Elevated Systemic Arterial Pressure Research Articles

Prevention of the development of heart failure and the regression of cardiac hypertrophy by captopril in the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) exhibits both a compensated phase of cardiac hypertrophy in which forward output is maintained despite persistently elevated systemic arterial pressures and a decompensated phase in which cardiac performance has deteriorated in spite of further hypertrophic growth. To determine whether chronic antihypertensive therapy prevents the development of heart failure and the progression of cardiac hypertrophy in SHR with advanced hypertension, captopril (2 g/l of drinking water), a converting enzyme inhibitor, was administered to 14 month old female SHR and normotensive American Wistar rats (NWR) for 10 months. The severe left ventricular hypertrophy of the 24 month old untreated SHR (4.37 +/- 0.2 mg/g v. 2.50 +/- 0.06 mg/g, untreated NWR) was markedly reduced (P less than 0.02) by captopril (3.01 +/- 0.1 mg/g). Chronic therapy prevented the reduction of both baseline and maximal cardiac indices in SHR, but did not alter blood flow in NWR. Left ventricular dilatation was present in 24 month old SHR and, as peak stroke volume index was diminished, the ejection fraction index of the SHR was reduced. Captopril restored this index in SHR to normal. The relation of ejection fraction index and afterload (peak systolic wall stress) was depressed in untreated SHR, but was normal in treated SHR. Thus, chronic therapy with captopril prevented the development of severe cardiac dysfunction and produced a marked regression of cardiac hypertrophy in SHR with advanced hypertensive heart disease.

Echocardiographic assessment of the left ventricle in juvenile hypertension

We studied with M-mode echocardiography the morphology and function of the left ventricle in a group of 36 juvenile hypertensives with borderline hypertension, whose cuff arm pressure exceeded 150 90 mmHg in at least three separate sessions. The results were compared with those of 23 age-matched normotensives with no evidence of any cardiovascular disease. Left ventricular hypertrophy (i.e. septum and/or posterior wall thicknesses in diastole ⩾ 12 mm) was present in 13 subjects of the hypertensive group (36%). Significant increase of interventricular septal thickness together with higher septum/posterior wall ratio and a higher incidence of asymmetric septal hypertrophy were the most characteristic findings in juvenile hypertensives. Of the functional parameters the only observed difference between the two groups was an elevated peak velocity of left ventricular contraction in hypertensives which tended to correlate inversely with the values of septum/posterior wall ratio. Additional comparison of electrocardiographic and echocardiographic detection of left ventricular hypertrophy in young hypertensives revealed a lower sensitivity but a satisfactory specificity of electrocardiography (31 and 87% respectively). The results indicate that besides an elevated systemic arterial pressure, other factors such as increased sympathetic or humoral activity may play a role in the incipient stage of essential hypertension and that isolated septal hypertrophy seems to be an early sign of cardiac involvement.

Experimental neurogenic pulmonary edema. Part 1: The role of systemic hypertension.

Neurogenic pulmonary edema (NPE) was produced consistently in normal cats by increasing intracranial pressure with an intraventricular infusion of mock cerebrospinal fluid. The usual elevation of systemic arterial pressure (SAP) that follows severe intracranial hypertension (the "Cushing response") was controlled by blood withdrawal at variable rates to achieve and maintain constant cerebral perfusion pressure (CPP) in three groups of cats of 50, 20, and 0 mm Hg, respectively, for 30 minutes. In this model, NPE occurs in the absence of increased SAP and in the presence of decreasing CPP. These results indicate that systemic arterial hypertension is not an essential stimulus for the development of NPE, and suggest that the lungs are directly affected by the intense sympathetic discharge evoked by severe intracranial hypertension.

Contraction of dog trachealis muscle in vivo: role of alpha-adrenergic receptors.

