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Biomedical subjects

R Lazzara

Publications and source records attributed to R Lazzara.

At least 91 records · Page 5Linked to original sources
PubMed1994

Role of Na+:Ca2+ exchange current in Cs(+)-induced early afterdepolarizations in Purkinje fibers.

INTRODUCTION: The ionic mechanisms for early afterdepolarizations (EADs) have not been fully clarified. It has been suggested that L-type Ca2+ current (ICaL) is the primary current generating EADs that occur near the plateau level (E-EADs) of the membrane potential (Vm) when ICaL is enhanced. The purpose of these studies was to determine accurately the range of Vm at which EADs occur in Purkinje fibers with K+ currents blocked by Cs+ and to investigate the importance of Na+:Ca2+ exchange current (INa:Ca) as opposed to ICaL and other currents in the generation of EADs occurring later during repolarization (L-EADs). METHODS AND RESULTS: Shortened Purkinje strands from dogs and guinea pigs were superfused with physiologic solution containing Cs+ (3.6 mM) and a low [K+]o (3.0 or 2.0 mM) to induce EADs. The Vm of origin of EADs and their evolution were measured with the aid of phase plane plots of the rate of repolarization against Vm. L-EADs occurred over a wide range of Vm (-35 to -90 mV), generally more negative in guinea pig than in dog. Elevation of [Ca2+]o from 1.8 to 3.6 mM suppressed L-EADs within a few cycles, and they returned with continued exposure. After repeated exposures to high [Ca2+]o, L-EADs migrated toward less negative Vm when [Ca2+]o was reestablished to 1.8 mM in the presence of Cs+. Reduction of [Na+]o from 147.5 to 112.5 mM by substitution with Li+ or sucrose also rapidly depressed L-EADs. CONCLUSIONS: The observation of Cs(+)-induced L-EADs over a wide range of Vm indicates that there is not a single inward gated current as a common ionic mechanism for L-EADs but does not exclude an important role for INa:Ca, which can operate over a wide range of Vm. The rapid suppression of L-EADs with elevated [Ca2+]o and reduced [Na+]o and the migration of EADs to more positive Vm after exposures to high [Ca2+]o are compatible with INa:Ca as the major charge carrier for L-EADs.

Action Potentials↗
PubMed1994

Elucidation of Prinzmetal's variant form of preexcitation.

BACKGROUND: In 1952, Prinzmetal induced preexcitation in the normal dog heart using subthreshold stimulation (SS) delivered to the right ventricle. METHODS AND RESULTS: In 12 dogs we recorded ECG leads II, aVR, His (Hb) and proximal right bundle potentials with electrode catheters at the aortic root and a special electrode that was inserted through the right ventricular (RV) free wall. In 12 others, SS was delivered to the Hb area by a catheter placed under the septal leaflet of the tricuspid valve. During SS, the HV interval shortened from 35 +/- 4 milliseconds (mean +/- SD) to 19 +/- 7 milliseconds (P = .0001), but AH intervals were unchanged. The ECG showed delta waves with aberrant QRS complexes. Endocardial electrograms showed that the origin of activation in the preexcitation beats was localized to the muscle adjacent to the Hb or proximal right bundle. When vagal stimulation induced sudden AV block, no ventricular excitation was seen, confirming the subthreshold nature of the applied stimulation. By adjusting the levels of SS, latent forms of preexcitation could be induced, eg, early local septal muscle activation but no change in the ECG leads. Premature ventricular stimuli delivered to the RV apex or outflow tract could cause manifest preexcitation in the ECG leads or inhibit expression of latent preexcitation in endocardial recordings. CONCLUSIONS: SS delivered to the RV apex or Hb area causes ventricular preexcitation, as shown previously by Prinzmetal et al. SS delivered at the insertion sites of an accessory pathway may facilitate localization of such abnormal connections, particularly when preexcitation is concealed.

Animals↗
PubMed1994

Radiofrequency catheter ablation of right atriofascicular (Mahaim) accessory pathways guided by accessory pathway activation potentials.

