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Biomedical subjects

D E Johnstone

Publications and source records attributed to D E Johnstone.

At least 19 recordsLinked to original sources
PubMed1992

Prolonged supramaximal stimulation of canine efferent sympathetic neurons induces desensitization of inotropic responses without a change in myocardial beta-adrenergic receptors.

OBJECTIVE: To investigate whether desensitization of inotropic responses elicited during prolonged efferent sympathetic neural stimulation is due to decreased responsiveness of myocardial beta-adrenergic receptors or to alterations in the efferent sympathetic neurons innervating the heart. DESIGN: Increasing doses of noradrenaline and isoproterenol were administered intravenously before and during prolonged (20 mins) stimulation of the intrathoracic efferent sympathetic nervous system of eight dogs. Cardiac augmentor responses were correlated with liberation of catecholamines by the heart. In a second group of experiments (nine dogs), right and left ventricular beta-adrenergic receptor number and affinity were determined before and during such stimulations. MAIN RESULTS: Similar ventricular augmentations were induced when isoproterenol or noradrenaline was administered before and after 20 mins of efferent sympathetic neural stimulation. During the early peak stimulation response, no further augmentations were induced by isoproterenol or noradrenaline. Liberation of noradrenaline by the heart followed a similar course after an initial peak, while noradrenaline values fell to levels which were 6% of those attained during peak response after 20 mins of continuous stimulation. The Bmax and Kd of ventricular beta-adrenergic receptors were similar before and after 20 mins of efferent sympathetic neural stimulation. CONCLUSIONS: Desensitization of ventricular inotropism that occurs during prolonged cardiac efferent sympathetic nervous system stimulation is not primarily due to alteration of myocyte cell surface beta-adrenergic receptors or to a change in myocyte responsiveness to beta-adrenergic agonists, but rather to a reduction in noradrenaline release by sympathetic efferent post ganglionic neurons presumably reflecting a reduction in the activity of these neurons despite continued stimulation.

Animals↗
PubMed1990

Effects of increasing heart rate induced by efferent sympathetic neuronal stimulation, isoproterenol or cardiac pacing on myocardial function and oxygen utilization.

The effects of increasing heart rate by six different methods on cardiac function were investigated in 17 open-chest anesthetized dogs. Heart rate was increased approximately 30% by (1) right interganglionic nerve stimulation, (2) atrial pacing, (3) ventricular pacing, (4) atrioventricular sequential pacing, (5) right stellate ganglion stimulation, and (6) isoproterenol administration. During heart rate increases induced by atrial pacing left ventricular intramyocardial pressure, coronary blood flow, oxygen delivery per unit of myocardial oxygen consumption, and myocardial efficiency were unchanged. Ventricular pacing reduced left ventricular cavity and septal intramyocardial pressure, while circumflex coronary flow increased, resulting in reduced oxygen delivery relative to myocardial oxygen consumption. Similarly, atrioventricular sequential pacing increased circumflex coronary artery flow and myocardial oxygen consumption, and decreased septal intramyocardial pressure and oxygen delivery per unit of myocardial oxygen consumption. Right stellate ganglion stimulation and isoproterenol increased left anterior descending and circumflex coronary artery blood flow, intramyocardial pressure, and myocardial oxygen consumption. Estimated myocardial efficiency (left ventricle) was decreased by ventricular pacing and isoproterenol, and was unchanged by atrial pacing and right interganglionic nerve stimulation. Increases in heart rate induced by right interganglionic nerve stimulation did not alter myocardial oxygen consumption, or the index of cardiac efficiency. It is concluded that augmentation of heart rate by either ventricular or atrioventricular pacing impairs myocardial function so that there is a decrease of left ventricular efficiency and isoproterenol augments chronotropism and myocardial force relative to cardiac external work so there is a reduction in cardiac efficiency. In contrast, atrial pacing or right interganglionic nerve stimulation augments chronotropism such that myocardial oxygen consumption and efficiency are unchanged.

Animals↗
PubMed1990

Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD).

Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p = 0.0001), plasma atrial natriuretic factor (p less than 0.0001), plasma arginine vasopressin (p = 0.006), and plasma renin activity (p = 0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased (p less than 0.05) in patients on diuretic therapy. We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure. Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy.

Arginine Vasopressin↗
PubMed1990

Exercise body surface potential mapping in single and multiple coronary artery disease.

