Evidence for Preserved Cardiopulmonary Baroreflex Control of Renal Cortical Blood Flow in Humans With Advanced Heart Failure
A Positron Emission Tomography Study
Background The effect of cardiopulmonary baroreflexes on the renal circulation in healthy humans and patients with heart failure is unknown because of the technical limitations of studying the renal circulation. Positron emission tomography (PET) imaging is a new method to measure renal cortical blood flow in humans that is precise, rapid, reproducible, and noninvasive. The purpose of this study was to compare the effect of acute cardiopulmonary baroreceptor unloading by phlebotomy on regional blood flow in healthy humans and humans with advanced heart failure.
Methods and Results We compared renal cortical blood flow and forearm blood flow in 10 healthy volunteers and 8 patients with heart failure (left ventricular ejection fraction, 0.24±0.02) during cardiopulmonary baroreceptor unloading with phlebotomy (450 mL). The major findings of this study are: (1) At rest, renal cortical blood flow is markedly diminished in humans with heart failure compared with healthy humans (heart failure, 2.4±0.1 versus healthy, 4.3±0.2 mL · min−1 · g−1, P<.001). (2) In healthy humans, during phlebotomy, forearm blood flow decreased substantially (basal, 3.3±0.4 versus phlebotomy, 2.6±0.3 mL · min−1 · 100 mL−1, P=.02) and renal cortical blood flow decreased slightly but significantly (basal, 4.3±0.2 versus phlebotomy, 4.0±0.3 mL · min−1 · g−1, P=.01). (3) The small magnitude of reflex renal vasoconstriction is not explained by the inability of the renal circulation to vasoconstrict, since the cold pressor stimulus induced substantial decreases in renal cortical blood flow in healthy subjects (basal, 4.4±0.1 versus cold pressor, 3.7±0.1 mL · min−1 · g−1, P=.003). (4) In humans with heart failure, during phlebotomy, forearm blood flow did not change (basal, 2.6±0.3 versus phlebotomy, 2.7±0.2 mL · min−1 · 100 mL−1, P=NS), but renal cortical blood flow decreased slightly but significantly (basal, 2.4±0.1 versus phlebotomy, 2.1±0.1 mL · min−1 · g−1, P=.01). (5) The cold pressor stimulus induced substantial decreases in renal cortical blood flow in patients with heart failure (basal, 2.9±0.1 versus cold pressor, 2.3±0.1 mL · min−1 · g−1, P=.008). Thus, in patients with heart failure, there is an abnormality in cardiopulmonary baroreflex control of the forearm circulation but not the renal circulation.
Conclusions This study demonstrates the power of PET imaging to study normal physiological and pathophysiological reflex control of the renal circulation in humans and describes the novel finding of selective dysfunction of cardiopulmonary baroreflex control of one vascular region but its preservation in another in patients with heart failure.
Cardiopulmonary baroreceptors with vagal afferents are intrathoracic mechanoreceptors that, in response to changes in cardiopulmonary blood volume, modulate efferent sympathetic neural outflow and vascular resistance.1 Cardiopulmonary baroreflex modulation of sympathetic nerve activity and vascular tone exhibits regional nonuniformity, the general pattern of which differs between nonprimate animals and humans.1 2 3 4 5 6 In animals, cardiopulmonary baroreflexes regulate efferent renal sympathetic nerve activity, renin release, and renal blood flow but not limb muscle sympathetic activity or blood flow.4 5 6 In humans, in contrast, cardiopulmonary baroreflexes regulate limb muscle sympathetic activity and blood flow but not renin release.1 2 3 The effect of the cardiopulmonary baroreflexes on efferent renal sympathetic nerve activity and renal blood flow in humans is currently unknown because of the technical limitations of accessing this remote vascular bed.1 2 3 4 5 6
Positron emission tomography (PET) with the blood flow agent [15O]water has recently been shown to provide a rapid, noninvasive, and quantitative method to measure renal cortical blood flow in humans.7 PET [15O]water measurement of renal cortical blood flow is precise and reproducible, with an intrastudy variability of 2%.7 Renal blood flow distribution is known to differ between the cortex and medulla, especially during renal nerve stimulation. Cortical blood flow is the region of particular interest, since cortical blood flow composes 80% to 90% of total renal blood flow.8 Therefore, the first aim of this study was to compare the effect of acute cardiopulmonary baroreceptor unloading by phlebotomy on renal cortical blood flow measured by dynamic PET [15O]water and forearm blood flow in healthy humans.
