Effect of reducing atrial pressure on atrial natriuretic factor and vasoactive hormones in congestive heart failure secondary to ischemic and nonischemic dilated cardiomyopathy

The effect of an acute and sustained reduction in atrial pressure on atrial natriuretic factor (ANF) and vasoactive hormone secretion was studied in 9 patients with congestive heart failure (CHF). Intravenous nitroglycerin was titrated to reduce the pulmonary artery wedge pressure by 30 to 50% and maintain this reduction for 4 hours. After 60 minutes of nitroglycerin administration, the mean decrement in wedge pressure was 10.0 +/- 1.7 (standard error) mm Hg (35%) and plasma ANF was 65.3 +/- 13.9 pmol/liter (35%). The initial decrease, sustained reduction and later increase in plasma ANF levels closely paralleled the changes in pulmonary arterial wedge (r = 0.94, p less than 0.0001) and right atrial pressures (r = 0.91, p less than 0.0001) during and immediately after the nitroglycerin infusion. Plasma aldosterone and cortisol levels increased during the first 2 hours of the nitroglycerin infusion, but there was little change in plasma norepinephrine or plasma renin activity. Although levels were elevated in CHF, plasma ANF still responded rapidly to changes in atrial pressure. A sustained reduction in pressure produced a sustained reduction in ANF levels. These findings provide further support for a regulatory role of ANF, even in chronic CHF.     

Atrial natriuretic factor during percutaneous transluminal coronary angioplasty.

To study the release of plasma atrial natriuretic factor (ANF) and to explain the mechanism underlying its increase during myocardial ischemia, we measured plasma ANF and mean pulmonary capillary wedge pressure (PCW) before, during and after percutaneous transluminal coronary angioplasty (PTCA) in eight patients. All patients were free of calcium channel antagonists and beta-blocking drugs. Evidence of myocardial ischemia was observed in all patients with an increase of PCW from 3.2 +/- 1.2 to 10.6 +/- 2.9 mm Hg (mean +/- SD; p less than 0.001). Heart rate and mean blood pressure did not change significantly. We observed an increase of plasma ANF during PTCA, from 53 +/- 24 to 100 +/- 37 pmol/L (mean +/- SD; p less than 0.005). There was a correlation between absolute values of ANF and PCW before and during PTCA (r = 0.64, p less than 0.01). After PTCA, ANF levels remained increased for at least twenty minutes (p less than 0.005 vs basal state) despite a decrease in PCW. Thus, increase of PCW during this very short-term left ventricular ischemic dysfunction induces an increase of plasma ANF, which persists during a certain time when PCW returns to normal.     

Atrial natriuretic peptide concentrations and pulmonary hemodynamics in patients with pulmonary artery hypertension

To define the relationship between plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) and hemodynamic parameters in patients with chronic pulmonary artery hypertension, we measured plasma concentrations of the peptide in 15 patients during right heart catheterization. Eleven patients had chronic obstructive pulmonary disease and 4 had pulmonary vascular disease of diverse etiology. At rest, plasma concentrations of IR-ANP positively correlated with mean pulmonary artery pressure (r = 0.70, p less than 0.01) and pulmonary vascular resistance (r = 0.88, p less than 0.001), but not with right atrial pressure. Nine of these patients, all with chronic obstructive pulmonary disease, were also evaluated during exercise. Plasma concentrations of IR-ANP increased from 131 +/- 22 to 191 +/- 30 pg/ml (p less than 0.003) at maximal exercise, whereas pulmonary artery pressure increased from 29 +/- 1.5 to 56 +/- 2.5 mm Hg and right atrial pressure from 5 +/- 1 to 13 +/- 2 mm Hg. Increases of plasma IR-ANP concentrations correlated with changes in pulmonary artery pressure and right atrial pressure but not with changes in pulmonary capillary wedge pressure. These findings suggest that ANP is released in response to an increase in pulmonary artery pressure and are consistent with the hypothesis that ANP could modulate the pulmonary vascular tone in patients with pulmonary artery hypertension.     

Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings

To characterize the neural excitatory state of heart failure, simultaneous measurements of efferent sympathetic nerve activity to muscle (by microneurography) and rest hemodynamics were obtained in 10 normal subjects (age 25 +/- 2 years, mean +/- SEM) and 29 patients with heart failure (age 49 +/- 2 years; New York Heart Association functional class II to IV; left ventricular ejection fraction 21 +/- 1%; cardiac index = 2.16 +/- 0.13 liters/min per m2; pulmonary capillary wedge pressure 23 +/- 2 mm Hg). Sympathetic nerve activity was significantly higher in the patients with heart failure (54.7 +/- 4.5 bursts/min) than in normal subjects (16.7 +/- 2.2 bursts/min, p less than 0.001). Multiple linear regression analyses indicated that sympathetic activity in these human subjects was most strongly and inversely correlated with left ventricular stroke work index (r = -0.86, p less than 0.0001) and stroke volume index (r = -0.85, p less than 0.0001). There was a strong positive correlation between sympathetic nerve activity and pulmonary artery diastolic (r = 0.82, p less than 0.0001) and mean (r = 0.81, p less than 0.0001) pressures. Similar correlations were seen when patients with heart failure were analyzed separately. There was no significant correlation between sympathetic nerve activity and mean arterial pressure, left ventricular ejection fraction (by radionuclide ventriculography), cardiac chamber size (by echocardiography) or arterial oxygen tension in the patients with heart failure. Direct measurements of sympathetic nerve activity correlated closely with plasma norepinephrine (r = 0.72, p less than 0.0001) in patients with heart failure. Thus, sympathetic nerve activity at rest parallels impairment of cardiac performance in patients with heart failure.     

Impaired response of atrial natriuretic factor to blood volume expansion in acute right ventricular infarction.

To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction.     

Influence of upright exercise on pulmonary hemodynamics in left heart failure.

Studies in severe chronic stable heart failure (HF) indicate that pulmonary resistance might remain unchanged during exercise and could subsequently contribute to limitation in exercise capacity of these patients. We assessed the possible role of the exercise decreases in mixed venous oxygen tension on this phenomenon in fifteen patients with chronic congestive heart failure (N.Y.H.A. functional classes II to IV) who underwent a symptom-limited treadmill exercise test with hemodynamic monitoring as well as repeated arterial and mixed venous blood gas analysis. For all patients there was an increase in cardiac output (from 3.7 +/- 0.2 to 6.7 +/- 0.5 l/min, p less than 0.001) and pulmonary wedge pressure (from 16 +/- 2 to 31 +/- 3 mm Hg, p less than 0.001) along with exercise with highly significant decrease in total systemic resistance and no significant (from 25.6 +/- 1.5 to 15.8 +/- 1.0 U, p less than 0.001) changes in pulmonary vascular resistances. Arterial blood oxygen tension increased from 86 +/- 3 to 99 +/- 3 mm Hg (p less than 0.001) and mixed venous oxygen tension (PvO2) decreased from 33 +/- 1 to 22 +/- 1 mm Hg (p less than 0.001). Changes in pulmonary vascular resistance during exercise were inversely related to changes in PvO2 (r = -0.61; p less than 0.05). We conclude that the observed decrease in PvO2 might be a determinant of unchanged pulmonary vascular resistance during treadmill-exercise test in severe heart failure patients.     

Preload, adrenergic activity, and aortic compliance in normal and hypertensive patients

