes, 32 minutes, 127 minutes, and 248 minutes, respectively. There were three operative deaths. All three dissections were ruptured ones, and the patients died of hemorrhage, deep coma, or multiple organ failure. One patient died of infection 3 months after operation. The remaining patients are alive and well without any detectable neurological deficit 1 month to 4 years postoperatively. This experience emphasizes that repair or replacement of acute type A aortic dissection involving the aortic arch can be performed safely by adequate selection of patients, supportive measures, and operative methods.

To evaluate clinical usefulness of sound spectral analysis in the early detection of prosthetic thrombosis, we analyzed specific patterns of thrombus formation in Björk-Shiley tilting standard disc prostheses in relation to the sound spectral analysis of their click sounds. Among a total of 365 Björk-Shiley tilting standard disc prostheses, nine became thrombotic. These consisted of seven prostheses in the mitral position and two in the aortic position, and the affected valves were replaced in all cases. The sound spectral analysis system includes a wide-frequency microphone and a sound spectral analyzer. To quantify the amplitude of the metallic clicks that are specific to the prosthetic valve sounds, we used a normalized maximal frequency as a diagnostic parameter for valve thrombosis. Thrombus formation was localized at the minor strut in two cases, and these demonstrated abnormally low normalized maximal frequency values only on opening clicks. In four cases thrombus formations were noted at both minor and major struts, and these showed abnormally low normalized maximal frequency values on both opening and closing clicks. In two cases with pannus formation, no abnormalities were found by sound spectral analysis. In one case, which had demonstrated abnormally decreased normalized maximal frequency values of both opening and closing clicks, the normalized maximal frequency values were normalized after thrombolytic therapy, suggesting resolved thrombosis. Reoperation, which was performed for concomitant complication of perivalvular leak, revealed no noticeable thrombus formation. The thrombi were seen on the minor strut during surgical procedures in all cases in which valve thrombosis was indicated by the sound spectral analysis. Therefore, the minor strut is considered to be the prevalent area of thrombus formation, and diagnosis could be made after observation of abnormally low normalized maximal frequency on opening clicks. We found the sound spectral analysis to be an extremely useful diagnostic tool for early detection of thrombosis in the Björk-Shiley tilting standard disc prostheses, especially because the opening clicks of the tilting disc valve were too low in amplitude for auscultation to detect the existence of mild abnormality.

SATO, N., UCHIDA, N., MIURA, M., OHMI, M., FUKUJU, T., TABAYASHI, K., HANEDA, K. and MOHRI, H. Risk Analysis of Low Cardiac Output Syndrome after Valve Replacement. Tohoku J. Exp. Med., 1993, 171 (1), 77-88-In order to obtain a better understanding of the pathogenesis of the postoperative low cardiac output syndrome (LOS), a multivariate regression analysis was performed, evaluating predictive risk factors quantitatively as a function of plural preoperative variables. A total of 145 cases including 76 MVR (MS 36 MR 40), 42 AVR and 27 DVR were analized in this study. Ten historical, 10 hemodynamic and 4 operative risk factors were collected to compose the data file with corresponding status of postoperative cardiac function which was classified as follows. Patients who were not associated with postoperative LOS (Score 1), associated with the LOS which required and responded to ordinal dosage of a catecholamine (Score 2) associated with the LOS which required and responded to maximal dosage of the catecholamine and/or mechanical circulatory support (Score 3), and died of LOS (Score 4). Variables with significant relationships to postoperative LOS, regression equation to LOS score and their multiple correlation coefficients (R) of each group were as follows. MVR group: technical trouble (TT), extracerporeal circulation time (ECCT), change of myocardial preservation methods, ΔLVSWI/ΔLVEDP, diseased duration, aortic cross clamping time, CTR, Y=-1.16+ 1.01(TT)+0.05(ECCT)+0.16(ΔLVSWI/ΔLVEDP)+0.02(CTR), R=0.76. AVR group: LVMMI, ECCT, cardiac failure, NYHA, Y=-0.71+ 0.03(LVMMI)+0.004(ECCT)+0.22(NYHA), R=0.78. DVR group: ΔLVWI/ΔLVEDP, LVMMI, NYHA, LV diastolic eccentricity ratio, ECCT, Y=-0.50+0.60 (ΔLVWI/ΔLVEDP)+0.003(LVMMI)+1.18(NYHA)+0.38(ΔLVSWI/ΔLVEDP)+0.003(ECCT), R=0.87. It was demonstrated that preoperative ergometer exercise study during cardiac catheterization was useful in prediction of postoperative outcomes, especially in the MVR (MS) group.

