Effect of Beta-adrenergic Blockade on Elevated Arterial Compliance and Low Systemic Vascular Resistance in Cirrhosis

Abstract Relaxin emanates from the corpus luteum of the ovary and circulates during pregnancy. Because the hormone is a potent renal vasodilator and mediates the renal vasodilation and hyperfiltration of pregnancy in conscious rats, we reasoned that it might also contribute to the broader cardiovascular changes of pregnancy. We began investigating this concept by testing whether relaxin can modify systemic arterial hemodynamics and load when chronically administered to nonpregnant rats. The major objectives of the present work were to determine whether relaxin administration to nonpregnant rats 1) modifies cardiac output (CO), systemic vascular resistance, and global arterial compliance (AC), and 2) regulates the passive mechanics of isolated arteries. To accomplish the first objective, we developed a conscious rat model for assessment of global AC. Passive mechanics of small renal arteries were assessed using a pressure arteriograph. Chronic administration of recombinant human relaxin by sc osmotic minipump to conscious, female, nonpregnant rats reduced the steady arterial load by decreasing systemic vascular resistance, increased CO, and reduced the pulsatile arterial load by increasing global AC as quantified by two indices—AC estimated from the diastolic decay of aortic pressure and CO and AC estimated by the ratio of stroke volume-to-pulse pressure. In another group of rats, relaxin administration also regulated the passive mechanics of small renal arteries, indicating that, in addition to reduction in vascular smooth muscle tone, modification of the vascular structure (e.g. extracellular matrix) contributes to the increase in global AC. These findings suggest a role for relaxin in the systemic hemodynamic changes of pregnancy, as well as novel therapeutic potential for relaxin in modifying arterial stiffness and cardiac afterload.

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Abstract 15631: The Hemodynamic Determinants and Physiologic Correlates of QTc Interval Using Impedance Cardiography in Heart Failure

Circulation ◽

10.1161/circ.132.suppl_3.15631 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Fadi Khraim ◽

Rodolfo Pike ◽

Jennifer Williams ◽

Salah S Al-Zaiti

Keyword(s):

Heart Failure ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Impedance Cardiography ◽

Arterial Compliance ◽

Qtc Interval ◽

Cardiac Events ◽

Heart Failure Patients ◽

Qrs Duration ◽

Duration Effect

Background: Prolonged QTc interval is a known risk factor for adverse cardiac events, including sudden and non-sudden cardiac death. Understanding the determinants and physiologic correlates of QTc can guide the proper strategy for the primary prevention of sudden death in high risk patients. Methods & Results: This was an observational study that recruited ambulatory heart failure patients (NYHA I-III) from an outpatient clinic in NL, Canada. In supine resting position, consented participants underwent non-invasive 12-lead ECG and hemodynamic monitoring using BioZ Dx Impedance Cardiography (Sonosite Inc., WA, USA). ECGs were evaluated by a reviewer blinded to clinical data. Participants with pacing (n=12) or left bundle branch block (n=9) were excluded. Three measures of interest were automatically computed: (1) QTc interval (i.e., from QRS onset to T offset), (2) QRS duration (i.e., from QRS onset to QRS offset), and (3) JTc (i.e., QTc interval minus QRS duration). Effect sizes were computed using Pearson’s r coefficients. The final sample (n=23) was 62±13 years of age and 70% male with LVEF of 34±10%. The mean QTc was 441±39 milliseconds, and 10 patients (43%) had prolonged QTc (≥450 milliseconds). QTc interval negatively correlated with cardiac output (r= -0.57), and positively correlated with systemic vascular resistance (r= +0.57), as well as thoracic fluid content (r= +0.43). QRS duration alone was not specifically associated with any hemodynamic parameter, but JTc interval positively correlated with total arterial compliance (r=+0.42). Conclusions: In heart failure patients, we interestingly found that increased systemic vascular resistance results in QTc interval prolongation, where repolarization time is specifically influenced by arterial compliance. This suggests potential benefit from antihypertensive therapy targeted at lowering systemic vascular resistance in those with prolonged QTc/JTc. Nevertheless, these intervals need to be interpreted with caution in patients with thoracic fluid overload (e.g., pulmonary edema).

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Sympathoadrenal mechanisms in hemodynamic responses to gastric distension in cats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1982.243.5.h748 ◽

1982 ◽

Vol 243 (5) ◽

pp. H748-H753 ◽

Cited By ~ 9

Author(s):

J. C. Longhurst ◽

J. Ibarra

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Adrenergic Receptor ◽

Contractile Response ◽

Bilateral Adrenalectomy ◽

Gastric Distension ◽

Adrenergic Blockade ◽

Receptor Stimulation

There is presently little information on the efferent mechanisms responsible for the reflex cardiovascular activation during passive gastric distension. Therefore, 40 cats anesthetized with alpha-chloralose were studied with passive gastric balloon distention before and during 1) two repeated gastric distensions, 2) beta-adrenergic blockade with propranolol, 3) alpha-adrenergic blockade with phentolamine, or 4) bilateral adrenalectomy. Before and during each distension mean arterial pressure, heart rate, cardiac output, rate of rise of left ventricular pressure (dP/dt) at 40 mmHg developed pressure and calculated systemic vascular resistance were determined. Repeated gastric distension caused similar hemodynamic responses without tachyphylaxis. beta-Blockade significantly reduced the increase in dP/dt from 893 +/- 362 to 150 +/- 63 mmHg/s. alpha-Blockade significantly altered the changes in mean arterial pressure from 33 +/- 5.0 to -2 +/- 4.7 mmHg and systemic vascular resistance from 0.114 +/- 0.019 to 0.004 +/- 0.031 peripheral resistance units. Bilateral adrenalectomy significantly diminished the contractile response from 525 +/- 107 to 50 +/- 85 mmHg/s but did not significantly alter the pressor and vasoconstrictor responses. We conclude that, during passive gastric distension in cats, the increase in myocardial contractility is mediated by beta-adrenergic-receptor stimulation, whereas the arterial vasoconstrictor and pressor responses are mediated by alpha-adrenergic receptor stimulation. Additionally, during gastric distension a substantial portion of the contractile response is dependent on the integrity of the adrenal glands.