Body surface ST integral maps were recorded in 36 coronary artery disease (CAD) patients at: rest; peak, angina-limited exercise; and, 1 and 5 min of recovery. They were compared to maps of 15 CAD patients who exercised to fatigue, without angina, and eight normal subjects. Peak exercise heart rates were similar (NS) in all groups. With exercise angina, patients with two and three vessel CAD had significantly (p less than 0.05) greater decrease in the body surface sum of ST integral values than patients with single vessel CAD. CAD patients with exercise fatigue, in the absence of angina, had decreased ST integrals similar (NS) to patients with single vessel CAD who manifested angina and the normal control subjects. There was, however, considerable overlap among individuals; some patients with single vessel CAD had as much exercise ST integral decrease as patients with three vessel CAD. All CAD patients had persistent ST integral decreases at 5 min of recovery and there was a direct correlation of the recovery and peak exercise ST changes. Exercise ST changes correlated, as well, with quantitative CAD angiographic scores, but not with thallium perfusion scores. These data suggest exercise ST integral body surface mapping allows quantitation of myocardium at ischemic risk in patients with CAD, irrespective of the presence or absence of ischemic symptoms during exercise. A major potential application of this technique is selection of CAD therapy guided by quantitative assessment of ischemic myocardial risk.

Adult↗
PubMed1989

Myocardial slice: a physiological approach to beta-adrenergic ([3H] CGP-12177) receptor binding in hamster and guinea pig heart.

A new technique is described for the characterization and quantification of beta-adrenergic receptors in biologically viable slices of myocardium from the hamster right ventricle using the hydrophilic radioligand, [3H]CGP-12177 (CGP). Binding was stereospecific, saturable, of high affinity, reversible, displaceable by appropriate drugs, and highly positively correlated with increasing tissue concentrations. Bmax for CGP binding to myocardial slices from 50-day-old male Golden Syrian hamsters was 3.28 +/- 0.15 fmol/mg wet weight, while Kd was 0.21 +/- 0.02 nM. Freezing resulted in a close to 50% loss of receptor number with no apparent change in affinity. The slice preparation may be utilized to detect in vivo changes in myocardial cell surface receptors, as evidenced by the fact that the number of receptors in slices from ischemic guinea pigs was increased (Bmax = 15.5 +/- 1.25 fmol/mg wet wt) compared with sham-operated controls (Bmax = 10.4 +/- 0.38 fmol/mg wet wt). The minimal tissue disruption associated with this procedure, as well as its speed, simplicity, and relatively low cost, suggest that the myocardial slice preparation provides an important methodology for the study of beta-adrenergic receptor binding in the semiintact myocardium.

Adrenergic beta-Antagonists↗
PubMed1989

Postnatal beta-adrenergic receptor [(3H] CGP-12177) binding in myocardial slices of cardiomyopathic hamsters.

A muscle slice technique was used to compare the development changes in binding of the beta-adrenergic antagonist, [3H]CGP-12177 (CGP), in right ventricles of male Canadian Hybrid Farms CHF 147 cardiomyopathic hamsters and two strains of control healthy animals, golden Syrian (GH) and CHF 148 albino noncardiomyopathic (AH) hamsters. CGP binding to myocardial slices was saturable, reversible, stereospecific, proportional to slice number and of high affinity. Bmax in GH and AH myocardium was not altered with age although there was a tendency to decrease between 16 and 30 days of age in both strains. In the cardiomyopathic ventricles, receptor number decreased between 30 (7.07 +/- 0.74 fmol/mg wet weight) and 60 days of age (4.58 +/- 0.52) (P less than 0.05) and remained at the lower level thereafter. Bmax in cardiomyopathics was slightly higher than that of either GH (5.01 +/- 0.88) or AH (5.05 +/- 0.82) at 30 days of age (P less than 0.05) but was not different at the other ages tested. Kd was decreased in GH at 30 days of age but was unaltered during postnatal development in either the AH or cardiomyopathic hearts. The elevated level of cell surface beta-adrenergic receptors in the cardiomyopathic ventricle at a time when necrotic lesions are developing may be important with respect to the pathogenesis of cardiomyopathy in these animals.

Age Factors↗
PubMed1989

Functional integrity of sympathetic efferent postganglionic axons in a region of stunned myocardium.

