Interleukin-10 treatment attenuates sinus node dysfunction caused by streptozotocin-induced hyperglycaemia in mice.

Aims: Diabetes, characterized by hyperglycaemia, causes sinus node dysfunction (SND) in several rodent models. Interleukin (IL)-10, which is a potent anti-inflammatory cytokine, has been reported to decrease in obese and diabetic patients. We tested the hypothesis that administration of IL-10 inhibits the development of SND caused by hyperglycaemia in streptozotocin (STZ)-induced diabetic mice. Methods and results: Six-week old CL57/B6 (WT) mice were divided into the following groups: control, STZ injection, and STZ injection with systemic administration of IL-10. IL-10 knockout mice were similarly treated. STZ-induced hyperglycaemia for 8 weeks significantly depressed serum levels of IL-10, but increased several proinflammatory cytokines in WT mice. STZ-induced hyperglycaemia-reduced resting heart rate (HR), and attenuated HR response to isoproterenol in WT mice. In isolated perfused heart experiments, corrected-sinus node recovery time was prolonged in WT mice with STZ injection. Sinus node tissue isolated from the WT-STZ group showed fibrosis, abundant infiltration of macrophages, increased production of reactive oxygen species (ROS), and depressed hyperpolarization activated cyclic nucleotide-gated potassium channel 4 (HCN4). However, the changes observed in the WT-STZ group were significantly attenuated by IL-10 administration and were further exaggerated in IL-10 knockout mice. In cultured cells, preincubation of IL-10 suppressed hyperglycaemia-induced apoptotic and profibrotic signals, and overproduction of ROS. IL-10 markedly inhibited the high glucose-induced p38 activation, and activated signal transducer and activator of transcription (STAT) 3 phosphorylation. Conclusions: Our results suggest that IL-10 attenuates ROS production, inflammation and fibrosis, and plays an important role in the inhibition of hyperglycaemia-induced SND by suppression of HCN4 downregulation. In addition, IL-10-mediated inhibition of p38 is dependent on STAT3 phosphorylation.

Mechanistic implication of decreased plasma atrial natriuretic peptide level for transient rise in the atrial capture threshold early after ICD or CRT-D implantation.

PURPOSE: Despite the use of steroid-eluting leads, a transient but not persistent rise in the atrial/ventricular capture threshold (TRACT/TRVCT) can occur early after pacemaker implantation in patients with sick sinus syndrome. This study aimed to assess the prevalence, predictors, and mechanisms of TRACT/TRVCT in patients with heart failure undergoing implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) implantation. METHOD: One hundred twenty consecutive patients underwent ICD (N = 70) or CRT (N = 50) implantation. Capture threshold was measured at implantation, 7-day, 1-month, and 6-month post-implantation. TRACT/TRVCT was defined as a threshold rise at 7 days by more than twice the height of the threshold at implantation, with full recovery during follow-up. Atrial and brain natriuretic peptide (ANP and BNP) levels were measured before implantation. RESULTS: TRACT and TRVCT were observed in 13 (11%) and 10 (8%) patients, respectively. Patients with TRACT had lower ANP level (median 72 [42-105] vs. 99 [49-198] pg/mL, P = 0.06), lower ANP/BNP ratio (0.29 [0.20-0.36] vs. 0.50 [0.33-0.70], P < 0.01), lower atrial sensing amplitude (2.0 ± 0.8 vs. 2.7 ± 1.3 mV, P = 0.02), and lower left ventricular ejection fraction (32 ± 12 vs. 40 ± 14%, P = 0.04) than those without TRACT. TRACT recovered within 1 month, whereas TRVCT recovered within 6 months. In multivariable analysis, ANP/BNP ratio was the only independent predictor of TRACT (OR, 0.018; 95% CI, 0.001-0.734; P = 0.034). CONCLUSIONS: Atrial degenerative change characterized by lower ANP/BNP ratio was associated with the occurrence of TRACT in patients with heart failure. TRVCT could also occur, but it required a longer recovery time than TRACT.

Red blood cell distribution width and atrial fibrillation in patients with sick sinus syndrome.

