Effects of vasopressin on the coronary circulation: reserve and regulation during ischemia

1985 ◽  
Vol 248 (4) ◽  
pp. H516-H522 ◽  
Author(s):  
M. A. Khayyal ◽  
C. Eng ◽  
D. Franzen ◽  
J. A. Breall ◽  
E. S. Kirk
Keyword(s):  
Blood Flow ◽  
Coronary Flow ◽  
Coronary Circulation ◽  
Reactive Hyperemia ◽  
Lactate Production ◽  
Coronary Perfusion ◽  
Coronary Vasculature ◽  
Blood Flow Reduction ◽  
Myogenic Factor ◽  
Hyperemic Flow

In 18 dogs, intracoronary infusion of vasopressin produced a 40% reduction in coronary flow without significantly affecting systemic hemodynamics. The blood flow reduction occurred in a uniform transmural pattern without evidence of a gradient. The reduction in coronary flow resulted in a decrease in regional contractility as determined by isometric strain gauge arches. The decrease in regional contractility was transiently reversed by bolus injection of adenosine into the perfusion line. This suggests that the reduction of blood flow due to vasopressin was causing ischemia. Evidence for ischemia was also supported by measurements of local vein and tissue lactate production. Despite the apparently ischemic conditions, the vascular bed demonstrated evidence for significant reserve and regulation. Pressure-flow relationships performed under control and during vasopressin infusion demonstrated that the coronary vasculature retained its ability to regulate or defend a given level of coronary flow over a range of coronary perfusion pressures. Vasopressin produced a mild decrease in the peak hyperemic flow after a 15-s coronary occlusion and shortened the duration of reactive hyperemia. These overall findings are compatible with a predominant vasoconstrictor effect on the distal coronary vasculature. A role for a myogenic factor in the control of the coronary circulation is suggested, which is amplified by vasopressin.

Alpha 2-adrenoceptor stimulation can augment coronary vasodilation maximally induced by adenosine in dogs

1989 ◽  
Vol 257 (1) ◽  
pp. H132-H140 ◽  
Author(s):  
M. Hori ◽  
M. Kitakaze ◽  
J. Tamai ◽  
K. Iwakura ◽  
A. Kitabatake ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Small Dose ◽  
Reactive Hyperemia ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Coronary Vasodilation ◽  
Beta Adrenoceptor ◽  
Adenosine Concentration ◽  
Hyperemic Flow

To determine whether alpha 2-adrenoceptor stimulation can augment adenosine-induced coronary vasodilation, 34 open-chest dogs were studied. When a small dose of clonidine (up to 0.24 micrograms.kg-1.min-1 ic) was administered under beta-adrenoceptor blockade, coronary blood flow [312 +/- 16 (SE) ml.100 g-1.min-1] maximally induced by intracoronary infusion of adenosine was further increased (P less than 0.05) by 66 +/- 16 ml.100 g-1.min-1, despite no significant changes in coronary perfusion pressure, myocardial oxygen consumption, and coronary venous adenosine concentration. However, when a larger dose of clonidine (0.36–0.60 micrograms.kg-1.min-1) was infused, adenosine-induced flow progressively decreased. This biphasic action of the alpha 2-adrenoceptor activity was also observed when the dose of norepinephrine was increased during alpha 1-adrenoceptor blockade with prazosin. Norepinephrine up to 0.24 micrograms.kg-1.min-1 (ic) further increased adenosine-induced coronary blood flow by 24 +/- 5% (P less than 0.001), whereas hyperemic flow was decreased by a larger dose of norepinephrine. In contrast to the alpha 2-adrenoceptor stimulation, the alpha 1-adrenoceptor stimulation (norepinephrine with yohimbine) progressively decreased coronary blood flow. Furthermore, with a small dose of clonidine, reactive hyperemic flow significantly increased compared with that without clonidine (303 +/- 13 vs. 355 +/- 13 ml.100 g-1.min-1, P less than 0.001), but a larger dose of clonidine adversely reduced reactive flow (254 +/- 18 ml.100 g-1.min-1, P less than 0.001). Adenosine release during reactive hyperemia with and without intracoronary infusions of clonidine were not altered significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of extravascular compression to reduction of maximal coronary blood flow

