Randomized,Controlled Trial of Carbon Dioxide Insufflation During Colonoscopy

INTRODUCTION: Insufflation of air is a cause of discomfort during and after colonoscopy. Although this can be minimized by good technique, the use of carbon dioxide insufflation may provide further benefits. Carbon dioxide is rapidly absorbed and excreted through the lungs. We hypothesized that carbon dioxide would alleviate postcolonoscopy discomfort. METHODS: After they had provided informed consent, patients presenting for colonoscopy were randomized into two groups: those in whom air was used for colonoscopy and those in whom carbon dioxide was used. Pain during and ten minutes after colonoscopy was measured on a ten-point analog scale. Data are mean and 95 percent confidence limits. RESULTS: There were 124 patients in the air group and 123 in the carbon dioxide group. Age, body mass index, indication, diagnosis, and number of procedures were similar for the two groups. There were no differences between the groups in the amounts of sedation or analgesia used, the percentage of examinations that were complete (air, 98.4 percent; carbon dioxide, 95.2 percent), or patient satisfaction (on a scale of 1 to 10: air, 9.4; carbon dioxide, 9.5). Although there were more females in the carbon dioxide group (69 vs. 51), hysterectomy rates were the same. Pain scores (mean ± 95 percent confidence interval; scale of 1 to 10) immediately after the examination were 4.3 ± 0.3 for air and 3.6 ± 0.3 for carbon dioxide (no significant difference). Pain scores 10 minutes later were 2.1 ± 0.2 for air and 0.9 ± 0.2 for carbon dioxide (P < 0.05, Students t-test). CONCLUSION: Because there was significantly less abdominal pain ten minutes after colonoscopy in the group in whom carbon dioxide was used, carbon dioxide should be considered as an insufflating gas for colonoscopy.     

NORCCAP (Norwegian colorectal cancer prevention): a randomised trial to assess the safety and efficacy of carbon dioxide versus air insufflation in colonoscopy

BACKGROUND: To eliminate the risk of combustion during electrosurgical procedures and to reduce patient discomfort, carbon dioxide (CO2) insufflation has been recommended during colonoscopy. However, air insufflation is still the standard method, perhaps due to the lack of suitable equipment and shortage of randomised studies. AIMS: This randomised controlled trial was conducted to assess patient tolerance and safety when using CO2 insufflation during colonoscopy. PATIENTS: Over an eight month period a successive series of patients referred for a baseline colonoscopy due to findings in a flexible sigmoidoscopy screening trial were randomly assigned to the use of either air or CO2 insufflation during colonoscopy. METHODS: End tidal CO2 (ETCO2), a non-invasive parameter of arterial pCO2, was registered before and repeatedly during and after the examination. The patient's experience of pain during and after the examination was registered using a visual analogue scale (VAS). Sedation was not used routinely. RESULTS: CO2 insufflation was used in 121 patients (51%) and air in 119 patients (49%). The groups were similar in age, sex, and caecal intubation rate. No rise in ETCO2 was registered. There were statistically significant differences in VAS scores between the groups with less pain reported when using CO2. CONCLUSIONS: This randomised study of unsedated patients shows that CO2 insufflation is safe during colonoscopy with no rise in ETCO2 level. CO2 was found to be superior to air in terms of pain experienced after the examination.     

Comparison of the Effects of Regional Ischemia and Hyperkalemia on the Membrane Action Potentials of the In Situ Pig Heart

APD During Ischemia. Introduction: This study was designed to determine the role of increased extracellular potassium [K⁺]_e on action potential duration (APD) in the in situ porcine heart during acute regional no-flow ischemia.
Methods and Results: In open chest, anesthetized swine, an arterial shunt from the carotid artery to the mid-left anterior descending coronary artery was created through which a solution of KCl was infused to raise [K⁺]_e, Myocardial [K⁺]_e, was determined by potassium-sensitive electrodes, and transmembrane action potential was recorded by floating glass microelectrode. During the first 2 minutes of ischemia, APD at 90% repolarization (APD₉₀) lengthened by 31.2 ± 1.1 msec (P < 0.05). The comparable increase in [K⁺]_e alone shortened APD₉₀, During the next 6 minutes of ischemia. [K⁺]_e, rose to 11.3 ± 0.3 mM and APD₉₀, showed a decrease. However, the comparable increase in |K⁺]_e, by infusion of KCl caused further shortening of APD₉₀, at similar levels of [K⁺]_e.
Conclusions: Acutely ischemic myocardium showed a brief increase in APD₉₀, during the first 2 minutes of ischemia, followed by a fall in APD₉₀, after 2 minutes of ischemia, but the shortening is less than anticipated by the rise in [K⁺]_e. Thus, we hypothesize that other component(s) of ischemia may inhibit action potential repolarization.     

