Effect of intra-operative intravenous lidocaine on opioid consumption after bariatric surgery: a prospective, randomised, blinded, placebo-controlled study.

Peri-operative lidocaine infusion warrants investigation in bariatric surgery because obese patients present different physiological and pharmacological risks. This single-centre, prospective, randomised double-blind placebo-controlled study enrolled obese patients scheduled for laparoscopic bariatric surgery using an enhanced recovery protocol. Patients received either lidocaine (bolus of 1.5 mg.kg-1 , then a continuous infusion of 2 mg.kg-1 .h-1 until the end of the surgery, then 1 mg.kg-1 .h-1 for 1 h in the recovery area) or identical volumes and rates of 0.9% saline. The primary outcome was the consumption of the equivalent of oxycodone consumption over the first 3 postoperative days. Secondary outcomes were: postoperative pain; incidence of nausea and vomiting; bowel function recovery; and lengths of stay in the recovery area and in hospital. Plasma concentrations of lidocaine were measured. On the 178 patients recruited, data were analysed from 176. The median (IQR [range]) equivalent intravenous oxycodone consumption was 3.3 mg (0.0-6.0 [0.0-14.5]) and 5.0 mg (3.3-7.0 [3.3-20.0]) in the lidocaine and saline groups, respectively (difference between medians (95%CI): 1.7 (0.6-3.4) mg; p = 0.004). Length of stay in the recovery area, postoperative pain, nausea and vomiting, day of recovery of bowel function, and length of stay in hospital were not different between groups. Mean (SD) lidocaine plasma concentrations were 2.44 (0.70) µg.ml-1 and 1.77 (0.51) µg.ml-1 at the end of surgery and 1 hour after the end of infusion, respectively. Lidocaine infusion during bariatric surgery resulted in a clinically non-relevant difference in postoperative oxycodone consumption.

Non-invasive positive-pressure ventilation with positive end-expiratory pressure counteracts inward air leaks during preoxygenation: a randomised crossover controlled study in healthy volunteers.

BACKGROUND: During preoxygenation, the lack of tight fit between the mask and the patient's face results in inward air leak preventing effective preoxygenation. We hypothesized that non-invasive positive-pressure ventilation and positive end-expiratory pressure (PEEP) could counteract inward air leak. METHODS: Healthy volunteers were randomly assigned to preoxygenated through spontaneous breathing without leak (SB), spontaneous breathing with a calibrated air leak (T-shaped piece between the mouth and the breathing system; SB-leak), or non-invasive positive inspiratory pressure ventilation (inspiratory support +6 cm H2O; PEEP +5 cm H2O) with calibrated leak (PPV-leak). The volunteers breathed through a mouthpiece connected to an anaesthesia ventilator. The expired oxygen fraction (FeO2) and air-leak flow (ml s-1) were measured. The primary end point was the proportion of volunteers with FeO2 >90% at 3 min. The secondary end points were FeO2 at 3 min, time to reach FeO2 of 90%, and the inspiratory air-leak flow. RESULTS: Twenty healthy volunteers were included. The proportion of volunteers with FeO2 >90% at 3 min was 0% in the SB-leak group, 95% in the SB group, and 100% in the PPV-leak group (P<0.001). At 3 min, the mean [standard deviation (sd)] FeO2 was 89 (1)%, 76 (1)%, and 90 (0)% in the SB, SB-leak, and PPV-leak groups, respectively (P<0.001). The mean (sd) inward air leak was 59 (12) ml s-1 in the SB-leak group, but 0 (0) ml s-1 in the PPV-leak group (P<0.001). CONCLUSIONS: Preoxygenation through non-invasive positive-pressure ventilation and PEEP provided effective preoxygenation despite an inward air leak. CLINICAL TRIAL REGISTRATION: NCT03087825.

Assessment of changes in lactate concentration with intravascular microdialysis during high-risk cardiac surgery using the trend interchangeability method.

