Baroreflex regulation of regional blood flow in congestive heart failure MARK A. CREAGER, ALAN T. HIRSCH, VICTOR J. DZAU, ELIZABETH G. NABEL, SALLY S. CUTLER, AND WILSON S. COLUCCI Divisions of Vascular Medicine and Atherosclerosis, and Cardiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115

MARK A., ALAN T. HIRSCH, VICTOR J. DZAU, G. NABEL, SALLY S. CUTLER, AND WILSON S. Baroreflex regulation of regional blood flow in congestive heart failure. Am. J. Physiol. 258 (Heart Circ. Physiol. 27): Hl409-Hl414,1990.-In patients with congestive heart failure (CHF), the distribution of the cardiac output is altered. Cardiopulmonary and arterial baroreceptors normally can regulate regional blood flow, but their contribution in heart failure is not known. To examine the role of baroreceptors in the regulation of regional blood flow in CHF, the effect of lower body negative pressure (LBNP) on forearm, renal, and splanchnic blood flow was evaluated in 12 patients with heart failure. Incremental LBNP at -10 and -40 mmHg decreased central venous pressure but had no effect on systolic blood pressure or pulse pressure. Renal blood flow decreased from 505 t 63 to 468 t 66 ml/min during LBNP -10 mmHg (P < 0.05) and to 376 t 74 ml/min during LBNP -40 mmHg (P < 0.01). Splanchnit blood flow decreased from 564 t 76 to 480 t 62 ml/min during LBNP -10 mmHg (P < 0.01) and to 303 t 45 ml/min during LBNP -40 mmHg (P < 0.01). Forearm blood flow did not decrease during LBNP -10 mmHg or -40 mmHg. To determine whether the absence of limb vasoconstriction during LBNP was confined to abnormalities in the baroreflex arc or was secondary to impaired end-organ responsiveness, six patients with heart failure and six normal subjects received an intrabrachial artery infusion of phenylephrine. Phenylephrine increased forearm vascular resistance comparably in each group. These data demonstrate that baroreceptors can regulate splanchnic and renal but not limb vascular resistance in patients with congestive heart failure and may contribute to the redistribution of blood flow that occurs in this disorder. CREAGER, ELIZABETH COLUCCI.

forearm blood pressoreceptors

flow; renal

blood

flow;

splanchnic

blood

flow;

PATIENTS with congestive heart failure, the distribution of the cardiac output is altered. Skin, splanchnic, and renal blood flow decreases, whereas limb, coronary, and cerebral blood flow is usually preserved (9, 26). Baroreceptors in the heart, lungs, and great vessels normally contribute to the distribution of cardiac output by regulating regional vascular resistance (2). It is not known, however, whether baroreceptors influence blood flow distribution in patients with congestive heart failure. Baroreceptor sensitivity is decreased in animal models of heart failure (14, 29). In humans with heart failure, baroreflex function is also abnormal, because the sysIN

0363-6135/90

$1.50 Copyright

temic vasoconstrictive and neurohormonal responses to tilt are blunted (&l&22). However, abnormal baroreflex control of the circulation may not involve all regional vascular beds. Indeed, studies conducted in different groups of patients with heart failure have shown that the limb vascular response to upright posture or lower body negative pressure is abolished, whereas the renal vasoconstrictive response to orthostasis is preserved (10, 12, 19). Preservation of the baroreflex control of the renal and splanchnic circulation may account for the selective vasoconstriction that occurs in these regions. Because systemic vascular resistance is an integrated parameter, measurement of regional blood flow during baroreceptor perturbation may provide more information about the role of baroreflex function in the distribution of cardiac output in patients with heart failure. Accordingly, the objective of this study was to determine whether unloading of baroreceptors alters the distribution of regional blood flow in patients with congestive heart failure. To achieve this goal, the study was designed to assess the effect of lower body negative pressure on forearm, renal, and splanchnic blood flow in patients with heart failure. METHODS

