Pulmonary hemodynamics and wave reflections in adults with atrial septal defects.

Using high-fidelity micromanometers and flow velocity sensors at right heart catheterization, we compared pulmonary hemodynamics and wave reflections in age-matched normal adults and those with atrial septal defects, separated into three subgroups based on levels of mean pulmonary artery pressure: low (<17 mmHg), intermediate (17-26 mmHg), high (>26 mmHg). We made baseline measurements in all groups and after intravenous sodium nitroprusside in the subgroups. All of the subgroups had higher than normal baseline pulmonary flows and corresponding power that did not differ among the subgroups. The pulmonary vascular resistance, input resistance, and characteristic impedance in the subgroups did not differ from normal. Aside from the elevated flow and power, the hemodynamics in the low subgroup did not differ from normal. The intermediate subgroup had significantly higher than normal right ventricular and pulmonary artery pressures, wave reflections, and shorter wave reflection time, which all reverted to normal after nitroprusside. The high subgroup had similar changes as the intermediate subgroup. Unlike that subgroup, however, the pressures, wave reflections, and reflection return time did not revert to normal after nitroprusside. Hence, elevated wave reflections, but not resistance or characteristic impedance, are the hallmark of pulmonary hypertension in adults with atrial septal defects. Our results demonstrate that detailed measurements of hemodynamics and assessment of responsiveness to vasodilators provide important information about the pulmonary circulation in atrial septal defect. Coupled with studies after defect closure, those results may be a better foundation than current ones for clinical decisions.

Endovascular Angioplasty of Celiac Axis Obstruction Prior to Pancreaticoduodenectomy in a Patient with Pancreatic Neuroendocrine Carcinoma.

UNLABELLED: In patients with celiac axis stenosis or occlusion, a pancreaticoduodenectomy procedure can increase the risk of hepato-pancreato-biliary and other organ ischemia or failure unless a complete revascularization of the celiac axis is performed prior to or simultaneous with such surgery. Celiac axis occlusion does not appear to be an uncommon finding in cases of pancreaticoduodenectomy. Preoperative abdominal angiography can play an important role in diagnosing this high risk comorbid disease, and adequate intervention can lead to a successful operation and good postoperative outcome. Herein, we reported a patient with periampullary malignancy and metastatic liver cancer, whose preoperative diagnosis of severe celiac axis stenosis was proved by preoperative abdominal angiography. Preoperative angioplasty was subsequently performed. After angioplasty, pancreaticoduodenectomy with resection of segments 4, 6 and 7 of liver was done and the postoperative course was uneventful. KEY WORDS: Celiac axis occlusion; Endovascular angioplasty; Pancreaticoduodenectomy.

Leptin to adiponectin ratio as a useful predictor for cardiac syndrome X.

OBJECTIVE: The role of adipokines in the development of cardiac syndrome X (CSX) remains unknown. METHODS: Fifty-nine CSX subjects were retrospectively enrolled from our catheterization databank. Another 54 subjects with valvular heart disease or arrhythmia served as controls. Adipokines were measured by ELISA tests. RESULTS: The CSX had lower circulating adiponectin but higher leptin and higher leptin/adiponectin ratio (×1000) (3.78 ± 4.96 vs. 2.14 ± 5.67, p < 0.001) than those of the controls. In a multivariate analysis, a higher leptin/adiponectin ratio was a predictor of CSX, while insulin-resistance index was not. CONCLUSIONS: Adipokines may be implicated in the pathogenesis of CSX.

Hypercalcemia-Induced New Onset Left Bundle Branch Block Mimicking Acute Myocardial Infarction in a Patient with Primary Hyperparathyroidism.

UNLABELLED: A 78-year-old women with a recent diagnosis of primary hyperparathyroidism presented with vague chest pain, and new onset left bundle block (LBBB) on the electrocardiogram (ECG) mimicking acute myocardial infarction (AMI). LBBB resolved without abnormal Q waves only after correction of hypercalcemia. The cardiac enzymes, including creatine kinase, creatine kinase-MB, and troponin-I were all within normal range. Hypercalcemia provoking ECG changes that mimic acute myocardial infarction is infrequently reported. To our knowledge, this is the first report of hypercalcemia-induced new onset LBBB mimicking AMI. Emergency physicians should include hypercalcemia-induced new onset LBBB on the ECG in the differential diagnosis of AMI. KEY WORDS: Acute myocardial infarction; Hypercalcemia; Hyperparathyroidism; left bundle branch block.