Symptoms of volume overload, such as orthopnea and edema, characterize congestive heart failure, although the mechanisms underlying this fluid retention are not fully understood. It has been hypothesized that fluid retention in heart failure may result in part from blunted baroreflex restraint of sympathetic neural outflow directed to kidneys, leading directly to renal vasoconstriction and sodium and water retention.9 10 11 Several lines of evidence support this concept. First, in healthy humans, arterial and cardiopulmonary baroreflexes exert a tonic inhibitory influence on central sympathetic neural outflow, but in humans with heart failure, increased sympathetic nerve activity is present in all organs normally subject to this baroreflex restraint, including the kidneys.12 Second, in patients with heart failure, baroreflex dysfunction has been demonstrated; for example, in response to cardiopulmonary baroreceptor unloading in patients with heart failure, forearm vasoconstriction is blunted or reversed.13 14 However, there is virtually no information on the effects of cardiopulmonary baroreflex control of renal cortical blood flow in these patients. Therefore, the second aim of this study was to compare the effect of acute cardiopulmonary baroreflex unloading on renal cortical blood flow and forearm blood flow in patients with advanced congestive heart failure.
After written informed consent had been obtained, 14 healthy volunteers (5 women, 9 men; mean age, 35±5 years) and 12 advanced congestive heart failure patients (1 woman, 11 men; mean age, 47±3 years) participated in these studies. The study protocols were approved by the UCLA Human Subject Protection Committee. The volunteers were healthy as confirmed by normal medical history and physical examinations, complete blood count, blood urea nitrogen, and serum creatinine and were not taking medications. In 5 heart failure patients, the cause of heart failure was coronary artery disease and in 7, idiopathic dilated cardiomyopathy. Medications, including vasodilators, diuretics, and digoxin, were discontinued 24 to 36 hours before the study under medical supervision in the UCLA Clinical Research Center. All patients had advanced (New York Heart Association functional class III to IV) congestive heart failure and were undergoing evaluation for heart transplantation. As measured by echocardiography, quantified mean left ventricular ejection fraction was 0.24±0.02. Patients and volunteers abstained from caffeine for 18 hours before the study but otherwise were on an uncontrolled diet. These studies were performed in the postabsorptive state.
Measurements of Intracardiac Filling Pressures
Intracardiac filling pressures were recorded directly. On the morning of the experimental protocol, heart failure patients were transferred to the Cardiac Special Procedures Suite for insertion, under fluoroscopic guidance, of an 8F pulmonary artery catheter via the internal jugular vein. In healthy volunteers, a 19-gauge polyethylene catheter (Becton, Dickinson and Co) was inserted into an antecubital vein and advanced to a vein in the thorax. The position of the catheter was confirmed from the waveform of the recorded signal and changes of this waveform in response to deep inspiration. After placement of the catheters, patients and volunteers rested in the Clinical Research Center for 30 to 60 minutes.
Measurement of Forearm Blood Flow
Forearm blood flow was measured by venous occlusion plethysmography. The arm was positioned above heart level to ensure adequate venous drainage. A mercury-filled Silastic tube attached to a low-pressure transducer was placed 5 cm below the antecubital crease and connected to a plethysmograph (Hokanson). Sphygmomanometer cuffs were placed around the wrist and upper arm. The wrist cuff was inflated to suprasystolic levels for 1 minute before flow measurement. At 15-second intervals, the upper arm cuff was inflated above venous pressure for 7 seconds. The rate of increase in strain reflects the rate of increase in forearm volume and arterial blood flow. Forearm blood flow (mL · min−1 · 100 mL tissue−1) was determined from a minimum of 8 separate readings. Forearm vascular resistance (arbitrary units [AU]) was calculated by dividing mean arterial pressure (one third of pulse pressure plus diastolic pressure) by forearm blood flow.