BACKGROUND: Accessory pathways (APs) exhibiting "Mahaim fiber" physiology (antegrade conduction only, long conduction time, and decremental properties) often connect the lateral right atrium to the right bundle branch (right atriofascicular pathways). Potentials from these pathways have not been recorded previously. The purpose of this study was to determine whether AP activation potentials could be recorded from right atriofascicular APs and to determine whether these potentials could be used to localize a site for catheter ablation. METHODS AND RESULTS: Of 26 consecutive patients referred for catheter ablation of an AP producing a preexcited (antidromic) atrioventricular (AV) reentrant tachycardia having a left bundle branch block pattern with short ventriculoatrial and long AV intervals, 23 (88.5%) were found to have a right atriofascicular AP. During antidromic AV reentrant tachycardia, (1) right atrial extrastimuli (that did not penetrant tachycardia, (1) right atrial extrastimuli (that did not penetrate the AV node) advanced the timing of the next QRS complex, indicating that the AP was connected to the right atrium; (2) earliest antegrade ventricular activation was recorded at the apical right ventricular free wall, and (3) ventricular activation was preceded by activation of the distal right bundle branch, indicating a fascicular insertion or a ventricular insertion close to the terminus of the right bundle branch. A single, discrete, high-frequency AP potential was recorded at the lateral, anterolateral, or posterolateral tricuspid annulus in 22 of the 23 patients 63 +/- 12 milliseconds after the local atrial potential and 83 +/- 23 milliseconds before the local ventricular potential during sinus rhythm. The AP potential was also recorded at sites along the right ventricular free wall between the tricuspid annulus and the site of earliest ventricular activation at the apical region. Programmed atrial stimulation and adenosine each produced prolongation of AP conduction time because of an increase in the A-AP interval and Wenckebach block proximal to the AP potential. Radiofrequency current applied at a site recording the AP potential (tricuspid annulus in 19 patients and right ventricular free wall in 3 patients) eliminated AP conduction in all 22 patients. Tachycardia has not recurred in any patient during 18 +/- 13 months of follow-up. AP conduction was absent in all 9 patients who had a follow-up electrophysiological study 3.8 +/- 1.7 months after ablation. CONCLUSIONS: Right atriofascicular APs consist of two components. The proximal component is located at the lateral, anterolateral, or posterolateral tricuspid annulus, does not generate an AP potential recordable by catheter electrodes, and is responsible for the decremental conduction properties. The "distal" component extends from the tricuspid annulus to the distal right bundle branch at the apical right ventricular free wall and generates a large, high-frequency AP potential that accurately identifies a site for ablation.

Action Potentials↗
PubMed1994

Facilitation of reentry by lidocaine in canine myocardial infarction.

Despite continuing controversies regarding its antiarrhythmic and antifibrillatory efficacy lidocaine is frequently used for the treatment of ventricular arrhythmias occurring in the early phase of acute myocardial infarction (MI). The authors studied the effects of lidocaine in 18 consecutive MI dogs 1-4 days (2.8 +/- 0.3 day) after the two-stage left anterior descending coronary artery (LAD) ligation and in 11 dogs, in which the LAD and the distal branches of the left circumflex artery was ligated 12-75 (mean 35) days prior to study. Electrophysiologic testing was performed in anesthetized post-infarction dogs using single, double or triple programmed extrastimuli or rapid bursts (3 beats at 240-420/min) delivered to the right ventricular outflow tract. Inducibility of SMVT (uniform QRS morphology lasting > 30 sec at a rate of > 250 beat/min) after an i.v. bolus of lidocaine (3-6 mg/kg) was compared in the same animal to the pre-drug state. During the control state, SMVT was inducible in 6/18 dogs. After the administration of lidocaine, electrically induced SMVT was initiated in additionally 9 dogs (which were previously non-inducible; post-lidocaine vs control p < 0.02). Sustained reentry was induced by 3 mg/kg lidocaine in 5 dogs (310 +/- 62 beat/min) and by 6 mg/kg in 4 (261 +/- 52 beat/min). In the 8 survivors of the chronic MI group, SMVT was inducible before lidocaine administration in one, but in 7 after lidocaine. The antiarrhythmic agent induced further rate-dependent slowing of conduction in the peri-infarction subepicardium, which at a critical value of rate and amount of conduction delay resulted in sustained reentrant monomorphic tachycardia. These results show that lidocaine has arrhythmogenic/proarrhythmic actions in these canine models of MI probably due to its depressant effect on moderately sick cardiac tissue. The 'modification' of the functional properties of the arrhythmia substrate by lidocaine can promote the formation of new reentrant pathways leading to manifest sustained ventricular reentry under electrophysiologic study.

