Selective large coronary endothelial dysfunction in conscious dogs with chronic coronary pressure overload

1998 ◽  
Vol 274 (2) ◽  
pp. H539-H551 ◽  
Author(s):  
Bijan Ghaleh ◽  
Luc Hittinger ◽  
Song-Jung Kim ◽  
Raymond K. Kudej ◽  
Mitsunori Iwase ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Perfusion Pressure ◽  
Pressure Overload ◽  
Coronary Perfusion Pressure ◽  
Conscious Dogs ◽  
Systemic Hypertension ◽  
Coronary Perfusion ◽  
Coronary Pressure ◽  
Large Coronary Arteries

Coronary vascular responses to acetylcholine (ACh, 3 μg/kg iv), nitroglycerin (NTG, 25 μg/kg iv), and a 20-s coronary artery occlusion (reactive hyperemia, RH) were investigated in seven conscious dogs with severe left ventricular (LV) hypertrophy and chronic coronary pressure overload (CCPO) due to supravalvular aortic banding and in seven control dogs. All dogs were instrumented for measurement of ultrasonic coronary diameter (CD) and Doppler coronary blood flow (CBF). LV-to-body weight ratio was increased by 82% in CCPO dogs. In control dogs, ACh increased CD (+5.9 ± 1.7%). This response was reduced ( P < 0.05) in CCPO dogs (+1.9 ± 0.9%). Similarly, flow-mediated increases in CD after RH were blunted ( P < 0.01) in CCPO (+2.1 ± 0.8) vs. control dogs (+6.8 ± 1.8%). In contrast, ACh and RH increased CBF similarly in both groups. Increases in both CD and CBF to NTG were not different between control dogs and CCPO. Peak systolic CBF velocity was greater, P< 0.01, in CCPO (94 ± 17 cm/s) compared with control (35 ± 7 cm/s) dogs, most likely secondary to the increased systolic coronary perfusion pressure (215 vs. 130 mmHg). Histological analyses of large coronary arteries in CCPO revealed medial thickening, intimal thickening, and disruption of the internal elastic lamina and endothelium. In contrast, small intramyocardial arterioles failed to show the intimal and endothelial lesions. Thus, in CCPO selective to the coronary arteries, i.e., a model independent from systemic hypertension and enhanced levels of plasma renin activity, endothelial control was impaired for both flow-mediated and receptor-mediated large coronary artery function, which could be accounted for by the major morphological changes in the large coronary arteries sparing the resistance vessels. The mechanism may involve chronically elevated systolic coronary perfusion pressure, CBF velocity, and potential disruption of laminar flow patterns.

Downregulation of ventricular contractile function during early ischemia is flow but not pressure dependent

1998 ◽  
Vol 275 (5) ◽  
pp. H1520-H1523 ◽  
Author(s):  
Miao-Xiang He ◽  
H. Fred Downey
Keyword(s):  
Coronary Artery ◽  
Perfusion Pressure ◽  
Contractile Function ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Rat Hearts ◽  
Myocardial Contractile Force ◽  
Myocardial Contractile ◽  
Artery Obstruction

The mechanism responsible for the abrupt fall in myocardial contractile function following coronary artery obstruction is unknown. The “vascular collapse theory” hypothesizes that the fall in coronary perfusion pressure after coronary artery obstruction is responsible for contractile failure during early ischemia. To test the role of vascular collapse in downregulating myocardial contractile force at the onset of ischemia, coronary flow of isolated rat hearts was abruptly decreased by 50, 70, 85, and 100% of baseline, and subsequent changes in coronary perfusion pressure and ventricular function were recorded at 0.5-s intervals. At 1.5 s after flow reductions ranging from 50 to 100%, decreases in contractile function did not differ, although perfusion pressure varied significantly from 45 ± 1 to 20 ± 2 mmHg. When function fell to 50% of baseline, perfusion pressures ranged from 35 ± 0.5 to 2.5 ± 1 mmHg for flow reductions ranging from 50 to 100%. Identical contractile function at widely differing coronary perfusion pressures is incompatible with the vascular collapse theory.

Coronary pressure-flow autoregulation protects myocardium from pressure-induced changes in oxygen consumption

1994 ◽  
Vol 266 (6) ◽  
pp. H2359-H2368 ◽  
Author(s):  
X. J. Bai ◽  
T. Iwamoto ◽  
A. G. Williams ◽  
W. L. Fan ◽  
H. F. Downey
Keyword(s):  
Oxygen Consumption ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Segment Length ◽  
Coronary Perfusion ◽  
Pressure Flow ◽  
Coronary Pressure ◽  
Anesthetized Dogs ◽  
Induced Changes