Aortic compliance is a major determinant of systolic blood pressure and of impedance to left ventricular ejection. However, little is known about its regulating factors. To assess the effects of preload and adrenergic activity on aortic compliance, we studied 10 normal subjects and nine untreated hypertensive patients at rest and during lower body negative pressure. Aortic compliance was measured invasively from the diastolic decay of the aortic pressure tracing and systemic vascular resistance. Preload was decreased stepwise by lower body negative pressure (-5 to -40 mm Hg) while adrenergic activity was assessed by the change in plasma norepinephrine at a maximum level of negative pressure suction. At rest, aortic compliance was lower in hypertensive subjects compared with its value in normal individuals (0.048 +/- 0.012 [SD] versus 0.071 +/- 0.009 units, p less than 0.001) but correlated inversely with systolic blood pressure in both groups (r = -0.64 in normotensive individuals, r = -0.83 in hypertensive subjects, r = -0.88 for the whole group, p less than 0.001 for all). Whereas resting pulmonary wedge pressure was higher in hypertensive subjects compared with normal individuals (16 +/- 4 [SD] versus 11 +/- 3 mm Hg, p less than 0.05), resting plasma norepinephrine levels were not different between the two groups (261 +/- 139 versus 251 +/- 103 pg/ml). Neither of these two resting indices correlated with baseline aortic compliance in both normotensive individuals and hypertensive patients. During lower body negative pressure (LBNP), cardiac filling pressure (right atrial pressure and pulmonary wedge pressure) as well as cardiac output decreased in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle sympathetic nerve activity and renal responsiveness to atrial natriuretic factor during the development of hepatic ascites.

PURPOSE: Sodium retention in cirrhosis has been attributed to an imbalance between vasoconstrictive antinatriuretic forces such as the sympathetic nervous system and vasodilatory natriuretic agents such as atrial natriuretic factor (ANF). With the development of refractory ascites, cirrhotic patients become unresponsive to the natriuretic effect of ANF. Animal data suggest that the sympathetic nervous system plays a key role in mediating the refractoriness to ANF. We therefore studied the relationship between sympathetic nerve activity (SNA) and the natriuretic response to ANF in normal subjects and cirrhotic patients. We also attempted to localize the intrarenal site of refractoriness to ANF by lithium clearance. PATIENTS AND METHODS: Twenty-six patients with biopsy-proven cirrhosis and seven age- and sex-matched normal volunteers were studied after a week of 20 mmol/day sodium intake and no diuretics. Muscle SNA was recorded from the peroneal nerve (microneurography) and correlated with responsiveness to a 2-hour ANF infusion. Lithium clearance was used as a marker of sodium reabsorption proximal to the intramedullary collecting duct, the main site of ANF action. Plasma norepinephrine, renin, and aldosterone levels were also determined. Patients were categorized into three groups: nine patients free of ascites (by ultrasonography), five ascitic patients who responded to a 2-hour ANF infusion (i.e., had a natriuretic response to ANF above 0.83 mmol/hour), and 12 ascitic patients who did not respond. RESULTS: Muscle SNA was greatly increased in the ascitic nonresponder patients compared with the normal subjects (64 +/- 4 versus 27 +/- 7 bursts/minute, p less than 0.001), moderately increased in ascitic responders (47 +/- 6 bursts/minute, p less than 0.05), but not significantly increased in nonascitic patients with cirrhosis (34 +/- 5 bursts/minute). SNA was positively correlated with plasma norepinephrine levels (r = 0.69; p less than 0.005) and inversely correlated with peak sodium excretion during the ANF infusion (r = -0.63; p less than 0.001). Plasma renin activity and aldosterone were markedly elevated in ascitic nonresponders, and normal in ascitic responders and nonascitic patients. Lithium clearance was reduced in ascitic patients compared with nonascitic patients, did not change after the ANF infusion, and correlated inversely with SNA (r = -0.61; p less than 0.01). CONCLUSION: These results support the concept that the sympathetic nervous system is a factor in renal sodium handling in cirrhosis, especially in the initiation of sodium retention and the development of refractory ascites. Refractoriness to ANF might be explained, at least in part, by increased neurally mediated sodium reabsorption proximal to the intramedullary collecting duct, the main site of ANF action.     

