Differential localization of carbachol- and bicuculline-sensitive pontine sites for eliciting REM sleep-like effects in anesthetized rats

Carbachol, a cholinergic agonist, and GABA_A receptor antagonists injected into the pontine dorsomedial reticular formation can trigger rapid eye movement (REM) sleep-like state. Data suggest that GABAergic and cholinergic effects interact to produce this effect but the sites where this occurs have not been delineated. In urethane-anesthetized rats, in which carbachol effectively elicits REM sleep-like episodes (REMSLE), we tested the ability of 10 nL microinjections of carbachol (10 m m ) and bicuculline (0.5 or 2 m m ) to elicit REMSLE at 47 sites located within the dorsal pontine reticular formation at the levels -8.00 to -10.80 from bregma (B) (Paxinos and Watson, The Rat Brain in Stereotaxic Coordinates , Academic Press, San Diego, 1997). At rostral levels, most carbachol and some bicuculline injections elicited REMSLE with latencies that gradually decreased from 242 to 12 s for carbachol and from 908 to 38 s for bicuculline for more caudal injection sites. As the latencies decreased, the durations of bicuculline-elicited REMSLE increased from 104 s to over 38 min, and the effect was dose dependent, whereas the duration of carbachol-elicited REMSLE changed little (104–354 s). Plots of REMSLE latency versus the antero-posterior coordinates revealed that both drugs were maximally effective near B-8.80. At levels caudal to B-8.80, carbachol was effective at few sites, whereas bicuculline-elicited REMSLE to at least B-9.30 level. Thus, the bicuculline-sensitive sites extended further caudally than those for carbachol and antagonism of GABA_A receptors both triggered REMSLE and controlled their duration, whereas carbachol effects on REMSLE duration were small or limited by its concurrent REMSLE-opposing actions.     

The Value of Transesophageal Atrial Pacing in Predicting the Efficacy of Antiarrhythmic Drugs in Patients with Paroxysmal Narrow QRS Complex Tachycardia

Transesophageal atrial pacing (TAP) is used in the diagnosis and treatment of paroxysmal narrow QRS complex tachycardia (NQT). The aim of this study was to assess the value of this technique in predicting the efficacy of antiarrhythmic therapy. The study group consisted of 30 consecutive patients with spontaneous NQT whose clinical tachycardia was inducible by TAP. Baseline TAP was performed off all antiarrhythmic medication and repeated during oral antiarrhythmic drug therapy. The pacing protocol consisted of three stages: a single extrastimulus introduced at progressively shorter coupling intervals during sinus rhythm, pacing at incremental rates to the point of second-degree AV block, and bursts of rapid pacing. On repeat stimulation while on oral antiarrhythmic therapy (37 pacing studies) NQT was still inducible in 12 cases. During the follow-up period ten patients developed a recurrence of NQT:nine cases out of 12 (75%), in whom NQT was inducible while on antiarrhythmic therapy, and one case out of 25 (4%), in whom NQT was not inducible (P less than 0.001). The sensitivity of TAP in predicting the outcome of the patients with NQT was 90%, and the specificity 89%. The negative predictive value of TAP (prediction of no recurrence of NQT) was 96%, and the positive predictive value (prediction of recurrence of NQT) was 75%. We conclude that TAP is a simple and accurate method for predicting the efficacy of antiarrhythmic treatment in patients with NQT.     