Acute Disease↗
PubMed1994

Effects of novel antiarrhythmic agents, BRB-I-28 and its derivatives, on the heart mitochondrial respiratory chain and sarcoplasmic reticulum Ca(2+)-ATPase.

The effects of BRB-I-28 and its derivatives (GLG-V-13, SAZ-VII-22 and SAZ-VII-23), a novel group of antiarrhythmic agents, were investigated on the rat heart mitochondrial respiratory chain. The results indicate that BRB-I-28 and its derivatives have concentration-dependent inhibitory effects on NADH oxidase and NADH-CoQ reductase (complex I), but they have no significant effects on succinate oxidase, succinate dehydrogenase (complex II), CoQ-cytochrome c reductase (complex III), cytochrome c oxidase (complex IV), and NADH-K3Fe(CN)6 reductase. The site of inhibition of BRB-I-28 and its derivatives on the respiratory chain was localized between flavoprotein n (FPn) and CoQ, which is similar to the effect of rotenone and several other antiarrhythmic drugs such as amiodarone, propranolol, etc. BRB-I-28 and its derivatives also have significant inhibitory effects on mitochondrial ATPase activity as reported for other antiarrhythmic drugs such as amiodarone, propranolol, quinidine, and lidocaine. However, BRB-I-28 and its derivatives have no direct effects on sarcoplasmic reticulum Ca(2+)-ATPase activity. The inhibitory effects of BRB-I-28 and its derivatives on mitochondrial oxidative phosphorylation may result in the depletion of ATP. This effect, in combination with their effects on Na+,K(+)-ATPase, could possibly produce an increase in Ca2+ concentration in cytosol. This may be another mechanism by which these DHBCN derivatives produce an increase in systemic arterial blood pressure and contractile force of isolated cardiac muscle. On the other hand, inhibition on mitochondrial respiration may account for some of the potential toxic effects of these diheterabicyclo[3.3.1]nonane derivatives.

Adenosine Triphosphatases↗
PubMed1993

Radiofrequency ablation of a concealed accessory pathway as treatment for incessant supraventricular tachycardia in a dog.

A new technique for the treatment of certain types of cardiac arrhythmias was used in a 3-year-old dog that was evaluated for incessant supraventricular tachycardia (220 to 280 beats/min), which had been refractory to several treatment regimens. The mechanism of supraventricular tachycardia was atrioventricular (AV) reentry, using a dorsoseptal accessory pathway (AP) for retrograde ventriculoatrial conduction (concealed AP). With the dog under general anesthesia and with fluoroscopic monitoring, electrode catheters were introduced into the heart via peripheral vessels. Electrical recordings allowed localization of the accessory AV pathway. Programmed electrical stimulation was used to verify the function of the abnormal AV connection. At the atrial insertion site of the AP, 2 applications of radiofrequency current (45 V, 21.6 W) were delivered to the dorsoseptal right atrium (near the coronary sinus ostium), which eliminated AP conduction and AV reentrant tachycardia. The dog has remained free of tachycardia and has not required medication during more than 1 year of follow-up.

Anesthesia, General↗
PubMed1993

Magnesium and the heart: antiarrhythmic therapy with magnesium.

