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Biliary strictures after liver transplantation are common and when refractive to endoscopic and percutaneous intervention require surgical revision. Robotic technology facilitates minimally invasive biliary reconstruction and has not previously been described after liver transplantation. Robotic biliary revisions were retrospectively compared to all the historical open cases over a time period from May 2013 to October 2020. During the study period there were 3 robotic and 4 open surgical biliary revisions with a follow-up of at least 6months. All cases were hepaticojejunostomies for late choledocho-choledochostomy anastomotic strictures presenting > 4 weeks after transplant and refractive to at least 3 endoscopic and/or percutaneous interventions. Median (range) case time was longer in the robotic group, 373 minutes (286-373) compared to open group, 280 minutes (163-321). The median length of stay was shorter in the robotic group, 4 days (1--4) compared to open group 7 days (4-10). Morbidity included 2 wound infections in the open group (grade II), 1 infected hematoma in the robotic group (grade Ilia), and 1 bile leak on the open group (grade Ilia). There was no biliary stricture recurrence or mortality in either group. Robotic biliary revision is a safe alternative to traditional open biliary revision for refractive biliary strictures after liver transplantation., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The study aim was to quantify the burden of complications of pancreatoduodenectomy (PD)., Background: The Postoperative Morbidity Index (PMI) is a quantitative measure of the average burden of complications of a procedure. It is based on highly validated systems--ACS-NSQIP and the Modified Accordion Severity Grading System., Methods: Nine centers contributed ACS-NSQIP complication data for 1589 patients undergoing PD from 2005 to 2011. Each complication was assigned a severity weight ranging from 0.11 for the least severe complication to 1.00 for postoperative death, and PMI was derived. Contribution to total burden by each complication grade was used to generate a severity profile ("spectrogram") for PD. Associations with PMI were determined by regression analysis., Results: ACS-NSQIP complications occurred in 528 cases (33.2%). The non-risk-adjusted PMI was 0.115 (SD = 0.023) for all centers and 0.113 (SD = 0.005) for the 7 centers that contributed at least 100 cases. Grade 2 complications were predominant in frequency, and the most common complication was postoperative bleeding/transfusion. Frequency and burden of complications differed markedly. For instance, severe complications (grades 4/5/6) accounted for only about 20% of complications but for more than 40% of the burden of complications. Organ space infection had the highest burden of any complication. The average burden in cases in which a complication actually occurred was 0.346., Conclusions: This study develops a quantitative non-risk-adjusted benchmark for postoperative morbidity of PD. The method quantifies the burden of types and grades of postoperative complications and should prove useful in identifying areas that require quality improvement.

The hemodynamic effects of a new Ic antiarrhythmic agent (Org 7797) were compared with those of flecainide and propafenone in anesthetized pigs with developing myocardial infarcts. One hour after acute coronary artery occlusion, the only significant hemodynamic effect of an intravenous (i.v.) dose of Org 7797 (0.5 mg/kg) known to prevent ischemia-induced ventricular fibrillation (VF) in dogs was a decrease in heart rate (HR) (of 3%) while cardiac output (CO), stroke volume (SV), and left ventricular (LV) dP/dtP-1 were unchanged. At four times this dose, the only sustained and significant responses to Org 7797 were decreased CO and bradycardia, whereas decreases in arterial and LV pressures (BP and LVP) and LVdP/dtP-1 were transient. In contrast, a therapeutic dose of flecainide (2 mg/kg) induced sustained reductions in CO, SV, LVdP/dtP-1, and LVP whereas a similar (therapeutic) dose of propafenone decreased LVP, reduced CO partly as a result of bradycardia and decreased LVdP/dtP-1 but not sufficiently to decrease SV. Two electrical deaths occurred in each of the propafenone (n = 6) and flecainide (n = 7) groups, but arrhythmic deaths did not occur in Org 7797- or saline-treated animals. We conclude that Org 7797 in therapeutic doses, unlike propafenone and especially flecainide, is not cardiodepressant in animals whose cardiac function is already compromised. In addition, there was no evidence of proarrhythmogenicity at the doses of Org 7797 used.

