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Biomedical subjects

D P Zipes

Publications and source records attributed to D P Zipes.

At least 19 recordsLinked to original sources
PubMed1992

Canine left ventricular hypertrophy predisposes to ventricular tachycardia induction by phase 2 early afterdepolarizations after administration of BAY K 8644.

OBJECTIVES: The purpose of this study was to test the hypothesis that the longer duration of ventricular action potentials in hypertrophied hearts predisposes to the development of early after-depolarizations and triggered ventricular tachyarrhythmias. BACKGROUND: For unknown reasons, the incidence of sudden death is greater in patients with myocardial hypertrophy. METHODS: We measured left ventricular monophasic action potentials in normal dogs and dogs with left ventricular hypertrophy before and after administration of the calcium agonist BAY K 8644 and the potassium channel blocker cesium. RESULTS: We demonstrated longer action potential durations in dogs with than in those without left ventricular hypertrophy. Also, BAY K 8644 produced phase 2 early afterdepolarizations and ventricular tachyarrhythmias more frequently in the dogs with than in those without left ventricular hypertrophy. Phenylephrine, an alpha agonist, further increased the action potential duration in hypertrophied hearts and the propensity to develop early afterdepolarizations and ventricular tachyarrhythmia after administration of BAY K 8644. Control and hypertrophied hearts developed early afterdepolarizations and ventricular tachyarrhythmia equally when exposed to cesium. CONCLUSIONS: Although in vitro studies have shown that fibers of hypertrophied ventricular myocardium can develop triggered activity as a result of both early and late afterdepolarizations, the present study is the first to show in vivo that the hypertrophied ventricular myocardium compared with the normal ventricle is predisposed to develop phase 2 early afterdepolarizations that appear to trigger ventricular tachyarrhythmia. It is possible that such a mechanism contributes to the development of ventricular tachyarrhythmia and sudden cardiac death in patients with left ventricular hypertrophy. If this is shown to be true, specific pharmacologic interventions can be suggested.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease.

BACKGROUND: Radiofrequency energy has been used safely and successfully to eliminate accessory pathways in patients with the Wolff-Parkinson-White syndrome and the substrate for atrioventricular nodal reentrant tachycardia. However, this form of ablation has had only limited success in eliminating ventricular tachycardia in patients with structural heart disease. In contrast, direct-current catheter ablation has been used successfully to eliminate ventricular tachycardia in patients with and without structural heart disease. The purpose of this study was to test whether radiofrequency energy can safely and effectively ablate ventricular tachycardia in patients without structural heart disease. METHODS AND RESULTS: Sixteen patients (nine women and seven men; mean age, 38 years; range, 18-55 years) without structural heart disease who had ventricular tachycardia underwent radiofrequency catheter ablation to eliminate the ventricular tachycardia. Two patients presented with syncope, nine with presyncope, and five with palpitations only. Mean duration of symptoms was 6.7 years (range, 0.5-20 years). Radiofrequency catheter ablation successfully eliminated ventricular tachycardia in 15 of 16 patients (94%). Sites of ventricular tachycardia origin included the high right ventricular outflow tract (12 patients), the right ventricular septum near the tricuspid valve (three patients), and the left ventricular septum (one patient). The only ablation failure was in a patient whose ventricular tachycardia arose from a region near the His bundle. An accurate pace map, early local endocardial activation, and firm catheter contact with endocardium were associated with successful ablation. Radiofrequency ablation did not cause arrhythmias, produced minimal cardiac enzyme rise, and resulted in no detectable change in cardiac function by Doppler echocardiography. CONCLUSIONS: Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease is effective and safe and may be considered as early therapy in these patients.

Adolescent↗
PubMed1992

Sympathetic stimulation and norepinephrine infusion modulate extracellular potassium concentration during acute myocardial ischemia.

