Prostaglandin E1 Infusion Research Articles

Patent ductus arteriosus ‘stenting’ as a life-saving approach in severe neonatal Ebsteinʼs anomaly

A critical 1-day-old male neonate was referred to cardiac evaluation because of deep cyanosis due to a severe tricuspid valve Ebstein's anomaly with large atrial right-to-left shunt and duct-dependent pulmonary circulation. Ductus arteriosus re-opening by prostaglandin infusion resulted in significant clinical improvement but, after a few hours, it irreversibly closed, and pulmonary vasodilator treatment with inhaled nitric oxide and oral sildenafil did not significantly increase the oxygen saturation. Therefore, it was decided to proceed to ductal recanalization and stenting as an alternative to the surgical shunt. After the procedure, oxygen saturation was raised to over 90%, allowing the baby to be weaned from mechanical ventilation. At 9-month follow-up, he was asymptomatic and showed a systemic saturation over 90% despite complete closure of the stented ductus. In conclusion, ductus arteriosus stenting might be considered to be a reliable and life-saving therapeutic option in severe forms of Ebstein's anomaly as a temporary support to a multidrug vasoactive therapy.

Effects of vasodilation on cardiac output measured by PulseCO™

The instability of cardiac output (CO) measured by PulseCO (LiDCO Ltd.) during cardiac surgery has been reported. In the present study, we investigated the effects of vasodilation by prostaglandin E1 (PGE1) on the relation between cardiac output measured by PulseCO and that by thermodilution. Twenty patients who underwent off-pump coronary artery bypass grafting (OPCAB) were enrolled in this study. After premedication with oral diazepam 10 mg, anesthesia was induced with midazolam, fentanyl and vecuronium. CO was measured after anesthesia induction, at PGE1 0.01, 0.02 and 0.04 microg/(kg min) and at 15 min after the stop of the infusion. Systemic vascular resistances (SVRs) by PGE1 at 0.02 and 0.04 microg/(kg min) were significantly lower than the control value. The correlation coefficient (R2) between the two techniques at each point, percentage error and limits of agreement (bias +/-2SD of bias) were 0.78, 3, 0.05 +/- 0.17 at 0.01 microg/(kg min), 0.20, 10, -0.18 +/- 0.12 at 0.02 microg/(kg min), 0.46, 28, -0.50 +/- 0.24 at 0.04 microg/(kg min) and 0.97, 1, 0.02 +/- 0.27 L/min at 15 min after stop of infusion, respectively. PulseCO might underestimate CO compared to that by bolus thermodilution method when simply decreasing the SVR by infusion of PGE1. Therefore, PulseCO might be unsuitable in cardiac surgery.

