Upgrade rate of core biopsy-determined atypical ductal hyperplasia by open excisional biopsy.

BACKGROUND: Core biopsy finding of atypical ductal hyperplasia (ADH) are generally followed by open biopsy to avoid underestimation of malignant disease. METHODS: Retrospective examination of 11 gauge stereotactic-guided vacuum-assisted core biopsies was made with respect to ADH diagnosis, follow-up open biopsy, and upgrade rate. Readily available clinical, mammographic, and pathologic features potentially contributory to an upgrade were studied. RESULTS: This series of 1,313 patients had 43 ADH diagnoses. Thirty-two had open follow-up. There were 4 upgrades. Mammographic indication for biopsy, age, removal of calcifications, and the percentage of ADH in the specimen were not significant in predicting an upgrade with all probabilities over 0.10, odds ratios not different than 1, and 95% bounds all encompassing 1. CONCLUSIONS: These data indicate a high upgrade rate (13%) for ADH-positive core biopsies with no definitive predictive criteria for an upgrade. Our data support follow-up excision of ADH lesions diagnosed by core biopsy.

Retaining the aortic fat pad during cardiac surgery decreases postoperative atrial fibrillation.

BACKGROUND: Atrial arrhythmias are a common and serious complication of cardiac surgical procedures. Reports describing pericardiac neurogenic tissue led us to hypothesize that removal of the aortic fat pad could cause an autonomic imbalance and contribute to atrial arrhythmias following cardiac surgery. METHODS: Patients (n=131) underwent either conventional cardiopulmonary bypass surgery (CPB) or off-pump coronary artery bypass (OPCAB) surgery. The aortic fat pad was either left intact or removed. The incidence of de novo atrial arrhythmias during the patient's hospital stay was tabulated. Patients with peri-operative myocardial infarction or pre-existing atrial or supraventricular arrhythmias were excluded. RESULTS: Demographics, preoperative medications, ASA and NYHA classifications, and complication rates (other than for atrial arrhythmias) did not differ among the groups. The STS-predicted mortality was higher in the CPB/Fat-Pad-Removed group (2.23 +/- 1.89) than in either the OPCAB/Fat-Pad-Intact (1.09 +/- 0.80) or OPCAB/Fat-Pad-Removed (1.02 +/- 0.62) groups (p < 0.05). Atrial arrhythmias were present in 19 of 131 patients (14.5%). Logistic regression demonstrated a significantly elevated atrial arrhythmia rate when the fat pad was removed (odds ratio = 3.49, 95% bounds = 1.09 to 11.18, p = 0.035). Neither the pump status nor the cross product of pump status by fat pad status were significant in this pilot study. CONCLUSIONS: Retaining the aortic fat pad during coronary artery bypass surgery is correlated with a decreased incidence of postoperative atrial arrhythmias.

Stereotactic breast biopsy in a community hospital setting.

Our institution began using a stereotactic core needle breast biopsy system for mammographically detected breast lesions in November 1996. The system consists of a LORAD stereo imaging table and an 11-gauge vacuum-assisted mammotome (Biopsys Medical, Irvine, CA). All biopsies were performed with the combined efforts of a radiologist and a surgeon. Three hundred sixteen biopsies were attempted in 279 patients, with multiple biopsies in 31 patients. Indications included microcalcifications in 52 per cent of patients and a mass in 48 per cent of patients. Biopsy was unsuccessful in 20 patients (6.3%). Pathologic diagnoses included invasive ductal carcinoma (19 patients), invasive lobular carcinoma (2), ductal carcinoma in situ (17), atypical ductal hyperplasia (8), atypical lobular hyperplasia (1), fibroadenoma (40), lymph node (7), and benign (202). Invasive cancer, in situ carcinoma, or atypical hyperplasia was diagnosed in 46 (15.6%) lesions. Thirty-six patients had open biopsies. The core biopsy diagnosis was correct in 27 lesions, unable to be confirmed in six cases and changed in four cases, with three lesions upgraded and one case downgraded. The 11-gauge vacuum-assisted mammotome provides excellent accuracy for diagnosing mammographic abnormalities. A combined effort between radiology and surgical services is an effective way of using the stereotactic biopsy system.

Endoscopic vein harvest for coronary artery bypass grafting: technique and outcomes.

