Effects of exercise training on diastolic and systolic dysfunction in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a complex syndrome characterized by a progressive reduction of the left ventricular (LV) contractility, low exercise tolerance, and increased mortality and morbidity. Diastolic dysfunction (DD) of the LV, is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases. Also, it is well estimated that exercise training induces several beneficial effects on patients with CHF. AIM: To evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction (EF) in patients with CHF. METHODS: Thirty-two stable patients with CHF (age: 56 ± 10 years, EF: 32% ± 8%, 88% men) participated in an exercise rehabilitation program. They were randomly assigned to aerobic exercise (AER) or combined aerobic and strength training (COM), based on age and peak oxygen uptake, as stratified randomization criteria. Before and after the program, they underwent a symptom-limited maximal cardiopulmonary exercise testing (CPET) and serial echocardiography evaluation to evaluate peak oxygen uptake (VO2peak), peak workload (Wpeak), DD grade, right ventricular systolic pressure (RVSP), and EF. RESULTS: The whole cohort improved VO2peak, and Wpeak, as well as DD grade (P < 0.05). Overall, 9 patients (28.1%) improved DD grade, while 23 (71.9%) remained at the same DD grade; this was a significant difference, considering DD grade at baseline (P < 0.05). In addition, the whole cohort improved RVSP and EF (P < 0.05). Not any between-group differences were observed in the variables assessed (P > 0.05). CONCLUSION: Exercise rehabilitation improves indices of diastolic and systolic dysfunction. Exercise protocol was not observed to affect outcomes. These results need to be further investigated in larger samples.

Intracoronary Administration of Allogeneic Cardiosphere-Derived Cells Immediately Prior to Reperfusion in Pigs With Acute Myocardial Infarction Reduces Infarct Size and Attenuates Adverse Cardiac Remodeling.

BACKGROUND: Allogeneic cardiosphere-derived cells (CDCs) exert cardioprotective effects when administered intracoronarily after reperfusion in animal models of acute myocardial infarction (AMI). The "no-reflow" phenomenon develops rapidly post-reperfusion and may undermine the efficacy of cell therapy, due to poor cell delivery in areas of microvascular obstruction (MVO). We hypothesized that CDC-induced cardioprotection would be enhanced by cell administration prior to reperfusion, when microvasculature is still relatively intact, to facilitate widespread cell delivery within the ischemic area. METHODS AND RESULTS: We studied 81 farm pigs; 55 completed the specified protocols. A dose-optimization study in infarcted pigs demonstrated that the doses of 5 million and 10 million CDCs are the maximum safe doses that can be administered intracoronarily at 5 minutes prior to and at 5 minutes post-reperfusion, respectively, without aggravating MVO. Quantification of acute cell retention by polymerase chain reaction demonstrated that cell delivery prior to reperfusion resulted in higher cardiac cell retention compared to delivery post-reperfusion. We then performed a randomized, placebo-controlled study to assess the long-term efficacy of intracoronary infusion of 5 million allogeneic CDCs, delivered at 5 minutes prior to reperfusion, in a porcine model of AMI. The CDC therapy resulted in decreased scar size, improved regional systolic function, and attenuation of adverse cardiac remodeling (manifested as preserved global systolic function, preserved end-systolic volume, and decreased interstitial fibrosis) compared to placebo at 30 days post-MI. CONCLUSIONS: Dose-optimized intracoronary infusion of allogeneic CDCs prior to reperfusion in a porcine model of AMI is feasible, safe and confers long-term benefits.

Value of apical circumferential strain in the early post-myocardial infarction period for prediction of left ventricular remodeling.

