Neurodevelopmental outcome after antenatal therapy for fetal supraventricular tachyarrhythmia: 3-year follow-up of multicenter trial.

OBJECTIVES: Although many studies have supported the efficacy of transplacental treatment for fetal supraventricular tachyarrhythmia, the long-term neurodevelopmental outcome after antenatal antiarrhythmic treatment is not well understood. The aim of this study was to investigate the prognosis and neurodevelopmental outcome at 36 months of corrected age and the incidence of tachyarrhythmia after birth, following protocol-defined antenatal therapy for fetal supraventricular tachyarrhythmia. METHODS: This was a 3-year follow-up study of a multicenter trial that evaluated the efficacy and safety of protocol-defined transplacental treatment for fetal supraventricular tachycardia (SVT) and atrial flutter (AFL). The primary endpoints were mortality and neurodevelopmental impairment (NDI) at 36 months of corrected age. NDI was defined as any of the following outcomes: cerebral palsy, bilateral blindness, bilateral deafness or neurodevelopmental delay. Neurodevelopmental delay was evaluated using appropriate developmental quotient scales, mainly the Kyoto Scale of Psychological Development, or examination by pediatric neurologists. The detection rate of tachyarrhythmia at birth and at 18 and 36 months of corrected age was also evaluated as the secondary endpoint. In addition, the association of NDI at 36 months with perinatal and postnatal factors was analyzed. RESULTS: Of 50 patients enrolled in the original trial, one withdrew consent and in two there was fetal death, leaving 47 patients available for enrollment in this follow-up study. Of these, 45 cases were available for analysis after two infants were lost to follow-up. The mortality rate was 2.2% (1/45) during a median follow-up of 3.2 (range, 2.1-9.4) years. The infant died at the age of 2.1 years. Another infant had missing neurodevelopmental assessment data. In the remaining 43 infants, at 36 months of corrected age, NDI was detected in 9.3% (4/43) overall and in two of three (66.7%) cases with fetal hydrops with subcutaneous edema. Cerebral palsy was noted in two infants with severe subcutaneous edema or ascites at an early gestational age. Neurodevelopmental delay was found in two infants with severe congenital abnormalities (one with tuberous sclerosis and the other with heterotaxy syndrome). Tachyarrhythmia was present in 31.9% (15/47) cases in the neonatal period and decreased to 8.9% (4/45) and 4.5% (2/44) at 18 and 36 months of corrected age, respectively. The median ventricular rate at diagnosis was significantly higher in infants with NDI compared to those without (265 vs 229 bpm; P = 0.003). In infants with NDI, compared to those without, fetal hydrops with subcutaneous edema at diagnosis was more common (50.0% vs 2.6%; P = 0.019) and the duration of fetal effusion was longer (median, 10.5 vs 0 days; P = 0.013). Postnatal arrhythmia and physical development abnormalities were not associated with NDI. CONCLUSIONS: This multicenter 3-year follow-up study is the first to demonstrate the long-term mortality and morbidity of infants born following protocol-defined transplacental treatment for fetal SVT and AFL. NDI was associated with the presence of fetal hydrops with subcutaneous edema at diagnosis and longer duration of fetal effusion. Neurodevelopmental delay was detected only in infants with severe congenital abnormalities. Therefore, in infants that have undergone antenatal treatment for fetal tachyarrhythmia and in which there are no comorbidities, the risk of NDI is low. However, in those with fetal hydrops with subcutaneous edema and/or associated severe congenital abnormalities, the risk for long-term neurologic morbidity might be considered somewhat increased. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Plasma natriuretic peptide levels in fetuses with congenital heart defect and/or arrhythmia.

