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Biomedical subjects

Douglas P Zipes

Publications and source records attributed to Douglas P Zipes.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of [11C]hemicholinium-15 and [18F]hemicholinium-15 as new potential PET tracers for the high-affinity choline uptake system in the heart.

[(11)C]Hemicholinium-15 ([(11)C]HC-15) and [(18)F]hemicholinium-15 ([(18)F]HC-15) have been synthesized as new potential PET tracers for the heart high-affinity choline uptake (HACU) system. [(11)C]HC-15 was prepared by N-[(11)C]methylation of the appropriate precursor, 4-methyl-2-phenyl-morpholin-2-ol, using [(11)C]CH(3)OTf in 55-70% radiochemical yield decay corrected to end of bombardment (EOB) and 2-3Ci/mumol specific activity at end of synthesis (EOS). [(18)F]HC-15 was prepared by N-[(18)F]fluoromethylation of the precursor using [(18)F]FCH(2)OTf in 20-30% radiochemical yield decay corrected to EOB and >1.0Ci/mumol specific activity at EOS. The biodistribution of both compounds was determined in rats at 20min post-intravenous injection, and the results show the heart region uptakes 1.32+/-0.75%ID/g in R-ventricle for [(11)C]HC-15 and 1.28+/-0.81%ID/g in L-ventricle for [(18)F]HC-15, respectively. The dynamic PET imaging studies of [(11)C]HC-15 in rats were acquired 60min post-intravenous injection of the tracer using the IndyPET-II scanner. For the blocking experiments, the rats were intravenously pretreated with 3.0mg/kg of unlabeled HC-15 prior to [(11)C]HC-15 injection. [(11)C]HC-15 rat heart PET studies show rapid heart uptake to give clear heart images. The rat heart PET blocking studies found no significant blocking effect. The dynamic PET studies in normal and ablated dogs were performed using Siemens PET scanner with [(13)N]NH(3), [(11)C]HC-15, and [(18)F]HC-15. PET studies in dogs of both [(11)C]HC-15 and [(18)F]HC-15 also show significant heart uptake and give images of the heart. However, there is no significant change in [(11)C]HC-15 L-ventricle uptake following radiofrequency ablation in the dog. These results suggest that the localization of HC-15 tracers in the heart is mediated by non-specific processes, and the visualization of HC-15 tracers on the heart is related to non-specific binding of HACU.

Animals↗
PubMed2006

Differences in arrhythmogenicity between the canine right ventricular outflow tract and anteroinferior right ventricle in a model of Brugada syndrome.

BACKGROUND: The Brugada syndrome is characterized by ST-segment elevation on the ECG, especially in the right precordial leads sensitive to the right ventricular outflow tract (RVOT). OBJECTIVES: The purpose of this study was to evaluate the hypothesis that right ventricular electrophysiologic heterogeneity caused arrhythmogenicity in the Brugada syndrome. METHODS: Action potentials (APs) were mapped on the epicardium of 14 RVOT preparations and on the transmural surfaces of 15 pairs of RVOT and right ventricular anteroinferior (RVAI) preparations isolated from canine hearts. Brugada ECG and arrhythmias were induced with pilsicainide (2.5-12.5 micromol/L), pinacidil (1.25-12.5 micromol/L), and terfenadine (2.0 micromol/L). RESULTS: Low doses of drugs elevated the J-ST segment and induced APs with both short and long action potential durations (APDs) in contiguous RVOT epicardial regions. In addition, APs in the RVOT had a larger phase 1 notch and longer APD than in RVAI. The longest APDs were in the epicardium in RVOT but in the endocardium in RVAI regions. High doses of drugs eliminated the phase 2 dome of the AP and abbreviated APDs in the epicardium but not in endocardium and reduced the epicardial heterogeneity of APs but increased the transmural gradient of APD in 14 (93%) of the RVOT preparations. In contrast, abbreviations of epicardial APDs occurred in only 4 (27%) of the RVAI preparations. Ventricular tachycardia occurred more frequently in the RVOT (47%) than in paired RVAI preparations (7%). Blocking the transient outward current reduced the heterogeneity of APs and eliminated arrhythmogenicity in all preparations. CONCLUSION: Compared with the RVAI region, the RVOT has greater electrophysiologic heterogeneity that contributes to arrhythmogenicity in this model of Brugada syndrome.

Action Potentials↗
PubMed2006

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death).

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Anti-Arrhythmia Agents↗
PubMed2006

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.

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Arrhythmias, Cardiac↗
PubMed2006

ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.

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American Heart Association↗
PubMed2006

Rosuvastatin: an independent analysis of risks and benefits.