Subjects. The effect of lower body negative pressure on regional blood flow was examined in 12 patients with congestive heart failure. They included 10 males and 2 females ranging in age from 46 to 81 yr old, and averaging 63 t 9 yr old (mean t SD). The etiology of heart failure was coronary artery disease in eight patients and primary cardiomyopathy in four patients. Seven of the patients were New York Heart Association (NYHA) functional class III and five were in NYHA functional class IV. Left ventricular ejection fraction assessed by radionuclide ventriculography ranged from 7 to 34% and averaged 16 -+ 8%. Right heart catheterization was performed in eight of the patients within 2 days of this study. In those patients, cardiac index averaged 2.2 t 1.1 1 min. m2 and pulmonary capillary wedge pressure averaged 33 t 8 mmHg. This research was approved by the Human Research Committee, and each subject provided written informed consent. A similar study had been conducted in this laboratory in 20 normal volunteers and was published as a separate report (16). Hemodynamic measurements. Forearm blood flow was

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determined by venous occlusion strain-gauge plethysmography (D. E. Hokanson, Issaquah, WA) (27). The arm was positioned above heart level, and hand blood flow was excluded by the use of a cuff placed around the wrist and inflated above systolic pressure during measurements. Venous occlusion was produced by sudden inflation of a sphygmomanometric cuff on the upper arm. The venous occlusion pressure required to obtain the maximum rate of increase in forearm circumference was determined at the beginning of each study and ranged from 30 to 40 mmHg. Circumferential change was measured by a calibrated strain gauge placed on the forearm. Forearm blood flow was derived from the rate of change in forearm circumference during venous occlusion (expressed as ml. 100 ml tissue-‘. min). Each determination of forearm blood flow comprised at least five separate measurements. Forearm blood flow measurements were recorded on a Gould physiological recorder. Forearm vascular resistance (expressed as resistance units reflecting mmHg/ml . 100 ml-’ min) was calculated as the ratio of mean blood pressure to forearm blood flow. Renal plasma flow was determined by infusion of paminohippurate (PAH) (5). A bolus of PAH (8 mg/kg) was followed by constant infusion (12 mg/min). After at least 30 min for equilibration was allowed, plasma samples were collected for determination of PAH concentrations every 15 min. The PAH concentration was measured spectrophotometrically with standard chemical assays. During constant infusion of PAH, we assumed that the infusion rate and renal excretion rate are identical. The clearance of PAH (&AH) is equivalent to renal plasma flow and is calculated as &An = IPAn x R/PpAn, where IPAn is the concentration of PAH in the infusate, R is the rate of infusion, and PPAn is the plasma concentration of PAH. Renal blood flow was ‘calculated as renal plasma flow/l - hematocrit. Renal vascular resistance (expressed as mmHg ml-’ l rein) was calculated as the ratio of mean blood pressure to renal blood flow. Splanchnic blood flow was estimated by indocyanine green (ICG) clearance (24). A bolus of ICG (5 mg) was followed by constant infusion (0.5 mg/min). After at least 30 min for equilibration was allowed, plasma samples were collected every 15 min for determination of ICG concentration. ICG concentration was measured spectrophotometrically. Assuming steady-state conditions, ICG clearance (Cico) was calculated as Cico = Irco x R/Pica, where Irco is the concentration of ICG in the perfusate and P Ice is the plasma concentration of ICG. Splanchnic blood flow was estimated as &o/l - hematocrit. For an accurate determination of splanchnic blood flow, it is necessary to measure hepatic extraction of ICG. This procedure requires a catheter in the hepatic vein to determine the arterial-venous difference. When no significant change in the extraction ratio is assumed, the clearance of ICG will reflect changes in splanchnic blood flow. Previous investigations using hepatic venous and peripheral venous sampling have determined that hepatic extraction of ICG does not change during progressive lower body negative pressure (LBNP) in normal subjects (17, 24, 25). Splanchnic vascular resistance (exl

