Sibley W. Hoobler

Blood pressure crisis following withdrawal of clonidine (Catapres, Catapresan), with special reference to arterial and urinary catecholamine levels, and suggestions for acute management

Abstract In five patients with severe essential hypertension, placebo was substituted after 24 to 48 months of treatment with clonidine and a diuretic. In the present study, four of the patients developed a marked blood pressure rise following withdrawal of clonidine which was rapidly reversed by intravenous administration of propranolol 0.2 mg. per kilogram of body weight and phentolamine 20 to 30 mg. The fifth patient was pretreated with reserpine 2.0 mg. intramuscularly for three days prior to withdrawal of clonidine, and the blood pressure rise which he experienced was far less impressive. All patients experienced similar “withdrawal” symptoms, consisting of headaches, insomnia, restlessness, tremor, and nausea. Catecholamines were determined in arterial blood and urine, before and during the overshoot. They revealed a marked increase, particularly in the urine samples, consistent with the appearance of a hyperadrenergic state.

Effect of an Intravenous Sodium Chloride Load on Renal Hemodynamics and Electrolyte Excretion in Essential Hypertension

Excretion of infused sodium, chloride, and water increased proportionately in patients with progressively more severe grades of hypertension and of increased renal vascular resistance. These relationships held so long as renal plasma flow and glomerular filtration rate were not greatly impaired. The abnormality was characterized by increased renal tubular rejection of sodium, chloride and water.

A Method for Studying Isolated Resistance Vessels from Rabbit Mesentery and Brain and Their Responses to Drugs

A technique has been developed for studying the reactivity of single, isolated resistance vessels, 50 to 250 μ o.d., perfused at constant flow rate. The validity of the method is established because responses to a given stimulating agent are reproducible and stable over a reasonable period of time. The magnitude of the response is dependent on the perfusion pressure, being maximal at a physiological pressure level. Resistance vessels from mesentery and brain of normal rabbits were compared with respect to their threshold for response to several vasoconstrictors. The results reaffirmed the individuality of smooth muscle from different vascular beds. Cerebral and mesenteric vessels are alike in the dose required for threshold constrictor response to KCl, angiotensin and plasma, but differ in that cerebral vessels have a higher threshold for response to epinephrine, norepinephrine and serotonin, and a lower threshold for response to vasopressin, than mesenteric vessels. Since the differences in threshold between vessels from the two sources are not the same for all stimulating agents, it seems probable that smooth muscle of the cerebral vessels is not generally less sensitive to all stimuli than that of mesenteric vessels, but that vessels from the two sources differ in the “number of receptors” for the several vasoactive agents.

The effects of splanchnicectomy on the blood pressure in hypertension; a controlled study.

The effect of supradiaphragmatic splanchnicectomy on the blood pressure of 294 hypertensive patients followed for 10 to 18 months after surgery is compared with the effects of nonspecific medical management in a control group of 79 patients similarly studied. The data are presented in simple graphic form. It is concluded that 29 per cent of the hypertensive patients had reductions in blood pressure outside the range of spontaneous variation, that the vascular complications of hypertension decreased the likelihood of a good result, and that extension of the sympathetic ganglionectomy upward appeared to increase the frequency of good results without requiring a two-stage operation or producing significant postoperative orthostatic hypotension.

Clonidine hydrochloride in the treatment of hypertension

Abstract Clonidine hydrochloride (Catapres) combined with a diuretic agent was given to 57 patients for a period of 6 months to 2 years. It was shown to be an effective agent for the long-term treatment of hypertension. It acts by central inhibition of adrenergic vasomotor stimulation; its withdrawal can cause transient sympathoadrenal hyperactivity. Dry mouth, constipation and transitory drowsiness were the most common side effects. They diminished with time, even when the dose was progressively increased. Bradycardia was produced by inhibition of cardiac sympathetic innervation, but no serious dysrhythmias occurred. The drug can be used to advantage as a replacement for guanethidine or methyldopa (Aldomet) but must be given with a diuretic agent. Orthostatic hypotension was rare. Addition of hydralazine or reserpine in conventional dosage decreased blood pressure very moderately. No change was observed when alpha methyldopa was added. On the contrary, administration of Clonidine to a patient exhibiting partial adrenergic blockade with guanethidine augmented the effects of such blockade, causing a further decline in both standing and recumbent blood pressure. This 3 year experience shows that clonidine is safe and free from toxicity. It is effective if patiently administered in increasing dosage until proper control of blood pressure is achieved.

Sodium Chloride Excretion Following Salt Loading in Hypertensive Subjects

Patients with essential hypertension show an altered renal excretory response to sodium chloride loading. Hypertensive patients acutely eliminate a greater proportion of a salt and water load than do normotensive subjects. This renal abnormality appears to be due to an augmented tubular rejection of sodium chloride and water. This study further defines the nature and extent of this alteration in electrolyte and water metabolism.

Effect of minoxidil on blood pressure and hemodynamics in severe hypertension

Eighteen patients with diastolic hypertension (100 to 120 mm Hg), in addition to propranolol, 160 mg daily, and hydrochlorothiazide, 100 mg daily, received progressively increased doses of either minoxidil or placebo in a double-blind crossover study. With minoxidil (average dose 19.7 mg) blood pressure decreased from 165/109 to 138/89 mm Hg without the appearance of orthostatic hypotension. Hypertrichosis and fluid retention did occur, with an average weight gain of 1.8 kg, concomitant with an increased plasma volume. Pulse rate and cardiac output increased; no significant changes were observed in plasma renin activity, renal plasma flow, glomerular filtration rate or excretion of catecholamines or aldosterone. Minoxidil appears to be a useful antihypertensive drug for treating patients who do not respond adequately to therapy with diuretic and beta adrenergic blocking agents.

