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Biomedical subjects

R M Robertson

Publications and source records attributed to R M Robertson.

At least 91 records · Page 5Linked to original sources
PubMed1986

Left ventricular dysfunction induced by cold exposure in patients with systemic sclerosis.

Raynaud's phenomenon and cardiac abnormalities are frequent in patients with systemic sclerosis. Radionuclide ventriculograms were obtained in 16 patients with Raynaud's phenomenon and systemic sclerosis or the related CREST syndrome and in 11 normal volunteers in order to evaluate changes in left ventricular function that might be induced by exposure to cold. Left ventricular regional wall motion abnormalities developed in nine of 16 patients during cooling compared with only one of 11 control subjects, despite a comparable rise in mean arterial pressure (p less than 0.02). The abnormalities occurred in seven of 11 patients with systemic sclerosis, one of four with CREST syndrome, and one with Raynaud's disease. To test the potential protective effect of nifedipine, radionuclide ventriculograms were then obtained during cooling after sublingual nifedipine (20 mg). Only five of 13 patients had wall motion abnormalities, and the severity of the abnormalities was significantly less than during the first cooling period (p = 0.03). Five of eight patients who had cold-induced wall motion abnormalities during the first cooling period had none after nifedipine, whereas two other patients demonstrated small abnormalities only during the second cooling period after treatment with nifedipine. It is concluded that cold induces segmental myocardial dysfunction in patients with systemic sclerosis and that nifedipine may blunt the severity of this abnormal response.

Adult↗
PubMed1986

Management of chronic orthostatic hypotension.

Chronic orthostatic hypotension is characterized by recurrent symptoms of cerebral hypoperfusion due to low upright blood pressure levels. The initial approach should be to identify and correct reversible causes. Persistence of orthostatic hypotension suggests autonomic failure. The goal of management is to minimize symptoms and maximize functional capacity; therefore the magnitude of blood pressure fall is not as important as the advent of symptoms. Therapy is based upon the underlying pathophysiology and the risk/benefit ratio of interventions. Patient education and nondrug measures form the cornerstone of management. Drug therapy is often limited by unacceptable supine hypertension. Rational drug use can be governed by individualized trials of therapy. Patients with moderate or severe orthostatic hypotension are difficult to treat, but can be helped toward resumption of a normal life.

Activities of Daily Living↗
PubMed1986

Use of alpha 2 adrenoreceptor agonists and antagonists in the functional assessment of the sympathetic nervous system.

We studied the effects of clonidine, an alpha 2-adrenoreceptor agonist, and yohimbine, an alpha 2-adrenoreceptor antagonist, on blood pressure, heart rate, and plasma catecholamines in 12 patients with autonomic dysfunction. Clonidine (0.1 mg, orally) lowered blood pressure 18 +/- 3 torr in six subjects and raised it 5 +/- 1 torr in six. The change in blood pressure in response to this dose of clonidine was inversely proportional to the supine level of norepinephrine (P less than 0.05). Yohimbine (4-64 micrograms/kg) raised plasma norepinephrine and blood pressure in six patients with degenerative autonomic dysfunction. Yohimbine also attenuated by 50% (P less than 0.05) the hypotensive response to head-up tilt of patients with degenerative autonomic dysfunction. Clonidine depends upon postjunctional hypersensitivity and the degree of autonomic insufficiency to elicit its pressor response. In contrast, the pressor response to yohimbine is related to the capacity of the sympathetic nervous system to be activated and release norepinephrine. If plasma norepinephrine levels following yohimbine administration are monitored, the biochemical and hemodynamic response to the drug may provide a sensitive indication of the capacity of the sympathetic nervous system to be activated in patients with autonomic dysfunction.

Adult↗
PubMed1986

Verapamil, diltiazem and nifedipine block the depolarization-induced potentiation of norepinephrine contractions in rabbit aorta and porcine coronary arteries.

