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Biomedical subjects

M D Carlson

Publications and source records attributed to M D Carlson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST).

BACKGROUND: The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular ectopy with antiarrhythmic drugs after a myocardial infarction reduces the incidence of sudden arrhythmic death. Patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The encainide and flecainide arms of the study were discontinued in 1989 (CAST-I) and the moricizine arm in 1991 (CAST-II) because of excess mortality. To explore the mechanisms of these adverse outcomes, we examined the interaction of baseline characteristics with the hazard of therapy with encainide, flecainide, or moricizine compared with their respective placebos. METHODS AND RESULTS: CAST-I comprised 755 patients assigned to flecainide or encainide and 743 patients assigned to placebo, whereas in CAST-II, 502 patients received moricizine and 491 patients received placebo. Clinical and laboratory baseline variables of patients receiving active drug and those receiving placebo were similar. In CAST-I patients, there was a significant interaction of active therapy with both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest for non-Q-wave myocardial infarction (total mortality hazard ratios, 1.8 versus 7.9 for Q-wave versus non-Q-wave infarction, P = .03). Ventricular premature depolarization (VPD) frequency > or = 50/h and heart rate > or = 74 beats per minute each interacted significantly with total mortality/cardiac arrest only. In the sicker CAST-II patients (ejection fraction < or = 40%), only diuretic use at baseline interacted significantly with moricizine use for both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest (total mortality hazard ratios, 1.9 versus 0.7 for diuretic use versus no use, P = .01). CONCLUSIONS: Although active treatment in CAST-I was associated with greater mortality than placebo with respect to almost all baseline variables, the therapeutic hazard was more than expected in patients with non-Q-wave myocardial infarction and (for total mortality) frequent premature VPDs and higher heart rates, suggesting that the adverse effect of encainide or flecainide therapy is greater when ischemic and electrical instability are present. The relative hazard of therapy with moricizine in the sicker CAST-II population was greater in those using diuretics. Thus, although these drugs have the common ability to suppress ventricular ectopy after myocardial infarction, their detrimental effects on survival may be mediated by different mechanisms in different populations, emphasizing the complex, poorly understood hazards associated with antiarrhythmic drug treatment.

Arrhythmias, Cardiac↗
PubMed1993

Naloxone does not prevent vasovagal syncope during simulated orthostasis in humans.

The mechanism of vasovagal syncope during orthostasis in humans is unknown. Opioid receptors have been implicated in the vasovagal-like responses to hemorrhagic hypotension in conscious animals. We sought to determine if opioid receptor blockade with naloxone (mu receptor antagonist) would prevent or delay the onset of vasovagal syncope in humans. Three protocols were performed in which heart rate, arterial pressure, sympathetic nerve activity, thoracic impedance and forearm vascular resistance were measured during stepwise steady-state increments of lower body negative pressure (LBNP) in nine healthy volunteers. In protocol 1, duplicate trials of LBNP to syncope or -60 mmHg were performed with a 30-45 minute rest period separating the trials. No significant differences in any physiologic responses or cumulative stress tolerance were found. In protocol 2, graded LBNP was repeated after administration of saline or naloxone (0.1 mg/kg) in six subjects in which vasovagal syncope occurred prior to -60 mmHg LBNP. The peak increase of sympathetic nerve activity during LBNP was augmented after naloxone (P = 0.02), but the occurrence of vasovagal syncope was not prevented nor was the cumulative stress tolerated affected (P = 0.42). The heart rate and arterial pressure responses to LBNP were not affected by naloxone. Similarly, in protocol 3, naloxone given just prior to the onset of pre-syncopal symptoms did not alter the physiologic response or the occurrence of vasovagal syncope. These data show that naloxone does not prevent or delay the onset of vasovagal syncope in humans which suggests that mu opioid receptors do not mediate the vasovagal response.

Adult↗
PubMed1993

Multiple monomorphic ventricular tachycardia configurations predict failure of antiarrhythmic drug therapy guided by electrophysiologic study.