BACKGROUND: Although the effectiveness of statins is well established, analyses of spontaneous adverse event reports have recently questioned the safety of rosuvastatin. METHODS AND RESULTS: We evaluated the risks and benefits of rosuvastatin and compared it with other statins presently on the market. Information was obtained from a search of medical and scientific literature that produced 3001 entries, of which 591 publications containing particularly relevant data were identified, and from the US Food and Drug Administration (FDA) Adverse Events Reporting System (AERS) and Spontaneous Reporting System through June 30, 2004. For the AERS data and to control for overreporting in the first postmarketing year and the effect on reporting due to the withdrawal of cerivastatin in 2001, we used the rate of a given adverse event among all adverse events as a measure of risk. We found that adverse effects of rosuvastatin in skeletal muscle, liver, and kidney function did not substantially differ in frequency from those reported for those of other statins in the market in 2004, except for the uncommon development of a mild form of presumably "tubular" proteinuria at doses of 40 mg/day or greater. In contrast, cerivastatin had significantly higher rates of myopathy and rhabdomyolysis than rosuvastatin's, but there was no additional effect on renal failure beyond that mediated through rhabdomyolysis. From our literature review, we found that rosuvastatin reduces abnormal lipids on a milligram-per-milligram comparison more than atorvastatin. CONCLUSION: We conclude that rosuvastatin at approved doses incurs no greater risk for adverse events than other marketed statins, except for a mild form of tubular proteinuria when doses at or above the maximum recommended levels (> or = 40 mg/day) were administered. Its risk-benefit ratio is acceptable when compared with other statins on the market in 2006.

Fluorobenzenes↗
PubMed2006

T wave alternans in an in vitro canine tissue model of Brugada syndrome.

Macroscopic T wave alternans (TWA) associated with increased occurrence of ventricular arrhythmias has been reported in patients with Brugada syndrome. However, the mechanisms in this syndrome are still unclear. We evaluated the hypothesis that TWA in Brugada syndrome was caused by the dynamic instability and heterogeneity of action potentials (APs) in the right ventricle. Using an optical mapping system, we mapped APs on the epicardium or transmural surfaces of 28 isolated and arterially perfused canine right ventricular preparations having drug-induced Brugada syndrome (in micromol/l: 2.5-15 pinacidil, 5.0 terfenadine, and 5.0-13 pilsicainide). Bradycardia at cycle length (CL) of 2,632 +/- 496 ms (n = 19) induced alternating deep and shallow T waves in the transmural electrocardiogram. Compared with the shallow T waves, deep T waves were associated with epicardial APs having longer durations and larger domes. Adjacent regions having APs with alternating domes, with constant domes, and without domes coexisted simultaneously in the epicardium and caused TWA. In contrast to the alternating epicardial APs, midmyocardial and endocardial APs did not change during TWA. Alternans could be terminated by rapid (CL: 529 +/- 168 ms, n = 7) or very slow (CL: 3,000 ms, n = 7) pacing. The heterogeneic APs during TWA augmented the dispersion of repolarization both within the epicardium and from the epicardium to the endocardium and caused phase 2 reentry. In this drug-induced model of Brugada syndrome, heterogeneic AP contours and dynamic alternans in the dome of right ventricular epicardial, but not midmyocardial or endocardial, APs caused TWA and heightened arrhythmogenicity in part by increasing the dispersion of repolarization.

Action Potentials↗
PubMed2006

A history of heart failure predicts arrhythmia treatment efficacy: data from the Antiarrythmics versus Implantable Defibrillators (AVID) study.

BACKGROUND: In survivors of life-threatening ventricular tachycardia (VT), a history of CHF (HxCHF) before the VT episode may provide different prognostic information than their measured left ventricular ejection fraction (LVEF). METHODS: We evaluated outcomes from patients in the AVID study. Patients were included in the study if they presented with ventricular fibrillation, VT with syncope or VT with hemodynamic compromise, and LVEF < or = 40%. Treatment options included implantable cardioverter defibrillator (ICD) or antiarrhythmic drugs (AAD), usually amiodarone. RESULTS: As expected, a HxCHF is associated with an increased and high risk of arrhythmic and nonarrhythmic death. However, an interaction was observed between arrhythmia treatment (ICD or AAD) and HxCHF status: the survival advantage with an ICD, as compared with AAD therapy, is largely restricted to HxCHF patients. CONCLUSIONS: The ICD is no better than AAD therapy in preventing arrhythmic death in patients with no HxCHF. In this data set, a HxCHF is somewhat more accurate in predicting prognosis and the response to therapy than a reduced LVEF.