1992 ◽  
Vol 262 (1) ◽  
pp. H68-H77
Author(s):  
F. L. Abel ◽  
R. R. Zhao ◽  
R. F. Bond
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Coronary Perfusion ◽  
Storage Site

Effects of ventricular compression on maximally dilated left circumflex coronary blood flow were investigated in seven mongrel dogs under pentobarbital anesthesia. The left circumflex artery was perfused with the animals' own blood at a constant pressure (63 mmHg) while left ventricular pressure was experimentally altered. Adenosine was infused to produce maximal vasodilation, verified by the hyperemic response to coronary occlusion. Alterations of peak left ventricular pressure from 50 to 250 mmHg resulted in a linear decrease in total circumflex flow of 1.10 ml.min-1 x 100 g heart wt-1 for each 10 mmHg of peak ventricular to coronary perfusion pressure gradient; a 2.6% decrease from control levels. Similar slopes were obtained for systolic and diastolic flows as for total mean flow, implying equal compressive forces in systole as in diastole. Increases in left ventricular end-diastolic pressure accounted for 29% of the flow changes associated with an increase in peak ventricular pressure. Doubling circumferential wall tension had a minimal effect on total circumflex flow. When the slopes were extrapolated to zero, assuming linearity, a peak left ventricular pressure of 385 mmHg greater than coronary perfusion pressure would be required to reduce coronary flow to zero. The experiments were repeated in five additional animals but at different perfusion pressures from 40 to 160 mmHg. Higher perfusion pressures gave similar results but with even less effect of ventricular pressure on coronary flow or coronary conductance. These results argue for an active storage site for systolic arterial flow in the dilated coronary system.

Abstract 3628: Neuronal Nitric Oxide Synthase (nNOS) Regulates Basal Flow in the Human Coronary Circulation I n Vivo

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mike Seddon ◽  
Phil Chowienczyk ◽  
Narbeh Melikian ◽  
Rafal Dworakowski ◽  
Barbara Casadei ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Coronary Flow ◽  
Vascular Tone ◽  
Coronary Circulation ◽  
Physiological Regulation ◽  
Intracoronary Doppler ◽  
Basal Flow

Endothelial NO synthase (eNOS) is thought to be the major source of nitric oxide (NO) involved in the local regulation of human vascular tone. However, in studies using a selective neuronal NOS (nNOS) inhibitor S-methyl-L-thiocitrulline (SMTC), we recently reported that basal human forearm blood flow is regulated by nNOS. SMTC had no effect on acetylcholine-induced vasodilatation which however was inhibited by the non-selective NOS inhibitor N G monomethyl-L-arginine (L-NMMA). This study investigated the effects of nNOS in the human coronary circulation in vivo . We studied patients undergoing diagnostic cardiac catheterisation who had angiographically normal coronary arteries. Coronary flow velocity was measured by an intracoronary Doppler wire and epicardial artery diameter by QCA. We compared the effects of intracoronary SMTC or L-NMMA infusion on basal flow and the responses to substance P and isosorbide dinitrate (endothelium-dependent and -independent dilators, respectively). L-NMMA (25 μmol/min) reduced basal coronary flow by 22.3±5.3% and inhibited dilation to substance P (20 pmol/min) by 57±5.7% (n=8; both P<0.01). SMTC (0.625 μmol/min) also reduced basal flow (−34.8±6.3%; n=8; P<0.01), but had no effect on the response to substance P (inhibited by −2±14%; P=NS). The effects of SMTC were abolished by L-arginine (240μmol/ min; n=3). Both L-NMMA and SMTC reduced epicardial artery diameter (−2.5±0.6% and −2.8±0.9% respectively; P<0.05) but only L-NMMA reduced dilatation to substance P (5.6±1.3% before versus 3.0±0.8% after L-NMMA; P<0.05). These data indicate that local nNOS-derived NO regulates basal coronary blood flow in humans in vivo , whereas substance P-stimulated vasodilatation is eNOS-mediated. Our results indicate that nNOS and eNOS have distinct local roles in the physiological regulation of human coronary vascular tone in vivo .

