Lower Peripheral Resistance Research Articles

The effect on the splanchnic blood flow and cardiac output of various carbon dioxide concentrations during fluroxene (Fluoromar) anaesthesia. An animal study.

Seven dogs premedicated with pethidine 10 mg/kg body weight, were anaesthetized with mebumal natrium 25 mg/kg body weight i.v. and gallamoni jodidum 80 mg, together with O2‐N2O in a ratio of 1 to 1. Thereafter four dogs were constantly hyperventilated and three constantly hypoventilated under stepwise increasing anaesthesia with fluoromar® (= fluroxene), up to 6% inspiratory concentration. A change was made between the groups at this fluoromar concentration, from hyper‐ to hypoventilation and vice versa, after which the fluoromar concentration was reduced stepwise to 0% inspiratory. During the course of this anaesthesia, the related values for flow, pressure and resistance in the systemic and splanchnic circulations were measured at fluoromar concentrations: 0–1 1/2–3‐6‐6‐3‐1 1/2‐0%.The relative changes in the systemic circulation during increasing concentrations of fluoromar are independent of hypo‐ or hypercapnia, while the absolute magnitudes of the measured parameters are strongly dependent on the CO2 tensions. The hypercapnic dogs had the highest cardiac output, stroke volume and most rapid pulse, as well as the lowest peripheral resistance. The same group of dogs had the lowest liver blood flow and the greatest splanchnic resistance. The mean pressures in the aorta, right atrium and portal vein were not different between the groups.A straight line dependence at 6% fluoromar, was demonstrated between cardiac index and Paco2: cardiac index (1‐min‐1‐m‐2) = 1.22 + 0.23 ± Paco2 (kPa), ((cardiac index (1‐min‐1‐m‐2) = 1.22 + 0.03 ± Paco2 (mmHg)), and peripheral resistance and Pao2: peripheral resistance (kPa 1‐1 min) = 12.85—0.5 ± Paco2 (kPa), ((peripheral resistance (dyn‐sec‐cm‐5 ± 10‐3) = 7.72‐0.04 ± Paco2 (mmHg)). The pressure in the portal vein appears to rise and the liver flow to fall with rising carbon dioxide tension, but the relationship is not significant.In the latter half of the investigation only small changes were demonstrated which could be related to the falling concentration of fluoromar. These were slight rises in the mean pressure of the aorta and cardiac frequency, similar for both groups. In addition, a slight rise in the peripheral resistance and splanchnic resistance were observed in the hypocapnic group. No changes were seen in the cardiac output and liver flow in any of the groups during falling fluoromar concentrations. The absolute magnitude of the measured parameters in relation to the CO2 tension reflects the conditions in the first half of the investigation, but the difference between the groups is less pronounced. This was partly due to the smaller difference in Paco2 between the groups in this part of the investigation and partly due to the time and experimental course.

Commentary

To ascertain whether diuretics have an antihypertensive effect independent of natriuresis, 12 stable patients on maintenance hemodialysis underwent a crossover evaluation with hydrochlorothiazide, 50 mg daily, metolazone, 5 mg daily, or placebo in 4‐wk treatment periods for 6 mo. Compliance was assured by pill counts and serum drug concentrations. All patients had daily urine < 100 mi. Pre‐ and postdialysis blood pressure, body weight, plasma volume, and plasma renin activity were monitored. Over the 6‐mo study period there were no statistically significant changes in any parameter related to diuretic therapy. It is concluded that afunctioning kidney with the ability to respond to diuretics with a natriuresis is necessary for the antihypertensive action of diuretics. Direct vascular effects of diuretics to lower peripheral resistance could not be demonstrated in this unique patient population.

Dobutamine: development of a new catecholamine to selectively increase cardiac contractility.