PET Measurement of Renal Cortical Blood Flow
Renal cortical blood flow was measured by dynamic PET with the blood flow agent [15O]water as previously reported.7 Renal cortical blood flow in the right and left kidneys was measured separately but simultaneously. In brief, after a 30-minute blank scan and a 20-minute transmission image had been obtained for photon attenuation correction, [15O]water emission images were acquired on a Siemens/CTI model 931/08-12 tomograph. This device records 15 image planes simultaneously. The axial field of view is 10.8 cm. Ultrasound guidance was used to position the kidneys in the field of view of the tomograph. All subjects were imaged in the supine position. The subjects were injected with 30 mCi [15O]water over a period of 30 seconds into a peripheral vein while acquisition of the serial transaxial tomographic images was started. The acquisition protocol was completed in 5 minutes and consisted of twelve 10-second, four 30-second, and one 60-second frame.
Cross-sectional images were reconstructed by use of a Shepp-Logan filter with a cutoff frequency of 0.30−1, yielding an in-plane spatial resolution at the center of the plane of approximately 10 mm full-width half-maximum. The arterial tracer input function was derived from dynamic PET measurements of the abdominal aortic activity.15 Time-activity curves of the renal cortex were generated by region-of-interest analysis and corrected for dead time of the scanner and partial-volume effects.7 Renal cortical blood flow was then estimated by fitting the time-activity curves measured by PET to the one-compartment model for [15O]water. The renal cortical blood flow (mL · min−1 · g−1) value for one kidney was calculated as the average value for all analyzed regions of interest per kidney. All analyses were performed by a single investigator (E.U.N.) blinded to the experimental conditions. Renal cortical vascular resistance (AU) was calculated by dividing mean arterial pressure (one third of pulse pressure plus diastolic pressure) by renal cortical blood flow.
Venous blood samples for norepinephrine and plasma renin activity were obtained from an indwelling antecubital line. Samples were collected in iced tubes, centrifuged at −5°C, and frozen at −80°C. Norepinephrine concentrations were measured by liquid chromatography with electrochemical detection.16 Plasma renin activity was measured by radioimmunoassay.17
Blood pressure was monitored noninvasively with an automated sphygmomanometer (Dinamap, Critikon Corp). Heart rate was monitored continuously through lead II of the ECG.
Protocol 1: Cardiopulmonary Baroreceptor Deactivation With Phlebotomy18
Ten healthy volunteers and 8 patients with heart failure were studied in the supine position in the PET scanner. The volunteer or patient rested during the 20-minute transmission scan, then renal cortical blood flow was determined with PET [15O]water as described above. Baseline measurements of blood pressure, heart rate, forearm blood flow, right atrial pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure were made. Blood samples were drawn for norepinephrine and plasma renin activity. Phlebotomy (450 mL) was performed. Venipunctures were performed by a trained UCLA phlebotomist in accordance with the regulations and rules of the American Association of Blood Banks. Blood was withdrawn over a period of 5 to 10 minutes from an antecubital vein into standard blood collection bags. Volunteers and patients were instructed not to perform handgrip during phlebotomy to avoid the potentially confounding influence of handgrip on renal cortical blood flow. Immediately after phlebotomy, measurements of renal cortical blood flow, blood pressure, heart rate, forearm blood flow, right atrial pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure were repeated. Blood samples were again drawn for norepinephrine and plasma renin activity.