OBJECTIVE: Diagnosing fetal heart failure remains challenging because it is difficult to know how well the fetal myocardium will perform as loading conditions change. In adult cardiology, natriuretic peptides (NPs) are established markers of heart failure. However, the number of studies investigating NP levels in fetuses is quite limited. The aim of this study was to evaluate the significance of plasma NP levels in the assessment of heart failure in fetuses with a congenital heart defect (CHD) and/or arrhythmia. METHODS: This was a prospective observational study conducted at a tertiary pediatric cardiac center. A total of 129 singletons with CHD and/or arrhythmia and 127 controls were analyzed between 2012 and 2015. Umbilical cord plasma atrial NP, brain NP and N-terminal pro-brain NP levels at birth were compared with ultrasonography findings indicating fetal heart failure, such as cardiovascular profile (CVP) score and morphological characteristics. RESULTS: Fetuses with CHD and/or arrhythmia had higher NP levels than did controls (P < 0.01). NP levels of fetuses with CHD and/or arrhythmia were correlated inversely with CVP score (P for trend < 0.01). No differences in NP levels were found in fetuses with CHD and/or arrhythmia and a CVP score of ≥ 8 in comparison to controls. Multivariate analysis showed that a CVP score of ≤ 5, tachy- or bradyarrhythmia at birth, preterm birth and umbilical artery pH < 7.15 were associated independently with high NP levels (P < 0.01). Among fetuses with a CVP score of ≤ 7, abnormal venous Doppler sonography findings were significantly more common and more severe in fetuses with tachy- or bradyarrhythmia than in those with CHD, and those with tachy- or bradyarrhythmia had higher NP levels than did those with CHD (P = 0.01). Fetuses with right-heart defect and moderate or severe tricuspid valve regurgitation had significantly higher NP levels than did fetuses with other types of CHD (P < 0.01). CONCLUSIONS: Plasma NP levels in fetuses with CHD and/or arrhythmia are correlated with the severity of fetal heart failure. Elevated NP levels are attributed mainly to an increase in central venous pressure secondary to arrhythmia or atrioventricular valve regurgitation due to CHD, rather than to the morphological abnormality itself. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[Video-assisted thoracic surgery for lung cancer at Kyoto City Hospital].

From April 1994 to April 2008, we were started on 313 cases video-assisted thoracic surgery (VATS) operations for primary lung cancer at the thoracic surgical department of Kyoto City Hospital. Exclude cases such as conversion to open surgery, partial resection and double primary cancer, 212 cases were evaluated. Most common surgical approach was 111 lobectomy cases (90%) and pneumonectomy is 3 cases. Histopathologic diagnosis was adenocarcinoma was 74% and squamous cell carcinoma was 22%. There were no intraoperative and hospital death. Most common complications were prolonged air leak in 20 cases (9.4%). Five year survival rate were stage IA 87.8%, IB 71.8%, II 52.4%, III 47.8%, IV 33.3%. Our data demonstrate thoracoscopic lobectomy for lung cancer is a safe procedure and excellent prognosis.

Myocardial Akt activation and gender: increased nuclear activity in females versus males.

Cardiovascular disease risk is higher in men than women, but the basis for this discrepancy remains controversial. Estrogenic stimulation of the myocardium or isolated cardiomyocytes has been purported to exert multiple beneficial effects associated with inhibition of maladaptive responses to pathogenic insults. This report describes a significant difference between the sexes in myocardial activation of Akt, a protein kinase that regulates a broad range of physiological responses including metabolism, gene transcription, and cell survival. We find that young women possess higher levels of nuclear-localized phospho-Akt(473) relative to comparably aged men or postmenopausal women. Both localization of phospho-Akt(473) in myocardial nuclei of sexually mature female mice versus males and Akt kinase activity in nuclear extracts of hearts from female mice versus males are elevated. Cytosolic localization of phospho-forkhead, a downstream nuclear target of Akt, is also increased in female relative to male mice, suggesting a potential mechanism for cardioprotective nuclear signaling resulting from Akt activation. Phospho-Akt(473) levels and localization at cardiac nuclei are similarly increased in transgenic mice with myocardium-specific expression of insulin-like growth factor I, a proven stimulus for Akt activation. Phospho-Akt(473) is also localized to the nucleus of cultured cardiomyocytes after exposure to 17beta-estradiol or genistein (a phytoestrogen in soy protein-based diets), and neonatal exposure of litters to genistein elevated nuclear phospho-Akt(473) localization. The activation of Akt in a gender-dependent manner may help explain differences observed in cardiovascular disease risk between the sexes and supports the potential beneficial effects of estrogenic stimulation.

Transformation of coronary artery aneurysm to obstructive lesion and the role of collateral vessels in myocardial perfusion in patients with Kawasaki disease.

