Plasma Atrial Natriuretic Factor Research Articles

Atrial natriuretic factor: is it responsible for hyponatremia and natriuresis in neurosurgery?

ObjectiveTo evaluate the presence of hyponatremia and natriuresis and their association with atrial natriuretic factor in neurosurgery patients.MethodsThe study included 30 patients who had been submitted to intracranial tumor resection and cerebral aneurism clipping. Both plasma and urinary sodium and plasma atrial natriuretic factor were measured during the preoperative and postoperative time periods.ResultsHyponatremia was present in 63.33% of the patients, particularly on the first postoperative day. Natriuresis was present in 93.33% of the patients, particularly on the second postoperative day. Plasma atrial natriuretic factor was increased in 92.60% of the patients in at least one of the postoperative days; however, there was no statistically significant association between the atrial natriuretic factor and plasma sodium and between the atrial natriuretic factor and urinary sodium.ConclusionHyponatremia and natriuresis were present in most patients after neurosurgery; however, the atrial natriuretic factor cannot be considered to be directly responsible for these alterations in neurosurgery patients. Other natriuretic factors are likely to be involved.

Uncoordinated regulation of atrial natriuretic factor and brain natriuretic peptide in lipopolysaccharide-treated Rats

We investigated the expression and secretion of the natriuretic peptides (NPs) ANF and BNP in lipopolysaccharide (LPS)-induced sepsis and its association with cytokines and other biologically active substances. LPS treatment increased plasma levels of ANF and BNP. The latter increase was larger than the increase in plasma ANF. LPS also increased cardiac content and gene expression of BNP but not of ANF. LPS treatment significantly increased gene expression cytokines, chemokines and proteases, which significantly correlated with BNP gene expression. SB203580, a p38 MAP kinase inhibitor, inhibited the elevation of BNP in plasma. The present work suggests that during inflammation, BNP gene expression and secretion is uniquely related to changes in gene expression in the absence of hemodynamic changes and hence differentiates ANF and BNP as biomarkers of cardiac disease.

Humoral and Renal Response to Acute Volume Loading in Patients with Essential Hypertension

The effect of acute volume expansion (2 liters of saline solution in 2 h) on plasma concentrations of atrial natriuretic factor (ANF), plasma aldosterone concentration (PAC), plasma renin activity (PRA) and their relationship to the renal excretion of urine, sodium and potassium were studied in 6 control subjects and 7 patients with essential hypertension (EH) WHO stage I. Saline infusion provoked comparable rise in plasma ANF in both groups (from 2.98 +/- 0.45 to 12.36 +/- 1.74 pmol/l in the control subjects and from 3.80 +/- 0.72 to 15.78 +/- 2.06 pmol/l in EH patients), significant drop in PRA (from 0.915 +/- 0.419 to 0.256 +/- 0.127 nmol/l/h in controls and from 1.711 +/- 0.324 to 0.714 +/- 0.128 nmol/l/h in EH) and in PAC (from 0.30 +/- 0.07 to 0.14 +/- 0.03 nmol/l in control subjects and from 0.53 +/- 0.13 to 0.24 +/- 0.07 nmol/l in EH). The increase of plasma ANF concentrations after volume expansion might be involved in the suppression of PRA and PAC found after this stimulus. Similar increase in plasma ANF after saline infusion in both groups was associated with significantly greater urine and sodium excretion in EH than in controls. From these results it may be suggested that the acute volume expansion during saline infusion evokes a comparable release of ANF into circulation in both EH patients and controls. In EH patients, however, the similar rise in ANF is accompanied by a more pronounced diuretic and natriuretic response. This exaggerated natriuresis after acute volume and sodium loading cannot be explained solely by a rise in ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial atrial natriuretic factor gene expression after coronary ligation in rats.

