Proof of principle of a novel co-pulsating intra-ventricular membrane pump.

In this proof of principle study, we investigated the effectiveness and safety of hemodynamic support with the Intra-Ventricular Membrane Pump (IVMP). The IVMP was implanted into the apex of the left ventricle. Hemodynamic assessment was performed in six ex vivo beating porcine hearts (PhysioHeart platform). The cardiac output (CO), mean arterial pressure (MAP), coronary flow (CF) and pulse pressure (PP) were obtained before and during IVMP support and reported as means ± standard deviations. In two additional visualization experiments, the integrity of the mitral valve was assessed during IVMP support. We found a significant increase of the CO (+1.4 ± 0.2 L/min, P < .001), MAP (+13 ± 6 mm Hg, P = .008), CF (+0.23 ± 0.1 L/min, P = .004), and PP (+15 ± 4 mm Hg, P = .002) during IVMP support, when compared to baseline. No interference of the IVMP with mitral valve function was observed. An increase of premature ventricular complexes (PVC) was observed during support with the IVMP (mean PVC-burden 4.3% vs. 0.7% at baseline), negatively influencing hemodynamic parameters. The IVMP is able to significantly improve hemodynamic parameters in a co-pulsatile fashion, without hampering the function of the mitral valve. These findings provide a basis for future development of a catheter-based IVMP.

Low-Intensity Ultrasound Modulation May Prevent Myocardial Infarction-induced Sympathetic Neural Activation and Ventricular Arrhythmia.

BACKGROUND: Low-intensity focused ultrasound (LIFU) has been shown to be a beneficial tool for autonomic nervous system modulation, but its effect on the left stellate ganglion (LSG) remains unknown. OBJECTIVE: To seek the effect of LIFU on myocardial infarction (MI)-induced LSG activation and ventricular arrhythmias (VAs). METHODS: In this study, 20 dogs were included and randomly divided into the LIFU (LIFU & MI, n = 8), Sham (sham LIFU & MI, n = 8), and Control group (sham LIFU & sham MI, n = 4). For each LIFU intervention (1.0-2.0 W, 10 minutes) of the LSG, the LSG function, ventricular effective refractory period (ERP), and temperature were tested pre-intervention and postintervention. Thereafter, MI was induced by left anterior artery ligation and VAs were recorded for 1 hour. At the end, both the LSG and the heart were extracted for biomedical and histological analysis. RESULTS: In the Sham group, no significant change was shown in ventricular ERP or LSG function for any intensity settings of sham LIFU intervention when compared with the group baseline. In the LIFU group, however, both 1.5 and 2.0 W LIFU modulation of LSG resulted in significant prolongation of ERP and attenuation of LSG function. Furthermore, the incidence of VAs was significantly attenuated in the LIFU group compared with the Sham group. Moreover, histological analysis showed that no damage or apoptosis was observed in LSG although a statistically significant increase was shown in temperature (maximal increase <1°C) with 1.5 and 2.0 W LIFU intervention. CONCLUSION: LIFU stimulation may be a safe and beneficial tool for LSG attenuation and VA prevention in the MI canine model.

Effects of renal denervation on 24-h heart rate and heart rate variability in resistant hypertension.

BACKGROUND: Catheter-based renal sympathetic denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in patients with hypertension. The present study aimed at investigating the effects of RDN on heart rate (HR), number of premature captions, and heart rate variability (HRV). METHODS: A total of 105 patients (67% male, age 63.5 ± 10 years) with resistant hypertension (BP 169 ± 22/89 ± 14 mmHg) underwent bilateral RDN using a radiofrequency catheter (Symplicity Flex, Medtronic). 24-h Holter monitoring was performed at baseline and after 6 months. Besides HR profile, the number of premature atrial (PAC) and ventricular captions (PVC), time and frequency domain-based HRV were analyzed. Data are presented as mean ± standard deviation or median (interquartile range). RESULTS: Office systolic and diastolic BP were reduced after RDN by 21.8 ± 25.2 mmHg and 8 ± 18.7 mmHg (p < 0.001 for both), respectively. Twenty-eight (27%) patients had a reduction of < 10 mmHg in systolic BP. At baseline, mean 24-h HR was 65.7 ± 9.9 bpm. The prevalence of PAC [median 1.2 (0.3-6.2)] and PVC [median 1.2 (0.1-13.9)] was low and values of HRV were within normal limits and not different between responders and non-responders. After 6 months, patients with a baseline HR > 72 min had a significant reduction in HR by 2.3 ± 7.1 bpm. Parameters of HRV did not significantly change during follow-up. In patients with ≥ 6 PAC per hour at baseline, a significant median reduction of - 12.4 (- 37.4 to - 2.3) PAC after 6 months was documented (p = 0.002), which occurred independently from BP effects. The number of PVC was not significantly altered after RDN. CONCLUSION: In patients with resistant hypertension and elevated HR or high burden of PACs, RDN was associated with a reduction of HR and number of PAC. Parameters of HRV were not changed after RDN nor were predictive of response to RDN.