In order to investigate whether brief, repeated episodes of acute myocardial ischemia impair the function of the intrinsic sympathetic efferent post ganglionic cardiac nerves, 12 cycles of left anterior descending coronary artery occlusions (5 mins) and reperfusions (10 mins) were successfully performed in 10 dogs. Following each brief occlusion percentage systolic shortening in the ventral myocardium was reduced, consistent with myocardial stunning. Stellate ganglion stimulation increased intramyocardial pressures in the ventral and lateral regions of the left ventricle before and after each of the artery occlusions in which stimulations were performed. Isoproterenol and tyramine also augmented intramyocardial pressures in those regions. When the coronary artery was occluded permanently in seven of the dogs tested, stellate ganglion stimulation continued to augment intramyocardial pressure in the ventral region of the left ventricle for up to 35 mins. These results indicate that following repetitive episodes of brief occlusion of a coronary artery that are reported to 'stun' the involved myocardium in a transmural distribution, sympathetic efferent post ganglionic axons can augment inotropism in the affected zone. Furthermore, when a coronary artery is totally occluded thereafter for up to 35 mins these efferent sympathetic post ganglionic nerves continue to function. It is concluded that sympathetic efferent post ganglionic neurons innervating the ventricle can augment cardiac inotropism in a region of stunned myocardium.

Animals↗
PubMed1988

Cardiac effects produced by long-term stimulation of thoracic autonomic ganglia or nerves: implications for interneuronal interactions within the thoracic autonomic nervous system.

Electrical stimulation of an acutely decentralized stellate or middle cervical ganglion or cardiopulmonary nerve augments cardiac chronotropism or inotropism; as the stimulation continues there is a gradual reduction of this augmentation following the peak response, i.e., an inhibition of augmentation. The amount of this inhibition was found to be dependent upon the region of the heart investigated and the neural structure stimulated. The cardiac parameters which were augmented the most displayed the greatest inhibition. Maximum augmentation or inhibition occurred, in most instances, when 5-20 Hz stimuli were used. Inhibition of augmentation was overcome when the stimulation frequency was subsequently increased or following the administration of nicotine or tyramine, indicating that the inhibition was not primarily due to the lack of availability of noradrenaline in the nerve terminals of the efferent postganglionic sympathetic neurons. Furthermore, as infusions of isoproterenol or noradrenaline during the period of inhibition could still augment cardiac responses, whereas during the early peak responses they did not, the inhibition of augmentation does not appear to be due primarily to down regulation of cardiac myocyte beta-adrenergic receptors. The inhibition was modified by hexamethonium but not by phentolamine or atropine. Inhibition occurred when all ipsilateral cardiopulmonary nerves connected with acutely decentralized middle cervical and stellate ganglia were stimulated, whereas significant inhibition did not occur when these nerves were stimulated after they had been disconnected from the ipsilateral decentralized ganglia. Taken together these data indicate that the inhibition of cardiac augmentation which occurs during relatively long-term stimulation of intrathoracic sympathetic neural elements is due in large part to nicotinic cholinergic synaptic mechanisms that lie primarily in the major thoracic autonomic ganglia. They also indicate that long-term stimulation in intrathoracic sympathetic neural elements with frequencies as low as 2 Hz may augment the heart as much as higher stimulation frequencies, depending upon the structure stimulated and the cardiovascular parameter monitored.

Adrenergic beta-Antagonists↗
PubMed1986

Electrocardiographic and ventriculographic recovery patterns in Q wave myocardial infarction.

To further define the capacity for recovery after acute phase electrical and mechanical injury in patients with Q wave myocardial infarction who were treated with standard measures, 120 lead body surface potential maps and radionuclide angiograms were recorded at day 5 before discharge and month 6 after infarction in 23 patients with a first infarction (12 anterior and 11 inferior by standard 12 lead electrocardiographic criteria). In addition to assessment of spatial changes in electrocardiographic and wall motion patterns, five quantitative variables were evaluated: minimal Q zone integral, sigma Q wave integral, maximal ST integral, left ventricular ejection fraction and left ventricular wall motion abnormality score. From day 5 to month 6 after infarction, the only change in the inferior infarction group was a gain in sigma Q wave (-91 +/- 40 mu V X s X 10(2) to -68 +/- 24 mu V X s X 10(2); p less than 0.05). In contrast, all variables improved over the same time period in the anterior infarction group: Q zone minimum, -34 +/- 20 to -24 +/- 13 mu V X s (p less than 0.05); sigma Q wave, -160 +/- 122 X 10(2) to -120 +/- 90 mu V X s X 10(2) (p less than 0.05); ST maximum, 44 +/- 19 to 18 +/- 9 mu V X s (p less than 0.01); ejection fraction, 54 +/- 7 to 63 +/- 17% (p less than 0.05); and wall motion score, 6 +/- 3 to 3 +/- 3 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1979

Multiple gated cardiac blood pool imaging for left ventricular ejection fraction: validation of the technique and assessment of variability.