Contraction, relaxation, and longitudinal tension were recorded by isometric strain gauge arches attached to cervical tracheal muscle (CTM) in 60 spontaneously breathing dogs anesthetized with pentobarbital. Intravenous norepinephrine (NE) (3 X 10(-9), 6 X 10(-9), 1.2 X 10(-8), and 2.4 x 10(-8) mol/kg) increased spontaneous mechanical activities (SMA) and caused dose related contraction of CTM in all dogs even though there was no pretreatment with beta-blockers. These activities were first potentiated by propranolol and then prevented by phentolamine. NE briefly decreased SMA and induced CTM relaxation prior to the onset of contraction in one-third of dogs. Propranolol prevented this initial relaxation. CTM responses induced by NE were 1) not significantly altered by atropine, tripelennamine, bilateral vagotomy, curarization, and complete tracheal transection below transducer sites; 2) unrelated to passive constriction of cervical trachea associated with airway elongation; and 3) independent of reflexes initiated by elevations of systemic arterial pressure. The moles per kilogram doses of acetylcholine were found to exceed those of NE when their intravenous administration caused equal CTM contractions in the same dog. These findings are consistent with the existence of alpha-adrenergic receptors in CTM.

Alterations of cardiac performance in rats with established spontaneous hypertension

To characterize intact cardiac performance during the progression from moderate to severe left ventricular hypertrophy, peak pumping ability, maximal pressure-generating capacity and passive pressure-volume relations were determined in ether-anesthetized 6 and 18 month old female spontaneously hypertensive rats, in 18 month old male spontaneously hypertensive rats and in sex- and age-matched normotensive rats. Ejection phase indexes of young female hypertensive rats were comparable with those of age-matched normotensive rats. Both groups ejected the same peak stroke volumes from similar end-diastolic volumes so that their indexes of ejection fraction were identical. However, in old female and male hypertensive rats, these characteristics of ventricular performance were greatly diminished. A reduced peak stroke volume was ejected from a normal end-diastolic volume in old female hypertensive rats and from a significantly larger end-diastolic volume in old male hypertensive rats, so that ejection fraction indexes were moderately and substantially reduced, respectively. Maximal pressure developed during an aortic occlusion was always significantly greater in hypertensive rats. Despite elevated systemic arterial blood pressures, young female hypertensive rats ejected a normal stroke volume from a normal end-diastolic volume. Even though the severity of hypertension did not further progress with age, cardiac mass increased, yet systolic function decreased in old hypertensive rats. Therefore, hypertrophic growth of the left ventricle in the hypertensive rat is associated with both a compensated and a depressed phase of cardiac performance.

Long term effects of the anorectic agent fenfluramine alone and in combination with aminorex on pulmonary and systemic circulation in the pig.

We have investigated the effects of chronic oral administration of two anorectic substances, fenfluramine and aminorex, especially on the pulmonary circulation in young pigs with one ligated pulmonary artery. The pulmonary vascular reactivity was tested by alveolar hypoxia, alveolar hyperoxia and infusion of prostaglandin F2ALPHA. No elevation of pulmonary arterial pressures or resistances were found due to the intake of fenfluramine or aminorex over a three month period. The responses to the vasoconstrictor stimuli, hypoxia and prostaglandin F2alpha, and to the vasodilator stimulus, hyperoxia, were equal and not augmented in the drug groups. Fenfluramine or aminorex could therefore could therefore not be shown to have an adverse effect on the pulmonary circulation or on the reactivity of the pulmonary vascular bed in the pig, but fenfluramine elevated systemic arterial pressure.

The Effect Of Penicillamine On Blood Pressure And Vascular Disease In Mice With Infarct-Kidney Hypertension

Treatment with penicillamine was capable of bringing down the elevated systemic arterial pressure in the thymus-dependent phase of infarct-kidney hypertension in mice; a marked improvement in the clinical condition of the treated animals was observed as compared with untreated hypertensive mice. No pathological changes in either kidney or heart could be attributed to toxic side effects of penicillamine either in normotensive or in hypertensive mice treated for several months with penicillamine. It is concluded that penicillamine may have an effect on thymus-dependent reactions, such as the increased blood pressure in the chronic phase of infarct-kidney hypertension in mice. In mice, the treatment can be extended over a considerable part of the animal's life span without apparently giving rise to toxic side effects on vital organs.

POSTOPERATIVE HYPERTENSION IN THE MANAGEMENT OF PATIENTS WITH INTRACRANIAL ARTERIAL ANEURYSMS

Elevation of systemic arterial pressure in seven patients with intracranial arterial aneurysms has been shown to be effective in alleviating ischemic symptoms attributed to cerebral vasospasm. Autoregulation is at least partially lost in patients with cerebral hemodynamic crisis. Blood volume expansion was used to augment vasopressors in maintenance of systemic hypertension. The management of these cases is discussed. Caution in the use of this technique is advised, since the regimen is not without risk.