Caffeic acid phenethyl ester inhibits proliferation and migration, and induces apoptosis in platelet-derived growth factor-BB-stimulated human coronary smooth muscle cells.

BACKGROUND/AIMS: Restenosis after a percutaneous coronary intervention (PCI) during treatment for coronary artery disease is closely related to smooth muscle cell (SMC) proliferation and migration. In this study, we investigated the effects of caffeic acid phenethyl ester (CAPE) and its underlying mechanism on human coronary SMCs (HCSMCs) after platelet-derived growth factor-BB (PDGF-BB) stimulation in vitro. METHODS AND RESULTS: The results showed that CAPE inhibited proliferation and migration, and induced apoptosis. Concomitantly, CAPE inhibited activation of AKT1, MEK1 and ERK1/2 signaling molecules at 10-60 min after CAPE treatment. As revealed by flow cytometry, DNA fragmentation and TUNEL assay, the cells accumulated at the sub-G(1) phase, and cell apoptosis was observed after 30 and 90 µM CAPE treatment for 72 h. CAPE triggered the release of cytochrome c from mitochondria to cytosol, upregulated the proapoptotic gene Bax and downregulated the antiapoptotic gene Bcl-2. Upregulation of caspase-9 and caspase-3 indicated that CAPE precipitated the mitochondrion-dependent apoptotic signaling pathway. CONCLUSIONS: These results provide a molecular explanation for the antiproliferation, antimigration and proapoptotic effects of CAPE on HCSMCs after PDGF-BB stimulation.

Novel tips for engaging the coronary sinus guided by right ventricular lead.

AIMS: This study investigated the relationship between the ostia of the coronary sinus (CS) and the tricuspid annulus (TA) for CS cannulation using a right ventricular (RV) lead, which could map out the TA by forming a curve when placed at the apex or low septum. METHODS AND RESULTS: Seventy patients (45 males, 67 ± 12 years) who were admitted for CRT device implant were included in the evaluation of the relationship between the CS ostia and TA. An electrophysiological (EP) mapping catheter was used to probe the CS. The ostium was shown by the CS venography at the left anterior oblique (LAO) 20° and caudal 20°. Local electrograms were collected with CS catheters in the CS or RV. Transthoracic echocardiography was evaluated before each procedure. All CS ostia were located within 3.75 cm around the tip of TA. Sixty-two subjects (Group I, 89%) had CS ostia located under the TA. Eight patients (Group II) with CS ostia over the TA revealed larger left ventricular (LV) size and a smaller ratio of left atrium (LA)/LV size. LV enlargement predicted the presence of CS ostia over the TA. Typical CS electrograms were used to further confirm if the EP catheter was in the CS in all the subjects. CONCLUSION: Use of the RV lead revealed that the CS ostia had a close relationship with the TA.

Comparison of quick optimization of interventricular delay between simple methods: intracardiac electrogram and surface electrocardiogram after cardiac resynchronization therapy.

AIMS: It is time consuming to obtain optimal interventricular (VV) delay by conventional methods. This study is designed to compare quick optimization between intracardiac electrogram (IEGM) with surface electrocardiogram (ECG)-guided VV delay optimization for cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Fifty-one heart failure patients (M/F = 34/17, age = 71 ± 10-year-old) scheduled for CRT implantation were included. After atrioventricular optimization, VV delay optimization was performed by either the IEGM or surface ECG method. Aortic velocity time integral (AVTI) was used  as a reference in comparing these two methods. Real-time three-dimensional echocardiography was studied under three varying parameters-CRT switched off or CRT switched on, and VV delay optimized by IEGM guided or surface ECG. The AVTI could be improved equally by either IEGM-guided or surface ECG-guided VV optimization. All the other parameters [QRS width, systolic dyssynchrony index (SDI), left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV)] could be improved by either the IEGM or ECG method in these patients. In the multivariate logistic regression analysis, the immediate improvement of acute LVEF was independently related to favourable outcomes (odds ratio 1.23, 95% CI = 1.03-1.47, P = 0.02). CONCLUSIONS: The AVTI, QRS width, SDI, LVEF, LVEDV, and LVESV could be improved equally by either IEGM-guided or surface ECG-guided method after CRT.

Recurrent vasodilator-refractory acute coronary syndrome as the exclusive manifestation of Graves disease.