BACKGROUND: Sick sinus syndrome (SSS) is associated with atrial fibrillation (AF). Red blood cell distribution width (RDW) is a marker of anisocytosis of erythrocytes and is related to inflammatory stress. Recently, RDW has been associated with AF. The aim of the present study was to evaluate the potential association of RDW with AF history in patients with SSS. METHODS: Consecutive patients with symptomatic SSS undergoing dual-chamber pacemaker implantation were screened. Baseline clinical, laboratory, echocardiographic, and electrocardiographic parameters were recorded. Conventional inflammatory indexes were also assessed. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis for parameters associated with AF were performed. RESULTS: The final study population consisted of 101 patients (47 men); median age: 77 [73-82] years. The demographic and clinical characteristics were comparable between tachy-brady (AF history) patients (n=32) and patients with other forms of SSS (n=69). Left atrial diameter was increased in tachy-brady patients [44 (39-48)mm vs. 39 (36-44)mm; p=0.05]. Also, the RDW was greater in these patients [14.7 (13.6-15.4)% vs. 13.7 (13.4-14.3)%; p=0.02]. Multivariate analysis showed that RDW is independently associated with AF (OR: 1.58; 95% CI: 1.06-2.85; p=0.04). The ROC curve analysis showed that the area under the curve was 0.69 (p=0.028). A RDW cut-off point of 14 was related to AF with a sensitivity of 70% and a specificity of 69%. CONCLUSION: RDW is associated with AF history in patients with SSS. The prognostic value of RDW in terms of future AF development and arrhythmia perpetuation in these patients should be further examined.

Elevated plasma norepinephrine level and sick sinus syndrome in patients with lone atrial fibrillation.

OBJECTIVE: Plasma norepinephrine (NE) level can be a guide to mortality in patients with heart failure. This study aimed to evaluate the significance of plasma NE level compared with plasma natriuretic peptides (atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) levels in patients with atrial fibrillation (AF). METHODS: Included in this study were 137 consecutive patients referred for catheter ablation of lone AF (paroxysmal in 90 and persistent in 47 patients). Blood samples for measurements of ANP, BNP and NE were drawn in the supine position before the procedure. RESULTS: ANP, BNP and NE levels were greater in patients with persistent AF than in patients with paroxysmal AF (median (25th-75th centile)=28 (18-49) vs 69 (36-106), p<0.0001; 28 (15-50) vs 94 (39-156), p<0.0001; and 315 (223-502) vs 382 (299-517) pg/mL, p=0.04, respectively). NE level correlated weakly with ANP and BNP levels (r=0.28 and r=0.23, respectively, p<0.01 for both). BNP and NE levels differed between patients with and without recurrence of AF (55 (26-135) vs 35 (18-64), p=0.005 and 431 (323-560) vs 302 (225-436) pg/mL, p<0.001, respectively). Of note, only NE level was significantly greater in patients with symptomatic sick sinus syndrome (SSS) (n=21) than in those without SSS (560 (466-632) vs 321 (242-437) pg/mL, p<0.0001). Logistic regression analysis showed NE level to be the only independent discriminator for SSS (OR 1.006, 95% CI 1.002 to 1.010, p=0.001). CONCLUSIONS: An increase in plasma NE level was observed in patients with AF and SSS. Although this implies a pathophysiological link between clinical manifestation of SSS and the autonomic nervous dysfunction, further studies are needed to clarify the mechanisms for this novel finding.

Neuroendocrine and haemodynamic changes in single-lead atrial pacing and dual-chamber pacing modes.

OBJECTIVES: Neuroendocrine and haemodynamic changes were compared between single-lead atrial (AAI) or dual-chamber (DDD) pacing modes in patients with sick sinus syndrome, in a crossover study. METHODS: Inpatients scheduled for their first pacemaker implantation were screened for the following inclusion criteria: sick sinus syndrome; intact atrioventricular conduction; normal QRS interval. All study patients were implanted with a dual-chamber pacemaker, programmed for AAI or DDD pacing mode. Patients were allocated randomly to AAI followed by DDD pacing or to DDD followed by AAI pacing, each mode being applied for 72 h. Echocardiographic, electrocardiographic and neuroendocrine parameters were tested at the end of each pacing mode. RESULTS: From 152 inpatients screened for inclusion, 28 were selected for treatment. Plasma levels of atrial natriuretic peptide (ANP), endothelin, aldosterone and angiotension II were significantly lower, and aortic flow velocity-time integral was significantly higher, in AAI mode than in DDD mode. Aortic pre-ejection interval, interventricular mechanical delay and QRS duration were significantly higher in DDD than in AAI mode. CONCLUSIONS: In patients with sick sinus syndrome, DDD pacing mode can induce neuroendocrine system activation, and left ventricular dysfunction and dyssynchrony. These findings discourage the routine use of DDD pacing in patients with sick sinus syndrome.

