Cardiovascular and renal actions of C-type natriuretic peptide

1992 ◽  
Vol 262 (1) ◽  
pp. H308-H312 ◽  
Author(s):  
A. J. Stingo ◽  
A. L. Clavell ◽  
L. L. Aarhus ◽  
J. C. Burnett
Keyword(s):  
Arterial Pressure ◽  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Sodium Reabsorption ◽  
Bolus Administration ◽  
Systemic Hemodynamic ◽  
Biological Responses ◽  
Anesthetized Dogs ◽  
Group 2 ◽  
Group 1

Studies were performed in two groups of anesthetized dogs (n = 5 per group) to determine the cardiovascular and renal actions of synthetic C-type natriuretic peptide (CNP). Systemic infusion of CNP (group 1; 10 and 50 ng.kg-1.min-1 iv) resulted in marked cardiovascular hemodynamic effects characterized by a decrease in mean arterial pressure, cardiac output, and atrial pressures in association with a decrease in sodium excretion. Bolus administration of CNP (group 2; 5 micrograms/kg iv) to minimize cardiovascular hemodynamic changes resulted in only a transient decrease in arterial pressure. Sodium excretion decreased despite a return of arterial pressure to baseline. These biological responses were associated with increases in plasma guanosine 3',5'-cyclic monophosphate (cGMP) in both groups but with no change in urinary cGMP. With both systemic infusion or bolus administration of CNP, significant increases in plasma aldosterone were observed in association with increases in distal nephron sodium reabsorption. This study demonstrates that CNP exhibits profound systemic hemodynamic actions and is indirectly, or perhaps directly, antinatriuretic.

Dopamine-1 receptor stimulation impairs intestinal oxygen utilization during critical hypoperfusion

2003 ◽  
Vol 284 (2) ◽  
pp. H668-H675 ◽  
Author(s):  
Jorge A. Guzman ◽  
Ariosto E. Rosado ◽  
James A. Kruse
Keyword(s):  
Blood Flow ◽  
Mucosal Blood Flow ◽  
Control Group ◽  
Oxygen Utilization ◽  
Hemorrhage Control ◽  
Receptor Stimulation ◽  
Anesthetized Dogs ◽  
Group 2 ◽  
Increased Susceptibility ◽  
Group 1

Effects of a dopamine-1 (DA-1) receptor agonist on systemic and intestinal oxygen delivery (D˙o 2)-uptake relationships were studied in anesthetized dogs during sequential hemorrhage. Control ( group 1) and experimental animals ( group 2) were treated similarly except for the addition of fenoldopam (1.0 μg · kg−1 · min−1) in group 2. Both groups had comparable systemic criticalD˙o 2(D˙o 2crit), but animals in group 2 had a higher gut D˙o 2crit(1.12 ± 1.13 vs. 0.80 ± 0.09 ml · kg−1 · min−1, P < 0.05). At the mucosal level, a clear biphasic delivery-uptake relationship was not observed in group 1; thus oxygen consumption by the mucosa may be supply dependent under physiological conditions. Group 2 demonstrated higher peak mucosal blood flow and lack of supply dependency at higher mucosalD˙o 2 levels. Fenoldopam resulted in a more conspicuous biphasic relationship at the mucosa and a rightward shift of overall splanchnic D˙o 2crit despite increased splanchnic blood flow. These findings suggest that DA-1 receptor stimulation results in increased gut perfusion heterogeneity and maldistribution of perfusion, resulting in increased susceptibility to ischemia.

scholarly journals Evaluation of the Accuracy of the Delta Life DL 1000 Oscillometric Monitor for Blood Pressure Measurement in Anesthetized Dogs of Different Weight Ranges

2020 ◽  
Vol 48 ◽  
Author(s):  
Bárbara Silva Correia ◽  
Eduardo Raposo Monteiro ◽  
João Victor Barbieri Ferronatto ◽  
Luciana Branquinho Queiroga ◽  
José Ricardo Herrera Becerra
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Pressure Measurement ◽  
Elective Surgery ◽  
Blood Pressure Measurement ◽  
Measurement Data ◽  
Arterial Blood ◽  
Anesthetized Dogs ◽  
Group 2 ◽  
Group 1