The atrial natriuretic factor (ANF) messenger RNA (mRNA) content was determined in a rat model of acute myocardial infarction. Non-infarcted tissue of left and right ventricles were examined soon after ligation of the left descending anterior coronary artery. In the left ventricles, ANF mRNA/alpha-actin mRNA ratio increased to reach a maximum on day 7 and was sustained while in the right ventricle, the maximum was reached on day 1. The plasma ANF was significantly (p < 0.01) elevated from days 1 to 28 after coronary ligation. The primary compensatory response of ANF within the first 7 days may be attributed not only its synthesis in the left ventricle but also to its generation in the right ventricle in acute heart failure.

Angiotensin II receptor antagonism reverts the selective cardiac BNP upregulation and secretion observed in myocarditis

The cardiac natriuretic peptides atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are discoordinately regulated in myocardial inflammation associated with acute allograft rejection in humans and during in vitro exposure of cardiocyte cultures to some proinflammatory cytokines. We used experimental autoimmune myocarditis (EAM) to determine whether the discoordinate regulation of ANF and BNP was specific to the situations above or was generally associated with other types of myocardial inflammation. The dependency of this process to angiotensin signaling was also determined, given that previous work demonstrated beneficial effects of the angiotensin receptor blocker olmesartan in myocarditis. Histopathological changes, plasma and cardiac ANF, BNP, and selected cytokines gene expression as well as plasma cytokine levels using a cytokine array were determined in EAM, angiotensin receptor blocker-treated, and control rats. It was found that EAM specifically increases BNP but not ANF circulating levels, thus mimicking the findings in acute cardiac allograft rejection and the effect of some proinflammatory cytokines on cardiocyte cultures in vitro. Plasma cytokine array and real-time PCR revealed that lipopolysaccharide-induced CXC chemokine, monocyte chemotactic protein-1, and tissue inhibitor of metalloproteinase-1 were increased in plasma and in the myocardium of EAM rats. Olmesartan treatment reversed virtually all neuroendocrine and histopathological cardiac changes induced by EAM, thus providing a mechanistic insight into this phenomenon. It is concluded that the inflammatory process contributes specific cytokines, leading to the disregulation of cardiac ANF and BNP production observed during myocardial inflammation, and that this process is angiotensin receptor 1 dependent.

Modification of atrial natriuretic factor by the AV transmission time in pacemaker patients

The possible relationship of variations in the programmed a-v interval on the peripheral-venous plasma level of the atrial natriuretic factor (ANF) was investigated in nine patients with dual-chamber pacemakers (DDD). During atrial and ventricular stimulation at 82 beats/min the pacemakers of the resting patients were programmed to give successive a-v intervals of 200, 175, 150, 125, 100, 50 and 15 ms. Blood samples were obtained from a peripheral arm vein ten minutes after each change of programme. ANF was extracted from each sample and determined by radioimmunoassay. Both the absolutely and relatively lowest plasma ANF level was obtained at an a-v interval of 175 ms. Lengthening the interval to 200 ms or shortening it to 150 ms or less increased the level. It is possible that both "too long" and "too short" a-v intervals produce an increase in atrial pressure and stretch, to which ANF reacts highly sensitively with an increase in peripheral-venous plasma levels of ANF.

Effects of Tangshenling Mixture and benazepril on rats with diabetic nephropathy and its mechanism

To investigate the effects of Tangshenling Mixture (TSLM) and benazepril on rats with diabetic nephropathy (DN) and its mechanism. Diabetic nephropathy was induced in rats by intraperitoneal injection of streptozotocin. Fifty-eight rats with DN were randomly divided into four groups: untreated group, TSLM-treated group, TSLM plus benazepril-treated group and benazepril-treated group. Another seven normal rats were included in normal control group. Then, rats in each group were accordingly given normal saline, TSLM, TSLM plus benazepril and benazepril orally for six weeks respectively. Blood and urine biochemical indexes, plasma atrial natriuretic factor (ANF), pathomorphology of renal tissue, transforming growth factor beta1 (TGF-beta1) and glucose transporter 1 (GLUT1) mRNAs in renal tissue were observed. Both TSLM and benazepril could decrease urinary albumin excretion rates, creatinine clearance and ratio of kidney weight to body weight of the rats with DN as well as reduce the pathological damages of the renal tissues. TSLM could reduce the level of plasma ANF and the expression of GLUT1 mRNA, but had no significant effect on the expression of TGF-beta1 mRNA. Benazepril could reduce the expression of TGF-beta1 mRNA, but had no significant effect on plasma ANF and the expression of GLUT1 mRNA. TSLM can reduce the pathological damages of renal tissues in rats with early-stage DN, and its mechanism may relate to decreasing the level of plasma ANF and the expression of GLUT1 mRNA which is different from that of benazepril. It seems that TSLM has synergetic effect with benazepril.