l

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pressed as mmHg ml-’ . min) was determined as the ratio of mean blood pressure to splanchnic blood flow. Blood pressure was determined by the sphygmomanometric method using an automated oscillometric technique (Dinamap, model 845XT, Critikon, Tampa, FL). Pulse pressure was calculated as the difference between systolic and diastolic blood pressure. Mean blood pressure was calculated as the sum of the diastolic blood pressure and one-third of the pulse pressure. A catheter was inserted into an antecubital vein and was advanced to the superior vena cava to determine central venous pressure. The catheter was attached to a Gould P-23 pressure transducer, and the central venous pressure measurement was displayed on a Gould physiological recorder. Zero reference was chosen to be at the right atrium, estimated to be 5 cm vertically beneath the sternal angle of Louis. Heart rate was determined by a simultaneously obtained electrocardiographic signal and was calculated from the R-R interval. Experimental protocol. All studies were conducted in the morning in the postabsorptive state without premedication. Water was permitted ad libitum. Alcohol, caffeine, and cigarettes were all prohibited within 12 h of study. Digitalis glycerides, diuretics, and vasodilator medications were withheld at least 24 h before the study. Subjects were positioned supine in a LBNP chamber (Bioengineering Dept., Univ. of Iowa, Iowa City, IA), with the chamber enclosing the subject’s legs with an airtight seal at the level of the iliac crests. Each study was conducted in a 22°C temperature-controlled laboratory, and all subjects were lightly clothed. After a 30-min stabilization period, base-line hemodynamic data were collected every 15 min for 1 h. Thereafter, patients underwent l-h periods of incremental LBNP at -10 and -40 mmHg. Blood pressure, central venous pressure, heart rate, and forearm blood flow were determined every 15 min during each experimental period. After 30 min for equilibration was allowed, blood samples for PAH and ICG were collected 30, 45, and 60 min into each experimental period. The experiment was terminated prematurely if symptomatic hypotension occurred. Intra-arterial infusion of phenylephrine. Abnormalities in the vasoconstrictor response to LBNP may be confined to the baroreflex arc or the end organ. To specifically study limb vascular responsiveness, forearm blood flow was measured during an intrabrachial artery infusion of phenylephrine in six additional patients with heart failure and six normal subjects. This group of heart failure patients comprised five males and one female, aged 31-64 yr (51 t 5). All had symptoms and physical findings consistent with this diagnosis, cardiomegaly on chest X-ray, and depressed left ventricular function (ejection fraction = 22 t 2%). The normal volunteers included five males and one female, aged 27-43 yr (34 t 3, P < 0.05 vs. heart failure patients). After basal determination of forearm blood flow, phenylephrine was infused at doses of 0.3, 1.0, and 3.0 pg/min, each for 5 min. Forearm blood flow was determined during the last minute of each infusion. StatisticaL analysis. The experimental results are prel

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sented as means t SE. For each participant, data from an LBNP period were excluded from analysis if the subject was unstable and was unable to complete the 60min intervention. Thus all data reported were collected under steady-state conditions. The data acquired before and during LBNP and during the phenylephrine infusion were compared by analysis of variance (ANOVA) for repeated measures with trend analysis (28). When the ANOVA indicated a statistically significant difference, Dunnett’s test was used to analyze the difference between two means (7). Statistical significance was accepted at the 95% confidence level (P < 0.05).

boseline LBNP

RESULTS

-IO

-40

(mmHg)

t

Systemic hemodynamic response to LBNP. Nine patients were able to complete the entire protocol. In three patients, systemic hypotension developed during the LBNP -40-mmHg period, requiring premature termination of the protocol. The effect of LBNP on blood pressure, heart rate, and central venous pressure is provided in Table 1. For the group, LBNP caused no significant change in systolic, diastolic, or mean blood pressure, pulse pressure, or heart rate. Base-line central venous pressure ranged from 2 to 14 mmHg and averaged 6.9 t 1.6 mmHg. The three patients in whom hypotension developed during LBNP -40 mmHg were those with the lowest base-line central venous pressure. For the group, incremental LBNP decreased central venous pressure to 4.4 t 1.6 mmHg at LBNP -10 mmHg (P < 0.01) and to 3.4 t 1.7 mmHg at LBNP -40 mmHg (P < 0.01). Regional hemodynamic response to LBNP. The forearm vascular response to LBNP is illustrated in Fig. 1. Base-line forearm blood flow was 1.9 t 0.2 ml. 100 ml-’ min. LBNP did not change forearm blood flow during the -lO-mmHg (1.9 t 0.2 ml. 100 ml-‘. min-‘, P = NS) or -40-mmHg periods (1.7 t 0.3 ml. 100 ml-’ min-‘, P = NS). Base-line forearm vascular resistance was 55 t 7 U. There was no further change in forearm vascular resistance during the LBNP -10-mmHg (55 t 7 U, P = NS) or -4O-mmHg (66 t 13 U, P = NS) periods. The renal hemodynamic response to LBNP is illustrated in Fig. 2. Basal renal blood flow was 505 t 63 ml/ min. In contrast to forearm blood flow, renal blood flow decreased progressively during application of LBNP to

01

boseline LBNP

FIG.