BACKGROUND: Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is related to increased morbidity and mortality. The aim of the present study was to examine whether LV deformational and torsional parameters can predict LV remodeling in patients with AMI. METHODS: Forty-two patients (age 57 ± 14 years) presenting with an anterior ST-elevation AMI and treated with primary percutaneous transluminal coronary angioplasty (PTCA) were included in the study. Four days post MI, LV ejection fraction (EF), LV torsion, longitudinal (4-, 3- & 2-chamber) and circumferential strain of the LV apex were evaluated by conventional and speckle-tracking echocardiography. The echocardiographic study was repeated at 3 months post-AMI and patients with LV remodeling, i.e. an increase >15% in LV end-systolic volume (LVESV), were identified. RESULTS: The 13 patients with LV remodeling had significantly more impaired apical circumferential strain (-7.3 ± 2.2% vs. -18.9 ± 5.2%, p=0.001), EF (42 ± 7% vs. 48.9 ± 6%, p=0.005), LV apical rotation (6.8 ± 4.8° vs. 11.1 ± 4.0°, p=0.027), and LV global longitudinal strain (-9.7 ± 1.9% vs. -12.9 ± 2.9%, p=0.03) on the 4th day post-AMI, in comparison to those without LV remodeling. Apical circumferential strain on the 4th day post-AMI showed the strongest correlation with the LVESV 3 months post-AMI (r=0.76, p=0.001), compared to EF (r=-0.60, p=0.001), global longitudinal strain (r=0.56, p=0.001), and LV apical rotation (r=-0.53, p=0.001). Furthermore, apical circumferential strain demonstrated the highest diagnostic accuracy: area under the receiver operating characteristic (ROC) curve 0.98, with sensitivity 100% and specificity 96% for prediction of LV remodeling, using a cutoff value <-11.0%. CONCLUSION: In patients with anterior AMI, LV apical circumferential strain in the early post-MI period constitutes a significant prognostic factor for LV remodeling at 3 months. Assessment of this parameter may identify patients at high risk for heart failure development.

Skeletal muscle microcirculatory abnormalities are associated with exercise intolerance, ventilatory inefficiency, and impaired autonomic control in heart failure.

BACKGROUND: Several skeletal muscle abnormalities have been identified in patients with chronic heart failure (CHF), including endothelial dysfunction. We hypothesized that skeletal muscle microcirculation, assessed by near-infrared spectroscopy (NIRS), is impaired in CHF patients and is associated with disease severity. METHODS: Eighty-three stable patients with mild-moderate CHF (72 males, mean age 54 ± 14 years, body mass index 26.7 ± 3.4 kg/m(2)) and 8 healthy subjects, matched for age, gender and body mass index, underwent NIRS with the vascular occlusion technique and cardiopulmonary exercise testing (CPET) evaluation on the same day. Tissue oxygen saturation (StO(2), %), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured in the thenar muscle by NIRS before, during and after 3-minute occlusion of the brachial artery. Measurements included StO(2), oxygen consumption rate (OCR, %/min) and reperfusion rate (RR, %/min). All subjects underwent a symptom-limited CPET on a cycle ergometer. Measurements included VO(2) at peak exercise (VO(2)peak, ml/kg/min) and anaerobic threshold (VO(2)AT, ml/kg/min), VE/VCO(2) slope, chronotropic reserve (CR, %) and heart rate recovery (HRR(1), bpm). RESULTS: CHF patients had significantly lower StO(2) (75 ± 8.2 vs 80.3 ± 6, p < 0.05), lower OCR (32.3 ± 10.4 vs 37.7 ± 5.5, p < 0.05) and lower RR (10 ± 2.8 vs 15.7 ± 6.3, p < 0.05) compared with healthy controls. CHF patients with RR ≥9.5 had a significantly greater VO(2)peak (p < 0.001), VO(2)AT (p < 0.01), CR (p = 0.01) and HRR(1) (p = 0.01), and lower VE/VCO(2) slope (p = 0.001), compared to those with RR <9.5. In a multivariate analysis, RR was identified as an independent predictor of VO(2)peak, VE/VCO(2) slope and HRR(1). CONCLUSIONS: Peripheral muscle microcirculation, as assessed by NIRS, is significantly impaired in CHF patients and is associated with disease severity.

The challenge of treating congestion in advanced heart failure.