To evaluate changes of the myocardial β-adrenergic receptors in acute cardiac graft rejection, the density and binding affinity value of the myocardial β-adrenergic receptors in heterotopically transplanted rat isografts and allografts were analyzed. Hearts from Fisher rat donors were transplanted either to the Fisher rats (isografts) or to Lewis rats (allografts). Histologic examination of the allografts showed mild to moderate rejection on the seventh and fourteenth days and showed severe rejection on the twenty-first day after transplantation. The density values in the allografts and isografts similarly increased significantly (p

To evaluate the effect of total artificial heart replacement on the autonomic nervous system, sympathetic neurograms were analyzed by power spectrum and coherence function. Two pneumatically driven, sac type ventricular assist devices were implanted as biventricular bypasses (BVB) in adult, mongrel dogs. After initiation of BVB pumping, the natural heart was electrically fibrillated to form a BVB TAH model. Renal sympathetic nerve activity (RSNA) was recorded using a bipolar electrode attached to the left renal sympathetic nerve. RSNA was amplified and integrated by use of an R-C integrator. Power spectra of the RSNA and values of squared coherence between the arterial pressure wave form and the RSNA were calculated by computer. In animals with total artificial hearts (TAHs), coherence at the cardiac rhythm frequency was decreased, and coherence at the TAH pumping rhythm frequency was increased. These results indicate that the arterial pulse wave observed in TAH animals contributed to the sympathetic neurogram.

Circulatory maintenance with a left ventricular assist device (LVAD) alone during cardiac arrest until heart transplantation has been evaluated. To assess the effect on the autonomic nervous system, the sympathetic neurogram was analyzed by power spectrum and coherence function. LVAD were inserted between the left atrium and the descending aorta in seven adult mongrel dogs and ventricular fibrillation was induced electrically. Renal sympathetic nerve activity (RSNA) was detected by bipolar electrodes attached to the left renal sympathetic nerve. Values of squared coherence between the arterial pulse wave and RSNA were calculated. Under the condition of circulatory maintenance with only LVAD, coherence at the cardiac rhythm frequency was decreased, and coherence at the LVAD pumping rhythm frequency was increased. These results indicate that the arterial pulse wave observed during maintenance of the circulation with only LVAD contributed to the sympathetic neurogram.

In order to evaluate the effect of ventricular assist device (VAD) driving on the autonomic nervous system, sympathetic neurograms during left ventricular (LV) assistance were analyzed by power spectrum and coherence function. Our TH–7B pneumatically–driven sac–type VAD was used in seven adult mongrel dogs. VADs were inserted between the left atrium and the descending aorta. Renal sympathetic nerve activity (RSN A) was detected by use of bipolar electrodes attached to the left renal sympathetic nerve via a retroperitoneal approach. Values of squared coherence between the arterial, pulse wave and RSNA were measured at the same frequency of cardiac and VAD pumping rhythms. During LV assistance, coherence at the cardiac rhythm frequency was decreased, and coherence at the VAD pumping rhythm frequency was increased. These results indicate that the arterial pulse wave, which was produced by the VAD assistance, contributed to postganglionic sympathetic nerve activity.

To determine the effect of left ventricular assist device (LVAD) pumping on sympathetic tone, renal sympathetic nerve activity (RSNA) was detected in acute animal experiments. Our TH-7B pneumatically driven, sac-type ventricular assist device was used in 7 adult mongrel dogs. RSNA was detected by the use of bipolar electrodes attached to the left renal sympathetic nerve. RSNA was amplified and integrated by use of an R-C integrator circuit. The area of the integrated nerve discharge per unit time was calculated in the computer system and expressed as RSNA per unit time. During LVAD pumping, RSNA decreased with increase in blood pressure, with an increase in pulmonary artery flow, and with a decrease in left atrial pressure. These data suggest that LVAD has an effect on the sympathetic nervous system which is mediated by the aortic and cardiopulmonary baroreflex system.

To evaluate the effects of 5% carbon dioxide (CO 2 ) administration for hypothermic circulatory arrest, neurological evaluation and pathological studies were carried out on the canine brain. Twenty-two dogs were assigned to five groups: Group 1: Three dogs without hypothermia were sacrificed as the control group. Group 2: Nine dogs were subjected to surface hypothermia (20 °C) under deep ether anesthesia with 100% oxygen (O 2 ) and hyperventilation. Circulatory arrest time was 30 min in Group 2A and 60 min in Group 2B. Group 3: Ten dogs were surface cooled (20 °C) under deep ether anesthesia with a 95% O 2 and 5% CO 2 mixture. Thirty minutes of circulatory arrest was instituted in Group 3A and 60 min in Group 3B. Dogs in Groups 2 and 3 were surface rewarmed and kept alive until they were sacrificed electively 6 or more months later. Results were as follows: (i) Postoperative neurological disturbance was detected in only two dogs in Group 2B. (ii) The percentage of damaged nerve cells among the total nerve cells counted in the cerebral cortex of the frontal lobe was significantly greater in Groups 2A (22.4%), 2B (30.1%), 3A (19.6%), and 3B (22.2%) compared with Group 1 (7.1%). (iii) The number of glia cells per nerve cell in the cerebellar dentate nucleus was significantly higher in Group 2B (27.2) than in Groups 1 (11.8), 2A (16.7), 3A (17.9), and 3B (18.6). (iv) The number of Purkinje cells in a 10-mm length of the cerebellum was markedly reduced to 89 in Group 2B compared with 122, 134, and 117 in Groups 1, 2A, and 3A, respectively. In conclusion, the results of quantitative pathological brain analysis reflected the incidence of postoperative neurological disturbance and suggested that the administration of 5% CO 2 could prolong the time limit for circulatory arrest.