Whether recurrent acute coronary syndrome could be the exclusive manifestation of Graves disease remains unreported. We describe a premenopausal woman who had angiographically normal coronary arteries yet had 3 episodes of acute coronary events in forms of unstable angina, ST elevation, and non-ST elevation myocardial infarction despite the active therapy of calcium-channel blockade. She was finally diagnosed as with Graves disease, treated with antithyroid medication, and free from any angina relapse for up to 18 months. Thus, recurrent coronary events might be the only manifestation of subclinical hyperthyroidism in patients with angiographically normal coronary arteries and could only be prevented by antithyroid agents instead of conventional vasodilators.

A secure and rapid method for orotracheal intubation of laboratory rats utilising handy instruments.

CONTEXT: Tracheal intubation of anaesthetised rats for laboratory experiments remains an essential yet challenging procedure. OBJECTIVE: We aimed to investigate whether tracheal intubation can be safely and securely accomplished in laboratory rats employing only handy instruments and with minimal experience. DESIGN: The feasibility and safety of a modified orotracheal intubation method was evaluated in rats undergoing open-chest surgery as part of another research protocol, and compared with an existing technique. SETTING: The study was carried out in a tertiary medical centre-affiliated animal laboratory. ANIMALS: Eighty-five rats weighing 250 to 350 g anaesthetised with intraperitoneal pentobarbital (60 mg kg(-1)). INTERVENTIONS: Orotracheal intubation was performed on 35 animals (group Jou) using a previously reported technique and then on another 50 rats (group New) using the modified method employing a 3-ml syringe-derived intubation wedge, a 0.025-inch guidewire and a 16-gauge 45-mm-long intravenous catheter. MAIN OUTCOME MEASURES: The time for completion, the number of attempts and the incidence of difficulties and complications were recorded. The intubated tracheas were subsequently examined macroscopically and microscopically to determine position of the intubation catheter and the integrity of epithelial lining. RESULTS: Compared with the previous technique, the new method was completed more rapidly (1 ± 0.2 vs. 5 ± 2.4 min; P < 0.001), more smoothly (difficulties encountered in 8 vs. 74%; P < 0.001), with greater overall success (100 vs. 86%; P=0.022) and with fewer attempts [1 (1 to 1) vs. 2 (2 to 4); P < 0.001) for the new and Jou techniques, respectively, and with a lower incidence of procedure-related complications. Postmortem analysis confirmed there was no microscopic injury to the tracheal epithelial lining with the new technique in contrast to 57% in those using the Jou technique (P < 0.001). CONCLUSION: Tracheal intubation for laboratory rats can be securely and safely completed with the modified method employing a short learning curve and easily available devices.

Pretreatment of BAPTA-AM suppresses the genesis of repetitive endocardial focal discharges and pacing-induced ventricular arrhythmia during global ischemia.

INTRODUCTION: In isolated rabbit hearts, repetitive endocardial focal discharges (REFDs) were consistently observed during ventricular fibrillation (VF) with prolonged (>5 minutes) global ischemia (GI). We hypothesized that BAPTA-AM, a calcium chelator, can suppress these REFDs. METHODS AND RESULTS: Using a two-camera optical mapping system, we simultaneously mapped endocardial (left ventricle, LV) and epicardial (both ventricles) activations during ventricular arrhythmia with GI. In 5 hearts (protocol I), we infused Tyrode's solution (no BAPTA-AM) for ≥30 minutes before the onset of no-flow GI. In 7 additional hearts (protocol II), BAPTA-AM (20 µmol/L) was infused for ≥30 minutes before the initiation of GI. In protocol I, sustained VF (>30 seconds) was successfully induced in all 5 hearts with prolonged GI. REFDs were present in >85 % of recording time. In protocol II, however, ventricular arrhythmia was not inducible and REFDs were not observed after 5-minute GI in 5 hearts. Effects of BAPTA-AM on intracellular calcium (Ca(i) ) at the LV endocardium were also evaluated in 5 hearts (protocol III) using dual Ca(i) /membrane potential mapping. GI, both without and with BAPTA-AM pretreatment, caused a decrease of Ca(i) amplitude during S(1) pacing. However, this effect was more pronounced in the hearts with BAPTA-AM pretreatment (P < 0.001). GI, without BAPTA-AM pretreatment, caused broadening of Ca(i) transient. In contrast, GI, with BAPTA-AM pretreatment, caused narrowing of Ca(i) transient. CONCLUSIONS: BAPTA-AM pretreatment attenuates Ca(i) transient, suppressing the genesis of REFDs and pacing-induced ventricular arrhythmia during GI. These findings support the notion that Ca(i) dynamics is important in the maintenance of REFDs.

