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Effects of hyperglycaemia on kidney function, atrial natriuretic factor and plasma renin in patients with insulin-dependent diabetes mellitus.

In normoalbuminuric patients with insulin-dependent diabetes mellitus, plasma atrial natriuretic factor (ANF), cyclic GMP and active renin and the renal clearances of [99Tcm]-diethylenetriaminepentaacetic acid (DTPA) lithium and sodium were studied on a hyperglycaemia day and a euglycaemia day. Baseline euglycaemia was achieved by an overnight variable insulin infusion, which during study days was fixed at the rate necessary to maintain euglycaemia in the morning. After a baseline euglycaemic clearance period of 90 min, measurements were repeated in a new 90-min period beginning 150 min later. On the hyperglycaemia day i.v. infusion of 20% glucose was started at the end of the euglycaemic baseline period, increasing blood glucose (5.3 +/- 1.3 vs 12.1 +/- 1.2 mmol l-1, p less than 0.01). On the euglycaemia day blood glucose declined (5.1 +/- 1.0 vs 4.2 +/- 1.0 mmol l-1, p less than 0.02). Glomerular filtration rate (GFR) was unchanged by acute hyperglycaemia (127 +/- 16 vs 129 +/- 24 ml min-1, NS), but nearly normalized during maintained euglycaemia on the euglycaemia day (124 +/- 17 vs 105 +/- 16 ml min-1, p less than 0.01). When comparing the hyperglycaemic study period with the similarly timed period on the euglycaemia day, GFR was elevated by hyperglycaemia (129 +/- 24 vs 105 +/- 16 ml min-1, p less than 0.01), while the renal clearances of lithium and sodium were similar. Consequently, the calculated absolute proximal reabsorption rate of sodium and water was elevated during hyperglycaemia. Hyperglycaemia reduced the slight decline in plasma concentrations of ANF and cyclic GMP observed on the euglycaemia day. Active renin, glucagon and plasma osmolality were unchanged. In conclusion, marked changes in glomerular filtration rate are induced by changes in blood glucose concentration, but the effect is delayed and thus not directly related to renal tubular transport of glucose. Hyperglycaemia does not affect renal clearances of lithium and sodium, while proximal tubular reabsorption is markedly stimulated. These changes are not related to changes in ANF, renin, glucagon or plasma osmolality.

Adult

Functional atrial natriuretic peptide receptor in human adrenal tumor.

The effects of synthetic human atrial natriuretic peptide (ANP) on the release of catecholamines, aldosterone, or cortisol were observed in human adrenal tumors obtained surgically from patients with pheochromocytoma, primary aldosteronism, or Cushing's syndrome, respectively. Each tumor tissue or adjacent normal cortical tissue was sectioned into slices, which were incubated in medium-199 in the presence or absence of adrenocorticotrophin (ACTH) and ANP. The amounts of epinephrine, norepinephrine, aldosterone, or cortisol released into the medium were measured. Existence of ANP receptors on the adrenal tissues was examined by binding assays, affinity labeling, and immunohistochemistry. Release of catecholamines from pheochromocytoma tissues was inhibited by ANP, and the presence of the ANP receptor on pheochromocytoma was further demonstrated by both binding assays and affinity labeling; Scatchard analysis revealed a single class of binding sites for ANP with a Kd of 1.0 nM and a Bmax of 0.4 pmol/mg of protein and the molecular size was estimated as 140 and a 70 kDa under nonreducing and reducing conditions, respectively. The presence of ANP receptors in pheochromocytoma was demonstrated by immunohistochemistry. ANP inhibited both basal and ACTH-stimulated aldosterone secretion in the slices of normal cortex, and localization of ANP receptors in zona glomerulosa cells was also demonstrated. However, ANP did not inhibit basal and ACTH-stimulated aldosterone and cortisol secretion in both tissue slices from aldosteronoma and Cushing's adenoma. Consistent with these observations, the absence of ANP receptors in adenoma tissues was determined by binding assays, affinity labeling, and immunohistochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex

Comparative values of the precordial and transesophageal approaches in the echocardiographic evaluation of atrial baffle function after an atrial correction procedure.