We systematically modified isoproterenol's chemical structure to reduce chronotropic, arrhythmogenic, and vascular side effects. Experiments on dogs showed that the resulting drug, dobutamine, had an inotropic efficacy as great as that of epinephrine due to a direct action on beta1 cardiac receptors. However, unlike epinephrine, dobutamine's effect on alpha and beta2 vascular receptors was slight. At equivalent inotropic doses, dobutamine had less than a fourth of the chronotropic effect of isoproterenol. Desmethylimipramine (DMI), which blocks the sympathetic nerve fiber uptake mechanism, had no effect on dobutamine's actions. In contrast, DMI antagonized dopamine's inotropic effect, and marked chronotropic and pressor responses occurred when we used doses of dopamine large enough to elicit a direct inotropic effect. Dobutamine increased the contractility of isolated cat papillary muscles more but the automaticity less than did isoproterenol. In ischemic dog hearts, dobutamine lacked significant arrhythmic activity, whereas dopamine, norepinephrine, and isoproterenol caused severe ectopic activity. In dogs with experimentally induced low cardiac contractility, low cardiac output, and hypotension, dobutamine produced dose-related increases in cardiac contractility and output, restored arterial blood pressure, and reduced total peripheral resistance slightly. In contrast, isoproterenol failed to restore blood pressure, had only a meager effect on cardiac contractility and output, cuased extreme tachycardia, and lowered peripheral resistance more than did dobutamine. Norepinephrine, which did not increase cardiac contractility or output as much as dobutamine, excessively elevated peripheral resistance and arterial blood pressure.

Influence of central and peripheral changes on the hydraulic input impedance of the systemic arterial tree.

The input impedance of the systemic arterial tree of the dog has been computed by Fourier analysis. It was shown that a distance between pressure and flow transducers of less than 2 cm results in appreciable errors which manifest themselves mainly in the phase of the input impedance. The input impedance for controls, occlusions at various locations in the aorta, and an increase and decrease of peripheral resistance were studied. For the same experiments, the total arterial compliance was calculated from the peripheral resistance of the diastolic aortic-pressure curve. The characterstic impedance of the ascending aorta was also estimated. The impedance in the control situation may be modelled by means of a 3-element Windkessel consisting of a peripheral resistance and (total) arterial compliance, together with a resistance equal to the characteristic impedance of the aorta. The occlusions of the aorta show that blockage at (and beyond) the trifurcation do not result in a detectable change in input impedance, except for a slight increase of the peripheral resistance. The more proximal an aortic occlusion, the more effect it has on the pattern of the input impedance. When the aorta is occluded at the diphragm, or higher, the single (uniform) tube appears to be a much better model than the Windkessel. Occlusion of one or both carotid arteries increases the mean pressure; consequently not only the peripheral resistance increases but also the total arterial compliance decreases. The Windkessel with increased peripheral resitance and decreased compliance is again a good model. After a sudden release of occlusion of the aorta, the arterial system has a low peripheral resistance and may also be modelled by the Windkessel.

Forward and backward waves in the arterial system.

The total amount of reflection in the arterial system of the dog is evaluated during control, high, and low peripheral resistance, and an occluded descending aorta. Pressure, as measured in the ascending aorta, may be separated into a (composite) wave travelling from the heart towards the periphery, the forward wave, and a (composite) wave that travels in the opposite direction, the backward wave. This is also true for aortic flow. One may distinguish between reflections at bifurcations of the large vessels and reflections at the arteriolar part of the arterial tree. The former contribute a small, rather constant amount to the returning wave, while the latter reflects a strongly variable amount.

Micturition syncope

The case history is presented of a 37-year-old pilot with micturition syncope. Three spontaneous nocturnal attacks were observed clinically and with EEG and ECG recording. These recordings started at the moment the patient went to bed. In this way the EEG and ECG on awaking during the night, rising from the bed and voiding while in the upright position were studied. Since fainting always occured some 30 sec after the patient had finished voiding and since no obstruction in the urogenital tract and bladder was found, and the patient denied straining on micturition, a Valsalva effect cannot be regarded as an important aetiological factor. The syndrome is considered to be a vaso-vagal or vasodepressor reaction upon assuming the upright position under special circumstances, in which a low heart rate combined with lowered peripheral vascular resistance is presumably the most important factor. From the EEG and ECG records it is clear that the attacks are not of epileptic origin and that they cannot be explained by slowing of the heart rate alone. EEG recording during an attack is considered to be essential for differentiating between this syndrome and epilepsy because they may resemble each other clinically and because the resting EEG nearly always shows a normal pattern. The syndrome was not considered as a contraindication for licensing the pilot.