The purpose of this study was to investigate whether sympathetic stimulation modulated the rise in extracellular K+ concentration ([K+]o) evoked by acute myocardial ischemia. In 35 alpha-chloralose-anesthetized dogs, we measured changes in [K+]o during acute myocardial ischemia in the presence and absence of sympathetic stimulation or norepinephrine infusion. A series of four 5-minute occlusions of the distal left anterior descending coronary artery (LAD) was completed in 18 dogs. Thirty minutes of reperfusion separated each LAD occlusion. Four to five K(+)-sensitive electrodes were inserted into the left ventricular midmyocardium that was perfused by the distal LAD. Lead II of the electrocardiogram, arterial pressure, and [K+]o were recorded, and the right atrium was paced at a constant cycle length. The first, second, and fourth LAD occlusions were done in the absence of sympathetic stimulation or norepinephrine infusion. The changes in [K+]o evoked by the first LAD occlusion differed (p < 0.05) from those elicited by the second and fourth occlusions. However, the changes in [K+]o during the second and fourth LAD occlusions were similar (p > 0.2) and served as controls for the responses obtained during the third occlusion. Two minutes before the third LAD occlusion, sympathetic stimulation (4 Hz) or norepinephrine infusion (0.25-0.5 micrograms/kg per minute i.v.) was begun and was continued until 2 minutes after reperfusion. We found that sympathetic stimulation and norepinephrine infusion increased (p < 0.05) myocardial blood flow in both normal and ischemic tissue. The mean response recorded by 23 K(+)-sensitive electrodes in 11 dogs showed that sympathetic stimulation increased (p < 0.001) the [K+]o at 1, 2, 3, 4, and 5 minutes after the onset of LAD occlusion compared with the second and fourth occlusions. In contrast, the mean response recorded by 20 K(+)-sensitive electrodes in seven dogs showed that norepinephrine infusion reduced (p < 0.02) the [K+]o at 4 and 5 minutes after the onset of LAD occlusion. These data show that sympathetic stimulation increased the [K+]o evoked by acute myocardial ischemia, an effect that was not mimicked by the intravenous administration of norepinephrine.

Animals↗
PubMed1992

Ischemic modulation of myocardial innervation.

This article focuses on the interplay existing between the autonomic nervous system and the myocardium, with novel observations related to arrhythmogenesis. Myocardial ischemia and infarction produce an efferent denervation involving both limbs of the autonomic nervous system. As a consequence of the sympathetic denervation, the myocardial norepinephrine content is reduced to a major extent. As a logical consequence, this is followed by the phenomenon called "denervation supersensitivity", i.e. the tissue deprived of its nerve supply responds to the neural mediator in an exaggerated fashion. This is manifested by an exaggerated shortening of the effective refractory period during infusion of norepinephrine and by increased propensity for arrhythmias. With time, denervation is followed by reinnervation. An interesting counterpart of these findings is the possibility to document in patients after myocardial infarction if denervation has occurred using the MIBG technique. Not only efferent but also afferent denervation does occur and this might be involved in painless ischemia. In another series of studies we have provided the evidence that the pericardium is not a mere inert sac but it actively acts as a functional membrane. Pericardial prostaglandins released into the pericardial fluid alter electrophysiologic properties by modulating mostly the sympathetic effects; this may serve as a physiologic negative feedback control mechanism regulating sympathetic effects on the heart contributing to prevention of ischemic arrhythmias.

3-Iodobenzylguanidine↗
PubMed1992

Catheter ablation of ventricular tachycardia using radiofrequency techniques in patients without structural heart disease.