Lithium-induced sinus node dysfunction at therapeutic levels.

Lithium is used as an antimanic and mood-stabilising drug. It can cause various adverse effects such as nausea, vomiting, polyuria, fine tremors, myocarditis and arrhythmias. We are describing a case of lithium induced sinus-node dysfunction in a patient with serum lithium levels in therapeutic range.

Comparison of right ventricular apex and right ventricular outflow tract septum pacing in the elderly with normal left ventricular ejection fraction: long-term follow-up.

BACKGROUND: Whether right ventricular outfow tract septum (RVOTS) pacing is superior to right ventricular apex (RVA) pacing with respect to left ventricular synchrony, cardiac function, and remodelling in the elderly with normal left ventricular ejection fraction (LVEF), is still unknown. AIM: To assess the impact of RVOTS vs. RVA pacing on the cardiac performance of the elderly with normal LVEF during a long-term observation. METHODS: From 2007 to 2010, 65 patients with standard pacing indications for permanent pacing were recruited and randomised to receive RVA (32 patients) or RVOTS pacing (33 patients). Over a median 28 months' follow-up, available data was summarised, including New York Heart Association (NYHA) functional class, echocardiographic and pacing parameters, axis, QRS duration and plasma B-type natriuretic peptide (BNP) level. Then these values were compared between the RVA group and the RVOTS group, as well as between pacemaker pre- and post-implantation in the RVA group and in the RVOTS group, respectively. RESULTS: There were no significant differences in baseline characteristics between the RVA group and the RVOTS group. The median pacing durations did not differ significantly between the groups (31.5 months in the RVA group vs. 28 months in the RVOTS group, p = 0.728). Compared to the baseline values, LVEF decreased with RVA pacing (from 59.5 ± 6.21 to 54.22 ± 8.73, p = 0.001), but LVEF did not markedly vary in the RVOTS group (57.82 ± 6.06 and 56.94 ± 5.54, p = 0.152). The number of patients with moderate tricuspid valve regurgitation remarkably increased in the RVA group, from six (18.75%) patients to 10 (31.3%) patients, preoperatively to postoperatively (p = 0.046), but this change was not statistically significant in the RVOTS group. Compared to the RVOTS group, NYHA functional class had a deteriorated tendency in the RVA group (p = 0.071). After the implantation, the increase of median BNP level was observed in the RVA group (35 pg/mL at preimplantation and 50 pg/mL at the end of follow-up, p = 0.007); No significant change was obtained in the RVOTS group (36.4 pg/mL at pre-implantation vs. 38 pg/ml at the end of follow-up, p = 0.102). Compared to the RVA pacing group, the mean QRS width narrowed substantially in the RVOTS pacing group (from 143.56 ± 12.90 to 105.52 ± 15.21, p = 0.000). In terms of the end diastolic and systolic diameters of the left ventricular, there were no statistical variations observed during the follow-up. CONCLUSIONS: Permanent RVA pacing in elderly patients with normal LVEF led to left ventricular systolic function deterioration denoted by lower LVEF and higher BNP level. When compared to RVA pacing, RVOTS pacing had no remarkable benefit in terms of preventing cardiac remodelling.

Brain natriuretic peptide: a marker of cardiac dysfunction with ventricular or dual-chamber pacing.

BACKGROUND/OBJECTIVES: The inability of trials to exhibit the superiority in survival of atrioventricular compared to ventricular pacing can be partially explained by the apical stimulation of the right ventricle, which adversely affects both short- and long-term ventricular performance. We evaluated the impact of pacing mode (DDDR vs. VVIR) on the brain natriuretic peptide (BNP) level in patients with sick-sinus syndrome (SSS). METHODS: Sixty-seven patients were treated with DDDR pacemaker implantation due to SSS. They were randomized during the first post-implant day either to DDDR or WIR pacing mode and were reevaluated after 30 days. Group A comprised 35 patients on DDDR pacing mode and group B 32 patients on WIR pacing mode. Peripheral blood samples were drawn for BNP measurement at the time of randomization and one month later. RESULTS: BNP levels increased significantly in both groups at 30 days (group A: 85.6 +/- 29.5 pg/ml to 107.2 +/- 34.6 pg/ml, group B: 82.7 +/- 27.6 pg/ml to 253.1 +/- 60.2 pg/ml). On day 30, BNP levels in group B were significantly higher than in group A (P < 0.0001). CONCLUSIONS: Pacing from the apex of the right ventricle provokes an increase in the BNP levels regardless of the pacing mode. BNP is probably a very early marker predicting the structural and/or functional heart changes after long-term pacing from the apex of the right ventricle.