Background: Blood lactate is a strong predictor of mortality, and repeated blood lactate assays are recommended during surgery in high-risk patients. We hypothesized that the use of intravascular microdialysis incorporated in a central venous catheter would be interchangeable with the reference blood gas technique to monitor changes in blood lactate. Methods: Microdialysis and central venous blood lactate measurements were recorded simultaneously in high-risk cardiac surgical patients. The correlation between absolute values was determined by linear regression, and the Bland-Altman test for repeated measurements was used to compare bias, precision, and limits of agreement. Changes in lactate measurements were evaluated with a four-quadrant plot and trend interchangeability method (TIM). Results: In the 23 patients analysed, the central venous catheter was used as part of standard care, with no complications. The correlation coefficient for absolute values ( n =104) was 0.96 ( P <0.0001). The bias, precision, and limits of agreement were -0.19, 0.51, and -1.20 to 0.82 mmol litre -1 , respectively. The concordance rate for changes in blood lactate measurements ( n =80) was 94% with the four-quadrant plot. In contrast, the TIM showed that 23 (29) changes in lactate measurements were not interpretable, and among the remaining 57 (71) interpretable changes, 18 (32) were interchangeable, 8 (14) were in the grey zone, and 31 (54) were not interchangeable. Conclusions: Microdialysis with a central venous catheter appears to provide reliable absolute blood lactate values. Although changes in blood lactate measurements showed an excellent concordance rate, changes between the two methods were poorly interchangeable with the TIM. Clinical trial registration: NCT02296593.

Assessment of changes in cardiac index and fluid responsiveness: a comparison of Nexfin and transpulmonary thermodilution.

BACKGROUND: The Nexfin device uses non-invasive photoplethysmography to monitor cardiac output and respiratory variations in pulse pressure and stroke volume. The aim of this study was to compare rapid changes in cardiac index after fluid challenge between Nexfin and bolus transpulmonary thermodilution and the ability to predict fluid responsiveness of dynamic indices given by Nexfin. METHODS: Simultaneous comparative cardiac index were collected from transpulmonary thermodilution and Nexfin before and after fluid challenge in 45 patients following conventional cardiac surgery. Correlations, Bland-Altman analyses and percentage errors were calculated. Pulse pressure variations and stroke volume variations before fluid challenge were collected to assess their discrimination in predicting fluid responsiveness. RESULTS: Eight (18%) patients were excluded. A weak positive relationship was found between rapid changes in cardiac index after fluid challenge given by both technologies (n = 37, r = 0.39, P = 0.019). Bias, precision and limits of agreements were 0.20 l/min/m(2) (95% confidence interval (CI) 0.02-0.40), 0.57 l/min/m(2) and ± 1.12 l/min/m(2) before fluid challenge, and 0.01 l/min/m(2) (95% CI -0.24 to 0.26), 0.74 l/min/m(2) and ± 1.45 l/min/m(2) after fluid challenge. Percentage errors between Nexfin and transpulmonary thermodilution were 55% and 58% before and after fluid challenge, respectively. Pulse pressure variations and stroke volume variations given by Nexfin were not discriminant to predict fluid responsiveness: areas under receiver operating characteristics curves 0.57 (95% CI 0.40-0.73) and 0.50 (0.33-0.67), respectively. CONCLUSIONS: The Nexfin cannot be used to measure rapid changes in cardiac index following fluid challenge and to predict fluid responsiveness after cardiac surgery.

Non-invasive continuous arterial pressure and cardiac index monitoring with Nexfin after cardiac surgery.

BACKGROUND: This observational study was designed to evaluate the reliability and precision of a new digital photoplethysmographic device (Nexfin, BMEYE B.V., Amsterdam, The Netherlands) for continuous and non-invasive assessment of arterial pressure and cardiac output. METHODS: Fifty consecutive adult subjects were prospectively enrolled at admission to the intensive care unit after conventional cardiac surgery and investigated hourly from T0 to T4. Simultaneous comparative systolic, diastolic, and mean arterial pressures and cardiac index (CI) data points were collected from an invasive radial artery catheter, transpulmonary thermodilution catheter, and the Nexfin device. Correlations were determined by linear regression. The Bland-Altman analysis was used to compare bias, precision, and limits of agreement. RESULTS: Six (12%) subjects were excluded from the analysis because of the inability to obtain a reliable photoplethysmographic signal. No complications were observed. A significant relationship was found between absolute values of photoplethysmographic and radial systolic (r(2)=0.56, P<0.001), diastolic (r(2)=0.61, P<0.001), and mean (r(2)=0.77, P<0.001) arterial pressures. A significant relationship was also found between transpulmonary thermodilution and Nexfin CI absolute values (r(2)=0.33, P<0.001). Bias, precision, and limits of agreement between the mean photoplethysmographic and radial arterial pressures were 4.6 (95% confidence interval: 3.7-5.5), 6.5, and -17.3 to 8.1 mm Hg, respectively. The percentage error between transpulmonary thermodilution and the Nexfin for CI measurement was 50%. CONCLUSIONS: The Nexfin device is safe, convenient, and reliable in measuring continuous non-invasive arterial pressure but not interchangeable with transpulmonary thermodilution to monitor CI.