It has been previously demonstrated that radiofrequency (RF) energy can be safely applied to successfully eliminate accessory pathways in patients with the Wolff-Parkinson-White syndrome. This technique may also be used to successfully eliminate atrioventricular (AV) nodal reentrant tachycardia by elimination of either the fast or slow AV nodal pathways. However, RF energy has achieved only limited success in eliminating ventricular tachycardia (VT) in patients with structural heart disease, such as coronary artery disease and dilated cardiomyopathy. Direct-current catheter techniques have successfully eliminated VT in patients with and without structural heart disease, but this technique is limited by the risk of barotrauma and proarrhythmia. We used RF catheter ablation techniques to eliminate VT in patients without structural heart disease. Our results from the basis of this report. 16 patients (nine women and seven men; mean age 38; range 18 to 55 years) who did not have any identifiable structural heart disease by echocardiography where included in this study. These patients underwent RF catheter ablation to eliminate VT. Two patients had presented with syncope, nine with presyncope and five with palpitations only. The mean duration of symptoms was 6.7 years (range 0.5 to 20 years). VT was successfully eliminated by RF catheter techniques in 15 of the 16 patients (a 94% success rate). Importantly, successful ablation sites included regions other than the right ventricular outflow tract. Areas of VT origin therefore included the high right ventricular outflow tract (twelve patients), right ventricular septum near the tricuspid valve (three patients), and the left ventricular septum (one patient). The only ablation failure was in a patient whose VT arose from a region near the His bundle. Successful ablation occurred in patients in whom an accurate pace map could be obtained and early local endocardial activation was obtainable. Further, firm catheter contact with endocardium was required for successful elimination of VT. RF ablation did not cause any identifiable arrhythmia and produced a minimal cardiac enzyme rise. It also resulted in no detectable change in cardiac function by Doppler echocardiography. Based on these findings, we conclude that RF catheter ablation of VT in patients without structural heart disease was highly effective and safe. It may therefore be considered as early therapy in these patients.

Adult↗
PubMed1992

Sudden cardiac death. Future approaches.

The purpose of the present review is to suggest future approaches to the problem of sudden cardiac death. Short-term efforts should be directed toward delivering cardiopulmonary resuscitation and electrical therapy as soon as possible after the onset of an arrest. Long-term efforts encompass four interrelated, stepwise objectives that include identification of individuals at risk, mechanisms responsible for the arrhythmias, and interventions to prevent the arrhythmias. This is then followed by large-scale testing of the interventions in high-risk populations. Present funding for such research is inadequate, and the National Heart, Lung, and Blood Institute should be encouraged to consider supporting a major research initiative to combat the problem of sudden cardiac death.

Arrhythmias, Cardiac↗
PubMed1991

Antitachycardia devices: realities and promises.

Nonpharmacologic therapy for ventricular arrhythmias has gained growing attention with the development of the implantable cardioverter-defibrillator. In addition, the reports of adverse effects of drug therapy from several studies, including the Cardiac Arrhythmia Suppression Trial (CAST), have supported the need for these devices. The development of new implantable cardioverter-defibrillators that have the capability of antitachycardia pacing, bradycardia pacing, cardioversion and defibrillation has enhanced their clinical utility. The currently available implantable cardioverter-defibrillators have been shown to significantly improve survival after sudden cardiac arrest in patients with life-threatening ventricular arrhythmias. Newer devices with expanded capabilities may reduce mortality even further. In this report the features of currently available antitachycardia devices and implantable cardioverter-defibrillators are reviewed and the features and current implant data on newer antitachycardia devices are discussed.

Arrhythmias, Cardiac↗
PubMed1991

Electrophysiologic and anatomic characteristics of ventricular tachycardia induced at the right ventricular outflow tract but not at the apex.

The site of ventricular stimulation is an important variable in the initiation of ventricular tachycardia (VT) by programmed ventricular stimulation. Among 169 patients studied consecutively, 17 (10%) had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex. Fourteen of these 17 patients had had prior myocardial infarction (12 had inferior, and two had both inferior and anterior myocardial infarction), two had a dilated cardiomyopathy, and one had a localized cardiomyopathy. Fourteen patients had echocardiograms suitable for analysis. Of these, 12 had posterior/inferior ventricular wall motion abnormalities located at the base of the heart. The ventricular effective refractory periods from the right ventricular outflow tract and right ventricular apex were 237 +/- 4 and 244 +/- 5 msec, respectively (p less than 0.05, mean +/- SEM). Induced VT had a cycle length of 229 +/- 4 msec and had the morphology of right bundle branch block in 12 patients, of left bundle branch block in three patients, and had both morphologies in two patients. In 14 patients the axis was superior. VT was initiated with two extrastimuli in 15 patients and with burst right ventricular pacing in two patients. Similar pacing techniques with identical pacing intervals did not induce VT at the right ventricular apex in 14 of these 17 patients. Further, among the 15 patients whose VT was induced at the right ventricular outflow tract with two extrastimuli, neither burst pacing (n = 13) nor two extrastimuli introduced at faster paced rates (n = 12) induced VT at the right ventricular apex.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed1991

Modulation of drug effects by regional sympathetic denervation and supersensitivity.