Predictors of Ventricular Tachvcardia Inducibility in Programmed Electrical Stimulation and the Effectiveness of Serial Drug Testing: Polish Multicenter Study

WNUK-WOJNAR, A.M., ET AL.: Predictors of Ventricular Tachycardia Inducibility in Programmed Electrical Stimulation and Effectiveness of Serial Drug Testing: Polish Multicenter Study. In 100 patients with IHD and complex ventricular arrhythmias, programmed electrical stimulation was performed using up to three extrastimuli at sinus rhythm, and paced 100, 120, and 140 beats/min delivered from the RV apex, outflow tract or the LV with ventricular mapping to evaluate late potentials (LP) in 41 patients. Sustained monomorphic VT (SMVT) was provoked in 91% of 42 patients with a history of VT/VF, p < 0.001, all five patients had SMVT in 24-hour ECG, p < 0.005, and 91% of 21 patients with LV dyskinesis, p < 0.01. After depolarizations were found in 62% of 21 patients with a history of VT, in 58% of 31 patients with inducible VT, p < 0.01 and in five of six patients with LV dyskinesis. In patients with inducible VT, LP had a higher amplitude (105 ± 35 vs 60 ± 47 µV) and were more delayed (202 ± 96 vs 133 ± 75 msec) than in noninducible patients. In 17 patients, serial drug testing was performed after oral administration using mexilitene, disopyramide, chinidine, propafenone, sotalol, and amiodarone. If one drug was tested, the therapy efficacy was 25% if two drugs-60%, and if three drugs-75%. In eight patients, VT was inducible in all tests, but in only one of these patients chronic antiarrhythmic therapy was not effective. We conclude that the most important predictors of VT inducibility are a history of VT or 24-hour ECG, and LV dyskinesis. Serial drug testing is efficient only when many drugs are tested, but even if VT is inducible, it does not exclude the possibility of a good clinical outcome in chronic therapy.     

Effects of Cimetidine on Sinus Node Function and Atrioventricular Conduction in Man

Electrophysiological effects of H2-receptor blockade 200 mg cimetidine IV on sinus node (SN) function and atrioventricular (AV) conduction were evaluated. Tests were performed in 21 people in basal state (group I), and in 14 people (group II) after autonomic blockade (AB) (propranolol 0.2 mg/kg, and atropine 0.04 mg/kg). We analyzed sinus cycle length (SCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), and secondary pause (SP) as the longest sinus pause after incremental overdrive pacing, sinoatrial conduction time (Strauss method) (SACT), Wenckebach point (WP), and blood pressure (BP). In group I, cimetidine prolonged SCL (717 ± 98 vs 860 ± 138 msec P < 0.001), SNRT (1161 ± 153 vs 1263 ± 163 msec P < 0.002), SP (943 ± 183 vs 1072 ± 187 msec P < 0.001), SACT (121 ± 20 msec vs 149 ± 21 msec P < 0.002), and lowered rate at which AV nodal Wenckebach point were observed (169 ± 24 vs 160 ± 26 beats/min P < 0.02). The drug did not produce significant change of the CSNRT (439 ± 121 vs 402 ± 107 msec. In group II, after AB cimetidine prolonged SCL (643 ± 79 vs 656 ± 86 msec P < 0.05), SP (686 ± 114 vs 717 ± 109 msec P < 0.05) and lowered WP (170 ± 19 vs 166 ± 19 beats/min P < 0.02) significantly. The effects of cimetidine, after AB on SNRT (894 ± 180 vs 920 ± 164 msec, CSNRT (243 ± 99 vs 255 ± 85 msec), SACT (85 ± 20 msec vs 90 ± 22 msec) were not significant. We conclude that H2-receptor blockade decreases SN automatically, prolongs SACT and AV conduction in man. The study suggests that histamine takes part in regulation of electrophysiological properties of the human heart in vivo.     

Predictive Value of Various Types of Ventricular Response to Programmed Ventricular Stimulation: Relation to Holter Monitoring

The study was performed to determine the predictive value of programmed stimulation for identification of pts with ventricular arrhythmias: 75 patients were studied by means of 24-hour ambulatory ECG (24 ECG) and programmed right (in some patients also left) ventricle stimulation at sinus and two or three pacing rates using two (standard) and three extrastimuli or burst stimulation (extensive protocol). Lown classes 0.1–3 and 4a–4h were observed in 24 ECG in 35, 14, and 26 patients, respectively. In programmed stimulation 1–6 repetitive ventricular responses (RVR) were found in 56 pts, nonsustained ventricular tachycardia in 11 and sustained ventricular tachycardia in 21 pts. High incidence of induced VT was found in pts with complex ventricular arrhythmia in 24 ECG, 81% of this group, in all but six pts only standard protocol was used. The 1–6 RVR were observed in almost 40% of pts without any arrhythmia. Conclusion; Only VT induction is a useful index for high risk patients.     