Reduced water and sodium intakes associated with high levels of natriuretic factor following common bile duct ligation in the rabbit

Renal failure complicating obstructive jaundice (OJ) is probably linked to reduction of the extracellular water compartment. To elucidate the mechanism by which OJ leads to isotonic water depletion we studied a group of rabbits with OJ after common bile duct ligation (n = 17) and another group of sham operated rabbits (n = 14) for 10 days. Water intake and balance for two study periods (1-4 and 7-10 days after operation) were calculated. Renal function, sodium balance and plasma atrial natriuretic factor were determined on the fourth and tenth days after operation. Water intake and balance were lower in the OJ group both in the first study period (230 versus 519 ml/days 1-4, P less than 0.001; and -2.4 versus 219 ml/days 1-4, P less than 0.0001 respectively) and in the second study period (260 versus 865 ml/days 7-10, P less than 0.0001; and 11 versus 379 ml/days 7-10, P less than 0.0001 respectively). Sodium intake was negligible in the OJ group both on day four (0.73 versus 7.15 mM/24 h, P less than 0.0001) and on day 10 (0.78 versus 15.78 mM/24 h, P less than 0.0001). As a result plasma osmolality did not change. Day 10 urine osmolality and osmolar clearance were reduced in the OJ group (653 versus 1103 mOsm/kg, P less than 0.0001 and 0.09 versus 0.25 ml/min, P less than 0.0001 respectively) together with a decreased creatinine clearance (3 versus 11 ml/min, P less than 0.0001). Atrial natriuretic factor was increased in jaundiced rabbits (day 4, 22.7 versus 7.5 fmol/ml, P less than 0.0001; and day 10, 26.5 versus 11.2 fmol/ml, P less than 0.02). These findings suggest that OJ leads to an isotonic volume depletion resulting from abnormalities of the extracellular volume regulating mechanisms. These appear to be secondary to an inappropriate elevation of the atrial natriuretic factor plasma concentration.

Acute Pressor and Hormonal Effects of β-Endorphin at High Doses in Healthy and Hypertensive Subjects: Role of Opioid Receptor Agonism

The opioid system is involved in blood pressure regulation in both normal humans and patients with essential hypertension. The objective of the study was to investigate the effects of a high-dose infusion of beta-endorphin, an opioid peptide, on blood pressure and on the hormonal profile in healthy subjects and in hypertensive patients and the mediation played by opioid receptor agonism. According to a randomized double-blind design, 11 healthy subjects (controls) and 12 hypertensive inpatients (mean age, 38.9 and 40.4 yr, respectively) received 1-h iv infusion of beta-endorphin (250 mug/h) and, on another occasion, the same infusion protocol preceded by the opioid antagonist naloxone (8 mg). Hemodynamic and hormonal measurements were performed at established times during the infusion protocols. At baseline, circulating beta-endorphin, norepinephrine, and endothelin-1 in hypertensive patients were significantly (P < 0.05) higher than in controls. In controls, beta-endorphin reduced blood pressure (P < 0.01) and circulating norepinephrine (P < 0.02) and increased plasma atrial natriuretic factor (P < 0.003) and GH (P < 0.0001). In hypertensive patients, beta-endorphin decreased systemic vascular resistance (P < 0.0001), blood pressure (P < 0.0001), and plasma norepinephrine (P < 0.0001) and endothelin-1 (P < 0.0001) and raised circulating atrial natriuretic factor (P < 0.0001), GH (P < 0.0001), and IGF-I (P < 0.0001). These hemodynamic and hormonal responses to beta-endorphin in hypertensive patients were significantly (P < 0.0001) greater than in controls but were annulled in all individuals when naloxone preceded beta-endorphin infusion. High doses of beta-endorphin induce hypotensive and beneficial hormonal effects in humans, which are enhanced in essential hypertension and are mediated by opioid receptors.