BACKGROUND: Regional sympathetic denervation, such as that produced by a myocardial infarction, causes electrophysiological heterogeneity in the ventricles. The purpose of this study was to test the hypothesis that such denervation could cause drugs to exert heterogeneous myocardial effects. METHODS AND RESULTS: Sympathetic stimulation increases the amplitude of cesium chloride-induced early afterdepolarizations (EADs). The amplitude of these induced EADs was used to determine whether drug responses were different in innervated versus denervated areas of the heart. A canine model of sympathetic denervation was created at the cardiac apex by either transmural myocardial infarction (n = 19) or phenol application (n = 11). Cesium chloride (84 mg/kg) was infused while monophasic action potential recordings were simultaneously obtained from the base and apex of the left ventricle using an epicardial contact electrode. We found that control (innervated) dogs (n = 17) showed no difference in the EAD amplitude recorded from the apex compared with the base. In dogs with apical sympathetic denervation, the EAD amplitude was greater at the innervated base during ansae subclaviae stimulation than at the denervated apex (25.8 +/- 6.6% at base versus 18.8 +/- 6.7% at apex, p less than 0.001). However, during norepinephrine infusion, the EADs recorded from the denervated apex were greater than those recorded from the innervated base (23.3 +/- 7.6% at apex versus 20.6 +/- 6.0% at base, p less than 0.02) due to denervation supersensitivity. CONCLUSIONS: These data show that regional myocardial denervation creates autonomic and electrophysiological heterogeneity and the substrate for heterogeneous drug actions. This drug-induced electrophysiological heterogeneity may be another mechanism for proarrhythmia.

Action Potentials↗
PubMed1990

Prostaglandin modulation of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium chloride combined with efferent cardiac sympathetic stimulation in dogs.

Prostaglandins inhibit efferent cardiac sympathetic nerve effects by acting at presynaptic sites and may act to suppress some arrhythmias. In the present study, the effects of intravenous administration of prostacyclin (PGI2) and prostaglandin E2 (PGE2) on early afterdepolarizations and ventricular tachycardia induced by cesium chloride (0.5 mmol/liter per kg body weight intravenously) combined with stimulation of bilateral ansae subclaviae in anesthetized dogs were examined. The right atrium was paced at a constant cycle length of 600 ms. A left ventricular endocardial monophasic action potential catheter was used to detect early afterdepolarizations. Prostacyclin (0.2 microgram/kg per min) reduced the amplitude of the early afterdepolarizations (39.2 +/- 8.4% of the monophasic action potential amplitude during control study to 28.7 +/- 5.5%, n = 10; p less than 0.001) as well as the prevalence of ventricular tachycardia (11 of 14 dogs during control study to 5 of 14 dogs; p = 0.031). Prostaglandin E2 (0.2 to 0.6 microgram/kg per min) did not significantly reduce the early afterdepolarization amplitude (34.7 +/- 8.9% to 25.1 +/- 10.7%, n = 8; p = 0.085) or the prevalence of ventricular tachycardia (8 of 10 versus 6 of 10 dogs; p = 0.50). Alpha- and beta-adrenoceptor blockade with combined intravenous administration of propranolol (0.5 mg/kg) and phentolamine (0.3 mg/kg) decreased the amplitude of the early afterdepolarizations induced by cesium chloride and bilateral ansae subclaviae stimulation from 38.6 +/- 11.2% to 18.8 +/- 3.3% (n = 6; p = 0.005). Additional administration of PGI2 further reduced the early afterdepolarization amplitude from 18.8 +/- 3.3% to 9.8 +/- 4.8% (n = 6; p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Alpha-adrenoceptor stimulation and blockade modulates cesium-induced early afterdepolarizations and ventricular tachyarrhythmias in dogs.