Intracoronary adenosine enhances myocardial reactive hyperemia after brief coronary occlusion

1985 ◽  
Vol 248 (6) ◽  
pp. H812-H817
Author(s):  
D. Saito ◽  
T. Hyodo ◽  
K. Takeda ◽  
Y. Abe ◽  
H. Tani ◽  
...  
Keyword(s):  
Blood Flow ◽  
Left Atrium ◽  
Coronary Occlusion ◽  
Reactive Hyperemia ◽  
Control Level ◽  
Direct Effects ◽  
Intracoronary Infusion ◽  
Hyperemic Flow ◽  
Hyperemic Response

Adenosine is a prime candidate for the role of mediator between myocardial metabolic state and coronary blood flow. However, there are few reports concerning the direct effects of exogenously added adenosine on coronary autoregulation. The present investigation in the open-chest dog studied the effects of a threshold dose of intracoronary adenosine infusion on reactive hyperemia following brief coronary occlusions. The infused dose did not increase nonocclusive flow by greater than 10%. Adenosine enhanced total hyperemic flow at all occlusions tested (5, 10, 15, 20, and 30 s). Aminophylline pretreatment reduced reactive hyperemia below the control level even in the presence of an intracoronary infusion of adenosine. Adenosine injected into the left atrium and intracoronarily infused papaverine did not affect hyperemic response to 5- and 15-s coronary occlusions. The results suggest that a minimum dose of exogenously added adenosine enhances myocardial reactive hyperemia, possibly by potentiating the effects of endogenous adenosine released during ischemia.

Left ventricular heat production measured by coronary flow and temperature gradient

1961 ◽  
Vol 16 (5) ◽  
pp. 883-890 ◽  
Author(s):  
William A. Neill ◽  
Herbert J. Levine ◽  
Richard J. Wagman ◽  
Joseph V. Messer ◽  
Norman Krasnow ◽  
...  
Keyword(s):  
Temperature Gradient ◽  
Flow Rate ◽  
Heat Production ◽  
Coronary Flow ◽  
Coronary Circulation ◽  
Heat Removal ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Coronary Perfusion

The study of energetics of the left ventricular myocardium, normally based on its oxygen consumption and mechanical work performance, can be extended by determining its heat production as well. By considering all forms of energy input and output of the left ventricle, calculations were made of left ventricular net heat production under a variety of hemodynamic conditions. One of the mechanisms for removal of the heat produced is provided by the coronary blood, which is warmed in transit through the myocardium. Direct measurements of the rate of heat removal by the coronary circulation were made from coronary flow rate and veno-arterial temperature gradient. The fraction of left ventricular net heat production which is removed by the coronary perfusion is proportional to coronary flow rate. The fraction at a given flow rate is sufficiently reproducible to permit estimation of total heat produced from the portion measured in the coronary circulation. Certain of the theoretical applications of heat data may require more accuracy than appears feasible by this method. Which of the applications discussed will prove practical remains to be determined. Submitted on February 13, 1961

Preservation of coronary flow reserve in stunned myocardium

1989 ◽  
Vol 256 (5) ◽  
pp. H1303-H1310
Author(s):  
R. W. Jeremy ◽  
L. Stahl ◽  
M. Gillinov ◽  
M. Litt ◽  
T. R. Aversano ◽  
...  
Keyword(s):  
Coronary Flow Reserve ◽  
Coronary Flow ◽  
Coronary Occlusion ◽  
Myocardial Dysfunction ◽  
Reactive Hyperemia ◽  
Stunned Myocardium ◽  
Flow Reserve ◽  
Before And After ◽  
Adenosine Antagonist ◽  
Hyperemic Flow