Effect of lipopolysaccharide, cytokines, and catecholamines on brain natriuretic peptide release from human myocardium.

BACKGROUND: During sepsis and septic shock, elevated plasma concentrations of brain natriuretic peptide (BNP) have been reported but may be related to several underlying mechanisms. The aim of the present experimental study was to investigate the effect of lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), dobutamine (Dobu), epinephrine (Epi), and norepinephrine (Nor) on BNP synthesis by atrial human myocardium in vitro. METHODS: After the approval of local ethics committee, right atrial appendages were obtained during cannulation for cardiac surgery and pinned in a isolated organ bath containing 15 ml of Tyrode's modified solution. Preparations were oxygenated, maintained at 36 ± 0.5°C and stimulated at a frequency of 1 Hz. A 60-min equilibration period was followed by 180-min exposure to 1 µM endothelin 1 (ET-1; n = 9), 20,000 pg/ml TNF-α (n = 10), 1000 pg/ml IL-1ß (n = 10), 5000 pg/ml IL-6 (n = 10), 10,000 pg/ml LPS (n = 10), 100 µM Epi (n = 9), 100 µM Nor (n = 10), and 100 µM Dobu (n = 8). No product was added in Control group (n = 10). Two BNP dosages were performed: the first after 60 min of stabilization and the second after 180 min of stimulation. Absolute and relative changes in BNP concentration were compared between groups. RESULTS: Exposure to ET-1 significantly increased BNP release as compared with Control group. Dobu, Epi, Nor, and LPS significantly increased BNP concentration but not TNF-α, IL-1ß, or IL-6. CONCLUSIONS: In vitro, LPS, Dobu, Epi, and Nor induced BNP synthesis by human atrial myocardium.

Mechanisms involved in the desflurane-induced post-conditioning of isolated human right atria from patients with type 2 diabetes.

BACKGROUND: Desflurane triggers post-conditioning in the diabetic human myocardium. We determined whether protein kinase C (PKC), mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channels, Akt, and glycogen synthase kinase-3ß (GSK-3ß) were involved in the in vitro desflurane-induced post-conditioning of human myocardium from patients with type 2 diabetes. METHODS: The isometric force of contraction (FoC) of human right atrial trabeculae obtained from patients with type 2 diabetes was recorded during 30 min of hypoxia followed by 60 min of reoxygenation. Desflurane (6%) was administered during the first 5 min of reoxygenation either alone or in the presence of calphostin C (PKC inhibitor) or 5-hydroxydecanoate (5-HD) (mitoK(ATP) channel antagonist). Phorbol 12-myristate 13-acetate (PKC activator) and diazoxide (a mitoK(ATP) channel opener) were superfused during early reoxygenation. The FoC at the end of the 60 min reoxygenation period was compared among treatment groups (FoC(60); mean and sd). The phosphorylation of Akt and GSK-3ß was studied using western blotting. RESULTS: Desflurane enhanced the recovery of force [FoC(60): 79 (3)% of baseline] after 60 min of reoxygenation when compared with the control group (P>0.0001). Calphostin C and 5-HD abolished the beneficial effect of desflurane-induced post-conditioning (both P<0.0001). Phorbol 12-myristate 13-acetate and diazoxide enhanced the FoC(60) when compared with the control group (both P<0.0001). Desflurane increased the level of phosphorylation of Akt and GSK-3ß (P<0.0001). CONCLUSIONS: Desflurane-induced post-conditioning in human myocardium from patients with type 2 diabetes was mediated by the activation of PKC, the opening of the mitoK(ATP) channels, and the phosphorylation of Akt and GSK-3ß.

