Holmium:yttrium-aluminium-garnet laser with MOSES technology is more efficient than thulium fibre laser in supine mini-percutaneous nephrolithotomy.

OBJECTIVES: To address the paucity of literature comparing outcomes achieved with utilisation of the high-power holmium:yttrium-aluminium-garnet (Ho:YAG) laser with MOSES technology vs those achieved with the thulium fibre laser (TFL) in mini-percutaneous nephrolithotomy (PCNL). METHODS: A retrospective review was performed of patients undergoing supine mini-PCNL between August 2021 and May 2023. Exclusion criteria were urinary diversion, simultaneous utilisation of >1 laser platform, use of any other form of fragmentation, and ureteric stones. The Ho:YAG platform (Lumenis Pulse P120H™ with MOSES technology, 120W; Boston Scientific®) and the TFL (Soltive SuperPulsed Thulium Fibre [SPTF], 60W; Olympus®) were compared. Data on stone-free rate (SFR) were determined by computed tomography performed on the first postoperative day and presented as absence of stone fragments, no fragments larger than 2 mm, or no fragments larger than 4 mm. RESULTS: A total of 100 patients met the inclusion criteria, 51 mini-PCNLs with the Ho:YAG laser and 49 with the SPTF laser. No significant differences in demographics or stone characteristics were detected between the two groups. The Ho:YAG laser utilised less energy and time, resulting in higher ablation efficiency (P < 0.05) and less total operating time (P < 0.05). Overall, there was no difference in SFR in any category between the Ho:YAG group and the SPTF group (no fragments: relative risk [RR] 0.81, 95% confidence interval [CI] 0.59-1.12, P = 0.21; fragments <2 mm: RR 0.86, 95% CI 0.67-1.10, P = 0.23; fragments <4 mm: RR 0.96, 95% CI 0.80-1.15, P = 0.67). CONCLUSIONS: Although we observed an equivalent postoperative SFR, this study supports a shorter operating time and greater intra-operative laser efficiency with the Ho:YAG laser over the SPTF laser in mini-PCNL.

Impact of Renal Access Angle and Speed of Nephroscope Retrieval Movements on the Vortex Effect.

OBJECTIVE: To analyze the influence of different renal access angles (AAs) and nephroscope retrieval speeds on the efficacy of the vortex effect (VE) in mini-percutaneous nephrolithotomy (mini-PCNL). This study aimed to understand the poorly understood physical components of the VE. MATERIALS AND METHODS: A Pexiglas™ (KUS®) model was built based on the dimensions of a 15/16 F mini-PCNL set (Karl Storz). The flow rate was continuous via an automatic pump and calibrated to achieve hydrodynamic equivalence to the real equipment. One experiment consisted of manually retrieving all 30 stone phantoms (3 mm diameter) utilizing only the VE. Cumulative time to retrieve all stones was measured. An accelerometer recorded instant speeds of the nephroscope every 0.08 seconds (s), and 3 experiments were performed at each angle (0°, 45°, and 90°). A logistic regression model was built utilizing maximum speeds and access angles to predict the effectiveness of the VE. RESULTS: Mean cumulative time for complete stone retrieval was 28.1 seconds at 0° vs 116.5 seconds at 45° vs 101.4 seconds at 90° (P < .01). We noted significantly higher speeds at 0° compared to 45° and 90° (P < .01); however, differences in average and maximum speed between 45° and 90° were not statistically significant (P = .21 and P = .25, respectively). The regression model demonstrated a negative association between increasing maximum speed and VE's effectiveness (OR 0.547, CI 95% 0.350-0.855, P < .01). When controlling for maximum speed, the 0° angle had significantly higher chances of achieving at least a partially effective VE. CONCLUSION: Increasing the renal access angle or nephroscope extraction speed negatively impacts the effectiveness of the VE. This significantly increased procedure time in the laboratory model, suggesting that the VE is less effective at higher sheath angles.

Prospective Trial of Water Vapor Thermal Therapy for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia in Subjects with a Large Prostate: 6- and 12-month Outcomes.