The prevalence of apical wall motion abnormalities in patients with long-term right ventricular apical pacing.

BACKGROUND: Long-term right ventricular apical pacing (RVAP) can lead to adverse clinical outcomes. Although left ventricular (LV) dyssynchrony is the major causative factor, other potential mechanisms are not fully understood. We sought to clarify whether RVAP elicits apical wall motion abnormalities that contribute to LV contractile dysfunction. METHODS: We studied annual echocardiographic data over a 5-year period after pacemaker implantation (PMI) for 74 patients who underwent RVAP. The patients were divided into two groups according to the percentage of ventricular pacing: right ventricular (RV) pacing < 50% and RV pacing ≥ 50%. We assessed LV ejection fraction, LV end-diastolic volume, and left atrial dimension. To assess regional wall motion abnormalities, the wall motion score index was calculated. RESULTS: LV wall motion abnormality was observed in 64% of the subjects and was more pronounced in apical segments than in other segments. At 2 years after PMI, brain natriuretic peptide levels were significantly higher in the group with RV pacing ≥ 50% than in the group with RV pacing < 50%. The subjects with RV pacing ≥ 50% had higher LV end-diastolic dimension and lower ejection fraction at 3 years after PMI. CONCLUSION: Long-term RVAP elicits apical wall motion abnormalities that could in part contribute to LV contractile dysfunction.

DDDR pacing results in left ventricular asynchrony with preservation of ejection fraction and NT-proBNP: a prospective study in sick sinus syndrome and normal ventricular function.

Desynchronization induced by right ventricular pacing may increase the risk for heart failure. We aimed to compare left ventricular (LV) function, synchrony and left atrial size along with NT-proBNP levels, in 2 different modes of pacing: AAIR versus DDDR. This was a prospective study of 60 patients with sick sinus syndrome, preserved LV function and normal atrioventricular conduction. Each pacing mode lasted at least 2 months, in every patient, after which period every patient was switched to the alternate pacing mode. Intraventricular asychrony was assessed by: 1) M-Mode septal-to-posterior wall motion delay (SPWMD), and 2) Tissue Doppler imaging (TDI) septal to lateral delay. NT-proBNP was measured at the end of each pacing mode. LV ejection fraction and left atrial diameter were not different in the 2 pacing modes, although asynchrony was induced in the DDDR arm (p<0.001 for TDI). NT-proBNP was lower in the DDDR compared to the AAIR mode (p=0.003, F=9.64). The NT-proBNP was inversely correlated to LV ejection fraction in the DDDR mode (p=0.0001, R=-0.75), whilst it was significantly correlated to the TDI septal-lateral delay and SPWMD (p=0.007, R=0.4 and p=0.002, R=0.5) in the AAIR mode. In conclusion in sick sinus syndrome with preserved LV function the DDDR mode does not compromise LV systolic function although it causes asynchrony. The NT-proBNP is lower when the right ventricle is paced, is inversely related to LV function and it is related to the degree of LV synchronization in the AAIR mode.

[Ser49gly polymorphism as predictor of development of hereditary sick sinus node syndrome].

We demonstrated for the first time on clinico-genetic material an association of hereditary sick sinus node syndrome (SSNS) with polymorphism of beta-adrenorecetor gene. We found that heterozygous variant of Ser49gly of beta-adrenoreceptor gene was significantly more often met in patients with SSNS and their healthy relatives than in subjects of control group. In the group of patients with SSNS contrary to control group we noted statistically significant preponderance of carriers of mutant Gly49 allele of.

The influence of permanent cardiac pacing on plasma levels of B-type natriuretic peptide in patients with sick sinus syndrome.

