The impact of gender on in-hospital outcomes after carotid endarterectomy or stenting.

AIM: We sought to better define the impact of sex on 'in-hospital outcomes' after carotid endarterectomy (CEA) or stenting (CAS). METHODS: Hospital discharge databases for all carotid interventions obtained from the New York State (NYS) Department of Health, Statewide Planning and Research Cooperative System between 2000 and 2009 (29,917 women, 39,771 men) were analysed. Mortality, stroke and composite event (stroke/death) were compared between procedures after matching of patients by propensity score. Acute myocardial infarction (AMI) was our secondary 'end' point. RESULTS: More than 90% of patients in both sexes were asymptomatic (27,439 women and 36,295 men). Compared to men, asymptomatic women experienced more strokes after CEA (women: 1.38%, men: 1.16%, P = 0.03) and higher AMI rates after both procedures (CEA; women: 0.75%, men: 0.51%, P = 0.0009, CAS; women: 0.96%, men: 0.28%, P = 0.01). Between procedures, symptomatic women undergoing CAS showed higher rates of mortality (CAS: 4.19%, CEA: 0.47%, P = 0.01) and combined (stroke/mortality) events (CAS: 12.09%, CEA: 6.05%, P = 0.02). In all other cohorts, no statistically significant difference was found between the procedures. CONCLUSIONS: Compared to CEA, CAS led to inferior in-hospital outcomes only in symptomatic women in the last decade in NYS. Men and asymptomatic women showed comparable outcomes after both procedures, whereas asymptomatic females were more prone to AMI after both interventions. These sex-associated differences should be taken into account for the treatment of carotid artery disease.

Long-term electrophysiological effects of regional cardiac sympathetic denervation of the neonatal dog.

OBJECTIVE: In many cardiac arrhythmias, both a triggering factor and a favorable myocardial substrate are required. Whereas the sympathetic nervous system may trigger tachyarrhythmias, its function as a long-term modulator of the myocardial substrate is less well understood. Therefore, we tested the hypothesis that regional sympathetic denervation at birth would produce an abnormal myocardial substrate. The comparator was the substrate associated with inherited, lethal tachyarrhythmias at 5 months of age in German shepherd dogs with incomplete sympathetic innervation. METHODS: Mongrel dogs underwent right cardiac stellectomy (RSX) within the first day of life and were terminally studied with control littermates at 5 months of age. RESULTS: On days 1-21 of life, RSX animals manifested significant QT prolongation on ECG and sudden, asystolic death. Beyond this age, QT intervals normalized and deaths did not occur. At 5 months, action potentials (AP) were recorded from Purkinje fibers (PF) and midmyocardial preparations in anteroseptal (AS) and posterobasal (PB) left ventricle. Early afterdepolarizations occurred only in left ventricular PF from RSX dogs. Isoproterenol prolonged AP duration in AS and shortened it in PB of RSX but not control dogs. The incidence of isoproterenol-initiated triggered activity and the amplitude of delayed afterdepolarizations were greater in RSX than control dogs. CONCLUSION: Five months after RSX heterogeneous alterations of LV electrophysiological properties were similar to those previously observed in animals having inherited deficits in sympathetic innervation and sudden death. This implicates the sympathetic nerves as long-term modulators of an arrhythmogenic substrate. That 5-month-old RSX dogs did not experience tachyarrhythmias or sudden death indicates that further anomalies--beyond those explicable by the substrate change--must exist to induce sudden death.

Impact of sex and gonadal steroids on prolongation of ventricular repolarization and arrhythmias induced by I(K)-blocking drugs.