Previous methods used to assess atrial baffle function after correction of transposition of the great arteries have included precordial echocardiography and cardiac catheterization. To evaluate whether single plane transesophageal echocardiography might provide additional information, its findings were correlated with information derived from both precordial echocardiography and cardiac catheterization in 15 patients (14 Mustard procedures, 1 Senning procedure) aged 4.2 to 33 years (mean 16.3). Precordial ultrasound with combined imaging, color flow mapping and pulsed Doppler ultrasound visualized the supramitral portion of the common systemic venous atrium in every case but could identify only superior limb obstruction in three of six patients, mid-baffle obstruction in zero of two and inferior limb obstruction in zero of two patients. Transesophageal studies with use of the same range of ultrasound methods demonstrated superior limb obstruction (severe in four, mild in two) in six of six patients, mid-baffle obstruction in two of two and inferior limb obstruction in two of two patients. The entire pulmonary venous atrium was equally well interrogated by either ultrasound approach, with both identifying three cases (two mild, one moderate) of mid-pulmonary venous atrium obstruction. However, individual pulmonary vein velocity profiles could only be recorded by transesophageal pulsed Doppler ultrasound. Precordial studies identified baffle leaks (1 large, 2 small) in only three patients, whereas transesophageal studies identified 11 such baffle leaks (1 large, 10 small), which were multiple in two patients. It is concluded that transesophageal echocardiography provides a more detailed and accurate assessment of atrial baffle morphology and function than is provided by either precordial ultrasound or cardiac catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Does atrial appendectomy aggravate secretory function of atrial natriuretic polypeptide?

The present study was designed to clarify how atrial appendectomy affects hemodynamics and secretory function of atrial natriuretic polypeptide in the failing heart. Eleven mongrel dogs were prepared for the experimental model of high-output heart failure by creation of arteriovenous fistulas between femoral arteries and veins. Two months after the first operation, effects of bilateral atrial appendectomies on basal and pacing-induced secretions of atrial natriuretic polypeptide were investigated in five dogs with simultaneous measurement of various hemodynamic indices. In the remaining six dogs, used as a control group, pacing-induced secretion of atrial natriuretic polypeptide was examined in the same way as in the appendectomy group. After excision of the atrial appendages, neither systolic blood pressure nor either atrial pressure changed, but plasma atrial natriuretic polypeptide level was decreased (292 +/- 54 to 188 +/- 47 pg/ml, p less than 0.01) and cardiac output fell (3.7 +/- 0.9 to 3.0 +/- 0.8 L/min, p less than 0.01). During pacing-induced tachycardia, the peak level of plasma atrial natriuretic polypeptide was lower in the appendectomy group than in the control groups (593 +/- 213 versus 1170 +/- 324 pg/ml, p less than 0.05), despite similar left atrial pressures in the two groups. The excised appendages contained approximately 30% of the total amount of atrial natriuretic polypeptide. These results demonstrate that atrial appendectomy decreases secretory function of atrial natriuretic polypeptide and reduces cardiac output in dogs with experimental high-output heart failure.

Animals

Return of atrial mechanical function following electrical conversion of atrial dysrhythmias.

The return of atrial mechanical function and its relationship to embolic events following cardioversion of atrial arrhythmias is controversial. Fourteen patients with atrial arrhythmias were evaluated with pulsed Doppler echocardiography before and after direct current (DC) cardioversion. The atrial filling fraction increased significantly: 1.14 +/- 4.3% at baseline versus 14.9 +/- 13.3%, 13.4 +/- 11.4%, and 21.9 +/- 13.5% at 5 minutes, 30 minutes, and 24 hours, respectively, following cardioversion. Absent atrial mechanical activity was noted in four patients immediately after cardioversion. Mechanical activity resumed by 30 minutes in one patient and at 24 hours in two others. Those with delayed atrial function had lower stroke volumes and atrial filling fractions following cardioversion. An embolic event occurred in one patient who had immediate return of atrial mechanical activity. This patient also had the largest atrial filling fraction of any patient at 24 hours (41%). These data suggest that the degree of atrial mechanical activity following cardioversion is variable and that embolic episodes are not necessarily related to delayed return of atrial mechanical activity following cardioversion.

