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Biomedical subjects

R A Nadeau

Publications and source records attributed to R A Nadeau.

At least 37 records · Page 2Linked to original sources

A comparative evaluation of three different approaches for detecting body surface isopotential map abnormalities in patients with myocardial infarction.

Three approaches for detecting abnormalities in body surface potential maps recorded from patients with myocardial infarction were evaluated. The maps are generated from 26 simultaneously recorded unipolar electrocardiograms. All three approaches detect the deviations in certain parameters from control values determined from 50 normal subjects. The first approach emphasizes qualitative deviations in the trajectories of the surface potential map extrema during QRS and correctly classified all but one infarct in a test group comprising 30 normals and 30 cases of myocardial infarction. The second approach classifies a test subject as abnormal if any one of his 26 lead waveforms deviates appreciably at any instant during QRS from the mean waveform for the particular lead plus or minus two standard deviations, these being determined from the control group. This method, while correctly identifying all infarcts, resulted in a large number of false positives, misclassifying 22 of 30 normals. A final method was to obtain an instant by instant plot of the correlation coefficient between the mean surface potential map during QRS for the 50 normals and that of the subject being tested. Test cases were classified as abnormal if any correlation coefficient value fell below an envelope determined from the correlation coefficient plots obtained by correlating the maps of all 50 normals with their own mean. Twenty-nine normals and 26 infarcts were correctly classified. On the basis of these results, the first approach is superior to the other two for detecting surface potential map abnormalities in patients with myocardial infarction.

Electrocardiography↗

Liberation of cyclic AMP and catecholamine from the heart during left stellate stimulation in the anesthetized dog.

In open-chest pentothal-chloralose anesthetized dogs, plasma catecholamine and cyclic AMP levels were evaluated in the aortic and coronary sinus blood, during stimulations of the left ansa subclavia (1, 2, and 4 Hz). Basal aortic and coronary sinus catecholamine levels were respectively 0.373 +/- 0.090 and 0.259 +/- 0.048 ng/mL and cyclic AMP levels averaged 21.4 +/- 1.4 and 20.9 +/- 1.6 pmol/mL. Statistically significant increases in cyclic AMP levels were induced by sympathetic stimulations at 1 Hz (2.0 +/- 0.6 pmol/mL, 2 Hz (2.5 +/- 1.2 pmol/mL) and 4 Hz (6.5 +/- 1.5 pmol/mL), concomitantly with elevations of coronary sinus catecholamine levels. Sotalol (5 mg/kg) abolished the increases in coronary sinus cyclic AMP levels induced in coronary sinus cyclic AMP output averaged 282 +/- 30 pmol/min (1 Hz), 662 +/- 160 pmol/min (2 Hz), and 1679 +/- 242 pmol/min (4 Hz). Sympathetically induced cyclic AMP output (4Hz) was blunted by sotalol (-81 +/- 14 pmol/min). Aortic cyclic AMP levels were not significantly influenced by stellate stimulation. Intense correlations were found between increased in coronary sinus plasma catecholamines and cyclic AMP concentration levels (r = 0.81, slope - 1.45, ordinate = -1.42, n = 15) as well as between delta cyclic AMP output versus delta catecholamine output values in the coronary sinus (r = 0.93. slope output levels. Intracoronary infusion of phenylephrine (10 micrograms/min) or nitroprusside (200 micrograms/min) had no influence on cyclic AMP plasma levels whereas aortic and coronary sinus levels were respectively increased 5.5 +/- 1.9 and 7.3 +/- 1.4 pmol/mL during the administration of isoproterenol (5 micrograms/min). These data suggested that plasma cyclic AMP constitutes a sensitive index of cardiac beta-adrenergic activity elicited by the release of endogenous catecholamine during stellate stimulations.

Adrenergic beta-Antagonists↗

Exercise plasma catecholamines in dogs: role of adrenals and cardiac nerve endings.

