Acute Phosphodiesterase 5 Inhibition Mimics Hemodynamic Effects of B-Type Natriuretic Peptide and Potentiates B-Type Natriuretic Peptide Effects in Failing But Not Normal Canine Heart
Paul R. Forfia, MD,
Myung Lee, MS,
Richard S. Tunin, MS,
Mobusher Mahmud, MD,
Hunter C. Champion, MD, PhD and
David A. Kass, MD*
Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland
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Figure 1 Hemodynamic Effects of BNP, SIL, or Both in Normal and Failing Hearts Assessed by Cardiac Pressure-Volume Loops
Representative left ventricular (LV) pressure-volume loops at baseline and after acute administration of B-type natriuretic peptide (BNP), sildenafil (SIL), or the combination of SIL + BNP. Top panels show pressure-volume loops for a non-failing dog (Normal) and the bottom panels for a dog after tachypacing-induced heart failure (Heart Failure).
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Figure 2 Baseline and Differential Change in Venous, Pulmonary, and Arterial Pressures to BNP, SIL, or Both in Normal and Failing Heart
Bar graphs illustrating the acute change in hemodynamics to B-type natriuretic peptide (BNP), sildenafil (SIL), or the combination of SIL + BNP in normal (left) and heart failure dogs (right). *p < 0.05 versus baseline;  p < 0.05 comparing SIL + BNP versus BNP alone; #p < 0.05 for the interaction between drug treatment and heart failure. CVP = central venous pressure; dPAP = diastolic pulmonary arterial pressure; MAP = mean arterial pressure; mPAP = mean pulmonary arterial pressure.
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Figure 3 Greater Decline in PVR by SIL ± BNP in Animals With Heart Failure Versus Control Animals
Bar graphs showing the change in pulmonary vascular resistance (PVR) in response to B-type natriuretic peptide (BNP), sildenafil (SIL), or the combination of SIL + BNP in non-failing (normal; solid bars) and failing (heart failure; hatched bars) dogs. *p < 0.05 versus baseline values.
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Figure 4 PDE5 Activity in Vascular and Renal Beds of Control and Heart Failure Animals
Bar graphs illustrating the percentage of total phoshodiesterase activity that is attributable to cyclic guanosine monophosphate-specific type 5 phosphodiesterase (PDE5) in vascular (A) and renal (B) tissue obtained from non-failing (normal) and failing (heart failure) dogs. *p < 0.05 versus values in normal dogs. cGMP = cyclic guanosine monophosphate; IMCD = inner medullary collecting ducts; IVC = inferior vena cava.
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Figure 5 BNP, cGMP, and Their Ratio in Plasma and Urine in Animals With Normal or Failing Hearts
Bar graphs showing the B-type natriuretic peptide (BNP) concentration (A), plasma cyclic guanosine monophosphate (cGMP) concentration (B), ratio of plasma cGMP to plasma BNP (C), urine cGMP concentration (D), and ratio of urine cGMP to plasma BNP (E) of normal (solid bars) and failing dogs (hatched bars) at baseline and in response to acute administration of BNP, sildenafil (SIL) (B only), and the combination of SIL + BNP. *p  0.03, #p = 0.06: within group comparison to baseline; p 0.03, ¶p < 0.005: between group (congestive heart failure [CHF] vs. normal) for same intervention;  p 0.04: within group, versus BNP alone.
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Figure 6 Urinary Flow and Sodium Excretion in Animals With Normal or Failing Hearts in Response to BNP, SIL, or Both Combined
Bar graphs demonstrating the effects of B-type natriuretic peptide (BNP), sildenafil (SIL), or the combination of SIL + BNP on urine flow rate and urine sodium excretion of normal (left; solid bars) and heart failure dogs (right; hatched bars). *p < 0.05 versus baseline.
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