Higher Total Peripheral Resistance Research Articles

New approaches to an understanding of the hemodynamic norm

Tetrapolar rheography was used to investigate central hemodynamics parameters in a group of 80 healthy subjects aged 25-68. Hyperkinetic, eukinetic and hypokinetic types of circulation were determined by interval distribution according to cardiac index. The proportion of the examinees by their hemodynamic type was: 16.3:63.7:20.0%. In hyperkinetic type the optimal level of average blood pressure was provided by a relatively high cardiac output (CO) and low total and specific peripheral resistance (TPR, SPR). The hypokinetic type of hemodynamics was characterized by a low level of CO and a high value of TPR and SPR. Subjects with eukinetic hemodynamic type were in an intermediate position. It is suggested to take into consideration the hemodynamic type in hypertensive subjects for drug selection and treatment control.

Relation of central hemodynamics to obesity and body fat distribution.

Central obesity increases the risk for cardiovascular disease, but little is known about its hemodynamic effects. The aims were to investigate the influence of obesity (as defined by body mass index) and abdominal fat accumulation (as defined by the waist/hip ratio) on hemodynamics at rest and during mental stress. Invasive hemodynamic studies were performed in 20 healthy, normotensive young men (aged 18-22 years) recruited from an unbiased population sample. Their body mass index and waist/hip ratio ranged between 18.5 and 30.2 (mean 24.1) and 0.77 and 0.98 (mean 0.87), respectively. Hemodynamics were related to the two anthropometric indexes by bivariate regression analyses. Cardiac output and stroke volume were positively correlated to body mass index (p = 0.05 and p = 0.005), but inversely to waist/hip ratio (p = 0.01 and p = 0.01). Mental stress augmented the hemodynamic patterns. Total peripheral resistance during stress correlated inversely to body mass index (p = 0.02), whereas high waist/hip ratio was associated with higher systemic vascular resistance p = 0.002). The delta CO/delta MAP ratio, i.e., relative contribution of cardiac output for the stress-induced increase in mean arterial pressure, showed a strong positive association with body mass index (p = 0.004), but was inversely related to the waist/hip ratio (p = 0.002). Serum insulin correlated significantly to the stress-induced change in total peripheral resistance (r = 0.54; p = 0.02), whereas the increase in cardiac output was inversely related to insulin (r = -0.59; p = 0.007). Thus, central obesity is associated with a specific hemodynamic pattern characterized by higher total peripheral resistance, lower cardiac output, and a vasoconstrictor response to psychosocial stress.

Abnormal renal function and autoregulation in essential hypertension.

The goal of this presentation has been to emphasize two fundamental mechanisms in the development of essential hypertension. These are: 1) The basic cause of essential hypertension is the inability of the kidneys to excrete an adequate volume of urine at normal arterial pressure. Therefore, fluid accumulates in the body until the pressure rises high enough to balance fluid output with fluid intake. This fluid balancing act is an infinite gain feedback system for controlling arterial pressure to a very precise level determined by the kidneys. Furthermore, this infinite gain allows the kidney mechanism to dominate the other pressure control mechanisms for long-term pressure control. Because of this domination, as long as a person has normal intake of water and electrolytes, essential hypertension cannot develop without an elevated pressure setting of the kidneys. 2) An increase in total peripheral resistance will not cause hypertension as long as the kidneys can still excrete normal amounts of water and electrolytes at normal arterial pressure, because loss of excess fluid volume at high pressures will simply reduce the cardiac output until the pressure falls back to normal. Therefore, what is the cause of the very high total peripheral resistance found in almost all patients with essential hypertension? The answer is likely the long-term blood flow autoregulation mechanism that occurs in virtually all tissues of the body. That is, when the pressure rises too high for whatever reason, this in turn forces too much blood flow through the tissues. In response, the local blood flow control mechanisms all over the body increase the vascular resistances until the flows return to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced orthostatic tolerance following 4 h head-down tilt

