Robert J. Howard

Response of atrial natriuretic factor to acute and chronic increases of atrial pressures in experimental heart failure in dogs. Role of changes in heart rate, atrial dimension, and cardiac tissue concentration.

BackgroundThis study evaluated the role of changes in heart rate, atrial pressure, volume, and cardiac tissue atrial natriuretic factor (ANF) concentration in the modulation of plasma ANF concentration in a model of pacing-induced heart failure. Methods and ResultsThe effects of acute right ventricular pacing (250 beats/min), acute volume expansion (35 ml/mmn), and volume expansion after 1 week of right ventricular pacing on plasma ANF concentration were compared in eight dogs (group 1). As shown during right ventricular pacing previously, volume expansion produced significant increases in cardiac filling pressures and left atrial volume. Right ventricular pacing and volume expansion produced similar increments in plasma ANF concentration: from 32±12 to 168±153 pg/ml (p < 0.05) and from 32±9 to 137±113 pg/ml (p < 0.05), respectively. When pacing was initiated after volume expansion, plasma ANF concentration increased further to 462 ±295 pg/ml (p < 0.S05) despite little change in filling pressures and left atrial volume. With repeated volume expansion after 1 week of pacing, there were no significant further increases in left atrial volume and plasma ANF concentrations (from 332±f121 to 407±113 pg/ml) despite significant increases in filling pressures. Atrial and ventricular tissue samples were also obtained from 21 dogs paced to severe heart failure (group 2) and from 14 normal dogs (controls). In all groups, atrial ANF was higher than ventricular ANF concentration. At 1 week (group 1), left atrial appendage ANF concentration (6.2±2.5 versus 16.1±10.3 ng/mg) was reduced, whereas left ventricular free wall ANF concentration (0.62±0.31 versus 0.24±0.16 pg/mg) was increased compared with that of controls (both p < 0.001). At severe heart failure (group 2), atrial ANF remained low, whereas ventricular ANF concentration was similar to that of the controls. ConclusionsThese data indicate that in pacing-induced heart failure, changes in heart rate, atrial pressure, and volume all contribute to the increased plasma ANF concentration. However, by 1 week (early heart failure), ANF release is attenuated, perhaps because of the inability of the atria to be stretched further and because of reduced atrial ANF concentration. In addition, the ventricle may be an additional source of ANF.

Dual natriuretic peptide system in experimental heart failure

OBJECTIVES The objectives of this study were 1) to define in an experimental model of heart failure the time course of changes in plasma brain natriuretic peptide concentrations during the development of and recovery from heart failure, and 2) to relate the changes to changes in atrial natriuretic peptide concentration and hemodynamic status. BACKGROUND Brain natriuretic peptide is a circulating peptide with homology to atrial natriuretic peptide. However, unlike the latter, its changes during heart failure and its relation to cardiac filling pressures have not been studied. METHODS Eight male mongrel dogs underwent right ventricular pacing at 250 beats/min for 3 weeks until heart failure occurred and were followed up during recovery for 4 weeks after cessation of pacing. RESULTS Heart failure was characterized by an increase in both left ventricular and end-diastolic pressure (6.6 +/- 4.1 mm Hg at the control measurements to 35.1 +/- 5.9 mm Hg at 3 weeks, p < 0.01) and right atrial pressure (6.7 +/- 1.1 to 11.4 +/- 2.1 mm Hg, p < 0.01). Recovery was accompanied by a return of cardiac filling pressures to control level. The time course of change of arterial plasma brain natriuretic peptide concentration was similar to that of atrial natriuretic peptide. Plasma concentrations of both peptides increased after 1 week of pacing (16 +/- 4 pg/ml at the control measurement to 59 +/- 20 pg/ml at 1 week, p < 0.001 for brain natriuretic peptide and 84 +/- 55 to 856 +/- 295 pg/ml, p < 0.001 for atrial natriuretic peptide). The level of both peptides then stayed level with no further increase at 3 weeks and returned to the control value by 4 weeks of recovery. There was an excellent correlation between plasma concentrations of the two peptides (r = 0.86, p < 0.001) and between the two peptides and cardiac filling pressures. However, compared with atrial natriuretic peptide, plasma brain natriuretic peptide concentration had a smaller percent increase during evolving heart failure and a slower rate of decline at recovery. CONCLUSIONS Brain and atrial natriuretic peptide constitute a dual natriuretic system and are both responsive to changes in cardiac filling pressures in heart failure. However, brain natriuretic peptide appears to be less responsive than atrial natriuretic peptide.

Plasma and cardiac tissue atrial and brain natriuretic peptides in experimental heart failure