The plasma norepinephrine concentration (NE, ng . ml-1) in the pulmonary artery of dogs increased above resting values (0.22 +/- 0.04) for moderate (0.53 +/- 0.06) and severe exercise (1.45 +/- 0.23) and during prolonged exercise of moderate intensity (2.06 +/- 0.14). The plasma epinephrine concentration (E) increased above resting values (0.14 +/- 0.04) for severe exercise only (0.76 +/- 0.10) or when moderate exercise was prolonged (1.81 +/- 0.24). The E response, which appeared greater than that found in humans, is probably related to the species difference in the vasomotor response to exercise between humans and dogs, the latter not being subjected to compensatory vasoconstriction in nonworking areas. The activity of the adrenal medulla is confirmed by the plasma catecholamine (CA) gradient between proximal and distal posterior vena cava at rest (0.20 +/- 0.09) and during short- (0.35 +/- 0.08) and long-duration exercise (1.37 +/- 0.23). On the contrary, the heart is not a source of plasma CA in dogs: coronary sinus CA did not exceed aortic CA at rest and for moderate exercise and was lower than aortic CA for severe exercise (4.80 +/- 0.25 vs. 6.55 +/- 0.76 ng . ml-1).. The sources of plasma NE remain unclear in exercising dogs. Significant amounts of NE may be released by the adrenal medulla.

Adrenal Glands↗

Plasma catecholamines in acute myocardial infarction.

Plasma catecholamine levels were determined in 26 cases of uncomplicated myocardial infarction within 24 hours of onset of acute chest pain. Blood samples were collected at time of entry and at 4-hour intervals during the 48 hours following admission. Average values of plasma catecholamines within 1 hour of onset of pain were 0.87 ng./ml +/- 0.21 and remained elevated during the first 24 hours period. A gradual fall in catecholamine values was observed during the second 24-hour period. Catecholamines were higher in patients with sinus tachycardia and lower in patients with sinus bradycardia, and were higher in patients with anterior or anterolateral infarction. Catecholamine values were significantly higher when determined while patients presented ventricular ectopic beats or ventricular tachycardia. Sinus tachycardia, ventricular arrhythmias, and elevated plasma catecholamine values may be considered indicators of pain, anxiety, and/or left ventricular dysfunction without necessarily being causally related between themselves.

Adult↗

Computer processing of intracardiac electrograms for conduction studies.

Computer techniques developed to process intracardiac signals recorded in dogs are presented. The signals under measurement are the auricular and ventricular monophasic action potentials and the His bundle electrogram. Computerized measurement of significant timing parameters on simultaneous recordings of these signals can assess quite precisely changes in the normal conduction scheme of the heart provoked by different experimental protocols. Increased accuracy is mainly due to the objective way of defining wave onsets and the processing power of the system used. Signal recording, signal acquisition, automatic waveform measurements, interactive process and production of end result graphs by computer are all described.

Action Potentials↗

Blood and plasma volume changes in dogs after sympathectomy with 6-hydroxydopamine.

The effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) on blood volume was studied in unanesthetized splenectomized and nonsplenectomized dogs. A significant increase in total blood volume essentially accounted for by a marked plasma volume expansion was found in both groups after 6-OHDA treatment (50 mg/kg). The red cell volume in the nonsplenectomized dogs was significantly reduced 3 and 7 days after sympathectomy but returned to normal after 15 days. In contrast, the red cell volume was unchanged in the splenectomized dogs after sympathectomy. The blood volume changes were accompanied in both groups by significant decreases in hematocrit in plasma sodium and potassium and in serum protein concentrations while serum calcium concentrations were only slightly increased. These results confirm that the inhibition of adrenergic tone directly influences blood volume. They also indicate that an increase in blood volume constitutes an important compensatory mechanism for the long-term maintenance of adequate blood pressure levels after chemical sympathectomy by 6-OHDA.

Animals↗

Increased circulating plasma catecholamines and plasma renin activity in dogs after chemical sympathectomy with 6-hydroxydopamine.