Background: Arterial blood pressure is one of the most commonly variables monitored during anesthetic procedures in veterinary patients. The most reliable method for measuring arterial blood pressure in dogs and cats is the direct (invasive) method. However, the oscillometric method is less complex and more practical for clinical routine in small animals. Nevertheless, oscillometric monitors present great variability in accuracy. The present study aimed to determine the accuracy of the Delta Life DL 1000 oscillometric monitor for measurement of systolic, mean and diastolic blood pressures (SAP, MAP and DAP, respectively) in anesthetized dogs of different weight ranges.Materials, Methods & Results: This study was approved by the Institutional Ethics Committee of Animal Use. Fifteen female dogs of different breeds, weighing 11.6 ± 10.0 kg and with a mean age of 48 ± 51 months were used. All animals were scheduled for elective surgery under general anesthesia in the Institution Veterinary Hospital. Dogs were anesthetized with morphine, propofol and isoflurane and had one 20 or 22 gauge catheter introduced into the dorsal pedal artery for continuous, invasive monitoring of SAP, MAP and DAP. A blood pressure cuff was positioned over the middle third of the radius and connected to Delta Life DL 1000 monitor. Oscillometric readings of SAP, MAP and DAP were registered every 5 minutes, and invasive values were simultaneously recorded. Values obtained with both methods were compared (invasive versus oscillometric) by use of the Bland Altman method to determine the bias, standard deviation of bias and 95% limits of agreement. The percentages of errors between the methods within 10 mmHg and within 20 mmHg were calculated. The results obtained were compared with the criteria from the American College of Veterinary Internal Medicine (ACVIM) for validation of indirect methods of arterial blood pressure measurement. Data were stratified into two groups according to the weight: < 10 kg (Group 1; n = 9); and ≥ 10 kg (Group 2; n = 6). In Group 1, 119 paired measurements were obtained, four of which classified as hypotension (SAP < 90 mmHg), 98 as normotension (SAP from 90 to 140mmHg) and 17 as hypertension (SAP > 140 mmHg). Bias (± SD) values in Group 1 were as follows: SAP, 5.2 ± 18.1 mmHg; MAP, -3.4 ± 17.2 mmHg; and DAP, 12.0 ± 17.5 mmHg. The percentages of errors within 10 mmHg were 40.3% for SAP; 45.4% for MAP and 28.6% for DAP. The percentages of errors within 20 mmHg were 72.3% for SAP, 84.0% for MAP and 68.1% for DAP. In Group 2, 66 paired measurements were obtained, nine of which classified as hypotension, 56 as normotension and one as hypertension. Bias (± SD) in Group 2 were as follows: SAP, 13.6 ± 14.3 mmHg; MAP, -1.1 ± 13.5 mmHg; and DAP, 8.2 ± 16.0 mmHg. The percentages of errors within 10 mmHg were 33.3% for SAP, 77.3% for MAP and 33.3% for DAP. The percentages of errors within 20 mmHg were 65.1% for SAP, 92.4% for MAP and 83.4% for DAP.Discussion: Based on the results of this study and reference criteria from the ACVIM, the Delta Life DL 1000 monitor had a poor accuracy for SAP, MAP and DAP and did not meet the criteria from the ACVIM in anesthetized dogs under 10 kg. Measurements of MAP in dogs ≥ 10 kg met the ACVIM criteria, but measurements of SAP and DAP did not. Based on the findings in this study, the DL 1000 oscillometric monitor is not recommended for blood pressure measurement in anesthetized dogs < 10 kg. In dogs ≥ 10 kg, measurements of MAP yielded acceptable values, but SAP and DAP measurements did not.

Normotensive sodium loading in normal man: regulation of renin secretion during β-receptor blockade

2009 ◽  
Vol 296 (2) ◽  
pp. R436-R445 ◽  
Author(s):  
Simon Mølstrøm ◽  
Nils H. Larsen ◽  
Jane A. Simonsen ◽  
Remon Washington ◽  
Peter Bie
Keyword(s):  
Arterial Pressure ◽  
Sodium Excretion ◽  
Sodium Intake ◽  
Venous Pressure ◽  
Macula Densa ◽  
Renin Secretion ◽  
Sodium Reabsorption ◽  
Plasma Sodium ◽  
Adrenergic Blockade ◽  
Saline Loading