Magnesium is an essential transmembrane and intracellular modulator of the electrical activity of cardiac cells. This review provides an up-to-date consideration of the cellular and clinical electrophysiological role of magnesium. This ubiquitous element seems to be important from both the theoretical and clinical point of view, because magnesium salts (MgSO4, MgCl2) administered intravenously are particularly effective in those arrhythmias in which the mechanism involves early or delayed after depolarization-induced triggered activity. The authors share the view that I.V. magnesium is the drug of choice in "torsade de pointes" ventricular tachycardia accompanying acquired long QT/QTU syndrome. It is complementary therapeutic agent in digitalis-induced tachycardias. Further studies are needed to elucidate magnesium's mode of action and efficacy in other types of clinical tachyarrhythmias.

Animals↗
PubMed1993

Antiarrhythmic drugs and torsade de pointes.

In the past decade there has been much progress in understanding the clinical features and associations of drug-induced long QT syndromes, their inter-relationships with other long QT syndromes, and electrophysiological mechanisms that may be involved in the development of torsade de pointes, the major proarrhythmic correlate of prolonged repolarization. The most likely electrophysiologic basis for torsade de pointes is the development of after-depolarizations facilitated by hypokalemia, bradycardia and lengthened QT intervals. Torsade de pointes can be produced by all antiarrhythmic agents that lengthen repolarization, although the precise incidence varies with different agents and is not quantitatively related to the degree of QT prolongation. Quinidine, disopyramide and procainamide (with its metabolite N-acetyl procainamide) are strongly concordant in the production of torsade de pointes. Such concordance suggests that there is an individual predisposition to the induction of early after-depolarizations (EAD) with exposure to agents that prolong repolarization. However, concordance with agents or other classes, such as sotalol, is less certain, and amiodarone appears to be discordant. The discordance between potency in prolonging the QT interval and the proclivity to induce torsade de pointes may hold the key to separating the salutary therapeutic antiarrhythmic effects from adverse proarrhythmic effects of class III agents. There is an optimistic perception that the development of new agents that potently prolong repolarization will give a modern realization of the old concept that prolongation of refractoriness is a uniquely powerful anti-re-entrant, antitachyarrhythmic action.

Action Potentials↗
PubMed1993

Electrophysiologic actions of BRB-I-28 in ischemically injured canine myocardium.

We examined the electrophysiologic actions of BRB-I-28 using two in vivo and two in vitro models of myocardial ischemic injury. In intact canine heart studied 4 days after anterior descending coronary artery occlusion, BRB-I-28 (3 and 6 mg/kg, i.v.) prolonged refractoriness in ischemically injured epicardium to an extent similar to that caused by lidocaine (3 and 6 mg/kg i.v.). BRB-I-28 produced less rate-dependent epicardial delay and, unlike lidocaine, failed to facilitate reentrant arrhythmia formation. Lidocaine and BRB-I-28 (3 and 6 mg/kg i.v.) produced similar rate-dependent prolongation of HV intervals in the normal His-Purkinje system, and produced both tonic and use-dependent conduction block in the ischemically injured His-Purkinje system studied 2 h after anteroseptal coronary artery ligation. In isolated superfused ventricular epicardium studied 1-4 days after anterior descending coronary artery ligation, BRB-I-28 reduced action potential amplitude (APA) and maximum phase 0 upstroke (Vmax) in normal (3.2 mg/L) and ischemically injured (1 and 3.2 mg/L) tissue, with marked tonic and use-dependent conduction block (3.2 mg/L). AP potential duration (APD) was unaltered. In isolated, superfused, ischemically injured canine endocardium studied 24 h after anterior descending coronary artery occlusion, BRB-I-28 (3.2 and 10 ml/L) reduced APA and Vmax and prolonged refractoriness and conduction times in ischemically injured tissue without altering APD. Tonic block was more prominent, and use-dependent block was observed at lower drug concentrations in ischemically injured tissue. The data demonstrate selective conduction depression and prolongation of refractoriness for BRB-I-28 in ischemically injured tissues. Both use-dependent and tonic conduction block contribute to the decrease in conduction observed with BRB-I-28 in ischemically injured myocardium, with more prominent tonic conduction block present in ischemically injured epicardium and His-Purkinje tissue at 2-24 h after coronary artery occlusion than in ischemically injured left ventricular (LV) epicardium studied 4 days after coronary artery occlusion.