Intracerebroventricular endothelin receptor-A blockade in rats decreases phase-II ventricular tachyarrhythmias during acute myocardial infarction.

Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis are unknown. We examined ventricular tachyarrhythmias after endothelin receptor-A blockade in the brain of Wistar rats with acute myocardial infarction. For this aim, BQ-123 (n=6) or phosphate-buffered saline (n=6) were injected intracerebroventricularly. After 10 min, the left coronary artery was ligated, followed by implantation of telemetry transmitters. Electrocardiography and voluntary activity (as a surrogate of acute left ventricular failure) were continuously monitored for 24 h. Infarct-size was similar in the two groups. There were fewer episodes of ventricular tachyarrhythmias of shorter average duration in treated rats, leading to markedly shorter total duration (12.3+/-8.9 s), when compared to controls (546.2+/-130.3 s). Voluntary activity increased in treated rats during the last hours of recording, but bradyarrhythmic episodes were comparable between the two groups. Endothelin receptor-A blockade in the brain of rats decreases the incidence of ventricular tachyarrhythmias post-ligation, without affecting bradyarrhythmic episodes. These findings call for further research on the pathophysiologic role of endothelin during acute myocardial infarction.

Noninvasive light emitting diode therapy: A novel approach for postinfarction ventricular arrhythmias and neuroimmune modulation.

BACKGROUND: Sympathetic neural activation plays a key role in the incidence and maintenance of acute myocardial infarction (AMI) induced ventricular arrhythmia (VA). Furthermore, previous studies showed that AMI might induce microglia and sympathetic activation and that microglial activation might contribute to sympathetic activation. Recently, studies showed that light emitting diode (LED) therapy might attenuate microglial activation. Therefore, we hypothesized that LED therapy might reduce AMI-induced VA by attenuating microglia and sympathetic activation. METHODS: Thirty anesthetized rats were randomly divided into three groups: the Control group (n = 6), AMI group (n = 12), and AMI + LED group (n = 12). Electrocardiogram (ECG) and left stellate ganglion (LSG) neural activity were continuously recorded. The incidence of VAs was recorded during the first hour after AMI. Furthermore, we sampled the brain and myocardium tissue of the different groups to examine the microglial activation and expression of nerve growth factor (NGF), interleukin-18 (IL-18), and IL-1ß, respectively. RESULTS: Compared to the AMI group, LED therapy significantly reduced the incidence of AMI-induced VAs (ventricular premature beats [VPB] number: 85.08 ± 13.91 vs 27.5 ± 9.168, P < .01; nonsustained ventricular tachycardia (nSVT) duration: 34.39 ± 8.562 vs 9.005 ± 3.442, P < .05; nSVT number: 18.92 ± 4.52 vs 7.583 ± 3.019, P < .05; incidence rate of SVT/VF: 58.33% vs. 8.33%, P < .05) and reduced the LSG neural activity (P < .01) in the AMI + LED group. Furthermore, LED significantly attenuated microglial activation and reduced IL-18, IL-1ß, and NGF expression in the peri-infarct myocardium. CONCLUSION: LED therapy may protect against AMI-induced VAs by suppressing sympathetic neural activity and the inflammatory response.

The Protective Effects of Preconditioning With Dioscin on Myocardial Ischemia/Reperfusion-Induced Ventricular Arrhythmias by Increasing Connexin 43 Expression in Rats.