BACKGROUND: The greater saphenous vein is a common conduit for coronary revascularizations. Traditional vein harvesting uses long incision(s) that can lead to significant morbidities. A minimally invasive technique has been developed that allows the harvest of much of the saphenous vein with one incision and fewer morbidities. METHODS: Our technique and outcomes on 110 patients with minimally invasive harvest (endoscopic vein harvesting) is presented. Comparisons are made with an equivalent retrospective group within the same hospital and to a smaller (n = 28) prospective group at other hospitals. RESULTS: Endoscopic vein harvesting has evolved to one above-knee incision of 3 cm length that allows for the harvest of 35 cm of vein. Harvest times were longer for endoscopic vein harvesting, showed a learning curve, and appeared to reach a baseline of 35 minutes. Incision closure times were less for the endoscopic vein harvesting group. Total skin to skin operating times for the entire cardiovascular procedure did not differ between the groups. In relatively homogeneous populations, leg infection rates did not differ, but other leg morbidities were less for the patients who underwent endoscopic vein harvesting. Hospital readmissions for leg wound care were low in both groups although the number of office visits required for leg care was higher for patients undergoing traditional vein harvesting. Pain perception by the patients was much less for the endoscopic vein harvesting and remained lower for up to 4 weeks. CONCLUSIONS: Although endoscopic vein harvesting is a relatively new procedure, it is safe, effective, and less painful for the patient and carries fewer morbidities.

Factors influencing bowel function following total abdominal colectomy.

PURPOSE: The purpose of this study was to determine which factors influenced bowel function following total abdominal colectomy. METHODS: Thirty-two patients who had undergone total abdominal colectomy were studied with regard to factors that are classically thought to influence bowel function, namely, residual stump length, transit time, and rectal stump manometry. In a limited subset of patients, anal manometry was done also. RESULTS: Transit time was the best predictor of bowel function following total abdominal colectomy. This was followed by stump length. If transit time was short, then stump length became important in predicting the occurrence of diarrhea following total abdominal colectomy. CONCLUSIONS: Two factors have an important influence on bowel function following total abdominal colectomy: transit time and rectal stump length. Rectal stump length is an anatomic factor that can be controlled by the surgeon. In total abdominal colectomy, rectal stump length of at least 20 cm is necessary if the patient is to have satisfactory postoperative bowel function. This may not always be possible. In these patients, modification of diet to influence transit time and methods to increase rectal compliance will be necessary.

Effects of granulocyte colony-stimulating factor in severe pancreatitis.

BACKGROUND: The effect of granulocyte colony-stimulating factor (G-CSF) on the rate of secondary infections in acute pancreatitis was evaluated in a canine model. Infectious complications are the major determinant of morbidity and mortality in severe pancreatitis. Bacterial translocation has been shown to be a cause of these secondary infections. The relative immunosuppression found with pancreatitis may promote translocation and the spread of bacteria to the pancreas. METHODS: Thirty-four mongrel dogs were studied. Pancreatitis was induced in 18 dogs; 9 were treated with 100 micrograms G-CSF/day and 9 were given only saline solution. Laparotomy alone was done in 16 dogs of which one half were given 100 micrograms G-CSF/day and one half were given saline solution. Daily blood counts and cultures were obtained. All dogs were killed on day 7, and the mesenteric lymph nodes, pancreas, liver, spleen, and peritoneal fluid were cultured and studied histologically. RESULTS: G-CSF caused a significant and sustained increase in mature granulocytes in dogs given pancreatitis. No difference was found in the rate of translocation to mesenteric lymph nodes in dogs given G-CSF (n = 4) versus dogs given saline solution (n = 6). However, a significant decrease occurred in the spread of bacteria to distant sites in dogs given G-CSF (1 versus 15, p < 0.05). CONCLUSIONS: Although G-CSF does not decrease the rate of translocation, it does decrease the rate of distant infection in severe acute pancreatitis.

Laparoscopic injection of fibrin glue to arrest intraparenchymal abdominal hemorrhage: an experimental study.