Cortical Hyperostosis Secondary to Prostaglandin E 1 Therapy

Infants born with ductal-dependent congenital heart defects often require prolonged treatment with prostaglandin E1 (PGE1) while awaiting corrective surgery. An uncommon, and frequently overlooked, adverse effect of prolonged PGE1 infusion is cortical hyperostosis. A 4-day-old female infant sustained cardiogenic shock resulting from coarctation of the aorta necessitating intravenous PGE1 (0.1 mcg/kg/min). Because of confounding disseminated herpes infection, corrective surgery could not be immediately performed. PGE1 was continued until palliative stent placement at 38 days of life. Alkaline phosphatase levels were noted to be elevated during the infant’s hospital course. (Figure 1; available at www.jpeds.com). A 5’ nucleotidase level in the reference range ruled out hepatic origin of the elevated alkaline phosphatase level. Chest roentograms (Figure 2) showed normal cortical bone at 10-days of age (A), with gradual increase in hyperostosis at 30 days (B) and 50 days (C) of age, seen best in the right humerus and clavicle. With cessation of PGE1 infusion, the alkaline phosphatase level began to decrease and continued to do so until the time of discharge from the hospital. Follow-up at 9 months of age showed both the alkaline phosphatase level and the radiography abnormalities had normalized.Figure 2This series of chest roentograms shows the gradual increase in cortical bone during treatment with prostaglandin E1. The findings are best seen in the right humerus and clavicle. The patient’s age at the time of the radiographs is 10-days (A), 30-days (B) and 50-days (C).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Prostaglandins of the E series have been shown to promote osteogenesis.1Udea K. Saito A. Nakano H. Aoshima M. Yokota M. Muraoka R. et al.Cortical hyperostosis following long-term administration of prostaglandin E1 in infants with cyanotic congenital heart disease.J Pediatr. 1980; 97: 834-836Abstract Full Text PDF PubMed Scopus (242) Google Scholar Infants with cyanotic heart defects are at high risk for the development of elevated circulating levels of PGE1 because of decreased pulmonary inactivation caused by right to left shunting and the administration of pharmacological amounts to ensure ductus arteriosus patency. A large number of infants receiving PGE1 while awaiting cardiac transplantation have radiographic evidence of cortical hyperostosis.2Woo K. Emery J. Peabody J. Cortical hyperostosis: a complication of prolonged prostaglandin infusion in infants awaiting cardiac transplantation.Pediatrics. 1994; 93: 417-420PubMed Google Scholar Risk of cortical hyperostosis increases with duration of continuous PGE1 infusion from 42% at <30 days to 100% at >60 days; the severity of cortical hyperostosis correlates with both duration and total dose of PGE1 infused.2Woo K. Emery J. Peabody J. Cortical hyperostosis: a complication of prolonged prostaglandin infusion in infants awaiting cardiac transplantation.Pediatrics. 1994; 93: 417-420PubMed Google Scholar Although most cases are asymptomatic, cortical hyperostosis can mimic osteomyleitis,3Velaphi S. Cilliers A. Beckh-Arnold E. Mockhachane M. Mphahlel R. Pettifor J. Cortical hyperostosis in an infant on prolonged prostaglandin infusion: case report and literature review.J Perinatol. 2004; 24: 263-265Crossref PubMed Scopus (16) Google Scholar thus complicating the decision making process on proceeding with further cardiac surgery. PGE1-induced cortical hyperostosis is benign, reversible, and self-resolving on withdrawal of PGE1 treatment.

Neonatal Patent Ductus Arteriosus Recanalization and Stenting in Critical Ebstein’s Anomaly

A critically ill 3-day-old neonate with severe tricuspid valve Ebstein's anomaly, functional pulmonary atresia, and closed ductus arteriosus, unresponsive to prostaglandin infusion, underwent percutaneous ductal recanalization and stenting as an alternative to a surgical shunt. After local prostaglandin infusion through an end-hole catheter, the ductus was passed using a hydrophilic, high-support coronary guidewire. It was then stabilized by coronary stent implantation, after which the arterial oxygen saturation showed a sudden rise. In conclusion, ductus arteriosus recanalization and stenting can be successfully achieved within a few days after spontaneous closure as a cost-effective alternative to a surgical shunt for critical neonatal, duct-dependent Ebstein's anomaly.

Management of Ebstein’s Anomaly and Pure Tricuspid Insufficiency in the Neonate

Because the pulmonary vascular resistance is very elevated at birth, severe tricuspid regurgitation is poorly tolerated and even life-threatening in the newborn. The etiology may be tricuspid valve papillary muscle rupture or the more ominous Ebstein's anomaly, with its associated dysfunctional right ventricle. After the diagnosis is established and the patient is supported with prostaglandin infusion and nitric oxide, definitive surgical management is undertaken with the expectation of excellent outcomes for isolated tricuspid valve regurgitation. For neonates with Ebstein's anomaly, therapy is tailored to the severity of the malformation and the degree of right ventricular outflow tract obstruction, assessed in the context of declining pulmonary vascular resistance. The surgical approach may involve ligation of a patent ductus arteriosus, placement of a systemic to pulmonary shunt, establishment of functional tricuspid atresia, or tricuspid valve repair. With the application of these various approaches, the outlook for neonatal Ebstein's anomaly has improved remarkably.