Circulatory reactions of normotensive and hypertensive subjects and of the children of normal and hypertensive parents

There is substantial agreement that high blood pressure is a familial trait.L-5 The careful studies of Miall and.Oldham’ and of Hamilton, Pickering, Roberts and Sowry indicate a higher average blood pressure among the relatives of hypertensive than of normotensive subjects. Hines, McIlhane~, :ind Gagez described the occurrence of hypertension in 8 pairs of identical twins, whereas in 3 pairs of fraternal twins the disease occurred in only one member. Despite these studies, few efforts have been made to identify the earliest age at which the blood pressure of the children of hypertensive parents ma)be expected to deviate from the values observed in the offspring of normal parents. .2ytnan,” however, found a blood pressure in excess of 140,/80 mm. Hg in 29 per cent of the progeny aged 14-39 of hypertensive parents, as compared to a 3 per cent incidence of similar blood pressure elevation in the offspring of normotensive parents. Although the familial aspects of hypertension have been agreed u~)on, the evidence is less consistent that exposure to various forms of stress ma!undul~~ elevate the blood pressure of prehypertensive subjects. Hines” reported subsequent hypertension in 9 per cent of 84 normal reactors and in 54 per cent of 105 hyperreactors to an ice-water immersion test. On the other hand, Harlan7 and Armstrong and Rafferty* could not confirm this finding. Hines also found an excessive rise in blood pressure to the cold pressor stimulus in hyl)ertensive patients, when compared to normal control subjects. Q*lo Other authors have fount1 less consistent differences in the cold pressor responsiveness of the normal ant1 the hypertensive subject”~‘? or have observed considerable inconsistent->. in the response of the same individual to repeated testing.7,*3 Other stimuli, such :\s breath-holding,14 exercise,‘” and change in posture, I6 have also been t rictl in (I further attempt to distinguish a normal from a hypertensive response.

Epidemiology of hypertension with particular reference to the Bahamas

Abstract 1. 1. Data on a blood pressure study of 3,594 Negro subjects in the Bahamas are presented. These data confirm previous observations that the prevalence of elevated blood pressure in this area is high. The percentage of males with a blood pressure of 150 90 mm. Hg or more was 25 per cent; of females, 30 per cent. 2. 2. Comparisons of these data with the blood pressure of white subjects in the United States revealed significantly higher systolic and diastolic blood pressures in both sexes and in all age groups in the Bahamas. 3. 3. Blood pressure levels of three different Negro populations (United States, Virgin Islands and the Bahamas) were compared and found to be similar in most age groups. This suggests that the blood pressure of Negroes is higher regardless of areas studied or level of “civilization.” Significant differences in blood pressure were not found between “rural” or “urban” areas in the Bahamas. 4. 4. Complications of elevated blood pressure, especially cerebral hemorrhage, are apparently common in the Bahamas. 5. 5. Although salt intake may be high in the natives of the Bahamas, familial factors may be of more importance in explaining the variability of prevalence in different island groups in this apparently “susceptible” population. 6. 6. Additional genetic and dietary studies are suggested in this group as well as in comparable Negro populations elsewhere in an effort to clarify the apparent “racial” susceptibility to hypertension.

Observations on the potential variations of the cavities of the right side of the human heart

I N 1934 Wilson, Johnston, and Hill’ published observations on the potential variations of the ventricular cavities of the dog’s heart and emphasized the bearing of their observations upon the interpretation of the QRS deflections of unipolar epicardial leads. The methods described and the principles laid down in their article were used later in the analysis of the precordial electrocardiogram” and have placed electrocardiographic interpretation upon a sounder and more logical basis. With the introduction of catheterization3 of the human heart it became possible to duplicate many of the observations made in the animal experiments referred to, and also to record the potential variations of the right auricular and right ventricular cavities in various types of cardiac abnormality which do not occur spontaneously in animals and cannot be simulated in experiments. The first report dealing with intracavitary potential variations in man was made by Hecht4 in 1946. He concluded that the principles based on animal experiments could be applied safely to the interpretation of the human electrocardiogram. In the following year Battro and Bidoggia5 studied twelve normal subjects and eleven patients with cardiac abnormalities. They pointed out the resemblance of the tracings obtained from the cavity of the right auricle to those recorded from the auricular levels of the esophagus. In their normal subjects, leads from the right ventricle displayed a small initial R wave, followed by a large S and a negative T deflection. In a case of right bundle branch block the cavity of the right ventricle was initially positive, whereas in one of left bundle branch block it was negative throughout the QRS interval. Shortly after this report appeared, Sodi-Pallares and associates6 published similar observations on six normal subjects, on twenty patients with heart disease, and on dogs studied under various experimental conditions. They found a great similarity between the records obtained in human bundle branch block and those obtained in dogs in which right or left bundle branch block had been produced experimentally. In their normal subjects, leads from the right ventricular cavity yielded curves similar to those described by other workers. With respect to the ventricular