Search PubMed⌕ Search

Biomedical subjects

R L Page

Publications and source records attributed to R L Page.

At least 55 records · Page 3Linked to original sources
PubMed1999

Treatment of cardiac arrhythmias during pregnancy: safety considerations.

Maternal and fetal arrhythmias occurring during pregnancy may jeopardise the life of the mother and the fetus. When arrhythmias are well tolerated and patients are minimally symptomatic, conservative therapy, such as observation and rest or vagal manoeuvres, should be employed. When arrhythmias cause debilitating symptoms or haemodynamic compromise, antiarrhythmic drug therapy is indicated. Although no antiarrhythmic drug is completely safe during pregnancy, most are well tolerated and can be given with relatively low risk. Physiological changes that occur during pregnancy mandate caution when administering antiarrhythmic drugs, with close monitoring of serum concentration and patient response. Drug therapy should be avoided during the first trimester of pregnancy if possible, and drugs with the longest record of safety should be used as first-line therapy. Several therapeutic options exist for most arrhythmias in the mother and fetus. Of the class IA agents, quinidine has the longest record of safety during pregnancy, and is generally well tolerated. Procainamide is also well tolerated, and should be a first line option for acute treatment of undiagnosed wide complex tachycardia. All IA agents should be administered in the hospital under cardiac monitoring due to the potential risk of ventricular arrhythmias (torsade de pointes). The IB agent, lidocaine (lignocaine), has local anaesthetic role but is also generally well tolerated as an antiarrhythmic agents. Phenytoin should be avoided due to the high risk of congenital malformations and limited role as an antiarrhythmic drug. Of the IC agents, flecainide has been shown to be very effective in treating fetal supraventricular tachycardia complicated by hydrops. Beta-Blockers are generally well tolerated and can be used with relative safety in pregnancy, although recent data suggest that they may cause intrauterine growth retardation if they are administered during the first trimester. Amiodarone, a class II agents with characteristics of the other antiarrhythmic drug classes, has been reported to cause congenital abnormalities; it should be avoided during the first trimester and used only to treat life-threatening arrhythmias that fail to respond to other therapies. Adenosine is generally safe to use in pregnancy, and is the drug of choice for acute termination of maternal supraventricular tachycardia. Digoxin has a long track record of treating both maternal and fetal arrhythmias, and is one of the safest antiarrhythmics to use during pregnancy. Direct current cardioversion to terminate maternal arrhythmias is well tolerated and effective, and should not be delayed if indicated. The use of an implantable cardioverter-defibrillator should be considered for women of childbearing potential with life-threatening ventricular arrhythmias.

Abnormalities, Drug-Induced↗
PubMed1997

Correlation between time-domain measures of heart rate variability and scatterplots in patients with healed myocardial infarcts and the influence of metoprolol.

Scatterplots (displays of each RR interval as a function of the preceding RR interval) provide a visual assessment of nonrandom variations in heart rate. In a recent study, scatterplot length, width, and area correlated with time-domain measures of heart rate variability (HRV) in survivors of recent myocardial infarction (MI) receiving a beta blocker. We performed this study to (1) assess the relation between time-domain measures of HRV and scatterplot indexes in survivors of remote MI not receiving metoprolol and (2) to determine if metoprolol influenced scatterplot indexes. In 28 survivors of remote MI, HRV time-domain variables and scatterplot indexes were measured after 2 weeks off and 2 weeks on metoprolol. Off metoprolol, scatterplot length correlated with long-term HRV variables (SD of the difference of all RR intervals [r = 0.98], SD of the average of all 5-minute intervals [r = 0.97]), and scatterplot width correlated with short-term HRV variables (root-mean-square successive differences between RR intrevals [rMSSD] [r = 0.88]). Metoprolol increased time-domain HRV variables (mean RR interval, rMSSD, and proportion of adjacent RR intervals differing by > 50 ms [pNN50 (%)]) but did not alter scatterplot indexes. Thus, scatterplot indexes correlate with time-domain measures of HRV in survivors of remote MI not receiving metoprolol. In contrast to HRV time-domain variables, scatterplot indexes are not influenced by metoprolol.

Adrenergic beta-Antagonists↗
PubMed1997

Initial experience with a high-impedance tined endocardial pacemaker lead: evidence for increased lead failure.