Myocardial ischemia-reperfusion (IR) injury is associated with high disability and mortality worldwide. This study was to explore the roles of dioscin in the myocardial IR rats and discover the related molecular mechanisms. Rats were divided into 5 groups: sham, IR, IR + 15 mg/kg dioscin, IR + 30 mg/kg dioscin, and IR + 60 mg/kg dioscin. Heart rate (HR), mean arterial blood pressure (MAP), and rate pressure product (RPP) were evaluated at 10 minutes before ischemia, immediately after ischemia, and at the beginning, middle, and end of reperfusion. Arrhythmia score and myocardial infarct size were examined in rats of all groups. The serum creatine kinase-muscle/brain (CKMB) and cardiac troponin I (cTnI) levels were analyzed via enzyme-linked immunosorbent assay. Protein amount of total connexin 43 (T-Cx43) and phosphorylated connexin 43 (P-Cx43) was evaluated by Western blot. Ischemia reperfusion significantly decreased HR, MAP, and RPP of rats compared to the sham group. However, dioscin significantly attenuated the above phenomena in a dose-dependent manner. Dioscin markedly inhibited IR-induced increase in arrhythmias score, infarct size, and serum CKMB and cTnI levels. In addition, dioscin strikingly induced IR-repressed expression of T-Cx43 and P-Cx43. Our results suggested that dioscin pretreatment exhibited protective effects against myocardial IR injury. Moreover, we found that dioscin attenuated myocardial IR-induced ventricular arrhythmias via upregulating Cx43 expression and activation.

Chronic median nerve modulation reduces ventricular arrhythmia and improves ventricular function in a postmyocardial infarction rabbit model.

AIM: Median nerve stimulation (MNS) is a novel neuromodulation approach for treatment of ventricular arrhythmia, but little is known about its chronic effects. The aim of this study was to investigate the effects of chronic MNS on ventricular arrhythmia and ventricular dysfunction postmyocardial infarction (MI). METHOD: Two weeks after MI, 12 rabbits were randomly divided into control and MNS groups, and chronic MNS was performed in MNS group for 2 weeks. Ventricular function and arrhythmias; sympathetic innervation and activity; and interleukin-1 ß (IL-1 ß) and norepinephrine (NE) levels were analyzed. RESULTS: Both the total number of premature ventricular complex and episodes of ventricular tachycardia were lower in MNS group than in control group (20 560 ± 10 314 beats vs 70 079 ± 37 184 beats, P = .021, and 115 ± 63 episodes vs 307 ± 164 episodes, P = .034, respectively). Compared with control group, MNS decreased the cardiac sympathetic nerve density and level of circulating NE in MNS group (1798.42 ± 644.07 µm2 /mm2 vs 1003.79 ± 453.00 µm2 /mm2, P = .041, and 20.86 ± 4.54 pg/mL vs 11.07 ± 1.43 pg/mL, P = .002, respectively). MNS also improved the left ventricular ejection fraction (59.07 ± 1.91% vs 49.77 ± 3.47%, P = .003) and inhibited the level of IL-1 ß in serum (69.19 ± 4.71 pg/mL vs 85.93 ± 12.80 pg/mL, P = .013). CONCLUSION: Chronic MNS appears to protect against ventricular arrhythmia and improves ventricular function post-MI, which may be mediated by suppressing cardiac sympathetic activity and anti-inflammatory effects.

The Effects of Continuous Positive Airway Pressure on Premature Ventricular Contractions and Ventricular Wall Stress in Patients with Heart Failure and Sleep Apnea.

Background: We aimed to investigate the effects of continuous positive airway pressure (CPAP) treatment on electrocardiography (ECG), premature ventricular contraction load on 24-hour Holter recordings, and implantable cardioverter defibrillator (ICD) shocks in patients with obstructive sleep apnea syndrome (OSAS) and heart failure. Methods: Patients with heart failure and ICD and patients with newly diagnosed OSAS were divided into two groups according to CPAP treatment. To compare the impact of CPAP on ECG parameters, both baseline and 6-month ECG, 24-hour Holter ECG, ambulatory blood pressure monitoring, echocardiography, polysomnography, and laboratory parameters were collected. Results: CPAP treatment significantly reduced the frequency of premature ventricular contractions, T-peak to T-end, corrected QT, corrected QT dispersion, and T-peak to T-end/corrected QT ratio in the study group (p < 0.001 for all). Although the baseline NT-pro-BNP levels were similar between study and control groups, after six months, the NT-pro-BNP levels of the study group were significantly lower than that of the control group (39.18 ± 7.57 versus 46.11 ± 7.65; p < 0.001). Conclusions: CPAP treatment in patients with heart failure and ICD and in patients with newly diagnosed OSAS may have beneficial effects on premature ventricular contractions and electrocardiographic arrhythmia indices and NT-pro-BNP levels. However, these results are needed to be clarified with further studies.