Background: Current guidelines recommend Rezum water vapor thermal therapy for the treatment of benign prostatic hyperplasia (BPH) for prostate glands ranging in volume from 30 to 80 cm3. Few prospective studies have specifically evaluated the use of Rezum for larger prostates. Objective: To evaluate the safety and efficacy of water vapor thermal therapy in patients with a prostate gland >80 cm3 and ≤150 cm3. Design setting and participants: In this prospective, single-arm study at seven centers in the USA, subjects were males aged >50 yr with symptomatic BPH and prostate volume of >80 cm3 and ≤150 cm3. Intervention: Rezum was used to deliver sterile water vapor via a transurethral approach to ablate targeted areas of prostate tissue. Outcome measurements and statistical analysis: The primary efficacy outcome was response to therapy, defined on a per-patient basis as a ≥30% improvement in International Prostate Symptom Score (IPSS) from baseline to 6 mo. The primary safety outcome was a composite of serious device-related safety events. Secondary outcomes included catheterization for device-related retention. IPSS outcomes over time were analyzed via generalized estimating equations. Results and limitations: Among 47 eligible patients, prostate volume ranged from 80.8 to 148.1 cm3. All patients completed 6-mo follow-up, and 40/47completed 12-mo follow-up. At 6 mo, 83% were treatment responders according to the primary efficacy endpoint. The mean IPSS improvement at 6 mo was 11.9 ± 7.5 points, reflecting significant improvement. The primary safety outcome was met, with no occurrence of device-related composite safety events. The study is limited by the nonrandomized design and early termination, unrelated to safety or effectiveness. Conclusions: Our results are consistent with previous findings for prostate glands of up to 80 cm3, and indicate the safety and efficacy of Rezum for BPH in patients with a larger prostate. Patient summary: Rezum therapy, in which water vapor is used to treat targeted areas of the prostate, is currently recommended for patients with benign enlargement of the prostate and a prostate size of up to 80 cm3. We found that this treatment was also effective and safe in patients with a larger prostate of 80-150 cm3.

The Vortex Effect in Minimally Invasive Percutaneous Nephrolithotomy.

OBJECTIVE: To describe the physical principles of the vortex effect to better understand its applicability in minimally invasive percutaneous nephrolithotomy (MIP) procedures. METHODS: Two acrylic phantom models were built based on the cross-sectional area (CSA) ratio of a MIP nephroscope and access sheaths (15/16F and 21/22F MIP-M, Karl Storz). The nephroscope phantom was 10 mm in diameter. The access sheaths had diameters of 14 mm (CSA ratio: 0.69) and 20 mm (CSA ratio: 0.30). The models were adapted to generate hydrolysis, and hydrogen bubbles enhanced flow visualization on a green laser background. After calibration, the experimental flow rate was set to 12.0 mL/s. Three 30-second trials assessing the flow were performed with each model. Computational fluid dynamic simulations were completed to determine the speed and pressure profiles. RESULTS: In both models, as the incoming fluid from the nephroscope phantom attempted to move toward the collecting system, a stagnation point was demonstrated. No fluid entered the collecting system phantom. Utilizing the 14 mm sheath, we observed a random generation of several vortices and a pressure gradient (PG) of 114.4 N/m2 between the nephroscope's tip and stagnation point. In contrast, examining the 20 mm sheath revealed a significantly smaller PG (19.4 N/m2) and no noticeable vortices were noted. CONCLUSION: The speed of the fluid and equipment geometry regulate the PG and the vortices field, which are responsible for the production of the vortex effect. Considering the same flow rate, a higher ratio between the CSA of the nephroscope and access sheath results in improved efficacy of the vortex effect.

Optimizing stone harvesting in miniaturized-PCNL: a critical examination of renal access angles, technology, and the role they play in operative efficiency.

PURPOSE: Stone retrieval can be a laborious aspect of percutaneous nephrolithotomy (PCNL). A unique phenomenon of mini-PCNL is the vortex-effect (VE), a hydrodynamic form of stone retrieval. Additionally, the vacuum-assisted sheath (VAS) was recently developed as a new tool for stone extraction. The purpose of our study is to investigate the impact of renal access angle (as a surrogate for patient positioning) on stone retrieval efficiency and compare the efficiency among methods of stone retrieval. METHODS: A kidney model was filled with 3 mm artificial stones. Access to the mid-calyx was obtained using a 15Fr sheath. Stones were retrieved over three minutes at angles of 0°, 25°, and 75° utilizing the VE, VAS, and basket. Stones were weighed for comparison of stones/retraction and stones/minute. Trials were repeated three times at each angle. RESULTS: Renal access angle of 0° was associated with increased stone retrieval for both the VE and VAS (p < 0.05). The VE was the most effective method for stones retrieved per individual retraction at an angle of 0° (p < 0.005), although when analyzed as stones retrieved per minute, the VE and VAS were no longer statistically different (p = 0.08). At 75°, none of the methods were statistically different, regardless if analyzed as stones per retraction or per minute (p = 0.20-0.40). CONCLUSIONS: Renal access angle of 0° is more efficient for stone retrieval than a steep upward angle. There is no difference in stone retrieval efficiency between the VE and VAS methods, although both are superior to the basket at lower sheath angles.