Postoperative hypertension in the management of patients with intracranial arterial aneurysms

Elevation of systemic arterial pressure in seven patients with intracranial arterial aneurysms has been shown to be effective in alleviating ischemic symptoms attributed to cerebral vasospasm. Autoregulation is at least partially lost in patients with cerebral hemodynamic crisis. Blood volume expansion was used to augment vasopressors in maintenance of systemic hypertension. The management of these cases is discussed. Caution in the use of this technique is advised, since the regimen is not without risk.

Response of the neonatal heart to a new inotropic agent, RO2-2985 (X537A).

The ionophore RO2-2985 did not produce a positive inotropic response in 1-day-old canine isolated ventricle. A gradual increase in inotropic response was seen with age. Isolated atria, however, exhibited a positive inotropic response at birth (50% increased dF/dt), which became progressively greater with age (100% increase in dF/dt at 15 days of age). In the neonatal heart in situ there was a positive inotropic response in 1-day-old puppies (40% increase in left ventricular dF/dt) with progressively greater responses with age (135% increase in left ventricular dF/dt at 11 days of age). There was a positive chronotropic (75-125% increase) response to RO2-2985 at all ages studied. The drug elevated systemic arterial pressure (150% increase in mean arterial pressure) to a similar degree in all ages studied. RO2-2985 depressed total calcium binding by both neonatal and adult isolated cardiac sarcoplasmic reticulum approximately 50%.

Use of indomethacin to reverse neonatal hypotension.

Treatment with indomethacin elevated systemic arterial pressure and pulmonary vascular resistance in hypotensive newborn goats. Indomethacin may be of value in restoration of systemic arterial pressure in stress-induced hypotension.

Cerebral blood flow, metabolism and mean arterial pressure changes following unilateral internal carotid endarterectomy: cerebral ischemia and elevated systemic arterial pressure.

Cerebral blood flow and metabolism studies were performed on 13 patients before and after unilateral carotid endarterectomy for severe atheromatous occlusive disease. Mean brachial arterial pressure was monitored during these studies. Postoperative studies compared to a control group revealed a rise in cerebral blood flow and a fall in mean arterial pressure and cerebral vascular resistance. The clinically recorded blood pressure in the study group compared to closely matched control patients with cerebral vascular disease showed a similar but not significant difference. Ten patients studied following ligation of a common carotid artery had a small but significant increase in mean systemic arterial pressure. These results suggest a relationship between systemic arterial pressure and cerebral ischemia. Some possibilities for this relationship are discussed.

Surgical resection of coarctation of the aorta in infancy

The results of resection for aortic coarctation with or without banding of the main pulmonary artery in 46 patients with intractable congestive heart failure are reported. There were 32 survivors (70%). Death occurred only in patients with pulmonary artery hypertension and mortality was higher in infants with an associated ventricular septal defect. In most survivors there was prompt relief of symptoms of heart failure. There have been no late deaths. Survivors have not had significant elevation of systemic arterial pressure or recurrent congestive heart failure. Some persisting mild aortic obstruction (or restenosis) is not uncommon. We have not yet had to perform secondary resections of residual obstructions though such may be necessary after longer periods of observation in some patients.

Methoxamine injections in the diagnosis of mitral insufficiency during routine right heart catheterizations.

Abstract. The effect of methoxamine on PCV pressure has been examined in 47 cases (24 with mitral valvular disease, 2 with aortic insufficiency, 12 with congenital heart disease, and 9 with no organic heart disease). The rise in v‐peak pressure related to the elevation in systemic arterial pressure (Δv/ΔA ratio) after methoxamine injection was measured. The ratio usually was higher in patients with mitral insufficiency than in other cases, but a marked overlapping was seen between the different patient groups. The methoxamine test during routine cardiac catheterization is therefore of limited value in the diagnosis of mitral insufficiency. A marked bradycardia was seen after methoxamine infusions in most cases. Four patients had transient conduction disturbances, but no serious complications were encountered. The effect of methoxamine on cardiac output was recorded in 13 cases. Methoxamine did not influence cardiac output significantly.