BACKGROUND: Unequivocal data presenting the impact of different pacing modes on B-type natriuretic peptide levels has never been published. The aim of the study was to assess changes of plasma B-type natriuretic peptide (BNP) during permanent cardiac pacing in patients with sick sinus syndrome (SSS). METHODS: Patients with SSS undergoing routine pacemaker implantation were enrolled. Each subject underwent medical history and examination, echocardiography and blood sampling. Analysis was performed on 12 females (42.9%) and 16 males (57.1%), mean age 71.3 +/- 9.03 years, range 49-90 years. There were 11 pacemakers with AAIR pacing mode (39.3%; AAI group) and 17 with DDDR mode (60.7%; DDD group) implanted. There were no significant differences in age, concomitant diseases or echocardiographic parameters between the groups in baseline characteristics or plasma BNP levels (94.05 +/- 54.1 vs. 73.57 +/- 70.13 pg/mL; p > 0.2). RESULTS: During six months follow-up no significant changes in plasma BNP levels in AAI group (94.05 +/- 54.1 vs. 94.05 +/- 54.1 pg/mL; p > 0.5) as well as in DDD group (73.57 +/- 70.1 vs. 82.39 +/- 58.9 pg/mL; p > 0.5) were noticed. CONCLUSIONS: Atrial (AAIR) and dual chamber (DDDR) pacing did not influence plasma BNP levels in patients with SSS and preserved left ventricular systolic function.

Interventricular mechanical dyssynchrony determines abnormal heightening of plasma N-terminal probrain natriuretic peptide level in symptomatic bradyarrhythmia patients with chronic dual-chamber vs. single-chamber atrial pacing.

OBJECTIVE: Debates about adverse effects of ventricular- vs. atrial-based pacing have never ended, especially regarding cardiovascular outcomes in common pacemaker populations. METHODS: To investigate the contribution of right ventricular apical pacing to the left ventricular negative remodeling, we measured the inter- and intraventricular mechanical dyssynchrony by echocardiography as well as plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level in 116 consecutive patients of symptomatic bradyarrhythmias including sinus node dysfunction (SND) in 80 and atrioventricular block in 36. Dual-chamber rate-modulated pacing (DDDR) pacemakers were implanted in 76 patients (SND, 40), and single-chamber ventricular rate-modulated pacing (AAIR) pacemakers in 40 (all SND). Clinical manifestations were retrospectively correlated. RESULTS: After 3.5 years of pacing, DDDR pacemaker patients demonstrated higher plasma NT-proBNP concentration (503 +/- 111 pg/ml) than AAIR patients (194 +/- 42 pg/ml, p = 0.002) despite similar cardiovascular function at baseline. Multivariate regression analysis revealed that the only predictor of the highest quartile of plasma NT-proBNP, i.e. >or=386 pg/ml, was the interventricular contraction time difference (p = 0.01). Reprogramming to minimize ventricular pacing percentage in 8 patients of SND caused parallel reduction of plasma NT-proBNP. CONCLUSION: Interventricular mechanical dyssynchrony, imposed mostly by right ventricular apical pacing, could lead to abnormal heightening of plasma NT-proBNP concentration after chronic DDDR pacing in common pacemaker patients with normal baseline left ventricular function.

Single-chamber ventricular pacing increases markers of left ventricular dysfunction compared with dual-chamber pacing.

AIMS: Large randomized trials comparing DDD with VVI pacing have shown no differences in mortality, but conflicting evidence exists in regard to heart failure endpoints. Here we evaluated the effect of pacing mode on serum levels of brain natriuretic peptide (BNP) and amino-terminal-proBNP (NT-proBNP). Methods Forty-one patients (age 73 +/- 10 years) with dual-chamber pacemakers were included in a prospective, single-blind, randomized crossover study evaluating the impact of DDD(R)/VDD versus VVI(R) mode on objective and functional parameters. Data were collected after a 2-week run-in phase and after 2 weeks each of VVI(R) and DDD(R)/VDD pacing or vice versa. Results BNP and NT-proBNP levels during DDD(R)/VDD stimulation (151 +/- 131 and 547 +/- 598 pg/mL) showed no change compared with baseline (154 +/- 130 and 565 +/- 555 pg/mL), but a significant 2.4-fold increase was observed during VVI(R) mode [360 +/- 221 and 1298 +/- 1032 pg/mL; P < 0.001 compared with DDD(R)/VDD]. The assessment of functional class, the presence of pacemaker syndrome [49% in VVI(R) mode] and the patients' preferred pacing mode showed significant differences in favour of DDD(R)/VDD pacing. CONCLUSION: Patients can differentiate between DDD(R)/VDD and VVI(R) pacing, and prefer the former. Compared with DDD(R)/VDD pacing, VVI(R) stimulation induces a two- to three-fold increase in serum BNP and NT-proBNP levels.