We report our initial clinical experience with a new tined ventricular endocardial pacemaker lead, the Medtronic model 5034. This lead has a reduced electrode tip size, which provides a higher impedance. Based on early evidence of elevation of pacing lead threshold, we compared our clinical experience with the performance of this lead with that of other similar models with larger surface area (Medtronic models 4024 and 5024). Of 17 implant procedures performed at our institution with the model 5034 lead, two (11.2%) developed high thresholds, versus 0% in 121 implant procedures with models 4024 or 5024 leads (p = 0.014). We conclude that there is evidence of increased failure caused by elevation of pacing threshold in this lead. This increased failure rate needs to be confirmed in a multicenter observational study or randomized trial.

Electrodes, Implanted↗
PubMed1997

Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm?

OBJECTIVES: This study sought to examine the hemodynamic and autonomic dose response to digoxin. BACKGROUND: Previous studies have demonstrated an increase in contractility and heart rate variability with digitalis preparations. However, little is known about the dose-response to digoxin, which has a narrow therapeutic window. METHODS: Nineteen patients with moderate heart failure and a left ventricular ejection fraction < 0.45 were studied hemodynamically using echocardiography and blood pressure at baseline and after 2 weeks of low dose (0.125 mg daily) and 2 weeks of moderate dose digoxin (0.25 mg daily). Loading conditions were altered with nitroprusside at each study. Autonomic function was studied by assessing heart rate variability on 24-h Holter monitoring and plasma norepinephrine levels during supine rest. RESULTS: Low dose digoxin provided a significant increase in ventricular performance, but no further increase was seen with the moderate dose. Low dose digoxin reduced heart rate and increased heart rate variability. Moderate dose digoxin produced no additional increase in heart rate variability or reduction in sympathetic activity, as manifested by heart rate, plasma norepinephrine or low frequency/high frequency power ratio. In addition, we did not find that either low or moderate dose digoxin increased parasympathetic activity. CONCLUSIONS: We conclude that moderate dose digoxin provides no additional hemodynamic or autonomic benefit for patients with mild to moderate heart failure over low dose digoxin. Because higher doses of digoxin may predispose to arrhythmogenesis, lower dose digoxin should be considered in patients with mild to moderate heart failure.

Cardiotonic Agents↗
PubMed1997

Determinants of nonthoracotomy biphasic defibrillation.

The clinical variables affecting DFT for ICD systems are not completely determined, especially with regard to biphasic shocking devices. To distinguish which factors correlate with DFT, we examined data from patients who were enrolled in the Ventak P2/Endotak protocol. A total of 284 patients were enrolled in the study. Two patients had a DFT > 25 J and did not receive the device; 154 did not undergo stepdown to failure DFT testing. The remaining 128 patients had formal DFT testing and were suitable for analysis. Variables available for analysis included age, body surface area (BSA), LVEF, gender, lead configuration, primary arrhythmia, primary cardiac disease, and use of cardioactive medication. Data were evaluated using regression analysis, fitting DFT (range, 1-25 J, mean 11 +/- 5 J) as a function of each variable. As a univariate predictor. BSA was found to be significant in predicting DFT, but accounted for only 9% of the total variation on the DFT (P < 0.01, r = 0.3). This study suggests that DFT using a biphasic shocking waveform is modestly in fluenced by the BSA of the patient. Other specific factors, including LVEF, do not predict DFT.

Age Factors↗
PubMed1997

Diagnostic approach to narrow complex tachycardia with VA block.

Narrow complex tachycardia with VA block is rare. The differential diagnosis usually consists of (1) junctional tachycardia (JT) with retrograde block; (2) AV nodal reentrant tachycardia (AVNRT) with proximal common pathway block; and finally (3) nodofascicular tachycardia using the His-Purkinje system for antegrade conduction and a nodofascicular pathway for retrograde conduction. Analysis of tachycardia onset and termination, the effect of bundle branch block on tachycardia cycle length, and the response to atrial and ventricular premature depolarization must be carefully done. Making the correct diagnosis is crucial as the success rate in eliminating the tachycardia will depend on tachycardia mechanism.

Atrioventricular Node↗
PubMed1997

Ablation of ventricular tachycardia associated with tetralogy of Fallot: demonstration of bidirectional block.

INTRODUCTION: Ventricular tachycardia is commonly seen in patients following surgical repair for tetralogy of Fallot. The technique of ablation for this arrhythmia is not well defined. METHODS AND RESULTS: In two patients with ventricular tachycardia following surgical repair of tetralogy of Fallot, the traditional indicators for a site for ventricular tachycardia ablation did not yield cure. Based on careful mapping, the circuit was found to involve the isthmus between the outflow tract patch and the tricuspid annulus; linear radiofrequency lesions across this isthmus resulted in cure of ventricular tachycardia. Not only was the tachycardia no longer inducible, but bidirectional block at the line of ablation confirmed interruption of the reentrant circuit. CONCLUSION: A linear radiofrequency lesion was effective in eliminating ventricular tachycardia in both patients. The demonstration of bidirectional block confirms a cure independent of inducibility of ventricular tachycardia.