One hundred sixty-six patients with tetralogy of Fallot including 15 pulmonary atresia repaired since 1971 were analyzed with respect to their physical activities, school or social life, hemodynamics, ECG, reoperation and late mortality. Follow-up period ranged from 1 to 19 years with an average of 9.1. There were 9 late deaths including 4 sudden deaths. Actuarial survival rates at 5 and 13 years were 96.4% and 90.5%, respectively. Eighty-five patients (72.0%) of 118 replied were in NYHA functional class I, 31 (26.3%) in class II and 2 (1.7%) in class III. Thirteen patients (7.8%) demonstrated right ventricular/left ventricular systolic pressure ratio over 0.80 because of inadequate relief of the pulmonary stenosis or obstruction, hypoplasia of the pulmonary artery or external conduit stenosis. Although the left ventricular ejection fraction was maintained at the normal range (0.65 +/- 0.09), that of the right ventricle was below the normal level (0.52 +/- 0.09). Two patients developed complete heart block postoperatively and underwent pacemaker implantations. Complete right bundle branch block was observed in 85 patients including 6 with left axis deviation. Most of the patients after correction of tetralogy of Fallot are in satisfactory conditions. However, some patients have limitations in school or social life because of residual lesions or postoperative complications. It is important to consider the proper operative procedures to avoid these problems.

It is very important to grasp the fluid-mechanial property of a prosthetic valve on the various driving conditions, in order to develop a ventricular assist device (VAD). Therefore, the flow characteristics of a newly designed ball valve which consisted of a silicone ball and a polycarbonate housing was analyzed by means of the quantitative flow visualization technique and was compared with the Bjork-Shiley prosthetic valve (BS-19ABP, spherical). The flow visualization were carried out on the four different flow rate conditions (3.0, 2.0, 1.5 and 1.0 L/min). It was observed that the decrease of the flow rate influenced neither on the maximum velocity nor on the velocity vector distributions of a ball valve in comparison with the Byirk-Shiley valve. Furthermore, even on the low flow rate condition (1.0 L/min), the decreases of the flow velocity and the shear rate, which might cause the thrombus formation, were not observed in the lower part of a ball valve. In conclusion, a newly designed ball valve has the fluid-mechanical property which meets the requirement of VAD.

We retrospectively reviewed our 20-year experience of patients with ventricular septal defect(VSD) and Down syndrome (DS) to evaluate operative mortality, morbidity, long-term survival, and quality of life after correction of VSD. Between 1971 and 1991, VSD was corrected on 32 patients with DS, 12 male and 20 female, with an average age of 1.9 years. Operative mortality was 3.1% (1/32). Few postoperative complications developed including transient cardiac arrhythmias and low cardiac output. All survivors were free from reoperation with an average follow-up period of 6.8 years. Actuarial survival at 20 years was 97.9%. As many as 93% of the survivors were in New York Heart Association functional class I. Average pulmonary artery pressure in the long-term period was significantly less than preoperative value. Although simple daily activities such as having meals and dressing themselves were performed satisfactorily by more than 90% of the survivors, only 26% of them were able to converse with full understanding. These data suggest the presence of DS does not present a disadvantage for correction of VSD, which may be followed by excellent survival and functional class in spite of limited social activity.

An 8-year-old male presented with persistent left superior vena cava draining into the left atrium, hemizygous continuation, double outlet right ventricle, cor triatriatum, and visceroatrial discordance. After correction of the double outlet right ventricle and cor triatriatum at the age of 5, he developed mild cyanosis due to a persistent left superior vena cava draining into the left atrium. At the age of 8, an intraatrial tunnel was successfully constructed with bovine pericardium to reroute the abnormal systemic venous flow.

Pacemaker implantation in premature infants presents technical problems because of the relatively larger size of the pulse generator compared with their bodies. A new technique with which successful generator implantation was performed in 2 premature infants less than 2,000 g of body weight is described. The generator is wrapped in a Gore-Tex surgical membrane. A piece of membrane overlying the electrical contact surface of the generator is removed, and the generator is fixed to the abdominal wall in the peritoneal cavity. The technique is simple to perform and would give relative ease in generator exchange.

Background. Among 120 infants less than 12 months of age who had lung biopsy and autopsy, 20 were inoperable because of severe irreversible pulmonary vascular disease. Methods. The infants were classified into three groups. Group 1 comprised 6 patients who showed complete obstruction of the small pulmonary arterial lumen and atrophy of the peripheral arterial media and who were considered to have absolute operative contraindications. Group 2 comprised 6 patients who had no pathologic findings of absolute operative contraindication and had an index of pulmonary vascular disease of more than 2.2. They were isolated as having advanced plexogenic pulmonary arteriopathy. Group 3 comprised 8 patients who had extremely thickened media of small pulmonary arteries, with abnormally thickened media extending into the small peripheral arteries characterized by extremely narrow lumina and medial thickness exceeding luminal diameter. Results. Six of the 9 patients in whom operative repair was abandoned on the basis of preoperative or intraoperative lung biopsy are still alive. Of the 11 patients who underwent operation without biopsy, none survived. Conclusions. Preoperative or intraoperative lung biopsy and assessment of arteriopathy based on the above criteria are recommended in all patients in whom fatal pulmonary vascular disease is suspected.