Adult

Complete heart block. Studies of atrial and ventricular pacemaker site and function.

Atrial and ventricular pacemaker function was studied in 20 patients with idiopathic chronic complete heart block using the rate response to an intravenous bolus dose of isoprenaline (5 mug/70 kg bodyweight). Pacemaker responses were compared with those of 16 normal control subjects. None of the patients was having syncopal attacks at the time of admission and they were therefore selected in that none required immediate pacing. Ten of the patients had His bundle electrograms; all were shown to have a pre-His type of atrioventricular block. Two major groups emerge from the responses to isoprenaline. (a) High risk group: 11 of the 14 patients with reduced ventricular pacemaker responses had frequent syncopal attacks; 8 of the patients with Adams-Stokes syncope had a bundle-branch block pattern, while 3 had a narrow QRS. These patients require pacing. (b) Low risk group: a low risk asymptomatic group (5 patients) was identified with atrial and ventricular responses to isoprenaline within normal range. One of these patients had a bundle-branch block pattern, while 4 had a narrow QRS. These patients might be managed without pacing. The atrial response to isoprenaline was reduced in 12 of the 20 cases, 10 of whom also had reduced ventricular responses. All 9 patients with bundle-branch block had reduced ventricular responses, while 7 had reduced atrial responses. This evidence indicates that cardiac conducting tissue pathophysiology is widespread in complete heart bolck. The present work suggests that consideration of the ventricular pacemaker function is important in assessing liability to syncope in complete heart block. While patients with Adams-Stokes attacks require pacing it is suggested that all asymptomatic patients with complete heart block and those with minor symptoms are assessed using studies of both ventricular pacemaker function and site. A low risk group not requiring a pacemaker may emerge after sufficient follow-up assessment.

Adams-Stokes Syndrome

Pulsed Doppler evaluation of atrial mechanical function after electrical cardioversion of atrial fibrillation.

Full recovery of atrial mechanical activity may not occur immediately after successful electrical cardioversion of atrial fibrillation to sinus rhythm. To examine the time course of recovery of left atrial mechanical function, serial two-dimensional, M-mode and transmitral pulsed Doppler echocardiographic studies were performed in 21 patients after elective direct current cardioversion of atrial fibrillation of 3 weeks' to 24 months' duration (mean 5 months). Over 3 months of follow-up, there were significant increases in both peak A wave velocity (p less than 0.005) and percent atrial contribution to total left ventricular filling (p less than 0.005). Compared with values in a normal control population, peak A wave velocity and percent atrial contribution to total left ventricular filling did not return to normal until 3 weeks after cardioversion in patients who remained in sinus rhythm. Left atrial dimension also decreased over the follow-up period (p less than 0.05) in patients with persistent sinus rhythm. These results may have important implications in guiding the appropriate duration of anticoagulant therapy after cardioversion, and in clinically assessing the hemodynamic benefit of restoring sinus rhythm in an individual patient.

Aged

Effect of the pericardium on atrial systolic function.

The effect of pericardial constraint on atrial systolic function was investigated in nine acutely instrumented anesthetized dogs. Left and right atrial pressures were recorded by high-fidelity catheters; auricular diameters and free wall segment lengths were measured by sonomicrometry. Atrial function curves were constructed by relating atrial systolic dimensional shortening to atrial end-diastolic pressure during progressive volume loading. With the pericardium closed, the function curves were shifted markedly downward and rightward, such that atrial systolic shortening was reduced at any given pressure. There was a concomitant leftward and upward shift of the atrial end-diastolic pressure-dimension relationship. The relationship between atrial systolic shortening and atrial end-diastolic dimension was not shifted. These results suggest that the apparent depression of atrial systolic function with the pericardium closed is due to a restrictive effect of the pericardium on atrial filling. In conclusion, in the acutely dilated heart, the pericardium restricts atrial filling and thus causes a reduction in atrial systolic contribution to ventricular filling.