The cardiovascular responses to a 10-min 1.22 rad (70 degrees) head-up tilt orthostatic tolerance test (OST) was observed in eight healthy men following each of a 5-min supine baseline (control), 4 h of 0.1 rad (6 degrees) head-down tilt (HDT), or 4 h 0.52 rad (30 degrees) head-up tilt (HUT). An important clinical observation was presyncopal symptoms in six of eight subjects following 4 h HDT, but in no subjects following 4 h HUT. Immediately prior to the OST, there were no differences in heart rate, stroke volume, cardiac output, mean arterial pressure and total peripheral resistance for HDT and HUT. However, stroke volume and cardiac output were greater for the control group. Mean arterial pressure for the control group was less than HDT but not HUT. Over the full 10-min period of OST, the mean arterial pressure was not different between groups. Heart rate increased to the same level for all three treatments. Stroke volume decreased across the full time period for control and HDT, but only at 3 and 9 min for HUT. There was a higher total peripheral resistance in the HDT group than control or HUT. The pre-ejection period to left ventricular ejection time ratio was less in HDT than for control or HUT groups. These data indicate a rapid adaptation of the cardiovascular system to 4 h HDT that appears to be inappropriate on reapplication of a head to foot gravity vector. We speculate that the cause of the impaired orthostatic tolerance is decreased tone in venous capacitance vessels so that venous return is inadequate.

Characteristics of systolic time intervals in patients with pheochromocytoma.

The effect of chronic catecholamine excess on cardiac function was assessed in 8 patients with surgically proven pheochromocytoma and the results compared with data obtained from normal controls and essential hypertensives. Major findings in systolic time intervals (STI) in patients with pheochromocytoma were a marked shortening of electromechanical systole and left ventricular ejection time (ET), but pre-ejection period (PEP) remained within normal limits. These findings were not altered by correction for heart rate. The ET/PEP ratio was very low (1.87 +/- 0.31) due to the remarkable shortening of ET. The ET/PEP ratio in essential hypertensives was also low (1.77 +/- 0.38), but this was mainly due to a remarkable prolongation of PEP. Low cardiac index, low stroke index and high total peripheral resistance index were preoperative characteristics in patients with pheochromocytoma, but returned to normal after operation. These results suggest that chronic excessive production of catecholamines from pheochromocytoma has deleterious effects on the heart, and that wide differences in STI exist between patients with pheochromocytoma and those with essential hypertension.

The role of multiple action agents in hypertension

A 20-year follow-up study of central hemodynamics in essential hypertension at rest and during exercise in 61 men with uncomplicated essential hypertension has clearly shown that hemodynamic disturbances depend on the age of the subjects and the severity of the hypertensive state and that a shift in the hemodynamic alterations take place over time. During 10- and 20-year follow-up, central hemodynamics changed towards a low cardiac-index (CI)-high total peripheral-resistance index (TPRI) pattern. With increasing age there was a gradual reduction in CI as well as stroke index (SI). The arteriovenous oxygen difference increased, particularly during exercise. The 20-year treatment with conventional drugs (beta-blockers and/or diuretics) did not prevent a marked increase in TPRI and a marked reduction in CI and SI in subjects initially 40-49 years of age. In recent years, beta-blockers with vasodilating activity have been introduced in the treatment of hypertension (labetalol, prizidilol, dilevalol and carvedilol). The hemodynamic effects of these compounds clearly differ from the changes induced during acute and chronic conventional beta-blocking treatment. In contrast to usual beta-blockers, these drugs reduce TPRI acutely and the reductions they produce in heart rate (HR) and CI are considerably lower. Our long-term data on labetalol (n = 15), prizidilol (n = 15) and dilevalol (n = 17) indicate a persistent reduction in TPRI and little or no decrease in exercise CI. Long-term data on carvedilol are not yet available. Approximately 70% of patients with mild to moderately severe essential hypertension achieved normal blood pressure during chronic treatment on beta-blockers with vasodilating activity.

Cardiovascular regulatory functions in elderly patients with hypertension.