Volume overload is a common manifestation of heart failure decompensation. Interaction between impaired renal and heart function constitutes an important pathophysiologic mechanism that leads to congestion. In addition to improving symptoms and volume status, reduction of rehospitalization rates, maintenance of renal function and improvement of survival are all important goals of every therapeutic strategy. Currently, the use of diuretics, vasodilators, inotropes and ultrafiltration, together with investigational agents such as oral vasopressin antagonists and adenosine A1-receptor antagonists, constitute the main therapeutic options for the congested heart failure patient.

Mechanical assistance by intra-aortic balloon pump counterpulsation during reperfusion increases coronary blood flow and mitigates the no-reflow phenomenon: an experimental study.

The effects of the intra-aortic balloon pump (IABP) counterpulsation on the extent of myocardial infarction (MI), the no-reflow phenomenon (NRP), and coronary blood flow (CBF) during reperfusion in an ischemia-reperfusion experimental model have not been clarified. Eleven pigs underwent occlusion of the mid left anterior descending coronary artery for 1 h, followed by reperfusion for 2 h. CBF, distal to the occlusion site, was measured. In six experiments, IABP support began 10 min before, and continued throughout reperfusion (IABP Group). Five pigs without IABP support served as controls. At the end of each experiment, the myocardial area at risk (MAR) of infarction and the extent of MI and NRP were measured. Hemodynamic measurements at baseline and during coronary occlusion were similar in both groups. During reperfusion, systolic aortic blood pressure was significantly lower in the IABP Group than in controls. In the IABP Group, CBF reached a peak at 5 min of reperfusion, gradually decreased, but remained higher than at baseline, and significantly higher than in controls throughout the 2 h of reperfusion. In controls, CBF increased significantly above baseline immediately after the onset of reperfusion, then returned to baseline within 90 min. The extent of NRP (37 ± 25% vs. 68 ± 17%, P = 0.047) and MI (39 ± 23% vs. 67 ± 13%, P = 0.036), both expressed as percentage of MAR, was significantly less in the IABP group than in controls. After prolonged myocardial ischemia, IABP assistance started just 10 min before and throughout reperfusion increased CBF and limited infarct size and extent of NRP.

Reverse electrophysiologic remodeling after cardiac mechanical unloading for end-stage nonischemic cardiomyopathy.

BACKGROUND: Left ventricular assist devices (LVAD)-induced unloading appear to cause reverse cardiac remodeling. However, its effect on arrhythmogenicity is a controversial issue, and prospective data are lacking. We sought to investigate the impact of LVAD-induced unloading on the electrical properties of the failing heart. METHODS: We prospectively studied the effects of LVAD therapy on QRS, QT, and QTc durations and ventricular arrhythmias from electrocardiograms and 24-hour ambulatory electrocardiograms recorded before and during 6 months of mechanical support in 12 LVAD patients and 7 other patients with advanced nonischemic cardiomyopathy untreated with LVAD. RESULTS: After 1 week of LVAD support, QTc duration had decreased from 479 ± 79 ms to 411 ± 57 ms (p = 0.037), and QRS duration from 150 ± 46 ms to 134 ± 32 ms (p = 0.029). At 6 months, QTc was found to be 372 ± 56 ms (p = 0.046 versus baseline, 15% shortening) and QRS 118 ± 25 ms (p = 0.028 versus baseline, 11% shortening). A strong correlation was found between QTc shortening and increase in left ventricular ejection fraction and decrease in left ventricular filling pressures. After 2 months of LVAD support, premature ventricular contractions had decreased from 3,507 ± 4,252 to 483 ± 417 in 24 hours (p = 0.043), ventricular couplets from 82 ± 99 to 29 ± 25 in 24 hours (p = 0.05), and ventricular runs from 9 ± 8 to 10 ± 9 (not significant). No patient died suddenly or suffered a symptomatic arrhythmic event during follow-up. No significant electrocardiographic, functional, or hemodynamic change was observed in the 7 patients untreated with LVAD. CONCLUSIONS: The LVAD support caused progressive shortening of QTc and QRS intervals, consistent with reverse remodeling of the failing heart's electrical properties, accompanied by a decrease in frequency of ventricular arrhythmias.