OBJECTIVES: The aim of this study was to examine the transformation of coronary artery aneurysms to obstructive lesions and to assess the role of collateral vessels in patients with Kawasaki disease. BACKGROUND: Coronary artery aneurysms, especially giant aneurysms, are known to become obstructive lesions in patients with Kawasaki disease. However, the process of transformation is not yet clear. METHODS: Thirty patients (average age 9.9 years) with obstructive lesions secondary to Kawasaki disease underwent repeated coronary artery angiography and thallium myocardial scintigraphy over a mean period of 7.7 years after the acute onset of Kawasaki disease. RESULTS: In the 27 patients who were enrolled in the acute phase of the disease because of coronary artery aneurysms, the later transformation to obstructive lesions was not significantly different between the 61 large and 6 medium-sized aneurysms. Obstructive transformation of aneurysms was more rapid in the right than in the left coronary artery (p < 0.001). From the last coronary angiogram obtained, the obstructive lesions were classified as localized stenosis > 90% in 10 vessels, occlusions in 6 vessels and segmental stenosis in 26 vessels. Both localized and segmental stenosis occurred significantly more often in the left anterior descending and the right coronary artery than in other vessels (p < 0.05). The incidence of collateral vessels was significantly correlated with a younger age at onset of Kawasaki disease, especially in patients with segmental stenosis (p < 0.001). Collateral vessels did not develop in the presence of localized stenosis regardless of the occurrence of myocardial ischemia. All occluded vessels had collateral development regardless of the presence of myocardial infarction. CONCLUSIONS: The treatment of localized stenosis may play an important role in preventing myocardial infarction in the chronic phase of Kawasaki disease.

Effect of new oral antidiabetic agent CS-045 on glucose tolerance and insulin secretion in patients with NIDDM.

OBJECTIVE: To study the effects of CS-045, a newly developed thiazolidine analogue, on glucose tolerance and insulin response to oral glucose load in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Nineteen NIDDM patients (mean +/- SD age 48.9 +/- 9.4 yr) whose previous glycemic control on diet and/or sulfonylurea (SU) therapy was judged stable but unsatisfactory (greater than 7.8 mM) were selected for this study. CS-045 (400 mg/day p.o.) was given alone or together with the previous SU drugs for 12 wk. A 75-g oral glucose tolerance test (OGTT) was performed before and after CS-045 treatment. RESULTS: The following results were found after CS-045 treatment. 1) Fasting plasma glucose (FPG) and HbA1c decreased (n = 19, FPG, 11.0 +/- 2.4 vs. 8.4 +/- 2.7 mM [before vs. after], P less than 0.001; HbA1c, 8.0 +/- 1.1 vs. 7.4 +/- 1.3%, P less than 0.005), and glucose tolerance markedly improved. 2) Fasting insulin (immunoreactive insulin [IRI]) and insulin response during OGTT decreased (n = 19, fasting IRI, 77.4 +/- 49.8 vs. 56.5 +/- 24.6 pM [before vs. after], P less than 0.05; area under the curve of IRI, 540.3 +/- 350.5 vs. 426.4 +/- 216.3 pM.h, P less than 0.05). CONCLUSIONS: CS-045 is effective in improving glucose tolerance without stimulation of insulin secretion in NIDDM, suggesting an effect in improving insulin sensitivity.

Characterization of the prandial plasma corticosterone peak in the freely moving rat.

To characterize the prandial plasma corticosterone peak, three experiments were done on adult male Wistar rats: (1) the prandial hormone peak was followed at three different times of day, 0800 h, 1900 h, and 0100 h, in starved rats; (2) a 20% glucose solution was infused into the jugular vein or was given as a drinking solution after a 24-h starvation; (3) in order to determine the role of vagal proprioceptive inputs, the hormone peak was examined at two times of day, 0800 h and 0100 h, in starved vagotomized rats. The prandial hormone peak was more conspicuous at midnight than in the daytime. Exposure to food pellets without feeding failed to induce a hormone rise. The peak appeared after oral ingestion, but not after intravenous infusion, of glucose solution. Ingestion of water alone was without effect. The peak was not affected by bilateral vagotomy. Thus, as far as glucose as a metabolite is concerned, the possibility that glucose per se works directly on the brain or indirectly through glucoreceptors in the gut was excluded. Possible modes of action of glucose ingestion are discussed.

Intraoperative balloon angioplasty for aortic coarctation after Norwood operation.