On the rocks: can urologists identify stone composition based on endoscopic images alone? A worldwide survey of urologists.

PURPOSE: As part of the management of nephrolithiasis, determination of chemical composition of stones is important. Our objective in this study is to assess urologists' accuracy in making visual, intraoperative determinations of stone composition. MATERIALS AND METHODS: We conducted a REDCap survey asking urologists to predict stone composition based on intraoperative images of 10 different pure-composition kidney stones of 7 different types: calcium oxalate monohydrate (COM), calcium oxalate dihydrate (COD), calcium phosphate (CP) apatite, CP brushite, uric acid (UA), struvite (ST) and cystine (CY). To evaluate experience, we examined specific endourologic training, years of experience, and number of ureteroscopy (URS) cases/week. A self-assessment of ability to identify stone composition was also required. RESULTS: With a response rate of 26% (366 completed surveys out of 1,370 deliveries), the overall accuracy of our cohort was 44%. COM, ST, and COD obtained the most successful identification rates (65.9%, 55.7%, and 52.0%, respectively). The most frequent misidentified stones were CP apatite (10.7%) and CY (14.2%). Predictors of increased overall accuracy included self-perceived ability to determine composition and number of ureteroscopies per week, while years of experience did not show a positive correlation. CONCLUSIONS: Although endoscopic stone recognition can be an important tool for surgeons, it is not reliable enough to be utilized as a single method for stone identification, suggesting that urologists need to refine their ability to successfully recognize specific stone compositions intraoperatively.

Breakage Costs in Flexible Ureteroscopy: Digital vs. Fiberoptic Modalities.

OBJECTIVE: To compare the maintenance costs of digital flexible ureteroscopes (DFU) versus fiberoptic flexible ureteroscopes (FFU) to understand the long-term financial impact associated with breakage in a flexible ureteroscopy (f-URS) program. METHODS: Data for breakage of FFU and DFU at an academic institution from 2019 to 2021 were obtained from our vendor (Karl Storz) and analyzed by month. Correlation test was used to evaluate significant differences in number of procedures, number of breakage events, breakage rates, and repair cost per month. Cumulative analyses were utilized to examine the number of procedures before failure (time to failure - TTF) and repair costs per procedure (RCpP). RESULTS: We performed a total of 2,154 f-URS, including 1,355 with FFU and 799 with DFU (P<.001). Although we found a higher number of breakage events in FFU (n=124) than DFU (n=73) (P<.001), the overall breakage rate was similar, 9.9% vs. 8.8%, respectively (P=0.86). On cumulative analysis, both modalities reached the same TTF plateau (11 cases) after 18 months. After 400 cases, the RCpP for DFU was 1.25 times higher than for FFU (P=0.04). CONCLUSION: Overall, we found no difference in overall scope breakage rates between DFU and FFU. Although there was no difference in TTF over time, at the beginning DFU displayed considerable higher durability, leading to lower RCpP. Furthermore, DFU's endurance leveled off to FFU over time, resulting in higher RCpP after 400 cases. This finding may be explained by the presence of renewed scopes after repair.

Image Distortion During Flexible Ureteroscopy: A Laboratory Model Comparing Super Pulsed Thulium Fiber Laser vs High-Power Ho:YAG Laser.