(LBNP). whereas t SE.

-10

-40

(mmHg1

1. Forearm vascular response to lower Twelve patients completed base-line only 9 patients completed -40-mmHg

B

body negative pressure and -lO-mmHg stages, stage. Values are means

800

ii

LBNP

(mmHg)

l

4( ~~0.05 vs. baseline # J(r wO.Ol vs. baseline

0’boselinI’e

l

TABLE

1. Systemic hemodynamic response to LBNP LBNP Base

Line -10

EBP DBP MBP PP HR CVP

mmHg

-40

mmHg

12 114t3

12 1lOt4

9 116k3

76t2 89k2

74k3

79t2

37t3 84k5

86t3 36k3 80t5

90t3 34t3 89t5

6.921.6

4.4&1.6*

3.4k1.7’”

Values are expressed as means t SE; n = no. of patients. LBNP, lower body negative pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; MBP, mean blood pressure; PP, pulse pressure; HR, heart rate (beats/min); and CVP, central venous pressure. All pressures are in mmHg. * P < 0.01.

LBNP FIG.

(LBNP). whereas t SE.

I

-IO

I

-40

(mmHg)

2. Renal vascular response to lower Twelve patients completed base-line only 9 patients completed -4O-mmHg

body negative pressure and -lO-mmHg stages, stage. Values are means

468 t 66 ml/ min at LBNP -10 mmHg (P < 0.05) and to 376 t 74 ml/min at LBNP -40 mmHg (P < 0.01). The resting renal vascular resistance was calculated as 0.21 t 0.03 mmHgoml-’ *min. At LBNP -10 mmHg, renal vascular resistance was 0.23 t 0.03 mmHg . ml. min-l (P = NS). LBNP -40 mmHg increased renal vascular resistance 39% to 0.29 t 0.04 mmHg=ml-’ .min (P c 0.01). The splanchnic vascular response to LBNP is illustrated in Fig. 3. Base-line splanchnic blood flow was 564 t 76 ml/min. As observed in the kidneys, splanchnic blood flow decreased progressively to 480 t 62 ml/min at LBNP -10 mmHg (P < 0.01) and to 303 t 45 ml/min at LBNP -40 mmHg (P < 0.01). The initial splanchnic vascular resistance was 0.20 t 0.03 mmHg ml-‘. min. At LBNP -10 mmHg, splanchnic vascular resistance was 0.24 t 0.04 mmHgoml-’ l min (P = NS). Significant l

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800

JOE

t5d n ” baseline

-10

LBNP(mmHg)

baseline

-IO

-40

LBNP(mmHg) FIG. 3. Splanchnic vascular sure (LBNP). Twelve patients stages, whereas only 9 patients are means t SE. AVI rt c 8

response to lower body negative prescompleted base-line and -IO-mmHg completed -40-mmHg stage. Values

100

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DISCUSSION

9. z” 5 --ICIL *zo,E 400 QO-

01

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O-O

CONTROL

a-0

HEART

N=6 FAILURE

PHENYLEPHRINE

**

N=6

DOSE

## T

pg/min

4. Effect of intra-arterial phenylephrine on forearm vascular resistance in normal subjects and in patients with congestive heart failure. Forearm vascular resistance at-base line and duri& each dose of phenylephrine was higher in heart failure patients than in normal subjects; however, dose-response curve was similar in each group. Values are means k SE. FIG.