To evaluate the efficacy of myocardial preservation during open heart surgery, we measured the viscoelasticity of the canine myocardium during cardioplegic arrest. A transfer function method was used for the measurement with a monitoring system consisting of a vibrator, a function generator, accerometers and a signal processor. Six mongrel dogs were put on cardiopulmonary bypass and after measurement of control hemodynamics, they were subjected to cardioplegic arrest at myocardial temperatures ranging from 4 to 32 degrees C. Viscoelasticity was measured at every 15 min and the cardioplegic solution was added every 30 min. After two hr of cardioplegic arrest, the myocardium was reperfused and postischemic hemodynamics were measured after 30 min of non-working beating. Satisfactory myocardial function returned in 3 hearts with the myocardial temperatures below 24 degrees C with myocardial viscoelasticity within the control range. Moderately decreased myocardial contractility was noted in a heart kept at temperature of 27 degrees C and its viscoelasticity remained in the control range of 90 min of ischemia and then began to decrease. In 2 hearts kept at temperatures higher than 29 degrees C, severely depressed myocardial contractility was noted, and viscoelasticity decreased transiently at 45 to 60 min and then returned to control levels. These results suggested usefulness of continuous monitoring of the viscoelasticity in early detection of its degenerative alterations due to impaired myocardial preservation during open heart surgery.

To assess the effect of artificial circulation on the circulatory regulatory system, rhythmical fluctuations in the cardiovascular system and autonomic nerve discharges were analyzed in animal experiments using adult mongrel dogs. Two pneumatically actuated ventricular assist devices were implanted as total biventricular bypass (BVB) under general anesthesia; then, the natural heart was electrically fibrillated to constitute the BVB part of the complete prosthetic circulation model. All hemodynamic data and sympathetic nerve discharges were recorded and calculated in the computer system by the use of spectral analyzing methods. In the power spectrum of the arterial blood pressure waveform during prosthetic circulation, the Mayer wave peak was significantly decreased though the respiratory wave peak was not signif icantly changed. However, the Mayer wave peak in sympathetic nerve discharges was significantly increased though the respiratory wave peak was not significantly changed. These results suggest that rhythmical fluctuations are a necessary response of the circulatory regulatory system including the autonomic nervous system. However, sympathetic nerve discharges respond to the artificial heart without rhythmical fluctuations.

HANEDA, K., SATO, N., TOGO, T., MIURA, M., HATA, M. and MOHRI, H. Late Results after Correction of Ventricular Septal Defect with Severe Pulmonary Hypertension. Tohoku J. Exp. Med., 1994, 174 (1), 41-48 - Fifty-eight patients with ventricular septal defect (VSD) associated with severe pulmonary hypertension (Pp/Ps≥0.90) were repaired between 1971 and 1992. Their preoperative Pp/Ps, Rp/Rs and Rp were 0.98±0.06, 2.37±1.20 and 4.81±3.06units•m2, respectively. Late results were analyzed in 56 operative survivors. The age at the time of operation ranged from 2 months to 32 years (average 4.1 years) and the postoperative follow-up period ranged from 1 month to 20 years (average 5.5 years). Eighty-two percent of the patients were in New York Heart Association functional class I, 15% were in class II and 3% in class III. The postoperative Pp/Ps and Rp/Rs significantly decreased to 0.41 ±0.13 (p

A vibrating flow pump (VFP), which can generate oscillated blood flow (10–50 Hz/min), has been developed by our team for the artificial heart system. However, the flow pattern of this pump was different from that of the natural heart; therefore, it is important to analyze the effect of this oscillated blood flow on the circulatory regulatory system. To analyze the hemodynamics of high frequency oscillated blood flow as an entity, (not decomposed), nonlinear mathematical techniques were utilized. VFPs were implanted between the left atrium in animal experiments using adult goats. After the implantation procedure, the ascending aorta was clamped to constitute the complete left heart circulation with VFP. Using a nonlinear mathematical technique, an arterial blood pressure waveform was embedded into four–dimensional phase space and projected into three–dimensional phase space. The Lyapunov numerical method was used as an adjunct to graphic analysis of the state space. Phase portrait of the attractor showed a high dimension complex structure, suggesting deterministic chaos during natural circulation. However, phase portrait of the hemodynamics during oscillated blood flow showed a single circle with banding and a forbidden zone, similar to a limit–cycle attractor, suggesting a lower dimensional dynamic system. Positive Lyapunov exponent during oscillated blood flow suggests the existence of lower dimensional chaotic dynamics. These results suggest that the circulatory regulatory system during oscillated blood flow may be a lower dimensional homeochaotic state; thus, hemodynamic parameters must be carefully regulated when unexpected external stimuli are present.

A 14-year-old girl underwent operation with the diagnosis of diverticulum of the superior vena cava. Microscopic findings revealed a diverticulum with venous architecture. This represents a rare case of a giant diverticulum of the superior vena cava.