Protective effect of fenofibrate against ischemia-/reperfusion-induced cardiac arrhythmias in isolated rat hearts.

Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase-dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating and cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase-inducing properties that lead to increase in endogenous EET production. In the current investigations, fenofibrate (100 mg/kg, orally) for 2 weeks decreased ischemia-/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) in the isolated rat hearts. Fenofibrate caused marked inhibition of the reperfusion-induced cardiac arrhythmias. The incidence of reperfusion-induced VF decreased from 80% in the control vehicle-treated animals to 33% in the fenofibrate-treated animals (P < 0.001). PVCs were also significantly (P < 0.01) decreased from 223.2 ± 51 in control vehicle-treated animals to 136.8 ± 22 in fenofibrate-treated animals. Total duration of reperfusion-induced VT decreased from 29.2 ± 6.3 s in control, vehicle-treated animals to 4.8 ± 1.3 s in fenofibrate-treated animals, P < 0.001. Heart rate and perfusion pressure were not significantly affected by fenofibrate pretreatment. Diltiazem, a clinically used anti-arrhythmic agent, produced complete protection against I/R-induced cardiac arrhythmias in this model reducing the incidence of VF from 80% in control, vehicle-treated animals to 10% in diltiazem-treated hearts. These findings indicate that fenofibrate suppresses arrhythmias in isolated rat hearts subjected to I/R-induced injury.

Cholinesterase inhibition reduces arrhythmias in asymptomatic Chagas disease.

INTRODUCTION: Parasympathetic dysfunction may play a role in the genesis of arrhythmias in Chagas disease. AIM: This study evaluates the acute effects of pyridostigmine (PYR), a reversible cholinesterase inhibitor, on the occurrence of arrhythmias in patients with Chagas cardiac disease. METHOD: Following a double-blind, randomized, placebo-controlled, cross-over protocol, 17 patients (age 50±2 years) with Chagas cardiac disease type B underwent 24-hour Holter recordings after oral administration of either pyridostigmine bromide (45 mg, 3 times/day) or placebo (PLA). RESULTS: Pyridostigmine reduced the 24-hours incidence (median [25%-75%]) of premature ventricular beats-PLA: 2998 (1920-4870), PYR: 2359 (940-3253), P=.044; ventricular couplets-PLA: 84 (15-159), PYR: 33 (6-94), P=.046. Although the total number of nonsustained ventricular tachycardia in the entire group was not different (P=.19) between PLA (1 [0-8]) and PYR (0 [0-4]), there were fewer episodes under PYR in 72% of the patients presenting this type of arrhythmia (P=.033). CONCLUSION: Acute administration of pyridostigmine reduced the incidence of nonsustained ventricular arrhythmias in patients with Chagas cardiac disease. Further studies that address the use of pyridostigmine by patients with Chagas cardiac disease under a more prolonged follow-up are warranted.

[Catheter ablation of ventricular extrasystoles and ventricular tachycardia in the elderly]. / Katheterablation ventrikulärer Extrasystolen und Kammertachykardien im hohen Alter.

BACKGROUND: The prevalence of structural heart disease increases with higher age, and thereby the basis for ventricular arrhythmias is created. Catheter ablation has been shown to be an effective therapy option that is very safe and achieves good long-term results in patients with recurrent ventricular tachycardia (VT). Data regarding ablation in patients older than 75 years is sparse, although this patient group was included as a minority in most published VT ablation studies. Data from younger patient collectives may not be transferable to older patient cohorts due to differences in patient comorbidities and baseline characteristics. METHODS: Studies with patient collectives ≥75 years or even ≥80 years show comparable efficacy of catheter ablation for VT; however, the complication rate is higher, mainly due to groin complications, increases. Catheter ablation of ischemic VT appears effective and safe even in ≥75 year olds; however, extensive data for other structural heart diseases are lacking. Epicardial procedures are also possible and safe in older patients (≥80 years). Due to the significant challenges of VT ablation in older patients, including the consideration of complex comorbidities, these should be performed in specialized centers with high expertise. CONCLUSION: The aim of catheter ablation in older patients is, above all, to improve quality of life and morbidity. Long-term survival is significantly lower due to the "near end of life" situation than in younger patients. Careful consideration of alternative therapy options, chances for success of the catheter ablation, and their risks, taking into account specific patient conditions and symptoms, is crucial in these patients.

Ventricular arrhythmia burst is an independent indicator of larger infarct size even in optimal reperfusion in STEMI.