To dissociate the effects of an elevated blood pressure on the cardiovascular regulatory functions from those of aging in the hypertensive elderly individual, resting hemodynamic measurements and circulatory autonomic functions in 30 elderly (mean age, 66 years) hypertensive (World Health Organization stages I and II) patients were compared with those in 30 healthy elderly (mean age, 65 years) normotensive volunteers. The elderly hypertensive group showed a significantly lower cardiac index and higher total peripheral resistance. beta-Receptor sensitivity, as determined by chronotropic dose of infused isoproterenol, and baroreceptor reflex sensitivity index, derived from phase II, but not phase IV, of Valsalva's maneuver, were only slightly but significantly reduced in the hypertensive group. The variability of heart rate at rest as an index of parasympathetic control of heart was similar between these two groups. Plasma norepinephrine level was significantly inversely related to resting mean blood pressure (r = -0.31, p less than 0.05) when analyzed as a whole group. Plasma renin activity, but not plasma aldosterone, was significantly decreased in the hypertensive group. To define the effects of age itself, these parameters in normotensive elderly subjects were also compared with those in 12 young normotensive subjects (mean age, 23 years). Although resting hemodynamic measurements did not differ, various circulatory autonomic functions were significantly different between these two age groups. The variability of heart rate in 24-hour ambulatory monitoring, beta-receptor responsiveness, resting vagal cardiac activity, and baroreceptor reflex sensitivity derived from phase IV of Valsalva's maneuver were significantly depressed in the elderly. Resting plasma norepinephrine level was elevated and renin-aldosterone system decreased in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

The importance of hemodynamic considerations in essential hypertension

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Antihypertensive therapy consistently reduces complications from stroke and congestive heart failure, whereas benefits from the treatment of ischemic heart disease events are variable. Several plausible explanations, including hemodynamic hypotheses, have been put forth to account for the failure of treatment to more favorably influence mortality from ischemic heart disease. The effect of hypertension on coronary heart disease is probably much more complex than a simple elevation of arterial pressure. Some of these complexities include the potential separate risks of high total peripheral resistance, high cardiac output, increased myocardial power that reflects pressure times flow, and several structural and functional vascular changes. These factors may act in concert to unfavorably alter the balance between myocardial oxygen supply and demand. Several of these factors will be highlighted in an attempt to offer alternative or adjunctive pathophysiologic examinations for the high-risk subgroups of obesity and the failure of antihypertensive therapy to normalize the rate of coronary heart disease events.

Transition from high cardiac output to elevated vascular resistance in hypertension

The early phase of hypertension (borderline hypertension) is characterized by a hyperkinetic circulation caused by excessive sympathetic drive and decreased parasympathetic inhibition to the heart. In later phases the cardiac output becomes normal, but the hypertension is still neurogenic, as demonstrated by the fact that continued pharmacologic parasympathetic, β- and α-adrenergic inhibition normalizes the blood pressure. In both of these phases of the process, plasma norepinephrine values are elevated. These patients also show characteristic behavioral patterns; they are outward oriented, submissive, but experience unexpressed anger and frequently harbor hostile feelings. In late phases of hypertension the cardiac output is normal and the total peripheral resistance is elevated. This hemodynamic transition can be explained by a secondary response to elevated blood pressure. The heart becomes less responsive as a result of altered receptor responsiveness and decreased cardiac compliance, whereas the responsiveness of arterioles increases because of vascular hypertrophy, which leads to changes in the wall-to-lumen ratio. However, one observation eludes explanation: the absence of plasma norepinephrine elevation in later phases of hypertension. We propose a new conceptual framework to explain the disappearance of elevated plasma norepinephrine in the course of hypertension. The concept is based on a wide range of observations with the use of various receptor-blocking agents during neurogenic pressor responses. Invariably, the blood pressure response is preserved, but the hemodynamic pattern can be altered from a high cardiac output to high total peripheral resistance or vice versa. The “blood pressure-seeking behavior” of the central nervous system suggests that the negative feedback to the central nervous system is pressure and not flow related. If the central nervous system indeed seeks to obtain a certain pressure and maintains the high blood pressure in early phases by an elevation in cardiac output, later as structural arteriolar changes evolve and the arterioles become hyperresponsive, the same blood pressure elevation could be achieved with less sympathetic drive, and the plasma norepinephrine values return to the normal range.