The effectiveness of verapamil, diltiazem and nifedipine in reducing potassium-induced enhancement of vascular responses to norepinephrine was studied in rabbit aorta and porcine coronary arteries. At multiple levels of external potassium concentration (4-28 mM), norepinephrine concentration-response curves were performed. Whereas the tissue was only slightly depolarized (about 5 mV) by an increase in external potassium to 20 mM, the norepinephrine response was markedly potentiated. For example, the EC50 of norepinephrine in aortic rings was reduced from 4.7 X 10(-8) M in 4 mM potassium to 4.7 X 10(-9) M in 20 mM potassium. Calcium channel blockers reduced potassium- and calcium-induced contractions, the IC50 being 6 X 10(-8) M for verapamil, 5 X 10(-7) M for diltiazem and 3 X 10(-9) M for nifedipine. These concentrations only minimally reduced norepinephrine contraction in 4 mM potassium but virtually abolished the depolarization-induced potentiation of the norepinephrine contraction. Even short exposures to levels of potassium, which resulted in little or no contraction by themselves, markedly potentiated the norepinephrine contraction. Therefore, the abolition of this potentiation by calcium channel blockers cannot be explained by a reduction of potassium-induced contraction. Similar observations were made in porcine coronary arteries. Thus, the potency of calcium channel blockers against norepinephrine-induced contractions is markedly increased in depolarized vascular smooth muscle. Calcium channel blockers may be especially effective in preventing enhanced vascular contractions resulting from physiological concentrations of catecholamines in partially depolarized vascular smooth muscle.

Animals↗
PubMed1985

Effects of indomethacin on systemic and coronary hemodynamics in patients with coronary artery disease.

The effects and possible mechanisms of actions of indomethacin on systemic and coronary hemodynamics were studied in 17 patients with coronary artery disease. Group I patients (12) were given either indomethacin or placebo in the absence of prior cyclooxygenase inhibition and group II (five) were given indomethacin after prior treatment with 2600 mg of aspirin. In group I, systolic blood pressure rose from a baseline of 136 +/- 5 mm Hg to a peak level of 158 +/- 8 mm Hg 5 minutes after drug (p less than 0.01). This was associated with a fall in coronary blood flow and a rise in coronary vascular resistance from a baseline of 1.36 +/- 0.4 mm Hg/ml/min to 1.99 +/- 0.7 mm Hg/ml/min 5 minutes after indomethacin (p less than 0.01). Immunoreactive thromboxane B2 levels fell from 191 to 1.4 ng/ml. No changes were noted in plasma renin activity, angiotensin II, or catecholamine levels. Immunoreactive thromboxane B2 levels were undetectable throughout the study period in group II patients and the blood pressure response to indomethacin was attenuated. Baseline coronary blood flow was significantly higher (p less than 0.01) and baseline coronary vascular resistance significantly lower (p less than 0.01) than in group I. At all time points after indomethacin, the fall in coronary blood flow was greater and the increase in coronary vascular resistance less in group II versus group I (p less than 0.001). These findings suggest a dissociation between the effect of indomethacin on systemic and coronary hemodynamics, the former apparently being more prostaglandin-dependent than the latter.

Adult↗
PubMed1985

Correlation of two-dimensional echocardiography and pathologic findings in porcine valve dysfunction.

Two-dimensional echocardiographic findings in porcine valve dysfunction were compared with pathologic findings in 10 patients (12 valves). Three specific echocardiographic findings were identified in patients with regurgitant lesions: prolapse, fracture and flail leaflets. Prolapse was associated pathologically with thinning of the leaflets, longitudinal tears close to the ring margin and acid mucopolysaccharide accumulation. Valve fracture was seen with and without prolapse and was accompanied pathologically by small pinpoint perforations or tears of the leaflet. A flail leaflet was seen with a linear tear of the free margin and was associated with calcific deposits. Mild degrees of fracture seen pathologically were missed on the echocardiographic study in five patients. Thickening or calcification, when present in moderate or severe amounts, was correctly identified by echocardiography. When all abnormal features were considered collectively, two-dimensional echocardiography correctly identified at least one of them in all patients. Therefore, two-dimensional echocardiography may prove useful in assessing the source of valvular regurgitation in patients with bioprosthetic valves.

Adult↗
PubMed1985

Reflexes unique to myocardial ischemia and infarction.