OBJECTIVES: The purpose of this study was to determine whether the induction at electrophysiologic study of sustained monomorphic ventricular tachycardias with multiple QRS complex configurations predicted failure of subsequent serial electrophysiologic study guided antiarrhythmic drug testing. BACKGROUND: Ventricular tachycardias with multiple QRS complex configurations are associated with failure of surgical therapy for ventricular tachycardia. As such, the presence of multiple monomorphic QRS complex ventricular tachycardias during electrophysiologic testing may predict failure of subsequent medical therapy. METHODS: Fifty-one consecutive patients with coronary artery disease had reproducible induction of monomorphic ventricular tachycardia during a baseline electrophysiologic study. Each patient then underwent a mean of 1.5 antiarrhythmic drug trials. An antiarrhythmic drug regimen that suppressed induction of ventricular tachycardia was identified in 13 (26%) of the 51 patients. RESULTS: Patients with only one inducible monomorphic QRS complex ventricular tachycardia at baseline study were more likely to have an antiarrhythmic drug regimen identified that suppressed inducible ventricular tachycardia than were patients with multiple monomorphic QRS complex ventricular tachycardias (12[36%] of 33 patients vs. 1 [6%] of 18, p = 0.04). In seven patients with only one induced configuration of ventricular tachycardia, a second monomorphic ventricular tachycardia with a different QRS complex configuration occurred during attempts at pacing termination of the induced ventricular tachycardia. None of these seven patients then had successful drug suppression of inducible ventricular tachycardia. Thus, 12 (46%) of 26 patients with a single monomorphic QRS complex ventricular tachycardia observed at baseline study had successful serial drug testing compared with 1 (4%) of 25 patients with multiple QRS complex ventricular tachycardia configurations (p = 0.002). CONCLUSIONS: The induction or observation of multiple monomorphic QRS complex ventricular tachycardias at baseline electrophysiologic study predicted failure of subsequent serial electrophysiologic study--guided antiarrhythmic drug therapy.

Adult↗
PubMed1992

Ventricular arrhythmias in perspective: a current view.

While clinical management of patients with ventricular arrhythmias continues to evolve, some basic principles are generally accepted. First, patients with sustained ventricular tachyarrhythmias (ventricular tachycardia or ventricular fibrillation) require treatment. Second, patients with frequent ventricular ectopy or nonsustained ventricular tachycardia in the absence of underlying structural heart disease do not require treatment except when relief of symptoms is warranted. However, the indication for treatment of patients with frequent ventricular ectopy or nonsustained ventricular tachycardia in the presence of underlying structural heart disease remains uncertain. The concern is that these ventricular arrhythmias may be a precursor for sustained, potentially life-threatening ventricular tachyarrhythmias. Available data suggest that patients with underlying structural heart disease, particularly coronary artery disease and a previous myocardial infarction, who manifest frequent ventricular ectopy or more particularly nonsustained ventricular tachycardia, are at increased risk for sudden cardiac death. However, no studies have demonstrated to date that treatment of these arrhythmias will favorably affect outcome. Data are accumulating to suggest that use of the principles of risk stratification permits identification of patients at very high risk for developing sustained ventricular tachyarrhythmias. Carefully designed clinical trials are required before firm guidelines for the management of these patients can be defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1992

Selective surgical approach for atrioventricular reentrant tachycardia.

From September 1986 through September 1990, 60 operations were performed in 55 patients (32 male and 23 female; age, 1 to 76 years) for ablation of accessory pathways of atrioventricular reentrant tachycardia; 6 patients had additional cardiac procedures. Between September 1986 and August 1988 the initial surgical approach was exclusively epicardial with adjuvant cryoablation (EPI) in 23 patients (group 1) for a left free wall (LFW) pathway in 11, right free wall (RFW) in 3, posteroseptal (PS) in 7, and anteroseptal in 2. During September 1988 through September 1990, 32 patients (group 2) had the initial surgical approach tailored to the location of the mapped accessory pathway: endocardial approach (ENDO) for LFW in 17 and for juxtanodal pathway in 2, EPI for RFW in 3 and for PS in 9, and combined ENDO and EPI for AS in 1. There was no early or late death in either group. In group 1, 2 patients with LFW pathway had development of recurrent preexcitation in the same compartment requiring ENDO reoperation 10 and 11 months later, 1 with anteroseptal pathway needed immediate ENDO and EPI reoperation, and another with LFW, who required pericardial patch repair of a left atrial tear, had a thromboembolic stroke 2 days later. No serious complications occurred in group 2, but 2 patients with PS required reoperation before discharge for a second accessory pathway in another compartment (1 RFW and 1 LFW). Additionally, 4 patients (2 in each group) had from the beginning ablation of two pathways in different compartments. On complete late follow-up (mean, 28 months) all patients are back to preoperative levels of activity and are free of preexcitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Strategies in the surgical treatment of malignant ventricular arrhythmias. An 8-year experience.