Effects of acute alterations in left ventricular loading conditions on peak filling rate in the denervated (transplanted) ventricle

Peak filling rate is an indicator of left ventricular (LV) diastolic function. It is influenced by heart rate, loading conditions, sympathetic nervous system activity, ejection fraction and other factors. To determine the effect of altered loading conditions on peak filling rate, independent of heart rate and sympathetic nervous system activity, 12 patients were studied 3 weeks after orthotopic heart transplantation. Plasma catecholamine level, heart rate and ejection fraction were not changed by any maneuver. Nitroglycerin caused a decrease in pulmonary artery wedge pressure (9 +/- 2 to 6 +/- 1 mm Hg, p less than 0.001) and in absolute peak filling rate (46.0 +/- 3.0 to 42.8 +/- 2.5 kcts/s, p less than 0.01), but no change in normalized peak filling rate. Volume infusion increased pulmonary artery wedge pressure (9 +/- 2 to 12 +/- 2 mm Hg, p less than 0.001) and absolute peak filling rate (46.0 +/- 3.0 to 51.5 +/- 5.3 kcts/s, p less than 0.01), but peak filling rate normalized to stroke volume was unchanged. During nitroglycerin and volume infusions, there was a high correlation between changes in pulmonary artery wedge pressure and absolute peak filling rate (r = 0.82, p less than 0.001). With normalization of peak filling rate, these variables correlated less well. With methoxamine, 4 patients demonstrating systolic dysfunction had a decrease in absolute and normalized peak filling rate despite a large increase in pulmonary artery wedge pressure. The other 8 patients without systolic dysfunction had an increase in pulmonary artery wedge pressure with increased absolute but unchanged normalized peak filling rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endogenous prostaglandin E2 metabolite levels, renin-angiotensin system and catecholamines versus acute hemodynamic response to captopril in chronic congestive heart failure

Hemodynamic and hormonal responses to captopril were measured in 10 patients with severe chronic heart failure poorly controlled by digitalis and diuretics. After administration of a 25-mg dose, stroke volume (SV) increased from 53 +/- 7 to 63 +/- 9 ml (p less than 0.05), while pulmonary wedge pressure (PWP) decreased from 20 +/- 2 to 14 +/- 2 mm Hg (p less than 0.01). The hemodynamic changes were associated with increases in plasma renin activity (PRA; p less than 0.05) and in plasma levels of a novel bicyclo-prostaglandin E2 metabolite (bicyclo-PGE-m; p less than 0.01), whereas norepinephrine (NE) showed a falling tendency. In general, basal hemodynamic and basal hormonal levels did not correlate. Captopril-induced changes in mean artery pressure (MAP) and mean pulmonary artery pressure (mPAP) were positively correlated to pre-captopril PRA (r = 0.74, p less than 0.01; r = 0.64, p less than 0.05) and to changes in PRA (r = 0.85, p less than 0.01; r = 0.80, p less than 0.01) with a similar trend for angiotensin II (AII); decreases of systemic vascular resistance were more pronounced in patients with higher control NE levels (r = 0.62, p less than 0.05), the reduction of NE levels being highest in patients with higher basal concentrations (p less than 0.001); the captopril-induced decreases of mPAP and PWP were inversely related to basal bicyclo-PGE-m levels (r = 0.60, p less than 0.05; r = 0.61, p less than 0.05), and changes in mPAP were closely related to basal ratios of AII/bicyclo-PGE-m (r = 0.67, p less than 0.01). Thus, captopril exerts its acute beneficial hemodynamic effect by inhibiting the generation of AII, associated with toning down of sympathetic stimulation and increased production of vasodilating prostaglandins, such as PGE2. The relation between AII and PGE2-counteracting substances-might determine the hemodynamic response to captopril in the patients.     

Atrial natriuretic factor, cardiac volumes and filling pressures during exercise in congestive heart failure.