splanchnic vasoconstriction occurred during the LBNP -40-mmHg period as splanchnic vascular resistance increased to 0.36 t 0.06 mmHg* ml-’ l min (P < 0.01). Limb vasoconstrictive resionse to phenylephrine. To examine whether the blunted limb vasoconstrictive response to LBNP involved the baroreflex arc or was secondary to the inability of the limb vasculature to respond to sympathetic stimuli, six normal subjects and six patients with heart failure received intrabrachial artery infusions of phenylephrine (Fig. 4). Basal forearm blood flow was lower (2.2 k-O.2 vs. 3.6% 0.5 ml 100 ml-’ Ionin+, P < O.Ol), and forearm vascular resistance was higher (43 t 4 vs. 26 t 4 U, P < 0.05) in the heart failure group. Despite these differences, intra-arterial phenylephrine induced comparable degrees of limb vasoconstriction. At the maximal phenylephrine dose of 3.0 ,ug/ min, forearm vascular resistance was 75 t 12 and 52 t 9 U in heart failure patients and normal subjects, respectively. l

Baroreceptors located in the heart, lungs, and great vessels respond to changes in pressure and volume by altering sympathetic and parasympathetic nervous system activity, hypophysial secretion of arginine vasopressin, and renal release of renin (2). By altering regional sympathetic tone and circulating levels of vasoactive hormones, cardiopulmonary and arterial baroreceptors are capable of modulating blood flow distribution in normal individuals. This study is the first to demonstrate that baroreceptors are capable of regulating both renal and splanchnic blood flow in patients with heart failure. Baroreceptor abnormalities have been reported in experimental models of heart failure and suggested by several experiments in humans with heart failure (8, 10, 13, 14, 18, 22, 29). Both the reflex chronotropic response to phenylephrine infusion and the vasoconstrictor response to carotid artery occlusion are impaired in animals with experimental low-output heart failure (13,14). In addition, neural recordings from baroreceptors in dogs with heart failure demonstrate a blunted response to volume expansion (29). Though important information is derived from the animal studies, one cannot necessarily extrapolate these findings to human congestive heart failure. Studies in humans have also suggested that baroreceptor function is abnormal. Arterial baroreceptor function has been evaluated by administering drugs that affect blood pressure. The infusion of nitroprusside causes a reflex increase in heart rate in normal subjects, but equivalent hypotensive doses do not elicit comparable chronotropic responses in patients with heart failure (22). Patients with heart failure also show less reflex bradycardia after hypertensive doses of phenylephrine. Abnormalities in end-organ responsiveness to autonomic stimuli, i.e., in the sinus node rather than in the baroreceptors, could account for the observed responses. Baroreflex function has also been evaluated during head-up tilt and LBNP. These maneuvers increase venous pooling and reduce atria1 and ventricular diastolic pressures, thereby decreasing the stimulus to cardiopulmonary baroreceptors. Reduction in stroke volume and pulse pressure as a result of decreased cardiac filling may also affect arterial baroreceptors. Normally, systemic vascular resistance and heart rate increase with head-up tilt and lower body negative pressure (2). In addition, plasma levels of norepinephrine, renin activity, and vasopressin increase (11, 20). In contrast, patients with congestive heart failure usually do not demonstrate changes in systemic vascular resistance or neurohormonal activity (4, 18, 22). Disparate regional blood flow responses to LBNP in congestive heart failure. Previous studies in patients with heart failure have examined the effect of baroreceptor perturbation on selective regional circulations. The forearm vasoconstrictive response to baroreceptor unloading is blunted in heart failure (10, 12). One early study even reported paradoxical forearm vasodilation with upright tilt (3). In contrast, Lilly et al. (19) reported that upright posture reduced both renal and hepatic blood flow in normonatremic heart failure patients but not in hypo-