Introduction of the automatic implantable cardioverter defibrillator (AICD) has dramatically affected the surgical treatment of malignant ventricular tachyarrhythmias. The authors continue to perform electrophysiologically directed subendocardial resection (SER) of left ventricular (LV) scars in selected patients, and we revascularize (CABG) those patients undergoing AICD implantation who have significant myocardial ischemia. In an attempt to define the optimal role of each procedure, this report analyzes our 8-year experience with 348 consecutive patients treated surgically for these arrhythmias (SER since 1983 and AICD since 1986). All patients undergoing SER had organized ventricular tachycardia (VT) as a result of myocardial infarction, and most had LV aneurysms; of those undergoing AICD or AICD/CABG, 60% had VT, 15% had ventricular fibrillation, and 25% had both or were noninducible. The thirty-day mortality rate was 1.5% (3/197) for AICD, 5.4% (5/93) for AICD/CABG, and 8.6% (5/58) for SER; these mortality figures are not significant different. Late deaths in all groups were predominantly due to congestive heart failure, and actuarial survival as well as freedom from sudden death was similar between the groups at 4 years. Recurrent VT occurred in 167 of 282 (59%) of long-term survivors of AICD or AICD/CABG during follow-up and in nine of 53 (17%) of those with SER. Forty-eight per cent of survivors of AICD or AICD/CABG required antiarrhythmic medications, whereas only 11% of those with SER required antiarrhythmics. Long-term survival in each group is much higher than that reported for comparable patients with severe LV dysfunction treated medically. In those patients with organized VT and LV aneurysm who are judged able to survive the procedure, SER offers a high likelihood of cure rather than simple prevention of sudden death.

Actuarial Analysis↗
PubMed1992

Ventricular tachycardia rate and morphology determine energy and current requirements for transthoracic cardioversion.

BACKGROUND: The electrical current and energy required to terminate ventricular tachyarrhythmias are known to vary by arrhythmia: Ventricular tachycardia (VT) is generally considered to require less energy than ventricular fibrillation (VF). The hypothesis of our study was that current requirements for transthoracic termination of VT are further determined by VT rate and QRS complex morphology. METHODS AND RESULTS: We prospectively studied 203 patients who received a total of 569 shocks for VT or VF by following a current-based protocol. This protocol recommended shocks for VT beginning at 18 A (70 +/- 22 J) and shocks for VF beginning at 25 or 30 A (137 +/- 52 J or 221 +/- 70 J). The ventricular tachyarrhythmias were subclassified as monomorphic VT (MVT): uniform QRS complex morphology on surface electrocardiogram and heart rate greater than 100 beats per minute; polymorphic VT (PVT): nonuniform QRS complex morphology and heart rate less than or equal to 300 beats per minute; or VF: nonuniform QRS complex morphology and heart rate greater than 300 beats per minute. We found that shocks of 18 A and 25 A for terminating MVT had success rates of 69% and 82%, respectively, whereas such low-current shocks were less successful for PVT (33% at 18 A) and for VF (19% at 18 A, 53% at 25 A). High-current shocks of 35 A and 40 A were equally successful for the three ventricular tachyarrhythmias. Subdividing MVT revealed that slower MVT (heart rate less than 200 beats per minute) had a significantly better success rate with low-current shocks of 18 A and 25 A than did faster MVT (greater than 200 beats per minute) (89% versus 72% success, p less than 0.01). Bundle branch block morphology, QRS axis, and duration of ventricular tachyarrhythmia did not alter current requirements. CONCLUSIONS: Heart rate and electrocardiographic degree of organization of ventricular tachycardia are important determinants of transthoracic energy and current requirements for cardioversion and defibrillation. Transthoracic termination of MVT requires relatively low current or energy, but PVT behaves more like VF and requires higher electrical current or energy.

Electric Countershock↗
PubMed1992

Selective stimulation of parasympathetic nerve fibers to the human sinoatrial node.

BACKGROUND: In animals, parasympathetic nerve fibers that innervate the sinoatrial node can be selectively stimulated to increase atrial cycle length. These nerve fibers course through an epicardial fat pad at the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium. We hypothesized that similar nerves exist and can be selectively stimulated in humans. METHODS AND RESULTS: Microscopic examination of fat pads excised from the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium during two human autopsies revealed the presence of nerve fibers and ganglia. We electrically stimulated this epicardial fat pad in 16 patients during cardiac surgery. The fat pads were stimulated with continuous-pulse trains for 15 seconds via a hand-held bipolar electrode using constant current (10-15 mA), constant pulse width (0.02-0.05 msec), and at 6.6, 10, 20, 25, and 30 Hz. The mean atrial cycle length +/- 1 SEM increased from 734 +/- 34 msec at baseline to a maximum of 823 +/- 61 msec at 6.6 Hz, 1,167 +/- 125 msec at 10 Hz, 1,734 +/- 281 msec at 20 Hz, 2,993 +/- 661 msec at 25 Hz, and 2,461 +/- 668 msec at 30 Hz during nerve stimulation. Linear regression analysis showed that the response of atrial cycle length to sinoatrial parasympathetic nerve stimulation was frequency dependent. The maximum response and complete decay of the response occurred within 4-8 seconds of initiation or termination of sinoatrial parasympathetic nerve stimulation. Atrioventricular conduction time and the PR interval did not change during sinoatrial parasympathetic nerve stimulation, even when the atria were paced at the baseline heart rate. CONCLUSIONS: Electrical stimulation of parasympathetic nerve fibers in a fat pad near the sinoatrial node increased atrial cycle length without affecting atrioventricular nodal conduction. This is the first study in which such nerve fibers that innervate the sinoatrial node have been selectively stimulated in humans.

