Effect of sildenafil on coronary active and reactive hyperemia

2000 ◽  
Vol 279 (5) ◽  
pp. H2319-H2325 ◽  
Author(s):  
Yingjie Chen ◽  
Ruisheng Du ◽  
Jay H. Traverse ◽  
Robert J. Bache
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Coronary Flow ◽  
Reactive Hyperemia ◽  
Time Derivative ◽  
Systolic Pressure ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Resistance Vessel ◽  
Phosphodiesterase Type

Sildenafil, a selective inhibitor of phosphodiesterase type 5, produces relaxation of isolated epicardial coronary artery segments by causing accumulation of cGMP. Because shear-induced nitric oxide-dependent vasodilation is mediated by cGMP, this study was performed to determine whether sildenafil would augment the coronary resistance vessel dilation that occurs during the high-flow states of exercise or reactive hyperemia. In chronically instrumented dogs, sildenafil (2 mg/kg per os) augmented the vasodilator response to acetylcholine, with a leftward shift of the dose-response curve relating coronary flow to acetylcholine dose. Sildenafil caused a 6.7 ± 2.1 mmHg decrease of mean aortic pressure, which was similar at rest and during treadmill exercise ( P < 0.05), with no change of heart rate, left ventricular (LV) systolic pressure, or LV maximal first time derivative of LV pressure. Sildenafil tended to increase myocardial blood flow at rest and during exercise (mean increase = 14 ± 3%; P < 0.05 by ANOVA), but this was associated with a significant decrease in hemoglobin, so that the relationship between myocardial oxygen consumption and oxygen delivery to the myocardium (myocardial blood flow × arterial O2 content) was unchanged. Furthermore, sildenafil did not alter coronary venous Po 2, indicating that the coupling between myocardial blood flow and myocardial oxygen demands was not altered. In addition, sildenafil did not alter the peak coronary flow rate, debt repayment, or duration of reactive hyperemia that followed a 10-s coronary occlusion. The findings suggest that cGMP-mediated resistance vessel dilation contributes little to the increase in myocardial flow that occurs during exercise or reactive hyperemia.

Effect of PDE5 inhibition on coronary hemodynamics in pacing-induced heart failure

2003 ◽  
Vol 284 (5) ◽  
pp. H1513-H1520 ◽  
Author(s):  
YingJie Chen ◽  
Jay H. Traverse ◽  
Mingxiao Hou ◽  
Yunfang Li ◽  
Ruisheng Du ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Time Derivative ◽  
Systolic Pressure ◽  
Coronary Vessels ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Pde5 Inhibition ◽  
Rapid Ventricular Pacing ◽  
Phosphodiesterase Type

Inhibition of phosphodiesterase type 5 (PDE5) can relax systemic and coronary vessels by causing accumulation of cGMP. Both the endothelial dysfunction with decreased nitric oxide production and increased natriuretic peptide levels in congestive heart failure (CHF) have the potential to alter cGMP production, thereby influencing the response to PDE5 inhibition. Consequently, this study examined the effects of PDE5 inhibition with sildenafil in dogs with CHF produced by rapid ventricular pacing. CHF resulted in decreases of left ventricular (LV) systolic pressure, coronary blood flow, and the maximal first time derivative of LV pressure (LV dP/d t max) at rest and during treadmill exercise compared with normal, whereas resting LV end-diastolic pressure increased from 10 ± 1.4 to 23 ± 1.4 mmHg. Sildenafil (2 and 10 mg/kg per os) caused a 5- to 6-mmHg decrease of aortic pressure ( P < 0.05), with no change of heart rate, LV systolic pressure, or LV dP/d t max. Sildenafil caused no change in coronary flow or myocardial oxygen consumption in animals with CHF at rest or during exercise. In contrast to findings in normal animals, sildenafil did not augment endothelium-dependent coronary vasodilation in response to acetylcholine in animals with CHF. Furthermore, Western blotting showed decreased PDE5 protein expression in myocardium from failing hearts. These findings demonstrate that PDE5 contributes little to regulation of coronary hemodynamics in CHF.