Animals↗
PubMed1993

Rapid inward current in ischemically-injured subepicardial myocytes bordering myocardial infarction.

INTRODUCTION: To determine if collagenase-dispersed epicardial myocytes overlying myocardial infarction reproduce the same altered electrophysiology observed in intact epicardium, multicellular tissue preparations and enzymatically-dispersed myocytes from ischemically-injured canine subepicardium were examined 1 and 4 days after myocardial infarction. METHODS AND RESULTS: The electrophysiologic changes observed with ischemic injury in enzymatically-dispersed myocytes were not different from changes observed in multicellular tissue preparations at 1 and 4 days postinfarction. Ischemically-injured myocytes were depolarized versus normal myocytes at [K0]+ (2.5 to 40 mM) with reduced membrane potentials also observed in injured subepicardial tissue preparations [K0]+ (4 to 24 mM). On day 1, the reduced Vmax and the prolonged recovery of Vmax from inactivation were consistent with the reduced membrane potentials observed at each [K0]+. The half-maximal Vmax, maximal Vmax, and Boltzmann constant (k) in injured myocytes were unchanged versus normal myocytes. On day 4 postinfarction, the half-maximal Vmax was shifted to a more negative membrane potential, the maximal Vmax was reduced, and k was increased in injured versus normal myocytes. Prolonged recovery from inactivation was observed with depressed membrane potentials in injured myocytes on day 4. CONCLUSION: Enzymatically-dispersed myocytes from ischemically-injured subepicardium closely reproduce altered cellular properties observed in multicellular tissue preparations. The data suggest that 1 day postinfarction, altered conduction and refractoriness largely result from a reduced membrane potential. At 4 days, a reduced maximal Vmax, a shift in the inactivation curve to more negative voltages, and prolonged recovery of Vmax from inactivation also contribute to slowed conduction and prolonged refractoriness.

Animals↗
PubMed1993

Critical analysis of the signal-averaged electrocardiogram. Improved identification of late potentials.

BACKGROUND: This study performed a critical analysis of signal-averaging methods. The objective was to optimize detection of late potentials. METHODS AND RESULTS: We studied two patient populations: a low-arrhythmia-risk group with no evidence of heart disease and a group with clinically documented ventricular tachycardia (VT). Filtered QRS duration (QRSD) and terminal QRS amplitude (RMS40) were measured from the vector magnitude. A QRS duration based on the latest detectable ventricular activity in any of the three individual XYZ leads was also measured. Because of improved signal-to-noise ratio, both individual lead analysis and extended (600-versus 200-beat) averaging yielded significant changes in signal-averaged ECG parameters. Both approaches gave an increased sensitivity for VT identification. Sensitivity, specificity, and accuracy were evaluated as functions of critical values of QRSD and RMS40. RMS measurements in the terminal QRS, ranging from 20 to 100 msec and including RMS40, did not contribute to maximizing sensitivity and were highly correlated with QRSD. Our results from the low-arrhythmia-risk group suggest that age and sex should be considered in the definition of late potentials. CONCLUSIONS: We propose a VT risk stratification scheme using signal-averaged ECG parameters obtained from both individual lead and vector magnitude analysis. This allows definition of four categories of VT risk derived statistically from the study data. This definition is based on combined measures of sensitivity, specificity, and negative and positive predictive value.

Aged↗
PubMed1993

Functional dissociation of cellular activation as a mechanism of Mobitz type II atrioventricular block.