To study the mechanism of atrial natriuretic factor (ANF) release in heart failure, we measured plasma ANF concentrations, cardiac volumes and filling pressures at rest and during three graded exercise levels (E1, E2, E3) in six male patients with congestive heart failure (CHF) and compared them with 13 normal male subjects. At rest, ANF concentrations were sixfold higher in patients with CHF than in normal subjects (at rest: 53 +/- 12 vs 8 +/- 1 pmol.l-1; P less than 0.02). End-systolic ventricular volumes were increased threefold in patients with CHF (P less than 0.02) despite normal mean central venous pressure, pulmonary artery pressure (PAP) and pulmonary wedge pressure (PWP). A positive correlation was found between end-systolic ventricular volumes and plasma ANF (r = 0.93, P less than 0.001). During exercise, ANF rose by 120% over basal values both in patients with CHF and in normal subjects (P less than 0.01). Volumes higher than normal in patients with CHF increased further at E2 (P less than 0.05) in contrast to a decrease of systolic volumes recorded in normal subjects (P less than 0.05). Filling pressures rising abnormally in patients with CHF correlated with plasma ANF during exercise (r = 0.53, P less than 0.02 for PAP; r = 0.51, P less than 0.05 for PWP). In conclusion, our data suggest that ANF release in CHF is regulated at rest by cardiac volumes when filling pressures are still normal. During exercise, ANF release is not impaired in CHF with normal rest filling pressures and is regulated during exercise by left filling pressures.     

Atrial natriuretic factor during exercise in patients with congestive heart failure

In order to evaluate the potential relationship between atrial pressure development and release of atrial natriuretic factor (ANF), 33 patients with congestive heart failure were investigated with right-sided heart catheterization during supine graded bicycle exercise. Resting plasma ANF levels were higher in patients with heart failure as compared with normal controls, 75.1 +/- 45.6 pmol/l vs 12.3 +/- 6.2 pmol/l (mean +/- SD, N = 33 and N = 42, respectively) and correlated with right atrial, pulmonary arterial and pulmonary capillary wedge pressures. During exercise, central pressures rose steeply with a simultaneous increase in plasma ANF in all patients. Plasma ANF levels correlated with heart rate at a workload of 25 w, to pulmonary arterial and pulmonary capillary wedge pressure at 50 w, and to pulmonary capillary wedge pressure at 75 w. The increments in ANF levels between the different workloads during exercise did not correlate with the corresponding increments in pressure values. In congestive heart failure, the capability of ANF secretion in consequence to pressure stimuli is preserved, and left atrial pressure seems to be the major stimulus for ANF release during exercise.     

Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans

To determine whether venous plasma norepinephrine concentrations consistently reflect changes in sympathetic nervous activity, the influence of mental arithmetic, static handgrip, and submaximal bicycle exercise on intra-arterial blood pressure, heart rate, and plasma norepinephrine was studied in 51 subjects with untreated essential hypertension (mean age, 46 years; range, 16-69 years). At rest, plasma norepinephrine was unrelated to age or blood pressure. Mental arithmetic increased mean arterial pressure from 108 +/- 18 to 127 +/- 18 mm Hg (mean +/- S.D.; p less than 0.001) and heart rate from 69 +/- 7 to 93 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (547 +/- 297 to 518 +/- 250 pg/ml). Isometric exercise raised mean arterial pressure from 115 +/- 18 to 148 +/- 21 mm Hg (p less than 0.001) and heart rate from 76 +/- 9 to 95 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (683 +/- 253 to 741 +/- 253 pg/ml). Bicycle exercise increased mean arterial pressure from 114 +/- 20 to 146 +/- 26 mm Hg (p less than 0.001), heart rate from 77 +/- 9 to 128 +/- 19 beats/min (p less than 0.001), and plasma norepinephrine from 645 +/- 228 to 1151 +/- 462 pg/ml (p less than 0.001). Both the maximum mean arterial pressure and the peak heart rate attained during bicycle exercise were related to the exercise plasma norepinephrine level (r = 0.33, p less than 0.02 and r = 0.28, p less than 0.03, respectively). Increases in plasma norepinephrine with exercise were not greater in older or more hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic and pulmonary hemodynamic responses to nicardipine during graded ergometric exercise in patients with moderate to severe essential hypertension