OBJECTIVE: We hypothesized that ventricular arrhythmia (VA) bursts during reperfusion phase are a marker of larger infarct size despite optimal epicardial and microvascular perfusion. METHODS: 126 STEMI patients were studied with 24h continuous, 12-lead Holter monitoring. Myocardial blush grade (MBG) was determined and VA bursts were identified against subject-specific background VA rates in core laboratories. Delayed-enhancement cardiovascular magnetic resonance imaging was used to determine infarct size. RESULTS: In the group with MBG 3 no significant differences were found for baseline characteristics between burst versus no burst (102 vs. 24). In those with optimal epicardial and microvascular reperfusion (TIMI 3, stable ST-recovery, and MBG 3), VA burst was associated with larger infarct size (N=102/126; median 11.0 vs. 5.1%; p=0.004). CONCLUSION: In the event of MBG 3, VA bursts were associated with significantly larger infarct size even if optimal epicardial and microvascular reperfusion was present.

The exercise heart rate profile in master athletes compared to healthy controls.

Endurance exercise protects the heart via effects on autonomic control of heart rate (HR); however, its effects on HR indices in healthy middle-aged men are unclear. This study compared HR profiles, including resting HR, increase in HR during exercise and HR recovery after exercise, in middle-aged athletes and controls. Fifty endurance-trained athletes and 50 controls (all male; mean age, 48·7 ± 5·8 years) performed an incremental symptom-limited exercise treadmill test. The electrocardiographic findings and HR profiles were evaluated. Maximal O2 uptake (52·6 ± 7·0 versus 34·8 ± 4·5 ml kg(-1)  min(-1) ; P<0·001) and the metabolic equivalent of task (15·4 ± 1·6 versus 12·2 ± 1·5; P<0·001) were significantly higher in athletes than in controls. Resting HR was significantly lower in athletes than in controls (62·8 ± 6·7 versus 74·0 ± 10·4 beats per minute (bpm), respectively; P<0·001). Athletes showed a greater increase in HR during exercise than controls (110·1 ± 11·0 versus 88·1 ± 15·4 bpm; P<0·001); however, there was no significant between-group difference in HR recovery at 1 min after cessation of exercise (22·9 ± 5·6 versus 21·3 ± 6·7 bpm; P = 0·20). Additionally, athletes showed a lower incidence of premature ventricular contractions (PVCs) during exercise (0·0% versus 24·0%; P<0·001). Healthy middle-aged men participating in regular endurance exercise showed more favourable exercise HR profiles and a lower incidence of PVCs during exercise than sedentary men. These results reflect the beneficial effect of endurance training on autonomic control of the heart.

Ablation of frequent PVC in patients meeting criteria for primary prevention ICD implant: Safety of withholding the implant.

BACKGROUND: Premature ventricular complex (PVC) ablation has been shown to improve left ventricular ejection fraction (LVEF) and New York Heart Association functional class in patients with left ventricular dysfunction. Both are considered key variables in predicting risk of sudden cardiac death. OBJECTIVE: The objective of this study was to assess whether ablation might remove the primary prevention (PP) implantable cardioverter-defibrillator (ICD) indication in patients with frequent PVC. METHODS: Sixty-six consecutive patients with PP-ICD indication and frequent PVC [33 (50%) men; mean age 53 ± 13 years; 11 (17%) with ischemic heart disease] underwent PVC ablation. The ICD was withheld and the indication was reevaluated at 6 and 12 months. RESULTS: LVEF progressively improved from 28% ± 4% at baseline to 42% ± 12% at 12 months (P < .001). New York Heart Association functional class improved from 2 patients with NYHA functional class I (3%) at baseline to 35 (53%) at 12 months (P < .001). The brain natriuretic peptide level decreased from 246 ± 187 to 176 ± 380 pg/mL (P = .004). The PP-ICD indication was removed in 42 patients (64%) during follow-up, from 38 (92%) of them at 6 months, showing an independent association with baseline PVC burden and successful sustained ablation. In patients with successful sustained ablation, a cutoff value of 13% PVC burden had a sensitivity of 100% and a specificity of 93% (area under the curve 99%) for removing ICD indication postablation. No sudden cardiac deaths or malignant ventricular arrhythmias were observed. CONCLUSION: In patients with frequent PVC and PP-ICD indication, ablation improves LVEF and, in most cases, allows removal of the indication. Withholding the ICD and reevaluating within 6 months of ablation seems to be a safe and appropriate strategy.