Circulating plasma catecholamines, plasma renin activity, and other variables were measured in unanesthetized dogs before and after chemical sympathectomy with 6-hydroxydopamine (6-OHDA, 50 mg/kg). Chemical sympathectomy resulted in an immediate fall in mean arterial blood pressure and a delayed reduction in heart rate. Significant increases in plasma glucose and lactate concentrations, circulating plasma catecholamines, and plasma renin activity were found 24 h after 6-OHDA treatment. Circulating catecholamine levels decreased rapidly as time elapsed after sympathectomy and were half the initial values after 2 weeks. Plasma renin activity remained elevated during the 1st week after 6-OHDA treatment and returned to control levels during the 2nd week. Significant correlations were found between circulating catecholamines and heart rate mean arterial pressure, and plasma glucose and lactate concentrations. A significant correlation was also found between plasma renin activity and the mean arterial blood pressure. These results confirm that the adrenal medulla increases its catecholamine secretion rate into the circulation to compensate for the loss of adrenergic innervation after 6-OHDA treatment. They also indicate that the renin-angiotensin system represents another important compensatory mechanism for circulatory homeostasis in sympathectomized animals.

Animals↗

Regulation of norepinephrine release from cardiac sympathetic fibers in the dog by presynaptic alpha- and beta-receptors.

The effect of phenoxybenzamine (PBA), desmethylimipramine (DMI), clonidine (CLND), sotalol (STL), and isoproterenol (ISPR) on the release of endogenous norepinephrine (NE) from the heart on right cardioaccelerator nerve stimulation was studied in anesthetized dogs. Under control conditions, the catecholamine levels in coronary sinus blood increased linearly with increasing frequencies of stimulation up to 10 Hz and did not increase further at 30 Hz. The release of NE was markedly enhanced after PBA (1 mg/kg, iv) and DMI (1 mg/kg, iv). The enhanced release of NE after DMI, but not after PBA, was associated with a prolonged response in heart rate. In contrast, NE release was reduced after CLND (15 microgram/kg, iv) at stimulation frequencies of 1 and 2 Hz and this was associated with reduced responses in heart rate and left ventricular dtp/dt. STL (5 mg/kg, iv) reduced significantly the release of NE at stimulation frequencies of 1-5 Hz, whereas ISPR enhanced NE outflow at frequencies of 1-4 Hz. These results support the existence of both negative and positive feedback mechanisms on the release of norepinephrine by cardiac sympathetic fibers mediated through presynaptic alpha- and beta-adrenoreceptors, respectively. The functional significance of these mechanisms is also suggested by the correlation found between changes in NE release and variations in cardiac responses under the various drug treatements.

Adrenergic Fibers↗

The effects of acetylstrophanthidin on the response of the AV junction to adrenergic stimulation studied in dogs.

The response of the AV junction to adrenergic stimulation was studied in 35 anesthetized open-chest dogs before and after the injection of acetylstrophanthidin (5mug) directly into the AV node artery. An AV junctional rhythm was obtained under control conditions by injecting norepinephrine (n = 9) or isoproterenol (n = 8) into the AV node artery and by stimulation of the left stellate ganglion (n = 11) after selectively injecting propranolol into the sinus node artery. Acetylstrophanthidin brought about various degrees of conduction block from simple PR interval prolongation to complete heart block, and decreased the chronotropic response of the AV junction to adrenergic stimulation. In seven animals the appearance of a spontaneous second degree AV block did not reduce the AV junctional response to adrenergic stimulation. Acetylstrophanthidin also reduced the ventricular acceleration produced by adrenergic stimulation during atrial fibrillation. These results suggest that the anti-adrenergic effect of cardiac glycosides may not only be involved in the mechanism of AV conduction disturbances during digitalis intoxication, but may also play a role in slowing the ventricular rate during atrial fibrillation.

Animals↗

Computer characterization of sinus rhythm.

