Classification of antiarrhythmic drugs based on ventricular fibrillation threshold

The antifibrillatory action of antiarrhythmic drugs, classified on the basis of their effects on ventricular fibrillation threshold (VFT), was investigated. The relation between drug action and cardiac excitability, orthodromic/antidromic conduction through Purkinje fibers and ventricular muscle and the restitution of premature action potential duration was studied. Drug classifications were: group A, VFT markedly increased; group B, VFT moderately increased; and group C, no significant change. Group A was subdivided according to presence or absence of the dip phenomenon and supernormal period in the anodal strength-interval curve. Drugs in group A significantly reduced the difference between effective refractory period of orthodromic and antidromic conduction and the range over which the premature action potential duration reappeared. In groups B and C, the effective refractory period in orthodromic conduction was longer than that in controls, and the range of the restitution of premature action potential duration for Purkinje fibers was reduced only slightly.     

Evidence that the Na+-Ca2+ exchange system is related to the antiarrhythmic action of disopyramide

1. Disopyramide induced a concentration-dependent decrease in action potential amplitude and Vmax, and prolonged action potential durations (APD50 and APD90) in ventricular muscle. 2. Na+-loaded membrane vesicles isolated from canine ventricular muscle rapidly accumulated Ca2+. 3. Monensin (10(-5) M) abolished Na+-dependent Ca2+ uptake, and Na+ enhanced Ca2+ efflux. 4. Na+-Ca2+ exchange by membrane vesicles was more active in preparations pretreated with disopyramide (10(-5) M) than in control membranes. 5. The results suggest that disopyramide changes Na+ influx from Na+ channel mediated to Na+-Ca2+ exchange mediated. This is verified in part by increased Ca2+ efflux.     

The effects of pulsatile and non-pulsatile cardiopulmonary bypass on renal blood flow and function

The physiologic effects of pulsatile and non-pulsatile flow in cardiopulmonary bypass were compared in terms of the relationship between different flow rates and what effects these had on pulsatile and non-pulsatile flow. Forty adult mongrel dogs were used in this study and divided into 5 groups, each comprised of 8 animals, according to the flow rate during cardiopulmonary bypass, namely; 40, 60, 80, 100, or 120 ml/kg/min. The animals were perfused with either pulsatile or non-pulsatile flow for 1 hour, given randomly at the same mean flow rate. At flow rates of 80 and 100 ml/kg/min, the mean arterial blood pressure and total peripheral vascular resistance were significantly lower in pulsatile flow than in non-pulsatile flow, and the renal blood flow was significantly greater in pulsatile flow than in non-pulsatile flow. The renal arterial-venous lactate difference was significantly less in pulsatile flow than in non-pulsatile flow at a flow rate of 80 ml/kg/min, and the renal lactate extraction was significantly higher in pulsatile flow than in non-pulsatile flow at the same flow rate. The renal excess lactate was significantly lower in pulsatile flow than in non-pulsatile flow at a flow rate of 100 ml/kg/min. There were no significant differences in these parameters between the two types of perfusion at flow rates of 40, 60 or 120 ml/kg/min. Pulsatile flow was therefore apparently advantageous, when compared to non-pulsatile flow, in terms of hemodynamics, renal circulation, and metabolism of the kidney at flow rates of 80 and 100 ml/kg/min. However, when the flow rate was 120 ml/kg/min, pulsatile flow and non-pulsatile flow had the same effects.     

Changes of the auditory system after cerebellopontine angle manipulations

The current tendency in acoustic neuroma surgery to attempt the preservation of hearing function and the problem of accidental hearing loss caused by microsurgical neurovascular decompression operations for hemifacial spasm or trigeminal neuralgia prompted us to study the exact surgical vulnerability of the auditory system. The surgical procedures for operation on the cerebellopontine angle of dogs were carried out according to the sequence of the posterior fossa transmeatal operation for acoustic neuroma. The operation was tentatively divided into three stages: (a) craniectomy and dural opening, (b) cerebellar retraction, and (c) identification of the cochlear nerve in the unroofed internal auditory canal (IAC). The postoperative behavior of the auditory system was evaluated electrocochleographically (EcochG) and histologically. Overzealous retraction of the cerebellar hemisphere caused transient disturbance of the EcochG pattern. Mechanical stretching of both the cochlear nerve and the internal auditory artery may cause a disturbance in the synchronized discharge of the cochlear neurons. Various manipulations at the porus acusticus internus or the IAC (such as pinching the nerve with forceps or electrocoagulation) produced thoroughly distorted EcochG patterns. From the histological findings, the main causative factor for these labyrinthine damages was considered to be vascular insufficiency. The current need for neurosurgical operations to preserve hearing is discussed in the light of these findings.     