Protocol 2: Cold Pressor Test
We considered the possibility that potentially large reflex changes in efferent renal sympathetic nerve activity would not result in large changes in renal cortical blood flow because of renal vascular autoregulation. The cold pressor test was used as a strong, non–baroreflex mediated stimulus to vasoconstriction to determine whether large reflex changes in renal cortical blood flow occur and are detectable by PET [15O]imaging in healthy humans and patients with heart failure.19
Five healthy volunteers and 4 patients with heart failure were studied in the supine position in the PET scanner. The volunteer or patient rested during the 20-minute transmission scan, then renal cortical blood flow was determined with PET [15O]water as described above. Baseline measurements of blood pressure and heart rate were made. The hand of the volunteer or patient was immersed in the ice-water slurry for 2 minutes. Volunteers and patients were instructed to avoid isometric contraction or Valsalva maneuver during the test. Measurements of blood pressure, heart rate, and renal cortical blood flow were repeated.
Statistical analysis was performed by two-tailed paired and unpaired t tests. Probability values of P<.05 were considered statistically significant. Values are presented as mean±SEM.
Basal Regional Blood Flow
Baseline blood flow data in healthy volunteers and heart failure patients are shown in the Table⇓. Baseline forearm blood flow tended to be lower and baseline forearm vascular resistance was higher in heart failure patients compared with healthy volunteers. Baseline renal cortical blood flow was lower and baseline renal cortical resistance was higher in heart failure patients compared with healthy volunteers.
Cardiopulmonary Baroreflex Unloading With Phlebotomy: Healthy Volunteers (n=10)
Phlebotomy significantly decreased central venous pressure (basal, 4.3±0.7 versus phlebotomy, 1.7±0.8 mm Hg, P<.001) but did not change mean arterial pressure (basal, 82±2 versus phlebotomy, 82±3 mm Hg, P=NS) or heart rate (basal, 64±5 versus phlebotomy, 65±5 beats per minute, P=NS).
Changes in forearm blood flow during phlebotomy are shown in Fig 1⇓. Forearm blood flow decreased (basal, 3.3±0.4 versus phlebotomy, 2.6±0.3 mL · min−1 · 100 mL−1, P=.02) and forearm vascular resistance increased (basal, 27±4 versus phlebotomy, 35±5 AU, P=.02) in response to phlebotomy. Changes in renal blood flow during phlebotomy are shown in Fig 2⇓. Right renal cortical blood flow decreased slightly but significantly (basal, 4.3±0.2 versus phlebotomy, 4.0±0.3 mL · min−1 · g−1, P=.01); similarly, right cortical vascular resistance increased slightly but significantly (basal, 19±1 versus phlebotomy, 22±2 AU, P=.02). Results were identical when changes in left renal cortical blood flow were compared.
Norepinephrine levels increased after phlebotomy (basal, 194±24 versus phlebotomy, 234±37 pg/mL, P=.01), but plasma renin activity did not change (basal, 1.4±0.4 versus phlebotomy, 1.6±0.5 ng · mL−1 · h−1, P=NS).
Cardiopulmonary Baroreflex Unloading With Phlebotomy: Heart Failure Patients (n=8)
Phlebotomy significantly decreased central venous pressure (basal, 3.4±0.8 versus phlebotomy, 0.1±0.7 mm Hg, P<.001), mean pulmonary artery pressure (basal, 27±4 versus phlebotomy, 20±3 mm Hg, P<.001), and pulmonary capillary wedge pressure (basal, 19±3 versus phlebotomy, 14±3 mm Hg, P<.008) but did not change mean arterial pressure (basal, 89±4 versus phlebotomy, 88±5 mm Hg, P=NS) or heart rate (basal, 70±4 versus phlebotomy, 69±5 beats per minute, P=NS).
Responses in the forearm circulation during phlebotomy are shown in Fig 1⇑. During phlebotomy, forearm blood flow did not change (basal, 2.6±0.3 versus phlebotomy, 2.7±0.2 mL · min−1 · 100 mL−1, P=NS), and forearm vascular resistance tended to decrease (basal, 39±4 versus phlebotomy, 34±3 AU, P=.06). Changes in renal blood flow during phlebotomy are shown in Fig 2⇑. Renal cortical blood flow decreased slightly but significantly (basal, 2.4±0.1 versus phlebotomy, 2.1±0.1 mL · min−1 · g−1, P=.003) in response to phlebotomy; similarly, renal cortical vascular resistance increased slightly but significantly during phlebotomy (basal, 38±3 versus phlebotomy, 44±4 AU, P=.05).