Continuous administration of remifentanil and sufentanil induces cardioprotection in human myocardium, in vitro.

BACKGROUND: Remifentanil and sufentanil are widely used opioids during general anaesthesia for cardiac and non-cardiac surgery. This study was conducted to evaluate the hypothesis that the continuous administration of remifentanil and sufentanil, at clinically relevant concentrations, could provide protection of human myocardium, in vitro, against hypoxia-reoxygenation injury. METHOD: Isometrically contracting isolated human right atrial trabeculae were exposed to 30 min of hypoxia and 60 min of reoxygenation. In separate groups, remifentanil at 10(-11), 10(-10), 10(-9), or sufentanil at 10(-11), 10(-10), 10(-9) M were administered 10 min before hypoxia until the end of the experiment. The force of contraction (FoC) of trabeculae was recorded continuously. Developed force was compared (mean ± standard deviation) between the groups using a variance analysis and post hoc tests. RESULTS: At the end of the 60-min reoxygenation, remifentanil 10(-11) M (FoC: 82 ± 7% of baseline), 10(-10) M (FoC: 78 ± 5% of baseline), 10(-9) M (FoC: 80 ± 4% of baseline) and sufentanil 10(-11) M (FoC: 78 ± 8% of baseline), 10(-10) M (FoC: 83 ± 6% of baseline), 10(-9) M (FoC: 83 ± 8% of baseline) enhanced the recovery of FoC as compared with the control group (53 ± 9% of baseline, P<0.0001). CONCLUSIONS: Remifentanil and sufentanil, at clinically relevant concentrations, confer cardioprotection of human myocardium against hypoxia reoxygenation, in vitro.

Sevoflurane- and desflurane-induced human myocardial post-conditioning through Phosphatidylinositol-3-kinase/Akt signalling.

BACKGROUND: The role of phosphatidylinositol-3-kinase (PI3K) in sevoflurane- and desflurane-induced myocardial post-conditioning remains unknown. METHODS: We recorded isometric contraction of isolated human right atrial trabeculae (oxygenated Tyrode's at 34 degrees C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by a 60-min reoxygenation period. At the onset of reoxygenation, muscles were exposed to 5 min of sevoflurane 1%, 2%, and 3%, and desflurane 3%, 6%, and 9%. In separate groups, sevoflurane 2% and desflurane 6% were administered in the presence of 100 nM wortmannin, a PI3K inhibitor. Recovery of force after the 60-min reoxygenation period was compared between groups (mean +/- SD). RESULT: As compared with the Control group (49 +/- 7% of baseline) PostC by sevoflurane 1%, 2%, and 3% (78 +/- 4%, 79 +/- 5%, and 85 +/- 4% of baseline, respectively) and desflurane 3%, 6%, and 9% (74 +/- 5%, 84 +/- 4%, and 86 +/- 11% of baseline, respectively) enhanced the recovery of force. This effect was abolished in the presence of wortmannin (56 +/- 5% of baseline for sevoflurane 2%+wortmannin; 56 +/- 3% of baseline for desflurane 6%+wortmannin). Wortmannin alone had no effect on the recovery of force (57 +/- 7% of baseline). CONCLUSION: In vitro, sevoflurane and desflurane post-conditioned human myocardium against hypoxia through activation of phosphatidylinositol-3-kinase.

Influence of bacterial resistance on mortality in intensive care units: a registry study from 2000 to 2013 (IICU Study).