二氧化碳灌注提高老年患者结肠镜检查舒适度的随机对照研究

背景：常规空气灌注式结肠镜检查往往会造成不同程度的腹痛、腹胀等不适,探求更好的结肠镜检查方式具有重要临床意义。目的：评价二氧化碳（CO2）灌注用于老年患者结肠镜检查的舒适度和安全性。方法：98例老年患者随机分为4组,各组基线情况基本一致,分别以空气或CO2为注气媒介,辅以或不辅以镇痛药行结肠镜检查。以直观模拟量表（VAS）评价检查中和检查后5、10、15、20min腹痛、腹胀情况。每组分别随机选取8例患者,8例于检查后10min行动脉血气分析,另8例于检查后60min拍摄腹部X线平片评价肠管扩张程度。结果：CO2组和CO2＋镇痛组各时点腹痛、腹胀VAS评分以及检查后肠管扩张程度评分分别显著低于空气组和空气＋镇痛组（P〈0．01）,CO2＋镇痛组检查中腹痛、腹胀VAS评分显著低于CO2组（P〈0．05）。四组间各项结肠镜操作参数以及动脉血pH值和PCO2差异无统计学意义,且均无严重并发症发生。结论：CO2灌注式结肠镜检查用于老年患者安全、有效,舒适度较空气灌注式结肠镜检查明显提高。     

二氧化碳灌注在结直肠息肉黏膜切除术中的应用

[目的]探讨二氧化碳(CO₂)作为灌注气体在结直肠息肉黏膜切除术(EMR)中应用的有效性和安全性。[方法]选取本院行结直肠息肉EMR患者84例,采用随机数字法分为空气组(42例)和CO₂组(42例),灌注气体分别采用空气和CO₂,记录每组患者EMR成功率、操作时间及出血、穿孔等并发症;记录术前、术中、术后心率(HR)、平均动脉压(MAP)、血氧饱和度(SpO₂)、经皮CO₂分压(PtcCO₂)的变化;记录术中、结束时、术后1 h、6 h和24 h患者的腹痛程度。[结果](1)空气组与CO₂组患者的年龄、性别、BMI、手术成功率、操作时间、肠道评分比较均差异无统计学意义(P>0.05);(2)CO₂组术中、结束时、术后1 h、6 h和24 h腹痛评分分别为(41.2±8.3)、(26.8±6.6)、(14.5±5.4)、(4.5±1.2)和(0.7±0.3),明显低于空气组的评分[(56.2±9.3)、(44.7±7.9)、(33.1±6.7)、(10.2±2.5)、(4.8±1.7)],2组比较差异有统计学意义(P<0.05);(3)2组患者术前、术中及术后HR、MAP、SpO₂、PtcCO₂比较均差异无统计学意义(P>0.05),术中、术后均无出血、穿孔等并发症。[结论]CO₂替代空气作为结直肠息肉EMR中的灌注气体安全性高,能明显减轻患者腹部不适感。     

Supplemental Oxygen During Endoscopic Variceal Ligation: Effects on Arterial Oxygenation and Cardiac Arrhythmia