Microvascular obstruction and persistent focal ischemia have been suggested as a possible cause of myocardial dysfunction (stunning) after brief coronary occlusion. Microvascular occlusion should result in a reduction in maximal coronary flow reserve, although resting transmural coronary flow may be maintained by release of local vasodilators, such as adenosine. To test the microvascular occlusion hypothesis, coronary flow reserve was measured in 14 anesthetized dogs, before and after myocardial stunning produced by 10 min of ischemia. Intracoronary adenosine infusion (5,900 microM/min) increased coronary flow to the same degree in normal [195 +/- 20 (SE) ml/min] and stunned (212 +/- 23 ml/min) myocardium. Peak hyperemic flow after 100 s of coronary occlusion was also similar in normal (205 +/- 25 ml/min) and stunned (218 +/- 23 ml/min) myocardium. The adenosine antagonist 8-phenyltheophylline (5 mg/kg) reduced the flow response to exogenous adenosine, but neither resting coronary flow nor peak hyperemic flow in stunned myocardium was altered. In stunned myocardium, myocardial shortening at rest (0.2 +/- 2.0%) increased during reactive hyperemia (to 13.8 +/- 2.5%, P less than 0.01), but shortening promptly returned to basal levels after each hyperemia. These findings indicate that fixed microvascular occlusion is unlikely to be an important factor in the pathogenesis of stunned myocardium and that local adenosine release does not appear to have a compensatory role in coronary vasoregulation in stunned myocardium.

scholarly journals Activation of ATP-sensitive potassium channels contributes to reactive hyperemia in humans

1996 ◽  
Vol 271 (4) ◽  
pp. H1594-H1598 ◽  
Author(s):  
P. F. Banitt ◽  
P. Smits ◽  
S. B. Williams ◽  
P. Ganz ◽  
M. A. Creager
Keyword(s):  
Blood Flow ◽  
Katp Channel ◽  
Forearm Blood Flow ◽  
Reactive Hyperemia ◽  
Katp Channels ◽  
Venous Occlusion ◽  
Membrane Hyperpolarization ◽  
Flow Response ◽  
Hyperemic Flow ◽  
Basal Flow

Activation of ATP-sensitive potassium (KATP) channels present on vascular smooth muscle cells causes membrane hyperpolarization and vasodilation. The purpose of this study was to determine whether KATP channels contribute to reactive hyperemia in humans. Accordingly, we studied the effect of tolbutamide, a KATP channel inhibitor, on reactive hyperemic forearm blood flow. Forearm blood flow was measured by venous occlusion plethysmography. Forearm ischemia was produced by inflating a sphygmomanometric cuff on the arm to suprasystolic pressures for 5 min. After cuff release, forearm blood flow was measured during the reactive hyperemic phase for 5 min. Tolbutamide (1 mM blood concentration, n = 6) did not affect basal (2.4 +/- 0.2 to 2.2 +/- 0.1 ml.100 ml-1.min-1) or peak reactive hyperemic forearm blood flow (21.9 +/- 3.8 to 22.6 +/- 2.9 ml.100 ml-1.min-1, each P = NS), but it significantly attenuated total hyperemic volume (12.6 +/- 1.7 vs. 9.2 +/- 1.8 ml/100 ml, P < 0.02). Vehicle (n = 6) did not affect basal flow, peak reactive hyperemic flow, or total hyperemia. To determine whether adenosine or endothelium-derived nitric oxide contribute to reactive hyperemia via KATP channels, adenosine (1.5-500 micro grams/min, n = 6) and acetylcholine (30 micrograms/min, n = 6) were infused before and during tolbutamide coinfusion. Tolbutamide did not significantly alter the forearm blood flow response to either adenosine or acetylcholine. In conclusion, KATP channels contribute to vasodilation during reactive hyperemia in humans.

Metabolic and functional consequences of blunted myocardial reactive hyperemia

1991 ◽  
Vol 261 (3) ◽  
pp. H892-H900 ◽  
Author(s):  
G. G. Schwartz ◽  
S. Schaefer ◽  
S. D. Trocha ◽  
S. Steinman ◽  
J. Gober ◽  
...  
Keyword(s):  
Blood Flow ◽  
Flow Rate ◽  
Coronary Flow ◽  
Coronary Occlusion ◽  
Reactive Hyperemia ◽  
Blood Flow Rate ◽  
Intracellular Acidosis ◽  
Ischemic Region ◽  
Phosphorus Metabolites ◽  
Contractile Recovery