BACKGROUND: Bacterial resistance to antibiotics is a daily concern in intensive care units. However, few data are available concerning the clinical consequences of in-vitro-defined resistance. AIM: To compare the mortality of patients with nosocomial infections according to bacterial resistance profiles. METHODS: The prospective surveillance registry in 29 French intensive care units (ICUs) participating during the years 2000-2013 was retrospectively analysed. All patients presenting with a nosocomial infection in ICU were included. FINDINGS: The registry contained 88,000 eligible patients, including 10,001 patients with a nosocomial infection. Among them, 3092 (36.7%) were related to resistant micro-organisms. Gram-negative bacilli exhibited the highest rate of resistance compared to Gram-positive cocci (52.8% vs 48.1%; P < 0.001). In-hospital mortality was higher in cases of patients with antibiotic-resistant infectious agents (51.9% vs 45.5%; P < 0.001), and critical care length of stay was longer (33 ± 26 vs 29 ± 22 days; P < 0.001). These results remained significant after SAPS II matching (P < 0.001) and in the Gram-negative bacilli and Gram-positive cocci subgroups. No difference in mortality was found with respect to origin prior to admission. CONCLUSION: Patients with bacterial resistance had higher ICU mortality and increased length of stay, regardless of the bacterial species or origin of the patient.

Video recording of cardiac surgical procedures: what the surgeon needs to know.

In the past, rudimentary devices were used to record surgical operations. Currently, the introduction of technologic advances such as high-definition television and the miniaturization of high-resolution digital video cameras provides an opportunity for making significantly enhanced surgical records. These enhancements, coupled with the recent advances in telemedicine and surgical simulation, will improve cardiac surgery training and skill acquisition, decrease operative times and costs, minimize morbidity, and improve overall patient care. The present paper provides a discussion of the media technology offered to surgeons for recording a surgical procedure on video. Hardware technology, including different types of cameras and analogical or digital post processing methods, are reviewed with a surgical ''eye''. This ''how to'' paper provides practical suggestions to surgeons in order to enhance surgical video recording.

Efficacy, safety and acceptability of a new two-layer bandage system for venous leg ulcers.

OBJECTIVE: To evaluate the efficacy, tolerability and acceptability of a new two-bandage compression system in the local management of venous or mixed aetiology ulcers predominantly of venous origin. METHOD: This was a prospective non-comparative open label phase III clinical study. Forty-two patients were recruited from 12 centres. Inclusion criteria included ulcers with at least 50% granulation tissue, a surface area of 2-20 cm2, an ulcer duration of 1-24 months, an ankle circumference of less than 28 cm, and no history of deep vein thrombosis in the three months before enrolment. The primary endpoint was reduction in ulcer surface area, and secondary endpoints were the evolution of leg oedema and patient comfort. During the six-week follow-up, patients underwent weekly clinical assessments and their ulcer surface area was measured by planimetry and photography every alternate week. RESULTS: The mean ulcer surface area at inclusion was 7 +/- 6 cm2. The mean surface reduction after six weeks was 58.5%, with 24% of the treated wounds healing in a mean time of 25.9 +/- 9.46 days. The patients considered that the new compression system had a better effect on quality of life, evaluated by parameters such as pain, heat, itching and general comfort, than the system worn before entry into the study. Patient concordance with the new system was excellent and 86% of leg ulcers improved or healed after six weeks. Local tolerance was considered very good. CONCLUSION: This new two-bandage compression system is effective and well accepted by patients.

[Pulmonary mucormycosis in a multiple-trauma patient]. / Mucormycose pulmonaire chez un patient polytraumatisé.

Mucormycosis are opportunist infections occurring usually among predisposed patients. We report a case of an 18-year-old male with a severe thoracic trauma who developed an Absidia infection on his contused pulmonary parenchyma, without presenting the usual risk factors (diabetes mellitus, immunodeficiency). The early diagnosis using bronchoscopy has probably improved the outcome by allowing a faster treatment. After 18-months, the infectious process resolved thanks to a combination of a medical treatment composed of high-dose amphotericin B lipid formulation, itraconazole and a complementary surgical treatment.

[Hypothermia after spinal anaesthesia: implication of morphine?]. / Hypothermie après rachianesthésie: rôle de la morphine?

Spinal anaesthesia is the gold standard for elective caesarean section. This technique presents several adverse effects. We report a severe case of hypothermia (33.3 degrees C) after spinal administration of bupivacaine (10 mg) and morphine (100 microg) for elective caesarean section. After excluding other causes of hypothermia, this one could be explained by both the own effects of local anaesthesia (i.e. peripheral vasodilatation) and by the central effect of intrathecal morphine. Because hypothermia is not predictable after spinal injection of morphine both monitoring of central temperature and active warming of the patients could be proposed. Naloxone has been proposed in a case of hypothermia related to spinal injection of morphine.