Objectives: Endoscopic variceal ligalion may affect cardiopulmonary function. The aim of this study was to determine the effect of either nasal oxygen (2 L/min) or no oxygen on arterial oxygenation and cardiac arrhythmia during variceai ligation.
Methods: A prospective, endoscopy team-blinded, randomized, cross-over study (first session vs second session) was conducted in 30 cirrhotic patients undergoing variceal ligation. Oxygen saturation (SaO₂) and cardiac arrhythmia were assessed by a pulse oximeter. In this study, 15 patients received supplemental oxygen in the first sessions, and 15 received oxygen in the second sessions.
Results: Oxygen desaturation (nadir SaO₂ < 90%) occurred in 23% of patients breathing room air but was prevented hy oxygen ( p < 0.01), and the nadir SaO₂ was significantly lower in patients breathing room air than in those receiving oxygen (93.2 ± 0.7% vs 98.3 ± 0.3%, p < 0.01). During the procedure, premature ventricular contraction was more frequently observed in patients breathing room air than in those receiving oxygen (14.0 ± 3.2/h vs 5.4 ± 1.5/r, p < 0.05).
Conclusions: These data suggest that oxygen desaturation and cardiac arrhythmia are common in patients undergoing variceal ligation and that low flow nasal oxygen can alleviate these events. Supplemental oxygen is therefore advisable to avoid potential serious cardiopulmonary accidents in patients undergoing variceal ligalion.     

Leucine and Glucose Turnover in Chronic Alcoholics During Early Abstinence and After an Ethanol Load

We studied leucine turnover using a primed infusion of [1-¹⁴C]- l -leucine and glucose turnover using a primed infusion of [6-³H]- d -glucose in five alcoholic patients without liver damage and five age-matched controls. Infusions were maintained for 6 hr, and at the end of the 3rd hour, a 0.8 g/kg iv ethanol load was administered in 20 min. Leucine flux, nonoxidative disposal and oxidation rates, and glucose rate of appearance were calculated during the 3rd and 6th hours of infusion. Ethanol disappearance rate and the percentage completely metabolized to CO₂ and H₂O in 3 hr were also calculated. Compared with controls, alcoholics had significantly higher basal leucine flux (55.6 ± 12 vs. 37.3 ± 9.3 μ m /m²/min) and nonoxidative disposal (48.7 ± 8.7 vs. 31.1 ± 7.5 μ m /m²/min). No differences were observed in basal glucose appearance rates in alcoholics and controls (397.6 ± 115.2 vs. 349.4 ± 120.6 μ m /m²/min). Compared with controls, alcoholics had a higher alcohol disappearance rate (2.72 ± 0.59 vs. 1.84 ± 0.43 m m /kg/min) and percentage of ethanol metabolized to CO₂ and H₂O in 3 hr (40.6 ± 10.2 vs. 22.9 ± 6.9%). After the ethanol load, both leucine turnover and glucose rate of appearance decreased significantly only in alcoholics. There was a positive correlation between the change in leucine flux and ethanol disappearance rate and percentage metabolized to CO₂ and H₂O in alcoholics.     

Efficacy of carbon dioxide-insufflating colonoscopy in patients with irritable bowel syndrome: A randomized double-blind study

Background and Aim: Colonoscopy has the disadvantage of pain and discomfort for patients. It has been shown in randomized controlled trials that carbon dioxide (CO₂) insufflations significantly reduce pain and discomfort in patients undergoing colonoscopy. However, there have been no studies in which CO₂ insufflation in colonoscopy of patients with irritable bowel syndrome (IBS) was investigated. Methods: Randomized double‐blind controlled study was conducted to assess the suffering from colonoscopy in patients with IBS and the efficacy of CO₂ insufflation in colonoscopy for patients with IBS. Patients with IBS and controls who received colonoscopy were randomized into an air or CO₂ insufflation group. Patients' symptoms such as distension and pain were compared using a 10‐cm visual analog scale (VAS). Results: There were 18 patients in the IBS/air group, 19 patients in the IBS/CO₂ group, 25 patients in the control/air group and 26 patients in the control/CO₂ group. The mean value of severity of distension after colonoscopy and the mean value of severity of pain from during examination to one hour after the examination were higher in the IBS group than in the control group. The severity of these symptoms was reduced earlier in the CO₂ group. CO₂ insufflation in colonoscopy was more effective in the IBS group than in the control group from 15 min to one hour after the examination. Conclusion: Regarding colonoscopy‐related suffering, IBS patients showed significant differences from non‐IBS patients. CO₂ insufflation in colonoscopy is effective for IBS patients, particularly for patients who commence activities after colonscopy.     