Norepinephrine levels increased after phlebotomy (basal, 318±66 versus phlebotomy, 378±73 pg/mL, P=.03), but plasma renin activity did not change (basal, 2.9±1.0 versus phlebotomy, 3.1±1.1 ng · mL−1 · h−1, P=NS).
Renal Vascular Response to Cold Pressor Test
The rationale for the cold pressor test was to determine whether large reflex changes in renal blood flow and resistance occurred and, if so, whether they were detectable by PET imaging. Changes in renal blood flow during the cold pressor test are shown in Fig 3⇓. In 5 healthy volunteers, in response to the cold pressor stimulus, renal cortical blood flow markedly decreased (basal, 4.4±0.1 versus cold pressor test, 3.7±0.1 mL · min−1 · g−1, P=.003) and renal cortical vascular resistance markedly increased (basal, 18±1 versus cold pressor test, 26±2 AU, P=.002).
Similarly, in 4 patients with heart failure, in response to the cold pressor stimulus, renal cortical blood flow markedly decreased (basal, 2.9±0.1 versus cold pressor test, 2.3±0.1 mL · min−1 · g−1, P=.008) and renal cortical vascular resistance markedly increased (basal, 29±1 versus cold pressor test, 41±2 AU, P=.02).
Until recently, our ability to study reflex control of the renal circulation in humans was impeded by the limitations of available technology.8 20 21 22 23 24 The classic “clearance” technique using para-aminohippuric acid (PAH) requires prolonged (hours) collection of blood or urine and thus is impractical for investigation of acute changes mediated by the baroreflexes.20 21 In addition, the PAH clearance technique can provide only an imprecise estimate of total renal blood flow, since PAH is incompletely extracted by the kidneys and is subject to extrarenal excretion.20 21 Intra-arterial Doppler ultrasound, although able to provide dynamic information about changes in renal arterial blood flow velocity, is not quantitative, and its application in human experimental studies is limited by its invasiveness.22 Inert gas washout methods, although specific for renal cortical blood flow, are invasive, requiring renal arterial injection of the agent.23 Fast computed tomography is a promising new noninvasive method that has been shown to measure renal cortical and medullary blood flow in animals, but it has not yet been applied to humans.24
We report simultaneous measurements of renal cortical blood flow determined with [15O]water and PET and forearm blood flow at rest and in response to cardiopulmonary baroreceptor unloading with phlebotomy in healthy humans and in humans with advanced congestive heart failure. The major findings of this study are that (1) renal cortical blood flow is markedly diminished at rest in patients with advanced heart failure compared with healthy subjects; (2) in healthy subjects during cardiopulmonary baroreceptor unloading, forearm vasoconstriction is substantial, whereas renal vasoconstriction is detectable but slight; (3) in humans with heart failure during cardiopulmonary baroreceptor unloading, forearm vasoconstriction is blunted, whereas renal vasoconstriction is preserved, despite markedly reduced baseline renal cortical blood flow; and (4) the small change in renal vasoconstriction during cardiopulmonary baroreceptor unloading is not explained by the inability of the renal circulation to vasoconstrict, since the cold pressor stimulus induces substantial increases in renal vasoconstriction in both healthy humans and patients with heart failure.
In this study, we chose to focus on the effects of the cardiopulmonary baroreflexes on the renal circulation. The cardiopulmonary baroreceptors are important intrathoracic volume receptors, which respond to small changes in cardiopulmonary blood volume insufficient to affect arterial pressure and arterial baroreceptors.1 To selectively unload the cardiopulmonary baroreceptors but not the arterial baroreceptors, we performed phlebotomy of 450 mL of blood, which decreased intrathoracic pressure without affecting mean arterial pressure or heart rate. We did not investigate the effects of cardiopulmonary baroreflex loading with volume expansion on renal blood flow in healthy humans, since renal sympathetic activity is believed to be too low at baseline to affect renal hemodynamics,25 and in patients with heart failure, acute volume expansion may significantly worsen congestive symptoms. Future studies of the effects of arterial baroreflex regulation of renal cortical blood flow may add to our understanding of reflex control of the renal circulation in humans.