Adult↗
PubMed1996

Selective radiofrequency ablation of the "slow" atrioventricular nodal pathway for control of the ventricular response to atrial fibrillation.

In summary, this study reports 2 important findings: (1) AV nodal modification using the conservative protocol we describe reduces long-term success for ventricular rate control during atrial fibrillation but eliminates the incidence of permanent AV block; (2) directed lesions that eliminate clinical AV nodal reentry slow ventricular response to acute atrial fibrillation but are not sufficient to control ventricular response of chronic atrial fibrillation. Further refinement of these techniques may allow an optimal balance between rate control and avoidance of permanent pacing.

Adult↗
PubMed1996

P-glycoprotein expression in canine lymphoma: a relevant, intermediate model of multidrug resistance.

BACKGROUND: Despite extensive investigation, the role of MDR of human cancer remains unclear. Canine lymphoma is a spontaneously arising correlate of human non-Hodgkin's lymphoma that may complement other in vivo models for investigation of issues related to MDR. METHODS: Immunoreactivity of primary antibodies to the human MDR1 gene product, p-glycoprotein 170 (Pgp), were determined in both a retrospective (n=76) and prospective (n=15) survey of canine lymphoma. Known prognostic factors and response to chemotherapy were correlated with categorical designations of Pgp expression. RESULTS: When combined, 61 of 91 samples (67%) were negative for Pgp, 16 of 91 (17.5%) had strong Pgp immunoreactivity in >50% of the malignant population and 14 of 91 (15.5%) had Pgp reactivity in 10-50% of cells. Pgp expression was greater after relapse compared with pretreatment samples [C494 83% vs. 25%; P=0.012 and C219 73% vs. 27%; P=0.04]. Pretreatment Pgp expression was an independent negative predictor of overall survival (median=225d vs. 367d; P=0.02). CONCLUSIONS: Pgp expression in spontaneous canine lymphoma is similar to that reported in human non-Hodgkin's lymphoma. Use of this model may expedite investigation of novel strategies for MDR prevention or modulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Radiation plus local hyperthermia versus radiation plus the combination of local and whole-body hyperthermia in canine sarcomas.

PURPOSE: The purpose of this study was to assess the effect of increasing intratumoral temperatures by the combination of local hyperthermia (LH) and whole body hyperthermia (WBH) on the radiation response of canine sarcomas. METHODS AND MATERIALS: Dogs with spontaneous soft tissue sarcomas and no evidence of metastasis were randomized to be treated with radiation combined with either LH alone or LH + WBH. Dogs were accessioned for treatment at two institutions. The radiation dose was 56.25 Gy, given in 25 2.25 Gy daily fractions. Two hyperthermia treatments were given; one during the first and one during the last week of treatment. Dogs were evaluated after treatment for local recurrence, metastasis, and complications. RESULTS: Sixty-four dogs were treated between 1989 and 1993. The use of LH+WBH resulted in statistically significant increases in the low and middle regions of the temperature distributions. The largest increase was in the low temperatures with median CEM 43 T90 values of 4 vs. 49 min for LH vs. LH + WBH, respectively (p<0.001). There was no difference in duration of local tumor control between hyperthermia groups (p = 0.59). The time to metastasis was shorter for dogs receiving LH + WBH (p = 0.02); the hazard ratio for metastatic disease for dogs in the LH + WBH group was 2.4 (95% confidence interval, 1.2-5.4) with respect to dogs in the LH group. Complications were greater in larger tumors and in tumors treated with LH + WBH, CONCLUSION: The combination of LH + WBH with radiation therapy, as described herein, was not associated with an increase in local tumor control in comparison to use of LH with radiation therapy. The combination of LH + WBH also appeared to alter the biology of the metastatic process and was associated with more complications than LH. We identified no rationale for further study of LH + WBH in combination with radiation for treatment of solid tumors.

Animals↗
PubMed1996

Influence of metoprolol on heart rate variability in survivors of remote myocardial infarction.