Hemiarthroplasty for rotator cufftear arthropathy

Treatment of rotator cuff tear arthropathy presents a formidable challenge for the shoulder surgeon. The alteredmechanical and nutritional environment of the shoulder thought to be responsible for the development and progression of the arthropathy also may contribute to the failures of surgical intervention. In the past, several surgical procedures, including total shoulder arthroplasty, have been used to treat rotator cuff tear arthropathy. However, hemiarthroplasty seems to have the most consistent and predictable long-term results. Even so, certain technical points must be considered while performing a hemiarthroplasty to minimize pain and maximize motion and function. These surgical considerations include mobilizing the rotator cuff and attempting to repair the tear whenever possible, appropriate sizing of the humeral head prosthesis, and placing the humeral head in increased retroversion.     

Primary liposarcoma of the mediastinum--a case report and review of the literature

Liposarcoma of the mediastinum is a rare disease. A 59 year old woman was seen with the complaint of dizziness. A chest radiogram taken during the course of investigation for hypertension revealed a large mass shadow 24 X 18.5 X 12 cm located in the anterior mediastinum. The tumor of the mediastinum was diagnosed as a benign lipoma when it was first resected, but subsequently proved to be a liposarcoma when it re-appeared 2 years and 10 month later. Based on the WHO classification, the mixed type of liposarcoma was diagnosed. The salient and pathological features of mediastinal liposarcoma are reviewed and compared with those nine cases reported in Japan and fifty in North America and European countries. Treatment by simple enucleation or shelling out of the tumor should be discouraged, since this seems to be the main cause of local recurrence. Surgical wide en bloc excision is the treatment of choice.     

A newly established human gestational choriocarcinoma cell line and its characterization

The cell biological characteristics of a newly established human gestational choriocarcinoma cell line, HM, were examined and compared with four other gestational and two nongestational choriocarcinoma cell lines. Striking heterogeneity in the production and secretion of hCG and its subunits was observed among the cell lines. The HM cell line consisted mainly of cytotrophoblast-like cells, and the hCG and its subunit values in both the cells and culture fluid were extremely low. The syncytiotrophoblast-like multinucleated giant cells which were occasionally seen in other cell lines were scarce in the HM cell line in vitro. On the other hand, deviation of the LDH isozyme pattern to the heart-type (LDH1) was characteristic of the HM cells in contrast to the other cell lines in which LDH3 was dominant. The HM cell line represents useful material for investigating the cell biological heterogeneity of human choriocarcinomas.     

Fundamental studies on tumor angiogenesis factors with a choriocarcinoma model

We have studied biologically active substances, tumor angiogenesis factors (TAF), which are supposed to be associated with the proliferation and metastases of choriocarcinoma cells. Eight human choriocarcinoma cell lines were used in the present study. TAF activity was assayed by bioassays using BALB/c mice subcutaneous tissue, chicken chorioallantoic membrane (CAM) and rabbit cornea in vivo and by proliferation of endothelial cells in vitro. 1. We found a positive correlation between the size of tumors developed in xenotransplantation and the number of blood vessels in the tumor tissues. A correlation between the number of blood vessels and TAF activity was also found. 2. With a gel-filtration method, TAF activity was observed in the common fractions in every cell line. The molecular weight of TAF was more than 10,000 daltons. 3. There was a heterogeneity of TAF activity among the cell lines. From these results, it appears that TAF initiates the choriocarcinoma cell-proliferation.     

Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value.

GAWK (chromogranin-B 420-493) is a 74 amino acid peptide recently isolated from human pituitaries. Using two different antibodies (directed against GAWK [1-17] and [20-38] fragments) GAWK-LI was measured in tumors from 194 patients and in the plasma of 434 patients by RIA. The highest tissue concentrations of GAWK-LI were found in pheochromocytoma (GAWK [1-17]-LI, 18,173 +/- 3,915; GAWK [20-38]-LI, 17,852 +/- 2,763 [mean +/- SEM] pmol/g wet wt tissue; n = 9), which were at least ten times higher than any other tumors producing GAWK-LI. High concentrations of GAWK-LI were also found in other types of endocrine tumors including carcinoid, medullary carcinoma of thyroid, pancreatic, and ACTH-producing lung tumors. On the other hand, low concentrations of GAWK-LI were found in nonendocrine tumors. Plasma concentrations of GAWK-LI were found to be elevated in patients with endocrine tumor, but more so in those with pancreatic tumors than with pheochromocytomas. Plasma concentrations returned to normal after successful tumor removal. Chromatographic profiles of GAWK-LI in extracts of pheochromocytomas and normal adrenals showed high molecular weight peaks that were absent in the extracts of other endocrine tumors and normal pancreas, suggesting differential tissue-specific processing. Thus GAWK-LI is produced by a variety of endocrine tumors and may serve as a plasma tumor marker, especially in patients with pancreatic endocrine tumors.