The adequacy of the circuits for brain perfusion has been explored by hemodynamic assessment using the ability of the brain to autoregulate blood flow as an indicator, and by morphologic observation using carbon black or Evans blue infusion into the brain perfused antegradely or retrogradely. It is concluded that the safe pressure of cerebral perfusion needed to maintain cerebral integrity is between 40 and 50 mm Hg in both normothermic and hypothermic perfusions, a pressure that can be generated by nonpulsatile pump flows through the pump greater than 40 mL.kg-1 x min-1. Morphologic studies revealed development of focal infarctions in the brain and destruction of the blood-brain barrier by retrograde cerebral perfusion. The retrograde approach, therefore, is definitely inferior to the antegrade method. Antegrade perfusion for 90 minutes, however, produced minimal cerebral edema, suggesting the need for further improvement even in techniques of antegrade perfusion.

Intraoperative sternal closure after cardiopulmonary bypass in patients with cardiac dilatation and dysfunction may cause fatal deterioration of their hemodynamics. To avoid this complication, a ceramic plate made from methyl methacrylate was used for sternal splinting. This simple splint can avoid chest wall compression to the overdilated heart, maintaining stable hemodynamics after cardiopulmonary bypass without postoperative respiratory complications or mediastinal infection.

Of 77 University of Tokyo ventricular assist devices used in a total of 70 patients at 21 institutions, 13 pumps were found to have macroscopic thrombus formations. Because 19 devices that were used for less than 24 hours showed no thrombus deposition, they were considered not to have been sufficiently exposed to the thrombogenic environment for macroscopic thrombus deposition and were removed from the subsequent multivariate study. A total of eight potential risk factors were assessed in relation to thrombosis. Prevalences of thrombus formation were compared between two groups with or without each of the risk factors. In a univariate analysis, the following categoric variables were demonstrated to be significantly associated with complications, in descending order of significance: use of gabexate mesilate (protease inhibitor) as an anticoagulant (p = 0.005), normal platelet count (p = 0.010), duration of support (p = 0.038), leukocytosis (p = 0.042), and minimum pumping flow (p = 0.042). Use of heparin and the consequent increase in activated clotting time showed no relationship. Multivariate discriminant analysis, which was done to identify risk factors rejecting cross correlation between each variable, demonstrated platelet count (p = 0.006), use of gabexate mesilate (p = 0.007), and minimum flow (p = 0.008) to have significant and independent risks. These results indicate the importance of maintaining pumping flow above a certain minimum level, addition of antiplatelet drugs to the antithrombogenic regimen, and nonuse of gabexate mesitate.

HANEDA, K., KONNAI, T., SATO, N., NICOLOFF, N.N. & MOHRI, H. Acute Hemodynamic Changes after Fontan Operation: An Experimental Study. Tohoku J. Exp. Med., 1993, 169 (2), 113-119 - Seven adult mongrel dogs with an average body weight of 11.3kg were subjected to experimental Fontan operation in order to evaluate acute hemodynamic changes at the Fontan circulation. The Fontan circulation was established by occlusion of the tricuspid valve with tightening a purse-string suture which was placed around the valve under inflow occlusion and was passed through the anterior right atrial wall, and by connection with a 10mm Gore-Tex graft between right atrium and pulmonary artery. When the Fontan circulation was established, aortic pressure and cardiac output (CO) decreased from 94.9±22.0mmHg to 41.9±6.0mmHg and 0.907±0.179 liter/min to 0.259±0.072 liter/min, respectively. There were no significant changes in heart rate and systemic vascular resistance between normal and the Fontan circulations. On the other hand, pulmonary vascular resistance (PVR) increased from 11.6±7.3 units in the normal circulation to 21.8±13.0 units in the Fontan circulation. From this study it was concluded that main changes in hemodynamic parameters immediately after establishing the Fontan circulation were marked decrease in systemic arterial pressure and CO, and an increase in PVR. Therefore, one should consider a possibility of an increase in the PVR to the critical level when the Fontan operation was applied to patients with pulmonary hypertension. - Fontan operation; tricuspid atresia; pulmonary hypertension

Antithrombogenic regimens for pneumatic ventricular assist devices (VADs) were evaluated in 77 VADs used clinically in a total of 70 patients. Macroscopic thrombus formation in the devices was assessed in relation to potential risk factors, including hematological and hemodynamic derangements, during use of the VAD. Effects of varions antithrombogenic regimens were assessed on the basis of this risk analysis. A thrombus score was used to quatititate the grade of thrombosis. As a linear increase in the thrombus score was noted in accordance with increase in support duration, a time-adjusted thrombus score was calculated to compare scores in anticoagulant groups with different pumping duration. The scores appeared to be high in patients in those groups which received gabexate mesilate (GM, a protease inhibitor). Heparin was not demonstrated to be effective in this study. Univariate risk analysis showed that the use of GM, low-flow pumping, prolonged pumping, and semi-normal platelet count were significantly correlated with the incidence and grade of thrombosis. A multivariate regression analysis also indicated that the use of GM, low-flow, and prolonged pumping were detrimental to anti-thrombogenicity. As the use of GM was demonstrated to be predominantly detrimental, its withdrawal from use should lead to a substantial reduction in the incidence and grade of thrombosis.

We have been involved for some time in the development and evaluation of an artificial heart system; in recent years we have developed a new type of electro-magnetically driven pump, designed with a high frequency vibrating flow [1], for a totally implantable total artificial heart and ventricular assist device.