Persistence of low cardiac output after relief of high output by thiamine in a case of alcoholic beriberi and cardiac myopathy

Physiologic observations on myocardial performance and coronary circulation were obtained in an alcoholic noncirrhotic subject with beriberi heart disease who developed low cardiac output failure shortly after successful treatment with thiamine. The initial cardiac study revealed biventricular failure, high cardiac index, low peripheral resistance, and increased coronary blood flow with a narrow myocardial arteriovenous oxygen difference. Neither exercise nor ouabain was effective in restoring circulatory dynamics toward normal. Thiamine improved myocardial function not only at rest, but also during exercise. During the state of low output failure, biventricular failure with low cardiac index and elevated peripheral resistance was observed. Coronary blood flow and myocardial oxygen consumption were normal. Exercise and thiamine were without effect; ouabain improved myocardial response to exercise.

Hyperthyroidism as a high cardiac output state

Hyperthyroidism is the most common cause of hyperkinetic circulatory disease. Thyroid hormone probably produces this high output state by inducing vasodilatation of the circulatory beds supplying muscle and skin. This hormone induced effect lowers the total peripheral resistance which increases cardiac output. The heart responds to the low peripheral resistance by accelerating the heart rate and augmenting stroke volume. In addition, the thyroid hormone enhances ventricular contractility. These cardiac responses are generated by a direct effect of thyroid hormone on the cardiovascular system and are essentially independent of autonomic influence. Thyrotoxicosis can induce congestive heart failure without complicating influences. Present information does not allow a full explanation of this phenomenon, but improper utilization of energy by an oversized heart may be a contributing factor. Adequate treatment of this high cardiac output state, whether or not it is accompanied by congestive heart failure, cannot be properly accomplished without vigorous treatment of the underlying endocrine disorder. Most adjunctive therapeutic measures presently recommended are of only slight and temporary benefit. Digitalis and diuretics can help control the manifestations of heart failure and should be used when these symptoms are present. Bed rest in a quiet environment is certainly more important in reducing the circulatory load of an already overstressed heart. Reserpine and other autonomic-blocking drugs cannot be recommended on a rational scientific basis. There is little evidence that these agents have any salutory effect on the circulatory disease of hyperthyroidism.

Effect of myocardial ischemia on left ventricular function after hypothermic cardiopulmonary bypass

Summary The acute effect of hypothermic total body perfusion at 20° C, and 27° C. was studied in dogs by comparing ventricular function curves at 37° C. before and after perfusion. A marked increase of systemic vascular resistance was noted after perfusion at 20° C. The effect of interruption of coronary flow following perfusion at 27° C. for 5, 10, 15, and 20 minutes duration was studied. Peripheral resistance had to be restored to the original state by a systemic arteriovenous shunt for valid comparison of ventricular function curves. A predictable relationship was demonstrated between duration of interruption of coronary flow and per cent of original left ventricular power persisting after hypothermic perfusion. Since a 10 minute period of myocardial ischemia permits retention of an average of 75 per cent of the original myocardial function, this duration is suggested as the upper limit for clinical use during perfusion at 27° C. Isopreterenol infusion improved cardiac performance and lowered peripheral resistance.

Estimation of blood flow in the Banti spleen on anatomical basis.