Pre-clinical detection of amiodarone-induced acute fibrosing alveolitis by intra-thoracic impedance monitor of an implantable cardioverter-defibrillator.

A 66-year-old male received an implant of a dual-chamber implantable cardioverter-defibrillator (ICD) and was prescribed amiodarone (400 mg/day). The intra-thoracic impedance monitor in the ICD antecedently detected amiodarone-induced acute fibrosing alveolitis >3 months prior to clinical symptoms.

Short-duration therapeutic hypothermia causes prompt connexin43 gap junction remodeling in isolated rabbit hearts.

BACKGROUND: Whether connexin43 gap junctions (Cx43 GJs) and spatial heterogeneity of conduction velocity (CV) restitutions are altered in hearts during moderate (MH; 33°C) and severe (SH; 30°C) hypothermia remains unclear. METHODS AND RESULTS: Using an optical mapping system, ventricular CV was evaluated by S1 pacing in 29 Langendorff-perfused isolated rabbit hearts at baseline (37°C, n=9), 30-min MH (n=6), 30-min SH (n=9), and rewarming (R, 30-min SH followed by 30-min 37°C, n=5). After CV evaluation, myocardium was collected to measure the level and distribution of non-phosphorylated (NP-Cx43) and total (T-Cx43) Cx43 by immunoblotting and immunoconfocal microscopy. In 6 additional hearts, Cx43 GJ remodeling was evaluated at 30-min SH with (n=3) or without (n=3) pretreatment of a protein kinase C (PKC) inhibitor. CV slowing and spatial heterogeneities of CV restitutions were enhanced in MH and SH hearts. NP-Cx43 was downregulated in MH (P=0.002) and SH (P<0.001) hearts. NP-Cx43 levels among 4 different ventricular sites became inhomogeneous in MH (P=0.017) and SH (P=0.046) hearts. However, T-Cx43 levels were unchanged. The percentages of lateralized NP- and T-Cx43 were increased in MH, SH, and R hearts. Pretreatment of PKC inhibitor attenuated SH-induced NP-Cx43 lateralization (P=0.0495). CONCLUSIONS: Short-duration (30 min) therapeutic hypothermia causes prompt Cx43 GJs remodeling, in which the PKC pathway is involved. Rewarming abolished hypothermia-induced conduction disturbance, while Cx43 GJs lateralization did not completely recover.

Mimetic total coronary sinus occlusion due to superselection with the balloon catheter.

A 77-year-old man with dilated cardiomyopathy, atrial fibrillation, QRS duration of 140 ms, and NYHA functional class III was referred for cardiac resynchronization therapy device implantation. Coronary sinus (CS) contrast venography by balloon catheter showed no evidence of tributary veins, mimicking total occlusion of the CS. It was found to be due to superselection of a side branch with the balloon catheter.

Therapeutic hypothermia (30 degrees C) enhances arrhythmogenic substrates, including spatially discordant alternans, and facilitates pacing-induced ventricular fibrillation in isolated rabbit hearts.

BACKGROUND: Therapeutic hypothermia (TH, 30 degrees C) protects the brain from hypoxic injury. However, TH may potentiate the occurrence of lethal ventricular fibrillation (VF), although the mechanism remains unclear. The present study explored the hypothesis that TH enhances wavebreaks during VF and S(1) pacing, facilitates pacing-induced spatially discordant alternans (SDA), and increases the vulnerability of pacing-induced VF. METHODS AND RESULTS: Using an optical mapping system, epicardial activations of VF were studied in 7 Langendorff-perfused isolated rabbit hearts at baseline (37 degrees C), TH (30 degrees C), and rewarming (37 degrees C). Action potential duration (APD)/conduction velocity (CV) restitution and APD alternans (n=6 hearts) were determined by S(1) pacing at these 3 stages. During TH, there was a higher percentage of VF duration containing epicardial repetitive activities (spatiotemporal periodicity) (P<0.001). However, TH increased phase singularity number (wavebreaks) during VF (P<0.05) and S(1) pacing (P<0.05). TH resulted in earlier onset of APD alternans (P<0.001), which was predominantly SDA (P<0.05), and increased pacing-induced VF episodes (P<0.05). TH also decreased CV, shortened wavelength, and enhanced APD dispersion and the spatial heterogeneity of CV restitution. CONCLUSIONS: TH (30 degrees C) increased the vulnerability of pacing-induced VF by (1)facilitating wavebreaks during VF and S(1) pacing, and (2)enhancing proarrhythmic electrophysiological parameters, including promoting earlier onset of APD alternans (predominantly SDA) during S(1) pacing.

Repetitive endocardial focal discharges during ventricular fibrillation with prolonged global ischemia in isolated rabbit hearts.

BACKGROUND: Ventricular fibrillation (VF) during prolonged (>5 min) global ischemia (GI) could be due to repetitive endocardial focal discharges (REFDs). This hypothesis was tested in isolated rabbit hearts. METHODS AND RESULTS: With optical mapping, simultaneous endocardial (left ventricle, LV) and epicardial (both ventricles) activations during VF with prolonged GI were studied (protocol I, 8 hearts). Lugol solution was applied to the LV endocardium in additional 5 hearts after 5-min GI (protocol II). During prolonged GI, sustained VF (>30 s) was successfully induced in 7 protocol I hearts. The dominant frequency of summed optical signals at the LV endocardium was higher than at the epicardium (P<0.05). Mapping data showed that after 5-min GI, REFDs were present in >90% for recording time. There were 18 windows of optical recording showing spontaneous VF termination. In 10, once REFDs ceased, the VF episode terminated immediately. Electrical defibrillation was also performed on 3 hearts. Eight shocks showed early VF recurrence after successful defibrillation. REFDs were consistently involved in the initiation period of recurrence. In protocol II, Lugol subendocardial ablation diminished REFD genesis during re-induced VF. These VF episodes were all non-sustained. CONCLUSIONS: REFDs at the LV endocardium were important for both VF maintenance and post-shock recurrence during prolonged GI in this model.

Immediate change in pulmonary venous flow pattern after deployment of occluder device for atrial septal defect.

Transcatheter closure of a secundum defect using a septal occluder is a safe and effective procedure based on long-term follow-up, but no clinical studies have examined immediate hemodynamic changes. We evaluated pulmonary venous flow velocity pattern before and immediately after deployment of the Amplatzer septal occluder for closure of atrial septal defect. From May 2003 to January 2005, 48 patients with secundum atrial septal defect received transcatheter closure with complete occlusion. Patients were divided into two groups according to age: pediatric group, under 16 years (n = 30, age 7.3 +/- 3.2 years), and adult group, 16 years or older (n = 18, age 30.1 +/- 11.4 years). Pulmonary venous flow pattern was recorded by transesophageal echocardiography before and immediately after occluder deployment. Immediately after deployment in both patient groups, pulmonary vein systolic (S) and diastolic (D) wave velocity decreased, but atrial reversal (AR) wave velocity increased. In the pediatric group, S-wave was 56.1 +/- 17.1 versus 35.5 +/- 11.3 cm/sec (P < 0.001); D-wave was 57.6 +/- 12.5 versus 42.9 +/- 11.8 cm/sec (P < 0.001); and AR wave velocity was 12.2 +/- 3.8 versus 15.5 +/- 4.1 cm/sec (P < 0.001). In the adult group, S-wave was 48.4 +/- 13.7 versus 32.7 +/- 10.3 cm/sec (P < 0.001); D-wave was 51.9 +/- 11.7 versus 38.0 +/- 8.5 m/sec (P < 0.001); and AR wave velocity was 12.1 +/- 4.1 versus 16.2 +/- 4.9 cm/sec (P < 0.001). Comparison of pulmonary venous flow before and immediately after deployment of the Amplatzer septal occluder provides an excellent model to evaluate the influence of an atrial communication on pulmonary venous flow. Pulmonary venous forward flow decreases following atrial septal defect (ASD) closure.

Acute embolic myocardial infarction in a patient with paroxysmal atrial fibrillation receiving direct-current cardioversion.

Coronary embolism with acute myocardial infarction (MI) following direct-current (DC) cardioversion of atrial fibrillation (AF) has rarely been reported. We present the case of a 34-year-old female with severe aortic regurgitation and highly symptomatic paroxysmal AF. Acute embolic MI occurred 4 days after DC cardioversion of AF, although there was no left atrial thrombus detected before this procedure. Insufficient anticoagulation therapy during the post-cardioversion period was the cause, leading to embolic MI.

Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes.