In 10 patients with moderate to severe hypertension, the hemodynamic effects of ergometric exercise and nicardipine, a dihydropyridine calcium channel antagonist, were characterized under basal conditions and after 1 week of therapy. The responses of plasma renin activity and catecholamines were also assessed. Nicardipine induced significant reductions of systolic, diastolic and mean blood pressure under conditions of rest and peak exercise (p less than 0.001), mediated by reversal of vasoconstriction (p less than 0.001). Overall, cardiac index and stroke volume index responses were not significantly altered by nicardipine. Although rest pulmonary wedge pressure was unchanged (6 +/- 3 to 5 +/- 4 mm Hg), peak exercise pulmonary wedge pressure decreased from 24 +/- 22 to 7 +/- 5 mm Hg (p less than 0.001) with nicardipine therapy. This effect of nicardipine on pulmonary wedge pressure was present across all work loads studied, and was accompanied by reduction of peak exercise pulmonary artery pressure from 43 +/- 10 to 25 +/- 7 mm Hg (p less than 0.001). Oxygen consumption was unchanged, associated with reduction of arteriovenous oxygen difference (p less than 0.02). Both plasma renin activity (p less than 0.05) and norepinephrine (p less than 0.005) were significantly increased with nicardipine therapy. Thus, nicardipine produced significant blood pressure reduction by reversal of vasoconstriction in patients with essential hypertension. The preservation of cardiac output, with markedly reduced pulmonary wedge pressure, indicated that nicardipine improved ventricular performance in response to reversal of vasoconstriction.     

Effects of atrial natriuretic factor on coronary hemodynamics and myocardial energetics in patients with heart failure

Synthetic analogues of atrial natriuretic factor (ANF) have been developed for potential use as therapeutic agents in the treatment of congestive heart failure and hypertension. We studied the effects of 14 intravenous infusions of synthetic ANF (anaritide, human ANF 102-126) on coronary hemodynamics and myocardial energetics in six patients with heart failure. ANF infusion caused no change in coronary blood flow and a fall in coronary vascular resistance from 1.22 +/- 0.22 to 1.08 +/- 0.18 mm Hg-min/ml (p less than 0.05). Myocardial oxygen and lactate consumption were unchanged from baseline values. Mean arterial pressure fell from 91 +/- 4 to 78 +/- 3 mm Hg (p less than 0.01), right atrial pressure fell from 10 +/- 1 to 8 +/- 1 mm Hg (p less than 0.01), pulmonary capillary wedge pressure fell from 21 +/- 3 to 16 +/- 2 mm Hg (p less than 0.01), heart rate and cardiac index were unchanged, and systemic vascular resistance fell from 1346 +/- 130 to 1087 +/- 98 dyne-sec/cm5 (p less than 0.05). We conclude that infusion of ANF in hemodynamically effective doses in patients with heart failure decreases coronary vascular resistance with no change in coronary blood flow or myocardial oxygen or lactate metabolism.     

Relationship between depressed baroreflex function and exaggerated sympathetic response to exercise in patients with heart failure

The relationship between impaired baroreflex sensitivity (BS) and the degree of sympathetic activation during exercise in patients with heart failure (HF) has not been studied in detail. For this purpose, we studied BS and measured plasma norepinephrine (NE) at rest, and during and after treadmill exercise in 15 patients and 10 controls. HF patients showed lower BS in comparison to controls (3. 51 +/- 3.62 vs. 9.74 +/- 4.56 ms/mm Hg; p < 0.001), and higher levels of plasma NE at rest (449.3 +/- 147.1 vs. 261.1 +/- 82.48 pg/ml; p < 0.001) and during exercise (1,542 +/- 361.2 vs. 524.6 +/- 92.61 pg/ml; p < 0.001). BS was directly related to pVO2 (r = 0.62; p = 0.0008) and inversely related to NE at peak exercise and to the increase in NE during exercise (r = 0.59, p = 0.005, and r = 0.53; p = 0.0058). Thus, during exercise, a marked sympathetic activation exists in patients with moderate HF. The relationship between increased plasma NE during exercise and decreased BS suggests that impaired baroreceptor function may be present in sympathetic activation in HF patients.     

Exercise hemodynamics and myocardial metabolism during long-term beta-adrenergic blockade in severe heart failure.