Splenomegaly in Banti's syndrome was found to be accompanied by a growth of the trunk of splenic artery. The blood flow Q of an artery is expressed as a function of the arterial radius r in the form of Q=qrn, q and n being constants. Accordingly, increased blood flow of the Banti spleen was presumed on the anatomical basis. This implies at the same time remarkably decreased resistance to blood flow, because the effective pressure difference between the splenic artery and vein is reduced on account of elevated portal pressure. However, the geometrical configuration of the splenic arterial tree from the trunk to its terminal arterioles was identical in both normal and Banti spleens. The blood pressure level at terminal arterioles in the Banti spleen was regarded as practically the same as in the normal spleen. Consequently, the mechanism of lowered resistance was sought in the structural transformation of the splenic cord. Histological examination demonstrated the presence of direct arteriolosinal shunts, which could be interpreted as one of the anatomical expressions of lowered peripheral resistance in the Banti spleen. No arterial growth was confirmed in splenomegaly not associated with portal hypertension.

Studies in clinical shock and hypotension. IV. Variations in reflex vasoconstriction and cardiac stimulation.

Hemodynamic studies were performed on 44 patients with nonhemorrhagic shock or hypotension in order to assess the degree of vasoconstriction and cardiac stimulation. In 19 patients, reflex adrenergic discharge was characterized by elevated total peripheral vascular resistance, a high ratio of central blood volume to total blood volume, tachycardia, and clinical signs of skin vasoconstriction. Reduced total blood volume in most of these patients at the time of study could be explained as the result of fever, administration of vasopressor drugs, or prolonged reflex vasoconstriction. Eight patients were hypotensive with low peripheral resistance usually associated with tachycardia and hypovolemia. The fact that all died within several hours suggests that this "irreversible" syndrome was related to local accumulation of acid metabolites with terminal failure of vasoconstriction. In 17 patients, absence of reflex vasoconstriction despite hypotension was manifested by low or normal peripheral resistance, low ratios of central blood volume to total blood volume, warm skin, and normal total blood volume. While tachycardia often was absent in this group, heart rate was more closely related to body temperature than to vasoconstriction. Lack of intense adrenergic discharge in these hypotensive patients could be attributed either to the absence of a hypovolemic stimulus or to impairment of normal sympathetic nervous system pathways. The high incidence of alcoholism, cirrhosis, malignancy, pulmonary emphysema, and diabetes in these patients suggests the possibility that adrenergic insufficiency was a factor in the failure of vasoconstriction in at least some of them. The frequency of hypovolemia in the patients with vasoconstriction stresses the need for recognition and correction of occult depletion of blood volume in shock of diverse etiologies.

An Analysis of the Left Ventricle as a Pressure and Flow Generator in the Intact Systemic Circulation

The effects of increasing and decreasing peripheral resistance on the relationship between aortic pressure and left heart output were investigated in 41 experiments in the dog. The data were analyzed in terms of the slope of the aortic pressure-cardiac output graphs. The results indicate a finite variable internal resistance for the left ventricle. In general it acts as a low resistance generator (constant pressure source) for situations of low peripheral resistance and as a higher resistance generator for situations of high peripheral resistance, although its constant pressure attributes were much more consistent and pronounced than its constant flow characteristics.

HEMODYNAMIC CHANGES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION.

The hemodynamic changes following acute myocardial infarction have been studied in patients in an intensive care unit. Serial determinations of cardiac output and blood pressure have shown a wide range of hemodynamic patterns in severely ill patients varying from a low cardiac output and high peripheral resistance to a high cardiac output and low peripheral resistance. The progression of changes during the illness and their relation to the clinical findings have been discussed.

Effect of posture on the cardiac response to increased peripheral demand.

Abstract In the present study the relationships of oxygen consumption to cardiac output, stroke volume, and heart rate were observed in normal subjects and patients with hyperdynamic circulatory states before and after the assumption of the head-up tilt posture. Under a variety of circulatory stresses, including the augmented metabolic demand of exercise and hyperthyroidism, the hemic demand of anemia, and the low peripheral resistance of arteriovenous communication, the assumption of the head-up tilt posture was associated with a diminished cardiac output and stroke volume and a rise in heart rate. These observations indicate the presence of an over-all decrease in the cardiac output response in the upright stance and are consistent with the thesis that the central blood volume performs an important regulatory function in cardiovascular dynamics.