The frequency-dependent electrophysiological effects of three class Ic agents, Org 7797 (0.5-5 microM), flecainide (1-20 microM), and propafenone (1-10 microM), were investigated using isolated guinea pig papillary muscle. Transmembrane cellular action potentials were recorded using conventional microelectrode techniques at driving frequencies of 0.3, 1.0, and 2.0 Hz. In concentrations inducing similar frequency-dependent decreases in Vmax, both flecainide and propafenone shortened action potential duration (APD) at the two lower stimulation frequencies, whereas increasing the driving frequency to 2 Hz attenuated drug-induced APD shortening. In contrast, Org 7797 did not shorten APD at any stimulation frequency, and indeed APD lengthening was observed at 2.0 Hz. Increases in the effective refractory period (ERP) were seen at 1.0 and 2.0 Hz in the presence of Org 7797 and at 2.0 Hz in the presence of flecainide, but ERP was either unchanged (2.0 Hz) or shortened by propafenone. The rate of onset of sodium channel block was faster in response to propafenone compared to Org 7797 and flecainide. It was concluded that all three drugs may inhibit outward repolarising potassium currents, especially at higher stimulation frequencies. However, the concentrations of Org 7797 necessary to influence repolarisation may be closer to those required to induce sodium channel block compared to flecainide and especially propafenone. These differences may influence drug-induced effects on wavelength resulting in differences in antifibrillatory efficacy.

The electrophysiological and antiarrhythmic effects of acute (2 and 10 mg/kg i.v.) and chronic (400 mg/day p.o. for 28 days) amiodarone (AM) treatment were compared in anaesthetised dogs with 5-6-day-old myocardial infarcts. Intravenous AM prolonged the RR interval, sinus node recovery time, the PR interval, and atrial to His conduction time by 36, 33, 25, and 36%, respectively. Corresponding increases after oral amiodarone were 50, 57, 12, and 26%. Atrial and His-Purkinje conduction times were unchanged. Atrial and ventricular refractory periods were increased especially after oral treatment. Oral AM additionally prolonged QRS, QT, and paced QT (by 4, 34, and 19%, respectively). Effects of oral AM on ventricular repolarisation and on the fast inward sodium current were confirmed in vitro. Both modes of AM administration protected against inducible arrhythmias, an effect that was more marked during normal sinus rhythm than during pacing in orally treated dogs. Oral amiodarone failed to protect against spontaneous late arrhythmias 24 h after infarction whilst both modes of administration noncompetitively inhibited isoprenaline-induced tachycardia. Oral AM reduced blood pressure (13%) and LV dP/dt/P (24%) whereas cardiac output was maintained by an increase in stroke volume. It was concluded that oral AM is haemodynamically well tolerated and that prolonged ventricular repolarisation enhanced by bradycardia together with sympatholytic actions may be important mechanisms for antiarrhythmic efficacy, whereas the mechanisms involved in i.v. efficacy are less clear but may depend, at least partly, on sympatholytic actions and perhaps (tentatively) on sodium channel block in Purkinje tissue.

The effects of bepridil (1-4 microM), a new antianginal agent which reduces the intensity of both the fast and slow inward ionic currents in myocardium, on reperfusion-induced arrhythmias (RA) in the isolated perfused rat heart were compared with those of tetrodotoxin (0.16-1.57 microM), verapamil (0.5-2 microM), diltiazem (1-2 microM), nifedipine (0.02-0.2 microM), and nitrendipine (0.02-0.2 microM). In comparable negative inotropic concentrations, neither nifedipine nor nitrendipine reduced the incidence of RA, whereas the other four agents did. Protection against RA does not appear to be related to coronary vasodilatation or to a reduction in the degree of ischaemia as assessed by lactate dehydrogenase release. However, negative chronotropism appears to be relevant in the mechanism of action of the calcium antagonists. Substantial protection against RA by all active drugs was associated with PR prolongation and/or atrioventricular block or suppression of sinus rhythm. It is concluded that bradycardia may play an important role in the antiarrhythmic action of bepridil, but the relative contributions made by inhibition of the inward calcium and/or sodium currents remain unclear.

The antiarrhythmic efficacies of intravenous quinidine (Q), disopyramide (D), prenylamine (P), bepridil (B), and practolol were compared in normokalaemic and dietary-induced hypokalaemic anaesthetised rats. Hypokalaemia markedly increased the severity of arrhythmias induced by coronary artery ligation and reduced the antiarrhythmic efficacy of all five drugs tested. After anaesthesia, hypokalaemia was associated with hypotension and bradycardia but not QTc prolongation. However, bradycardia was not seen in conscious hypokalaemic animals. Papillary muscles taken from hypokalaemic rats displayed a longer action potential duration but no increase in Vmax compared with tissue taken from normokalaemic animals. It is concluded that hypokalaemia in the rat causes electrophysiological disturbances which may contribute both to the observed exacerbation of ischaemia-induced arrhythmias and to the reduced efficacy of Q, D, P, and B. The reduced efficacy of practolol might be explained by other consequences of hypokalaemia.