The laparoscope offers a novel avenue for the diagnosis of intra-abdominal injury and the use of fibrin glue (FG) as a treatment for hemorrhage in trauma patients. This study was undertaken to assess the practicality and effectiveness of FG injection under laparoscopic direction to arrest hemorrhage in solid viscera. Twenty dogs were randomized into a control group (CG) and a treatment group (TG). All animals underwent laparotomy to surgically induce uniform injuries to the hepatic and splenic parenchyma. The TG animals (n = 12) were allowed to hemorrhage for 30 minutes. The injuries were then visualized and FG injected intraparenchymally under laparoscopic direction. The average duration of the procedure was 25 minutes (range, 15-50). No hemostatic interventions were performed on the CG animals (n = 8). Mortality in the CG was 63% (5 of 8); there were no deaths in TG animals prior to sacrifice. Necropsy of TG animals revealed progressively healing hepatic and splenic injuries with no gross evidence of pulmonary FG emboli, intraparenchymal microemboli, or increased adhesion formation. No other complications were noted. This study demonstrates that hemorrhage from the liver and spleen can be successfully controlled using the laparoscope to direct the intraparenchymal injection of FG. In this experimental model, the procedure can be performed expeditiously. It is associated with reduction of mortality to zero when compared with controls. No complications associated with laparoscopy or FG injection were recognized. This technique may have potential for application in the management of stable patients who manifest evidence of intraperitoneal hemorrhage as a result of solid organ injury.

Cost-effectiveness of neonatal screening for Duchenne muscular dystrophy--how does this compare to existing neonatal screening for metabolic disorders?

Costs of screening a series of 18,152 newborn males for Duchenne muscular dystrophy (DMD) in Canada were evaluated. The final aim of neonatal screening for DMD is the avoidance of additional cases in the families identified. Total costs to avoid one case of DMD were estimated at Cdn. $172,000, while the incremental costs were found to be $83,000. Reagent costs, test sensitivity, efficacy of screening and compliance with genetic advice were identified as factors crucial for cost-effectiveness. Costs of neonatal screening for DMD are compared with costs of neonatal screening for inborn metabolic disorders. It is found that the two programmes are similar in costs. Earlier predictions of inordinate costs of screening for DMD are refuted.

Impact of genetic counselling after neonatal screening for Duchenne muscular dystrophy.

In a pilot neonatal screening programme for Duchenne muscular dystrophy (DMD) conducted in the Canadian province of Manitoba, a cohort of eight affected males was identified between 1 January 1986 and 31 December 1989. Demographic information, knowledge of DMD, reproductive outcome, and attitudes to prenatal diagnosis and neonatal screening for DMD were obtained through questionnaires distributed in May 1992 to the eight sets of parents of index cases, two high probability carrier aunts, and one high probability carrier sister. Personal interviews were subsequently conducted in the summer of 1992. Although there is overall consensus among the families in favour of routine neonatal screening for DMD, five of seven subsequent pregnancies reported in six women were not monitored by prenatal diagnosis and have resulted in the birth of two affected boys. In a comparable time interval, prenatal diagnosis was acceptable to carrier females whose affected male relatives were traditionally diagnosed at four or five years. We conclude that, although molecular genetic analysis now allows for precise diagnosis of DMD, highly accurate carrier testing and prenatal diagnosis, very early DMD carrier identification, and genetic counselling after the identification of DMD males in a population based neonatal screening programme may not be an effective way of decreasing the number of repeat cases of DMD within families or the overall population frequency of DMD.

Congenital hydrocephalus secondary to Walker-Warburg syndrome identified on the Manitoba Neonatal Screening Programme for Duchenne muscular dystrophy.

This report describes our first experience with a clinically important true false positive neonatal screening test for Duchenne muscular dystrophy (DMD). Neonatal screening for DMD began as a pilot programme in Manitoba on 1 January 1986 by analysis of creatine kinase (CK) activity in dried filter paper blood spots. To date, all except two males with positive initial and follow up neonatal CK screening tests were subsequently diagnosed as having DMD. Of these two, one was a newborn male with congenital hydrocephalus whose positive DMD screening test led to the identification of an associated congenital myopathy and confirmation of the diagnosis of Walker-Warburg syndrome.

Effect of somatostatin analogue and cholecystokinin receptor antagonist on bile-induced acute canine pancreatitis.