We report intraoperative balloon angioplasty for recurrent aortic coarctation in hypoplastic left heart syndrome. After bidirectional Glenn anastomosis, balloon angioplasty was performed via ascending aorta. Pressure gradient across the coarctation decreased from 45 to 8 mm Hg. Intravascular ultrasound revealed successful splits of thickened intima without any extensive dissection. Intraoperative balloon angioplasty is a safe and favorable procedure for hypoplastic left heart syndrome because balloon inflation before bidirectional Glenn anastomosis could induce serious ventricular collapse or arrhythmias.

Helical computed tomographic angiography in obstructed total anomalous pulmonary venous drainage.

Helical computed tomographic angiography with differential color imaging technique clearly demonstrated pulmonary venous obstruction in an infant with total anomalous pulmonary venous drainage before and after operation. This technique is less invasive and provides precise spatial information of complicated vascular anomalies.

Elevated ratio of summed serum proinsulin to insulin response after oral glucose load in type 2 diabetes decreases following sulfonylurea treatment.

We showed previously that the disproportionate elevation of serum proinsulin at fasting and after glucose ingestion in Type 2 diabetes is reduced to nearly normal after improvement of glycemic control by diet therapy. In this study, we investigated the effect of sulfonylurea (SU) treatment on serum proinsulin levels and proinsulin/insulin ratio (PI/I) during oral glucose tolerance test in patients with Type 2 diabetes. Thirteen diabetic patients (age 56 +/- 9 years, body mass index 22.4 +/- 1.9 kg/m2, mean +/- SD) were examined by 75 g oral glucose tolerance test (OGTT) before and after glycemic control by SU therapy. Mean interval of two OGTTs was 126 days. Serum proinsulin was measured by the radioimmunoassay using a human proinsulin-specific antiserum. When glycemic control improved after SU therapy (mean fasting plasma glucose 11.5 and 6.0 mmol/l, before and after SU treatment), fasting insulin, proinsulin and PI/I ratio did not change significantly. Insulin response during OGTT markedly increased after SU therapy. Summed value of insulin (sigma I) increased from 634 to 1064 pmol/l after SU (P < 0.01), whereas summed proinsulin (sigma PI) did not change significantly (146 and 159 pmol/l), resulting in a significant decrease in sigma PI/sigma I (23.6-15.1%, P < 0.05). We conclude that the disproportionate elevation of proinsulin during OGTT in patients with Type 2 diabetes can be reduced after glycemic control by SU treatment, chiefly by a selective increase in insulin response.

Effect of islet amyloid polypeptide (IAPP/amylin) on 2-deoxyglucose uptake in mouse pancreatic acini.

In order to examine the effect of islet amyloid polypeptide (IAPP/amylin), a product of the pancreatic beta cell and a major component of islet amyloid deposits, on exocrine pancreatic function, we studied the effect of rat IAPP amide (IAPP-NH2) on 2-deoxy-D-glucose (2-DG) uptake in isolated mouse pancreatic acini. Mouse pancreatic acini were preincubated for 80 min with various concentrations of IAPP-NH2 (1 nM-1 microM) and [3H]2-DG uptake for 20 min was measured. The full effect of IAPP-NH2 on this function was not immediate but increased linearly with time for up to 80 min of incubation. IAPP-NH2 caused a dose-dependent stimulation of 2-DG uptake by mouse acini; a detectable effect at 10 nM and a maximal effect at 1 microM. In the presence of 1 microM IAPP-NH2, 2-DG uptake increased by 69 +/- 8% above basal (mean +/- SD, n = 6). The results indicate that IAPP-NH2 stimulates glucose uptake in mouse pancreatic acini, and raise the possibility that IAPP-NH2 plays some physiological role in the insuloacinar axis in mouse pancreas.

Three-dimensional observation with a confocal scanning laser microscope of fibronectin immunolabeling during cardiac looping in the chick embryo.