Purpose: Digital ureteroscopes employ "chip-on-the-tip" technology that allows for significant improvement in image resolution. However, image distortion often occurs during laser lithotripsy owing to acoustic wave production. We sought to compare image distortion using different laser power settings and distances from the laser fiber tip to the scope for the Super Pulsed Thulium Fiber (SPTF) laser and high-power Holmium:YAG (Ho:YAG) laser. Materials and Methods: Ureteroscopy was simulated using a silicon kidney-ureter-bladder model fitted with a 12F/14F access sheath and the Lithovue™ (Boston Scientific), disposable digital flexible ureteroscope. At defined laser parameters (10, 20, 30 and 40 W, short pulse), a 200-µm laser fiber was slowly retracted toward the tip of the ureteroscope during laser activation. Image distortion was identified, and distance from the laser tip to the scope tip was determined. Data from the two lasers were compared utilizing t-tests. Results: After controlling for frequency, power, and laser mode, utilizing 1.0 J of energy was significantly associated with less feedback than 0.5 J (-0.091 mm, p ≤ 0.05). Increased power was associated with larger feedback distance (0.016 mm, p ≤ 0.05); however, increase in frequency did not have a significant effect (-0.001 mm, p = 0.39). The SPFT laser had significantly less feedback when compared with all Holmium laser modes. Conclusions: Increased total power results in image distortion occurring at greater distances from the tip of the ureteroscope during laser activation. Image distortion occurs further from the ureteroscope with Ho:YAG laser than with SPTF fibers at the same laser settings. In clinical practice, the tip of the laser fiber should be kept further away from the tip of the scope during ureteroscopy as the power increases as well as when utilizing the Ho:YAG system compared with the SPTF laser platform. The SPTF laser may have a better safety profile in terms of potential scope damage.

Year-round trace gas measurements in the central Arctic during the MOSAiC expedition.

Despite the key role of the Arctic in the global Earth system, year-round in-situ atmospheric composition observations within the Arctic are sparse and mostly rely on measurements at ground-based coastal stations. Measurements of a suite of in-situ trace gases were performed in the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition. These observations give a comprehensive picture of year-round near-surface atmospheric abundances of key greenhouse and trace gases, i.e., carbon dioxide, methane, nitrous oxide, ozone, carbon monoxide, dimethylsulfide, sulfur dioxide, elemental mercury, and selected volatile organic compounds (VOCs). Redundancy in certain measurements supported continuity and permitted cross-evaluation and validation of the data. This paper gives an overview of the trace gas measurements conducted during MOSAiC and highlights the high quality of the monitoring activities. In addition, in the case of redundant measurements, merged datasets are provided and recommended for further use by the scientific community.

Stone size on endoscopic view as a predictor of successful stone retrieval during flexible ureteroscopy: an in vitro analysis.

PURPOSE: Basketing plays an important role during flexible ureteroscopy, but it can be time-consuming, especially when fragments are too large to pass through the ureteral access sheath. We aim to present the optimal on-screen, endoscopic stone size that predicts successful basketing through various access sheaths. METHODS: A tipless basket, individually extended to 5 mm from multiple ureteroscopes: (Flex-Xc, Karl Storz; Flex-X2s, Karl Storz; LithoVue, Boston Scientific; or URF-P6R, Olympus) and via differently sized access sheaths (10-12 Fr through 13-15 Fr), was used in retrieval attempts of various artificial stone sizes (2 mm through 5 mm). A relative endoscopic stone size was recorded as the stone's maximum diameter on endoscopic view compared to the total image diameter. RESULTS: Basketing of stones up to 2.5 mm, yielding relative endoscopic stone sizes of 0.38 (Flex-Xc), 0.30 (Flex-X2s), 0.32 (LithoVue), and 0.34 (URF-P6R), was successful using all access sheaths. Only the 12-14 Fr and greater sheaths allowed for successful basketing of 3 mm stones. Larger stones did not successfully pass through any of the access sheaths. CONCLUSION: Successful stone retrieval can be predicted by estimating the stone's size on screen, which is influenced by the type of flexible ureteroscope and access sheath. In our testing, stones of approximately one-third of the screen size passed successfully in all cases.

Rates of Behavioral Health Conditions and Health Risk Behaviors in Operators and Support Personnel in U.S. Special Operations Forces.