BACKGROUND: Several mechanisms have been advanced to explain Mobitz type II atrioventricular block in the ischemically damaged His-Purkinje system. Only recently, however, has an animal model been developed to study this form of conduction defect in vivo and in vitro. METHODS AND RESULTS: Conduction defects were induced in anesthetized dogs by ischemic damage to the proximal His-Purkinje system after anterior septal artery ligation. Stable 2:1 atrioventricular block, localized within the His bundle or in the proximal bundle branches, was obtained in each dog by atrial pacing at an average rate of 239 +/- 20 beats per minute (n = 12). In vitro studies were then performed from the same hearts. Action potentials and electrograms were simultaneously recorded from the His bundle and the proximal right bundle branch at the site of damage. At slow rates of pacing (40-60 beats per minute), the action potential amplitude was 85 +/- 4 mV, and some cells (10 +/- 3%) showed dissociation from the electrical activity in the bundle. At fast rates (149 +/- 11 beats per minute), during 1:1 conduction, the frequency of cellular dissociation increased to 57 +/- 6% (p < 0.001), and the action potential amplitude decreased (-31 +/- 4%, p < 0.001). The frequency of dissociation closely correlated with the reduction in action potential amplitude (r = 0.87, p < 0.001). These changes were markedly attenuated once 2:1 block developed. The site of block was not constant but rather showed a dynamic behavior with spatial shifting in response to changes in pacing rate or the introduction of extrastimuli. CONCLUSIONS: These results indicate that in the ischemically damaged proximal His-Purkinje system, an increase in rate leads to reduced and asynchronous cellular activation before 2:1 block. The latter provides a more stable activation pattern, because the frequency of dissociation is markedly reduced.

Action Potentials↗
PubMed1993

Variant forms of AV and VA conduction in the canine heart.

In 19 pentobarbital anesthetized dogs subjected to right thoracotomy, plunge wire and catheter electrodes were positioned to record and pace from the high right atrium, coronary sinus os, aortic root (for His bundle electrograms), and the right ventricular outflow tract and apex. A deflectable-tip catheter electrode was placed under the septal tricuspid leaflet for pacing the right ventricular septal crest. Electrocardiographic leads II and aVR were also recorded during atrial and ventricular pacing in the control state and during low- and high-intensity left vagosympathetic trunk stimulation. Pacing from each A or V site in 12 dogs showed normal atrioventricular (AV) and ventriculoatrial (VA) conduction over a wide range of heart rates (120-360 beats/min) with progressive AV and VA delay at each heart rate until Wenckebach cycles occurred (AV Wenckebach cycle averaged 325 +/- 44 beats/min; VA Wenckebach cycle averaged 246 +/- 52 beats/min). In two dogs, pacing from the coronary sinus os showed a 30-beat/min difference in the Wenckebach cycle rate compared to high right atrium pacing, and the AH intervals for the former were relatively insensitive to vagosympathetic trunk stimulation compared with the latter. In five other dogs, retrograde VA and HA intervals showed little, if any, decrement over a wide range of heart rates, with no immediate response to low-intensity vagal stimulation. After 7-22 seconds of continuous vagal stimulation, VA intervals abruptly prolonged and/or blocked. In all, second-degree heart block occurred at ventricular pacing rates > or = 300 beats/min in the form of atypical Wenckebach cycles. In all cases, the earliest atrial activation, as measured by a close bipolar probing electrode, was in the posterior septum adjacent to the coronary sinus os. In one dog, VA block occurred as a Mobitz type II with paroxysmal complete VA block (sinus escape rhythm) during continuous ventricular pacing at 330 beats/min. After radiofrequency ablation of the earliest atrial activation site typical VA Wenckebach cycles, immediately responsive to vagal stimulation, was then observed at a ventricular pacing rate of 150 beats/min. These data suggest that AV and VA connections in some canine hearts show varying degrees of bypass of the AV node, similar to cases reported in the clinical literature.

