Indomethacin and the prostaglandin hypothesis of coronary blood flow regulation

Afonso, Skoda; Bandow, George T.; Rowe, George G.

doi:10.1113/jphysiol.1974.sp010657

Cited by 78 publications

(21 citation statements)

References 13 publications

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“…5 In our experiments the increase in the volume of coronary blood flow during hypoxia was also not substantially altered by the inhibition of PG synthesis. Afonso et al, 4 on the other hand, reported that IND administration slightly reduced the peak increase in flow following similar exposures to hypoxia. However, measurement of volumeflow is a better indicator of oxygen delivery to the tissue during hypoxia than measurement of peak flow.…”

Section: Discussionmentioning

confidence: 96%

“…It was reported recently that prostaglandins not only are released into the myocardial circulation during episodes of hypoxia, 4 anoxia, 5 and following coronary artery occlusion 6 -7 or administration of bradykinin, 8 but also that the ensuing increase in blood flow is attenuated in the presence of PG synthesis inhibitors. Other investigators, using similar experimental techniques, have found that the inhibitors had no significant effect on the vascular responses of coronary blood vessels.…”

mentioning

confidence: 99%

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Prostaglandins and the control of blood flow in the canine myocardium.

Hintze¹,

Kaley²

1977

Circulation Research

108

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SUMMARY A comprehensive study was undertaken to evaluate the effects of inhibition of prostaglandin (PG) synthesis on a variety of reactions in the coronary vascular bed of anesthetized, open-chest dogs. In 23 dogs an electromagnetic flow probe (EMFP) and hydraulic occluder were placed around either the left anterior descending or circumflex branches of the coronary artery and a needle was inserted distal to the EMFP. Injections into the coronary artery of arachidonic acid (AA), bradykinin, adenosine, angiotensin, and PGE 2 were given before and after inhibition of PG synthesis by indomethacin (IND) or meclofenamate (MF). The effects of the inhibitors on reactive hyperemia resulting from S-, 10-, 15-, and 20-second occlusions and the dilation resulting from 90-second exposure to 8% O 2 were also examined. In each experiment, inhibition of PG synthesis was ascertained by the elimination of vasodilation to AA. After administration of IND or MF, while baseline coronary blood flow was slightly reduced, the total increment of blood flow to vasodilator agents was not significantly altered. Whereas the peak dilation and volume of reactive hyperemia were decreased, the percent flow debt repaid was unchanged and total increment of coronary flow due to hypoxia-induced vasodilation was not significantly modified. Vasoconstrictor responses to angiotensin were also unchanged. These results indicate that while inhibitors of PG synthesis increase coronary resistance, they do not adversely affect vascular responsiveness. We conclude that prostaglandins play little, if any, role in modulating coronary blood flow.A NUMBER of reports assign an important role for prostaglandins in the regulation of coronary blood flow. The recent discovery that the nonsteroidal anti-inflammatory agents have in common the ability to inhibit prostaglandin (PG) synthesis' has made possible the study of the physiological role of these agents in a number of circulatory beds. The ubiquity of prostaglandins in tissues, 2 their release after pharmacological stimulation of vascular tissue, and the reduction in blood flow after the administration of inhibitors of PG synthesis 3 are all factors that support the hypothesis that prostaglandins of the E series, which are generally vasodilator, 2 are important modulators of vascular tone. Whether prostaglandins subserve this function in the coronary vascular bed, however, is still open to question.It was reported recently that prostaglandins not only are released into the myocardial circulation during episodes of hypoxia, 4 anoxia, 5 and following coronary artery occlusion 6 -7 or administration of bradykinin, 8 but also that the ensuing increase in blood flow is attenuated in the presence of PG synthesis inhibitors. Other investigators, using similar experimental techniques, have found that the inhibitors had no significant effect on the vascular responses of coronary blood vessels. 9 In view of this controversy, we undertook a comprehensive study to investigate the possible role of endogenously produced prostag...

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Prostaglandins and the control of blood flow in the canine myocardium.

Hintze¹,

Kaley²

1977

Circulation Research

108

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“…Other possible explanations might relate to inhibition of histamine release [24] , its role as an oxygen radical scavenger [25] , inhibition of calcium in smooth muscle cells [6] or modulation of the adrenergic neurotransmission to blood vessels [26] . In experimental studies on anaesthetized dogs by Afonso et al [9] , intra-coronary infusion of prostaglandins E 1 and E 2 were 5-10 times more effective in increasing coronary sinus blood flow than adenosine.…”

Section: Prostaglandins: Role In Modulation Of Systemic Flow Haemodynmentioning

confidence: 99%

“…Previous experimental data have suggested that prostaglandins play an important role in autoregulation of coronary artery blood flow [9] . Interference with this autoregulatory mechanism could alter coronary perfusion, which in turn could potentially affect myocardial function.…”

Section: Indomethacin and Coronary Blood Flowmentioning

confidence: 99%

Indomethacin Impairs Coronary Perfusion in Infants with Hemodynamically Significant Ductus Arteriosus