We considered the possibility that cardiopulmonary control of efferent renal sympathetic nerve activity was marked but that sympathetically mediated vasoconstriction was offset by renal autoregulatory mechanisms that maintained renal blood flow at the baseline level. To investigate this possibility, we used a strong stimulus to sympathetic nerve activation and vasoconstriction, the cold pressor test, to determine whether a large decrease in renal blood flow would occur and would be measurable by PET ([15O]water) imaging in humans. Cold pressor stimulation elicited a marked decrease in renal cortical blood flow in healthy humans and patients with heart failure, providing reassurance that if a similar change mediated by the cardiopulmonary baroreflexes were present, it would have been detectable. We cannot exclude the possibility that part of the increased renal resistance may be an autoregulatory response to the rise in arterial pressure, but autoregulation would not be expected to decrease renal blood flow below control levels, as seen in these studies.
Baroreflex control of sympathetic nerve activity and blood flow has been shown to exhibit regional nonuniformity in both animals and humans.1 2 3 4 5 6 In animals, renin release and renal blood flow are modulated by cardiopulmonary baroreceptors with vagal afferents, but limb blood flow is largely free from cardiopulmonary baroreceptor control. In the present study conducted in healthy humans, acute cardiopulmonary baroreceptor unloading with phlebotomy elicited a substantial reduction in forearm blood flow but only a small reduction in renal cortical blood flow. This finding is consistent with nonuniform cardiopulmonary baroreflex control of limb and renal blood flow in healthy humans.
A substantial body of knowledge is available about arterial and cardiopulmonary baroreflex control of efferent renal sympathetic nerve activity in animal models of heart failure. In these experimental models, blunted baroreflex control of efferent renal sympathetic nerve activity has been described.26 27 In elegant studies using a rat model of heart failure, DiBona and Sawin26 localized the abnormality of cardiopulmonary baroreflex control to the level of the afferent cardiopulmonary baroreceptor and not to the central nervous system. Dibner-Dunlap and Thames,27 using a dog model of heart failure, found that afferent cardiopulmonary and arterial baroreceptor control of efferent renal sympathetic nerve activity was blunted. Interestingly, these investigators found that the integrated baroreflex control of efferent renal sympathetic nerve activity was preserved, consistent with central nervous system compensation for attenuated afferent input (increased central gain).
We measured forearm blood flow by the well-established method of venous plethysmography. Although it would have been ideal to use the same technique to measure blood flow in both the renal and forearm vascular regions, the measurement of forearm blood flow by PET has not yet been established or validated. Our measurements of forearm blood flow during cardiac baroreceptor unloading in heart failure patients are consistent with those reported previously by others.13 Ferguson and colleagues13 found that during lower-body negative pressure in heart failure patients, baroreflex-mediated forearm vasoconstriction was blunted or even paradoxically reversed. This blunted forearm vasoconstriction was not explained by maximal baseline vascular tone in heart failure, since forearm vasoconstriction did increase further during the cold pressor stimulus.13 In the present study of humans with heart failure, we also found that the cardiopulmonary baroreflex control of limb blood flow was blunted or even reversed. However, cardiopulmonary baroreflex control of renal cortical blood flow was preserved in these patients with severe congestive heart failure, despite markedly diminished baseline renal blood flow. Although cardiopulmonary baroreflex control of regional blood flow is normally nonuniform, this study describes selective dysfunction of cardiopulmonary baroreflex control of one vascular region but its preservation in another. This novel finding of selective cardiopulmonary baroreflex dysfunction may have important implications for our understanding of the mechanisms underlying abnormal sympathetic excitation and vasoconstriction in humans with heart failure.