Persistence of bilateral arterial ducts in pulmonary atresia despite confluent branch pulmonary arteries: Opportunity for two percutaneous therapeautic alternatives

We present a case of a newborn infant with double inlet left ventricle, pulmonary atresia, confluent pulmonary arteries, and bilateral arterial ducts (AD), to discuss the therapeutic alternatives offered by interventional catheterization techniques in this anatomic arrangement. The infant initially underwent stenting of the right AD to stabilize pulmonary blood flow off of prostaglandin infusion. Three weeks later, she developed left pulmonary artery isolation upon closure of the left arterial duct. An additional stent was placed in the pulmonary artery confluence, restoring blood flow to the left lung and significantly improving her oxygen saturations. At 6 months of age she underwent her first surgical procedure, a successful bidirectional cavopulmonary anastomosis with removal of the left pulmonary artery stent and patch enlargement of the pulmonary artery confluence. She continues to do well in clinical follow-up at 16 months of age.

Stimulation of prostanoid IP and EP 2 receptors dilates retinal arterioles and increases retinal and choroidal blood flow in rats

We examined the effects of vasodilatory prostaglandins (prostacyclin and prostaglandin E 2) and selective agonists for prostanoid EP 2 and EP 4 receptor on the diameters of retinal blood vessels and fundus (retinal/choroidal) blood flow in rats. Male Wistar rats (8- to 10-week-old) were treated with tetrodotoxin (50 μg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye and infused with a mixture solution of norepinephrine and epinephrine (1:9) to maintain adequate systemic circulation under artificial ventilation. Fundus images were captured with a digital camera that was equipped with the special objective lens for small animals, and the diameters of retinal arterioles and venules were measured on a personal computer. Fundus blood flow was estimated using a laser Doppler flowmetry. Intravenous infusions of prostacyclin and prostaglandin E 2 dilated retinal blood vessels, increased fundus blood flow and decreased systemic blood pressure in a dose-dependent manner. The effects of vasodilatory prostaglandins on retinal arterioles were greater than those on retinal venules. Similarly, a prostanoid EP 2 receptor agonist (ONO-AE1-259-01) dilated retinal blood vessels, and increased fundus blood flow and decreased systemic blood pressure. However, a prostanoid EP 4 receptor agonist (ONO-AE1-329) failed to increase fundus blood flow, despite its comparable depressor response with those to vasodilatory prostaglandins and the prostanoid EP 2 receptor agonist. The responses to forskolin, an activator of adenylyl cyclase, were very similar to those to prostacyclin and the prostanoid EP 2 receptor agonist. These results suggest that prostacyclin and prostaglandin E 2 act as vasodilators in retinal and choroidal circulation, and prostanoid IP and EP 2 receptors play an important role in the regulation of ocular hemodynamics in rats.

Reduced regional right ventricular wall motion after transventricular repair of tetralogy of Fallot

ably high. 4 Based on the above facts, we integrated the catheterbased devices and the traditional surgical procedure for PAIVS as initial management. In this hybrid beating-heart procedure, first we perforate the PV with the needle and then deliver the balloon through the RV free wall to the pulmonary trunk. Epicardial echocardiography was used not only to guide the procedure with real-time imaging but also to evaluate the effectiveness of valvuloplasty with monitoring of the trans-PV flow and gradient pressure. In percutaneous catheter therapy, if the newborn could not be weaned from the prostaglandin infusion, an urgent BT shunt would be considered. Such a delayed decision could result in postoperative hypoxia and thus increased mortality. Because the operative field was offered by the open-chest approach, we regularly placed a BT shunt simultaneously. Ligation of the patent ductus arteriosus was performed to prevent the excess augmentation of blood flow to the lung, and then prostaglandin infusion was ceased immediately in the operating room.

Fate of the “opened” arterial duct: Lessons learned from bilateral pulmonary artery banding for hypoplastic left heart syndrome under the continuous infusion of prostaglandin E1

Fate of the “opened” arterial duct: Lessons learned from bilateral pulmonary artery banding for hypoplastic left heart syndrome under the continuous infusion of prostaglandin E1

Presentation of Congenital Heart Disease in the Neonate and Young Infant

Presentation of Congenital Heart Disease in the Neonate and Young Infant

HIGH MORTALITY RATES FOR PREMATURE INFANTS WITH PROSTAGLANDIN-DEPENDENT CONGENITAL HEART DISEASE.