The intrinsic variability and accuracy of left ventricular ejection fraction determined by multiple gated cardiac blood pool imaging was evaluated in 83 patients. Ejection fraction by gated studies correlated well with data from first pass radionuclide angiocardiography (r = 0.94) and from contrast angiography (r = 0.84). Intra- and interobserver variabilities of absolute ejection fraction were minimal (mean +/- standard deviation 1.4 +/- 1.2 and 1.6 +/- 1.5 percent, respectively) and were not different for normal (ejection fraction 55 percent or greater) and abnormal patients. Ejection fraction was determined twice in 70 patients: on the same day at intervals separated by 1 to 2 hours (41 patients) and on 2 different days (29 patients). Ejection fraction ranged from 18 to 91 percent and was normal in 37 patients. There was no difference in mean serial variabilities of absolute ejection fraction for all repeat studies performed on the same and separate days (3.3 +/- 3.1 versus 4.3 +/- 3.1 percent (not significantly different). The mean variability of absolute ejection fraction for repeat studies in normal patients was significantly greater than in abnormal patients (5.4 +/- 4.4 versus 2.1 +/- 2.0 percent, P less than 0.01). The incidence rate of absolute interstudy changes of 5 percent or more was significantly higher in normal than in abnormal patients (P less than 0.01). This differential variability should be considered in interpreting sequential changes in left ventricular ejection fraction. To be attributed to nonrandom physiologic alterations, the absolute change in ejection fraction should be 10 percent or more in normal patients and 5 percent or more in abnormal patients.

Angiocardiography↗
PubMed1979

Response of right ventricular ejection fraction to upright bicycle exercise in coronary artery disease.

The right ventricular (RV) response to exercise was assessed in 32 patients with angiographically documented coronary artery disease and in 14 normal controls without cardiopulmonary disease. The relationships between exercise RV reserve, exercise left ventricular (LV) reserve, and the presence of proximal right coronary stenosis were also evaluated. RV and LV ejection fractions were determined using first-pass radionuclide angiocardiograms. The normal response to exercise was at least a 5% absolute increase in RV and LV ejection fractions. In the group with coronary artery disease, RV ejection fraction either decreased or remained the same with exercise (abnormal exercise RV reserve) in 19 of 32 patients. LV exercise reserve was abnormal in 26 of 32 patients. All 19 patients with abnormal exercise RV reserve had abnormal exercise LV reserve, and all six patients with normal LV reserve had normal RV reserve. There was a significant linear relationship between the direction and magnitude of change from rest to exercise of LV ejection fraction and RV ejection fraction (r = 0.77). In contrast, the RV response to exercise was not primarily dependent upon the presence or absence of proximal right coronary stenosis. These data suggest that abnormal exercise RV reserve occurs frequently in coronary artery disease and that the concomitant LV response to exercise appears to be its major determinant.

Adult↗
PubMed1979

Two pediatric allergists' sojourn in the People's Republic of China.

One cannot visit modern day mainland China without being impressed with the apparent vastness of the population which seems ever on the move. While manifestations of allergic disease among Chinese children resemble those seen in western countries, some factors peculiar to China, such as life style, diet, housing and absence of household pets, influence age of onset and geographic distribution of some allergic syndromes in Chinese children.

China↗
PubMed1977

Alpha-1 antitrypsin in childhood asthma.

Alpha-1 antitrypsin (AAT) phenotypes and serum levels were studied in two childhood perennial asthmatic populations. The first was an ambulatory, mostly mild nonsteroid-dependent group living in Rochester, N.Y. The second was a more severe mostly steroid-dependent group residing at an asthma residential treatment center in Denver, Colo. The prevalences of alpha-1 antitrypsin protease inhibitor (Pi) tyes were the same for bothe groups and similar to prevalences in a random population. Alpha-1 antitrypsin serum levels were significantly elevated for the mild nonsteroid-dependent group when compared to the more severe steroid-dependent group. The steroid-dependent group had serum levels similar to a group of nonasthmatic control children. These findings indicate that there is not a strong association of alpha-1 antitrypsin Pi variants such as Pi MZ or Pi MS with more severe asthma. Elevated serum levels in the milk perennial asthmatic group may be the result of chronic inflammatory processes. Normal levels in the sterioid-dependent group may be the result of corticosteroid control of inflammation associated with asthma.

Adolescent↗
PubMed1977

The natural history of allergic disease in children.

Optimal care of allergic children requires certain knowledge on the part of parents, primary physicians and allergists. One needs to be familiar with not only the mechanisms of allergic disease, the factors which may potentiate or "turn on" allergic symptoms in children of allergic families, but also the natural history of the commonest allergic syndromes in infancy and children. If a physician is thus prepared he can be of significant help in the prevention, amelioration and prognostication of the future course of allergic disease in children.

Adolescent↗