LV pressure-volume area and oxygen consumption: evaluation in intact dog by fast CT

1990 ◽  
Vol 258 (4) ◽  
pp. H1208-H1215
Author(s):  
N. Chung ◽  
X. Wu ◽  
K. R. Bailey ◽  
E. L. Ritman
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Myocardial Blood Flow ◽  
Myocardial Oxygen Consumption ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Adrenergic Blockade ◽  
Ct Scanner ◽  
Beta Adrenergic ◽  
The Relationship

The relationship between left ventricular (LV) myocardial oxygen consumption (MVO2) and LV systolic pressure-volume area (PVA) was investigated in anesthetized closed-chest dogs with intact reflexes and subsequently with beta-adrenergic blockade, with or without simultaneous muscarinic blockade. LV chamber volumes were measured using a fast computerized tomography (CT) scanner (dynamic spatial reconstructor, DSR) at 33-ms intervals. Myocardial blood flow was measured from the DSR scans of aortic root angiograms. With intact reflexes, LV MVO2 (Y) related to PVA (X) values as Y = (4.28 +/- 1.81)X + (1.94 +/- 6.0) (n = 24) (mJ.g-1.cycle-1). With beta-adrenergic blockade, LV MVO2 (Y) related to PVA (X) value as Y = (4.24 +/- 1.03)X - (6.43 +/- 6.5), (n = 9) (mJ.g-1.cycle-1). With beta-adrenergic and muscarinic blockade, LV MVO2 (Y) related to PVA (X) value as Y = (2.84 +/- 1.72)X + (3.51 +/- 5.15), (n = 13) (mJ.g-1.cycle-1). The slopes of these regressions are higher than the slopes demonstrated by others in isolated ventricles but very similar to those demonstrated in open-chest dogs.

Depression of regional blood flow and wall thickening after brief coronary occlusions

1978 ◽  
Vol 234 (6) ◽  
pp. H653-H659 ◽  
Author(s):  
G. R. Heyndrickx ◽  
H. Baig ◽  
P. Nellens ◽  
I. Leusen ◽  
M. C. Fishbein ◽  
...  
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Coronary Occlusion ◽  
Reactive Hyperemia ◽  
Left Ventricular ◽  
Regional Myocardial Blood Flow ◽  
Wall Thickening ◽  
Flow Ratio ◽  
Systolic Wall Thickening ◽  
Regional Myocardial Blood

The effects of a 15-min coronary occlusion and subsequent reperfusion were investigated in conscious dogs previously instrumented for measurement of left ventricular pressure, dP/dt, regional wall thickening, electrograms, and myocardial blood flow. Coronary occlussion reduced overall left ventricular function only slightly but eliminated systolic wall thickening in the ischemic zone and reduced regional myocardial blood flow in the ischemic zone from 1.04 +/- 0.04 to 0.27 +/- 0.02 ml/min per g and the endo/epi flow ratio from 1.23 +/- 0.04 to 0.44 +/- 0.04, while S-T segment elevation increased from 1.1 +/- 0.3 to 8.2 +/- 0.9 mV. After release of the occlusion, S-T segment elevation disappeared within 1 min while reactive hyperemia in the previously occluded artery and a transient increase in cardiac diastolic wall thickness occurred and then subsided by 15 min. In contrast, systolic wall thickening and the endo/epi flow ratio remained significantly depressed for more than 3 h. Thus reperfusion after a 15 minute coronary occlusion results in a prolonged period of reduced regional myocardial blood flow, particularly in the endocardial layers, which correlates with the prolonged depression of regional myocardial shortening and wall thickening.