Respiratory-related heart rate variability in progressive experimental heart failure

Heart failure is associated with autonomic imbalance, and this can be evaluated by a spectral analysis of heart rate variability. However, the time course of low-frequency (LF) and high-frequency (HF) heart rate variability changes, and their functional correlates during progression of the disease are not exactly known. Progressive heart failure was induced in 16 beagle dogs over a 7-wk period by rapid ventricular pacing. Spectral analysis of heart rate variability and respiration, echocardiography, hemodynamic measurements, plasma atrial natriuretic factor, and norepinephrine was obtained at baseline and every week, 30 min after pacing interruption. Progressive heart failure increased heart rate (from 91 +/- 4 to 136 +/- 5 beats/min; P < 0.001) and decreased absolute and normalized (percentage of total power) HF variability from week 1 and 2, respectively (P < 0.01). Absolute LF variability did not change during the study until it disappeared in two dogs at week 7 (P < 0.05). Normalized LF variability increased in moderate heart failure (P < 0.01), leading to an increased LF-to-HF ratio (P < 0.05), but decreased in severe heart failure (P < 0.044; week 7 vs. week 5). Stepwise regression analysis revealed that among heart rate variables, absolute HF variability was closely associated with wedge pressure, right atrial and pulmonary arterial pressure, left ventricular ejection fraction and volume, ratio of maximal velocity of early (E) and atrial (A) mitral flow waves, left atrial diameter, plasma norepinephrine, and atrial natriuretic peptide (0.45 < r < 0.65, all P < 0.001). In tachycardia-induced heart failure, absolute HF heart rate variability is a more reliable indicator of cardiac dysfunction and neurohumoral activation than LF heart rate variability.

Neuroendocrine Profiling of Humans Receiving Cardiac Allografts

Several studies have investigated changes in circulating hormones and markers of cardiac status after heart transplantation in humans. As a result, plasma levels of various hormones and autocoids have been associated with cardiac allograft rejection status. However, no clear associations can be defined given the highly contradictory nature of the available literature. In this study of 69 consecutive heart transplant patients followed for >2 years we examine the relationship between neurohumors potentially related to allograft rejection and endomyocardial biopsy grade of rejection (according to the ISHLT) and hemodynamic status. Markers assessed include brain natriuretic peptide (BNP), amino-terminal pro-BNP (N-BNP), atrial natriuretic factor (ANF), adrenomedullin, interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, troponin C and C-reactive protein. The highest plasma levels for most neurohumors were found shortly after surgery and showed a trend towards normalization with time. BNP and N-BNP were the only significantly elevated plasma analytes for patients with Grade 3 rejection as compared with other ISHLT grades. ANF plasma levels correlated with BNP and N-BNP in Grades 0 to 2, but not in Grade 3, suggesting that in this rejection grade the usual coordinated changes observed in BNP and ANF secretion no longer exist. Cardiac filling pressures were correlated with plasma BNP, N-BNP and ANF levels only for Grades 0 and 1. The timing of blood sampling after transplantation influences the level of the neurohumors measured, which may help explain the conflicting literature reports on the association between neurohumor levels and rejection grade. The significant increase in circulating levels of BNP and N-BNP observed in most cases of Grade 3 rejection occurred with no apparent relationship to post-transplantation time, which suggests a specific influence of acute rejection on BNP gene expression.