We assessed the influence of metoprolol on heart rate variability in survivors of remote myocardial infarction. In 43 survivors of myocardial infarction 12 to 18 months previously (26 men and 17 women, aged 38 to 69 years), two 24-hour ambulatory electrocardiograms were recorded 2 weeks apart. In patients in group A (n=28), who had taken metoprolol for the previous year, the drug was discontinued for 2 weeks, after which the first recording was done. The second recording was done 2 weeks after metoprolol was resumed. In patients in group B (n=15), who had not taken metoprolol for the previous year, it continued to be withheld, and two 24-hour recordings were done 2 weeks apart. In group A, metoprolol increased the time domain variables indicative of enhanced vagal tone; root-mean-square successive difference in normal RR (NN) intervals was 20 +/- 11 ms (mean +/- SD) without and 24 +/- 9 ms with metoprolol (p<0.05), and the proportion of NN that differ by >50 ms (pNN50%) was 3.6 +/- 6.0 without and 5.5 +/- 6.0 with metoprolol (p<0.05). In the frequency domain, the logarithms of the 24-hour very low frequency and the 24-hour high-frequency power (reflecting parasympathetic activity) were increased (5.12 +/- 1.03 and 4.48 +/- 1.51, respectively, without metoprolol; 5.32 +/- 0.99 and 4.83 +/- 1.24, respectively, with metoprolol, p <0.05 for both). Thus, in survivors of remote myocardial infarction, metoprolol enhances parasympathetic cardiac activity in the time and frequency domain measures of heart rate variability.

Adult↗
PubMed1996

Effect of biphasic endocardial countershock on pacing thresholds in humans.

The use of non-thoracotomy endocardial implantable defibrillators with pacing capabilities has increased substantially over the past 2 years. This report demonstrates that the pacing threshold increases in some patients after endocardial defibrillation, and substantiates the practice of using maximal pacing output after endocardial defibrillation.

Adult↗
PubMed1996

Effect of continuous vagal enhancement on concealed conduction and refractoriness within the atrioventricular node.

This study examined the complex interaction between vagal enhancement and how a concealed atrial impulse alters atrioventricular (AV) nodal function. In theory, vagal augmentation could increase or decrease the effect that a premature atrial beat has on the subsequent beat. In 10 patients we established the AV nodal effective refractory period (ERP) without and with a conditioning atrial stimulus (Sc); the stimulation protocol was then repeated after enhancing reflex vagal tone with a continuous phenylephrine infusion. During phenylephrine infusion, the sinus cycle length prolonged from 827 +/- 99 to 1,029 +/- 223 ms (p < 0.001) and AV nodal ERP increased from 331 +/- 51 to 425 +/- 64 ms (p < 0.005). At control, AV nodal ERP in the presence of Sc prolonged to 536 +/- 69 ms (p < 0.001), and during phenylephrine infusion increased to 579 +/- 57 ms (p < 0.01), a change significantly less than during control (58 +/- 14% vs 31 +/- 14%, respectively, p < 0.01). Further experiments suggest that the effect of Sc was reduced because it occurred earlier relative to the vagally prolonged AV nodal ERP. In conclusion, this study demonstrates a complex relation between the timing of a premature atrial beat causing concealed conduction and the degree of vagal tone. The concealed beat, as related to the AV node ERP, has a substantial effect on subsequent AV nodal conduction. These data give insights into clinical AV nodal function.

Adrenergic beta-Agonists↗
PubMed1996

Pharmacokinetics and toxicity of oral and intravenous lonidamine in dogs.

Plasma lonidamine concentration and toxicity were investigated in dogs receiving 100, 200, 400, 800, 1200 mg/m2 orally twice daily for 30 days and in dogs receiving single intravenous doses of 200, 400, 800, 1200 mg/m2. Physical or laboratory signs of toxicity were not observed in dogs receiving oral lonidamine, but severe vomiting and signs of acute hepatic and pancreatic toxicity were observed in dogs receiving intravenous doses that exceeded 400 mg/m2. The area under the lonidamine concentration versus time curve (AUC) in dogs receiving 200, 400, and 800 mg/m2 of lonidamine intravenously was a 1.8-, 3.3-, and 8.7-fold higher than in dogs receiving oral lonidamine. This suggests that the bioavailability of oral lonidamine may be limited. However, centrilobular hepatocellular swelling and vacuolation were observed in dogs receiving oral lonidamine. Serum alanine aminotransferase (ALT) activity was increased in dogs receiving intra-venous lonidamine. These findings suggest that lonidamine is hepatotoxic in dogs. However, serum ALT was increased in only 1/4 dogs receiving 400 mg/m2 of lonidamine intravenously and plasma concentration were within the range capable of sensitizing hyperthermia and chemotherapy. Therefore, this dose and route appears to be a viable and controllable method for prospective quantification of lonidamine interaction with systemic chemotherapy and/or hyperthermia.

Administration, Oral↗