Myocardial sympathetic innervation and long-term left ventricular mechanical unloading.

OBJECTIVES: The purpose of this study was to analyze the effects of left ventricular assist devices (LVADs) on myocardial sympathetic innervation of the failing heart. BACKGROUND: Ventricular unloading by LVADs seems to cause reverse remodeling of the failing heart, but little is known about the sympathetic nerve activity during long-term mechanical unloading. METHODS: We studied the effects of LVADs on myocardial sympathetic innervation, by iodine 123-meta-iodobenzylguanidine (123I-mIBG) scintigraphy performed before and 3 months after LVAD implantation in 12 end-stage heart failure patients. We calculated the: 1) heart-to-mediastinum (H/M) uptake ratio on early and delayed images, indicating myocardial accumulation of 123I-mIBG; and 2) rate of 123I-mIBG washout after initial accumulation. Similar 123I-mIBG imaging and functional and hemodynamic measurements were made 3 months apart in 6 other heart failure patients not treated with an LVAD. RESULTS: After 3 months of LVAD support, the mean left ventricular ejection fraction had increased from 19+/-6% to 29 +/- 9% (p=0.006), peak oxygen consumption increased from 9+/-4 ml/kg/min to 13+/-3 ml/kg/min (p=0.058), serum sodium increased from 135+/-4 mEq/l to 140+/-2 mEq/l (p=0.014), whereas the left ventricular end-diastolic diameter decreased from 72+/-7 mm to 56+/-3 mm (p=0.002), pulmonary capillary wedge pressure decreased from 30+/-6 mm Hg to 5+/-3 mm Hg (p=0.012), serum creatinine decreased from 1.5+/-0.6 mg/dl to 1.0+/-0.4 mg/dl (p=0.011), and B-type natriuretic peptide decreased from 2,279+/-1,900 pg/ml to 102+/-5 pg/ml (p=0.003). After 3 months of LVAD, the H/M ratio increased on delayed images from 1.25+/-0.18 to 1.43+/-0.13 (p=0.01) and on early images from 1.35+/-0.19 to 1.44+/-0.11 (p=0.028), and the washout rate decreased from 51.0+/-23.2% to 30.6+/-8.7%, (p=0.015). There was a significant correlation between the late H/M mIBG ratio and B-type natriuretic peptide (R=0.77, p=0.01) and systolic pulmonary pressure (R=0.7, p=0.05). No significant scintigraphic, functional or hemodynamic change was observed between the 2 evaluations in the 6 patients not treated with an LVAD. CONCLUSIONS: Ventricular unloading caused clinical, functional, and hemodynamic improvements accompanied by improvements in sympathetic innervation in the failing heart.

Multicenter randomized trial of facilitated percutaneous coronary intervention with low-dose tenecteplase in patients with acute myocardial infarction: the Athens PCI trial.

OBJECTIVES: To examine the safety and efficacy of low-dose tenecteplase, administered before facilitated percutaneous coronary intervention (PCI) to restore Thrombolysis In Myocardial Infarction (TIMI) grade 2 or 3 blood flow in the infarct related artery (IRA) in patients with ST elevation myocardial infarction (STEMI) scheduled to undergo PCI with a shortest anticipated delay of 30 min. BACKGROUND: PCI preceded by administration of glycoprotein IIb/IIIa inhibitors, full-dose thrombolytics, or both, is associated with no benefit or a higher incidence of adverse events than PCI alone. METHODS: Patients with STEMI < 6 hr in duration were randomly assigned to PCI preceded by tenecteplase, 10 mg (facilitated PCI group, n = 143) versus standard PCI (control group, n = 141). All patients received aspirin and unfractionated heparin (70 IU/kg bolus) at time of randomization. Both groups received IIb/IIIa inhibitors in the catheterization laboratory and for at least 20 hr after PCI. RESULTS: The median door-to-balloon time was 122 min (91-175) in the facilitated PCI versus 120 min (89-175) in the control group. IRA patency on arrival in the catheterization laboratory was 59.5% in the facilitated PCI (24% TIMI-2, 35% TIMI-3), versus 37% in the control (8% TIMI-2, 29% TIMI-3) group (P = 0.0001). During hospitalization, 9 patients (6%) died in the facilitated PCI versus 5 patients (3.5%) in the control group (P = 0.572). A single patient in the facilitated PCI group suffered a non-fatal ischemic stroke. CONCLUSIONS: Facilitated PCI with low-dose tenecteplase in patients presenting with STEMI was associated with a high IRA patency rate before PCI.