Animals↗
PubMed1993

The comparative antiarrhythmic and proarrhythmic activity of a 3,7-diheterobicyclo[3.3.1]nonane, BRB-I-28, and lidocaine in the 1-4-day-old infarcted dog heart.

We compared the electrophysiological effects and quantified the antiarrhythmic/proarrhythmic potential of the 3,7-diheterobicyclo[3.3.1]nonane-derivative, BRB-I-28 and lidocaine in 15 consecutive postinfarction dogs. Electrophysiologic studies were performed in anesthetized animals, 1-4 days (mean +/- SE = 2.47 +/- 0.36) after the two-stage ligation of the left anterior descending coronary artery. Inducibility of sustained monomorphic ventricular tachycardia (SMVT) was compared in the pre-drug state, and after i.v. lidocaine (3 and 6 mg/kg) and BRB-I-28 (3 and 6 mg/kg) administration. During the control state, SMVT was inducible in 6/15 dogs (40%). After the administration of lidocaine, the rate of the inducible SMVT slowed (353 +/- 91 to 272 +/- 96 beat/min; p < 0.01), but due to the proarrhythmic action of the drug, SMVT became inducible in 13/15 dogs (87%). Sustained reentry was induced after 3 mg/kg lidocaine in 3 dogs and after 6 mg/kg in 4. The mean aortic blood pressure in these SMVTs was 36 +/- 8 mm Hg. After administration of BRB-I-28 (6 mg/kg) SMVT was not inducible in 2/6 and in 4 the SMVT rate was slowed (380 +/- 104 to 208 +/- 105 beat/min; p < 0.005) before termination in 3. In 2 dogs SMVT was induced after BRB-I-28 was given whereas they were non-inducible in the control state (proarrhythmic effect: 13%). Furthermore the hemodynamic state during the SMVTs was more stable after BRB-I-28 (mean aortic blood pressure = 65 +/- 7 mm Hg; post-BRB-I-28 vs post-lidocaine, p < 0.001). During sinus rhythm, lidocaine caused a transient lowering of the MBP (105 +/- 17 to 84 +/- 18 mm Hg; p < 0.001), whereas, BRB-I-28, induced a consistent but short-lasting pressor response (98 +/- 18 to 120 +/- 29 mm Hg; p < 0.001) after its bolus injection. The low proarrhythmic activity and the lack of a cardiodepressant action makes this new chemical class of antiarrhythmics worthy of further development.

Animals↗
PubMed1993

A functional approach to the preexcitation syndromes.

Electrophysiologic studies have been used to elicit the mechanisms of the preexcitation syndromes and have become a therapeutic tool over the past decade. A thorough understanding of the physiology and anatomy of accessory pathways that are responsible for preexcitation and the associated arrhythmias is necessary before considering the various forms of intervention. The approach to patients with preexcitation syndromes is discussed, with an emphasis on the functional properties of accessory pathways and the associated arrhythmias.

Electrocardiography↗
PubMed1992

High-performance liquid chromatographic determination of BRB-I-28, a novel antiarrhythmic agent, in dog plasma and urine.

A sensitive reversed-phase high-performance liquid chromatographic (HPLC) technique with ultraviolet detection has been developed to determine the concentration of BRB-I-28 (I), a novel antiarrhythmic agent, in dog plasma and urine. The mobile phase was acetonitrile-methanol-37.5 mM phosphate buffer, pH 6.8-triethylamine (50:50:75:0.1, v/v). The compound was extracted from dog plasma and urine with chloroform after alkalinization with sodium hydroxide. The extraction recovery was 83% from plasma and 84% from urine. Good linearity (r > 0.996) was observed throughout the ranges 0.1-12.0 micrograms/ml (plasma) and 0.1-8.0 micrograms/ml (urine). Intra- and inter-assay variabilities were less than 4%. The lower limit of quantitation was 0.08 microgram/ml in either plasma or urine. HPLC analysis of plasma and urine samples from a dog treated with I has demonstrated that the method was accurate and reproducible.

Animals↗