Adipose Tissue↗
PubMed1992

General evaluation of out-of-hospital sudden cardiac death survivors.

Survivors of out-of-hospital sudden cardiac death may have any of a number of etiologies as the cause. Careful in-hospital evaluation is necessary for providing adequate therapy for such patients. In the great majority of survivors of out-of-hospital sudden cardiac death, such evaluation necessarily includes invasive electrophysiological testing for both diagnostic and therapeutic indications. Given the high incidence of recurrence, effective therapy, based on individualized evaluation, must be found.

Cardiac Catheterization↗
PubMed1990

Accumulated glutamate levels in the synaptic vesicle are not maintained in the absence of active transport.

We have investigated factors which may affect accumulated glutamate levels in synaptic vesicles and glutamate efflux. Agents which dissipate the electrochemical proton gradient resulted in a rapid reduction of steady-state vesicular glutamate levels, which was prevented by N-ethylmaleimide. Glutamate efflux was found to occur even in the presence of an electrochemical proton gradient, but was effectively inhibited by N-ethylmaleimide. These results suggest that accumulated glutamate levels in synaptic vesicles are not maintained unless glutamate is taken up continuously by an active transport mechanism, and they could provide an explanation for the lack of convincing evidence for the enrichment of endogenous glutamate in isolated synaptic vesicles.

Adenosine Triphosphate↗
PubMed1990

A perspective on ventricular arrhythmias: patient assessment for therapy and outcome.

Clinical management of patients with ventricular arrhythmias continues to evolve. It is generally accepted that patients with sustained ventricular tachyarrhythmias (ventricular tachycardia [VT] or fibrillation) require treatment. It is also generally accepted that patients with frequent or complex ventricular ectopy or nonsustained VT, in the absence of underlying heart disease, do not require treatment unless relief of symptoms is warranted. Whether patients with frequent or complex ventricular ectopy or nonsustained VT require treatment in the presence of underlying organic heart disease remains uncertain. The concern is that these ventricular arrhythmias may be a precursor for sustained, potentially life-threatening ventricular tachyarrhythmias. Available data suggest that patients with underlying heart disease, particularly coronary artery disease and a previous myocardial infarction, who manifest frequent or complex ventricular ectopy or nonsustained VT are at increased risk for sudden cardiac death. However, no studies have shown that treatment of these arrhythmias will affect outcome. Data are accumulating to suggest that use of the principles of risk stratification permits identification of patients at very high risk for developing sustained ventricular tachyarrhythmias. Carefully designed clinical trials are required before one can provide firm guidelines for the management of these patients. Nevertheless, when several risk factors for sudden cardiac death (e.g., abnormal ejection fraction, a late potential on a signal-averaged electrocardiogram, and frequent or complex ventricular ectopy or nonsustained VT) are present in a patient, especially after a recent myocardial infarction, invasive electrophysiologic testing may help identify those who need treatment (sustained VT is inducible) and those who do not (no sustained VT is inducible).

Arrhythmias, Cardiac↗
PubMed1990

Evolving patterns in the surgical treatment of malignant ventricular tachyarrhythmias.

The advent of the automatic implantable cardioverter defibrillator (AICD), generally viewed as a safe and effective intervention, has in some measure discouraged the use of electrophysiologically directed endocardial resection for intractable ventricular arrhythmias. We reviewed the records of 127 patients undergoing either AICD procedures or resection over a 6-year period. Thirty-day mortality was 5.6% (5/89 patients) for all AICD procedures, 10.7% (3/28) for AICD placement plus coronary artery bypass grafting, and 11.8% (4/34) for resection. These mortality figures are not significantly different. Patients undergoing resection were less likely to require antiarrhythmic agents than patients given an AICD (33% versus 61%). Survival at 2 years was 78% in the resection group and 72% in the AICD group. Survival at 4 years was still 78% in the resection group. Only 1 late sudden death occurred in the AICD group and none in the resection group. We conclude that resection continues to be a valuable alternative, offering a greater overall benefit at only slightly increased risk.