Use of diuretic agents in obese or black patients with systemic hypertension

Any increase in arterial pressure is the result of either an increase in cardiac output, an increase in total peripheral resistance or a combination of the two. Hypertension is not a homogeneous disease, however, and different mechanisms may be operative during the life span of the patient. Hypertension in the young, nonobese patient is usually hemodynamically characterized by high cardiac output, normal to slightly contracted intravascular volume and numerically normal total peripheral resistance. In contrast, hypertension in the middle-aged or elderly patient is usually hemodynamically characterized by normal to low cardiac output, contracted intravascular volume and high total peripheral resistance. Two further subgroups of hypertensive patients can be identified: obese patients, whose hypertension is characterized by high cardiac output, expanded intravascular volume and normal or low total peripheral resistance, and black patients, whose hemodynamic and fluid volume findings are similar to those of their white counterparts, but who tend to have lower heart rates and greater responsiveness to intravascular volume depletion than white hypertensive subjects. A rational therapeutic approach to essential hypertension should take into account these variable pathophysiologic features. Thiazide diuretics continue to be appropriate and generally well-tolerated choices for initial antihypertensive therapy in obese or in black patients. Many obese patients or black patients, however, are likely to develop early left ventricular (LV) hypertrophy. Patients with electrocardiographic or echocardiographic evidence of LV hypertrophy have been shown to have a higher prevalence of ventricular ectopic activity and to be at higher risk of sudden death than patients without evidence of LV hypertrophy. Some studies have shown that obese patients and black patients are at higher risk of developing LV hypertrophy. Thiazide diuretic-induced hypokalemia may exacerbate ventricular ectopic activity and cause more serious arrhythmias. Potassium depletion should, therefore, be prevented in patients with evidence of the LV hypertrophy. If thiazide diuretics are used in this context, the addition of a potassium sparing agent, such as amiloride, is recommended.

Does gravitational pressure of blood hinder flow to the brain of the giraffe?

1. 1. Vascular pressure consists of the sum of two pressures: (a) pressure developed by the pumping of the ventricles against the resistance of vessels, designated as viscous flow pressure, and (b) pressure caused by gravity, traditionally called hydrostatic, better described as gravitational pressure. 2. 2. In a conduit, both of these pressures must be overcome when a liquid is discharged to a higher level of gravitational potential energy. If a liquid is returned to its original level, gravity neither helps nor hinders flow because of the siphon effect. This circumstance prevails in the circulatory system. Hence, P 1− P 2 in the Poiseuille equation excludes gravitational pressure between those points. The long neck of the giraffe, therefore, poses no impediment to blood flow in the erect posture. 3. 3. The giraffe has a high aortic pressure. This is not for driving the blood to its head but is for minimizing the gravitational drop of intravascular pressure and collapse of the vessels. The cerebral circulation is protected by the cerebrospinal fluid which undergoes parallel changes in pressure with posture. Other vessels in the head are less protected by connective tissue, surrounding muscles and other structures. 4. 4. The high aortic pressure in the giraffe is probably caused by the high total peripheral resistance of the systemic circuit due to vascular adaptations related to the overall height of the animal.

Left ventricular function in early primary hypertension. Functional consequences of cardiovascular structural changes.

An increase in left ventricular (LV) wall thickness will lead to decreased LV distensibility during both LV passive filling and left atrial contraction. Reduced LV distensibility will change the filling pattern of the left ventricle, and a proportionally smaller part of the stroke volume will be delivered during the passive filling of the preceding diastole and a larger part during late diastole by a more powerful left atrial contraction. With a more pronounced increase in LV wall thickness a reduced distensibility of venous capacitance vessels (functional or structural) will probably help to preserve LV pump function by influencing LV filling and use of the Frank-Starling mechanism. LV wall stress (peak and end-systolic) is high and LV intrinsic contractility is normal or supernormal in early primary hypertension, as judged from the relationship between end-systolic wall stress and different indices of LV function (fractional shortening, mean velocity of circumferential fiber shortening, ejection fraction). Great differences in peak systolic wall stress may be recorded among groups with comparable values for LV end-systolic wall stress, which may be explained by very different degrees of cardiovascular structural changes, with higher values for peak systolic wall stress seen in hypertension caused by high output than those values seen in hypertension caused by high total peripheral resistance. Signs of supernormal LV systolic function are common in high output hypertension, which is also at least partly due to an increase in LV end-diastolic volume and use of the Frank-Starling mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamics and the baroreflex function in borderline hypertension.