Pressure-flow autoregulation minimizes changes in coronary blood flow (CBF) when coronary perfusion pressure (CPP) is altered. This investigation determined if autoregulation also minimizes CPP-induced changes in coronary vascular volume (CVV) and CVV-dependent changes in myocardial oxygen consumption (MVO2). In 11 anesthetized dogs, the left anterior descending coronary artery was cannulated, and responses to 20-mmHg changes in CPP were examined over a range of CPP from 60 to 180 mmHg. Changes in CPP had no significant effect on systemic hemodynamics or on left ventricular end-diastolic segment length, end-systolic segment length, or percent segment shortening. In hearts with effective pressure-flow autoregulation [closed-loop gain (GC) > 0.4], CVV increased 0.06%/mmHg change in CPP. For the same hearts, MVO2 increased 0.04%/mmHg change in CPP. In hearts with ineffective autoregulation (GC < 0.4), CVV increased 0.97%/mmHg (P < 0.001 vs. autoregulating hearts), and MVO2 increased 0.41%/mmHg (P < 0.001 vs. autoregulating hearts). MVO2 and CVV were correlated (r = 0.69, P < 0.0001) independently of autoregulatory capability, but only when autoregulation was poor and capacitance was elevated did CPP significantly affect MVO2. We conclude that pressure-flow autoregulation protects myocardium from CPP-induced changes in CVV, which in turn produces changes in oxygen consumption.

Downward shift of coronary pressure-flow relationship following a brief period of ischemia in dogs

1995 ◽  
Vol 269 (4) ◽  
pp. H1237-H1245
Author(s):  
T. Morioka ◽  
M. Kitakaze ◽  
T. Minamino ◽  
S. Takashima ◽  
K. Node ◽  
...  
Keyword(s):  
Blood Flow ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Pressure Flow ◽  
Coronary Pressure ◽  
Downward Shift ◽  
Myocardial Contractile ◽  
Hyperemic Flow ◽  
Fractional Shortening

This study was undertaken to test whether a brief period of ischemia affects the coronary pressure-flow relationship during reduction of coronary perfusion pressure (CPP). The left anterior descending coronary artery was cannulated and perfused with blood from the left carotid artery in 40 open-chest dogs. Coronary blood flow (CBF) was measured during intracoronary administrations of papaverine and adenosine. The coronary pressure-flow relationship was assessed during transient reduction of CPP from 100 to 30 mmHg. Coronary hyperemic flow due to adenosine and papaverine was attenuated 30 min after transient 10- and 15-min periods of ischemia. In the group of transient 10-min ischemia, both fractional shortening (FS) and CBF returned to the preischemic values at 30 and 60 min of reperfusion; however, marked decreases in CBF (35 +/- 5 vs. 56 +/- 4 ml.100 g-1.min-1 at CPP = 60 mmHg, P < 0.01) during graded reductions in CPP were observed. The endomyocardial blood flow was reduced relative to the control condition. Furthermore, both FS (6 +/- 1 vs. 14 +/- 1% at CPP = 60 mmHg, P < 0.01) and lactate extraction ratio (-41 +/- 15 vs. 1 +/- 6% at CPP = 60 mmHg, P < 0.05) were decreased. The downward shift of the CPP-CBF relationship and the deterioration of myocardial contractile and metabolic function during reduction of CPP were restored 60 min after the onset of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of low perfusion pressure on effect of endothelin on coronary vascular bed

1991 ◽  
Vol 260 (3) ◽  
pp. H893-H901 ◽  
Author(s):  
J. P. Clozel ◽  
U. Sprecher
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Perfusion Pressure ◽  
Coronary Spasm ◽  
Electromagnetic Flowmeter ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Cross Sectional ◽  
Coronary Vasoconstriction

The goal of this study was to evaluate the influence of low coronary perfusion pressure on the coronary vasoconstriction induced by endothelin. For this purpose, the circumflex coronary arteries of 12 open-chest dogs were cannulated and perfused at a controlled pressure. Total coronary blood flow was measured with an electromagnetic flowmeter and the transmural distribution of coronary blood flow with the radioactive microspheres technique. In addition, the circumflex coronary artery diameter was measured by sonomicrometry with piezoelectric crystals, and the coronary cross-sectional area was calculated. At a coronary perfusion pressure of 100 mmHg, endothelin induced a marked coronary vasoconstriction and a redistribution of coronary blood flow toward the endocardium. At a low coronary perfusion pressure of 40 mmHg, these effects of endothelin were still present. The constriction of the large coronary artery occurred even with a lower dose of endothelin at a low coronary perfusion pressure compared with the normal perfusion pressure. This was not the case when angiotensin II was given the same way. We conclude that endothelin is a potent coronary vasoconstrictor even at a low perfusion pressure. Thus one may speculate that endothelin plays a role in the coronary spasm which has been shown in patients with angina pectoris.