Adolescent↗
PubMed1990

Cardiac electrical responses to vagal stimulation of fibers to discrete cardiac regions.

We stimulated regional intracardiac parasympathetic nerve fibers to the atrioventricular (AV) nodal area (AVP stimuli) or to the sinoatrial (SA) nodal area (SAP stimuli) in autonomically decentralized, anesthetized dogs. AVP stimuli increased the AV interval (AV conduction time); the magnitude of the response depended directly on the stimulation frequency. AVP stimuli did not alter the atrial interval (heart period) in spontaneously beating hearts. The magnitude of the negative dromotropic response increased when the atrial interval was shortened. SAP stimuli increased the atrial interval, and the magnitude of the response depended directly on the stimulation frequency. SAP stimuli evoked little or no change in the AV interval in the unpaced heart. When the atrium was paced, SAP stimuli did not change the AV interval in about half of the preparations, and there was a small but significant change in the remaining preparations. The negative dromotropic or chronotropic response to AVP or SAP stimuli was potentiated by physostigmine and blocked by atropine. These results suggest that 1) AVP stimuli induce a selective negative dromotropic response, and 2) this negative dromotropic effect is secondarily affected by heart period, by the pacemaking site, and by atrial activation patterns, but it does not affect the sinus cycle length in the dog heart.

Animals↗
PubMed1989

Characterization of the solubilized and reconstituted ATP-dependent vesicular glutamate uptake system.

We have previously provided evidence for ATP-dependent glutamate uptake into synaptic vesicles, and, based upon the unique properties of the vesicular uptake system, we have proposed that the vesicular glutamate translocator plays a crucial role in selecting glutamate for neurotransmission. In this study, we have solubilized the vesicular glutamate uptake system, proposed to consist of at least a glutamate translocator and a proton pump Mg-ATPase, from rat brain synaptic vesicles, and reconstituted the functional ATP-dependent glutamate uptake system into liposomes. The glutamate uptake in the reconstituted system is dependent upon ATP, markedly potentiated by low millimolar concentrations of chloride and inhibited by agents known to dissipate electrochemical proton gradients. Moreover, it exhibited low affinity for glutamate (Km = 2 mM), yet high specificity for glutamate; thus, it did not recognize aspartate and other agents known to interact with glutamate receptors. These properties are indistinguishable from those observed in intact synaptic vesicles. The solubilized functional components of the glutamate uptake system, alone or as a complex, have been estimated to have a Stokes radius in the range of 69 to 84 A. The reconstitution experiments described here provide a functional assay for the solubilized vesicular glutamate uptake system and represent an initial step towards the purification of the glutamate translocator.

Adenosine Triphosphate↗
PubMed1989

Prolongation of cardiac cycle length attenuates negative dromotropic response to selective vagal stimuli.

We stimulated intracardiac parasympathetic nerve fibers that selectively innervated the atrioventricular (AV) nodal area (AV parasympathetic stimulation), and the sinoatrial (SA) nodal area (SA parasympathetic stimulation), in autonomically decentralized, anesthetized dogs. We then compared these responses to those elicited by stimulation of the cervical vagus nerves. We investigated the interactions between the dromotropic and chronotropic responses to simultaneous AV and SA parasympathetic stimulation. AV parasympathetic stimulation increased the AV interval (AV conduction time) but did not alter the interval between atrial depolarizations (sinus cycle length). SA parasympathetic stimulation increased the sinus cycle length and evoked small changes in the AV interval. Simultaneous AV and SA parasympathetic stimulation, at different combinations of frequencies, induced negative dromotropic and chronotropic responses that were similar to those evoked by cervical vagal stimulation. The greater the increase in sinus cycle length, the less did a given parasympathetic stimulation prolong the AV interval. The prolongation of the AV interval by parasympathetic stimulation did not affect the sinus cycle length. These results suggest that the direct pure negative dromotropic response to parasympathetic nerve stimulation is attenuated by the prolongation of the sinus cycle length, e.g. a concomitant negative chronotropic effect of the parasympathetic stimulation, in the dog heart. This attenuation reflects a mechanism that does not depend on the relative timing of the stimulus impulses in the cardiac cycle, i.e. a phase-independent, as well as the previously reported phase-dependent, mechanism.

Animals↗