OBJECTIVES This study evaluated the role of changes in heart rate, cardiac filling pressures and cardiac tissue atrial and brain natriuretic peptides in the modulation of their plasma levels in a model of heart failure. BACKGROUND Atrial and brain natriuretic peptides constitute a dual natriuretic peptide system that regulates circulatory homeostasis. METHODS The effects of 1) acute ventricular pacing, 2) acute volume expansion, and 3) volume expansion after 1 week of continuous pacing on plasma atrial and brain natriuretic peptide levels were compared in eight dogs. Atrial and ventricular tissue levels of the peptides were examined in 5 normal dogs (control group), 21 dogs paced for 1 week (group 1) and 10 dogs paced for 3 weeks (group 2). RESULTS Both acute pacing and volume expansion increased plasma atrial natriuretic peptide levels (from 53 +/- 41 to 263 +/- 143 pg/ml [mean +/- SD], p < 0.01, and from 38 +/- 23 to 405 +/- 221 pg/ml, p < 0.001, respectively). After 1 week, there was a marked increase in plasma levels of atrial natriuretic peptide, but the level did not increase further with volume expansion (from 535 +/- 144 to 448 +/- 140 pg/ml, p = 0.72). By contrast, plasma brain natriuretic peptide levels increased only modestly with acute pacing (from 12 +/- 4 to 20 +/- 8 pg/ml, p < 0.05) and after pacing for 1 week (from 13 +/- 4 to 48 +/- 20 pg/ml, p < 0.05) but did not change with acute or repeat volume expansion. In groups 1 and 2, atrial tissue levels of atrial natriuretic peptide (1.9 +/- 1.3 and 2.0 +/- 0.9 ng/mg, respectively) were lower than those in the control group (11.7 +/- 6.8 ng/mg, both p < 0.001), whereas ventricular levels were similar to those in the control group. Atrial tissue brain natriuretic peptide levels in groups 1 and 2 were similar to those in the control group. However, ventricular levels in group 2 (0.018 +/- 0.006 ng/mg) were increased compared with those in the control group (0.013 +/- 0.006 ng/mg, p < 0.05) and in group 1 (0.011 +/- 0.006 ng/mg, p < 0.05). CONCLUSIONS Atrial and brain natriuretic peptides respond differently to changes in heart rate and atrial pressures. Reduced atrial tissue atrial natriuretic peptide levels in heart failure may indicate reduced storage after enhanced cardiac release. However, the relatively modest change in cardiac tissue brain natriuretic peptide levels suggests that the elevated plasma levels may be mediated by mechanisms other than increased atrial pressures.

Response of atrial natriuretic factor to postural change in patients with heart failure versus subject with normal hemodynamics

The response of atrial natriuretic factor to an acute increase in atrial pressures produced by changing from a 45 degrees upright to a -15 degrees Trendelenburg tilt was examined in 21 patients with heart failure and 8 control subjects with normal hemodynamics. In the control subjects, baseline (45 degrees upright tilt) pulmonary capillary wedge and right atrial pressures increased from 3.1 +/- 0.9 (mean +/- SEM) and 4.4 +/- 0.3 mm Hg to 6.9 +/- 1.9 and 8.5 +/- 0.4 mm Hg, respectively (p less than 0.05 for both), 30 min after the -15 degrees tilt. Baseline arterial plasma atrial natriuretic factor concentration increased from 34 +/- 4 to 44 +/- 1 pg/ml (p less than 0.05) 30 min after the tilt, with an increase observed in every patient. In the group with heart failure, baseline pulmonary capillary wedge and right atrial pressures increased from 17.5 +/- 2.0 and 5.3 +/- 1.2 mm Hg to 24.6 +/- 1.8 and 9.7 +/- 1.3 mm Hg, respectively (p less than 0.01 for both), 30 min after the tilt. Plasma atrial natriuretic factor concentration was 326 +/- 38 pg/ml at baseline and 347 +/- 34 pg/ml (p = NS) 30 min after tilt. Compared with the 7 patients with heart failure who had increased atrial natriuretic factor concentrations after the tilt (responders), the 14 patients with unchanged or decreased atrial natriuretic factor concentrations after the tilt (nonresponders) had a higher baseline right atrial pressure and atrial natriuretic factor concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Biatrial appendage hypertrophy but not ventricular hypertrophy: A unique feature of canine pacing-induced heart failure

BACKGROUND The canine model of pacing-induced heart failure is characterized by an absence of ventricular hypertrophy despite severe hemodynamic stress and neurohormonal activation. Given the mode of ventricular pacing, hypertrophy might occur in the atrial appendage. METHODS AND RESULTS Seventeen dogs underwent continuous right ventricular pacing for 3 weeks to severe heart failure. Twelve normal dogs served as control subjects. Pacing produced marked increases in both pulmonary capillary wedge pressure (7.6 +/- 1.8 mmHg at baseline to 32.6 +/- 7.5 mmHg at 3 weeks, P < .001) and right atrial pressure (6.5 +/- 1.8 to 15.1 +/- 2.4 mmHg, P < .001), marked increases in normalized left ventricular volume (3.0 +/- 0.5 to 4.6 +/- 0.5 mL/kg, P < .001) and left atrial volume (1.0 +/- 0.2 to 2.6 +/- 0.5 mL/kg, P < .001), but no change in left ventricular mass (2.3 +/- 0.4 to 2.6 +/- 0.5 g/kg, differences not significant), indicating no ventricular hypertrophy. Compared to the control dogs, total heart weight in the test animals was similar, but both the left appendage (0.18 +/- 0.04 vs 0.10 +/- 0.03 g/kg, P < .001) and right atrial appendage (0.15 +/- 0.03 vs 0.12 +/- 0.02 g/kg, P = .004) were much heavier than those of the control dogs. CONCLUSIONS Rapid right ventricular pacing in the dog induces severe heart failure associated with a dichotomous response in the atrial appendage versus the ventricle. Aside from being a useful heart failure model that simulates the human condition, this unique feature may have physiologic implications in terms of atrial mechanical and endocrine functions and have applications for future studies into the mechanisms of cardiac remodeling and hypertrophy.