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natremic patients. The data reported herein demonstrated that LBNP did not affect forearm blood flow or forearm vascular resistance. Yet, significant renal and splanchnic vasoconstriction occurred during LBNP -40 mmHg. These data suggest that baroreceptors are capable of modulating renal and splanchnic blood flow in patients with heart failure. This observation may explain the selective vasoconstriction that occurs in these vascular beds. These regionally disparate responses may reflect differences in the activity of specific baroreceptor subgroups, i.e., the cardiopulmonary and arterial baroreceptors. In animals, cardiac baroreceptors preferentially regulate renal blood flow, whereas arterial baroreceptors preferentially regulate skeletal muscle blood flow (6, 21). The situation in humans appears to be different. Studies in normal human subjects have suggested that cardiopulmonary baroreceptors predominately control limb blood flow, whereas carotid baroreceptors tend to control splanchnic blood flow (1, 17). In a study conducted in normal human volunteers in this laboratory, low levels of LBNP sufficient to unload cardiopulmonary baroreceptors caused forearm vasoconstriction (16). Renal and splanchnic vasoconstriction occurred only during the more negative levels of LBNP that perturb both cardiopulmonary and arterial baroreceptors. These findings suggest that different sets of receptors are capable of regulating blood flow to specific regions in humans. In patients with heart failure, dysfunction of cardiopulmonary baroreceptors would prevent forearm vasoconstriction, whereas preservation of arterial baroreceptor function could cause renal and splanchnic vasoconstriction during LBNP. In the patients with heart failure reported in this study, LBNP caused a progressive decrease in central venous pressure but did not affect systolic or mean blood pressure or pulse pressure. Though some might argue that arterial baroreceptors were not affected, vasoconstriction during sustained LBNP may have corrected an early fall in blood pressure. Limb vascular responses to adrenergic stimulation. Impaired end-organ responsiveness to efferent neural stimuli may be pertinent to the blunted forearm vasoconstrictive response to LBNP. To examine this issue further, forearm blood flow was measured in patients with heart failure and in normal subjects during intra-arterial administration of phenylephrine. The vasoconstrictive response to phenylephrine was comparable in each group, even though basal forearm vascular resistance was higher in the patients with heart failure. This observation argues against the possibility that the limb vasculature is less responsive to sympathetic stimuli in the patients with heart failure. Furthermore, our data are consistent with a study previously reported by Ferguson et al. (lo), in which intra-arterial norepinephrine induced forearm vasoconstriction in patients with left ventricular dysfunction. Limitations of study. In this study, LBNP was used to perturb cardiopulmonary and arterial baroreceptors. By comparing the regional vascular effects of this intervention in heart failure patients with those of normal subjects, one could conclude that baroreflex control of renal

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and splanchnic blood flow is preserved in patients with heart failure. It is conceivable that effects of LBNP on hepatic and renal venous pressure elicited local venoarterial reflexes to account for the vasoconstriction observed in these regions. These reflexes, however, are activated by increases in venous pressure, whereas LBNP decreases venous pressure (23). It is also unlikely that LBNP reduced splanchnic or renal blood flow directly by decreasing extravascular pressure, because the chamber envelops the body below the level of the arteries supplying these organs. Moreover, a decrease in extravascular pressure would most likely favor an increase in blood flow, not a decrease as observed in this study. An important concern is that there was no concurrent control group with which one might compare the regional vascular responses with LBNP. However, we had previously conducted a similar study in normal subjects that examined the differential contributions of cardiopulmonary and arterial baroreceptors to regional blood flow (16). In that study, limb vascular resistance increased during low levels of LBNP (-10 mmHg), whereas both renal and splanchnic vascular resistance increased only during high levels of LBNP (-20 and -40 mmHg). The principal difference between the findings in the two studies is that limb vasoconstriction did not occur in heart failure subjects during the unloading maneuver. We assume that the variable responsible for this difference is the presence of left ventricular dysfunction. This assumption is supported by several other published reports (3, 10, 12) We cannot, however, exclude age or physical conditioning as contributing factors, because our normal subjects were younger and better fit than our patients with heart failure. Conclusions. These data suggest that baroreceptors regulate splanchnic and renal vascular resistance but not limb vascular resistance in patients with congestive heart failure. Selective regulation of regional circulations may contribute to the redistribution of blood flow that occurs in this disorder. This study was supported by National Heart, Blood, and Lung Institute Grants HL-36348 and HL-36568. M. A. Creager is a recipient of a Research Career Development Award (HL-01768). V. J. Dzau and W. S. Colucci are Established Investigators of the American Heart Association. Address %r reprint requests: M. . ‘reager, Div. of Vascular Medicine and At1 erosclerosis, Brigham anU Women’s Hospital, 75 Francis Street, Boston, MA 02115. Received

2 March

1989; accepted

in final

form

13 December

1989.