From the beginning of cardiac myofibrillogenesis in the chick embryo, developing myofibrils at the bottom of the inner myocardial cell layer facing the cardiac jelly are already aligned circumferentially in the direction of the heart tube. To elucidate the mechanism of this alignment, we investigated the temporal and spatial expression of fibronectin and its relationship to actin filaments before and during looping (4- to 13-somite stages) by using a confocal scanning laser microscope. Serial optical tomograms were obtained from whole-mounted heart tubes stained with fluorescein-conjugated antibody against cellular fibronectin and rhodamine-conjugated phalloidin. Before looping (4- to 7-somite stages), particulate and speckled fibronectin formed loose networks. At the onset of looping (8- to 9-somite stages), fine fibrils of fibronectin appeared. They became dense and were arranged circumferentially in the direction of the heart tube. They were aligned parallel with the thick actin bundles that appeared as an initial stage of developing myofibrils. During looping, (10- to 13-somite stages), fibronectin fibrils were fragmented and showed a speckled pattern, while the number of circumferentially aligned mature striated myofibrils increased. These observations suggest that the temporal arrangement of fibronectin fibrils at the beginning of looping plays a role in the circumferential alignment of developing myofibrils.

3-D observation of N-cadherin expression during cardiac myofibrillogenesis of the chick embryo using a confocal laser scanning microscope.

It is not yet understood whether cell adhesion molecules play an active role in early cardiac morphogenesis or not. We present here the spatial and temporal expressions of N-cadherin and its relationships to actin filaments during looping (7- to 13-somite stages) of the chick embryonic heart tube observed by means of a confocal laser scanning microscope. Serial optical tomograms were obtained from the whole-mounted heart tubes stained with antibody to N-cadherin (fluorescein-conjugated) and phalloidin (rhodamine-conjugated). Three patterns of N-cadherin expression were observed during looping; a belt-like pattern, speckled pattern, and clumped pattern, corresponding to adhesion belt, nonjunctional cell contact and early intercalated disks, respectively. At the 7-somite stage, myocytes expressed N-cadherin as adhesion belt and nonjunctional cell contact. At the 8- to 10-somite stages, the clumped pattern of N-cadherin was detected before striated myofibrils appeared. Myofibrils began to develop across the clumps to form transcellular networks in the outer layer, and to form circumferential alignments in the inner layer. These results suggest that N-cadherin is responsible for the connection of myofibrils between the neighboring myocytes, and the alignment of the two layers in the developing heart tube.

3-D observation of actin filaments during cardiac myofibrinogenesis in chick embryo using a confocal laser scanning microscope.

Using a confocal laser scanning microscope (CLSM), we observed subcellular three-dimensional (3-D) arrangements of actin filaments stained with fluorescein-labeled phalloidin during myofibrinogenesis of chick embryonic heart (7- to 13-somite stages). Serial optical tomograms were obtained from whole-mounted heart tubes and reconstructed into stereoscopic images. Development of myofibrils in myocardial differentiation considerably differed in inner and outer myocardial cell layers. In the outer layer, initial myofibrils appeared along cell membranes at the 8-somite stage. They increased rapidly and constituted network structures with spatial extension over cell-cell junctions. In the inner layer, myofibrils appeared at the bottom, facing the cardiac jelly, at the 10-somite stage, and, when the straight heart tube began to bend, they were already aligned circumferentially in the direction of the heart tube. Double staining of fluorescein-phalloidin and DiI [1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine perchlorate; DiI-C18-(3)] of the looped heart revealed that while myocytes in the outer layer were round, those of the inner layer were spindle-shaped, and their long axes coincided with the circumferential direction. These results suggest that the circumferentially arranged myofibrils at the bottom of the inner layer may play an important role in the looping of the heart tube.

Temporal and spatial patterns of phosphotyrosine immunolocalization during cardiac myofibrillogenesis of the chicken embryo.

To investigate the possible role of phosphorylation of protein tyrosine during myofibrillogenesis (6- to 13-somite stages) of the chicken embryonic heart tube, immunolocalization of phosphotyrosine (P-Tyr) and the relationship between P-Tyr and developing myofibrils were studied by means of confocal scanning laser microscopy and immuno-electron microscopy. The staining pattern of P-Tyr varied in different sites of myocytes at different stages of embryonic development: At the cell-cell boundaries, P-Tyr was localized at the adhesion belt of outer myocardial layer cells (6- to 13-somite stages), non-junctional cell-cell contacts (6- to 13-somite stages) and early intercalated disks of both the outer and inner myocardial layer cells (8- to 13-somite stages). At the cell-extracellular matrix boundaries of inner layer cells, the first stages of myofibril formation appeared as serially aligned areas of P-Tyr localization closely associated with circumferentially aligned thick actin bundles (8- to 9-somite stages). This P-Tyr immunostaining decreased when the thick actin bundles developed into mature striated myofibrils at the 10- to 13-somite stages. These findings suggest that the phosphorylation of protein tyrosine residues is primarily concentrated at the modulating cell-cell and cell-matrix adhesion sites of developing myocytes and myofibrils.