Hemodynamics and myocardial metabolism at rest and during exercise were investigated in 21 patients with heart failure. The patients were evaluated before and after long-term treatment (14 +/- 7 months) with the beta-adrenergic blocking agent metoprolol. Clinical improvement with increased functional capacity occurred during treatment. Maximal work load increased by 25% (104 to 130 W; p less than 0.001). Hemodynamic data showed an increased cardiac index (3.8 to 4.6 liters/min per m2; p less than 0.02) during exercise. Pulmonary capillary wedge pressure decreased at rest (20 to 13 mm Hg; p less than 0.01) and during exercise (32 to 28 mm Hg; p = NS). Stroke volume index (30 to 39 g.m/m2; p less than 0.006) and stroke work index (28 to 46 g.m/m2; p less than 0.006) increased during exercise and long-term metoprolol treatment. The arterial norepinephrine concentration decreased at rest (3.72 to 2.19 nmol/liter; p less than 0.02) but not during exercise (13.2 to 11.1 nmol/liter; p = NS). The arterial-coronary sinus norepinephrine difference suggested a decrease in myocardial spillover during metoprolol treatment (-0.28 to -0.13 nmol/liter; p = NS at rest and -1.13 to -0.27 nmol/liter; p less than 0.05 during exercise). Coronary sinus blood flow was unchanged during treatment. Four patients produced myocardial lactate before the study, but none produced lactate after beta-blockade (p less than 0.05). There was no obvious improvement in a subgroup of patients with ischemic cardiomyopathy. In summary, there were signs of increased myocardial work load without higher metabolic costs after treatment with metoprolol.     

Influence of dilated cardiomyopathy, myocarditis and cardiac transplantation on the relation between plasma atrial natriuretic factor and atrial pressures.

To determine whether dilated cardiomyopathy, myocarditis or cardiac transplantation affect the relation between plasma immunoreactive atrial natriuretic factor (ANF) and cardiac filling pressures, right atrial plasma ANF concentration, pulmonary arterial wedge pressure and right atrial pressure were measured in patients with dilated cardiomyopathy (n = 48), dilated cardiomyopathy secondary to myocarditis (n = 20) and prior cardiac transplantation (n = 34). ANF level significantly correlated with both pulmonary arterial wedge and right atrial pressures in patients with dilated cardiomyopathy; however, the presence or absence of myocarditis did not significantly alter these relations (p = 0.88 and p = 0.33 for interaction terms, respectively). For the combined group the ANF-pulmonary arterial wedge pressure relation had a slope of 8.1 pg/ml/mm Hg (95% confidence interval (CI), 5.4 to 10.8; p = 0.0001) and the ANF-right atrial pressure relation a slope of 13.6 pg/ml/mm Hg (CI, 8.5 to 18.7; p = 0.0001). Receiver operator curve analysis identified an optimal dividing point of ANF 150 pg/ml with 100% (CI, 72 to 100%) of patients with right atrial pressure greater than or equal to 8 mm Hg having ANF greater than or equal to 150 pg/ml, but only 56% (CI, 42 to 69%) with pressure less than 8 mm Hg having ANF less than 150 pg/ml. Unlike the patients with cardiomyopathy (with or without myocarditis), cardiac transplant recipients displayed no correlation between ANF level and either pulmonary arterial wedge pressure (p = 0.50) or right atrial pressure (p = 0.29) despite similarly elevated ANF concentrations (mean +/- standard deviation 168 (83) pg/ml in transplant patients versus 185 (114) pg/ml in cardiomyopathy patients). It is concluded that left and right intracardiac pressures are important determinants of circulating ANF level unaffected by inflammation in patients with cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary artery pressure and left ventricular late diastolic pressure in rest and during dynamic load. Comparative studies on pressure transmission in the pulmonary circulation during simultaneous determination]