Carbon dioxide-insufflated colonoscopy: an ignored superior technique

Colonoscopy and barium enema are complementary studies in the diagnosis of the cause of lower intestinal bleeding. The air usually insufflated during colonoscopy often makes it impossible to perform a good barium enema on the same day. As a possible solution to this problem, we studied the quality of barium enemas performed immediately following carbon dioxide-insufflated colonoscopy. All 15 patients who underwent unsuccessful total colonoscopies using carbon dioxide insufflation were able to have barium enemas performed the same day in contrast to only one out of 15 patients who had air-insufflated colonoscopy. In a survey of all hospitals in Illinois with 150 beds or more, we found only 15 of 146 hospitals used carbon dioxide for colonoscopy insufflation. We recommend the routine use of carbon dioxide for colonoscopic insufflation not only for greater safety and comfort for the patient, but also for the convenience and cost savings.     

Blood Gas Studies in Some Abnormal Haemoglobin Syndromes

S ummary . Arterial oxygen and carbon dioxide tensions, pH, and haemoglobin concentrations, were determined in 50 Nigerian patients with abnormal haemoglobins SS, SC or CC who were not in crisis. As control subjects, 50 healthy Nigerians awaiting minor surgical procedures were also studied along the same lines. The values obtained for P a,CO₂ and pH in the two groups were similar. The values obtained for P a,O₂ in the abnormal haemoglobin group were significantly lower than in the control group ( P <0.001). In the control group, the values obtained for the P a,O₂ showed correlation with age, whereas in the abnormal haemoglobin group there was no correlation with age. The haemoglobin concentration was found to be significantly lower in the abnormal haemoglobin group than in the control group ( P <0.001).     

Carbon dioxide insufflation reduces discomfort due to flexible sigmoidoscopy in colorectal cancer screening

BACKGROUND: Flexible sigmoidoscopy is currently recommended as a screening modality for colorectal cancer. However, a substantial number of patients experience discomfort because of the procedure. possibly limiting compliance and thus screening success. During endoscopy, air is commonly used to insufflate the bowel. Carbon dioxide rather than air insufflation has been shown to reduce procedure-related pain and discomfort in colonoscopy. The aim of the present study was to evaluate whether carbon dioxide insufflation reduces discomfort during and after flexible sigmoidoscopy for colorectal cancer screening. METHODS: In a randomized, double-blinded design, 230 consecutive participants in a population-based flexible sigmoidoscopy colorectal cancer screening trial were assigned to have their examination performed with either carbon dioxide or air insufflation. Patients were asked to grade discomfort experienced both during and in the hours after the procedure on a visual analogue scale. RESULTS: Carbon dioxide insufflation significantly reduced the amount of discomfort at 1, 3 and 6 h after the sigmoidoscopy. One hour after the examination. 84% of patients in the CO2 group reported no discomfort, compared to 64% in the air group (P = 0.006). No differences between the groups were observed during the examination. CONCLUSIONS: Carbon dioxide insufflation significantly reduced post-examination discomfort. The use of carbon dioxide rather than air insufflation may contribute to better public acceptance for flexible sigmoidoscopy screening.     

Carbon Dioxide Insufflation Reduces Discomfort Due to Flexible Sigmoidoscopy in Colorectal Cancer Screening

Background: Flexible sigmoidoscopy is currently recommended as a screening modality for colorectal cancer. However, a substantial number of patients experience discomfort because of the procedure, possibly limiting compliance and thus screening success. During endoscopy, air is commonly used to insufflate the bowel. Carbon dioxide rather than air insufflation has been shown to reduce procedurerelated pain and discomfort in colonoscopy. The aim of the present study was to evaluate whether carbon dioxide insufflation reduces discomfort during and after flexible sigmoidoscopy for colorectal cancer screening. Methods: In a randomized, double-blinded design, 230 consecutive participants in a population-based flexible sigmoidoscopy colorectal cancer screening trial were assigned to have their examination performed with either carbon dioxide or air insufflation. Patients were asked to grade discomfort experienced both during and in the hours after the procedure on a visual analogue scale. Results: Carbon dioxide insufflation significantly reduced the amount of discomfort at 1, 3 and 6 h after the sigmoidoscopy. One hour after the examination, 84% of patients in the CO 2 group reported no discomfort, compared to 64% in the air group ( P = 0.006). No differences between the groups were observed during the examination. Conclusions: Carbon dioxide insufflation significantly reduced postexamination discomfort. The use of carbon dioxide rather than air insufflation may contribute to better public acceptance for flexible sigmoidoscopy screening.     