Effects of dopamine on the liver before and following administration of endotoxin

These studies were conducted to determine the effects of dopamine on the canine liver before and following endotoxin administration. Isolated, denervated livers were perfused via arterial and venous inflow vessels at constant rates by donor dogs. Weights were continuously recorded throughout the experiments. There were marked reductions in liver weight with dopamine infusion before endotoxin administration and continued reductions at slower rates following endotoxin. The mechanism of liver shrinkage is postulated to be primarily due to sinusoidal contractions independent of changes in liver venous resistances. Dopamine markedly increased hepatic artery pressures; thus hepatic artery resistances increased since the flows were constant. In the donor animal, dopamine elevated systemic arterial pressure, pulse pressure, and heart rates.

Effects of acute elevation in blood pressure and of atropine on heart rate in Chagas' disease. A preliminary report.

Degeneration of the parasympathetic ganglia in the heart and in the smooth muscle (esophagus, colon, and bronchi) is known to occur in Chagas' disease. The reflex bradycardia associated with acute elevation in systemic arterial pressure and the blocking of this reflex effect with atropine are used in this investigation to study vagotonic influences on the heart in patients with Chagas' disease. Failure to increase heart rate following administration of atropine observed in cases of chronic Chagas' heart disease is believed to be a functional disorder related to degeneration of the neuronal supply to the sino-atrial region of the heart. To the authors' knowledge this report provides the first existing physiological investigation concerning the cardiovascular system in Chagas' disease.

EFFECTS OF ANGIOTENSIN ON PULMONARY AND SYSTEMIC HEMODYNAMICS

In ten morphine-urethan anesthetized dogs single injections of 2.0 µg/kg of synthetic valine 5 angiotensin II amide elevated systemic and pulmonary arterial pressures and depressed heart rate. Thirty-minute intravenous infusions of angiotensin (0.4 and 1.0 µg/kg/min) in eight dogs elevated systemic arterial pressure and diminished heart rate. Pulmonary arterial, pulmonary wedge, left ventricular end-diastolic, and right atrial pressures were all slightly elevated; mean cardiac output did not change. Calculated total pulmonary resistance and pulmonary arterial resistance were diminished; central blood volume was elevated. These findings suggest that elevated systemic pressure and resistance increase myocardial work and induce reflex bradycardia, thereby elevating left ventricular end-diastolic, pulmonary wedge, and pulmonary arterial pressures. Systemic vasoconstriction also contributes to the elevated right atrial pressure and distention of the pulmonary vascular bed, which diminishes total pulmonary and pulmonary arterial resistance. These findings are not incompatible with the theory that the renin-angiotensin system is active in essential hypertension.

Observations on some clinical features of extreme obesity, with particular reference to cardiorespiratory effects