Defective endothelium-mediated control of coronary circulation in conscious dogs after heart failure

1994 ◽  
Vol 266 (2) ◽  
pp. H670-H680 ◽  
Author(s):  
J. Wang ◽  
N. Seyedi ◽  
X. B. Xu ◽  
M. S. Wolin ◽  
T. H. Hintze
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Coronary Circulation ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Large Coronary Arteries

The goal of this study was to determine whether coronary endothelial function was altered after pacing-induced heart failure in conscious dogs. Fourteen mongrel dogs were chronically instrumented for measurements of systemic hemodynamics, left circumflex coronary artery diameter (CD) and blood flow, and for left ventricular pacing for 4 wk. Heart failure developed during this pacing regimen and was characterized by a significant reduction in arterial pressure, an increase in left atrial pressure, a resting tachycardia, a depression of left ventricular dP/dt to isoproterenol injection, a significant reduction of the slope of the end-systolic pressure-diameter relationship, and all of the characteristic clinical signs. During heart failure, the dilation of CD after release of a brief coronary artery occlusion, acetylcholine, and arachidonic acid was attenuated, whereas prostaglandin (PG) I2- and nitroglycerin-induced dilations of CD were unchanged. The coronary blood flow responses to occlusion, acetylcholine, and nitroglycerin were depressed, but not to PG. Large coronary arteries and microvessels were isolated from normal and failing hearts. Both isolated large coronary arteries and microvessels from failing hearts produced significantly less nitrite, the immediate metabolite of nitric oxide in aqueous solution, than those of normal hearts. Thus endothelium-mediated control of the coronary circulation was depressed during heart failure. A decrease in the production of nitric oxide-endothelium-derived relaxing factor was most likely responsible for this depression.

Ouabain-induced reflex coronary vasodilatation mediated by cardiac receptors

1984 ◽  
Vol 246 (5) ◽  
pp. H664-H670 ◽  
Author(s):  
B. Trimarco ◽  
S. Chierchia ◽  
B. Ricciardelli ◽  
A. Cuocolo ◽  
M. Volpe ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Reflex Response ◽  
Coronary Perfusion ◽  
Coronary Vasodilator ◽  
Coronary Vasodilatation ◽  
Combined Administration ◽  
Anesthetized Dogs ◽  
Cardiac Receptors

Experiments were performed to determine the effects of digitalis-induced stimulation of cardiac receptors on the coronary circulation. In chloralose-anesthetized dogs, left circumflex coronary artery was perfused at constant flow, and heart rate was maintained constant by electric pacing. Ouabain injection in the perfused coronary artery produced a significant decrease in coronary perfusion pressure. Epicardial application of lidocaine completely blocked the reflex response. Vagotomy also prevented this reflex response. Sympathetic blockade with intravenous guanethidine or intracoronary phentolamine partially reduced the reflex coronary vasodilatation. Intracoronary atropine also partially reduced the coronary vasodilator response to ouabain. The combined administration of guanethidine and atropine completely abolished the coronary reflex response. These data demonstrate that ouabain can evoke reflex coronary vasodilation by stimulating cardiac receptors. This reflex response is mediated by activating cholinergic vasodilator fibers and inhibiting sympathetic vasoconstrictor fibers.

Effects of epoxyeicosatrienoic acids on isolated hearts and ventricular myocytes

1993 ◽  
Vol 264 (4) ◽  
pp. H1154-H1160 ◽  
Author(s):  
M. P. Moffat ◽  
C. A. Ward ◽  
J. R. Bend ◽  
T. Mock ◽  
P. Farhangkhoee ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cell Function ◽  
Perfusion Pressure ◽  
Ventricular Myocytes ◽  
Coronary Perfusion Pressure ◽  
Low Flow ◽  
Epoxyeicosatrienoic Acids ◽  
Coronary Perfusion ◽  
Isolated Hearts ◽  
Coronary Pressure

Effects of cytochrome P-450 metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETS; 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET), were examined in isolated guinea pig hearts and ventricular myocytes. Addition of 1-16 ng/ml EETs to normal isolated hearts produced no effects on contractility or coronary pressure. In hearts subjected to 60 min of low-flow ischemia, impairment of contractility and declines in heart rate and coronary perfusion pressure were similar in the presence or absence of 1 ng/ml EETs. However, in the presence of either 5,6- or 11,12-EET, recovery was delayed for the first 10 min only. No significant differences were found in any group regarding heart rate, coronary perfusion pressure, or energy metabolite content after 30 min of reperfusion. In myocytes, both 5,6- and 11,12-EET (100 pg/ml, 1.0 ng/ml, and 20 ng/ml) significantly increased cell shortening as well as intracellular calcium concentrations, whereas 8,9- or 14,15-EET was without effect on these parameters. These results describe for the first time the direct effects of various EETs on cardiac cell function as well as their ability to modulate some of the myocardial responses to postischemic reperfusion. The results suggest a potential role for these substances in the response of the heart to pathological insult.

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