[Phaeochromocytoma as an unusual aetiology of cardiogenic shock]. / Le phéochromocytome comme cause inhabituelle de choc cardiogénique.

The authors reported a case involving a young patient with a cardiogenic shock associated to an acute pulmonary oedema. According to the seriousness of the shock, an external ventricular assist device (VAD) was initially inserted and replaced thereafter because of the cardiovascular instability, by an external pneumatic biventricular assist device. A cardiogenic shock induced by an acute adrenergic myocarditis due to a phaeochromocytoma was diagnosed. The patient was weaned from the VAD on day 84 and was scheduled for elective surgery of the phaeochromocytoma on day 93. The authors discussed the time of the surgery according to the anticoagulation therapy necessary to the VAD and the necessary caution taken if a cardiogenic shock appeared around surgery.

Residents in tutored practice exchange groups have better medical reasoning as measured by script concordance test: a controlled, nonrandomized study.

STUDY OBJECTIVE: Clinical reasoning by anesthesiology residents in emergency situations where optimal management is uncertain could be improved by setting up a tutored practice exchange group. This study attempted to evaluate the impact of a practice exchange group (PEG), tutored by a senior anesthesiologist, on anesthesiology residents in emergency situations. Changes in clinical reasoning were measured by script concordance tests (SCT). DESIGN: We conducted a controlled, non-randomized study. SETTING AND PARTICIPANTS: Participants are residents in anesthesiology in Rouen, Caen and Amiens University Hospitals. INTERVENTIONS: Two resident groups were made up without randomization. The first group was the control group and consisted of residents from Amiens University Hospital and Caen University Hospital. The second study group (PEG group) consisted of residents from Rouen University Hospital, who followed weekly PEG sessions. Two groups had the same learning objectives except the PEG. MEASUREMENTS: In both the control group and the study group, each resident's clinical reasoning was assessed in the same formal manner by SCT. The primary outcome measurement of this study was to compare SCT results in the study group with PEG training (PEG group) with those without (control group). MAIN RESULTS: Performance in the SCT, expressed as degree of concordance with the expert panel (95% CI), was better in the PEG group (64% [62.1%-66%]) than in control group (60% [57.5%-62.8%])) (P= .004). CONCLUSION: Our study strongly suggests that an expert-directed, peer-conducted educational training program may improve the clinical reasoning of anesthesiology residents as measured by SCT.

Clinical pharmacokinetics after repeated intrapleural bupivacaine administration.

Patients (n = 14) who underwent thoracotomy during surgery of the oesophagus for cancer received an initial intrapleural dose of 10 ml bupivacaine hydrochloride 2.5 mg/ml followed by repeated administration every 8 hours from the first to the fourth postoperative day. The mean (+/- SD) peak plasma drug concentration (Cmax) [352 +/- 120 micrograms/L], time to peak (tmax) [0.83 +/- 0.51 h], and first-order absorption rate constant (ka) [5.46 +/- 4.95 h-1] after the twelfth dose were significantly different from the Cmax (206 +/- 81 micrograms/L), tmax (1.8 +/- 1.2h), and ka (1.8 +/- 1.47 h-1) determined after the first dose. Half-life (3.5 +/- 2.2h) and mean concentration (204 +/- 105 micrograms/L) were not significantly different on the fourth day from those on the first (4.1 +/- 2.6h and 142 +/- 71 micrograms/L, respectively). No sharp peak corresponding to systemic toxicity and no accumulation could be expected with these low doses, administered at short intervals and providing good pain relief in this surgical series.

KATP channels and 'border zone' arrhythmias: role of the repolarization dispersion between normal and ischaemic ventricular regions.