以二氧化碳为媒介的老年人结肠镜检查的安全性和舒适性

目的分析评价二氧化碳（C02）为媒介的结肠镜检查应用于老年患者的安全性和舒适性。方法这是一项随机双盲对照研究。选取110例老年人,随机分为以空气为媒介的结肠镜组（n=55）和以CO2为媒介的结肠镜组（n=55）。通过腹痛和腹胀的问卷调查、腹部平片肠管积气程度、经皮CO2分压连续测定等结果,分析比较两组间的差异性。结果CO2组平均插入时间短,且成功率高,与空气组比较差异有统计学意义[（7．0±4．9）vs（9．0±3．7）min;P〈0．05];结肠镜检查后5,10,15,20min不同时间点进行的腹痛、腹胀的问卷调查评分中,C02组的评分明显低于空气组,差异有统计学意义[5min：（15．4±2．1）VS（63．5±13．5）,10min：（5．1±1．3）vs（60．3±10．9）,15min：（0．5±0．7）vs（58．6±11．6）,20min：（0．0±O．7）vs（50．4±8．2）;P〈0．01];C02组的肠管扩张程度评分明显低于空气组,差异有统计学意义[（1．2±0．5）vs（3．6±0．9）;P〈0．05];结肠镜检查前、到达回盲部、退回至直肠、检查结束后10min4个时间点记录经皮呼气末CO2分压,差异均无统计学意义。结论与以空气为媒介的结肠镜比较,以CO2为媒介的结肠镜检查应用于老年人,安全可靠,并且具有痛苦小、操作时间短、耐受性好的显著优势。     

Drug Delivery at the Aortic Valve Tissues of Healthy Domestic Pigs with a Paclitaxel-Eluting Valvuloplasty Balloon

Background: Restenosis occurs invariably within 1 year following balloon valvulopasty in aortic valve stenosis. The mechanism of restenosis seems to involve a dynamic cellular component that could be a target for drug inhibition. We investigated the feasibility of local drug delivery at the aortic valve tissues of healthy pigs with a paclitaxel-eluting balloon.
Methods: Aortic valvuloplasty was performed in eight anesthetized domestic pigs using paclitaxel-eluting balloons (3 μg/mm² balloon surface area). They were assigned to two or four times 15-second balloon inflations and were sacrificed 30 minutes after final balloon inflation.
Results: The aortic annulus to balloon diameter ratio was 1.15 ± 0.07. The mean paclitaxel concentration in the aortic valve leaflets was 0.91 ± 1.36 μg/mL (0.34 ± 0.05 μg/mL in the two-inflation group, 1.48 ± 1.86 μg/mL in the four-inflation group, P = 0.23). The percentage of the total paclitaxel dose recovered in the aortic valve leaflets was 18 ± 11⁻⁶% (13 ± 6⁻⁶% and 25 ± 14⁻⁶% in the two- and four-inflation group, P = 0.16).
Conclusion: Local drug delivery at the aortic valve leaflets of healthy pigs with a paclitaxel-eluting balloon is feasible and concentrations within the therapeutic window are detected 30 minutes after the procedure. The antirestenotic potential of this treatment should be studied.     

Evaluation of an extremely flatulent patient

We recently encountered a patient with severe flatulence who previously had been subjected to innumerable diagnostic tests and ineffective therapies based on the belief that his rectal gas was produced in the colon. Analysis of three flatus samples demonstrated that nitrogen (N₂) was the predominant flatus gas whereas the three gases produced in the gut (CO₂, H₂ [hydrogen], and CH₄ [methane]) comprised  <16%  of rectal gas. This result plus a series of other diagnostic tests clearly indicated that the patient's flatus was derived almost entirely from swallowed air. Based on this case, the present report summarizes available data on excessive flatulence and suggests a rational approach to the patient complaining of this problem. Particular emphasis is placed upon a sequential strategy consisting of: 1) a count of flatus passages to determine if the subject truly is abnormal (normal:  <20 passages/day  ); 2) an analysis of flatus to determine if the flatus originates from swallowed air (predominantly nitrogen) or intraluminal production (predominantly CO₂, H₂, and CH₄); and 3) treatment based upon the origin of the rectal gas.     