Left ventricular function during and after right ventricular pacing.

OBJECTIVES: The aim of this research was to evaluate right ventricular pacing effects on left ventricular function. BACKGROUND: Right ventricular pacing alters the ventricular activation sequence and reduces left ventricular ejection fraction (EF). It is unclear whether the observed reduction in EF can be completely attributed to the alteration in activation sequence. METHODS: Twelve subjects (eight women), mean age 68 +/- 12 years, with transvenous dual-chamber pacemakers, normal left ventricular function, and intact atrioventricular (AV) conduction were studied with serial-gated blood pool studies. Left ventricular EF was measured at a fixed rate after at least 1 week of atrial pacing only (baseline), during short-term (2 h) and mid-term (1 week) AV sequential pacing with a short AV delay, and after short- and mid-term AV pacing. RESULTS: Baseline EF was 66.5 +/- 4.5%. Short-term AV pacing resulted in a decrease in EF to 60.3 +/- 5.2% (p < 0.0002). After one week of AV pacing, there was a further decline in EF to 52.9 +/- 8.3% (p < 0.0001). After cessation of mid-term pacing, EF was 57.3 +/- 5.9% (p < 0.0001 vs. baseline). A total of 2, 5, 8, and 24 h later, EF remained depressed (59% to 60%, p < 0.007). At 32 h, EF was 62.9 +/- 7.6% (p < 0.11 compared with baseline). CONCLUSIONS: The abnormal activation sequence resulting from right ventricular pacing accounts for only part of the reduction in EF as mid-term pacing is associated with a lower EF than short-term pacing, and EF remains depressed after cessation of AV pacing. Changes in ventricular function induced by right ventricular pacing may account for some of its associated adverse effects.

Clinical significance of preserving spontaneous QRS wave in the therapy of DDD pacing for sick sinus syndrome.

The aim of this clinical crossover study was to elucidate the effects of atrioventricular (AV) synchronous pacing on cardiac function in patients with sick sinus syndrome (SSS). Thirty SSS patients, each with dual chamber pacemaker (DDD), were enrolled and divided into two groups based on echocardiographic findings. Group A (n = 16) had hypertensive heart disease (wall thickness 11 approximately 12 mm) or mitral or aortic regurgitation (Grade I or II). Group B (n = 14) had no organic heart disease. Three successive 3-month pacing periods were tested. For the first 3 months, long AV delay that achieved > 80% ventricular sensing was chosen. For the next 3 months, AV delay was abbreviated to achieve > 80% ventricular pacing at an optimal AV interval. For the final 3 months, the first setting was resumed. At the end of each period, M mode echocardiography, pulsed-Doppler study, and measurement of plasma brain natriuretic peptide (BNP) level were conducted. In both groups, echocardiographic parameters were not significantly changed during the evaluation. In group A, plasma BNP level was significantly higher at the end of the short AV delay period than at the long AV delay period (P = 0.009), while in group B it did not differ during each period. AV synchronous pacing (> 80% ventricular pacing) in the SSS patients with a DDD pacemaker implanted could increase the ventricular load, and it is better to preserve the spontaneous QRS with the DDD mode with prolonged AV delay in patients with mild hypertensive or valvular disease.

Estudo da função ventricular na técnica de plicatura da parede livre do ventrículo esquerdo em cães / Left ventricular function after plication of the left ventricular free wall in dogs