In order to determine optimal drive conditions for the total artificial heart (TAH) from the neurophysiological point of view, power spectral analysis of the hemodynamic parameters in animals chronically implanted with TAH was performed to analyze the rhythmical fluctuations that reflect the operation of cardiovascular regulatory systems. Two ventricular assist devices were implanted as total biventricular bypasses (BVB) in chronic animal experiments with adult goats. Natural hearts were then electrically fibril-lated to constitute the BVB type of TAH model for comparison of the circulation in animals with a natural heart and those with a TAH. Mayer waves and respiratory waves were clearly observed in the arterial pressure of the TAH animal, these fluctuations being significantly influenced by the TAH driving conditions. These results suggest that fluctuations in the hemodynamics of animals with TAH can provide information for TAH control systems.

In order to investigate the origin of the fluctuations in hemodynamic parameters, total artificial heart (TAH) replacement was performed in chronic animal experiments using adult goats. Two ventricular assist devices were implanted as total biventricular bypass (BVB) and natural heart was electrically fibrillated. The results suggest that fluctuations in the hemodynamics of the TAH animal are originated from the periodicity of the peripheral and pulmonary vascular resistance.

A quantitative analysis of small pulmonary arteries, pulmonary veins, and lymphatic vessels was conducted in autopsy cases of total anomalous pulmonary venous connection. The materials were obtained from 60 cases of total anomalous pulmonary venous connection without asplenia or pulmonary stenosis, ages ranging from 2 days to 19 months at the time of death (mean age 2.2 months). Pulmonary arterial pressure had been measured in 32 of these patients before death. Twenty cases of ventricular septal defect with pulmonary hypertension and 15 normal individuals were used as the control group. The mean thickness of the media of small pulmonary arteries and veins was 12.7 and 7.6 microns, respectively, in the total anomalous pulmonary venous connection cases, both values being significantly larger than those for normal and ventricular septal defect cases. No changes in thickness with aging were found. Medial thickness in the arteries and veins was greater in the cases of pulmonary venous obstruction than in those without such obstruction. The medial thickness of small pulmonary arteries in total anomalous pulmonary venous connection cases correlated with increased pulmonary arterial pressure. When the patients with the same pulmonary arterial pressure levels were compared, the medial thickness was always greater in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect. The medial thickness of pulmonary veins was also highly correlated with increased pulmonary arterial pressure in total anomalous pulmonary venous connection. The severity of the intimal lesions was milder in those who had total anomalous pulmonary venous connection than in those who had ventricular septal defect, suggesting the protective role of the thickened pulmonary arterial media against development of intimal lesions. Intimal fibrous thickening of pulmonary veins was not seen in the cases of ventricular septal defect, but it was present in 45% of the total anomalous pulmonary venous connection cases. Lymphangiectasia was characteristically present in 62% of the total anomalous pulmonary venous connection cases. Interstitial emphysema was often a complication of lymphangiectasia, and it led to eight postoperative deaths.

Thirty-one patients over the age of 70 years (group A) and 72 patients less than 69 years (group B) underwent a variety of thoracic aortic surgical procedures. Early and long-term results and cerebral function were compared between the two groups. Preoperative and postoperative cerebral function was evaluated using mini mental state-Himeji and Wechsler adult intelligence scale tests. The operative mortality of groups A and B was 12.9% and 11.1%, respectively (not significant). There were no significant differences in postoperative complications between the two groups. The late mortality rates of groups A and B were 11.1% and 9.3%, respectively (not significant). There were no significant differences between the two groups in the mini mental state-Himeji test, digit symbol, vocabulary, and total Wechsler adult intelligence scale scores before and after operation. We conclude that thoracic aortic surgical procedures in patients over 70 years of age can be performed with acceptable mortality and morbidity risks. Most patients showed symptomatic improvement.

ENDO, M., HANEDA, K., MOHRI, H. and YAMAKI, S. Tetralogy of Fallot with Anomalous Origin of Left Pulmonary Artery. Tohoku J. Exp. Med., 1992, 167 (1), 69-77-Between 1971 and 1990, 7 patients of tetralogy of Fallot with anomalous origin of left pulmonary artery underwent intracardiac repairs at Tohoku University Hospital. They were 2 males and 5 females with ages ranging from 4 to 26 years old. The right pulmonary artery connected to right ventricle in all cases, whereas no communications between right ventricle and the left pulmonary artery were found. The left pulmonary artery directly originated from the ascending aorta in 2 patients (group I) and connected to the ductus arteriosus in 5 patients (groups II and III). In 2 patients (group II), the left pulmonary artery was separated from the pulmonary arterial trunk by the intraluminal membrane, receiving blood supply through the ductus. In the remaining 3 patients (group III), there were no continuations between both pulmonary arteries. At the correction, communication between the left pulmonary artery and the pulmonary arterial trunk could be reconstructed in groups I and II. However, it was not possible in group III, because the ductus arteriosus and the left pulmonary artery had already been occluded before the intracardiac repair. In group III, ventricular septal defect was closed using a one-way valved patch or a perforated patch to decrease supersystemic right ventricular pressure. Postoperative right ventricular aortic pressure ratio was between 0.5 and 0.8 in groups I and II, and between 0.8 and 1.0 in group III. Three patients (one in each group) died after the operation. Severe pulmonary vascular obstructive disease was found in the left lung of group I. Tetralogy of Fallot with anomalous origin of unilateral pulmonary artery should be corrected before the advance of pulmonary vascular obstructive disease in case pulmonary artery originates from the ascending aorta, and before the occlusion of the ductus arteriosus in case pulmonary artery originates from it.