Characterization of energy metabolism and blood flow distribution in myocardial ischemia in hemorrhagic shock

1997 ◽  
Vol 273 (2) ◽  
pp. H600-H607 ◽  
Author(s):  
K. Miyazaki ◽  
S. Hori ◽  
S. Inoue ◽  
T. Adachi ◽  
M. Bessho ◽  
...  
Keyword(s):  
Blood Flow ◽  
Myocardial Ischemia ◽  
Hemorrhagic Shock ◽  
Reactive Hyperemia ◽  
Flow Distribution ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Cross Sectional ◽  
Axis Length ◽  
High Level

To characterize the mechanisms for myocardial ischemia induced by hemorrhagic shock, 29 dogs were subjected to hemorrhage at a mean aortic pressure (MAoP) of 30-60 mmHg. After 10 min of hemorrhage, the beating hearts were rapidly cross sectioned and freeze clamped to visualize the two-dimensional distribution of myocardial ischemia with NADH fluorescence (NADH-F) in 22 dogs. NADH-F was developed at an MAoP of 40 mmHg or less and involved both the subendocardial half and the subepicardial half of the left ventricle [34 +/- 14 vs. 20 +/- 14% (P < 0.05) and 65 +/- 16 vs. 52 +/- 15% (not significant) of the cross-sectional area of the left ventricular slice at MAoP levels of 40 and 30 mmHg, respectively]. Magnified NADH-F photography demonstrated heterogeneously distributed microischemic lesions with a columnar shape (mode of short-axis length, 60-80 microns). NADH-F-guided microsamplings revealed higher NADH and lactate concentrations in a positive NADH-F area than those in a negative NADH-F area. The ratio of endocardial to epicardial blood flow was maintained at a relatively high level (1.07 +/- 0.07 and 0.88 +/- 0.07 at MAoP levels of 40 and 30 mmHg, respectively; n = 7 dogs), and the reactive hyperemia was preserved as well. In conclusion, myocardial ischemia in early hemorrhagic shock was characterized by minimal transmural heterogeneity and marked heterogeneity between contiguous small regions.

Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts

2002 ◽  
Vol 282 (4) ◽  
pp. H1359-H1369 ◽  
Author(s):  
Gregory B. Dalshaug ◽  
Thomas D. Scholz ◽  
Oliva M. Smith ◽  
Kurt A. Bedell ◽  
Christopher A. Caldarone ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Myocardial Blood Flow ◽  
Coronary Flow Reserve ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Blood Flows ◽  
Flow Reserve ◽  
Arterial Blood

To test the hypothesis that coronary flow and coronary flow reserve are developmentally regulated, we used fluorescent microspheres to investigate the effects of acute (6 h) pulmonary artery banding (PAB) on baseline and adenosine-enhanced right (RV) and left ventricular (LV) blood flow in two groups of twin ovine fetuses (100 and 128 days of gestation, term 145 days, n = 6 fetuses/group). Within each group, one fetus underwent PAB to constrict the main pulmonary artery diameter by 50%, and the other twin served as a nonbanded control. Physiological measurements were made 6 h after the surgery was completed; tissues were then harvested for analysis of selected genes that may be involved in the early phase of coronary vascular remodeling. Within each age group, arterial blood gas values, heart rate, and mean arterial blood pressure were similar between control and PAB fetuses. Baseline endocardial blood flow in both ventricles was greater in 100 than 128-day fetuses (RV: 341 ± 20 vs. 230 ± 17 ml · min−1 · 100 g−1; LV: 258 ± 18 vs. 172 ± 23 ml · min−1 · 100 g−1, both P < 0.05). In both age groups, RV and LV endocardial blood flows increased significantly in control animals during adenosine infusion and were greater in PAB compared with control fetuses. After PAB, adenosine further increased RV blood flow in 128-day fetuses (from 416 ± 30 to 598 ± 33 ml · min−1 · 100 g−1, P < 0.05) but did not enhance blood flow in 100-day animals (490 ± 59 to 545 ± 42 ml · min−1 · 100 g−1, P > 0.2). RV vascular endothelial growth factor and Flk-1 mRNA levels were increased relative to controls ( P < 0.05) in 128 but not 100-day PAB fetuses. We conclude that in the ovine fetus, developmentally related differences exist in 1) baseline myocardial blood flows, 2) the adaptive response of myocardial blood flow to acute systolic pressure load, and 3) the responses of selected genes involved in vasculogenesis to increased load in the fetal myocardium.