BACKGROUND: Mechanisms for longer rate-corrected QT intervals and higher incidences of drug-induced torsade de pointes in women than in men are incompletely defined, although gonadal steroids are assumed to be important determinants of these differences. METHODS AND RESULTS: We used microelectrode techniques to study isolated rabbit right ventricular endocardium from control male and female and castrated male (ORCH) and female (OVX) rabbits. Action potential duration to 30% repolarization (APD(30)) was significantly shorter in male than female and in ORCH than OVX at a cycle length of 500 ms. The I(Ks) blocker chromanol 293B had no effect on APD in males or females. The I(Kr) blocker dofetilide prolonged APD in female and ORCH more than in male and OVX. At 10(-)(6) mol/L dofetilide (cycle length=1 second), the incidence of early afterdepolarizations was: female, 67%; ORCH, 56%; male, 40%; and OVX, 28%. Serum 17beta-estradiol levels were unrelated to the effects of dofetilide, but as testosterone levels increased, the dofetilide effect to increase APD diminished, as did early afterdepolarization incidence. CONCLUSIONS: Sex-related differences in basal right ventricular endocardial AP configuration persist in castrated rabbits, suggesting that extragonadal factors contribute to the differences in ventricular repolarization. In this model, drugs that block I(Kr) but not I(Ks) prolong repolarization in a way that suggests that protection from excess prolongation in males is attributable to testosterone, whereas the risk of excess prolongation of repolarization in females is related to sex-determined factors in addition to estrogen.

beta(1) and beta(2)-adrenergic receptor subtype effects in German shepherd dogs with inherited lethal ventricular arrhythmias.

OBJECTIVE: Delayed afterdepolarization-induced triggered activity originating in ventricular myocardium is a mechanism for some age-dependent, inherited ventricular tachycardias in a colony of German shepherd dogs. METHODS: We used standard microelectrode techniques to study beta-adrenergic receptor subtype modulation of the triggered activity in anteroseptal left ventricular myocardium from eleven of these dogs and seven unafflicted, age-matched German shepherd controls. RESULTS: During sustained stimulation at cycle lengths of 300-4000 ms, 10(-9)-10(-7) M isoproterenol concentration-dependently shortened action potential duration (APD) to 90% repolarization more in myocardium from afflicted than from unafflicted dogs. This shortening was prevented by a beta(1)-blocker CGP20712A (10(-7) M) while a beta(2)-blocker ICI118551 (10(-7) M) did not modify the effect of isoproterenol in either group. The beta(2)-agonist zinterol 10(-8)-10(-6) M had no effect on APD. Stimulation at a cycle length of 250 ms in the presence of 10(-7) M isoproterenol induced more triggered AP in myocardium from afflicted than unafflicted dogs. beta(1)-Blockade completely eliminated, while beta(2)-blockade facilitated, and the beta(2)-agonist zinterol did not induce triggered activity in the two groups. CONCLUSION: Isoproterenol effects on APD and triggered activity in the myocardium of dogs with inherited arrhythmias are due primarily to an abnormality of beta(1)-adrenoceptor mediated signaling that is subject to beta(2)-adrenergic modulation.

Effects of mibefradil, a T-type calcium current antagonist, on electrophysiology of Purkinje fibers that survived in the infarcted canine heart.

INTRODUCTION: We studied the effects of mibefradil (MIB), a nondihydropyridine T-type Ca2+ channel antagonist, on T- and L-type Ca2+ (I(CaT), I(CaL)) currents in Purkinje myocytes dispersed from the subendocardium of the left ventricle of normal (NZPC) and 48-hour infarcted (IZPC) hearts. METHODS AND RESULTS: Currents were recorded with Cs+- and EGTA-rich pipettes and in Na+-K+-free external solutions to eliminate overlapping currents. In all cells, I(Ca) was reduced by MIB (0.1 to 10 microM). No change in the time course of decay of peak I(Ca) was noted. Average peak T/L ratio decreased in NZPCs but not IZPCs with 1 microM MIB. Steady-state availability of I(CaL) was altered with 1 microM MIB in both cell types (mean +/- SEM) (V0.5 = -22 +/- 4 mV for NZPC and -25 +/- 5 mV for IZPC before drug; -63 +/- 9 mV for NZPC and -67 +/- 6 mV for IZPC after drug; P < 0.05). For I(CaT), V0.5 (-50 +/- 3 mV for NZPC and -52 +/- 1 mV for IZPC before drug) shifted to -60 +/- 2 mV (NZPC) and -62 +/- 3 mV (IZPC) (P < 0.05) after drug. We also determined the effects of MIB on spontaneously beating Purkinje normal fibers and on depolarized abnormally automatic fibers from the infarcted heart using standard microelectrode techniques. When NZPC and IZPC fibers were superfused with [K+]o = 2.7 mM, MIB 3 microM and 10 microM had no effect on rate or the maximum diastolic potential, but action potential plateau shifted to more negative values, the slope of repolarization phase 3 decreased, and action potential duration increased. CONCLUSION: MIB blocks L- and T-type Ca2+ currents in Purkinje myocytes but lacks an effect on either normal or abnormal automaticity in Purkinje fibers.

Abnormal cardiac repolarization and impulse initiation in German shepherd dogs with inherited ventricular arrhythmias and sudden death.

OBJECTIVE: We tested the hypothesis that delayed afterdepolarization (DAD)-associated rhythms in German shepherd dogs with reduced anteroseptal left ventricular (LV) sympathetic innervation derive from abnormal beta-adrenergic receptor effector coupling. METHODS AND RESULTS: In anteroseptal LV midmyocardium of afflicted dogs, beta-receptor density was greater than that in normal dogs (P < .05), with affinity being equal in both groups. Basal and maximum isoproterenol (ISO) stimulated adenylyl cyclase activity of anteroseptal LV of afflicted dogs was greater than that in normal dogs (P < .05). Isolated anteroseptal M cell preparations of afflicted dogs studied with microelectrodes showed abnormal lengthening, rather than shortening of action potential duration in response to ISO, as well as a 61% incidence of 10(-7) mol/l ISO-induced triggered activity as compared to 12% in normals (P < .05). In contrast, there was no difference between afflicted and control dogs in triggered activity, beta-receptors or adenylyl cyclase activity in a normally innervated region of the ventricles. CONCLUSION: In this model there is an increase in beta-receptor density and beta-adrenergic stimulation of adenylyl cyclase and of triggered activity in anteroseptal myocardium but not in a normally innervated region of the heart. Hence, abnormal beta-adrenergic signal transduction appears associated with the neural abnormality identified in dogs with inherited VT.

Electrophysiological effects of LU111995 on canine hearts: in vivo and in vitro studies.

We studied the electrophysiological effects of LU111995 (1-15 mg/kg p.o.) in conscious dogs with chronic atrioventricular block and ventricular pacing at 50 to 130 beats/min. LU111995 had no effects on idioventricular rhythm, QRS duration, and ventricular conduction time. It significantly prolonged Q-T interval (by 5-8%) and effective refractory period (ERP) (by 5-12%) with the maximal effect at 4 h after a 10 mg/kg dose. At 10 and 15 mg/kg, it increased the ERP/Q-T ratio. In vitro, the effects of LU111995 (1 x 10(-7) to 1 x 10(-5) M) on action potentials of Purkinje fibers (PFs) and M cells were studied at cycle lengths (CL) of 300 to 2000 ms. It had no effects on maximum diastolic potential and action potential amplitude in either tissue. High concentrations induced a moderate, rate-independent decrease of Vmax in M cells. In PFs and M cells, it produced reverse use-dependent lengthening of action potential duration (APD). In PFs at long CL, the drug exhibited a biphasic concentration-dependent effect on APD: maximum prolongation (by 26% at a CL of 2000 ms) was attained at 1 x 10(-6) M, and a decrease of APD occurred at higher concentrations. In M cells, the maximum effect on APD occurred at 3 x 10(-6) M. Early afterdepolarizations were seen in 50% of M cell preparations but only at CL of 2000 ms. Triggered activity did not occur. In summary, LU111995 prolongs the Q-T interval to a limited degree and is not arrhythmogenic over the physiological range of CLs.

Transient outward current, Ito1, is altered in cardiac memory.

BACKGROUND: Cardiac memory refers to an altered T-wave morphology induced by ventricular pacing or arrhythmias that persist for variable intervals after resumption of sinus rhythm. METHODS AND RESULTS: We induced long-term cardiac memory (LTM) in conscious dogs by pacing the ventricles at 120 bpm for 3 weeks. ECGs were recorded daily for 1 hour, during which time pacing was discontinued. At terminal study, the heart was removed and the electrophysiology of left ventricular epicardial myocytes was investigated. Control (C) and LTM ECG did not differ, except for T-wave amplitude, which decreased from 0.12+/-0.18 to -0.34+/-0.21 mV (+/-SEM, P<0.05), and T-wave vector, which shifted from -37+/-12 degrees to -143+/-4 degrees (P<0.05). Epicardial action potentials revealed loss of the notch and lengthening of duration at 20 days (both P<0.05). Calcium-insensitive transient outward current (Ito) was investigated by whole-cell patch clamp. No difference in capacitance was seen in C and LTM myocytes. Ito activated on membrane depolarization to -25+/-1 mV in C and -7+/-1 mV (P<0.05) in LTM myocytes, indicating a positive voltage shift of activation. Ito density was reduced in LTM myocytes, and a decreased mRNA level for Kv4.3 was observed. Recovery of Ito from inactivation was significantly prolonged: it was 531+/-80 ms (n=10) in LTM and 27+/-6 ms (n=9) in C (P<0.05) at -65 mV. CONCLUSIONS: Ito changes are associated with and can provide at least a partial explanation for action-potential and T-wave changes occurring with LTM.

The controversial M cell.

A recent publication by us has been interpreted by some as arguing against the existence and importance of M cells. We suppose this is the reason we have been asked to write this "controversy." Regrettably for the controversy, neither our work nor we deny the existence of M cells. Rather, we have confirmed, conceivably ad nauseum, that M cells do exist and contribute importantly to the expression of electrical activity in the intact myocardium. What controversy there is relates to (1) whether there is an inhomogeneous transmural gradient for ventricular repolarization in normal hearts, and (2) why the electrophysiologic properties of different myocardial sites differ so markedly at the level of the isolated tissue and single cell and yet become so much more homogenous in the intact ventricle. These issues are addressed on the following pages.

Evolution and resolution of long-term cardiac memory.

BACKGROUND: Cardiac memory (CM) refers to T-wave changes induced by ventricular pacing or arrhythmia that accumulate in magnitude and duration with repeated episodes of abnormal activation. We report herein the kinetics of long-term CM and its association with the ventricular action potential. METHODS AND RESULTS: Dogs were paced from the ventricles at rates of 110 to 120 bpm for approximately 3 weeks. CM characterized by gradual sinus rhythm T vector rotation toward the paced QRS vector evolved in all dogs regardless of pacing site (left ventricular [LV] anterior apex or base, posterior LV, or right ventricular free wall). Cardiac hemodynamics and myocardial flow (microsphere studies) were unaltered by the pacing. Recovery time for the memory T wave to return to control increased with duration of the previous pacing. The protein synthesis inhibitor cycloheximide markedly (P<.05) and reproducibly attenuated evolution of CM. When pacing was performed from the atrium, CM did not occur. Standard microelectrode techniques were used to study action potential from the LV free wall of control and CM dogs. CM was associated with increased action potential duration in epicardial and endocardial but not midmyocardial cells, significantly altering the transmyocardial gradient for repolarization. CONCLUSIONS: CM is a dynamic process for which the final T vector is predicted by the paced QRS vector and which is associated with significant changes in epicardial and endocardial but not midmyocardial cell action potential duration, such that the transmural gradient of repolarization is altered. It is unaccompanied by evidence of altered hemodynamics or flow, requires a change in pathway of activation, and appears to require new protein synthesis.

Weak combined magnetic field affects basic and morphine-induced rat's EEG.

The present study was undertaken to find out, whether weak combined magnetic field (CMF) with intensity comparable to that of the Earth's static magnetic field can influence the EEG activity of the rat's brain at normal (non-treated animals) conditions and after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of morphine in experimental animals bearing chronically implanted electrodes and cannules. Most of the experiments were performed using CMF containing co-linear static (20.9 microT) and alternating sinusoidal (20.9 microT, 48 Hz) components, i.e., tuned for Ca2+-resonance. The effects of the field were estimated by comparison of the averaged EEG frequency spectra in the range of frequencies between 0.8-23 Hz in experimental and control animals. Statistically significant effects of CMF were observed both in non-treated and morphine-treated rats. However, the most profound effect-the drastic power reduction at most EEG frequencies-appeared in the animals subjected to the i.p.-injection of morphine. These results show that weak CMF can influence the spontaneous electrical brain activity. The data obtained are consistent with the findings of other groups demonstrating that weak magnetic fields may drastically modify the effects of both exogenous and endogenous opioids on different basic functions in vertebrates and invertebrates. Possible mechanisms for the observed effects are discussed.

Effects of quinidine on repolarization in canine epicardium, midmyocardium, and endocardium: I. In vitro study.

BACKGROUND: The antiarrhythmic action of quinidine is associated with a slowing of conduction and prolongation of repolarization. The latter effect has no consistent correlation with quinidine actions on action potential duration (APD) in isolated tissue experiments. To enhance our understanding of the mechanisms of quinidine action, we studied its effect on APD in canine epicardial, midmyocardial, and endocardial tissues. METHODS AND RESULTS: Standard microelectrode techniques were used to study the effects of quinidine 2.5 to 20 micromol/L on APD in ventricular epicardial, endocardial, and transmural (M-cell) slabs at cycle lengths (CLs) from 300 to 4000 ms. Qualitatively different time courses of actions and concentration- and rate-dependent effects were seen in M cells compared with the others. In endocardium and epicardium, quinidine induced monotonic and concentration-dependent APD prolongation at all CLs. In contrast, the effects of quinidine in M cells varied from prolongation to shortening, depending on duration of superfusion, concentration, and CL. Experiments with E4031 and TTX suggested that in M cells, quinidine-induced APD lengthening was attributable to block of delayed rectifier potassium current and APD shortening was due to inhibition of TTX-sensitive steady-state sodium current. CONCLUSIONS: In vitro, there is a significant difference of quinidine effects in M cells versus epicardial and endocardial cells that appears to reflect differences in the contributions of specific ion channels to the APD at the three sites. The differences may influence the actions of quinidine on repolarization of the heart in situ and determine both the proarrhythmic and antiarrhythmic actions of the drug.

Effects of quinidine on repolarization in canine epicardium, midmyocardium, and endocardium: II. In vivo study.

BACKGROUND: In the companion article, we report a significant difference in quinidine effects on the action potential duration between surface (epicardial and endocardial) cells and midmyocardial cells (M cells) of canine left ventricle in vitro. This article considers two questions raised by the previous study: (1) Are the complex quinidine effects in vitro reflected in its actions on the heart in situ? (2) What are the cellular determinants of quinidine effects on QT interval in ECG? METHODS AND RESULTS: We used plunge and surface electrodes to measure activation-recovery intervals (ARIs) of bipolar electrograms obtained from epicardium, endocardium, and midmyocardium (3, 5, and 9 mm from epicardium) of canine left ventricle in conditions of AV block and right ventricular pacing. Quinidine was infused continuously; its plasma level increased from 1.6+/-0.1 microg/mL at 30 minutes to 7.6+/-0.7 microg/mL at 180 minutes. At cycle lengths (CLs) from 300 to 1500 ms, there was no ARI gradient across the ventricular wall before and during quinidine infusion. At a CL of 300 ms, therapeutic concentrations of quinidine prolonged ARIs and QT intervals. At a CL of 1500 ms, ARIs were significantly prolonged at low quinidine concentrations. With an increase of quinidine concentration, this effect subsided and disappeared. CONCLUSIONS: In situ, quinidine-induced prolongation of repolarization is uniform in all myocardial layers and follows the pattern observed in M cells in vitro. The ability of quinidine in therapeutic concentrations to prolong repolarization at rapid heart rates can contribute to its antiarrhythmic efficacy.