HANEDA, K., TOGO, T., SATO, N., OGATA, H. and MOHRI, H. Late Results after Repair of Complete Atrioventricular Canal. Tohoku J. Exp. Med., 1992, 166 (2), 201-208-Twenty-five patients with complete atrioventricular canal including 10 Down's syndrome patients repaired since 1972 were analyzed with respect to their physical activities, hemodynamics, ECG, reoperation and late mortality. Follow-up period ranged from 1 to 17 years with an average of 7.0 years. There was 1 late death. Actuarial survival rate was 0.86±0.13 (mean±S.D.) at 12 years. Fourteen patients (70%) of 20 evaluated were in New York Heart Association functional class I, and 4 (20%) were in class II and 2 (10%) in class III. In 23 patients without pulmonary stenosis, preoperative values of peak pulmonary to systemic pressure ratio (Pp/Ps) and pulmonary to systemic arterial resistance ratio (Rp/Rs) were 0.64±0.28 and 0.36±0.31, respectively. Postoperative Pp/Ps and Rp/Rs significantly decreased to 0.37±0.14 and to 0.20±0.14, respectively. In Down patients, postoperative Pp/Ps, Rp/Rs and pulmonary arterial resistance were significantly greater than in non-Down patients (0.50±0.07 vs. 0.25±0.05, 0.30±0.13 vs. 0.10±0.03 and 4.4±1.8 vs. 1.8±0.6 units•m2, respectively). Complete heart block developed in 1 patient postoperatively. Sick sinus syndrome was observed in 3 patients, transient Mobitz II A-V block in 2, ventricular premature contractions of Lown's Grade II in 1 and atrial fibrillation in 1. Five patients demonstrated severe mitral regurgitation equal to or more than Grade III and 2 of them underwent mitral valve replacement 6 months and 12 years after the initial operation. Most of the patients were leading in active school or social lives. However, progression of pulmonary vascular obstructive disease especially in Down's syndrome patients, mitral regurgitation and heart rhythm disturbances still create late postoperative problems.

This study explored myocardial protective effects of allopurinol at various doses. Ninety patients undergoing coronary artery bypass or repair or replacement of cardiac valves were divided into three groups of 30 patients each in accordance with the amount of allopurinol administered to patients in each group. Patients in group I received no allopurinol, those in group II received low-dose allopurinol (total dose 1200 mg), and those in group III received high-dose allopurinol (total dose 2400 mg). Aspartate aminotransferase, cardiac isoenzyme of creatine kinase, and lactic dehydrogenase levels were measured up to 5 days after operation. Concentrations of allopurinol and oxypurinol were also measured before initiation of cardiopulmonary bypass and at the start and at the end of aortic crossclamping. Postoperative aspartate aminotransferase, creatine kinase, and lactate dehydrogenase 1 plus lactate dehydrogenase 2 levels in group III were significantly lower than those in groups I and II. Aspartate aminotransferase, creatine kinase, and lactate dehydrogenase 1 plus lactate dehydrogenase 2 levels in group II were lower than those in group I, without statistically significant differences. Plasma oxypurinol concentrations were significantly higher in group III than in group II. It was concluded that allopurinol had resultant high myocardial protective effects in dose-related fashion, but its effect might be attributed to oxypurinol levels formed by its degradation.

YAMBE, T., NITTA, S., CHIBA, S., SAIJOH, Y., NAGANUMA, S., AKIHO, H., KAKINUMA, Y., IZUTSU, K., KIKUCHI, Y., NAGANUMA, T., SUGAWARA, S., TANAKA, M., MEGURO, T., SASAKI, H., MITSUOKA, M., TERASAWA, Y., NITTA, K., KATAHIRA, Y., OHTOMO, T., ENDOH, N., TAKEDA, H., SONOBE, T., TAKAHASHI, K., MIURA, M., SATO, N. and MOHRI, H. Silent Obstruction of the Coronary Stenosis between Diagnostic Angiography and Later Percutaneous Transluminal Coronary Angioplasty without Myocardial Infarction. Tohoku J. Exp. Med., 1991, 163 (3), 167-174 - Among 204 patients with severe coronary artery senosis amenable to percutaneous transluminal coronary angioplasty (PTCA), 5 (2.5%) developed new silent total coronary occlusion of the vessel to be dilated without any chest symptom during the period between diagnostic coronary angiography and repeat coronary angiography at the time of the operation. We evaluated the clinical and angiographical characteristics of the patients with silent obstruction of the coronary artery in a short time, compared with the patients with unstable angina pectoris, who is considered to be suffering from acute myocardial infarction with severe chest symptom. None of the clinical variables studied showed a significant difference between the two groups. Among the angiographic variables, the degree of collateral was higher and impaired coronary perfusion distal to the lesion was more frequently found in unstable angina group. These results suggest that unstable angina is in a later stage of the ischemic heart disease compared with the time of the diagnostic angiography in patients with silent obstruction. Silent obstruction of high degree coronary stenosis is presumably due to the development of collateral circulation.

