atrial-natriuretic-factor and Tachycardia--Ventricular

Ventricular arrhythmias are common in patients with congestive heart failure (CHF) and may be exacerbated by positive inotropic therapy. Because human B-type natriuretic peptide (nesiritide), an arterial and venodilator, inhibits sympathetic activity, it may decrease the incidence of arrhythmias. Our investigation compares the arrhythmogenicity of dobutamine with nesiritide. A total of 305 patients with decompensated CHF requiring intravenous vasoactive therapy were randomized to receive standard therapy (n = 102) or nesiritide (0.015 microg/kg/min [n = 103] or 0.030 microg/kg/min [n = 100]) to gain additional data on the relative safety and efficacy of nesiritide compared with standard parenteral care. Dobutamine was chosen as the standard care agent in 58 subjects. During study drug infusion, all patients had continuous clinical hemodynamic and electrocardiographic monitoring. The dobutamine and nesiritide groups were similar with respect to baseline use of antiarrhythmic agents, including beta blockers. Serious arrhythmias and the incidence of cardiac arrest were more common in patients who received dobutamine than in those taking nesiritide: sustained ventricular tachycardia, 4 (7%) versus 2 (1%), respectively (p = 0.014); nonsustained ventricular tachycardia, 10 (17%) versus 23 (11%), respectively (p = 0.029); cardiac arrest, 3 (5%) versus 0, respectively (p = 0.011). We conclude that among patients with decompensated CHF for whom dobutamine is selected as standard therapy, the incidence of serious ventricular arrhythmias and cardiac arrest is significantly greater than the incidence of these events in patients randomized to nesiritide.

Topics: Aged; Atrial Natriuretic Factor; Cardiotonic Agents; Dobutamine; Double-Blind Method; Female; Heart Failure; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Statistics, Nonparametric; Tachycardia, Ventricular; Treatment Outcome

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal ventricular arrhythmia evoked by physical or emotional stress. Recessively inherited CPVT is caused by either missense or null-allele mutations in the cardiac calsequestrin (CASQ2) gene. It was suggested that defects in CASQ2 cause protein deficiency and impair Ca(2+) uptake to the sarcoplasmic reticulum and Ca(2+)-dependent inhibition of ryanodine channels, leading to diastolic Ca(2+) leak, after-depolarizations, and arrhythmia. To examine the effect of exercise training on left ventricular remodeling and arrhythmia, CASQ2 knockout (KO) mice and wild-type controls underwent echocardiography and heart rhythm telemetry before and after 6 wk of training by treadmill exercise. qRT-PCR and Western blotting were used to measure gene and protein expression. Left ventricular fractional shortening was impaired in KO (33 ± 5 vs. 51 ± 7% in controls, P < 0.05) and improved after training (43 ± 12 and 51 ± 9% in KO and control mice, respectively, P = nonsignificant). The exercise tolerance was low in KO mice (16 ± 1 vs. 29 ± 2 min in controls, P < 0.01), but improved in trained animals (26 ± 2 vs. 30 ± 3 min, P = nonsignificant). The hearts of KO mice had a higher basal expression of the brain natriuretic peptide gene. After training, the expression of natriuretic peptide genes markedly decreased, with no difference between KO and controls. Exercise training was not associated with a change in ventricular tachycardia prevalence, but appeared to reduce arrhythmia load, as manifested by a decrease in ventricular beats during stress. We conclude that, in KO mice, which recapitulate the phenotype of human CPVT2, exercise training is well tolerated and could offer a strategy for heart conditioning against stress-induced arrhythmia.

Topics: Animals; Atrial Natriuretic Factor; Blotting, Western; Calsequestrin; Disease Models, Animal; Exercise Therapy; Exercise Tolerance; Gene Expression Regulation; Genetic Predisposition to Disease; Male; Mice; Mice, Knockout; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Phenotype; Real-Time Polymerase Chain Reaction; Recovery of Function; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tachycardia, Ventricular; Time Factors; Ventricular Function, Left; Ventricular Remodeling