Multiform accelerated idioventricular rhythm (AIVR) in a child with acute myocarditis.

Acute myocarditis is complicated by various types of conducting disturbances and heart failure. We describe the case of a school boy with acute myocarditis, who developed various types of conduction disturbances, including multiform accelerated idioventricular rhythm (AIVR), during convalescence from severe pump failure. Multiform AIVR has been reported mostly in adults but, to the best of our knowledge, not in children. The arrhythmia noted in our patient persisted for only 2 days and disappeared with recovery.

Lower levels of vitamin C in plasma and urine of Japanese male smokers.

We studied the vitamin C status of smokers and nonsmokers among staff members of our university in 1982. This paper describes the results from the 1983-85 studies. Plasma vitamin C levels (M +/- SD, mg/dl) from smokers and nonsmokers, respectively, were as follows: 0.49 +/- 0.15 (n = 51) and 0.72 +/- 0.23 (n = 73) in 1983, 0.56 +/- 0.13 (n = 48) and 0.84 +/- 0.21 (n = 88) in 1984, and 0.52 +/- 0.15 (n = 56) and 0.86 +/- 0.24 (n = 93) in 1985. The differences between smokers and nonsmokers are all highly significant. Urinary vitamin C levels (M +/- SD, mg/dl) from smokers and nonsmokers, respectively, were 1.8 +/- 0.6 and 2.6 +/- 0.9 in 1983 and 2.0 +/- 0.7 and 2.9 +/- 1.0 in 1984. These differences between the two groups are also highly significant. Both groups were similar in age, height, weight, general health parameters, and vegetable and fruit consumption. Plasma and urinary vitamin C levels were significantly higher in smokers taking vitamin C supplement than in those not taking vitamin C supplement.

Pulmonary hypertension as a fatal complication of extrahepatic portal hypertension.

Pulmonary hypertension is an uncommon complication of portal hypertension seen in cirrhotic as well as noncirrhotic patients. We report a 10-year-old girl who presented with extrahepatic portal hypertension and pulmonary hypertension in the absence of intrinsic liver disease. Further investigations revealed high serum concentrations of prostaglandin F2 alpha, thromboxane B2 in the inferior vena cava, and angiotensin I in the inferior vena cava and right ventricle. The increased levels of these vasoconstrictive substances strongly suggest that the possible mechanism for the pulmonary hypertension in such patients with extrahepatic portal hypertension include shunting of vasoactive agents from the splanchnic circulation to the pulmonary vascular bed.

[Appraisal of ultradian components in the ethosecretogram of rat].

An ethosecretogram, which illustrates phase relation between animal's behavior and plasma hormone levels, was constructed in conscious rats. A catheter was placed into the right atrium in male rats at least 2 days prior to blood sampling. Plasma corticosterone levels were monitored individually through the catheter every 5 min over a period of several hours under freely moving conditions on an Animex which records spontaneous locomotor activity. Furthermore, phase relation of ultradian components in both variables were analyzed in separate series of experiments. Results obtained are as follows; Both locomotor activity and plasma corticosterone level in the ethosecretogram exhibited ultradian components with a 60-90 min cycle. Ultradian components of both variables were phase-locked, the bursts of locomotor activity preceding the hormone peak by 15 min. As to the type of locomotor activity, feeding and grooming were significantly correlated with a subsequent hormone elevation, whereas drinking was not. Feeding-induced hormonal elevation was greater in response at dark phase (especially at midnight) than at light phase. Drinking of glucose solution induced a hormone elevation similar to feeding, whereas intravenous infusion of glucose solution did not. Feeding-induced hormone elevation was not abolished even when the vagi were effectively cut at a subdiaphragmatic level. It was assumed that the information from digestive organs to the CNS was not transmitted neurally via the sensory vagal nerves, but humorally via a humoral factor(s) released from digestive organs.