Hemodynamic effects of levosimendan in acute myocardial infarction complicated by cardiogenic shock and high systemic vascular resistance.

BACKGROUND: Levosimendan (LEVO), a new inodilator, improves hemodynamic function in patients with decompensated heart failure and preserved arterial blood pressure. Data on its use in patients with cardiogenic shock (CS) are scarce. The present study was undertaken to evaluate the hemodynamic effects of supplemental therapy with levosimendan (LEVO) in acute myocardial infarction (MI) and refractory cardiogenic shock (CS). METHODS: In 25 patients presenting in CS after acute MI, LEVO was administered for 24 h in doses ranging between 0.05 and 0.20 microg/kg/min, as tolerated, preceded by 6-microg/kg over 10 min, in addition to catecholamines. Hemodynamic measurements were made before and 24 h after initiation of the LEVO infusion. RESULTS: Hemodynamic improvement was limited to 13 patients with systemic vascular resistances (SVR) > or =18 W. LEVO increased the cardiac index from 1.5+/-0.3 l/min/m2 to 2.1+/-0.4 l/min/m2 (P = 0.002) and cardiac power from 0.462+/-0.164 W to 0.645+/-0.179 W (P = 0.022), and decreased SVR from 23+/-5 to 21+/-6.7 Wood units (P = 0.001) and pulmonary capillary wedge pressure from 24+/-9 mmHg to 16+/-11 mmHg (P = 0.059). No hemodynamic improvement was observed during LEVO administration in 12 patients with SVR < 18 W. CONCLUSION: The hemodynamic benefit conferred by LEVO added to catecholamines in patients with CS after acute MI was limited to patients with high SVR.

Intra-aortic balloon counterpulsation and delayed revascularization for myocardial infarction and shock in the absence of primary angioplasty: a treatment strategy with or without thrombolysis?

OBJECTIVE: When revascularization facilities are not available, thrombolytic therapy (TT) added to intra-aortic balloon counterpulsation (IABC) has been proposed as initial therapy for the management of patients presenting with postmyocardial infarction (MI) cardiogenic shock, followed by prompt transfer to another institution for revascularization. The use of TT in this setting, however, remains controversial. METHODS: We reviewed the records of 81 consecutive patients admitted with cardiogenic shock after acute MI and compared the outcomes of patients initially stabilized, including IABC as an adjunct to TT (IABC+TT group, n=40), with those patients initially stabilized with IABC and no TT (IABC group, n=41). RESULTS: The baseline characteristics of the two study groups were similar. The in-hospital and 6-month survival rates were 47.5 and 33.3% in the IABC+TT group versus 43.9 and 31.6% in the IABC group, respectively (NS). Except for mechanical ventilation more frequently required in the IABC group, other outcome measures were similar in both groups. The in-hospital (76.5 vs. 36.5%, P=0.008) and 6-month (60 vs. 25.4%, P=0.01) survival rates were significantly higher in patients who underwent delayed invasive revascularization, than in patients who underwent no invasive revascularization attempt. CONCLUSION: In patients presenting with acute MI and cardiogenic shock, TT as an adjunct to IABC added no therapeutic benefit when compared with IABC alone. In contrast, the survival of patients was significantly increased by delayed invasive revascularization in both treatment groups. These observations suggest that, when revascularization facilities are not available, stabilization with IABC, followed by prompt transfer for delayed revascularization to a tertiary care hospital, might be the preferred management strategy for patients presenting with post-MI cardiogenic shock.

Depressed coronary flow reserve is associated with decreased myocardial capillary density in patients with heart failure due to idiopathic dilated cardiomyopathy.