Brugada Syndrome Phenotype Elimination by Epicardial Substrate Ablation.

BACKGROUND: Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may be definitively eliminated by radiofrequency ablation, remains unknown. METHODS AND RESULTS: Patients with BrS underwent epicardial mapping to identify areas of abnormal electrograms as target for radiofrequency ablation. Substrate identification consisted in mapping right ventricle epicardial surface before and after flecainide (2 mg/kg per 10 minutes). After radiofrequency ablation, flecainide and remap confirmed elimination of abnormal substrate, BrS ECG pattern, and ventricular tachycardia/ventricular fibrillation inducibility. Flecainide testing was performed at each follow-up visits ≤6 months. Fourteen patients with BrS, median age 39 years (30.3-42.3) with implantable cardioverter-defibrillator were enrolled. Low-voltage areas (<1.5 mV) were commonly identified on the anterior right free wall and right ventricular outflow tract, which increased after flecainide from 17.6 cm(2) (12.1-24.2) to 28.5 cm(2) (21.6-30.2; P=0.001). Similarly, areas with abnormal electrograms increased after flecainide from 19.0 (17.5-23.6) to 27.3 cm(2) (24.0-31.2; P=0.001). After 23.8 minutes (18.1-28.5) of radiofrequency ablation, abnormal electrograms disappeared, whereas low-voltage areas were replaced by scar areas (<0.5 mV) of 25.9 cm(2) (19.6-31.0). Substrate elimination resulted in BrS ECG pattern disappearance and no ventricular tachycardia/ventricular fibrillation inducibility without complications. After a median follow-up of 5 months (3.8-5.3), ECG remained normal despite flecainide. CONCLUSIONS: In patients with BrS, there is a relationship between abnormal ECG pattern, the extent of abnormal epicardial substrate, and ventricular tachycardia/ventricular fibrillation inducibility. Ablation of the substrate identified in the presence of flecainide can eliminate the BrS phenotype and warrants further study.

Chronic pantoprazole administration and ischemia--reperfusion arrhythmias in vivo in rats--antiarrhythmic or arrhythmogenic?

BACKGROUND: The safety of all proton pump inhibitors (PPIs) in patients with intrinsic cardiac disease has not been well studied. In the present study, the effect of PPI pantoprazole on ventricular arrhythmias induced by either ischemia or ischemia-reperfusion (I/R) was studied. METHODS: The left main coronary artery (LAD) was ligated for 30 or 10 min followed by a 30-min reperfusion in anesthetized rats. Rats were pretreated with pantoprazole (1.3 mg/kg) or vehicle by gastric gavage (daily for 3 weeks) before ligation. Serum electrolytes levels were measured by the end of the third week before coronary ligation. Lactate dehydrogenase (LDH) activity and nitric oxide (NO) concentrations were measured at the end of the ischemia and IR injury. RESULTS: Pantoprazole caused significant hyperkalemia by the end of third week compared with vehicle-treated rats. After LAD ligation (30 min), ventricular premature contractions (VPC), ventricular tachycardia (VT) and ventricular fibrillation (VF) were recorded in rats of the vehicle ischemia group. Pantoprazole pretreatment aggravate these arrhythmias and increased mortality. A 10-min period of ischemia followed by a 30-min reperfusion induced high incidence of VT (100%) and VF (80%) in the vehicle-treated group. The group of rats administered pantoprazole had significantly lower incidence and durations of VT and VF together with reduction of mortality rate. Pantoprazole significantly reduced serum LDH activity and NO release from myocardial tissue after both ischemia and I/R injury. CONCLUSION: Pantoprazole aggravated ischemia-induced arrhythmias but had a significant antiarrhythmic effect on I/R-induced ventricular arrhythmias.

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model.

OBJECTIVES: The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery. METHODS: Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n = 7), the single bolus group (SB) (n = 7, 15 × 10(7) ASCs), or the divided dose group (DD) (n = 7, 5 × 10(7) ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4(+) T and CD8(+) T cells were measured. RESULTS: The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4 ± 0.9%, 3.7 ± 0.7%, and -0.4 ± 0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3 ± 1.8 and -11.5 ± 2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9 ± 0.2, 0.8 ± 0.1, and 0.2 ± 0.2, respectively). The circulating number of CD8(+) T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687 ± 317/µL, 3,454 ± 787/µL, and 1,928 ± 457/µL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area. CONCLUSIONS: Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue.