Termination of atrial flutter by directed transesophageal atrial pacing during transesophageal echocardiography.

INTRODUCTION: The purpose of this study was to evaluate termination of atrial flutter (AFL) by directed rapid transesophageal atrial pacing (TAP) with and without simultaneous transesophageal echocardiography (TEE) performed using a novel TEE tube electrode. MATERIALS AND METHODS, AND RESULTS: A total of 16 AFL patients (age 63+/-12 years; 13 males) with mean AFL cycle length of 224+/-24 ms (n=12) and mean ventricular cycle length of 448+/-47 ms (n=12) were analyzed using either an esophageal TO electrode (n=10) or a novel TEE tube electrode consisting of a tube with four hemispherical electrodes that is pulled over the echo probe (n=6). AFL could be terminated by directed rapid TAP using an esophageal TO electrode, leading to induction of atrial fibrillation (AF) (n=6), induction of AF and spontaneous conversion to sinus rhythm (SR) (n=3), and with conversion to SR (n=1). AFL could also be terminated by directed rapid TAP using the TEE tube electrode, with induction of AF (n=3) or induction of AF and spontaneous conversion to SR (n=3). CONCLUSION: AFL can be terminated by directed rapid TAP with hemispherical electrodes with and without simultaneous TEE. TAP with the directed TEE tube electrode is a safe, simple, and useful method for terminating AFL.     

Transesophageal left ventricular posterior wall potential in heart failure patients with biventricular pacing.

INTRODUCTION: Biventricular (BV) pacing is an established therapy for heart failure (HF) patients with intraventricular conduction delay, but not all patients improved clinically. We investigated the interventricular delay (IVD) by means of the transesophageal left ventricular posterior wall potential (LVPWP). MATERIALS AND METHODS, AND RESULTS: A total of 18 HF patients (age 62+/-9 years; 15 males) with NYHA class 3.1+/-0.3, LV ejection fraction 22+/-7%, left bundle branch block and a QRS duration (QRSD) of 171+/-27 ms were analyzed using transesophageal LVPWP before implantation of a BV pacing device. The median follow up was 14+/-14 months. In 14 responders, IVD was 81+/-25 ms with a QRSD/IVD ratio of 2.2+/-0.3 with reclassification of NYHA class 3.1+/-0.3 to 2.0+/-0.5 (p<0.001) and an increase in LV ejection fraction from 22+/-7% to 36+/-11% (p=0.001) during long-term BV pacing. In four non-responders, transesophageal IVD was significantly smaller at 30+/-11 ms (p=0.001). CONCLUSION: Transesophageal IVD may be a useful method to detect responders to BV pacing. Transesophageal LVPWP may be a simple and useful technique to detect clinical responders to BV pacing in HF patients.     

Fast pacing facilitates discontinuous action potential propagation between rabbit atrial cells

We examined the critical coupling conductance (G(C)) for propagation at different pacing cycle lengths (CLs) (1,000 and 400 ms). As G(C) was progressively reduced, propagation failed at a CL of 1,000 ms, whereas propagation succeeded at a CL of 400 ms over a range of G(C) values before failing at a CL of 400 ms at a lower G(C), showing facilitation of propagation at the shorter CL. Critical G(C) was (means +/- SE) 0.8 +/- 0.1 nS for a CL of 400 ms and 1.3 +/- 0.1 nS for a CL of 1,000 ms (a 63% increase, P < 0.002, n = 9 cell pairs). In 14 uncoupled cells, action potential duration at 30% repolarization (APD(30)) increased from 19.9 +/- 2.5 to 41.8 +/- 2.6 ms (P < 0.001) as CL decreased from 1,000 to 400 ms. In five cell pairs, critical G(C) with 4-aminopyridine (4-AP) was reduced to 0.4 +/- 0.1 nS at a CL of 1,000 ms (P < 0.05 compared with control solution), and critical G(C) in 4-AP was unchanged by decreasing CL to 400 ms. It is possible that the "remodeling" of atrial cells due to atrial fibrillation or tachycardia, which has been shown to produce a decrease in the transient outward current, may result in an enhanced ability to propagate, possibly facilitating further development of fibrillation under conditions of decreased cellular coupling.     

Rate-dependent [K+](o) accumulation in canine right atria in vivo: electrophysiological consequences

Sudden increases in heart rate cause accumulation of K+ in the extracellular space. However, the exact relationship between rate and extracellular K+ concentration ([K+](o)) in vivo is unknown. We measured [K+](o) in right atria of anesthetized dogs by using K(+)-sensitive electrodes. Peak increase in [K+](o) ranged from 0.18 +/- 0.04 mM [means +/- SE; cycle length (CL) = 350 ms] to 0.80 +/- 0.09 mM (CL = 250 ms) above baseline (3.50 +/- 0.08 mM at CL = 380 ms; n = 5). During rapid pacing-induced atrial fibrillation, peak increase in [K+](o) averaged 0.80 +/- 0.07 mM (n = 5). Whole cell current-clamp measurements in single right atrial myocytes (n = 5) showed that raising [K+](o) from 3 to 5 mM in 1-mM steps progressively depolarized resting membrane potential and reduced both phase 0 action potential amplitude and maximal upstroke velocity. Multisite epicardial mapping (n = 4) demonstrated that sudden rate increases changed longitudinal conduction velocity (CV(L)) by -3.6 +/- 1.8% to -5.9 +/- 1.2% over a CL range of 330 to 250 ms. Our observations suggest that rate-related [K+](o) accumulation in vivo is of sufficient magnitude to modulate those cellular electrophysiological properties that determine atrial CV(L).     

Chronic nicotine in hearts with healed ventricular myocardial infarction promotes atrial flutter that resembles typical human atrial flutter

The potential of chronic nicotine exposure for atrial fibrillation (AF) and atrial flutter (AFL) in hearts with and without chronic myocardial infarction (MI) remains poorly explored. MI was created in dogs by permanent occlusion of the left anterior descending coronary artery, and dogs were administered nicotine (5 mg.kg(-1).day(-1) sc) for 1 mo using osmotic minipumps. High-resolution epicardial (1,792 bipolar electrodes) and endocardial Halo catheters were used to map activation during induced atrial rhythms. Nicotine promoted inducible sustained AFL at a mean cycle length of 134 +/- 10 ms in all MI dogs (n = 6) requiring pacing and electrical shocks for termination. No AFL could be induced in MI dogs (n = 6), control (non-MI) dogs (n = 3) not exposed to nicotine, and dogs with no MI and exposed to nicotine (n = 3). Activation maps during AFL showed a single reentrant wavefront in the right atrium that rotated either clockwise (60%) or counterclockwise (40%) around the crista terminalis and through the isthmus. Ablation of the isthmus prevented the induction of AFL. Nicotine caused a significant (P < 0.01) but highly heterogeneous increase in atrial interstitial fibrosis (2- to 10-fold increase in left and right atria, respectively) in the MI group but only a 2-fold increase in the right atrium in the non-MI group. Nicotine also flattened (P < 0.05) the slope of the epicardial monophasic action potential duration (electrical restitution) curve of both atria in the MI but not in non-MI dogs. Two-dimensional simulation in an excitable matrix containing an isthmus and nicotine's restitutional and reduced gap junctional coupling (fibrosis) parameters replicated the experiments. Chronic nicotine in hearts with MI promotes AFL that closely resembles typical human AFL. Increased atrial interstitial fibrosis and flattened electrical restitution are important substrates for the AFL.     

Effects of reduced PO2 on rapid-drive-induced hyperpolarization of diastolic transmembrane potential in feline cardiac Purkinje strands

Using standard microelectrode techniques, we evaluated effects of diminished oxygen tension on the magnitude and time course of frequency dependent changes in maximum diastolic transmembrane potential (MDP) and on alteration of action potential duration (APD) in feline Purkinje fibers. MDP was recorded continuously during a control period (cycle length (CL) = 1000 ms), during a 5-min period of rapid drive (CL = 400 ms) and following return to pacing CL = 1000 ms. Rapid drive resulted in hyperpolarization of MDP from control value; and after return to pacing CL = 1000 ms. MDP gradually depolarized, eventually attaining a steady state value within +/- 0.5 mV of the control value. The difference between hyperpolarized MDP value and final steady-state value was designated VH, and the decline of MDP towards steady-state value approximated an exponential function (time constant = tau VH). Exposure to reduced PO2 (75 +/- 2.1 mmHg vs. control 473 +/- 39.1 mmHg) (1 mmHg = 133.322 Pa) resulted in reduction in the magnitude of VH (6.2 +/- 3.43 mV vs. 7.8 +/- 2.73 mV, mean +/- SD, p less than 0.005) and shortening of APD within 0-24 min, while measurable prolongation of tau VH (75 +/- 18.5 vs. 54 +/- 9.0 s, p less than 0.005) began at 25-49 min following onset of reduced PO2. These observations suggest that rate-related changes of MDP in cardiac tissues are oxygen dependent, and they support previously reported analagous observations in nerve which suggested that frequency dependent potential changes may in part reflect alterations of electrogenic Na-K pump activity.     

Calcium mobilization as the endothelium-independent mechanism of action involved in the vasorelaxant response induced by the aqueous fraction of the ethanol extract of Albizia inopinata G. P. Lewis (AFL) in the rat aorta.

In a previous work, we demonstrated that, in normotensive rats, AFL induced a marked hypotension due to a decrease in total peripheral resistances (TPR), partially secondary to the release of NO by the endothelium. NO did not, however, account for the total vasodilation produced by AFL in these rats. The aim of this study was to determine the involvement of the intracellular calcium mobilization in the vasorelaxant action induced by AFL in the rat aorta. In aorta of normotensive rats AFL (10, 20, 40 and 80 microg/ml) inhibited the sustained contractions induced by KCl (80 and 30 mM) and phenylephrine (Phe, 1 microM) with similar IC50 values (54 +/- 6, 52 +/- 4 and 65 +/- 4 microg/ml, respectively). The relaxing response induced by AFL against Phe-induced contractions was modified significantly by the endothelium removal (IC50 = 132 +/- 23 and 65 +/- 4 microg/ml, endothelium removed and intact endothelium aortic rings, respectively). Nevertheless, removal of the endothelium did not significantly change IC50 values when KCl (30 and 80 mM) was used as the contractile agent. The inhibitory effect induced by AFL on high (64.5 mM) K+-induced contraction was potentiated slightly (p < 0.05) by the decrease (from 2.5 to 0.3 mM, Ca2+) and attenuated by the increase (from 2.5 to 7.5 mM Ca2+) in the external [Ca2+]. In addition, in aortas from normotensive rats, AFL antagonized transient contractions induced in Ca2+-free media induced by 1 microM noradrenaline in a concentration-dependent manner, but not those induced by 20 mM caffeine. It is suggested that the remaining vasodilator effect of AFL in normotensive rats is probably due to an inhibition of Ca2+ influx and/or inhibition of intracellular Ca2+ mobilization from the noradrenaline-sensitive stores.     

Effect of beta-adrenergic blockade on dynamic electrical restitution in vivo

The slope of the action potential duration (APD) restitution curve may be a significant determinant of the propensity to develop ventricular fibrillation, with steeper slopes associated with a more arrhythmogenic substrate. We hypothesized that one mechanism by which beta-blockers reduce sudden cardiac death is by flattening the APD restitution curve. Therefore, we investigated whether infusion of esmolol modulates the APD restitution curve in vivo. In 10 Yorkshire pigs, dynamic APD restitution curves were determined from measurements of APD at 90% repolarization with a monophasic action potential catheter positioned against the right ventricular septum during right ventricular apical pacing in the basal state and during infusion of esmolol. APD restitution curves were fitted to the three-parameter (a, b, c) exponential equation, APD = a.[1 - e((-b.DI))] + c, where DI is the diastolic interval. Esmolol decreased the maximal APD slope, 0.68 +/- 0.14 vs. 0.94 +/- 0.24 (baseline), P = 0.002, and flattened the APD restitution curve at shorter DIs, 75 and 100 ms (P < 0.05). To compare the slopes of the APD restitution curves at similar steady states, slopes were also computed at points of intersection between the restitution curve and the lines representing pacing at a fixed cycle length (CL) of 200, 225, 250, 275, and 300 ms using the relationship CL = APD + DI. Esmolol decreased APD restitution slopes at CLs 200-275 ms (P < 0.05). Esmolol flattens the cardiac APD restitution curve in vivo, particularly at shorter CLs and DIs. This may represent a novel mechanism by which beta-blockers prevent sudden cardiac death.     

Electrically evoked isometric and isokinetic properties of the triceps surae in young male subjects

The relationship between electrically evoked isometric and isokinetic properties of the triceps surae have been studied in 11 healthy male subjects. The results showed that the time to peak tension (TPT) and half relaxation time (1/2 RT) of the maximal twitch were 110 +/- 11 ms and 82 +/- 11 ms respectively, and the peak rates of rise of contraction (delta P50, delta P200) and relaxation (delta PR50, delta PR200) at 50 and 200 Hz were 0.36 +/- 0.07, 0.48 +/- 0.08 and 1.27 +/- 0.33, 1.25 +/- 0.27% Po ms-1 respectively. The decline in force during a fatigue test was significantly (P less than 0.02) associated with the decrease in maximal relaxation rate (r = 0.79). The TPT was significantly (P less than 0.05) and inversely related to delta P50 and delta P200. The mean angle specific torque-velocity relationship for the 11 subjects was adequately described by the empirical exponential equation of the form: V = 16.5 (e-P/30.8-e-84.3/30.8) where V = velocity (rads s-1) and P = torque (Nm). The only significant association found between the isometric and isokinetic properties of the muscle was between delta PR200 and the torque expressed at a given velocity of 4 rads s-1. This lack of association between the two variables is difficult to explain with certainty but it is suggested that it may be due to the differential effects of Ca2+ release and uptake and cross-bridge turnover rate in the two situations.     

Phospholipid scramblase-3 regulates cardiolipin de novo biosynthesis and its resynthesis in growing HeLa cells

PLS3 (phospholipid scramblase-3) is a new member of the family of phospholipid scramblases and transports CL (cardiolipin) from the inner to the outer mitochondrial membrane. In the present paper we examined whether changing the levels of functional PLS3 in HeLa cells altered de novo CL biosynthesis and its resynthesis. HeLa cells overexpressing PLS3 or expressing a disrupted PLS3 (F258V) or control were incubated with [1,3-3H]glycerol and radioactivity incorporated into CL was determined. CL biosynthesis from [1,3-3H]glycerol was increased 1.8-fold in PLS3 cells and 2.1-fold in F258V cells compared with control. This was due to a 64% (P<0.05) and 2.6-fold (P<0.05) elevation in CL synthase activity in PLS3 and F258V cells respectively, compared with control, and not due to changes in phosphatidylglycerolphosphate synthase activity. The increase in CL synthase activity in these cells was due to an increase in its mRNA expression. In contrast, resynthesis of CL from [1-14C]linoleic acid was reduced 52% (P<0.05) in PLS3 and 45% (P<0.05) in F258V cells compared with control and this was due to a reduction in mitochondrial monolysocardiolipin acyltransferase activity. Although protein levels of mitochondrial monolysocardiolipin acyltransferase were unaltered, activity and mRNA expression of endoplasmic reticulum monolysocardiolipin acyltransferase was upregulated in PLS3 and F258V cells compared with controls. These data indicate that the CL resynthesis in HeLa cells is sensitive to the mitochondrial localization of CL and not the level of the reacylating enzymes. Alterations in functional PLS3 levels in PLS3 or F258V cells did not affect the mitochondrial decarboxylation of phosphatidylserine to phosphatidylethanolamine indicating that the biosynthetic changes to CL were specific for this mitochondrial phospholipid. We hypothesize that the cardiolipin resynthesis machinery in the cell 'senses' altered levels of CL on mitochondrial membranes and that de novo CL biosynthesis is up-regulated in HeLa cells as a compensatory mechanism in response to altered movement of mitochondrial CL. The results identify PLS3 as a novel regulator of CL de novo biosynthesis and its resynthesis.     

Effect of near physiologic insulin therapy on hypoglycemia counterregulation in type-1 diabetes

OBJECTIVES: The aim of this study was to examine hormonal counterregulation during insulin-induced hypoglycemia in type-1 diabetic patients during long-term near normoglycemic insulin therapy and intensive clinical care. METHODS: Type-1 diabetic patients (age 35.3 +/- 2 years, body mass index 22.8 +/- 1 kg x m(-2), mean diabetes duration 13.6 (11-17 years), mean HbA1c during the last year 6.6 +/- 0.1%) and nondiabetic subjects were studied during (0-120 min) and after (120-240 min) hypoglycemic (3.05 mmol/l) hyperinsulinemic (approximately 330 pmol/l) clamp tests. RESULTS: During hypoglycemia peak plasma concentrations of glucagon (199 +/- 16 vs. 155 +/- 11 ng/l, p < 0.05), epinephrine (4,514 +/- 644 vs. 1,676 +/- 513 pmol/l, p < 0.001), norepinephrine (2.21 +/- 0.14 vs. 1.35 +/- 0.19 nmol/l, p < 0.01) and cortisol (532 +/- 44 vs. 334 +/- 61 nmol/l) were reduced in the diabetic patients. Plasma lactate did not change from baseline values (0.51 +/- 0.06 mmol/l) in diabetic but doubled in healthy subjects (1.13 +/- 0.111 mmol/l, p < 0.001 vs. control). During the posthypoglycemic recovery period plasma concentrations of free fatty acids were higher in diabetic patients at 240 min (1.34 +/- 0.12 vs. 2.01 +/- 0.23 mmol/l, p < 0.05). CONCLUSION: Despite long-term near physiologic insulin substitution and the low incidence of hypoglycemia, hormonal hypoglycemia counterregulation was impaired in type-1 diabetic patients after a diabetes duration of more than 10 years.     

The influence of the corpus luteum on ovarian follicular dynamics during estrous synchronization in goats

Ovarian follicular dynamics and fertility are unaffected by the presence or absence of a corpus luteum during synchronization of estrus with progestins in goats. On day 5 of the estrous cycle (estrus= day 0), a gestagen-containing sponge was inserted in the vagina for 11 days. To remove corpora lutea, one group of goats (CL-, n=41) received 7.5 mg of luprostiol on days 7 and 8 of the estrous cycle. The second group of goats retained the CL (CL+, n=38). Growth and development of follicles > or =4 mm in diameter were measured daily from onset of estrus to 2 days after subsequent ovulation in seven goats from each group, using rectal ultrasonography. Estrus was detected by the use of a reproductively sterilized buck and estrous does were subsequently mated. The number of waves of follicular development (CL- =3.57+/-0.2 versus CL+ =3.14+/-0.14; P>0.05) did not differ between groups. The second wave of follicular development was present at the time of progesterone decline in the CL- group and neither its duration (CL- =4.8+/-0.4 versus CL+=5.6+/-0.7 days; P>0.05) nor the day of commencement of the third wave of follicular development (CL -=11.6+/-0.7 versus CL+=11.8+/-0.6; P>0.05) were altered by the concentration of endogenous progesterone. The pregnancy rate was similar between the two groups. (CL-=68.29% versus CL+=65.79%; P>0.05). Thus, in goats, ovarian follicular dynamics and fertility were not altered by the presence or absence of a corpus luteum during estrous synchronization.     

Comparison of the effect of natural mating, LH, and GnRH on interval to ovulation and luteal function in llamas

Gonadotropins and GnRH have been used to electively induce ovulation in llamas and alpacas, but critical evaluation of the natural interval to ovulation after mating has not been performed nor has a direct comparison of the effects of natural mating versus hormone treatments on this interval and subsequent luteal development. The objectives of this study were to compare the effects of hormonal treatments and natural mating on ovulation induction, interval to ovulation, and luteal development in llamas. The ovaries of llamas were examined by transrectal ultrasonography once daily. Llamas with a large follicle were assigned randomly to be: (1) mated with an intact male (mated; n=10); (2) given 5 mg of LH im (LH; n=11); or (3) 50 microg of GnRH im (GnRH; n=10). Ultrasound examinations were performed every 4h from treatment (day 0) to ovulation and thereafter once daily for 15 consecutive days to monitor CL growth and regression (n=5 per group). Plasma progesterone concentrations were measured at days 0, 3, 6, 9, and 12 after treatment to evaluate CL function. The size of the largest preovulatory follicle at the time of treatment did not differ among groups (11+/-0.6, 10.5+/-0.8, 11.8+/-0.9 mm, for mated, LH, and GnRH groups, respectively; P=0.6). No differences were detected among groups (mated, LH, and GnRH) in ovulation rate (80%, 91%, 80%, respectively; P=0.6), or interval from treatment to ovulation (30.0+/-0.5, 29.3+/-0.6, 29.3+/-0.7h, respectively; P=0.9). Similarly, no differences were detected among groups (mated, LH, and GnRH) in maximum CL diameter (14.2+/-0.3, 13.2+/-0.5, and 13.0+/-0.7 mm, respectively; P=0.5), the day of maximum CL diameter (7.6+/-0.2, 7.6+/-0.2, and 7.4+/-0.4 mm, respectively; P=0.6), or the day on which the CL began to regress (12.3+/-0.3 [non-pregnant, n=3], 11.8+/-0.6, 12.2+/-0.4, respectively; P=0.4). The diameter of the CL and plasma progesterone concentrations changed over days (P<0.0001) but the profiles did not differ among groups. In summary, ovulation rate, interval to ovulation, and luteal development were similar among llamas that were mated naturally or treated with LH or GnRH. We conclude that both hormonal preparations are equally reliable for inducing ovulation and suitable for synchronization for artificial insemination or embryo transfer program.     

去甲肾上腺素、乙酰胆碱对绵羊心肌浦肯野纤维瞬时性内向离子流的影响

用电压箝制术观察了去甲肾上腺素、乙酰胆碱对绵羊浦肯野纤维由乙酰毒毛旋花子甙元诱发的瞬时性内向离子流(I_Ti)的效应。当乙酰毒毛旋花子甙元浓度为4.5×10~(-8)mol/L 时,诱发出的I_(T1)稳定并能维持约1.5h。去甲肾上腺素1.5×10~(-6)mol/L,可使I_(Ti)的峰值由11.4±2.5nA 增加到14.5±4.1nA(n=11,P相似文献   

Echocardiographic and cardiac single photon emission computed tomography predictors of left ventricle reverse remodeling after surgical revascularization in patients with ischemic cardiomyopathy and left ventricle systolic dysfunction

Background: The extent of scar or viable hypocontractile myocardial tissue determines postinfarction left ventricle remodeling. The aim of this pilot study was to evaluate the revascularization effect in a group of patients with ischemic cardiomyopathy and LV systolic dysfunction indicated for surgical revascularization, based on evidence for multivessel disease on coronarography and viable myocardium (CMR, SPECT). Aims: To evaluate the revascularization effect in patients with ischemic LV systolic dysfunction and to find preoperative predictors of revascularization effect. Methods: 33 patients (64+/-11 years) with baseline LVEF 34.9+/-9.3 % were included in the study. After a follow-up of 10.7+/-1.2 months, ECHO and SPECT were performed again. The whole group of patients was divided according to revascularization effect (postoperative increase LVEF > 5 % and postoperative decrease LVESV > 5 % compared with baseline) into revascularization responders (R, n = 22) and nonresponders (NR, n = 11). Results: At baseline there was no difference between the subgroups in LVEF (R = 35.7+/-11.0 % vs. NR = 34.3+/-8.2 %), EDV (R = 183.6+/-43.2 vs. NR = 180.2+/-80.5 ml), ESV (R = 118.5+/-40.4 vs. NR = 119.7+/-55.2 ml). The responders showed in a revascularization effect subanalysis differences in the values of LVEF (+9.8+/-8.1 %, p < 0.009), reduction of EDV (-39.9+/-50.9 ml, p = 0.05) and ESV (-35.4+/-42.6 ml, p = 0,002) compared with baseline. The only preoperative parameters predicting LV reverse remodeling were the T(E-Em) (R = -10.6+/-44.1 vs. NR = 29.7+/-43.7 ms, p = 0.037) and the size of fixed perfusion defect (FPD) (R = 11.9+/-13.5 vs. NR = 22.9+/-15.3 % of LV, p = 0.044). Conclusions: Patients with ischemic LV systolic dysfunction with a preoperatively determined myocardial viability develop LV reverse remodeling. The only preoperative parameters predicting LV reverse remodeling were echocardiographic T(E-Em) and FPD on SPECT.     

Contributions of heart rate and contractility to myocardial oxygen balance during exercise

The respective contributions of heart rate (HR) reduction and left ventricular (LV) negative inotropy to the effects of antianginal drugs are debated. Accordingly, eight instrumented dogs were investigated during exercise at spontaneous and paced HR (250 beats/min) after administration of either saline, atenolol, or ivabradine (selective pacemaker current channel blocker). During exercise, atenolol and ivabradine (both 1 mg/kg iv) similarly reduced HR (-30% from 222 +/- 5 beats/min), and LV mean ejection wall stress was not altered. LV dP/dt(max) was reduced by atenolol but not ivabradine. Diastolic time (DT) was increased by atenolol versus saline (195 +/- 6 vs. 123 +/- 4 ms, respectively) and to a greater extent by ivabradine (233 +/- 11 ms). Myocardial oxygen consumption (MVo(2)) was lower under ivabradine and atenolol versus saline (6.7 +/- 0.6 and 4.7 +/- 0.4 vs. 8.1 +/- 0.6 ml/min, respectively, P < 0.05). Under pacing, DT and MVo(2) were similar between ivabradine and saline but significantly reduced with atenolol. Thus HR reduction and negative inotropy equally contribute to the reduction in MVo(2) during exercise in the normal heart. The negative inotropy limits the increase in DT afforded by HR reduction.     

Risk and Outcome after Ablation of Isthmus-Dependent Atrial Flutter in Elderly Patients

MethodsA total of 1187 patients with a mean age 65±12 years consecutively referred for AFL ablation were retrospectively analyzed in the study.Results445 (37.5%) patients were aged ≥70 (range 70 to 93) among which 345 were aged 70 to 79 years (29.1%) and 100 were aged ≥80 (8.4%). In multivariable analysis, AFL-related rhythmic cardiomyopathy and presentation with 1/1 AFL were less frequent (respectively adjusted OR = 0.44, 0.27–0.74, p = 0.002 and adjusted OR = 0.29, 0.16–0.52, p<0.0001). AFL ablation-related major complications were more frequent in patients ≥70 although remained lower than 10% (7.4% in ≥70 vs. 4.2% in <70, adjusted OR = 1.74, 1.04–2.89, p = 0.03). After 2.1±2.7 years, AFL recurrence was less frequent in patients ≥70 (adjusted OR = 0.54, 0.37–0.80, p = 0.002) whereas atrial fibrillation (AF) occurrence was as frequent in the 70–79 and ≥80 age subsets. As expected, cardiac mortality was higher in older patients. Patients aged ≥80 also had a low probability of AFL recurrence (5.0%) and AF onset (19.0%).ConclusionsOlder patients represent 37.5% of patients referred for AFL ablation and displayed a <10% risk of ablation-related complications. Importantly, AFL recurrences were less frequent in patients ≥70 while AF occurrence was as frequent as in patients <70. Similar observations were made in patients ≥80 years. AFL ablation appears to be safe and efficient and should not be ruled out in elderly patients.     

Quantitative light microscopic analysis of corpus luteum growth during pseudopregnancy in the rabbit

We employed stereological methods at the light-microscope level to examine the mechanism by which corpora lutea (CL) grow during the course of pseudopregnancy in the rabbit. Corpus luteum volume per ovary, the absolute volume of luteal cells per CL, individual luteal cell volume, the number of luteal and endothelial cells per CL, and capillary surface area per CL were examined in rabbits at Days 1, 4, 7, 11, and 18 of pseudopregnancy. Total CL volume increased from 3.7 +/- 0.1 microliter to 30.3 +/- 0.5 microliter over Days 1 to 11 and thereafter decreased to 15.2 +/- 1.1 microliter by Day 18. Stereological analyses showed that the increases in CL volume from Day 1 to Day 11 were due primarily to increases in the volume of individual luteal cells (from 2.6 +/- 0.2 pl on Day 1 to 23.5 +/- 1.7 pl on Day 11, 1 pl = (10 mu)3; r = 0.96), and that the decrease in CL volume after Day 11 resulted largely from a decrease in luteal cell volume (to 12.8 +/- 1.5 pl). In contrast, no change was seen in the number of luteal cells per CL (range 9.1 x 10(5)-12.5 x 10(5)). These data show that CL growth and subsequent regression during pseudopregnancy result primarily from changes in the volume of individual luteal cells, and not from changes in the number of luteal cells. These data support the hypothesis that modulation of progesterone production during pseudopregnancy is due to changes in individual luteal cell volume and not to changes in cell number.     

Rapid dilation of arterioles with single contraction of hamster skeletal muscle

Skeletal muscle blood flow increases rapidly with exercise onset, but little is known of where or how the rapid onset of vasodilation (ROV) is governed within the microcirculation. In the retractor muscle of anesthetized hamsters (n = 26), we tested the following: 1) where in the resistance network ROV occurred, 2) how microvascular responses were affected by the duration of contraction, and 3) whether ROV involved muscarinic receptor activation. Single tetanic contractions were evoked using supramaximal field stimulation (100 Hz) to depolarize motor end plates. In response to a 200-ms contraction, red blood cell (rbc) velocity (V(rbc)) in feed arteries (FA; rest: 17.8 +/- 2 mm/s) increased within 1 s; a transient first peak (P1; 50 +/- 7% increase) occurred at approximately 5 s; and a second peak (P2; 50 +/- 15% increase) occurred at approximately 15-20 s. For vasodilation, P1 increased in frequency from proximal FA (2/7) and 1A arterioles (2/7) to distal 2A (4/7) and 3A (7/8) arterioles (P < 0.05). Relative to resting (and maximal, 10 microM sodium nitroprusside) diameters, P1 increased from proximal (FA, 3 +/- 2% from 57 +/- 5 microm) to distal (3A, 27 +/- 6% from 14 +/- 1 microm) vessel branches (P < 0.05). P2 was manifest in all vessels and increased relative to resting diameters from FA (11 +/- 3%) to 3A (36 +/- 6%) branches (P < 0.01). Extending a contraction from 200 to 1,000 ms (tension x time integral from 17 +/- 2 to 73 +/- 4 mN/mm2 x s) increased P1 and P2 for V(rbc) and for diameter (P < 0.05) while reducing the time of onset for P2 (P < 0.05). Superfusion with atropine (10 microM) attenuated P1 of vasodilation (200 ms contraction) from 26 +/- 8% to 6 +/- 2% (n = 7 across branches; P < 0.05) and reduced the diameter x time integral by 46 +/- 13% (P < 0.05) without changing P2. We conclude that ROV in the hamster retractor muscle is initiated in distal arterioles, increases with the duration of muscle contraction, and involves muscarinic receptor activation.     

Synthesis and in vitro and in vivo evaluation of [11C]methyl-BIII277CL for imaging the PCP-binding site of the NMDA receptor by pet

A new benzomorphane derivative, [11C]methyl-BIII277CL, was evaluated as a potential radiotracer for visualizing the PCP-binding site of the N-methyl-D-aspartate (NMDA) receptor by positron emission tomography (PET). Methyl-BIII277CL was prepared by reacting the desmethyl compound (BIII277CL) with dimethylsulfate. The pharmacological profile of methyl-BIII277CL was determined by in vitro receptor-screening assays. At a concentration of 100 nM, methyl-BIII277CL showed a significant interaction with the PCP-binding site of the NMDA receptor (79% inhibition of specific binding) and the sigma-binding site (46% inhibition). In displacement assays using mice cortical membranes, methyl-BIII277CL displayed a high affinity at the PCP-binding site of the NMDA receptor (Ki = 49 +/- 14 nmol/L) and a 130-fold lower interaction with the sigma1-binding site (Ki = 6.35 +/- 0.26 micromol/L). For saturation experiments and in vivo studies, methyl-BIII277CL was radiolabeled with 11C at the O-position of the desmethyl precursor (BIII277CL) using [11C]methyliodide with a specific activity of 35-70 GBq/micromol at the end of synthesis (EOS). In saturation assays using rat whole brain membranes [11C]methyl-BIII277CL showed a Kd of 6 +/- 1 nmol/L and a Bmax of 670 +/- 154 fmol/mg protein. Biodistribution and PET studies in rats and pigs, however, indicated a lack of specific binding and unfavorable pharmacokinetics. Kinetic modeling using the 1-tissue compartment model demonstrated for [11C]methyl-BIII277CL a low distribution volume (Dv = 0.98 mL/mL(tissue)) and very high values for the kinetic parameters K1 and k2 (K1 = 0.36 mL/mL(tissue)/min and k2 = 0.37min(-1)) in pig cortex. [11C]methyl-BIII277CL, due to the lack of specificity in vivo, may not be a candidate for imaging the PCP-binding site of the NMDA receptor.