OBJECTIVES: We sought to examine the relationship between coronary flow reserve (CFR) and myocardial capillary density (MCD) in patients with idiopathic dilated cardiomyopathy, heart failure, and normal coronary arteries. BACKGROUND: Coronary flow reserve is depressed in patients with idiopathic dilated cardiomyopathy, particularly in those with end-stage congestive heart failure. METHODS: We studied 18 patients, 48 +/- 10 years of age, who had a mean New York Heart Association functional class of 2.9 +/- 1.3, mean left ventricular ejection fraction of 22 +/- 8%, and mean pulmonary capillary wedge pressure of 23 +/- 10 mm Hg. CFR measurements were made with a 0.014-inch pressure-temperature sensor-tipped guide wire placed in the distal left anterior descending coronary artery. Thermodilution curves were constructed in triplicate at baseline and during maximum hyperemia induced by intravenous adenosine. CFR was calculated from the ratio of mean transit times. Right heart endomyocardial biopsies were performed during the same procedure. Autopsied specimens from nonfailing hearts were used as controls. The tissue was histochemically stained with CD-34 for morphometric measurements of MCD. RESULTS: We observed a close linear relationship between CFR and MCD (r = 0.756, p = 0.0001). The MCD in 7 patients with a CFR >or=2.5 (73.2 +/- 16) was similar to that measured in normal control patients, (85 +/- 11, p = NS). In contrast, the MCD in 11 patients with a CFR <2.5 was 33.2 +/- 14, which was significantly lower than in patients with heart failure and normal CFR (73.2 +/- 16, p = 0.001) or in controls (85 +/- 11, p < 0.0001). CONCLUSIONS: A marked decrease in MCD was found in patients presenting with congestive heart failure as the result of idiopathic dilated cardiomyopathy and a depressed CFR.

Immediate relief of congestive heart failure by ventricular pacing in chronic bradycardia.

We report the case of a patient with chronic bradycardia and congestive heart failure whose clinical and hemodynamic status improved immediately after the implantation of a VVI pacing system. The role of chronic bradycardia in the development of congestive heart failure is discussed.

Efficacy and safety of intermittent, long-term, concomitant dobutamine and levosimendan infusions in severe heart failure refractory to dobutamine alone.

Thirty-six consecutive patients in New York Heart Association functional class IV, who were resistant to 24-hour continuous dobutamine infusion, were treated with continuous infusions of dobutamine 10 microg/kg/min for > or =48 hours (group I, n = 18), followed by weekly intermittent 8-hour infusions or more often if needed. In group II (n = 18), after the initial 24-hour infusion of dobutamine, a 24-hour levosimendan infusion was added followed by biweekly 24-hour infusions. The addition of intermittent levosimendan infusions prolonged the survival of patients with advanced heart failure refractory to intermittent dobutamine infusions (45-day survival rates were 6% and 61% in groups I and II, respectively; p = 0.0002, log-rank test).

Comparison of pulsatile with nonpulsatile mechanical support in a porcine model of profound cardiogenic shock.

The aim of this study was to examine whether pulsatility by intraaortic balloon counterpulsation (IABP) is an important adjunct to the treatment of profound cardiogenic shock (CS) with a widely used, nonpulsatile centrifugal pump (CP). In each of 18 anesthetized, open chest pigs, the outflow cannula of the CP was inserted in the aortic arch through the right external carotid artery, and the inflow cannula of the CP was placed in the left atrium. A 40 cc IABP was subsequently placed in the descending aorta through the left external carotid artery. CS was induced by occlusion of coronary arteries and the infusion of propranolol and crystalloid fluid. Mean aortic pressure, pulse pressure, aortic end diastolic pressure, left ventricular end diastolic pressure, right atrial pressure, and heart rate were monitored. Cardiac output and left anterior descending artery flow were measured with a transit time ultrasound flowmeter. During profound CS, life sustaining hemodynamics were maintained only with the support of the assist devices. Hemodynamic support with the CP was associated with a nearly nonpulsatile flow and a pulse pressure of 7 +/- 4 mm Hg, which increased to 33 +/- 10 mm Hg (p = 0.000) after combining the CP with the IABP. Compared with the hemodynamic support offered by the CP alone, addition of the IABP increased mean aortic pressure from 40 +/- 15 to 50 +/- 16 mm Hg (p = 0.000), cardiac output from 810 +/- 194 to 1,200 +/- 234 ml/min (p = 0.003), and left anterior descending artery flow from 26 +/- 10 to 39 +/- 14 ml/min (p = 0.001). In profound CS, mechanical support provided by a continuous flow CP is enhanced by the added pulsatility of the IABP.