Saline administration may change renin-angiotensin-aldosterone system (RAAS) activity and sodium excretion at constant mean arterial pressure (MAP). We hypothesized that such responses are elicited mainly by renal sympathetic nerve activity by β1-receptors (β1-RSNA), and tested the hypothesis by studying RAAS and renal excretion during slow saline loading at constant plasma sodium concentration (Na+ loading; 12 μmol Na+·kg−1·min−1 for 4 h). Normal subjects were studied on low-sodium intake with and without β1-adrenergic blockade by metoprolol. Metoprolol per se reduced RAAS activity as expected. Na+ loading decreased plasma renin concentration (PRC) by one-third, plasma ANG II by one-half, and plasma aldosterone by two-thirds (all P < 0.05); surprisingly, these changes were found without, as well as during, acute metoprolol administration. Concomitantly, sodium excretion increased indistinguishably with and without metoprolol (16 ± 2 to 71 ± 14 μmol/min; 13 ± 2 to 55 ± 13 μmol/min, respectively). Na+ loading did not increase plasma atrial natriuretic peptide, glomerular filtration rate (GFR by 51Cr-EDTA), MAP, or cardiac output (CO by impedance cardiography), but increased central venous pressure (CVP) by ∼2.0 mmHg ( P < 0.05). During Na+ loading, sodium excretion increased with CVP at an average slope of 7 μmol·min−1·mmHg−1. Concomitantly, plasma vasopressin decreased by 30–40% ( P < 0.05). In conclusion, β1-adrenoceptor blockade affects neither the acute saline-mediated deactivation of RAAS nor the associated natriuretic response, and the RAAS response to modest saline loading seems independent of changes in MAP, CO, GFR, β1-mediated effects of norepinephrine, and ANP. Unexpectedly, the results do not allow assessment of the relative importance of RAAS-dependent and -independent regulation of renal sodium excretion. The results are compatible with the notion that at constant arterial pressure, a volume receptor elicited reduction in RSNA via receptors other than β1-adrenoceptors, decreases renal tubular sodium reabsorption proximal to the macula densa leading to increased NaCl concentration at the macula densa, and subsequent inhibition of renin secretion.

Mechanisms of angiotensin II natriuresis and antinatriuresis

1985 ◽  
Vol 249 (2) ◽  
pp. F299-F307 ◽  
Author(s):  
M. E. Olsen ◽  
J. E. Hall ◽  
J. P. Montani ◽  
A. C. Guyton ◽  
H. G. Langford ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Sodium Excretion ◽  
Distal Tubule ◽  
Urinary Sodium Excretion ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Sodium Load ◽  
Proximal Tubular ◽  
Anesthetized Dogs

The aim of this study was to determine the role of changes in renal arterial pressure (RAP), renal hemodynamics, and tubular reabsorption in mediating the natriuretic and antinatriuretic actions of angiotensin II (ANG II). In seven anesthetized dogs, endogenous ANG II formation was blocked with captopril, and ANG II was infused intravenously at rates of 5-1,215 ng X kg-1 X min-1 while RAP was either servo-controlled at the preinfusion level or permitted to increase. When RAP was servo-controlled, ANG II infusion at all rates from 5-1,215 ng X kg-1 X min-1 decreased urinary sodium excretion (UNaV) and fractional sodium excretion (FENa) while increasing fractional reabsorption of lithium (FRLi) (an index of proximal tubular fractional sodium reabsorption) and causing no change in calculated distal tubule fractional sodium reabsorption (FRDNa). When RAP was permitted to increase, ANG II infusion rates up to 45 ng X kg-1. min-1 also decreased UNaV and FENa while increasing FRLi and causing no change in FRDNa. However, at 135 ng X kg-1 X min-1 and above, UNaV and FENa increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though renal blood flow and filtration fraction were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during ANG II infusion compared with when RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of ANG II cause antinatriuresis when RAP is prevented from increasing.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal localization and actions of adrenomedullin: a natriuretic peptide

1995 ◽  
Vol 268 (4) ◽  
pp. F657-F663 ◽  
Author(s):  
M. Jougasaki ◽  
C. M. Wei ◽  
L. L. Aarhus ◽  
D. M. Heublein ◽  
S. M. Sandberg ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Collecting Duct ◽  
Plasma Concentrations ◽  
In Vivo Studies ◽  
Sodium Reabsorption ◽  
Contralateral Kidney ◽  
Arterial Blood ◽  
Group I