Objective: Rates of behavioral health disorders and potential protective factors in U.S. Special Operations Forces (SOF) have not been well studied, including differences between Operators and Support personnel, despite very high levels of combat exposure in these military personnel. The present study examined the prevalence of endorsed behavioral health problems and protective factors within a large sample of SOF personnel. Method: Anonymized data from 16,284 active duty SOF Service members from the 2016 Preservation of the Force and Family (POTFF) needs survey were analyzed. Results: Overall, the prevalence of PTSD (7.6%), depression (8.4%), alcohol misuse (12.8%), and nicotine use (28%) were comparable or lower than reported in conventional military populations. There were significant differences between Operators and Support personnel in a number of demographic and service-related variables. Operators also endorsed more direct combat exposure and scored higher on resilience and social support, and reported better quality and quantity of sleep. There were no significant group differences in rates of PTSD and depression, except lower odds (adjusted OR = 0.81) for alcohol problems in Support personnel (11.6%) compared to Operators (14.0%), p <.001, 95% CI [0.72, 0.91]. Conclusions: SOF personnel experience considerably higher exposure to combat deployments than conventional forces, yet the data from this study showed comparable or lower levels of behavioral health conditions. Although Operators were somewhat more likely than Support personnel to experience alcohol problems, they showed enhanced resilience, social support, and sleep health. Alcohol misuse is one potential target for preventive health efforts.

Duloxetine for the treatment of post-prostatectomy stress urinary incontinence.

OBJECTIVES: Stress urinary incontinence (SUI) is a known complication following prostatectomy. Duloxetine, a combined serotonin/norepinephrine reuptake inhibitor, can decrease SUI by increasing urethral sphincter contractility. We examined the outcomes of patients with mild to moderate post-prostatectomy SUI treated with duloxetine. METHODS: We conducted a retrospective review of men treated with duloxetine to manage mild to moderate post-prostatectomy SUI from 2006 to 2012. All patients received oral duloxetine 30 mg once a week, then 60 mg thereafter. Patients were seen one month later to determine drug efficacy and side effects. RESULTS: In total, 94 men were included in the study. Daily pad usage decreased from 2.9 (range: 1-5) to 1.6 (range: 0-4) (p < 0.05). Incontinence Impact Questionnaire (IIQ-7) scores decreased from 13.0 (range: 6-18) to 7.9 (range: 2-16) (p < 0.05). Linear satisfaction scores improved from 0.8 (range: 0-2) to 2.0 (range: 1-3) (p < 0.05). Following a 1-month duloxetine trial, 33/94 (35%) men reported satisfactory SUI improvement and requested to continue the medication. The drug was discontinued in 61/94 (65%) patients due to poor efficacy in 32/94 (34%), intolerable side effects in 14/94 (15%) or both in 15/94 (16%). Reported side effects included fatigue, light-headedness, insomnia, nausea and dry mouth. CONCLUSIONS: Duloxetine improved post-prostatectomy SUI in 47/94 (50%) men following a 1-month trial. However, only 33/94 (35%) patients were able to tolerate the drug. Duloxetine may be considered a treatment option for men with mild to moderate post-prostatectomy SUI.

Laparoscopic mesh herniorrhaphy: impact on outcomes associated with radical retropubic prostatectomy.

OBJECTIVES: Laparoscopic herniorrhaphy employing non-absorbable mesh (LMH) is a frequently performed procedure for groin hernia. Multiple case reports in the urologic literature have identified LMH as a complicating factor in patients undergoing open radical retropubic prostatectomy (RRP) for prostate cancer. The purpose of this study was to review our experience and outcomes in patients with a prior LMH undergoing open RRP. METHODS: After institutional review board approval, a retrospective review of all open RRPs performed by a single surgeon between 2003 and 2008 was used to identify patients with a history of a prior LMH. The outcomes of these patients were compared with a contemporary cohort of patients undergoing RRP by the same surgeon. RESULTS: Eighteen patients with a prior LMH underwent RRP. Five of the 18 had bilateral LMH, with unilateral LMH in the remainder. Outcomes in this group were compared with 38 patients without prior LMH. There was no difference between the groups in terms of age, preoperative PSA, prostate size, preoperative Gleason score, or body mass index, and RRP was successfully performed in all 18 LMH patients. One of 18 patients had a postoperative complication (persistent JP drainage). Compared with the control group, differences in operative time and blood loss bordered on statistical significance. CONCLUSIONS: Prior LMH is not a contraindication to RRP. While resulting in slightly longer operating times and higher blood loss, our experience suggests that RRP can be safely performed in these patients.

Inhibition of glycogen synthase kinase enhances isoflurane-induced protection against myocardial infarction during early reperfusion in vivo.