AIMS: The objective of this study was to investigate whether a cytoprotective herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial effect on doxorubicin-induced cardiac toxicity in vitro and in vivo. METHODS AND RESULTS: Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 microM), EGb761 (25 microg/mL), or EGb761 plus doxorubicin. After 24 h, doxorubicin upregulated p53 mRNA expression, disturbed Bcl-2 family protein balance, disrupted mitochondrial membrane potential, precipitated mitochondrion-dependent apoptotic signalling, induced apoptotic cell death, and reduced viability of cardiomyocytes, whereas EGb761 pretreatment suppressed all the actions of doxorubicin. Similarly, rats treated with doxorubicin [3 mg/kg intraperitoneally (i.p.) three doses every other day] displayed retarded growth of body and heart as well as elevated apoptotic indexes in heart tissue at both 7 and 28 days after exposure, whereas EGb761 pretreatment (5 mg/kg i.p. 1 day before each dose of doxorubicin) effectively neutralized the aforementioned gross and cellular adverse effects of doxorubicin. CONCLUSION: Doxorubicin impairs viability of cardiomyocytes at least partially by activating the p53-mediated, mitochondrion-dependent apoptotic signalling. EGb761 can effectively and extensively counteract this action of doxorubicin, and may potentially protect the heart from the severe toxicity of doxorubicin.

Arterial Hemodynamics in Prehypertensives.

Compared to age-matched normotensive adults, those with essential hypertension have been shown to have distinct arterial hemodynamic abnormalities consisting of increased peripheral resistance, pulse wave velocity, and wave reflection magnitude as well as decreased wave reflection time and aortic compliance. These abnormalities are further exacerbated by beta-adrenergic blockade. To see if there are similar hemodynamic abnormalities that antedate the onset of fixed hypertension, we compared age-matched normotensives with prehypertensives selected from patients undergoing diagnostic cardiac catheterization. Ascending aortic pressure and flow were measured with a micromanometer and flow velocity sensor in the baseline state and after beta-adrenergic blockade. In the baseline state the prehypertensive compared to the normotensive group had elevated blood pressure, resistance, left ventricular end-diastolic pressure (LVEDP), and wave reflections. Beta-adrenergic blockade increased resistance, LVEDP, and wave reflections in both groups. Some of these findings are the same as those we previously reported in young persons with established, essential hypertension. The differences in LVEDP and wave reflections, both in the baseline state and after beta-blockade, were still present in subgroups with no differences in blood pressure. Hence, the elevated wave reflections in prehypertensives do not appear to be directly related to the level of blood pressure. These results support the notion that the elevated blood pressure in hypertension may represent a later manifestation of an already abnormal vascular system rather than the vascular abnormalities resulting from hypertension. Consequently, even before blood pressure becomes elevated, early diagnosis and treatment of the vascular abnormalities in prehypertensives may be warranted.

Early recurrence of ventricular fibrillation after successful defibrillation during prolonged global ischemia in isolated rabbit hearts.

INTRODUCTION: The mechanisms that lower the efficacy of electrical defibrillation during prolonged global ischemia remain unclear. METHODS AND RESULTS: Epicardial activation patterns during attempted electrical defibrillation were studied in 18 Langendorff-perfused rabbit hearts at baseline, after 5-minute no-flow global ischemia and after 10-minute reperfusion. DFT(50) (voltage required to achieve 50% probability of successful defibrillation) was determined at each stage. Defibrillation was considered successful if postshock sinus/idioventricular rhythm was present. Prolonged global ischemia converted type 1 VF (multiple wandering wavelets) into type 2 VF (repetitive epicardial breakthroughs, REBs). The mean DFT(50) after 5-minute ischemia (96 +/- 39 V) was significantly lower when compared with that at baseline (154 +/- 47 V, P < 0.0001) and after 10-minute reperfusion (145 +/- 47 V, P < 0.001). However, the incidence of early (within 10 seconds) VF recurrence after successful shock during prolonged global ischemia (23 of 78, 29.5%) was much higher than that at baseline (2 of 60, 3.3%) and after 10-minute reperfusion (5 of 63, 7.9%; P < 0.0001). Mapping data showed that the VF wavefronts during prolonged global ischemia were initially halted by the shock, followed by one to five ventricular escape beats. These beats then triggered REBs and early VF recurrence. In eight out of 11 episodes, the REBs before and after successful shock arose from the same location near the interventricular septum. CONCLUSIONS: There is a significant reduction of DFT(50) during prolonged global ischemia. However, defibrillation appears to fail when the preexisting REBs near the interventricular septum induce early VF recurrence. Shock per se cannot eliminate the substrates of these REBs.