Animals

[Left ventricular function during atrial fibrillation assessed by left ventricular function curve using ECG-gated blood pool scintigraphy].

Cardiac function is difficult to assess in patients with atrial fibrillation due to the widely fluctuating cycle lengths resulting in variable ventricular hemodynamics. With respect to ECG-gated blood pool scintigraphy, distortion of the time activity curve occurs due to a summation of irregular cycle lengths. Therefore, performing such a study has been regarded meaningless. To evaluate left ventricular function during atrial fibrillation using scintigraphic technique, a new processing algorithm was devised to make multiple gated images which are discriminated by the preceding R-R interval, and left ventricular filling and function curves were established. The left ventricular filling curve, obtained by plotting end-diastolic volume against the preceding R-R intervals demonstrated an impairment of blood filling in cases of mitral stenosis and constrictive pericarditis, which resolved after mitral commissurotomy in case of mitral stenosis. The left ventricular function curve, established by plotting stroke volume against end-diastolic volume, was analyzed according to indices such as "slope" and "position". Both of these indices were significantly reduced in relation to the severity of heart failure according to the NYHA's functional classification and cardiomegaly on chest radiography. On individual comparisons of underlying diseases, the indices decreased in the following order; lone atrial fibrillation, hyperthyroidism, aging, hypertension, mitral valve disease, ischemic heart disease, dilated cardiomyopathy and aortic regurgitation. The indices correlated closely with ejection fraction. In cases of mitral regurgitation, however, the function curves were situated to the right and above those of lone atrial fibrillation and decreased in slope despite the fairly well-maintained ejection fraction. After treatment with digitalis and/or diuretics, the function curves shifted to the left and upward. In conclusion, left ventricular filling and function curves based on a newly-devised algorithm of ECG-gated blood pool scintigraphy are of considerable clinical value in evaluating cardiac performance in patients with atrial fibrillation. They are widely applicable to the assessment of therapeutic and interventional effects.

Atrial Fibrillation

Echo-Doppler evaluation of the effects of heart rate increments on left atrial pump function in normal human subjects.

It is commonly believed that the atrial contribution to left ventricular filling increases during heart rate increments. However, the relative contribution of the pump function (atrial systole) and of the passive role (diastasis and reservoir) of the atrium to end-diastolic left ventricular filling is not well known. In order to investigate this problem, we performed a two-dimensional echo-Doppler study during right atrial pacing. Transmitral flow velocity curves were obtained by means of pulsed Doppler. Pacing was performed (1) at the lowest heart rate at which it was possible to obtain a stable capture of the atria, (2) at the heart rate at which the early and late Doppler filling waves almost completely overlapped. In both stages pacing was interrupted for a few seconds to obtain some post-pacing beats. Doppler tracing recorded at rest, during pacing and in the immediate post-pacing beats were analysed to obtain well-known parameters of atrial contribution; atrial peak flow velocity, early to atrial peak flow velocity ratio, and time-velocity integral of the atrial wave. Furthermore, in order to distinguish end-diastolic passive flow from the active contribution of atrial systole to filling, we superimposed the envelope of the last Doppler curve obtained during atrial pacing over the envelope of the first post-pacing curve. In this way the area of the atrial wave of the paced beat was divided by the mid-diastolic part of the post-pacing one into two areas, the integrals of which correspond to the active and passive atrial contribution respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Electrocardiographic signs of atrial overload in hypertensive patients: indexes of abnormality of atrial morphology or function?