To determine whether a synthetic somatostatin analogue, octreotide, and a cholecystokinin receptor antagonist, L-364,718, may be beneficial in acute pancreatitis, 33 dogs were assigned to four groups. Each dog underwent laparotomy with injection of autologous bile into the dorsal pancreatic duct. Thirty minutes after the induction of pancreatitis, Group 1 received a subcutaneous injection of octreotide (200 micrograms/kg), Group 2 received an equal volume of the octreotide carrier, Group 3 received an hourly intravenous bolus of L-364,718 (60 micrograms/kg), and Group 4 received an equal volume of the L-364,718 carrier. Hemodynamic profiles, arterial blood gases, plasma glucose, and serum amylase were obtained before laparotomy, at bile injection, and at hourly intervals. The pancreas was removed after 8 hours for gross evaluation, measurement of water content, and histologic examination. A significant decrease in cardiac index and a significant increase in serum amylase and pancreatic edema occurred in all four groups 8 hours after the induction of pancreatitis (P less than 0.05), but there was no statistical difference between any group. Likewise, there was no difference in gross or histologic changes in the pancreas of any group. The somatostatin analogue, octreotide, and the cholecystokinin receptor antagonist, L-364,718, did not ameliorate the effects of severe, bile-induced pancreatitis in dogs.

Three years' experience with neonatal screening for Duchenne/Becker muscular dystrophy: gene analysis, gene expression, and phenotype prediction.

Neonatal screening for Duchenne/Becker Muscular dystrophy (DMD/BMD) was begun as a pilot program on January 1, 1986. The aim of this program was to reduce the incidence of this X-linked recessive degenerative neuromuscular disease. The neonatal detection of a boy with DMD allows early identification of carriers and genetic counselling. This may avert the birth of other affected males born prior to clinical diagnosis of DMD in the propositus at about age 5 years. Between January 1, 1986, and December 31, 1988, we identified and characterized a cohort of 8 asymptomatic infant boys with grossly elevated levels of creatine kinase, an active primary dystrophic process of muscle and complete dystrophin deficiency. Five of 8 males have detectable DNA alterations involving the DMD/BMD locus. Based on current hypotheses, characterization of dystrophin expression of this cohort allows us to predict a DMD phenotype in all 8 boys. To date, no additional males with DMD have been born in these families. Prospective follow-up will allow us to test the validity of dystrophin testing in predicting the clinical course and impact of this program on reproductive decision making in these families.

Calcitonin gene-related peptide increases coronary flow and decreases coronary resistance.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator, but its effects on in situ ventricular function are unknown. We studied effects of intracoronary CGRP (100, 200, and 600 pmole/min, for 10 min) in 21 open-chest chloralose-anesthetized dogs. Systemic, pulmonary, left ventricular (LVP), central venous, and pulmonary capillary wedge pressures were continuously monitored. Left ventricular wall thickness (WT) and circumflex coronary blood flow were also measured. CGRP was infused into the proximal circumflex artery. During CGRP infusion there were no changes in heart rate, cardiac index, pulmonary artery pressure, or systemic vascular resistance, no percentage change in ventricular WT, and no changes in dWT/dt, peak dP/dt, or the slope of end-systolic points on WT/LVP loops. But there were significant changes in coronary flow (CQ), coronary resistance (CRES) and mean arterial blood pressure (MAP) from control (C)* (P less than 0.05). (table; see text) CGRP is a potent coronary artery vasodilator causing notable dose-dependent decreases in coronary resistance and a rise in myocardial flow, despite a decreased MAP (all P less than 0.05). CGRP does not affect ventricular contractility in vivo.

Is DNA ploidy of prognostic significance in stage I cutaneous melanoma?

Recent studies have suggested that the presence of DNA aneuploidy in stage I cutaneous melanoma carries a poor prognosis. To see if our experience correlated with these reports, we used DNA analysis by flow cytometry of propidium iodide-stained nuclei disaggregated from formalin-fixed paraffin-embedded tissue of biopsy specimens to retrospectively study 55 patients who had cutaneous stage I melanomas. The patients had been treated from 1977 to 1987 with a mean follow-up of 5.4 years. Thirty-nine (71%) of the 55 histograms were diploid, and 16 (29%) of the histograms were aneuploid. DNA content was significantly associated with other conventional prognostic factors, including growth pattern, ulceration, pathologic stage, tumor thickness, and Clark's level. DNA aneuploidy was significantly related to disease-free survival and predicted a poorer prognosis (p less than 0.05), but when stratified for tumor thickness it lost significance. A multivariate discriminant function analysis of 12 factors in melanoma showed six factors to be independently significant in determining prognosis. DNA content (p = 0.034) ranked fifth in importance behind growth pattern (p less than 0.001), ulceration (p less than 0.001), thickness (p = 0.001), and pathologic stage (p less than 0.005). DNA content, although significantly associated with conventional prognostic factors and disease-free survival, is not the best indicator of biologic behavior of melanomas in this study. Further investigation into its usefulness is necessary before DNA content can become a routine diagnostic modality in the work-up of stage I cutaneous melanomas.