REFERENCES ABBOUD, F. M., D. L. ECKBERG, U. L. JOHANNSEN, AND A. L. MARK. Carotid and cardiopulmonary baroreceptor control of splanchnic and forearm vascular resistance during venous pooling in man. J. Physiol. Lond. 286: 173-184, 1979. ABBOUD, F. M., D. D. HEISTAD, A. L. MARK, AND P. G. SCHMID. Reflex control of the peripheral circulation. Prog. Cardiovasc. Dis. 18: 371-403, 1976. BRIGDEN, W., AND E. P. SHARPEY-SHAFER. Postural changes in peripheral blood flow in cases with left heart failure. Clin. Sci. Lond. 9: 93-100,195O. CODY, R. J., K. W. FRANKLIN, J. KLUGER, AND J. H. LARAGH. Mechanisms governing the postural response and baroreceptor abnormalities in chronic congestive heart failure: effects of acute

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and long-term converting enzyme inhibition. CircuZation 66: 135142, 1982. COLE, B. R., J. GIANGIACOMO, J. R. INGELFINGER, AND A. M. ROBSON. Measurement of renal function without urine collection. N. Engl. J. Med. 287: 1109-1114, 1972. DORWARD, P. K., W. RIEDEL, S. L. BURKE, J. GIPOPS, AND P. I. KORNER. The renal sympathetic baroreflex in the rabbit. Arterial and cardiac baroreceptor influences, resetting and effect of anesthesia. Circ. Res. 57: 618-633, 1985. DUNNETT, C. W. New tables for multiple comparisons with a control. Biometrics 20: 482-494, 1964. ECKBERG, D. L., M. DRABINSKY, AND E. BRANUWALD. Defective cardiac parasympathetic control in patients with heart disease. N. Engl. J. Med. 285: 877-883, 1971. FAXON, D. P., M. A. CREAGER, J. L. HALPERIN, D. B. BERNARD, AND T. J. RYAN. Redistribution of regional blood flow following angiotensin-converting enzyme inhibition. Comparison of normal subjects and patients with heart failure. Am. J. Med. 76: 104-110, 1984. FERGUSON, D. W., F. M. ABBOUD, AND A. L. MARK. Selective impairment of baroreflex-mediated vasoconstrictor responses in patients with ventricular dysfunction. Circulation 69: 451-460, 1984. GOLDSMITH, S. R., G. S. FRANCIS, A. W. COWLEY, AND J. N. COHN. Response of vasopressin and norepinephrine to lower body negative pressure in normal humans. Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H970-H973, 1982. GOLDSMITH, S. R., G. S. FRANCIS, T. B. LEVINE, AND J. N. COHN. Regional blood flow response to orthostasis in patients with congestive heart failure. J. Am. CoZZ. Cardiol. 1: 1391-1395, 1983. GREENBERG, T. T., W. H. RICHMOND, R. A. STOCKING, P. D. GUPTA, J. P. MEEHAN, AND J. P. HENRY. Impaired atria1 receptor responses in dogs with heart failure due to tricuspid insufficiency and pulmonary artery stenosis. Circ. Res. 32: 424-433, 1973. HIGGINS, C. B., S. F. VATNER, D. L. ECKBERG, AND E. BRAUNWALD. Alterations in the baroreceptor reflex in conscious dogs with heart failure. J. CZin. Inuest. 51: 715-724, 1982. HIRSCH, A. T., V. J. DZAU, AND M. A. CREAGER. Baroreceptor function in congestive heart failure: effect on neurohumoral activation and regional vascular resistance. Circulation 75, Suppl. IV: IV-36-IV-48, 1987. HIRSCH, A. T., D. J. LEVENSON, V. J. DZAU, S. S. CUTLER, A. R. DOHERTY, AND M. A. CREAGER. Regional vascular response to

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Baroreflex regulation of regional blood flow in congestive heart failure.

In patients with congestive heart failure (CHF), the distribution of the cardiac output is altered. Cardiopulmonary and arterial baroreceptors normall...
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