OBJETIVO: Avaliar os efeitos da técnica na função ventricular esquerda em cães hígidos e com cardiomiopatia dilatada induzida pela doxorrubicina. MÉTODO: De 13 cães, oito receberam doxorrubicina até que a fração de encurtamento (FE) fosse menor que 20 por cento. Destes, quatro animais e os cinco não induzidos foram submetidos à plicatura da parede livre do ventrículo esquerdo (PPLVE). Os demais cães não foram operados. Foram avaliados débito cardíaco (DC), pressão arterial, exame físico, eletrocardiografia, sistema "Holter" e ecocardiografia, por 180 dias. RESULTADOS: Houve redução do volume ventricular esquerdo. Os cães induzidos melhoraram após a operação e a fração de ejeção (FEj) retornou aos valores normais para a espécie. O DC e a FE aumentaram após a operação. Um cão foi a óbito. Nos cães não operados, a FE diminuiu e foram a óbito em torno de 40 dias após a indução; nos cães não induzidos, esta não se alterou. Houve extra-sístoles ventriculares, que se resolveram espontaneamente. CONCLUSÕES: A PPLVE sem circulação extracorpórea reduz o volume ventricular esquerdo e melhora a função cardíaca dos cães com cardiomiopatia dilatada induzida pela doxorrubicina, demonstrando baixa morbidade e mortalidade tardia.

[Comparison of the prothrombin levels between the patients with atrial fibrillation and patients with cardiac pacemaker implantation due to sick sinus syndrome during anticoagulation therapy with warfarin].

We measured the fully carboxylated prothrombin levels using the Carinactivase-1 (CA-1) test and thus compared prothrombin levels between patients having atrial fibrillation (Af) without pacemaking and those having sick sinus syndrome due to Af with cardiac pacemaker implantation during anticoagulation therapy with warfarin. Total plasma samples were assayed for the CA-1 test, the prothrombin time international normalized ratio (PT-INR) and the thrombotest (TT). This prospective randomized study was carried out on 641 samples obtained at the Fukuoka University Hospital Department of Cardiovascular Surgery between May 1997 and March 1999. The patients were divided into 2 groups consisting of: group A; 144 patients having sick sinus syndrome due to Af implanted with a cardiac pacemaker who were treated with warfarin, group B; 497 patients atrial fibrillation without pacemaking who were treated with warfarin. The prothrombin levels in each group were 65.5 +/- 25.2 and 76.1 +/- 47.7 micrograms/ml, respectively. The normal prothrombin levels of group A decreased more significantly than in group B. Therefore, the PT-INR and TT were not significantly different between groups A and B. The dose of warfarin in each group was 2.4 +/- 1.0 and 2.6 +/- 1.4 g/day, respectively. The dose of warfarin in group A therefore decreased significantly different more than in group B. In conclusion, the normal prothrombin levels of patients atrial fibrillation increased more significantly than patients having sick sinus syndrome due to Af implanted with a cardiac pacemaker.

Plasma natriuretic peptide levels and daily physical activity in patients with pacemaker implantation.

To determine whether plasma ANP and/or BNP levels can be used to detect limitations in daily physical activity after pacemaker implantation, we measured plasma ANP and BNP levels at a pacemaker follow-up clinic in 56 patients (62+/-15 yrs, 2AAI, 9VVI, 34DDD, 7VDD and 4 rate-responsive modes), daily physical activity evaluated by a specific activity scale questionnaire (METs) and VO2 max obtained by expired gas analysis during ergometer exercise. A very close correlation (n=6, r=0.89, p<0.05) was obseved between. ANP in patients with daily physical activity class III (2-4 METs, n=21) was significantly higher than class II (5-6 METs, n=23, p<0.01) and class I (>7 METs, n=8, p<0.01), while BNP in class III patients was significantly higher than in class II (p<0.0001) and class I (p<0.0001) patients. Significant correlations between daily physical activity and BNP (r=-0.64, p<0.0001) and ANP (r=-0.43, p<0.001) were observed. Physiological pacing mode did not necessarily offer a better profile for BNP levels compared with non-physiological pacing modes. Patients with ventricular pacing (wide QRS: VDD, RR-VVI and VVI) showed significantly high ANP (p<0.01) and BNP (p<0.01) levels compared with those in patients with atrial pacing (narrow QRS: AAI and RR-AAI). During exercise, plasma catecholamines and ANP levels were significantly elevated, however, BNP levels, which were already elevated at rest, did not change significantly, and reflected a limitation of daily physical activity. The present study revealed that 37.5% of the patients displayed an elevation in BNP and this was judged to be a limitation of physical activity class III being equivalent to NYHA II or more. Elevated resting BNP levels reflected a limitation in daily physical activity in these patients. These findings suggested a third condition for physiological pacing--synchronization of ventricular contraction (narrow QRS pacing)--in addition to the two conventional conditions of atrioventricular synchrony and rate-responsiveness.