Inhibition of glycogen synthase kinase (GSK)-beta protects against ischemia-reperfusion injury. Brief exposure to isoflurane before and during early reperfusion after coronary artery occlusion also protects against infarction. Whether GSK-beta mediates this action is unknown. We tested the hypothesis that GSK inhibition enhances isoflurane-induced postconditioning. Rabbits (n = 88; 6 to 7 per group) subjected to a 30-min coronary occlusion followed by 3 h reperfusion received saline, isoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]) administered for 3 min before and 2 min after reperfusion, the selective GSK inhibitor SB216763 (SB21; 0.2 or 0.6 mg/kg), or 0.5 MAC isoflurane plus 0.2 mg/kg SB21. Other groups of rabbits pretreated with phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin (0.6 mg/kg), 70-kDa ribosomal protein s6 kinase (p70s6K) inhibitor rapamycin (0.25 mg/kg), or mitochondrial permeability transition pore (mPTP) opener atractyloside (5 mg/kg) received 0.6 mg/kg SB21 or 0.5 MAC isoflurane plus 0.2 mg/kg SB21. Additional groups received the mPTP inhibitor, cyclosporin A (5 mg/kg), plus 0.2 mg/kg SB21 with or without atractyloside pretreatment. Isoflurane (1.0 but not 0.5 MAC) and SB21 (0.6 but not 0.2 mg/kg) reduced (P < 0.05) infarct size (21% +/- 5%, 44% +/- 7%, 23% +/- 4%, and 46% +/- 2%, respectively, of left ventricular area at risk, mean+/- sd; triphenyltetrazolium staining) as compared with control (42% +/- 6%). Isoflurane (0.5 MAC) plus 0.2 mg/kg SB21 and cyclosporin A plus 0.2 mg/kg SB21 produced similar degrees of protection (24% +/- 4% and 27% +/- 6%, respectively). Atractyloside but not wortmannin or rapamycin abolished protection produced by 0.6 mg/kg SB21 and 0.5 MAC isoflurane plus 0.2 mg/kg SB21. Thus, GSK inhibition enhances isoflurane-induced protection against infarction during early reperfusion via a mPTP-dependent mechanism.

The influence of B-cell lymphoma 2 protein, an antiapoptotic regulator of mitochondrial permeability transition, on isoflurane-induced and ischemic postconditioning in rabbits.

Brief exposure to isoflurane or repetitive, transient ischemia during early reperfusion after prolonged coronary artery occlusion protects against myocardial infarction by inhibiting the mitochondrial permeability transition pore (mPTP). Inhibition of mPTP during delayed ischemic preconditioning occurred concomitant with enhanced expression of the antiapoptotic protein B cell lymphoma-2 (Bcl-2). We tested the hypothesis that Bcl-2 mediates myocardial protection by isoflurane or brief ischemic episodes during reperfusion in rabbits (n = 91) subjected to a 30-min left anterior descending coronary artery occlusion followed by 3 h reperfusion. Rabbits received 0.9% saline, isoflurane (0.5 or 1.0 minimum alveolar concentration, MAC) administered for 3 min before and 2 min after reperfusion, 3 cycles of postconditioning ischemia (10 or 20 s each) during early reperfusion, 0.5 MAC isoflurane plus 3 cycles of postconditioning ischemia (10 s), or the direct mPTP inhibitor cyclosporin A (CsA, 10 mg/kg) in the presence or absence of the selective Bcl-2 inhibitor HA14-1 (2 mg/kg, i.p.). Isoflurane (1.0, but not 0.5, MAC) and postconditioning ischemia (20 s but not 10 s) significantly (P < 0.05) reduced infarct size (mean +/- sd, 21% +/- 4%, 43% +/- 7%, 19% +/- 7%, and 39% +/- 11%, respectively, of left ventricular area at risk) as compared with control (44% +/- 4%). Isoflurane (0.5 MAC) plus 10 s postconditioning ischemia and CsA alone also exerted protection. HA14-1 alone did not affect infarct size nor block protection produced by CsA but abolished reductions in infarct size caused by 1.0 MAC isoflurane, 20 s postconditioning ischemia, and 0.5 MAC isoflurane plus 10 s postconditioning ischemia. The results suggest that Bcl-2 mediates isoflurane-induced and ischemic postconditioning by indirectly modulating mPTP activity in vivo.