Effect of systole on coronary pressure-flow relations in the right ventricle of the dog

1980 ◽  
Vol 238 (4) ◽  
pp. H481-H486 ◽  
Author(s):  
R. F. Bellamy ◽  
H. S. Lowensohn
Keyword(s):  
Blood Flow ◽  
Right Ventricular ◽  
Coronary Blood Flow ◽  
Reactive Hyperemia ◽  
Systolic Pressure ◽  
Aortic Pressure ◽  
Ventricular Pressure ◽  
Pressure Flow ◽  
Ventricular Systole ◽  
Coronary Pressure

Downey and Kirk's hypothesis that ventricular systole inhibits coronary blood flow by forming vascular waterfalls was examined in conscious chronically instrumented dogs by studying the effect of right ventricular systole on right coronary blood flow. Diastolic and systolic pressure-flow relations were constructed at resting-level flow and peak flow reactive hyperemia from phasic pressure and flow tracings recorded in nine dogs with right ventricular pressures ranging between 14 and 154 mmHg. Linear relations were found between aortic pressure and right coronary flow during diastolic and during systole when peak ventricular pressure was less than systemic. At resting-level flow and when peak ventricular pressure was less than one-half systemic, systole translated the diastolic relation to a higher zero-flow-intercept pressure and did not alter the slope of the relation. We interpret the data as showing that ventricular systole inhibits coronary blood flow by augmenting a vascular waterfall mechanism that exists during diastole.

Myocardial blood flow and VO2 in lambs with an aortopulmonary shunt during strenuous exercise

1993 ◽  
Vol 264 (3) ◽  
pp. H938-H945
Author(s):  
J. W. Gratama ◽  
J. J. Meuzelaar ◽  
M. Dalinghaus ◽  
J. H. Koers ◽  
A. M. Gerding ◽  
...  
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Left Atrial ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Strenuous Exercise ◽  
Additional Load ◽  
Volume Load ◽  
Left Ventricular Output ◽  
Myocardial O2 Consumption

To determine how much myocardial O2 consumption (VO2) would increase during an additional load on the heart in shunt as compared with control lambs, we studied 12 7-wk-old lambs with an aortopulmonary left-to-right shunt (59 +/- 3% of left ventricular output, mean +/- SE) and 11 control lambs during exercise at 80% of their predetermined peak VO2 (VO2peak), at 12 +/- 1 days after surgery. During exercise, systolic aortic pressure increased by 25% in the two groups. Left atrial pressure and left ventricular stroke volume did not change significantly and remained considerably higher in shunt than in control lambs. Heart rate, however, increased less in shunt than in control lambs (163 +/- 8 to 235 +/- 8 vs. 107 +/- 7 to 230 +/- 8 beats/min). The same was true for left ventricular myocardial blood flow (245 +/- 19 to 391 +/- 27 vs. 128 +/- 10 to 320 +/- 45 ml.min-1 x 100 g-1) and myocardial VO2 (847 +/- 101 to 1,692 +/- 136 vs. 528 +/- 58 to 1,579 +/- 178 mumol O2 x min-1 x 100 g-1). We conclude that, despite the volume load, myocardial VO2 of shunt lambs does not increase to a greater extent than in control lambs during a considerable additional load on the heart.