A wide variety of clinical blood pumps including powering systems have been developed and evaluated for totally implantable support systems [1–6]. However, there are still several serious problems, such as thromboembolic episodes, size, and weight, affecting prolonged survival of a total system inside the body.

In order to develop the real-time control system of a total artificial heart (TAH), we use the sympathetic tone and the hemodynamic parameters. Moving averages of the mean left atrial pressure and mean aortic pressure were used as the parameters of the preload and the afterload in the circulatory system. Also, renal sympathetic nerve activity (RSNA) was utilized as the parameter of the sympathetic tone. A functional formula which prospectively indicated cardiac output, was calculated using the multiple regression analysis of the time series data in the acute animal experiments using adult mongrel dogs. Also, a functional formula which prospectively indicated heart rate was determined through the time series data of the RSNA.

We have been involved in the development of a clinical ventricular assist device (VAD) system. Here, we report our investigation of in vitro and in vivo stability and sensibility of pressure microsensors. The sensors were mounted in the inflow and outflow cannulae wall to measure the left atrial and aortic pressures during VAD pumping. The pressure sensitive surface of the piezoresistive effect absolute pressure sensor was coated with a thromboresistant polymer, as was the inner surface of the cannulae of the VAD. In the in vitro and chronic animal experiments which were of more than a month duration, reliable stability and sensitivity, without any thrombus formation on the blood contacting surface of the sensors, and high sensitivity were observed. After chronic experiments, the sensitivity of sensors was reevaluated in the mock circulatory system as compared to reference values. The relationship between the output of the micro-sensors and the reference value was linear and correlated well.

This study was designed to evaluate the usefulness of the ratio of the preoperative regurgitant stroke volume to left ventricular end-diastolic volume (RSV/LVEDV) for assessing the left ventricular function preoperatively. In 26 patients with aortic regurgitation (AR), the percent decrease in LVEDV was compared with the preoperative RSV/LVEDV, ejection fraction (EF), LVEDV, left ventricular end-systolic volume (LVESV) or left ventricular end-diastolic pressure (LVEDP). There was a significant correlation between the percent decrease in LVEDV and RSV/LVEDV. Patients with RSV/LVEDV of more than 0.26 had a significantly smaller postoperative left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-systolic volume index (LVESVI), and a greater postoperative EF than patients with smaller RSV/LVEDV. All but one patient with RSI/LVEDVI larger than 0.0016 LVEDVI had normal postoperative LVEDVI. Based on these findings, it is concluded that the RSV/LVEDV is an useful indicator for preoperative evaluation of left ventricular functions in patients with AR. Surgical intervention for patients with AR should be recommended before the RSI/LVEDVI drops to less than 0.0016 LVEDVI, to expect good postoperative ventricular responses.

In a previous paper, it was stated that open lung biopsy for determination of operative indications could be recommended if pulmonary vascular resistance (PVR) were higher than 8 units · m2 in patients with ventricular septal defect (VSD) and/or patent ductus arteriosus (PDA) with severe pulmonary hypertension. In the present study, oxygen inhalation or Tolazoline administration tests with or without occlusion of ductus arteriosus were performed during cardiac catheterization in 47 patients with VSD and/or PDA with severe pulmonary hypertension. The results obtained were compared with the operability based on our histopathological diagnostic criteria. There was no correlation between the oxygen, Tolazoline, or ductus occlusion hemodynamics and the baseline hemodynamics for better prediction of the biopsy results. It was concluded that open lung biopsy should be performed for the determination of operative indication when patients with VSD and/or PDA have a PVR higher than 8 units.m2, and if the PVR is greater than 4 units.m2 with the oxygen inhalation test or 7 units.m2 with the Tolazoline test.

Pulmonary vascular disease (PVD) was histologically evaluated and its severity was expressed as an index of PVD in 14 autopsied and eight biopsied cases of complete transposition of the great arteries (TGA) in patients more than 6 months of age. The index varied from 1.0 to 2.3 in six patients who had survived complete surgical repair and ranged from 2.3 to 3.3 in five patients who had died of PVD postoperatively. Consequently, an index of 2.2 could be regarded as an upper limit of PVD for complete surgical repair. The index was significantly correlated to some hemodynamic factors. From the regression equation, the value 2.2 of histologic index could be translated into the clinical factors concerning hemodynamics. We consider that patients with pulmonary vascular resistance of less than 10.6 units . m2, and pulmonary arterial mean pressure less than 51 mm Hg, are suitable candidates for complete surgical repair in TGA, if more than 6 months of age. Thus histologic assessment of PVD in a lung biopsy as an indication for total correction of TGA with pulmonary hypertension appears to be useful in patients who are in borderline hemodynamic condition or in whom the hemodynamics could not be evaluated although pulmonary hypertension was suspected.

肺葉切除が行われた19例を対象とし, 6種の血清糖蛋白を術前および術後経時的に測定し, これら血清糖蛋白値およびその変動と, 肺癌進展度ならびに術後経過との関係について検討した.肺癌病期分類別による血清糖蛋白値の変動では, pn因子においてα1AG値がpn1群に比べpn2群で有意 (p