Oligopeptidase B from Trypanosoma evansi: A PARASITE PEPTIDASE THAT INACTIVATES ATRIAL NATRIURETIC FACTOR IN THE BLOODSTREAM OF INFECTED HOSTS

Serine oligopeptidases of trypanosomatids are emerging as important virulence factors and therapeutic targets in trypanosome infections. We report here the isolation and characterization of oligopeptidase B (OpdB) and its corresponding gene from Trypanosoma evansi, a pathogen of significant veterinary importance. The T. evansi opdB gene was present as a single copy per haploid genome containing an open reading frame of 2148 bp encoding a protein of 80.664 kDa. Purified OpdB hydrolyzed substrates with basic residues in P1 (k(cat)/K(m) for carbobenzyloxy-L-arginyl-L-arginyl-7-amido-4-methylcoumarin, 337 s(-1) x microm(-1)) and exhibited potent arginyl carboxypeptidase activity (k(cat)/K(m) for Val-Lys-Arg Arg-OH, 231 s(-1) x mM(-1)). While not secreted, T. evansi released OpdB into the plasma of infected hosts where it retained catalytic activity. Plasma OpdB levels correlated with blood parasitemia. In vitro, OpdB cleaved the peptide hormone atrial natriuretic factor (ANF) at four sites: Arg3 Arg4, Arg4 Ser5, Arg11 Ile12, and Arg27 Tyr28, thereby abrogating smooth muscle relaxant and prohypotensive properties of ANF. Circulating plasma ANF levels in T. evansi-infected rats were depressed from 130 to 8 pg x ml(-1), and plasma ANF levels inversely correlated with plasma OpdB activity. The in vitro half-life of ANF in rat plasma was reduced 300-fold in plasma from T. evansi-infected rodents, which contains high levels of OpdB activity. Addition of OpdB inhibitors to cell-free plasma from infected rodents significantly abrogated this ANF hydrolysis. Furthermore the in vivo ANF half-life was reduced 5-fold in T. evansi-infected rats. Thus, we propose a role for OpdB in peptide hormone dysregulation in trypanosomiasis, specifically in generating the depressed plasma levels of ANF in mammals infected with T. evansi.

Natriuretic peptides as prognostic and diagnostic markers in Chagas' disease

Atrial natriuretic factor (ANF) is a hormone secreted predominantly from atrial myocardium in response to changes in wall tension. Chagas' disease is caused by the parasite Trypanosom cruzi (T. cruzi), the heart being one of the most affected organs, resulting in myocarditis and chronic cardiomyopathy. The inflammatory response of the myocardium may be the result of factors such as ischemia, direct parasite invasion, and autoimmune mechanisms. In this review, we discuss the current knowledge about ANF in Chagas' disease and describe our findings in studying: (1) the development of chagasic cardiomyophathy in T. cruzi-infected rats and its relationship with plasma ANF levels; (2) the evolution of plasma ANF in chagasic patients in different stages (asymptomatic, with conduction defects and with chronic heart failure [CHF]); and (3) the possible usefulness of plasma ANF as a prognostic factor of development of myocardial compromise and survival. In rats, the elevated ANF levels found could mirror the inflammatory response of myocardial cells to acute T. cruzi infection and of progressive failure of cardiac function in the chronic infection. In patients, plasma ANF could be a sensitive marker capable of detecting gradual impairments in cardiac function and poor survival in CHF patients and of myocardiopathy development in the asymptomatic state.