Cerebral arteriovenous fistula producing cardiac failure in the newborn infant: Case report and review

Summary In the newborn infant, extracardiac causes of congestive failure with associated marked cardiomegaly include: (1) patent ductus arteriosus, (2) hemolytic anemias, (3) multiple telangiectasias of the cerebral vessels, and (4) cerebral arteriovenous aneurysm. The clinical and pathologic findings are presented of a newborn infant who had cardiomegaly, cardiac failure, and at postmortem examination was found to have a cerebral arteriovenous fistula. Congenital cerebral arteriovenous aneurysms most frequently involve the middle cerebral artery. The usual clinical picture is described, and cases with cardiovascular complications in infancy are listed. As a result of lowered peripheral resistance, arteriovenous fistulas are frequently associated with (1) an increased cardiac output, (2) cardiac dilatation, (3) lowering of the diastolic pressure, (4) occasional evidence of myocardial damage on the electrocardiogram, and (5) cardiac failure. The mechanisms for these findings are discussed briefly. While cerebral arteriovenous fistulas are a very rare cause of extracardiac heart failure and gross cardiomegaly in the newborn period, it is pointed out that the possibility should be kept in mind.

The hemodynamic response to exercise in patients with Laennec's cirrhosis.

Previous studies in this laboratory have shown that some patients with chronic alcoholism and Laennec's cirrhosis at rest in the supine position have a high cardiac output and low peripheral vascular resistance (1). The cardiac output in such subjects is increased out of proportion to the oxygen consumption, i.e., the arteriovenous oxygen difference is unusually small. The present study of the hemodynamic response to exercise in patients with Laennec's cirrhosis was carried out to assess the cardiac reserve, and to determine whether individuals with elevated cardiac output and lowered peripheral vascular resistance at rest are capable of further decrease in peripheral resistance during exercise.

Functional cardiovascular disturbances—Their response to drugs acting on the autonomic nervous system

1. 1. Two types of hemodynamic disturbances are observed in neurocirculatory asthenia. These per se physiologic states are pathologic only if they are not commensurate with the physiologic demands of the organism: 1.1. (a) “Ergotropic” state—hyper-responsive circulation with a high stroke and minute volume, lowered peripheral resistance and a tendency toward hypertension. 1.2. (b) “Histotropic” state—reduced circulation with a low stroke and minute volume and a tendency to hypotension. 2. 2. It has been shown that Bellergal, a combination of Bellafoline, ergotamine tartrate, and phenobarbital may normalize both types of circulatory dystonia. 3. 3. Ergotamine tartrate intravenously depresses the circulation in the “ergotropic” and normal individual and increases circulation only in the extreme “histotropic” patient. 4. 4. Bellafoline intravenously increases the “histotropically” depressed circulation and depresses the “ergotropically” elevated circulation. 5. 5. Phenobarbital intravenously depresses the “ergotropic” circulation and may in some “histotropic” cases raise the stroke and minute volume. 6. 6. The combination of these three substances (intravenously) in “ergotropic” and normal states leads to a drop in stroke and minute volumes. An increase in circulatory values occurs in some “histotropic” individuals. 7. 7. Bellergal by mouth normalizes the “ergotropic” state as well as the “histotropic” circulatory state after several days of administration.

EXPERIMENTAL STUDIES IN ARTERIOVENOUS FISTULAS

In Part I, the abnormal hydraulics of the circulatory system in the presence of an arteriovenous fistula was discussed and the following points emphasized: (1) An arteriovenous fistula introduces into the normal circulation consisting of heart-artery-capillary bed-vein, a second system of circulating blood consisting of heart-artery-fistula vein, the latter with a markedly diminished peripheral resistance; (2) the existence of four variable factors to maintain the normal circulation of blood at a definite blood pressure level, namely: (a) cardiac output or pulse rate, (b) total capacity of system as determined by contraction or dilatation of the vessel walls, (c) total volume of circulating blood, and (d) peripheral resistance. To compensate for the lowered peripheral resistance in the presence of a fistula, and to provide for the leakage of blood through the area of lowered resistance, thereby maintaining an adequate blood pressure level, an increase in total volume of circulating blood was