Left ventricular enddiastolic pressure (LVEDP), mean pulmonary artery pressure (PAPM) and enddiastolic pulmonary artery pressure (PADP) were simultaneously recorded in 19 subjects with normal left ventricular (LV) function, and in 109 patients with LV-dysfunction, 83 of whom were also studied during exercise. Patients with valvular heart disease or atrial fibrillation were excluded from this study. LVEDP and mean pulmonary capillary wedge (PCW) pressure were simultaneously recorded in 81 patients at rest, andin 16 patients also during exercise; the LV diastolic pressure prior to atrial contraction (LVPpreA) could accurately be identified in 45 patients at rest and in 23 patients with exercise. In contrast to the widely accepted opinion of others, the PADP (mean 8.2 +/- 2.2 mm Hg at rest and 12.3 +/- 3.4 mm Hg with exercise) showed a close approximation of LVEDP (10.0 +/- mm Hg at rest and 16.2 +/- 3.5 mm Hg with exercise) only in normal subjects at rest (p less than 0.05 and p less than 0.01 respectively). In patients with LV dysfunction there was no significant difference between PADP (11.7 +/- 4.5 mm Hg and 23.0 +/- 8.9 mm Hg), PCW (11.6 +/- 5.1 mm Hg and 24.1 +/- 11.9 mm Hg) and LVPpreA (12.5 +/- 5.5 and 21.5 +/- 7.7 mm Hg) at rest and during exercise. LVEDP could be estimated with sufficient accuracy only from the PAPM (18.9 +/- 6.5 and 35.7 +/- 10.8 mm Hg). The increase in LVEDP (14.7 +/- 7.7 mm Hg) with exercise was not significantly different from the increase in PAPM (16.8 +/- 7.1 mm Hg). There were highly significant correlations (p less than 0.001) between LVEDP and PADP (r = 0.85) as well as PAPM (r = 0.86) at rest and during exercise with the regressionline being closest to the line of identity for LVEDP and PAPM. The pressure gradient between LVEDP and PADP (LVEDP - PADP = 6.3 mm Hg with exercise) equaled the pressure increase in LV by atrial contraction (LVEDP - LVPpreA = 6.3 and 13.3 mm Hg). The pressure difference between PADP or PAPM and LVEDP remained constant despite marked variation of other hemodynamic parameters, e.g. stroke volume index (SVI), heart rate (HR) and cardiac index(CI). These data suggest that an elevated LVEDP is caused mainly by an augmented atrial contraction in patients with LV dysfunction at rest and with exercise. This mechanism precludes an enddiastolic pressure equilibrium between pulmonary artery and left ventricel. PAPM allows the best estimation of LVEDP independent from other hemodynamic variables.     

Echocardiographic contractility reserve and invasive hemodynamics in physical stress in probands with healthy hearts and patients with dilated cardiomyopathy

In the present study, 17 patients with angiographically proven dilative cardiomyopathy (CM) were investigated simultaneously by both invasive right heart catheter and 1D/2D echocardiography at rest (R) and during bicycle exercise (E) stress test. They were compared with 14 normal subjects (N). The echocardiographic contractility reserve was determined as an increase in the systolic pump function (shortening fraction-SF, ejection fraction - EF) and compared with pulmonary capillary wedge pressure during exercise. 14/17 echocardiograms of dilative cardiomyopathy and all echocardiograms of normal subjects at rest as well as during exercise could be accepted. In N, echocardiographic parameters of systolic function significantly increased during exercise, whereas dilative cardiomyopathy showed decreased contractility reserve with no increase in pump function (for CM patients, at rest SF: 21.3% +/- 8%; EF: 41.6% +/- 14%; exercise SF: 21.3 +/- 9%; EF: 40.7% +/- 15%). Hemodynamic investigation in CM showed no increase in stroke volume accompanied by a pathologic increase in pulmonary wedge pressure, ranging from x = 16.4 mmHg at rest, up to 30.0 mm Hg in exercise (p less than 0.001), whereas in normal subjects, no pathologic increase in pressure was present (from 10.3 mm Hg at rest to 13.7 mm Hg during exercise). There were closed relations between invasive and non-invasive data. The relative alteration of stroke volume during E showed in N and in CM good correlation with echocardiography (N + 19%, CM -2%) and invasive data (N + 18%, CM + 2%). FSe during stress and PCPm showed a closed inverse correlation during exercise (p less than 0.001; r = 0.8). The lower the contractility in echocardiogram, the higher PCPm was in exercise.