Hyperaldosteronism and Hypertension

The purpose of this study is to evaluate the relationship between aldosterone and blood pressure in a total of 220 normotensive and 293 essential hypertensive subjects in 2 genetically distinct populations-blacks and white French Canadians. The 24-hour blood pressure monitoring was performed under standardized conditions after discontinuing antihypertensive medications. Plasma renin activity and plasma aldosterone were measured in the supine position and after standing for 10 minutes. Plasma atrial natriuretic factor was also measured. Supine and standing plasma renin activities were lower (P< or =0.01), plasma aldosterone was higher (P<0.0001), and the aldosterone/renin ratios were higher (P<0.0001) in the hypertensive subjects. Atrial natriuretic factor was also higher in the hypertensive subjects (P<0.0001). Among blacks, blood pressures did not correlate with plasma renin activity. However, both average daytime and nighttime systolic and diastolic blood pressures were correlated with supine and standing plasma aldosterone and with the aldosterone/renin ratio (P<0.005 or less). In French Canadians, blood pressures tended to be positively correlated with standing plasma renin activity and aldosterone, but not with the aldosterone/renin ratio. Correlations of blood pressure with aldosterone were more consistent and more striking in blacks than in French Canadians. In both ethnic groups, there were inconsistent correlations of blood pressure with atrial natriuretic factor. These observations are consistent with the hypothesis that aldosterone-induced volume expansion is an important contributor to hypertension, especially in blacks.

Echocardiographic features of Radiation-Associated valvular disease

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Atrial natriuretic factor as marker of myocardial compromise in Chagas' disease.

This study investigated the evolution of plasma atrial natriuretic factor (ANF) in patients in different stages of Chagas' disease and analyzed its usefulness as prognostic factor of the development of myocardial compromise in asymptomatic chagasic patients. Chagas' disease, a determinant of heart failure, is caused by the parasite Trypanosoma cruzi. A total of 21 chagasic patients were studied: 9 in the asymptomatic stage, 6 with conduction defects (CD), and 6 with chronic heart failure (CHF); and 31 controls: 16 healthy, 6 with CD, and 9 with CHF. Plasma ANF radioimmunoassay (RIA) and complementary studies were performed twice for each patient, with an interval period of 12 months. First sample: chagasic patients showed higher ANF levels in the CHF group than in CD and asymptomatic subjects; second sample: the peptide levels were higher in CHF patients than in the asymptomatic group. In non-chagasic CHF patients, ANF levels were higher than in CD patients and controls in both samples. ANF levels were not able to differentiate chagasic asymptomatic and CD patients from healthy subjects and CD controls; meanwhile, chagasic CHF patients showed lower plasma ANF than their controls. Furthermore, ANF is a sensitive marker capable of detecting gradual impairments in cardiac function in all patients studied.

Impaired Response to Insulin Associated with Protein Kinase C in Chronic Fructose-induced Hypertension

A fructose-enriched diet induces an increase in blood pressure associated with metabolic alterations in rats. Our hypothesis was that an increase in protein kinase C (PKC) activation, reported in the acute period of fructose overload, and an impaired vessel's response to vasoactive substances contribute to maintain elevated blood pressure levels in the chronic period. The aims of this study were to investigate in this animal model of hypertension: (1) if the increase in PKC activation was also found in the chronic stage; (2) the involvement of nitric oxide and insulin in the vessel's response; and plasma atrial natriuretic factor and nitrites/nitrates (nitric oxide metabolites) behavior. We evaluated the effects of: PKCstimulator 12,13-phorbol dibutyrate, phenylephrine, insulin, nitric oxide synthase-inhibitor N G -nitro- L arginine methyl esther (L-NAME) and PKC-inhibitor Calphostin C on aortic rings responses of Sprague- Dawley rats: fructose-fed and control. The fructose-fed group showed higher contractility to 12,13- phorbol dibutyrate than the control group in aortic rings pre-incubated with insulin, and this difference disappeared with L-NAME. The response to phenylephrine in rings pre-incubated with Calphostin C was decreased in the fructose-fed group and increased with Calphostin C plus L-NAME. Fructose-fed rats showed higher levels of plasma atrial natriuretic factor and nitrites/nitrates than controls. In conclusion, chronic fructose feeding seems to develop an impaired response to insulin, dependent on nitric oxide, suggesting a PKC alteration. Vasorelaxant agents, such as atrial natriuretic factor and nitric oxide, would behave as compensatory mechanisms in response to high blood pressure.