1. In order to investigate the role of KATP channel activation and repolarization dispersion on the 'border zone' arrhythmias induced by ischaemia-reperfusion, the effects of glibenclamide and bimakalim, agents modifying action potential (AP) duration, were studied in an in vitro model of myocardial 'border zone'. 2. The electrophysiological effects of 10 microM glibenclamide and 1 microM bimakalim (n=8 each), respectively KATP channel blocker and activator, were investigated on guinea-pig ventricular strips submitted partly to normal conditions (normal zone, NZ) and partly to simulated ischaemic then reperfused conditions (altered zone, AZ). 3. By preventing the ischaemia-induced AP shortening (P<0.0001), glibenclamide reduced the dispersion of AP duration 90% (APD90) between NZ and AZ (P<0.0001), and concomitantly inhibited the 'border zone' arrhythmias induced by an extrastimulus (ES), their absence being significantly related to the lessened APD90 dispersion (chi2=8.28, P<0.01). 4. Bimakalim, which also reduced the APD90 dispersion (P<0.005) due to differential AP shortening in normal and ischaemic tissues, decreased the incidence of myocardial conduction blocks (25% of preparations versus 83% in control, n=12, P<0.05) and favoured 'border zone' spontaneous arrhythmias (75% of preparations versus 25% in control, P<0.05). 5. During reperfusion, unlike bimakalim, glibenclamide inhibited the ES-induced arrhythmias and reduced the incidence of the spontaneous ones (12% of preparations versus 92% in control, P<0.05), this latter effect being significantly related (chi2=6.13, P<0.02) to the lessened ischaemia-induced AP shortening in the presence of glibenclamide (P<0.0001). 6. These results suggest that KATP blockade may protect the ischaemic-reperfused myocardium from 'border zone' arrhythmias concomitantly with a reduction of APD90 dispersion between normal and ischaemic regions. Conversely, KATP channel activation may modify the incidence of conduction blocks and exacerbate the ischaemia-induced 'border zone' arrhythmias.

Aortopulmonary fistula: an uncommon complication in dystrophic aortic aneurysm.

Wall dissection is a typical complication in the evolution of Marfan aortic aneurysm and usually is associated with valve regurgitation. Formation of a fistula with adjacent structures is very uncommon. We report the case of a 32-year-old man who presented with the typical features of Marfan's syndrome, with chronic aneurysm of the ascending aorta and acute aortopulmonary fistula. Diagnosis was made preoperatively by aortography; operation was performed successfully. A review of the literature only shows a few cases of aortopulmonary fistula in atherosclerotic, syphilitic, or postendocarditis disease.

Cardiac and hemodynamic profile of the new cardiotonic agent, DPI 201-106, in the conscious dog.

The cardiac and hemodynamic effects of increasing doses (0.1-3 mg/kg i.v.) of the novel cardiotonic agent, DPI 201-106 (DPI), were investigated over a 60 min period in conscious dogs chronically instrumented for the measurement of arterial pressure, heart rate, left ventricular pressure (LVP), LV (+) dP/dtmax and cardiac output. LV (+) dP/dtmax, cardiac output and stroke volume were significantly increased by DPI whereas the total peripheral resistance was significantly decreased. These effects were dose-dependent in intensity and in duration. The mean arterial pressure and heart rate remained unaffected, except by the 3 mg/kg dose, which increased them slightly. Autonomic blockade with hexamethonium, atropine and propranolol did not alter the positive inotropic properties of DPI but unmasked its intrinsic bradycardic effect. At equipotent positive inotropic doses, DPI (0.3 mg/kg), milrinone (40 micrograms/kg) and dobutamine (5 micrograms/kg per min) induced similar increases in cardiac output and similar decreases in total peripheral resistance, but only dobutamine and milrinone accelerated the heart rate, whereas ouabain (17.5 micrograms/kg) induced a strong rise in the total peripheral resistance and markedly lowered the heart rate and cardiac output. After coadministration of DPI and ouabain, LV (+) dP/dtmax was further increased whereas the ouabain-induced bradycardia, the rise in the total peripheral resistance and the decrease in cardiac output were reinforced, halved and unaltered, respectively. We conclude that (a) DPI exhibits potent and direct positive inotropic properties, associated with a peripheral vasodilating action, and almost no positive chronotropic effects, and (b) coadministration of DPI and ouabain results in synergistic positive inotropic effects.