Association between angiotensin-converting enzyme gene polymorphisms and exercise performance in patients with COPD

Background and objective:   Recent studies have shown that polymorphisms of the angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary disorders. The ACE gene is involved in the regulation of inflammatory reactions to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The hypothesis for this study was that the ACE gene may be associated with the ventilatory response to exercise and the aerobic work efficiency of skeletal muscle in patients with COPD.
Methods:   Sixty-one Chinese Han COPD patients and 57 healthy control subjects performed incremental cardiopulmonary exercise testing on a cycle ergometer. ACE genotypes were determined using PCR amplification.
Results:   Resting lung function and blood gas index were not significantly different among the three ACE genotype COPD groups. Similarly, there were no significant differences in AT, maximal O₂ uptake, maximal O₂ pulse, maximal dyspnoea index, ventilatory response (ΔVE/ΔVCO₂), O₂ cost of ventilation (VO₂/W/VE), end-tidal partial pressure of carbon dioxide at maximal exercise and maximal SaO₂ among the three ACE genotype COPD patients. Maximal work load and aerobic work efficiency were higher in the COPD group with the II genotype than in those with the ID or DD genotype. There were no significant differences in resting lung function and cardiopulmonary exercise testing parameters among the three ACE genotype control groups.
Conclusions:   The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.     

The Phosphodiesterase III Inhibitor Olprinone Decreases Sensitivity of Rat Kupffer Cells to Endotoxin

Background: Sensitivity of Kupffer cells to endotoxin [lipopolysaccharide (LPS)] and overproduction of tumor necrosis factor-α (TNF-α) are critical for progression of alcoholic liver injury. Therefore, suppression of TNF-α should prove useful for treatment of alcoholic liver injury. However, a transient increase of intracellular calcium ([Ca²⁺]_i) is required for LPS-induced TNF-α production by the macrophage cell line. The phosphodiesterase III inhibitor olprinone has been shown to suppress [Ca²⁺]_i level in vascular smooth muscle cells. Accordingly, the purpose of this study was to determine whether olprinone could prevent sensitization of Kupffer cells to endotoxin.
Methods: Kupffer cells were isolated by collagenase digestion and differential centrifugation. LPS was added to Kupffer cells 24 hr after incubation with or without olprinone (0.1 μmol/liter). After addition of LPS (10 μg/ml) to culture media, [Ca²⁺]_i was measured using a fluorescent indicator, fura-2.
Results: LPS increased [Ca²⁺]_i of Kupffer cells in control rats from basal levels (28 ± 4 nmol/liter) to 280 ± 14 nmol/liter. This increase was blunted by olprinone (91 ± 8 nmol/liter). Similarly, olprinone diminished the LPS (1 μg/ml)-induced TNF-α production by Kupffer cells by 30% (2220 ± 116 vs. 1386 ± 199 pg/ml; p < 0.05).
Conclusions: These results indicate that olprinone decreases sensitivity of Kupffer cells to endotoxin.     

Fecal Hydrogen Sulfide Production in Ulcerative Colitis

Objective: Sulfide, a product of sulfate-reducing bacteria, has been proposed to play an etiologic role in ulcerative colitis. Ulcerative colitis feces have increased numbers and activity of sulfate-reducing bacteria, but only modestly increased sulfide. However, fecal sulfide exists largely in the volatile, highly toxic H₂S form that moves rapidly from feces to surrounding gas. Our aim was to quantify the fecal release of H₂S and other volatiles (CO₂, H₂, CH₂, methanethiol, and dimethylsulfide).
Methods: Fecal samples from 25 subjects with ulcerative colitis and 17 controls were incubated in 4-L containers, and gas release was assessed at intervals over 24 h.
Results: H₂S release by ulcerative colitis feces was elevated 3–4-fold at every measurement point compared with normal feces (   p < 0.003  at 24 h). The only other significant difference was increased CO₂ release by ulcerative colitis feces at 1 h. Supplementation of fecal homogenates with sulfur-containing substrates showed that organic compounds (mucin, cysteine, taurocholate) provided more readily utilizable substrate for H₂S production than did sulfate.
Conclusions: Increased H₂S release is a relatively localized metabolic aberration of ulcerative colitis feces. This increased H₂S may reflect abnormalities of the fecal bacteria and/or substrate availability.     