Adrenomedullin (ADM) is a newly described 52-amino acid peptide originally isolated from extracts of human pheochromocytoma and, more recently, detected in human plasma. Based on the report that ADM mRNA and immunoreactivity are present in the kidney, the current study was designed to determine the renal distribution of ADM by immunohistochemistry and the renal biological actions of ADM. In the immunohistochemical studies, the present investigation demonstrated the localization of ADM in glomeruli, cortical distal tubules, and medullary collecting duct cells of the normal canine kidney. In the in vivo studies, ADM was administered (0.25 ng.kg-1.min-1 in group I and 1, 5, and 25 ng.kg-1.min-1 in group II) intrarenally in normal mongrel dogs with the contralateral kidney receiving only saline vehicle. Intrarenal infusion of ADM resulted in a marked diuretic and natriuretic response, whereas the contralateral kidney showed no renal effects. These significant natriuresis and diuresis in the ADM kidney were associated with increases in glomerular filtration rate and fractional sodium excretion and with a decrease in distal tubular sodium reabsorption. Intrarenal infusion of ADM also caused an increase in mean arterial blood pressure and a decrease in heart rate. Plasma concentrations of atrial natriuretic peptide, renin activity, aldosterone, and guanosine 3',5'-cyclic monophosphate were not changed during the infusion of ADM. The current study demonstrates that ADM is present in renal glomerular and tubular cells and is a potent natriuretic peptide that may play an important role in the regulation of sodium excretion.

Micropuncture study of the effect of ANP on the papillary collecting duct in the rat

1988 ◽  
Vol 254 (4) ◽  
pp. F477-F483 ◽  
Author(s):  
A. van de Stolpe ◽  
R. L. Jamison
Keyword(s):  
Collecting Duct ◽  
Sodium Concentration ◽  
Sodium Reabsorption ◽  
Micropuncture Study ◽  
Papillary Collecting Duct ◽  
Group 3 ◽  
Group 2 ◽  
Tubule Fluid ◽  
Group 1

Micropuncture collections were obtained from the terminal collecting duct (CD) at base and tip of the renal papilla of the rat. Group 1 was studied before and during infusion with atrial natriuretic peptide (ANP), group 2 was administered the vehicle only, and group 3 received acetazolamide to increase sodium delivery to the base to a similar extent as after ANP. ANP caused a decrease in blood pressure, a slight increase in GFR, natriuresis, and diuresis. Sodium delivery to the collecting duct at the base of the papilla increased. Between base and tip, sodium reabsorption was inhibited. Tubule fluid sodium concentration (TFNa) was increased at the base and remained high at the tip; in contrast TFNa fell between base and tip in control and acetazolamide groups. After acetazolamide, sodium reabsorption in the terminal CD was not inhibited. These results demonstrate that in vivo ANP 1) increases the delivery of sodium to the terminal CD and 2) inhibits sodium reabsorption in the terminal CD. The findings for chloride were similar to those for sodium. ANP also increased delivery of H2O, K, Ca, and Mg to the CD at the papillary base but did not significantly affect their transport by the terminal CD.

scholarly journals Receptor-mediated vascular and metabolic actions of endothelin-1 in canine small intestine

1999 ◽  
Vol 276 (5) ◽  
pp. G1131-G1136 ◽  
Author(s):  
Cheryl E. King-VanVlack ◽  
Jeffrey D. Mewburn ◽  
Christopher K. Chapler
Keyword(s):  
Small Intestine ◽  
Constant Pressure ◽  
Perfusion Pressure ◽  
Venous Blood ◽  
Receptor Blockade ◽  
Endothelin 1 ◽  
A Value ◽  
Anesthetized Dogs ◽  
Group 2 ◽  
Group 1