Aged↗
PubMed2006

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death--executive summary: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.

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Anti-Arrhythmia Agents↗
PubMed2005

Facile synthesis and PET imaging of a novel potential heart acetylcholinesterase tracer N-[11C]methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2',2'-diphenylpropionoxymethyl)pyridinium.

A new AChE tracer N-[(11)C]methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2',2'-diphenylpropionoxymethyl)pyridinium ([(11)C]MDDP, [(11)C]1) has been synthesized in 40-65% radiochemical yield. Initial PET dynamic studies of [(11)C]MDDP in rat heart showed rapid heart uptake and blood pool clearance to give high-quality heart images. Blocking studies of [(11)C]MDDP with pretreatment drug neostigmine in rats found only minor reductions in rat heart [(11)C]MDDP retention. The results suggest that [(11)C]MDDP delineates the heart very clearly, and the uptakes of [(11)C]MDDP in rat heart might be related to non-specific binding.

Acetylcholinesterase↗
PubMed2005

Coronary occlusion and reperfusion promote early afterdepolarizations and ventricular tachycardia in a canine tissue model of type 3 long QT syndrome.

Although long QT syndrome (LQTS) and coronary occlusion-reperfusion (O/R) are arrhythmogenic, they affect ventricular action potential duration (APD) differently. In contrast to the prolonged APD in LQTS, ischemia abbreviates APD after a transient prolongation. Thus we hypothesized that the dynamic interactive effects of ischemia and LQTS on APD and its dispersion would affect ventricular arrhythmogenicity. We mapped transmural distribution of action potentials in 6 groups of 10 isolated wedges of canine ventricular walls: LQTS-O/R, LQTS only, and O/R only, with separate groups for pacing cycle lengths (PCL) of 1,000 and 2,000 ms. We created type 3 LQTS with anemone toxin (ATX) II followed >30 min later by arterial occlusion (40 min) and reperfusion (>100 min). Arterial occlusion initially (first 4 min) prolonged and then shortened APD. Early afterdepolarizations (EADs) occurred during the initial 4 min of occlusion in 4 of the 10 LQTS-O/R wedges at PCL of 2,000 ms but not in the other groups. Reperfusion restored APD in the O/R-only groups but caused APD to overshoot its original duration, indicating depressed repolarization reserve, in the LQTS-O/R group. Reperfusion increased the dispersion of APDs and initiated ventricular tachycardia-fibrillation in 7 of 10 and 6 of 10 LQTS-O/R wedges and in 2 of 10 and 1 of 10 O/R-only wedges at PCLs of 1,000 and 2,000 ms, respectively. The LQTS-only wedges exhibited neither EADs nor ventricular tachycardia. We conclude that coronary O/R increased the arrhythmogenicity of LQTS via cumulative prolongation of APD, increase in repolarization dispersion, and suppression of repolarization reserve.

Action Potentials↗
PubMed2005

Thoracic spinal cord stimulation reduces the risk of ischemic ventricular arrhythmias in a postinfarction heart failure canine model.

BACKGROUND: Thoracic spinal cord stimulation (SCS) is a promising therapy in treating refractory angina. This study was designed to investigate SCS with regard to the risk of arrhythmias during myocardial ischemia and its cardiac electrophysiological effects. METHODS AND RESULTS: We studied 22 dogs with healed anterior myocardial infarction (MI) and superimposed heart failure (HF) induced by rapid ventricular pacing. SCS was applied at the dorsal T1-T2 segments of the spinal cord (at 50 Hz, 0.2 ms) for 15 minutes. Transient (2-minute) myocardial ischemia was induced on 2 separate occasions (no SCS and SCS) to provoke ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation; VT/VF). Ischemic episodes were separated by 90 minutes, and dogs were randomly assigned to receive SCS or no SCS before the first or second ischemic episode. SCS reduced the occurrence of VT/VF from 59% to 23% when SCS was applied during transient myocardial ischemia (odds ratio, 0.36; 95% confidence interval, 0.1626 to 0.5646; P=0.0009). SCS also decreased sinus rate by 7.5+/-14 bpm (P=0.048), increased the PR interval by 11.1+/-14.7 ms (P=0.009), and reduced systolic blood pressure by 9.8+/-13.6 mm Hg (P=0.02). CONCLUSIONS: Thoracic SCS appears to protect against ischemic VT/VF in a canine model of healed MI and HF. SCS reduced sinus rate and systolic blood pressure, changes consistent with the previously known antisympathetic effect of SCS, which may have contributed to the antiarrhythmic benefits.

Animals↗