Effects of transient myocardial ischemia on the ventricular defibrillation threshold.

BACKGROUND: Acute myocardial ischemia and the mode of ventricular fibrillation (VF) induction influence the ventricular defibrillation threshold (DFT). OBJECTIVES: The purpose of this study was to determine the effects of transient regional left ventricular (LV) ischemia on the DFT. METHODS: Ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT), and DFT were measured under nonischemic conditions (control) in 26 pigs weighing 25-35 kg. Myocardial ischemia was then induced by occlusion of the mid left anterior descending coronary artery, and measurements of ERP and VFT were repeated after 2 minutes of occlusion. The coronary artery ligation was released immediately after the onset of VF and DFT was measured. RESULTS: LV ERP was unchanged by ischemia (199 +/- 19 ms at control vs. 200 +/- 22 ms under ischemic conditions, P = 0.799), whereas VFT was significantly lower during coronary occlusion (10.7 +/- 5.4 mA vs. 37.7 +/- 13 mA, P = 0.000). Brief myocardial ischemia caused a significant increase in DFT (13.5 +/- 12.6 J after coronary occlusion vs. 6.8 +/- 6.8 J at control, P = 0.023). The duration of coronary occlusion was not correlated with the amounts of energy required to defibrillate (P = 0.526). CONCLUSIONS: This experimental study shows that transient myocardial ischemia markedly increases the DFT, suggesting that specific defibrillation algorithms should be designed for recipients of implantable defibrillators at risk of myocardial ischemia.

Time course of fibrillation and defibrillation thresholds after an intravenous bolus of amiodarone--an experimental study.

UNLABELLED: Experimental studies have described an increase in ventricular fibrillation threshold (VFT) by intravenous amiodarone. The aim of this study was to examine the early time course of changes in VFT and defibrillation thresholds (DFT) after an intravenous bolus of amiodarone in an experimental pig model of transient myocardial ischemia. METHODS AND RESULTS: VFT and relative effective ventricular refractory period (ERP) were measured in 15 anaesthetized open-chest pigs after 3 min of regional coronary ischaemia before (time 0) and 2, 15, 30, 60, and 90 min after the intravenous injection of normal saline (group A, n = 5) or amiodarone, 5 mg/kg over 15 s (group B, n = 10). DFT was measured by increasing the strength of DC shocks until defibrillation was accomplished. Amiodarone caused an increase in VFT, starting at 2 min after the infusion (11.4 +/- 8.4 mA versus 9.2 +/- 4.6 mA, P = 0.03), became significant at 15 min (13.7 +/- 6.5 mA, P = 0.009), continued to rise at 30 min (34.2 +/- 28.7 mA, P = 0.03) and reached a plateau at 60 min (50.3 +/- 37.8 mA, P = 0.008). An increase was also observed in the ERP (204 +/- 25 ms at 2 min versus 197 +/- 26 ms at baseline, P = 0.074, 211 +/- 38 ms at 15 min, P = 0.084, 212 +/- 40 ms at 30 min, P = 0.037, 220 +/- 34 ms at 60 min, P = 0.002, and 227 +/- 32 ms at 90 min, P = 0.008). No change was observed in DFT after amiodarone administration. No significant change in VFT, ERP, or DFT occurred in the control group. CONCLUSION: In this porcine model, the intravenous administration of amiodarone increased VFT and ERP over 60 min after the injection, without effect on DFT.