Although arrhythmias caused by myocardial ischemia are a well recognized cause of sudden death, the potential influence of cardiogenic reflexes originating in areas of ischemia has received less attention. In this study, 12 patients with well documented single vessel coronary artery spasm, with a total of 2,240 episodes of transient transmural ischemia, are described. Continuous electrocardiographic and hemodynamic recordings were analyzed to determine possible relations between the anatomic area of ischemia and patterns of change in blood pressure and heart rate. Of seven patients with ischemia of the posterior or inferior left ventricular wall, six had associated bradycardia and hypotension, an apparent Bezold-Jarisch response. Only one of five patients with anterior ischemia had a similar response. A hypertensive, tachycardiac response resembling the James reflex was seen in two of the patients with anterior ischemia, with an increase in blood pressure of 36/22 +/- 12/6 mm Hg and an increase in heart rate of 8 +/- 3 beats/min. This increase began before the onset of chest pain and was seen even in asymptomatic episodes. These reflexly mediated hemodynamic responses may modulate the direct effects of myocardial ischemia and could play a role in sudden cardiac death.

Angina Pectoris↗
PubMed1985

Neural circuits in the flight system of the locust.

Circuitry in the flight system of the locust, Locusta migratoria, was investigated by use of intracellular recording and staining techniques. Neuronal connections were established by recording simultaneously from neuropile segments of pairs of identified interneurons. Brief depolarizing current pulses delivered to interneurons 301 and 501 reset the flight rhythm in a phase-dependent manner, thus establishing the importance of these neurons in rhythm generation. Interneuron 301 was found to make a strong delayed excitatory connection with 501 and to receive a short-latency inhibitory connection from 501. The circuit formed by 301 and 501 appears suited for promoting rhythmicity in the flight system. The delayed excitatory potential recorded in 501 following each spike of 301 was reversed by hyperpolarizing 501. This potential and short-latency inhibitory postsynaptic potentials from 301 to other interneurons were blocked with the application of picrotoxin. We conclude that the delayed excitation is produced via a disynaptic pathway from 301 to 501, with 301 inhibiting in a graded manner the tonic release of transmitter from one or more unidentified intercalated neurons. Interconnections between the 301-501 circuit and other identified interneurons were discovered. This circuitry can account for two features of the flight motor pattern recorded in deafferented preparations. These features are the constant-latency relationship between depolarizations in elevator and depressor motoneurons and the relatively constant duration of depressor motoneuron bursts. The locust flight system shares general features with other described rhythm-generating systems. These include the occurrence of graded interactions, the probability of multiple oscillatory mechanisms, and a predominance of inhibitory connections. Its uniqueness lies in the way that components and processes are assembled and operate.

Animals↗
PubMed1985

Endogenous biosynthesis of prostacyclin during cardiac catheterization and angiography in man.

The potent platelet inhibitory and vasodilator properties of prostacyclin suggest that levels of this substance may be of relevance to drug action and pathologic processes in the coronary vascular bed. Attempts to estimate the coronary secretion rate of prostacyclin have relied on measurements of metabolites obtained via cardiac catheter, usually as an adjunct to coronary angiography. To test the hypothesis that such procedures might themselves perturb endogenous biosynthesis of prostacyclin we used mass spectrometry to measure plasma levels of 6-keto-prostaglandin (PG) F1 alpha across the coronary vascular bed, as well as to assess the excretion of a major urinary metabolite, 2,3-dinor-6-keto-PGF1 alpha (PGI-M), in patients undergoing cardiac catheterization. PGI-M excretion increased variably from a median 100 to 205 pg/mg creatinine (p less than .01) during catheterization with angiography and remained elevated 2 to 4 hr after initiation of the procedure. However, cardiac catheterization without angiography also stimulated metabolite excretion, perhaps reflecting catheter-induced vascular trauma. The direct effect of radiocontrast media on vascular release of prostacyclin was indicated by increased PGI-M excretion in healthy volunteers administered intravenous radiocontrast and by studies of the canine coronary artery and jugular vein in vitro. Measurement of plasma 6-keto-PGF1 alpha after left heart catheterization showed that levels in aortic (21 +/- 8 pg/ml) and coronary sinus (14 +/- 2 pg/ml) blood were increased compared with peripheral venous levels (less than or equal to 4 + 1 pg/ml) determined before this procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1985

The QRS complex during transient myocardial ischemia: studies in patients with variant angina pectoris and in a canine preparation.