The effect of parathyroid hormone on the acutely ischemic myocardium.

UNLABELLED: Parathyroid hormone (PTH) is reported to be a potent vasodilator. To determine if this action is beneficial in acute myocardial infarction (AMI) and is due to changes in prostacyclin or thomboxane, thirty dogs were anesthetized and instrumented (left atrial, coronary sinus, left main coronary, pulmonary artery and femoral artery catheters). AMI was induced by ligating the left anterior descending coronary artery. Either pentobarbital or alpha chloralose anesthesia was randomly assigned. Following LAD ligation, animals were randomized to receive PTH 0.008 nm/kg over 10 minutes every 30 minutes during the ischemic period or an equal volume of saline. Cardiac index, regional myocardial blood flow, O2 consumption and lactate production were measured. Infarct size was determined by computerized planimetry. PTH bioactivity was verified by adenyalate cyclase stimulating activity in rat osteosarcoma cells. Myocardial blood flow ranged from 81.5 to 155.2 ml/min/kg for normal myocardium. Cardiac index, O2 consumption, lactate production and myocardial perfusion was unaltered by the PTH administration. PTH reduced infarct size in dogs receiving pentobarbital but was deleterious in those receiving alpha chloralose. There was no difference in prostacyclin and thromboxane levels among groups. CONCLUSION: PTH is not beneficial in acute myocardial infarction.

Angina and other risk factors in patients with cardiac diseases undergoing noncardiac operations.

Six hundred eighty-eight consecutive patients with cardiac diseases or who were older than 70 yr of age, all of whom were undergoing noncardiac operations, were studied. Twenty-four preoperative risk factors were analyzed for the outcome of perioperative myocardial infarction (PMI) or cardiac death using stepwise logistic regression. Old age, emergency operation, angina, previous myocardial infarction, electrocardiographic signs of ischemia, type of surgical procedure, and hypokalemia were identified as individual factors useful in predicting outcome. Thirty-two patients (4.65%) developed PMI. Seven of these 32 patients (21.9%) and eight more patients without PMI--a total of 15 patients (2.2%)--died a cardiac death. Nonfatal but serious complications occurred in 23% of the patients. Patients undergoing emergency operations and patients with chronic stable angina, previous myocardial infarction, and electrocardiographic signs of ischemia were found to be at increased risk for PMI and cardiac death.

Gene studies in newborn males with Duchenne muscular dystrophy detected by neonatal screening.

18,000 newborn males were screened for Duchenne muscular dystrophy (DMD) by creatine kinase (CK) analysis of filter paper blood spots between Jan 1, 1986, and Dec 31, 1987. 5 affected boys have been identified, and in 3 of 5 probands molecular deletions or duplications have been found. 3 of 5 mothers were judged highly likely to be carriers of DMD because of repeatedly raised CK levels, identified gene rearrangements, or both abnormalities. 1 mother has a very low probability of being a carrier and 1 is at an intermediate risk. The use of DNA analyses in new DMD probands identified by neonatal screening has allowed confirmation of the diagnosis and accurate assignment of carrier status in mothers and female relatives in over half the cases studied, and may help to reduce the population incidence of DMD by avoiding delay before clinical diagnosis.

Identification of amiloride-sensitive Na+/H+ exchange in rat NB2 node lymphoma cells. Stimulation by 12-O-tetradecanoyl-phorbol-13-acetate.