Effect of NO on transmural distribution of blood flow in hypertrophied left ventricle during exercise

1999 ◽  
Vol 276 (4) ◽  
pp. H1305-H1312 ◽  
Author(s):  
Dirk J. Duncker ◽  
Jay H. Traverse ◽  
Yutaka Ishibashi ◽  
Robert J. Bache
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Aortic Banding ◽  
No Donor ◽  
Subendocardial Ischemia ◽  
Intracoronary Infusion ◽  
Control Exercise

When exercise in the presence of a coronary artery stenosis results in subendocardial ischemia, administration of a nitric oxide (NO) donor increases subendocardial blood flow, whereas NO synthesis blockade worsens subendocardial hypoperfusion. Because left ventricular hypertrophy (LVH) is also associated with subendocardial hypoperfusion during exercise, this study tested the hypothesis that alterations of NO availability can similarly influence subendocardial blood flow in the hypertrophied heart. Studies were performed in seven dogs in which ascending aortic banding resulted in an 80% increase in LV weight. Myocardial blood flow was measured with microspheres during treadmill exercise that increased heart rates to 216 ± 8 beats/min. During control exercise, mean myocardial blood flow in animals with LVH was similar to that in historic controls, but the ratio of subendocardial to subepicardial blood flow was lower in animals with hypertrophy (0.88 ± 0.07) than in controls (1.36 ± 0.08; P < 0.05). Blockade of NO synthesis with N G-nitro-l-arginine (l-NNA; 1.5 mg/kg ic) caused no change in heart rate or LV systolic pressure during exercise. Furthermore, l-NNA did not worsen subendocardial hypoperfusion during exercise. Intracoronary infusion of nitroglycerin (0.4 μg ⋅ kg−1 ⋅ min−1) did not significantly alter either mean blood flow or the transmural distribution of perfusion during exercise in the hypertrophied hearts. Thus, unlike the subendocardial underperfusion that occurs when a stenosis limits coronary blood flow, alterations of NO availability did not alter subendocardial hypoperfusion in the hypertrophied hearts.

Computer Simulation of Coronary Flow Waveforms during Caval Occlusion

2009 ◽  
Vol 48 (02) ◽  
pp. 113-122 ◽  
Author(s):  
D. Neglia ◽  
G. Ferrari ◽  
F. Bernini ◽  
M. Micalizzi ◽  
A L’Abbate ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiovascular System ◽  
Coronary Flow ◽  
Coronary Circulation ◽  
Left Ventricular Pressure ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Lumped Parameter ◽  
Flow Waveforms

Summary Objectives: Mathematical modeling of the cardiovascular system is a powerful tool to extract physiologically relevant information from multi-parametric experiments. The purpose of the present work was to reproduce by means of a computer simulator, systemic and coronary measurements obtained by in vivo experiments in the pig. Methods: We monitored in anesthetized open-chest pig the phasic blood flow of the left descending coronary artery, aortic pressure, left ventricular pressure and volume. Data were acquired before, during, and after caval occlusion.Inside the software simulator (CARDIOSIM©) of the cardiovascular system, coronary circulation was modeled in three parallel branching sections. Both systemic and pulmonary circulations were simulated using a lumped parameter mathematical model. Variable elastance model reproduced Starling’s law of the heart. Results: Different left ventricular pressure-volume loops during experimental caval occlusion and simulated cardiac loops are presented. The sequence of coronary flow-aortic pressure loops obtained in vivo during caval occlusion together with the simulated loops reproduced by the software simulator are reported. Finally experimental and simulated instantaneous coronary blood flow waveforms are shown. Conclusions: The lumped parameter model of the coronary circulation, together with the cardiovascular system model, is capable of reproducing the changes during caval occlusion, with the profound shape deformation of the flow signal observed during the in vivo experiment. In perspectives, the results of the present model could offer new tool for studying the role of the different determinants of myocardial perfusion, by using the coronary loop shape as a “sensor” of ventricular mechanics in various physiological and pathophysiological conditions.

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