This study determined whether the rapidity of myocardial metabolic and contractile recovery after brief coronary occlusion depends upon the intensity of reactive hyperemia. We also tested the hypothesis that coronary flow rate modulates contractility after brief myocardial ischemia, independent of changes in phosphorus metabolites. Eight open-chest pigs were studied with phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy with 14 s time resolution. After a 29-s anterior descending coronary occlusion, peak Doppler coronary flow velocity was alternately unrestricted (normal hyperemia, 443 +/- 40% of control) or limited to 159 +/- 9% of control. During 29 s coronary occlusion, phosphocreatine-to-inorganic phosphate ratio (PCr/Pi) and systolic segment shortening in the ischemic region fell to 28 +/- 4 and 7 +/- 7% of control, respectively. With normal hyperemia, PCr/Pi and segment shortening recovered within 29 s. With blunted hyperemia, recovery of both parameters was delayed an additional 29-43 s, associated with reduced subendocardial blood flow (measured with radioactive microspheres) and persistent intracellular acidosis. However, the relationship between segment shortening and PCr/Pi was unaffected by the intensity of reactive hyperemia. Thus blunted reactive hyperemia significantly delays metabolic and contractile recovery from brief ischemia, probably via transient maldistribution of transmural perfusion. However, coronary blood flow rate does not independently modulate contractility after brief reversible ischemia.

Effects of exercise training on coronary reactive hyperemia and blood flow in the dog

1978 ◽  
Vol 45 (4) ◽  
pp. 604-610 ◽  
Author(s):  
M. H. Laughlin ◽  
J. N. Diana ◽  
C. M. Tipton
Keyword(s):  
Exercise Training ◽  
Coronary Flow ◽  
Reactive Hyperemia ◽  
Base Line ◽  
Chronic Exercise ◽  
Sedentary Control ◽  
Beneficial Effects ◽  
Anesthetized Dogs ◽  
Isoproterenol Infusion ◽  
Hyperemic Flow

The reactive hyperemic responses to 10-s coronary occlusions were studied in seven sedentary-control (C) and eight exercise-trained (T) anesthetized dogs, with electromagnetic flowmeters placed on the left anterior descending coronary artery. Radiolabeled microspheres (9 +/- 0.8 micron) were used to measure resting coronary flow per gram and to study the effects of isoproterenol infusion (ISO) (1 mg/kg-min) on total and regional coronary flow. Base-line coronary flow per 100 g was significantly greater in the T dogs (122 +/- 7) than in C dogs (100 +/- 4). During ISO, T and C coronary resistances did not differ significantly, whereas the effects of ISO on total and regional coronary flow were quite different in T dogs as compared to C dogs. C and T hyperemic flow debt repayments did not differ significantly; however, the peak reactive hyperemic flow in T dogs (344 +/- 12%) was significantly greater than the control (306 +/- 10%). Since resting coronary flow per gram was greater in T dogs, the greater peak reactive hyperemic flow implies that T dogs have an increased coronary reserve. Although the mechanisms involved are unclear, the results of this study indicate that chronic exercise training may have beneficial effects on coronary physiology.

Decreased reactive hyperemia after coronary perfusion with nonoxygenated solution

1978 ◽  
Vol 234 (5) ◽  
pp. H625-H628
Author(s):  
Y. Sugishita ◽  
M. Kakihana ◽  
S. Murao
Keyword(s):  
Oxygen Uptake ◽  
Comparative Studies ◽  
Coronary Occlusion ◽  
Myocardial Function ◽  
Oxygen Deficiency ◽  
Reactive Hyperemia ◽  
Coronary Vessels ◽  
Coronary Perfusion ◽  
Tyrode Solution ◽  
Hyperemic Flow

To gain more knowledge about the factors involved in reactive hyperemia in the coronary vessels, we performed comparative studies on the reactive hyperemia occurring after coronary occlusion and after coronary perfusion with nonoxygenated Tyrode solution. The peak coronary reactive hyperemic flow following 3 min of coronary perfusion with nonoxygenated Tyrode solution increased to only 142 +/- 16% of the control in contrast to 455 +/- 75% following 3 min of coronary occlusion alone. Myocardial oxygen uptake during reactive hyperemia was also much smaller after perfusion with Tyrode solution. First, the evidence suggests that the decreased reactive hyperemia after coronary perfusion with the nonoxygenated Tyrode solution is due to "washout" of the vasodilatory metabolites from the myocardium. Second, it suggests that there is a smaller "energy debt" during perfusion with Tyrode solution, so that deterioration of myocardial function due to oxygen deficiency is less severe than in coronary occlusion alone.

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