In 84 open-chest dogs, we studied the effects on early afterdepolarizations (EADs) and ventricular tachyarrhythmias (VTs) induced by cesium chloride (168 mg/kg i.v.) of alpha-adrenoceptor stimulation with phenylephrine (100 micrograms plus 0.25 microgram/kg/min i.v.) and with left ansa subclavia stimulation (LAS; 2 Hz, 4 msec, 2 mA) after propranolol (0.5 mg/kg) administration. We also studied the effects of alpha-adrenoceptor blockade with phentolamine (3 mg/kg), prazosin (25-500 micrograms/kg), yohimbine (10-500 micrograms/kg), WB 4101 (2 mg/kg), and benoxathian (2 mg/kg) during decentralized LAS. EAD amplitude, presented as a percentage of monophasic action potential amplitude, was recorded simultaneously with contact electrodes from the right and left ventricular endocardium. Phenylephrine and LAS plus propranolol increased EAD amplitude (31.5 +/- 8.8% to 47.8 +/- 9.7% and 34.8 +/- 4.1% to 46.1 +/- 6.4%, respectively) and the prevalence of VT (from three to nine of 11 dogs and from the three to five of six dogs, respectively). Prazosin produced a dose-response decrease in EAD amplitude and reduced the prevalence of VT. Yohimbine did not alter the amplitude of EADs or the prevalence of VT. WB 4101 and phentolamine reduced the amplitude of EADs produced by cesium and LAS (from 44.3 +/- 10.2% to 32.6 +/- 9.4% and from 39.8 +/- 6.9% to 30.3 +/- 6.3%, respectively) and the prevalence of VT (from eight to one of 10 dogs and from 13 to 5 of 20 dogs, respectively). Benoxathian did not alter significantly the amplitude of EADs (41.6 +/- 11.4% to 37.5 +/- 9.4%) or the prevalence of VT (from six to five of 10 dogs).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1990

Clinical features of amiodarone-induced pulmonary toxicity.

The incidence and clinical predictors of amiodarone pulmonary toxicity were examined in 573 patients treated with amiodarone for recurrent ventricular (456 patients) or supraventricular (117 patients) tachyarrhythmias. Amiodarone pulmonary toxicity was diagnosed in 33 of the 573 patients (5.8%), based on symptoms and new chest radiographic abnormalities (32 of 33 patients) and supported by abnormal pulmonary biopsy (13 of 14 patients), low pulmonary diffusion capacity (DLCO) (nine of 13 patients), and/or abnormal gallium lung scan (11 of 16 patients). Toxicity occurred between 6 days and 60 months of treatment for a cumulative risk of 9.1%, with the highest incidence occurring during the first 12 months (18 of 33 patients). Older patients developed it more frequently (62.7 +/- 1.7 versus 57.4 +/- 0.5 years, p = 0.018), with no cases diagnosed in patients who started therapy at less than 40 years of age. Gender, underlying heart disease, arrhythmia, and pretreatment chest radiographic, spirometric, or lung volume abnormalities did not predict development of amiodarone pulmonary toxicity, whereas pretreatment DLCO was lower in the group developing it (76.0 +/- 5.5% versus 90.4 +/- 1.4%, p = 0.01). There was a higher mean daily amiodarone maintenance dose in the pulmonary toxicity group (517 +/- 25 versus 409 +/- 6 mg, p less than 0.001) but no difference in loading dose. No patient receiving a mean daily maintenance dose less than 305 mg developed pulmonary toxicity. Patients who developed toxicity had higher plasma desethylamiodarone (2.34 +/- 0.18 versus 1.92 +/- 0.04 micrograms/ml, p = 0.009) but not amiodarone concentrations during maintenance therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1990

Effect of atrioventricular interval during pacing or reciprocating tachycardia on atrial size, pressure, and refractory period. Contraction-excitation feedback in human atrium.