We made continuous electrocardiographic recordings on magnetic tape during 15 episodes of ischemia in five patients with variant angina to determine the characteristics of the QRS changes. Orthogonal leads were used and the electrocardiograms were analyzed visually and by digital computer. Changes were quantified by subtracting baseline electrocardiograms from those obtained during ischemia. Large changes in the QRS occurred during ischemia but the waveform quickly returned to baseline when the episode subsided. In all patients there was prolongation of the QRS duration and an increase in QRS voltage during the terminal 40 msec of the waveform in the lead(s) showing the most marked ST displacement. The increase in the terminal QRS could be represented by a vector directed toward the ischemic zone. In a given patient the amplitude of ST displacement varied between episodes, presumably because of variation in the intensity of ischemia, but the QRS changes were directionally similar in each episode. In two patients there was also a smaller change involving the initial 40 msec of the QRS that could be represented by a vector directed away from the ischemic zone. To determine the possible mechanism for the electrocardiographic changes, ischemic episodes of 120 to 150 sec were produced in seven dogs and electrocardiographic recording and analysis techniques similar to those used in patients were employed. Myocardial conduction velocity was measured in three directions in the ischemic zone and was correlated with simultaneous electrocardiographic recordings from the body surface. The electrocardiographic changes in the dog preparation were virtually identical to those in the patients and strongly correlated with a fall in myocardial conduction velocity. We conclude that the QRS changes during variant angina result from the altered excitation pattern produced by conduction delay in the ischemic zone. The probable cause for the increase in terminal QRS voltage is delayed (and uncancelled) activation of the ischemic zone.

Angina Pectoris, Variant↗
PubMed1984

Effect of tyramine on myocardial catecholamine release in coronary heart disease.

The influence of tyramine on myocardial catecholamine release and on coronary blood flow has not previously been determined in man. Therefore, the effect of tyramine was measured on coronary and systemic hemodynamics and on norepinephrine (NE) and epinephrine levels in blood from the aorta and coronary sinus in 9 patients with coronary artery disease. Tyramine produced a striking increase in coronary sinus NE, from a baseline of 344 +/- 56 to a peak level of 1416 +/- 310 pg/ml (p less than 0.01) 2 minutes after tyramine. The increase in aortic NE was less striking, from 265 +/- 32 to 421 +/- 63 pg/ml (difference not significant). Therefore, the net release of NE from the heart was increased by tyramine from 12,007 +/- 393 to 139,357 +/- 46,156 pg/ml/min (p less than 0.03). There was no release of epinephrine across the coronary bed. There was a variable response of coronary blood flow and resistance after tyramine. Thus, the rich innervation of the heart by sympathetic nerve endings can result in marked NE release into the coronary sinus.

Adult↗
PubMed1984

Two-dimensional echocardiography in the diagnosis of carcinoid heart disease.

Tricuspid valve disease accounts for significant morbidity and mortality in the carcinoid syndrome, but M-mode echocardiography is often insensitive in completely defining the tricuspid valve. We performed two-dimensional echocardiography (2DE) in seven patients with proven carcinoid syndrome. There were five males and two females whose ages ranged from 53 to 79 years. The carcinoid syndrome had been present by symptoms for 12 to 84 months and by 5-HIAA levels for 6 to 84 months prior to 2DE. Short, thickened, immobile tricuspid valve leaflets, fixed in a partially open position, were visualized in two patients and confirmed in one patient at surgery. Tricuspid regurgitation was demonstrated angiographically in one and by contrast 2DE in the other. A third patient had clinical evidence of tricuspid stenosis with a doming tricuspid valve on 2DE. The motion of the tricuspid value viewed in real time was clearly distinct in these two situations. Four patients had both normal M-mode and 2DE studies despite the fact that clinical and biochemical evidence of carcinoid disease had been present for equally long periods of time. The tricuspid valve was best visualized in the parasternal right ventricular long-axis and short-axis views. The apical four-chamber view was less helpful. Thus, 2DE demonstrated specific tricuspid valve abnormalities in the carcinoid syndrome with thickening, shortening, and immobility of the leaflets when valvular regurgitation was present and thickening and doming when the valve was stenotic. 2DE should be a useful method in the diagnosis and sequential evaluation of patients with carcinoid heart disease.