Electrophysiologic effects of nibentan (HE-11) on canine cardiac tissue.

We studied the effects of nibentan on transmembrane action potentials of canine Purkinje fibers (PF), ventricular epicardial and endocardial tissues and atrial tissue. Nibentan (1 x 10(-8) to 5 x 10(-6) M) had no effects on maximum diastolic potential of all tissues and produced a modest concentration- and use-dependent decrease in V(max). However, a remarkable tissue specificity was observed in its effects on action potential duration (APD). In PF, the concentration-dependent effect was biphasic: maximum APD prolongation was attained at 10(-7) M, and a decrease in APD was seen at higher concentrations. In contrast, in ventricular tissue, nibentan prolonged APD monotonically to a steady state at 10(-6) M. In atrial tissue, a monotonic, concentration-dependent increase in APD was observed through the highest concentration. The ability of nibentan to prolong PF APD significantly diminished as the cycle length shortened (from 2000 to 300 ms), whereas in ventricular and atrial tissues, it showed no reverse use-dependence. In the physiological range of cycle length, nibentan did not enhance the spatial inhomogeneity of repolarization. In PF, it prolonged APD, slightly inhibited V(max) of Ca++-induced action potentials and completely eliminated the effects of isoproterenol on normal automaticity. We conclude that 1) nibentan is an antiarrhythmic with a profound ability to prolong repolarization while decreasing heterogeneity of repolarization and 2) the extent of nibentan's APD prolongation effect is significantly different in different cardiac tissues.

Regional differences in electrophysiological properties of epicardium, midmyocardium, and endocardium. In vitro and in vivo correlations.

BACKGROUND: Microelectrode studies have described a population of cells within the midmyocardium (M cells) displaying a steep rate dependence of action potential duration (APD) and high Vmax compared with endocardial (Endo) and epicardial (Epi) cells. METHODS AND RESULTS: We studied repolarization in different myocardial layers in vitro and in situ. In addition to confirming the results of earlier studies, we found that after abrupt lengthening of the cycle length (CL), APDs in M cells reached a new steady state faster than in Epi or Endo cells: the time to achieve 90% of the difference in APD (t90) was 13.3 +/- 0.7 minutes in Endo cells, 12.8 +/- 1.1 minutes in Epi cells, and 2.6 +/- 0.4 minutes in M cells (P < .05 compared with Epi or Endo) when CL changed from 400 to 1000 ms. In situ, we registered activation-recovery intervals (ARIs) in bipolar electrograms obtained from different myocardial layers in conditions of AV block and His-bundle pacing. At all CLs from 300 to 2000 ms, ARIs were equal in all myocardial layers from Epi to Endo cells. Steady-state ARIs coincided with APD of M cells registered in vitro in the physiological range of CL from 300 to 700 ms. When CL was changed from 300 to 1000 ms, the ARI followed the rapid time course typical of M cells (t90 = 2.6 +/- 0.5, 2.2 +/- 0.4, 2.5 +/- 0.4, 2.6 +/- 0.5, and 2.3 +/- 0.4 minutes for Epi; 3-, 5-, and 7-mm sub-Epi; and Endo cells, respectively). CONCLUSIONS: In contrast to in vitro results, there is no significant difference in repolarization among myocardial layers in the intact normal canine heart.