Alpha1-Adrenergic Receptor Modulation of Repolarization in Canine Purkinje Fibers

Alpha-Agonists and Repolarization. Introduction: Alpha-adrenergic receptor stimulation increases contractility and prolongs repolarization. These effects are modulated by α₁-adrenergic receptor-mediated inhibition of transsarcolemmal potassium currents.
Methods and Results: We used standard microelectrode techniques to study the actions of 4-aminopyridine (4-AP), which blocks the transient outward current, I_to, and WAY-123,398, which blocks the delayed rectifier, I_k, on canine Purkinje fiber action potential prolongation induced by phenylephrine. At a basic cycle length of 1 second, phenylephrine (0.1 to 10 μ) dose-dependently prolonged action potential duration at 90% repolarization (APD₉₀) from 331 ± 10 msec to 400 ± 12 msec (P < 0.05) at phenylephrine, 10 μ. Phenylephrine did not change phase 1 or plateau height. 4-AP (0.1 mM) decreased phase 1 magnitude, shifted plateau height to more positive potentials (from 0.1 ± 1.8 mV to 14.3 ± 1.1 mV [P < 0.05]), and shortened APD₉₀ from 318 ± 9 msec to 294 ± 8 msec (P < 0.05). 4-AP did not block phenylephrine effects on APD₉₀, which increased, at 10 μ phenylephrine, from 294 ± 8 msec to 342 ± 6 msec (P < 0.05). In contrast, WAY-123,398 (0.1 μ) prolonged APD₉₀ from 360 ± 6 msec to 452 ± 6 msec (P < 0.05), and had no effect on plateau height. In the presence of WAY-123,398, phenylephrine no longer increased APD_9o.
Conclusion: (1) Agents that block I_to shorten APD in Purkinje fibers; and (2) the α-agonist mediated increase of APD in canine Purkinje fibers can be explained by inhibition of I_k.     

Potent Antiarrhythmic Effects of Chronic Amiodarone in Canine Pulmonary Vein Sleeve Preparations

Objectives: To examine the effects of chronic amiodarone on the electrophysiology of canine pulmonary vein (PV) sleeve preparations and left ventricular wedge preparation.
Background: Amiodarone is commonly used for the treatment of ventricular and supraventricular arrhythmias. Ectopic activity arising from the PV plays a prominent role in the development of atrial fibrillation (AF).
Methods: Standard microelectrode techniques were used to evaluate the electrophysiological characteristics of superfused PV sleeve (left superior or inferior) and arterially perfused left ventricular (LV) wedge preparations isolated from untreated and chronic amiodarone-treated dogs (amiodarone, 40 mg/kg daily for 6 weeks).
Results: In PV sleeves, chronic amiodarone (n = 6) induced a significant increase in action potential duration at 90% repolarization (APD₉₀) and a significant use-dependent reduction in V_max leading to 1:1 activation failure at long cycle lengths (basic cycle length of 124 ± 15 ms in control vs 420 ± 320 ms after chronic amiodarone [P < 0.01]). Diastolic threshold of excitation increased from 0.3 ± 0.2 to 1.8 ± 0.7 mA (P < 0.01). Delayed and late phase 3 early afterdepolarizations and triggered activity could be induced in PV sleeve preparations using acetylcholine (ACh, 1 μM), high calcium ([Ca²⁺]_o= 5.4 mM), isoproterenol (Iso, 1 μM), or their combination in 6 of 6 untreated PV sleeves, but in only 1 of 5 chronic amiodarone-treated PV sleeve preparations. V_max, conduction velocity, and 1:1 activation failure were much more affected in PV sleeves versus LV wedge preparations isolated from amiodarone-treated animals.
Conclusions: The results point to potent effects of chronic amiodarone to preferentially suppress arrhythmogenic substrates and triggers arising from the PV sleeves of the dog.