Angiotensin receptor blockers (ARBs) reduce adverse left ventricular (LV) remodeling and improve LV function and survival when started postmyocardial infarction (MI). ARBs also reduce ventricular arrhythmias during ischemia-reperfusion injury when started pre-MI. No information exists regarding their efficacy and safety when started pre-MI and continued peri- and post-MI. We evaluated whether the ARB losartan improves the outcome when started pre-MI and continued peri- and post-MI. Male Wistar rats (n = 502) were treated for 7 days pre-MI with losartan at a high dose (30 mg.kg(-1).day(-1)), progressively increasing dose (3 mg.kg(-1).day(-1) increased to 10 mg.kg(-1).day(-1) 10 days and 30 mg.kg(-1).day(-1) 20 days post-MI), or no treatment. Ambulatory systolic blood pressure and Holter monitoring were performed for 24 h post-MI. Echocardiography was done 30 days post-MI, and LV remodeling, cardiac hemodynamics, and fetal gene expression were assessed 38 days post-MI. High-dose losartan reduced 24-h post-MI survival compared with the progressive dose and control (21.9% vs. 36.6% and 38.1%, P = 0.033 and P = 0.009, respectively). This was associated with greater hypotension in the high dose and no change in ventricular arrhythmias in all groups. In 24-h post-MI survivors, the progressive dose group had reduced mortality from 24 h to 38 days (8.5% vs. 28.6% for control vs. 38.9% for high dose, P = 0.032 and P = 0.01, respectively). Survivors of both losartan groups demonstrated improved LV remodeling, cardiac hemodynamics, preserved GLUT-4, and reduced cardiac fetal gene expression. Pretreatment with ARBs does not reduce 24-h post-MI ventricular arrhythmias or survival, and high doses increase mortality by causing excessive hypotension. In 24-h post-MI survivors, progressively increasing doses of losartan have multiple beneficial effects, including improved survival.

Topics: Actins; Angiotensin II Type 1 Receptor Blockers; Animals; Atrial Natriuretic Factor; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiac Volume; Dose-Response Relationship, Drug; Echocardiography; Glucose Transporter Type 4; Incidence; Losartan; Male; Monosaccharide Transport Proteins; Muscle Proteins; Myocardial Infarction; Myosin Heavy Chains; Polymerase Chain Reaction; Rats; Rats, Wistar; RNA, Messenger; Tachycardia, Ventricular; Ventricular Fibrillation; Ventricular Pressure; Ventricular Remodeling

Atrial tachycardia and chronic heart failure (CHF) are associated with elevated levels of atrial natriuretic peptide (ANP) and its amino terminal part NT-ANP. Chronic high atrial rates may cause CHF due to a rapid ventricular response. The aim of this study was to establish the contribution of elevated atrial rate and of high ventricular rate, resulting in CHF, on ANP and NT-ANP levels during chronic atrial tachycardia.. Thirteen goats (AV-paced group) were subjected to 4 weeks of rapid AV pacing with an atrial and ventricular rate of 240 beats/min. Another five goats (A-paced group) were subjected to 4 weeks of atrial pacing at 240 beats/min while the ventricular rate was kept low and regular at 80 beats/min. Pacing was interrupted only for measurement of right atrial (RA) and left ventricular (LV) diameter and sampling for ANP, NT-ANP, and renin. In the AV-paced group, RA and LV diameter reached 152% and 109% of baseline values, respectively. Both ANP and NT-ANP (8.3 +/- 9.2 pmol/L and 0.5 +/- 0.4 nmol/L at baseline, respectively) increased progressively (53.1 +/- 37.9 pmol/L and 2.0 +/- 0.9 nmol/L, respectively, after 4 weeks). There was a significant correlation between the magnitude of atrial dilation and natriuretic peptide levels after 3 days. In A-paced goats, however, RA and LV diameters did not change. Furthermore, ANP and NT-ANP levels (9.1 +/- 6.0 pmol/L and 0.8 +/- 0.2 nmol/L at baseline, respectively) were unchanged after 4 weeks (5.3 +/- 3.4 pmol/L and 0.6 +/- 0.2 nmol/L, respectively).. Elevated levels of ANPs during chronic atrial tachycardia are related to a high ventricular rate rather than a high atrial rate alone. Rather than atrial tachycardia, the atrial hemodynamic burden is an important determinant of the sustained ANP response.

Topics: Animals; Atrial Natriuretic Factor; Female; Goats; Heart Failure; Tachycardia, Ectopic Atrial; Tachycardia, Ventricular

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Female; Goats; Heart Failure; Tachycardia, Ectopic Atrial; Tachycardia, Ventricular