The effects of endothelin-1 (ET-1) infusion on blood flow (Q˙G) and O2 uptake (V˙o 2G) were examined in the small intestine of anesthetized dogs ( n = 10). Arterial and venous flows of a gut segment were isolated, and the segment was perfused at constant pressure. Arterial and gut venous blood samples were taken, gut perfusion pressure andQ˙G were measured, and O2 extraction ratio (OERG) andV˙o 2Gwere calculated. ET-1 was infused (0.118 μg ⋅ kg−1 ⋅ min−1ia) throughout the experiment. In group 1 ( n = 5), ETA receptors were blocked using BQ-123 (0.143 mg ⋅ kg−1 ⋅ min−1ia) followed by blockade of ETBreceptors with BQ-788 (0.145 mg ⋅ kg−1 ⋅ min−1ia). The order of ETA and ETB receptor blockade was reversed in group 2( n = 5). In group 1, the decrease inQ˙G observed with ET-1 infusion was partially reversed with BQ-123; no further change occurred after BQ-788 administration. In group 2, addition of BQ-788 to the infusate further decreasedQ˙G, whereas addition of BQ-123 returnedQ˙G to a value not different from that with ET-1 infusion alone. These data indicated that ET-1-induced vasoconstriction in the gut was mediated via ETA receptors and that this constriction was buffered by activation of ETB receptors.V˙o 2Gdecreased in proportion to the decrease inQ˙G with ET-1, decreased further with ET-1 plus ETB receptor blockade ( group 2), and increased in proportion to the increases in Q˙Gwith ETA receptor blockade (both groups). No changes in OERGoccurred during ETA and ETB receptor antagonism in either group. This study is the first to demonstrate that a flow-limited decrease in gutV˙o 2Goccurred with infusion of ET-1 in gut vasculature. An intriguing and novel finding was that, during O2limitation, OERG was only 50% of that normally associated with ischemia in this tissue.

scholarly journals ANP-mediated inhibition of distal nephron fractional sodium reabsorption in wild-type and mice overexpressing natriuretic peptide receptor

2010 ◽  
Vol 298 (1) ◽  
pp. F103-F108 ◽  
Author(s):  
Di Zhao ◽  
Kailash N. Pandey ◽  
L. Gabriel Navar
Keyword(s):  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Sodium Reabsorption ◽  
Natriuretic Peptide Receptor ◽  
Distal Nephron ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
Npr1 Gene

Atrial natriuretic peptide (ANP) elicits natriuresis; however, the relative contributions of proximal and distal nephron segments to the overall ANP-induced natriuresis have remained uncertain. This study was performed to characterize the effects of ANP on distal nephron sodium reabsorption determined after blockade of the two major distal nephron sodium transporters with amiloride (5 μg/g body wt) plus bendroflumethiazide (12 μg/g body wt) in male anesthetized C57/BL6 and natriuretic peptide receptor-A gene (Npr1) targeted four-copy mice. The lower dose of ANP (0.1 ng·g body wt−1·min−1, n = 6) increased distal sodium delivery (DSD, 2.4 ± 0.4 vs. 1.6 ± 0.2 μeq/min, P < 0.05) but did not change fractional reabsorption of DSD compared with control (86.3 ± 2.0 vs. 83.9 ± 3.6%, P > 0.05), thus limiting the magnitude of the natriuresis. In contrast, the higher dose (0.2 ng·g body wt−1·min−1, n = 6) increased DSD (2.8 ± 0.3 μeq/min, P < 0.01) and also decreased fractional reabsorption of DSD (67.4 ± 4.5%, P < 0.01), which markedly augmented the natriuresis. In Npr1 gene-duplicated four-copy mice ( n = 6), the lower dose of ANP increased urinary sodium excretion (0.6 ± 0.1 vs. 0.3 ± 0.1 μeq/min, P < 0.05) and decreased fractional reabsorption of DSD compared with control (72.2 ± 3.4%, P < 0.05) at similar mean arterial pressures (91 ± 6 vs. 92 ± 3 mmHg, P > 0.05). These results provide in vivo evidence that ANP-mediated increases in DSD alone exert modest effects on sodium excretion and that inhibition of fractional reabsorption of distal sodium delivery is requisite for the augmented natriuresis in response to the higher dose of ANP or in Npr1 gene-duplicated mice.