The nature, incidence and pathogenesis of some clinical features in fifty patients with extreme obesity have been analyzed, utilizing several kinds of relevant information. Exertional dyspnea (84 per cent), joint pains (72 per cent) and somnolence (52 per cent) were common symptoms. The incidence of blood pressure elevation (58 per cent) and peripheral edema (64 per cent) was relatively high, and roentgenographic evidence of cardiomegaly was quite regularly present, as indicated by comparison of the observed transverse cardiac diameter with that predicted for the ideal body weight by the Ungerleider-Clark table. Since one-third of the patients were normotensive, it was concluded that blood pressure elevation is by no means an invariable accompaniment of obesity, even when extreme. No correlation was found between the level of systemic blood pressure and the amount of excess weight. Comparison of blood pressure measurements by direct intra-arterial recording and the standard cuff method yielded falsely elevated values using the cuff 25 per cent of the time, but in only 8 per cent of the cases was this discrepancy large. Actually, the cuff method gave a falsely low estimate as frequently as it did a high one, so that a high reading obtained with the cuff was usually a valid indication of systemic arterial hypertension. The frequency and severity of peripheral edema could not be correlated with the amount of excess weight or with the level of the central venous pressure. Although elevated intra-abdominal pressure and varicose veins may play a role, mechanisms of edema formation in obesity seem poorly defined at present. Incidence and degree of somnolence were not correlated with amount of excess weight, arterial oxygen saturation, central venous pressure, or level of cerebral blood flow and oxygen consumption. Analysis of the relation between arterial carbon dioxide tension and degree of somnolence showed that all six patients with carbon dioxide retention had a tendency to somnolence. However, neither the presence of somnolence nor its severity could be related to the level of arterial carbon dioxide tension. The occurrence of pronounced somnolence without carbon dioxide retention has been taken as evidence denying a causal relationship involving carbon dioxide retention alone. It has been concluded that while carbon dioxide retention may aggravate a tendency to somnolence, the chief mechanisms responsible for development of somnolence in the obese state are not well defined at this time. Polycythemia was not observed in this series, although its occurrence in obese patients is well recognized. On the basis of our experience and published reports of larger series it has been concluded that the incidence of polycythemia is 5 per cent or less in patients with uncomplicated obesity. Mechanisms of dyspnea in the obese state have been reviewed in the light of demands upon the respiratory apparatus and its response. There was poor correlation between the severity of the dyspnea and the observed body weight or the amount of excess weight. A concept of the sequence of events leading to cardiomegaly and congestive heart failure in patients with extreme obesity has been advanced, and the so-called Pickwickian syndrome of obesity has been discussed with particular reference to the development of hypoventilation and cor pulmonale. Presently available data suggest that the incidence of hypoventilation is of the order of 10 per cent in patients with uncomplicated extreme obesity, as found in this study, and therefore this feature is representative at best of only a small segment of this obese population. Congestive heart failure, although uncommon, may occur in extremely obese patients with or without elevation of systemic arterial pressure. It is usually characterized by high cardiac output and insufficiency of both ventricles, predominantly the left. It has been concluded further that there is as yet no convincing evidence to indicate that uncomplicated obesity of extreme degree gives rise to the development of isolated cor pulmonale.

Effects of angiotensin on pulmonary and systemic hemodynamics.

In ten morphine-urethan anesthetized dogs single injections of 2.0 µg/kg of synthetic valine 5 angiotensin II amide elevated systemic and pulmonary arterial pressures and depressed heart rate. Thirty-minute intravenous infusions of angiotensin (0.4 and 1.0 µg/kg/min) in eight dogs elevated systemic arterial pressure and diminished heart rate. Pulmonary arterial, pulmonary wedge, left ventricular end-diastolic, and right atrial pressures were all slightly elevated; mean cardiac output did not change. Calculated total pulmonary resistance and pulmonary arterial resistance were diminished; central blood volume was elevated. These findings suggest that elevated systemic pressure and resistance increase myocardial work and induce reflex bradycardia, thereby elevating left ventricular end-diastolic, pulmonary wedge, and pulmonary arterial pressures. Systemic vasoconstriction also contributes to the elevated right atrial pressure and distention of the pulmonary vascular bed, which diminishes total pulmonary and pulmonary arterial resistance. These findings are not incompatible with the theory that the renin-angiotensin system is active in essential hypertension.

Hemodynamic effects of methoxamine in mitral valve disease.

The hemodynamic changes following elevation of systemic arterial pressure and total systemic resistance by methoxamine were studied by right heart catheterization in 18 patients with mitral valve disease and 4 patients with no significant cardiovascular abnormality. This is the first detailed report of the circulatory effects of this drug in man. Changes in oxygen consumption, arterial oxygen saturation, stroke index and pulmonary artery to pulmonary "capillary" mean pressure gradient were insignificant. Forward cardiac index and heart rate decreased significantly while arteriovenous oxygen difference increased markedly in all groups of patients. The hemodynamic mechanisms involved in the changes observed during methoxamine infusion are discussed. Characteristic of patients with mitral insufficiency were significant increments of pulmonary arterial mean, pulmonary "capillary" mean, and pulmonary "capillary" V peak pressures. These subjects also had significantly greater increments in "left heart" resistance than patients without mitral insufficiency. An elevation of pulmonary "capillary" V peak pressure of 35 per cent or more of the elevation of systemic arterial systolic pressure was found to be a useful index of the presence of mitral insufficiency. Study of the pulmonary "capillary" pressure records during methoxamine infusion may obviate the necessity of left heart catheterization in the detection of significant mitral insufficiency.