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Peripheral circulatory control of preload-afterload mismatch with angiotensin in dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.253.1.h126 ◽

1987 ◽

Vol 253 (1) ◽

pp. H126-H132

Author(s):

R. W. Lee ◽

L. D. Lancaster ◽

D. Buckley ◽

S. Goldman

Keyword(s):

Heart Rate ◽

Cardiac Output ◽

Stroke Volume ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Arterial Compliance ◽

Peripheral Circulation ◽

Aortic Pressure ◽

Venous Compliance ◽

Mean Aortic Pressure

To determine whether changes in the venous circulation were responsible for preload-afterload mismatch with angiotensin, we examined the changes in the heart and the peripheral circulation in six splenectomized dogs after ganglion blockade during an angiotensin infusion to increase mean aortic pressure 25 and then 50%. The peripheral circulation was evaluated by measuring mean circulatory filling pressure (MCFP), arterial compliance, and venous compliance. A 25% increase in mean aortic pressure increased MCFP from 6.2 +/- 0.3 to 7.6 +/- 0.3 mmHg (P less than 0.001) but did not change cardiac output, heart rate, or stroke volume. Systemic vascular resistance increased (P less than 0.01) from 0.50 +/- 0.02 to 0.59 +/- 0.03 mmHg X min X kg X ml-1. Arterial and venous compliances decreased (P less than 0.01) from 0.08 +/- 0.03 to 0.06 +/- 0.03 ml X mmHg-1 X kg-1 and from 2.1 +/- 0.1 to 1.6 +/- 0.1 ml X mmHg-1 X kg-1, respectively. A 50% elevation in mean aortic pressure increased MCFP from 7.1 +/- 0.4 to 9.5 +/- 0.9 mmHg (P less than 0.001) but did not change heart rate. At this level of aortic pressure, cardiac output and stroke volume decreased (P less than 0.01) 12 and 19%, respectively, whereas systemic vascular resistance increased (P less than 0.001) from 0.48 +/- 0.03 to 0.83 +/- 0.05 mmHg X min X kg X ml-1. Arterial and venous compliances decreased (P less than 0.01) from 0.08 +/- 0.01 to 0.05 +/- 0.01 ml X mmHg-1 X kg-1 and from 2.1 +/- 0.1 to 1.4 +/- 0.1 ml X mmHg-1 X kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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Influence of critical closing pressure on systemic vascular resistance and total arterial compliance: A clinical invasive study

Archives of Cardiovascular Diseases ◽

10.1016/j.acvd.2017.03.008 ◽

2017 ◽

Vol 110 (12) ◽

pp. 659-666 ◽

Cited By ~ 4

Author(s):

Denis Chemla ◽

Edmund M.T. Lau ◽

Philippe Hervé ◽

Sandrine Millasseau ◽

Mabrouk Brahimi ◽

...

Keyword(s):

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Arterial Compliance ◽

Total Arterial Compliance ◽

Critical Closing Pressure ◽

Closing Pressure

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Arterial Stiffness Is Associated With QTc Interval Prolongation in Patients With Heart Failure

Biological Research For Nursing ◽

10.1177/1099800417737835 ◽

2017 ◽

Vol 20 (3) ◽

pp. 255-263

Author(s):

Salah Al-Zaiti ◽

Samir Saba ◽

Rodolfo Pike ◽

Jennifer Williams ◽

Fadi Khraim

Keyword(s):

Heart Failure ◽

Arterial Stiffness ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Arterial Compliance ◽

Qtc Interval ◽

Interval Prolongation ◽

Indirect Measure ◽

Total Arterial Compliance ◽

Qtc Interval Prolongation

Background: A prolonged corrected QT (QTc) interval is a known risk factor for adverse cardiac events. Understanding the determinants and physiologic correlates of QTc is necessary for selecting proper strategies to reduce the risk of adverse events in high-risk patients. We sought to evaluate the role of arterial stiffness in heart failure as a determinant of QTc prolongation. Method: This was an observational study that recruited ambulatory heart failure patients (New York Heart Association Classes I–II) from an outpatient heart failure clinic. In the supine resting position, consented patients underwent noninvasive 12-lead electrocardiograph (ECG) and hemodynamic monitoring using BioZ Dx impedance cardiography. ECGs were evaluated by a reviewer blinded to clinical data, and QTc interval was automatically computed. Patients with pacing or bundle branch block (BBB) were analyzed separately. Strengths of associations were evaluated using Pearson’s r coefficients and multivariate linear regression. Results: The final sample ( N = 44) was 62 ± 13 years of age and 64% male with ejection fraction of 34% ± 12%. At univariate level, QTc interval moderately ( r > .50) correlated with cardiac output, left cardiac work index, systemic vascular resistance, and total arterial compliance in patients with intrinsically narrow QRS complexes. At the multivariate level, increasing systemic vascular resistance and decreasing total arterial compliance remained independent predictors of widening QTc interval in this group ( R2 = .54). No significant correlations were seen in patients with pacing or BBB. Conclusions: In the absence of conduction abnormalities, magnitude of arterial stiffness, an indirect measure of endothelial dysfunction, is associated with QTc interval prolongation.

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