Progression of heart failure after myocardial infarction in the rat

This study examined the early neurohumoral events in the progression of congestive heart failure (CHF) after myocardial infarction (MI) in rats. Immediately after MI was induced by coronary artery ligation, rats had severely depressed left ventricular systolic function and increased left ventricular end-diastolic volume (LVEDV). Both left ventricular function and the neurohumoral indicators of CHF underwent dynamic changes over the next 6 wk. LVEDV increased continuously over the study interval, whereas left ventricular stroke volume increased but reached a plateau at 4 wk. Plasma renin activity (PRA), arginine vasopressin, and atrial natriuretic factor all increased, but with differing time courses. PRA declined to a lower steady-state level by 4 wk. Six to 8 wk after MI, CHF rats had enhanced renal sympathetic nerve activity and blunted baroreflex regulation. These findings demonstrate that the early course of heart failure is characterized not by a simple "switching on" of neurohumoral drive, but rather by dynamic fluctuations in neurohumoral regulation that are linked to the process of left ventricular remodeling.

Behavior of atrial natriuretic factor in an experimental model of Trypanosoma cruzi infection in rats.

Enhanced atrial natriuretic factor (ANF) production by the heart is related to hemodynamic overload, cardiac growth, and hypertrophy. The heart is one of the most affected organs during Trypanosoma cruzi infection. We tested the hypothesis that myocarditis produced by parasite infection alters the natriuretic peptide system by investigating the behavior of plasma ANF during the acute and chronic stages of T. cruzi infection in rats. Sprague-Dawley rats were infected with T. cruzi clone Sylvio-X10/7. Cardiac morphology showed damage to myocardial cells and lymphocyte infiltration in the acute phase; and fibrosis and cell atrophy in the chronic period. Plasma ANF levels (radioimmunoassay) were significantly higher in acute (348 +/- 40 vs. 195 +/- 36 pg/ml, P < 0.05, n = 17) and chronic T. cruzi myocarditis (545 +/- 81 vs. 229 +/- 38 pg/ml, P < 0.001, n = 11) than in their respective controls (n = 10 and 14). Rats in the chronic phase also showed higher levels than rats in the acute phase (P < 0.01). The damage of myocardial cells produced by the parasite and the subsequent inflammatory response could be responsible for the elevation of plasma ANF during the acute period of T. cruzi infection. The highest plasma ANF levels found in chronically infected rats could be derived from the progressive failure of cardiac function.

Hormonal response to dobutamine cardiac stress testing in a conscious canine model of early left ventricular dysfunction induced by chronic rate overload

The aims of this study were to investigate (1) hormonal activation before and during dobutamine cardiac stress testing (DST) in a canine model of early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP) and (2) the relationship between this hormonal profile and carnitine concentrations. Before the pacing period, the 6 dogs were assigned to 2 groups according their baseline total plasma carnitine concentration. A DST was performed on each dog before activation of the pacemaker and every 3 to 4 days during development of 3 progressive stages of ELVD (stages 1, 2 and 3). Plasma atrial natriuretic factor (ANF), angiotensin II (ANG II) and endothelin-1 (ET-1) levels were measured at the start and at the end of each DST. Effects of ELVD, DST and plasma carnitine concentration on these measurements were tested. The RRVP induced a significant increase of ANF and ANG II and a non significant trend toward increase of ET-1 in all dogs. Before the pacing period, ANF remained constant during the DST in dogs with normal total plasma carnitine concentration, while it significantly decreased in dogs with low total plasma carnitine concentration. Dobutamine stress testing induced a significant decrease in ANF in all dogs in ELVD. Dobutamine infusion induced a significant increase in ANG II in all dogs before as well as during the pacing period while ET-1 was unchanged. These results suggest that investigation of the hormonal profile before and after a dobutamine challenge might provide important diagnostic information in dogs with asymptomatic or mildly symptomatic cardiac dysfunction of different origins.