We investigated the potential antidysrhythmic effects of bepridil, a new antianginal agent, on dysrhythmias of supraventricular origin. Intravenous bepridil (5 mg/kg) suppressed dysrhythmias evoked by local application of aconitine to the left atria of anesthetized cats. After the aconitine-induced dysrhythmias had subsided, cardiac function was better maintained in animals given bepridil than in the controls. The effects of bepridil on the maximum following frequency (MFF) and transmembrane action potentials of isolated guinea pig atria and on cells displaying phase 4 depolarization were also examined. Both bepridil (5--120 microM) and verapamil (0.02--1 microM) induced a dose-dependent reduction in contractility of driven left atria, whereas only bepridil reduced MFF. The effects of bepridil (10--40 microM) on the cellular action potentials of left atria were a dose-dependent decrease in the maximum rate of depolarization of phase 0 associated with a reduction in action potential height and a marked prolongation of the action potential duration. In similar concentrations, bepridil reduced the spontaneous rate of the right atrium and reduced the slope of phase 4 depolarization. We conclude that the action of bepridil in suppressing supraventricular dysrhythmias may be partly explained by depression of automaticity together with a reduction in the intensity of the inward sodium current.

The potential antiarrhythmic and electrophysiological effects of prolonged oral dosing with amiodarone (20 mg/kg/day) or disopyramide (25 or 50 mg/kg b.i.d.) were compared in normokalaemic (NK) and diet-induced hypokalaemic (HK) anaesthetised rats. In NK rats, amiodarone reduced the number of electrical deaths consequent upon coronary artery ligation and prolonged action potential duration (APD50) of papillary muscle. Disopyramide conferred marked protection against arrhythmias in NK animals, prolonged APD50, reduced the maximum rate of depolarisation, and induced bradycardia. Hypokalaemia inhibited both the antiarrhythmic efficacy and these electrophysiological actions of amiodarone and disopyramide. However, prolongation of APD90 by both drugs was little affected by hypokalaemia. Amiodarone prolonged QTc both in NK and HK rats, whilst disopyramide only prolonged QTc in NK rats and only at the higher dose. It is concluded that reduced antiarrhythmic efficacy of the two drugs by hypokalaemia may be due to altered electrophysiological responses. QTc prolongation per se appears to be associated with antiarrhythmic, not arrhythmogenic, actions in this experimental model.

The arrhythmogenic and hemodynamic effects of 0.04% aconitine solution applied locally to the left atria of cats and the effects of amiodarone (10 mg/kg) and atropine (0.2 mg/kg) on the responses to aconitine were investigated. Cats were anesthetized with sodium pentobarbital. The left atrial and limb lead electrocardiograms and the arterial pressure were recorded. Cardiac output was determined with the thermo dilution technique. Aconitine nitrate induced dysrhythmias lasting for a mean of 111 min. Atrial fibrillation occurred in 47% of the animals. A long-lasting (at least 3 hr) cardiodepressant action was seen in response to aconitine. Pretreatment with atropine largely prevented the hemodynamic effects of aconitine and prevented fibrillation. However, mean maximum atrial rates recorded during successive 5 min intervals were similar in control and atropine-treated animals. Amiodarone suppressed dysrhythmias in both atropine-treated and nontreated animals at a dose which exerted only minimal cardiodepression. The method described for evaluating potential activity against supraventricular dysrhythmias in the cat is relatively simple, reproducible, and suitable for statistical analyses. Aconitine appears to exert a long-lasting cholinergic action which may be involved in the genesis of aconitine-induced atrial fibrillation.