2011

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Background: A haemodynamically significant ductus arteriosus (HSDA) is commonly associated with morbidity in preterm infants. Aim: To study the effect of the first dose of indomethacin on coronary blood flow in preterm neonates diagnosed with an HSDA. Method: A prospective observational echocardiographic study was performed on preterm infants. A single study dose of intravenous indomethacin (0.1 mg/kg) was administered over 1 h. Serial echocardiography was performed before and after indomethacin treatment to study the effect on coronary artery perfusion and cardiovascular performance. Results: Eighteen infants born at a median gestation of 25.8 (24.2, 28.1) weeks and a birth weight of 773 g (704, 1,002) were evaluated. The median age at indomethacin administration was 7.5 days (4, 17). There was no significant change in arterial pressure or ventilatory indices. Left anterior descending artery diastolic velocity and time integral declined from 0.3 ± 0.1 and 3.19 ± 1.2 m/s to 0.22 ± 0.08 and 2.01 ± 0.9 m/s, respectively, within 10 min of completion of infusion. These indices showed partial recovery when reassessed after 60 min. There were no changes in left ventricular output or transductal flow. Conclusions: Intravenous indomethacin was followed by a decline in coronary arterial diastolic blood flow.

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“…The vasodilating ac tion of PGI2 may contribute to the signifi cant increase in coronary blood flow during reperfusion regardless of the temperature during ischemia under CP. Regarding the reactive hyperemia and PGI2, Alexander et al [14] and Afonso et al [15] reported that PGI2 might closely accompany the coronary flow rate. Adenosine has been shown to have a major role in reactive hyperemia following myocardial ischemia [16,17].…”

Section: Role O F Pgi2 Release During Reperfusionmentioning

confidence: 99%

Assessment of Prostacyclin and Thromboxane A<sub>2</sub> Release during Reperfusion after Global Ischemia Induced by Crystalloid Cardioplegia – Comparison between Warm and Cold Ischemia

Nomura¹,

Matsuda²,

Hirose³

et al. 1988

Eur Surg Res

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The metabolites of prostacyclin (PGI2) and thromboxane A₂ (TxA₂), 6-keto-PGFι_α and thromboxane B₂ (TXB2), were investigated during reperfusion (RP) following warm (37 °C, 60 min, n = 9) or cold (15 °C, 120 min, n = 11) ischemia induced by cold (4 ° C) or normothermic (30 °C) K⁺ cardioplegia (CP) in isolated canine hearts subjected to global ischemia and RP. 6-Keto-PGF_1α flux was significantly higher (p < 0.025) in the warm group at 1, 5, and 10 min of RP (4,202 ± 1,412, 2,475 ± 1,875, and 1,255 ± 633 pg/g·min, mean ± SD) compared to those in the cold group (1,504 ± 1,245, 434 ± 641, and 370 ± 329 pg/g·min). TxB₂ flux was small in amount compared to 6-keto-PGF_1α in both groups. Regarding the coronary hemodynamics, the cold group alone showed statistically significant relationships of coronary sinus blood flow to TxB₂ level and TxB₂/6-keto-PGF_1α ratio in coronary sinus blood. Also, coronary vascular resistance showed linear relations to these two parameters of the metabolites. In a supplementary experiment only with cold ischemia for 180 min, 6-keto-PGF_1α was released at each coronary flush-out by CP and the incremental amount showed a gradual increase during ischemia. These results indicated that significant production and release of PGI₂ occurred during ischemia and RP following CP arrest and these related to the degree of myocardial damage while the response of TxA₂ seemed less significant. The role of PGI₂ release during RP following cardioplegic arrest was discussed.

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Indomethacin and the prostaglandin hypothesis of coronary blood flow regulation

Cited by 78 publications

References 13 publications

Prostaglandins and the control of blood flow in the canine myocardium.

Prostaglandins and the control of blood flow in the canine myocardium.

Indomethacin Impairs Coronary Perfusion in Infants with Hemodynamically Significant Ductus Arteriosus

Assessment of Prostacyclin and Thromboxane A<sub>2</sub> Release during Reperfusion after Global Ischemia Induced by Crystalloid Cardioplegia – Comparison between Warm and Cold Ischemia

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Indomethacin and the prostaglandin hypothesis of coronary blood flow regulation

Cited by 78 publications

References 13 publications

Prostaglandins and the control of blood flow in the canine myocardium.

Prostaglandins and the control of blood flow in the canine myocardium.

Indomethacin Impairs Coronary Perfusion in Infants with Hemodynamically Significant Ductus Arteriosus

Assessment of Prostacyclin and Thromboxane A<sub>2</sub> Release during Reperfusion after Global Ischemia Induced by Crystalloid Cardioplegia &ndash; Comparison between Warm and Cold Ischemia

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Assessment of Prostacyclin and Thromboxane A<sub>2</sub> Release during Reperfusion after Global Ischemia Induced by Crystalloid Cardioplegia – Comparison between Warm and Cold Ischemia