Sinus rhythm tracings, including sinus tachycardia and bradycardia, are characterized quantitatively by means of an ECG measurement program which has been subjected to rigorous evaluation. The analysis is performed on tracings of short duration (10 sec). The features of regularity and stability are considered for the R wavetrain. Regularity is evaluated from the normalized differences between sucessive RR intervals. Stability is determined by the ratio of maximum and minimum RR interval durations. Due to the difficulities of automatic beat-to-beat detection and measurement of P waves, an estimate of the PR interval is obtained from a pseudo-PR interval determined from certain features of the P and R wavetrains. The constancy of this pseudo-PR interval is evaluated, and its absolute value is uded as a characteristic of the type of sinus rhythm.

Adult↗

Roles of the AV junction in determining the ventricular response to atrial fibrillation.

The statistical properties of RR interval sequences during cholinergic atrial fibrillation were studied in anesthetized dogs both in control conditions and after the selective injection of dromotropic agents into the atrioventricular (AV) node artery. It was observed that RR interval histogram configurations depended mainly on the mean heart rate, regardless of whether it was a control or a post-injection sequence. The sequences were found to vary from almost regular at fast rates to highly irregular at slow rates, covering all intermediate possibilities. Since the injections of dromotropic agents into the AV node artery were carried out during sinus rhythm between the episodes of fibrillation, their influences on the AV junction, as reflected both on the length of the PR interval during sinus rhythm and on the RR interval dispersion during fibrillation, could be compared. The dispersion of RR intervals was found to increase as the PR interval duration became longer. In addition, it was observed that the generally random character of the RR interval sequences during fibrillation was not affected by the injection of dromotropic agents into the AV node artery. These results were interpreted as an indication that, for a well-established atrial fibrillation, the degree of ventricular irregularity (dispersion of RR intervals) is related to the conductivity within the AV junction and that the random character of RR interval sequences is related to the atrial fibrillatory activity itself.

Acetylcholine↗

The development of sympathetic innervation and the functional state of the cardiovascular system in newborn dogs.

The present study in dogs indicates that the peripheral sympathetic fibers develop mostly after birth and reach a full maturity at about 2 months of life. The norepinephrine content of the heart, spleen, intestine, salivary glands, and adrenal glands increased from birth to 56 days of age. In contrast, the content of the stellate ganglia decreased during this period. In most of the organs studied, the uptake of [3H] norepinephrine developed in parallel with the norepinephrine content, except in the right atrium and salivary glands where it was fully developed soon after birth. During development, the systemic blood pressure increased from 40 to 100 mm Hg. Bilateral adrenal vessel clamping failed to induce a fall in blood pressure in growing dogs which indicates that the adrenal medulla or the baroreceptors did not fully compensate for the lack of peripheral sympathetic fibers and for the lower blood pressure in newborn animals. Although cardiac norepinephrine content was still very low in 10-day-old animals, cardiovascular responses to direct and reflex sympathetic stimulation were similar to those observed in 56-day-old animals. These results indicate that the sympathetic nervous system becomes functional before the fibers reach their full maturity.

Adrenal Glands↗

Computation of aortic pulse wave velocity and aortic pulse wave velocity and aortic extensibility from pressure gradient measurements.

This study is concerned with the computation of aortic pulse wave velocity based on simultaneous recordings of the aortic pressure gradient and first-time derivative of aortic pressure. These variables were recorded by means of a double-lumen catheter introduced in the aorta of four anesthetized closed chest dogs, and connected to critically damped manometer systems. Results of aortic pulse wave velocity were then compared: (i) to the true phase velocity obtained from spectra of apparent phase velocity, and (ii) to the pulse wave velocity computed from the time shift between maximum slopes of the pressure wave. From the aortic valves to 37 cm down the aortic trunk, pulse wave velocity increased from 410-460 cm/s to approximately 600-800 cm/s. Based on the wave propagation equation presented of Bramwell and Hill (Bramwell, J.C., and Hill, A. V. 1922. Proc. R. Soc. 93, 298-306), volumetric extensibility coefficients were computed from pulse wave velocity data. Results indicated that, from the aortic valves to 37 cm down to the aorta, the mean volumetric extensibility decreased from 0.43-0.56% deltaV/cm H2O to 0.16-0.25% deltaV/cm H2O (1 cm H2O = 94.1 N/m2).

Animals↗