Hypokalaemia (HK) is a risk factor for development of clinical arrhythmias, and epinephrine (Epi), released after myocardial infarction, may itself induce HK. The effects of selective beta 1- and beta 2-blockade with metoprolol (M) and ICI 118551 (I), respectively, and non-selective blockade with propranolol (P) against early ischaemia-induced arrhythmias were therefore compared in normokalaemic (NK) and dietary-induced HK rats. Plasma Epi, norepinephrine (NE), and K+ levels were also measured. All three blockers [5-10 mg/kg intravenously (i.v.)] were antifibrillatory in NK rats, whereas I and P (2-10 mg/kg) additionally reduced the number of ventricular premature beats. Coronary artery ligation increased plasma Epi levels in both NK an HK rats, but plasma NE increased further in HK rats. HK was also associated with an increased arrhythmia severity and negation of the antifibrillatory action of M. In contrast, I and P retained antiarrhythmic and antifibrillatory effects in HK animals and increased survival. Both I and P increased plasma K+ levels in both NK and HK animals whereas M did not. We concluded that beta 2-receptor-mediated HK after coronary occlusion may play a substantial role in arrhythmogenesis. Protection afforded by beta 2-blocking agents may be due to alleviation of HK in HK rats or to induction of hyperkalaemia in NK rats.

The electrophysiological actions of bepridil were compared with those of disopyramide in rabbit atrial, Purkinje, and papillary muscles in both normokalaemic (5.6 mM K+) and low K+ medium. In normokalaemic medium, the major electrophysiological effects of bepridil (10-40 microM) were a reduction in the maximum rate of rise of phase 0 of the action potential (MRD) of atrial and Purkinje fibres and prolongation of the atrial action potential duration (APD). Higher concentrations (40-100 microM) reduced MRD of papillary muscle without markedly affecting APD. Disopyramide (40-100 microM) reduced MRD and prolonged APD in similar concentrations in all three tissues. Reducing extracellular (EC) K+ to 2.8 mM decreased the effects of bepridil on MRD in all tissues but only significantly reduced the response to disopyramide in papillary muscle. Enhancement of APD prolongation by disopyramide in all tissues resulted when EC K+ was reduced, whereas only papillary muscle APD showed a marked prolongation in response to bepridil. These results demonstrate that the class I effect of bepridil is highly K+ dependent. It may be expected that QTc prolongation produced by both these drugs will be more marked in patients with low serum potassium levels.

The in vitro electrophysiologic effects of a new class I steroidal antiarrhythmic agent, Org 7797 (2-10 microM) were evaluated in porcine ventricular and Purkinje tissue using conventional microelectrode techniques. Org 7797-induced decreases in Vmax were both frequency- and voltage-dependent. Both the rate of onset and the time course of decay of sodium channel block were slow and similar to those obtained with the 1c drug propafenone. The kinetics of block by lignocaine (1b) were fast whereas those of disopyramide (1a) were intermediate. Rate constants (determined at 1.0 Hz) were 0.187, 0.078, and 0.074 for disopyramide, propafenone, and Org 7797, respectively, in concentrations giving approximately equivalent decreases in Vmax. Onset block with lignocaine was too fast to measure. The effective refractory period (ERP) was prolonged to a greater extent by lignocaine and disopyramide than by propafenone or Org 7797, but the increase in ERP in response to disopyramide resulted largely from prolongation of action potential duration (APD). The effects of Org 7797 on ERP relative to APD were more similar to those of propafenone. We conclude that Org 7797 is a class 1c agent.

The antidysrhythmic effects of a new antianginal agent, bepridil, were compared with those of disopyramide, a known antidysrhythmic drug. Bepridil (20, 50, and 100 mg/kg, i.p.) conferred little protection against aconitine-induced dysrhythmias in mice, whereas similar doses of disopyramide exerted a marked dose-dependent antidysrhythmic effect. Intravenous administration of either bepridil (2 mg/kg) or disopyramide (10 mg/kg) significantly reduced the number of ventricular extrasystoles and completely abolished the occurrence of ventricular fibrillation following coronary artery ligation in the rat. Local anesthetic and electrophysiological effects in vitro of bepridil were also investigated. A marked but slowly developing reduction in action potential height of desheathed frog sciatic nerves was observed at concentrations of 0.01-0.05 mM. In sheep Purkinje fibres, a similar decrease in action potential height, associated with a pronounced reduction in the maximum rate of depolarization of phase zero of the action potential (MRD) was seen with bepridil (0.5-2 X 10(-5) M). Higher concentrations (2-8 X 10(-5) M) were required to reduce MRD of guinea pig ventricular muscle. The antidysrhythmic actions of bepridil may at least in part be explained by the electrophysiological effects observed.