Inverse Correlation of Venous Brain Natriuretic Peptide Levels with Body Mass Index Is due to Decreased Production

Cardiology ◽  
2017 ◽  
Vol 137 (3) ◽  
pp. 159-166 ◽  
Author(s):  
Zubair Shah ◽  
Mark Wiley ◽  
Arun Mahankali Sridhar ◽  
Reza Masoomi ◽  
Mazda Biria ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Body Mass ◽  
Inverse Relationship ◽  
Univariate Analysis ◽  
Cardiac Resynchronization ◽  
The Mean ◽  
Group 2 ◽  
Group 1

Objective: The aim of this paper was to study the association between body mass index (BMI) and coronary sinus (CS) brain natriuretic peptide (BNP) levels in patients with heart failure and reduced systolic function (HFrEF). Background: There is an inverse relationship between systemic venous BNP (V-BNP) levels and BMI in patients with HFrEF. It is unclear whether this finding is due to decreased production or due to an increased metabolism of BNP. Since CS-BNP levels reflect BNP production, we hypothesized that assessing the correlation of CS-BNP levels with BMI would provide insight into the mechanism of this inverse relationship of V-BNP and BMI. Methods: We prospectively enrolled 54 subjects with HFrEF who were to undergo cardiac resynchronization device implantation. CS-BNP, V-BNP, and arterial BNP (A-BNP) levels were measured during the implant procedure. Subjects were divided into 2 groups based on their BMI (group 1: BMI <30 and group 2: BMI ≥30). Results: The mean age of the overall study group was 64 ± 10 years. Average BMI for group 1 was 25.8 ± 2.8 and 36.8 ± 4.6 for group 2 (p < 0.03). A history of hypertension was present in 55% (n = 26) of the subjects, while diabetes was reported in 31% (n = 15). Serum creatinine was 1.0 ± 0.2 mg/dL and TSH 2.1 ± 1.4 mIU/L. 79% of the subjects were receiving β-blockers, while 94% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The mean CS-BNP, V-BNP, and A-BNP levels in group 2 were significantly lower than in group 1 (286.2 ± 170.5 vs. 417.5 ± 247.5 pg/mL, p = 0.04; 126.6 ± 32.5 vs. 228 ± 96.4 pg/mL, p = 0.01; and 151.9 ± 28.6 vs. 242 ± 88.8 pg/mL, p = 0.04, respectively). Univariate analysis and multivariate regression adjusted for age, diabetes mellitus, sex, glomerular filtration rate, and left atrial size confirmed BMI as an independent predictor of CS-BNP levels (β = -0.372, p = 0. 03) in our study. Conclusions: In this study, we demonstrate an inverse relationship between CS-BNP levels and BMI in patients with HFrEF. These findings suggest that the previously established inverse relationship between V-BNP and BMI is due to a decreased cardiac production of BNP in obese patients rather than from increased peripheral metabolism.

Effects of altered left atrial pressure on pulmonary vascular pressure-flow relationships

1988 ◽  
Vol 255 (1) ◽  
pp. H19-H25 ◽  
Author(s):  
J. Ducas ◽  
U. Schick ◽  
L. Girling ◽  
R. M. Prewitt
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Vasculature ◽  
Pressure Flow ◽  
Artery Pressure ◽  
Time Control ◽  
Pulmonary Capillary ◽  
Anesthetized Dogs ◽  
Group 2 ◽  
Group 1

We studied the effects of changes in pulmonary capillary wedge pressure (PCWP) on the slope (incremental resistance) and the extrapolated pressure intercept (PI) of the mean pulmonary artery pressure (PAP)-cardiac output (CO) relationship. Multipoint plots of PAP against CO were obtained in intact anesthetized dogs. Group 1 consisted of six dogs entirely in West zone 3 and group 2 of four dogs with mixed West zone 2-3. The four conditions studied were the following: 1) fixed low PCWP, 2) fixed high PCWP, 3) variable PCWP, and 4) time-control repeat of condition 1. The PI significantly exceeded PCWP at fixed low PCWP (group 1, 9.3 vs. 11.1 mmHg, group 2, 6.6 vs. 3.9 mmHg). PI became identical to PCWP only at fixed high PCWP in group 1 (19 +/- 2.0 vs. 19 +/- 1.1 mmHg). Thus PCWP reflects the effective vascular outflow pressure when PCWP is fixed and high. For both groups of dogs in condition 3, when PCWP was varied with CO, the slope of the resulting PAP-CO plot was significantly greater than when PCWP was constant. Also in 9 of 10 dogs, PI was less than PCWP when PCWP was varied. These findings demonstrate that when changes in PCWP are allowed to occur during the generation of a pulmonary artery pressure-flow plot, the resulting slope and intercept, as defined by a Starling resistor model, do not accurately represent the incremental resistance and outflow pressure of the pulmonary vasculature.

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