Intravenous injection of cesium chloride (Cs) causes ventricular tachyarrhythmias in rabbits. We investigated whether these tachyarrhythmias were caused by increased pressure load and whether they could be suppressed by atrial natriuretic peptide (ANP).. Cs was injected in a bolus dose (1.5 mmol/kg), which was repeated 20 minutes later. Rabbits were then divided into 3 groups: control, ANP-treated, and hydralazine-treated groups. ANP or hydralazine was administered between the first and second Cs injections. The experiments were performed during intrinsic sinus rhythm (protocol A) or during ventricular pacing (protocol B). In protocol A, the second injection of Cs in the control group induced early afterdepolarizations and ventricular tachycardia, which were preceded by a marked increase in left ventricular end-diastolic pressure (LVEDP). Both ANP and hydralazine significantly suppressed Cs-induced increase in LVEDP. The arrhythmia score after the second injection of Cs was significantly lower in the ANP-treated and hydralazine-treated group compared with the control group (P < .005 and P < .05, respectively). In protocol B, the duration of left ventricular monophasic action potential and early afterdepolarization amplitude before and/or after the injections of Cs did not differ significantly between control and ANP-treated groups.. Our results suggest that increased pressure load may play a role in the arrhythmogenic effect of Cs. The protective effect of ANP against Cs-induced ventricular tachycardia may be explained in part by a reduction in pressure overload. However, this effect might also be explained by the diverse action of ANP on the cardiovascular system.

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Cesium; Chlorides; Diastole; Hydralazine; Male; Rabbits; Tachycardia, Ventricular; Vasodilator Agents; Ventricular Function, Left

Topics: Atrial Natriuretic Factor; Electrocardiography, Ambulatory; Heart Failure; Humans; Natriuretic Peptide, Brain; Tachycardia, Ventricular; Ventricular Function, Left

Ventriculoatrial (VA) sequence and neurohumoral responses may be important modulators of hemodynamic recovery during VT. We studied the effects of VA conduction on blood pressure recovery, and levels of atrial natriuretic peptide (ANP), epinephrine, and norepinephrine during simulated VT. After diagnostic coronary angiography, VT was simulated by rapid right ventricular pacing (150 beats/min, 3 mins) in a consecutive series of patients. Whenever the patients demonstrated VA dissociation during ventricular pacing, they were included in the study. After 10 minutes of recovery, a group of nine patients then underwent an additional VA pacing (150 beats/min, 3 mins, VA delay of 150 msec). Intra-arterial blood pressure was continuously monitored, and plasma ANP and catecholamine levels were measured before, during, and after both pacing protocols. The mean arterial pressures declined rapidly by 26% and 30% after initiation of ventricular and VA pacing, respectively. The blood pressure then gradually recovered, the hemodynamic recovery being better during VA pacing. Plasma ANP and catecholamine levels increased toward the end of both pacing periods. The observed increase in ANP concentration was more prominent during VA pacing than ventricular pacing (P < 0.001), whereas catecholamine levels increased similarly. The results show that during simulated VT hemodynamic recovery is partially dependent on VA sequence. The increases in circulating ANP and catecholamines occur too slowly to account for the rapid changes in blood pressures observed after initiation of simulated VT. Therefore, other mechanisms, such as reflex stimulation of the sympathoadrenergic nervous system, must be involved, too. ANP release increases when atrial contraction frequency increases, but the exact determinants for this release remain unknown.

Topics: Adult; Aged; Atrial Natriuretic Factor; Atrioventricular Node; Blood Pressure; Electrocardiography; Epinephrine; Female; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Tachycardia, Ventricular

Plasma levels of atrial natriuretic factor (ANF) and norepinephrine are markedly elevated during episodes of ventricular tachycardia. Although atrial distention appears to be the major stimulus for ANF release, reflex changes in autonomic tone might also contribute. Plasma ANF and norepinephrine levels, sinus node cycle length, systolic blood pressure, and mean right atrial pressure were therefore assessed during rapid right ventricular pacing at 150 beats/min for 10 minutes. In five patients (group 1) observations were made without autonomic blockade, and another five patients (group 2) had ventricular pacing after cardiac autonomic blockade. In group 1 systolic blood pressure fell during ventricular pacing from 122 +/- 4 to 105 +/- 5 mm Hg (p < 0.02), norepinephrine levels increased from 195 +/- 26 to 411 +/- 71 pg/ml (p < 0.02), and sinus node cycle length decreased from 936 +/- 99 to 688 +/- 58 msec (p < 0.02). Right atrial pressure was elevated from 2.6 +/- 0.6 to 7.4 +/- 0.6 mm Hg (p < 0.02), and ANF levels increased from 161 +/- 23 to 240 +/- 26 pg/ml (p < 0.05). Whereas systolic blood pressure, norepinephrine, sinus cycle length, and right atrial pressure returned promptly to baseline levels when ventricular pacing was stopped, ANF levels continued to rise (296 +/- 37 pg/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Atropine; Autonomic Nervous System; Blood Pressure; Cardiac Pacing, Artificial; Electrocardiography; Female; Humans; Male; Middle Aged; Norepinephrine; Propranolol; Tachycardia, Ventricular