The association of –262C/T polymorphism in the catalase gene and delayed graft function of kidney allografts

Background: Catalase is an intracellular antioxidant enzyme that is mainly located in cellular peroxisomes and in the cytosol. This enzyme plays a significant role in the development of tolerance to oxidative stress in the adaptive response of cells and tissues. The aim of the present study was to examine the association between the –262C/T polymorphism in the catalase gene and delayed graft function (DGF), acute rejection and chronic allograft nephropathy of kidney allografts. Methods: One hundred eighty‐seven recipients of first renal transplants were included in the study. The histories of the patients were analysed regarding DGF, acute rejection and chronic allograft nephropathy. The polymorphism –262C/T in the catalase gene was analysed using the polymerase chain reaction – restriction fragment length polymorphism (PCR‐RFLP) method. Results: The risk of DGF was significantly lower in T allele carriers compared with CC homozygotes: odds ratio = 0.34, 95% confidence interval = 0.17–0.67, P = 0.001. There were no statistically significant associations between the studied polymorphism and acute rejection or chronic allograft nephropathy. Conclusion: The results of this study suggest that –262C/T polymorphism in the catalase gene is associated with DGF in kidney allograft recipients.     

Heart Rate Variability: Its Association with Hemodynamic Function of the Left Ventricle in Patients with Coronary Heart Disease

Patients with heart failure secondary to coronary heart disease (CHD) are characterized by an imbalance of the autonomic nervous system, which can be assessed by analysis of the heart rate variability (HRV). However it is still unclear whether all patients with CHD reveal suppression of HRV and if it is related to hemodynamic function and contractile disturbances of the left ventricle. To answer these questions data from 105 consecutive patients were analyzed and compared with 17 healthy subjects. All study participants underwent 24-hour ambulatory ECG recordings with calculation of HRV parameters and angiographic examination after collection of clinical data and other noninvasive evaluations. Time- (SDRR, SDANN, SD, pNN50) and frequency- (LF, HF) domain parameters of HRV were assessed. All ventriculographic and hemodynamic measurements were used in the analysis. Highly significant correlations were found between all HRV parameters, and left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (P < 0.001). Patients with LVEF < 40% were characterized by significantly lower values of HRV and impairment or lack (LVEF < 20%) of diurnal variation of frequency-domain measurements of HRV. Patients with segmental akinesis or dyskinesis also had lower values of HRV. The group with dyskinesis was characterized by significantly lower diurnal rhythms of LF and HF, independent of LVEF.     

Synthesis of N-(4-aminobenzoyl)-γ-oligo (L-glutamic acid)s*

N-(4-aminobenzoyl)-γ-oligo (l -glutamic acid)s (6) containing from two to six glutamic residues have been prepared in solution using Nα-Boc-α-Bzl protections and isobutyl-chlorocarbonate activation. Key steps in the synthesis were the coupling of γ-oligo(α-benzyl l -glutamate) benzyl esters (1) with N-(4-benzyl-oxycarbonylaminobenzoyl)-l -glutamic acid α-benzyl ester (4) to blocked precursors of N-(4-aminobenzoyl)-γ-oligo (l -glutamic acid)s (5) and catalytic hydrogenolysis of 5 to 6. Elaboration of the required oligo γ-l -glutamate chains (1) was achieved step by step beginning with the coupling of glutamic acid dibenzylester with N-(t-butoxycarbonyl)-l -glutamic acid α-benzyl ester (2) to 3 followed by selective removal of the Boc from 3 with HCl-dioxane followed by coupling with 2.