The hemodynamics and the baroreflex function were studied and compared between patients with borderline and established hypertension. 1) As compared to patients with established hypertension, the heart rate, the cardiac output and the left ventricular ejection fraction were higher in patients with borderline hypertension in the young group, but these characteristics were not found in the patients of the middle-aged group. 2) In regard to the cardiac output and the total peripheral resistance, patients with borderline hypertension predominantly showed a high cardiac output, especially in the young group, while patients with established hypertension predominantly showed a high total peripheral resistance, especially in the middle-aged group. 3) At higher and lower blood pressure levels during one day, no difference of hemodynamic pattern was observed in the same subjects. 4) The hemodynamic response to exercise, isoproterenol and noradrenaline was greatest in the borderline hypertensives of the young group. 5) The baroreceptor slope decreased in the order of normal subjects, borderline hypertensives and established hypertensives. It decreased with age in each group. The hemodynamics and the baroreflex function in borderline hypertensives differed slightly between the young and the middle-aged groups. Although the borderline hypertension in the middle-aged group is considered to be a pre-stage of established hypertension, detailed analysis of case histories may be required to assess how borderline hypertension develops into established hypertension in the young group.

CARDIOVASCULAR EFFECTS OF OBESITY AND HYPERTENSION

Although often coexisting in the same patient, obesity and essential hypertension exert disparate cardiovascular effects. An excess of adipose tissue augments cardiac output, stroke volume, and left ventricular filling pressure, expands intravascular volume, and lowers total peripheral resistance. In contrast, essential hypertension in a non-obese patient is associated with a contracted intravascular volume, high total peripheral resistance, and normal cardiac output, but increased left ventricular stroke work due to high afterload. Left ventricular adaptation will consist of eccentric hypertrophy in the obese (irrespective of arterial pressure) and concentric hypertrophy in the non-obese hypertensive patient. The combination of obesity and hypertension burdens the heart with high preload and high afterload, thereby greatly enhancing the risk of congestive heart failure. Peripheral resistance and intravascular volume may be normal in mildly hypertensive obese patients because of the mutually antagonising effects of the increase in arterial pressure and the increase in body weight. The fall in arterial pressure associated with weight loss seems to be caused by a decrease in adrenergic activity which leads to a fall in cardiac output without change in vascular resistance. Obesity hypertension may be the result of an inappropriately raised cardiac output in the presence of a relatively restricted arterial capacity due to the low vascularity of adipose tissue. In morbid obesity increased blood viscosity may contribute to the raised arterial pressure.

Haemodynamic changes in essential hypertension in young subjects.

The haemodynamic changes in essential hypertension were investigated in 7 girls and 4 boys under the age of 18 years. The Fick method was used for the estimation of cardiac output (CO). The cardiac indices (CIs) ranged form 2.8 to 6.6 litres/min/m2 and the total peripheral resistance (TPR) from 1,100 to 2,860 dyn/s/cm-5 X m2. Comparison of the results with normal values reported earlier showed that the CIs in the present series were increased in 2 patients and normal in the others. The stroke volume was increased in 3 patients. TPR was elevated in 4 patients. It is proposed that essential hypertension does not always begin with an increase in CO, and that some forms of essential hypertensions can have a high TPR already at the onset of the disease.

Hypertension in the Elderly: Haemodynamic, Fluid Volume and Endocrine Findings

1. Systemic and renal haemodynamics, intravascular volume, circulating catecholamines and plasma renin activity were measured in 18 patients with established essential hypertension who were older than 60 years of age. Each patient was matched with respect to mean arterial pressure, body surface area, race and sex with a patient that was younger than 42 years of age. 2. When compared with the younger group, elderly patients had a lower cardiac output, impaired myocardial reserve, lesser aortic elasticity, higher total peripheral resistance, more contracted intravascular volume and higher circulating noradrenaline levels. 3. Similar effects of age, although less pronounced, have been reported in normotensive subjects. We conclude that essential hypertension is a pathophysiological process that seems to accelerate the natural physiological haemodynamic, fluid volume and endocrine processes of aging.