Aged↗
PubMed1984

Increased vascular beta2-adrenoceptor responsiveness in autonomic dysfunction.

Responsiveness to the vasopressor, vasodepressor and chronotropic effects of several sympathomimetic amines was assessed in 12 patients with severe autonomic dysfunction and in 8 age-matched control subjects. The patients with autonomic dysfunction showed a profound increase in responsiveness to both isoproterenol and phenylephrine as compared with control subjects. The mean bolus dose of isoproterenol required to increase heart rate by 25 beats/min was 0.9 + 0.2 microgram in the patients and 5.4 + 2.1 micrograms in the control subjects. The dose of isoproterenol required to reduce mean blood pressure by 25 mm Hg was 0.3 + 0.2 and 5.2 + 1.8 micrograms, respectively. Thus, although there is a 6-fold increase in responsiveness to the chronotropic effect of isoproterenol in autonomic dysfunction, the responsiveness to the drug's depressor effect is increased 17-fold. This enhanced depressor sensitivity is quite marked, even with oral beta-adrenoceptor agonists. Beta-adrenoceptor agonists must be used with caution in conditions associated with autonomic dysfunction if dangerous hypotension is to be avoided.

Aged↗
PubMed1984

The effects of organic nitrates on prostacyclin biosynthesis and platelet function in humans.

The results of prior studies indicate that nitroglycerin stimulates prostacyclin release by cultured endothelium and by the coronary vasculature in vivo. However, the accuracy of these findings in coronary vasculature relies on plasma samples obtained from the circulation via cardiac catheters, a procedure we have shown to stimulate prostacyclin release, thereby confounding interpretation of drug action. We studied the effects of short-acting (nitroglycerin) and long-acting (isosorbide dinitrate) nitrates on a noninvasive index of prostacyclin synthesis, excretion of urinary 2,3-dinor-6-keto-PGF1 alpha. Nitroglycerin was infused into six subjects to either a maximum of 480 micrograms/min or until mean arterial pressure fell by 20 mm Hg. Urine was collected for negative ion chemical ionization gas chromatographic, mass spectrometric analysis before and during the nitroglycerin infusion and for two 2 hr periods after nitroglycerin. The peak nitroglycerin infusion rate was 387 +/- 67 micrograms/min, which caused a fall in supine blood pressure (systolic/diastolic) of 11 +/- 5/14 +/- 4 mm Hg and a 12 +/- 3 beats/min increase in heart rate. Excretion of 2,3-dinor-6-keto-PGF1 alpha (pg/mg creatinine) was unchanged from control infusion values (106 +/- 19.5) either during (123 +/- 21) or after (134 +/- 14.6; 139 +/- 36) nitroglycerin infusion. Platelet aggregation to arachidonic acid (0.33 to 1.33 microM) and epinephrine (1 to 10 microM) ex vivo was inhibited in only one subject in whom excretion of 2,3-dinor-6-keto-PGF1 alpha was unaltered. Serum thromboxane B2 was not changed by nitroglycerin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Mitral anular calcification in chronic renal failure.

In order to determine the incidence and pathogenesis of mitral anular calcification (MAC) in chronic renal failure, we analyzed biochemical, hemodynamic and echocardiographic data in 168 patients on long-term hemodialysis. Mitral anular calcification is more common in patients with chronic renal failure than in other patients of similar age. Its pathogenesis appears to be due to abnormal calcium-phosphorus homeostasis in the setting of secondary hyperparathyroidism. Hypertension did not appear to be an important etiologic factor in our patients. Meticulous control of hyperphosphatemia would appear to be the most important therapeutic measure in preventing this complication.

Adult↗