This finding of preserved reflex renal vasoconstriction yet profoundly abnormal reflex forearm vasoconstriction during cardiopulmonary baroreceptor deactivation in humans with heart failure cannot be explained by a single abnormality at the level of the afferent receptor. There are two possible explanations for this selective abnormality: First, it is possible, although unlikely, that in humans with heart failure, unlike animals, afferent cardiopulmonary baroreceptors are completely normal and the abnormality occurs elsewhere in the integrated cardiopulmonary reflex control of forearm blood flow. Alternatively, if we accept the substantial evidence in animals supporting the presence of an abnormality at the afferent receptor, we must then postulate a compensatory mechanism located elsewhere in the integrated cardiopulmonary reflex control of renal cortical blood flow in humans with heart failure. Possible mechanisms include (1) an increase in central gain for renal, but not muscle, efferent sympathetic nerve activity in humans with heart failure; (2) enhanced renal, compared with limb, vascular sensitivity to norepinephrine in heart failure; (3) cardiopulmonary baroreflex–mediated release of renin in humans with heart failure, facilitating angiotensin-mediated renal vasoconstriction; and (4) activation of another reflex system during phlebotomy in patients with heart failure, such as the arterial baroreflex, which then acts selectively on the renal vascular bed. The present study was not designed to distinguish between these and other potential mechanisms.
Hirsch and colleagues28 studied renal blood flow in healthy humans and, in contrast to our findings, detected no change in renal blood flow during cardiopulmonary baroreceptor unloading. Methodologically, their study differed from ours in several important ways. Hirsch used PAH clearance to estimate total renal blood flow, whereas we used PET [15O]water to measure renal cortical blood flow. Second, they studied the effects of chronic cardiopulmonary baroreceptor unloading, since acute changes in renal blood flow are not measurable by the PAH clearance technique. In contrast, we studied acute changes in renal cortical blood flow. These investigators used the same methods to study patients with congestive heart failure29 and reported a small but significant fall in renal blood flow during cardiopulmonary baroreceptor unloading. They concluded that the vascular territories regulated by the cardiopulmonary baroreflexes differed between healthy humans and humans with heart failure: In healthy humans, cardiopulmonary baroreflexes were found to regulate limb, but not renal, blood flow, but in humans with heart failure, cardiopulmonary baroreflexes regulated renal, but not limb, blood flow. In contrast, our findings of a small but significant decrease in renal blood flow in both healthy and heart failure subjects but no change in forearm blood flow in heart failure compared with healthy subjects support the concept of selective dysfunction of cardiopulmonary baroreflex control of the circulation in humans with heart failure.
In summary, we used a new method, PET imaging with [15O]-labeled water, to study reflex control of renal cortical blood flow in healthy humans and in humans with heart failure. Cardiopulmonary baroreflex control of renal cortical blood flow is slight, but present, in healthy humans. This control is selectively preserved in humans with advanced congestive heart failure. The selective nature of the cardiopulmonary dysfunction is a new finding, with implications for our understanding of the sympathetic activation and vasoconstriction that characterize patients with heart failure.
Operated for the US Department of Energy by the University of California under contract DE-FC03-87ER60615. This work was supported in part by the Director of the Office of Energy Research, Office of Health and Environmental Research, Washington, DC; by research grants HL-29845 and HL-33177, National Institutes of Health, Bethesda, Md; by an Investigative Group Award by the Greater Los Angeles Affiliate of the American Heart Association, Los Angeles, Calif; by US Public Health Service grant M01-RR-00865; and by a Grant-in-Aid from the American Heart Association, Greater Los Angeles Affiliate. The authors are grateful to Leila Terada and Julie A. Walden, MN, for facilitating patient enrollment and to the nurses and staff of the UCLA Clinical Research Center for excellent patient care. Finally, the authors thank the PET technologists Ronald Sumida, Lawrence Peng, Francine Aquilar, Der-Jenn Liu, and Mark Hulgan for performing the PET scanning.
- Received November 15, 1994.
- Revision received January 16, 1995.
- Accepted January 22, 1995.
- Copyright © 1995 by American Heart Association
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