A pathophysiologic study of the hypertension associated with burn injury in children.

Measurements of cardiac output, blood volume, plasma renin activity (PRA), serum aldosterone, plasma and urinary catecholamine levels, serum and urinary electrolyte levels, and of transfusion and fluid therapy have been made in eight hypertensive and seven normotensive burned children. Studies were conducted during the acute phase of burn injury when hypertension was first diagnosed and were repeated just before discharge from the hospital. Hypertensive patients perfused at an inappropriately high total peripheral resistance and hypervolemia was demonstrated in the hypertensive patients. No differences could be demonstrated between hypertensive or normotensive patients in PRA, aldosterone, catecholamine, or electrolyte levels. These data indicate that both the hypervolemia and the vasoconstrictor activity of PRA and/or catecholamines are present when hypertension develops in these patients. These data suggest that the renin-angiotension-aldosterone system is directly stimulated as part of the neuroendocrine response to trauma.

Haemodynamics of stable renal transplant recipients.

1. Haemodynamics, blood volume, plasma renin concentration and creatinine clearance were evaluated in 24 stable renal transplant recipients. 2. The mean cardiac index of the transplant recipients was not different from that of the normal subjects. 3. The transplant recipients comprised eight hypertensive and 16 normotensive patients. The mean cardiac index was the same in eight hypertensive and 16 normotensive patients. Thus the hypertension of stable renal transplant recipients is sustained by a high total peripheral resistance. 4. The mean blood volume, plasma renin concentration and creatinine clearance were similar in eight hypertensive and 16 normotensive patients. Therefore the hypertension of stable renal transplant recipients is not related to blood volume expansion, elevated peripheral renin or low creatinine clearance. The cause of the elevated total peripheral resistance in hypertension in stable renal transplant recipients remains to be elucidated.

Altered hemodynamic responses to acute hypoxemia in spontaneously hypertensive rats.

Conscious spontaneously hypertensive rats (SHR), 5--7 wk old, were studied hemodynamically by the direct Fick procedure to determine whether high total peripheral resistance (TPR) coexisted with increased oxygen consumption (QO2) at an early stage of hypertension development. Since under resting conditions cardiac output in SHR was not significantly different from normotensive controls, the elevated arterial pressure and QO2 were associated with increased TPR. Arterial hypoxemia was induced to reduce oxygen availability and to assess whether increased TPR in SHR could be reversed by this procedure. During hypoxemia, normotensive controls (WKY) responded with increased cardiac output and decreased arterial pressure and TPR. In contrast, arterial pressure and cardiac output fell in SHR; and the increased TPR persisted. QO2 fell in hypoxemic SHR demonstrating that the relationship between total body oxygen consumption and cardiac output was abnormal in young SHR, and that increased TPR in SHR was not dependent on resting levels of QO2 or oxygen availability. Although QO2 was elevated in SHR compared to age-matched WKY, this condition was not essential for maintained elevated vascular resistance.

Haemodynamic and blood volume studies in long-term haemodialysis patients, and in patients with successfully transplanted kidneys.

1. Stabilized hypertensive haemodialysis patients, as well as those with normotension, had a greatly elevated cardiac index (CI) that was not due to hypervolemia, but was most likely secondary to their anaemic condition. The hypertension itself was not accompanied by hypervolaemia, but was associated with a relatively very high total peripheral resistance. 2. In eight patients with successfully transplanted kidneys the following results were found. (a) Five were clearly hypertensive and had supine mean arterial pressure between 117 and 143 mmHg. It is noted that they were receiving prednisone at the time of the studies. (b) CI was normal in seven. (c) Total blood volume was normal in all. (d) The presence of wide-open arterio-venous fistulae was not associated with an increase in CI.