Left atrial electrocardiographic (ECG) abnormalities have been reported as common findings in hypertension; however, their relationships with atrial anatomy are still uncertain. In addition, in arterial hypertension several studies demonstrated an abnormal left ventricular filling. The aim of this study was to investigate the relationships of the ECG signs of left atrial abnormality to atrial anatomy and left ventricular filling as evaluated by pulsed-wave (PW) Doppler in a group of patients with uncomplicated essential hypertension. To this end, 53 untreated essential hypertensive patients (age 44 +/- 8 years; blood pressure 160.5 +/- 21.5/104.7 +/- 13.5 mm Hg) underwent a complete 12-lead ECG and a PW Doppler study of the transmitral flow velocities. The ECG criteria of left atrial abnormality were: P wave wider than 0.12 (or 0.10) second or higher than 0.25 mV in lead II; P wave/PR segment ratio (Macruz index) greater than 1.6 in lead II; and P wave terminal forces in lead V1 equal to or more negative than 0.04. Echocardiographic measurements were made according to American Society of Echocardiography (ASE) convention. Doppler parameters of left ventricular filling were measured as E and A peak velocity, A/E ratio, and the ratio between the velocity-time integral under the E peak and that of the whole diastolic flow, which represents the rapid filling fraction (RFF). At least one ECG sign of atrial abnormality was present in 34 patients (64%); the Macruz index gave the most common ECG index of atrial abnormality (31 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Mechanism of augmented left atrial pump function in myocardial infarction and essential hypertension evaluated by left atrial pressure-dimension relation.

To analyze left atrial (LA) pump function in normal subjects, in patients with essential hypertension and in patients with a healed myocardial infarction, LA dimension (aortic-root echogram) and pressure (catheter-tip manometer) were simultaneously recorded in 25 patients (8 normal subjects, 7 with hypertension and 10 with myocardial infarction). The pressure-dimension relation of the left atrium was composed of 2 loops: the A loop (expressing the pump function of the left atrium) and the V loop. LA dimension at the beginning of active LA shortening was significantly greater in hypertensive subjects (33 +/- 3 mm) and in those with myocardial infarction (32 +/- 4 mm) than in normal subjects (28 +/- 3 mm) (p less than 0.01, p less than 0.05, respectively). The area of the A loop significantly increased in subjects with hypertension (48 +/- 3 mm Hg.mm, p less than 0.01) and in subjects with myocardial infarction (29 +/- 10 mm Hg.mm, p less than 0.05), compared with normal subjects (20 +/- 8 mm Hg.mm). The mean fractional shortening velocity of the left atrium significantly increased in subjects with hypertension, compared with normal subjects and those with myocardial infarction (p less than 0.05 for both). LA peak wall tension during the LA active contraction period significantly increased with hypertension and with myocardial infarction, compared with normal subjects (p less than 0.01, p less than 0.05, respectively). The area of the A loop was directly proportional to the LA dimension at the beginning of active LA shortening (r = 0.53), p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Endocrine function of the heart. Structure and biological properties of peptides secreted by the heart atrium].

Apart from the generally known functions, the heart has also an endocrine function. Atrial cardiocytes, being typical secretory cells, release peptide hormones into the blood stream: atrial natriuretic peptide containing 28 amino acids and cardiodilatin. The structure of atrial peptides was determined. It was shown that both peptides were derived from their common precursor, a protein containing 151 amino acids. The presence of specific receptors is demonstrated on plasmatic membranes of cells of kidney epithelium, arterial smooth muscle, arterial endothelium, kidney cortex and hypophysis. The interaction of atrial peptides with these receptors activates the guanylate cyclase system. The biological action of atrial peptides manifests itself in the quick, massive and instantaneous increase of diuresis and electrolyte excretion, elevated clearance of creatinine, decrease of kidney vascular resistance, intensification of glomerular filtration, inhibition of stimulated secretion of aldosterone, relaxation of blood vessels, elimination of arterial and intestinal spasm induced by various endogenous and exogenous vasoconstrictors and in correction of kidney hypertension. Various radioimmunoassays for the presence of atrial peptides in human plasma were developed; it was shown that in patients with congestive heart failure the content of atrial peptides is increased.

Amino Acid Sequence