To determine whether a contraction-excitation feedback mechanism exists in human atrium, we investigated the effects of varying the atrioventricular (AV) interval from 0 to 360 msec during AV pacing at a cycle length of 400 msec on atrial pressure, size, and refractoriness in 10 patients (group 1, without supraventricular tachycardia). The same parameters were determined in another 10 patients (group 2, with different spontaneous AV relations) during AV reciprocating tachycardia or AV nodal reciprocating tachycardia and during high right atrial (RA) pacing at the tachycardia cycle length. In group 1 patients, peak and mean RA pressure, RA effective refractory period (RA-ERP), and left atrial (LA) size all decreased to minimal values at an AV interval of 120 msec and remained low as the AV interval was increased and approached 400 msec. The increase in each of the variables from its lowest to greatest value was as follows: Mean systemic blood pressure, 20.9 +/- 3.1 mm Hg; LA size, 0.55 +/- 0.05 cm; RA peak pressure, 10.4 +/- 1.8 mm Hg; RA mean pressure, 3.5 +/- 0.6 mm Hg; and RA-ERP, 22.5 +/- 3.0 msec, p less than 0.001 for each. The weighted mean correlation coefficient with RA-ERP was significant for RA peak pressure and LA size (p less than 0.001 for each). These same relations were investigated in five patients with the Wolff-Parkinson-White syndrome and AV reciprocating tachycardia and five patients with AV nodal reciprocating tachycardia (group 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Pericardial prostaglandin biosynthesis prevents the increased incidence of reperfusion-induced ventricular fibrillation produced by efferent sympathetic stimulation in dogs.

This study tested the hypothesis that sympathetic neural stimulation increases the prevalence of reperfusion-induced ventricular fibrillation and explored the mechanisms by which this occurs and how it may be prevented. In anesthetized, autonomically denervated dogs, we examined the effects of bilateral ansae subclaviae stimulation (SS) and of induction of pericardial biosynthesis of prostaglandins, an intervention that reduces SS effects by acting at presynaptic sites. A 5-minute occlusion of the left anterior descending coronary artery distal to the first or second diagonal branch was performed during SS. Heart rate was maintained constant by atrial pacing. In the absence of SS, one of 23 dogs developed ventricular fibrillation during occlusion, and three of the remaining 22 dogs developed ventricular fibrillation upon reperfusion. SS did not increase the prevalence of occlusion-induced ventricular fibrillation (four of 23 dogs) but increased the prevalence of reperfusion-induced ventricular fibrillation (12 of the remaining 19 dogs, p = 0.01). SS did not affect occlusion-induced decrease in local electrogram amplitude recorded from the ischemic myocardium or myocardial blood flow to the ischemic myocardium during occlusion or reperfusion. SS, however, prevented occlusion-induced increase in diastolic excitability threshold. Instillation into the pericardial cavity of arachidonic acid solution (3 micrograms/ml) resulted in release of prostacyclin, measured by radioimmunoassay as a stable metabolite 6-ketoprostaglandin F1 alpha (63.1 +/- 11.3 ng/ml, n = 11, mean +/- SEM), and of prostaglandin E2 (7.0 +/- 0.9 ng/ml, n = 11). This pericardial solution blunted SS-induced increase in mean arterial blood pressure and reduced the prevalence of ventricular fibrillation during reperfusion (six dogs to one dog, p less than 0.05). Blood flow to the ischemic myocardium remained unaffected. Indomethacin, when added to the solution (3 micrograms/ml), reversed the effects of prostaglandin release and arrhythmia development. These data indicate that efferent sympathetic stimulation during a coronary occlusion and reperfusion sequence increases the prevalence of reperfusion-induced ventricular fibrillation that is reduced by pericardial biosynthesis of prostaglandins. Pericardial prostaglandin synthesis may serve as a unique antiarrhythmic function by regulating efferent cardiac sympathetic nerve effects.

Animals↗