Stimulation of mitogenesis in rat Nb2 node lymphoma cells by human (h) PRL was inhibited by inhibitors of Na+/H+ exchange (viz. amiloride and its analogs) and inhibitors of protein kinases (isoquinolinesulfonamide derivatives). The most potent were ethylisopropylamiloride (EP-Am) (IC50, 13 microM) and H-7, selective for protein kinase C (IC50, 23 microM), suggesting the possible involvement of Na+/H+ exchange and protein kinase C in mediating Nb2 cell mitogenesis. In the presence of hPRL, the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to activate the Na+/H+ antiporter as well as protein kinase C in other cell systems, enhanced the hPRL-stimulated Nb2 cell mitogenesis. TPA alone caused a dose- and time-dependent stimulation of H+ efflux in stationary cultures of Nb2 cells but had no effect on cell growth. From 25-100 nM TPA, the increase in the rate of H+ efflux was detectable by 3 min, reached a maximum by 15 min, and was sustained 30 min after the addition of TPA. The TPA-stimulated H+ efflux was dependent on extracellular Na+ and was almost completely inhibited after a 10 min preincubation with 25 microM EP-Am. TPA also increased the intracellular pH (pHi) of stationary cultures of Nb2 cells from 7.29 +/- 0.02 (n = 8) to a maximum of 7.45 +/- 0.03 (n = 10). The most rapid and greatest response was observed with 40 nM TPA which gave a detectable increase in pHi within 1 min and reached a maximum alkalinization by 6 min. Higher concentrations of TPA had no additional effect. The nontumor promoter phorbol 12,13,20-triacetate (PTA), either alone or in the presence of hPRL, had no effect on Nb2 cell proliferation or on H+ efflux or pHi in Hb2 cells. The TPA-induced increase in pHi was Na+-dependent and was inhibited by EP-Am and H-7. A preincubation with EP-Am (25 microM) for 5-10 min abolished the TPA-induced increase in pHi whereas prolonged incubation with H-7 (50 microM) for up to 3 h was required to decrease the stimulatory effect of TPA by approximately 50%. Although activation of the Na+/H+ exchange system is clearly an early consequence of the action of TPA on Nb2 cells, the failure of TPA to stimulate Nb2 cell proliferation suggests that stimulation of Na+/H+ exchange and protein kinase C activity are not sufficient to generate a mitogenic response in these cells.

Skeletal muscle insulin unresponsiveness during chronic hyperdynamic sepsis in the dog.

Recent reports from our laboratory and others have documented changes in insulin unresponsiveness and electrolyte and hormonal changes characteristic of hypodynamic shock states in anesthetized animals. Since most acute shock protocols do not adequately mimic the clinical profile of sepsis, the present study was undertaken to document the hemodynamic and metabolic changes associated with chronic hyperdynamic peritonitis in dogs. Mongrel dogs of either sex weighing 20 +/- 2 kg were surgically instrumented with an electromagnetic aortic flow probe for monitoring cardiac output determinations, and aortic and central venous catheters for withdrawing blood for blood pressure and chemical analyses. Following a recovery period (7-10 days) control hemodynamic and metabolic measurements were made. Sepsis was induced (peritoneal abscess) by implanting a 4" X 4" gauze sponge, previously inoculated with human fecal bacteria, amid the intestines. Experimental (N = 18) and pair-fed control (N = 6) animals were monitored daily for 21 days or until death. During the septic protocol, cardiac index increased from a control value of 3.4 L/min/m2 to 5.5 L/min/m2 by the end of the experimental period. Mean arterial blood pressure, total peripheral resistance index, body weight, and plasma Ca++ fell below control values during the experimental period. Body temperature, plasma glucose, insulin, glucagon, and Mg++ were all elevated with sepsis. At the end of the chronic experimental period, skeletal muscle insulin responsiveness was assessed in the isolated, innervated, constantly perfused gracilis muscle preparation. Pair-fed control animals responded to various concentrations of local insulin infusion by increasing glucose uptake by the gracilis muscle. However, septic animals had a blunted response to local insulin infusion resulting in a decrease in the maximum dose response effect. These data demonstrate that: chronic, hyperdynamic peritonitis in the dog more closely mimics the human clinical profile of sepsis; and hyperdynamic sepsis is associated with a state of skeletal muscle insulin unresponsiveness which results from a post-receptor defect.

Cardiac electrophysiologic effects of pancuronium.

A microelectrode examination of guinea pig left ventricular papillary muscle was performed to determine whether there was a direct effect of pancuronium on cardiac cells and, if so, to attempt to ascertain the mechanism of this effect. Electrical events were measured before and during superfusion with pancuronium, epinephrine, propranolol, and verapamil; alone and in various combinations. Pancuronium prolonged the duration of the action potential (AP); increased resting potential (Em), AP magnitude, and rate of rise of the AP (dV/dt); and resulted in spontaneity in 12% of the muscles. Epinephrine and pancuronium combined caused spontaneity in 80% of the muscles and oscillatory behavior. Additionally, this combination decreased AP magnitude, Em, and dV/dt in several preparations--a pattern of response similar to that seen in ouabain-treated myocardial cells under the influence of catecholamines. These changes were always reversed by verapamil or by perfusion with a drug-free medium, and were usually reversed by propranolol. The data suggest a combined pancuronium/epinephrine induced increase in cardiac membrane permeability to Ca2+.