Chronic in vivo and in vitro effects of amiodarone on guinea pig hearts.

To study the electrophysiologic effects of chronically administered amiodarone and its interaction with an I(Kr) blocker, amiodarone was injected i.p. daily for 7 days into male guinea pigs. Control animals received vehicle only. At 80 mg/kg, RR and rate corrected QT (QT(C)) intervals increased after 4 days from 209 +/- 5 ms and 162 +/- 3 respectively to 285 +/- 13 ms and 176 +/- 3 (P < .05, n = 10), respectively, and remained significantly high on the 8th day (256 +/- 14 ms and 173 +/- 4). Neither RR nor QT(C) intervals changed significantly in control animals. Twenty-four hours after the last injection, papillary muscles were isolated from both ventricles and superfused with Tyrode's solution not containing amiodarone. The preparations from amiodarone-treated animals manifested a statistically significant prolongation of action potential duration (APD) at all pacing cycle lengths (CL) (from 300 to 1500 ms). The amiodarone-induced increase of APD diminished with elevation of potassium concentration ([K+]O). Amiodarone did not modify the dependence of Vmax on membrane potential at different [K+]O. There was minimal to no summation of effects of chronic amiodarone and acute super-fusion of the I(Kr) blocker, E-4031 (3 x 10(-6) M) on APD at CL = 1500 ms. The data demonstrate that in chronically treated guinea pigs, amiodarone prolongs repolarization, manifests minimum reverse use-dependent in APD prolongation, and, at low pacing rate, shows no additive actions with an acutely superfused blocker of I(Kr).

Effects of exogenous neuropeptide Y on automaticity of isolated Purkinje fibers and atrium.

Neuropeptide Y exerts prejunctional effects on automaticity in cardiac pacemaker tissue and postjunctional effects on contractile activity of cardiomyocytes. It is uncertain whether neuropeptide Y has postjunctional effects on cardiac automaticity. This paper reports a study of the actions of exogenous neuropeptide Y (10(-10)-10(-6) M) on automaticity of isolated preparations of canine Purkinje fibers and guinea-pig right atrium. Neuropeptide Y had no effect on the rate of normal and abnormal (barium-induced) automaticity and did not modify the effect of norepinephrine on canine Purkinje fibers. Neuropeptide Y did not affect normal sinus rhythm in guinea-pig right atrium. The influence of neuropeptide Y (5 x 10(-7) M) on the response to field stimulation in guinea-pig right atrium was also studied: neuropeptide Y reduced the vagal component of response three-fold (P < 0.05) and insignificantly diminished the sympathetic component. Neuropeptide Y fragment 18-36 suppressed the vagal effect of neuropeptide Y by approximately 50% (P < 0.05). These results suggest that neuropeptide Y does not influence automaticity directly in canine Purkinje fibers and guinea-pig right atria. A prejunctional action to inhibit release of acetylcholine from parasympathetic nerve endings is implied by experiments on field-stimulated right atrium, but based on results with fragment 18-36, postjunctional actions may also occur here.

[The effect of a combination of N-propylajmaline bromide and trimecaine on heart arrhythmias of different origins and on the electrophysiological parameters of the myocardium]. / Vliianie kombinatsii N-propilaimalinbromida i trimekaina na aritmii serdtsa raznogo geneza i élektrofiziologicheskie parametry miokarda.

In experiments on dogs and cats with disorders of the atrial and ventricular rhythms of various genesis the combination of N-propylaymalinebromide and trimecaine (the antiarrhythmic drugs of classes IA and IB) was found to potentiate the antiarrhythmic action. This effect was studied in electrophysiological experiments by using the microelectrode technique or on the dog and rat myocardium tissue. The combination of the antiarrhythmic drugs was shown to exert a more significant effect on some electrophysiological parameters determining the arrhythmic readiness of the myocardium.