Background Using prostaglandin (PGE1) infusion to stabilize circulation prior to corrective surgery is standard of care for term infants with severe congenital heart disease (CHD). There is limited information on PGE1 therapy and outcomes for low birth weight (LBW) infants with CHD. Objective To study mortality rates for LBW infants with complex CHD requiring PGE1 infusion as a bridge to surgery. Methods We reviewed 5 years of our experience with infants Results Forty-three infants Conclusion We found a high rate of mortality and syndromes among infants

Experiences and problems pre‐operative anti‐CD20 monoclonal antibody infusion therapy with splenectomy and plasma exchange for ABO‐incompatible living‐donor liver transplantation

ABO-incompatible living-donor liver transplantation (LDLT) requires a reduction of the anti-ABO antibody titer to <16 before transplantation, which is usually achieved by pre-operative plasma exchange (PE) or double-filtration plasmapheresis. ABO-incompatible transplantations have been performed after a splenectomy with heavy drug immunosupression plus B-cell-specific drugs. Here, we evaluated a pre-transplantation infusion protocol with an anti-CD20 monoclonal antibody (rituximab) for ABO-incompatible LDLT. Between March 2002 and December 2005, 73 adult patients underwent LDLT without retransplantation in our institution. Among these cases, 57 were ABO-identical, 11 were ABO-compatible and five were ABO-incompatible. The rituximab infusion protocol consisted of a weekly infusion of rituximab (375 mg/m(2)) for three wk, which was administered to three of the five ABO-incompatible LDLT patients. All three patients underwent a pre-operative PE, as well as a splenectomy during the operation. A triple immunosuppression protocol of tacrolimus, low-dose steroids and mycophenolate mofetil (1500 mg/d) was administered post-operatively. In addition, the patients received a continuous intra-arterial infusion of prostaglandin E(1) and methylprednisolone, and a continuous intra-portal infusion of a protease inhibitor for three and two wk after transplantation, respectively. After the first rituximab infusion, the peripheral blood CD19(+) B cell count rapidly decreased to <1%. All three patients treated with rituximab subsequently received an ABO-incompatible LDLT, with donor/recipient blood groups of B/O, A(1)/B and A(1)/O. In two cases, the ABO-antibody level transiently increased post-operatively, then decreased and remained low. Rituximab infusion therapy did not develop any direct side effect except for mild allergic reaction to the first infusion, but post-operatively all three patients suffered a cytomegalovirus and were successfully treated with ganciclovir, and one patient had a MRSA-positive intra-abdominal abscess. Two patients are currently alive at 20 and 18 months respectively, and show normal graft-liver function. But one patient died of sepsis because of intra-abdominal abscess. Although the protocol of rituximab administration is a conventional and safe regimen with no major side effects, the development of a new protocol is needed for prevention of the infection with bone suppression.

The Effect of Intraportal Prostaglandin E1 on Adhesion Molecule Expression, Inflammatory Modulator Function, and Histology in Canine Hepatic Ischemia/Reperfusion Injury

Prostaglandin E1 (PGE1) is known to protect the liver from I/R, however, the mechanism of cytoprotection is not well understood. This study investigates the effect of intraportal infusion of PGE1 in a warm liver ischemia/reperfusion (I/R) model on cytokines, adhesion molecules and liver structure. Twenty dogs underwent laparotomy under general anesthesia. PGE1 (0.02 microg\kg\min) was perfused through the portal vein in the PGE1 group (n = 10), or a similar volume of Ringer's solution in the control group (n = 10) for 15 min. Liver ischemia was induced by hepatic artery and portal vein occlusion and PGE1 was infused via the portal vein for 60 min. The occlusion was released and PGE1 infusion recommenced for 30 min. Blood and liver biopsies were sampled at baseline, 60 min ischemia, and 30 min reperfusion and assessed for transaminases, cytokines, adhesion molecules, and electron microscopy. PGE1 infusion significantly reduced transaminases TNF-alpha, sICAM-1, sP-selectin, and sE-selectin on ischemia and reperfusion. PGE1 reduced hepatocytic degeneration, portal and central ICAM-1 expression, central and sinusoidal VCAM-1 expression, portal and central P-selectin expression, and portal and sinusoidal E-selectin expression on reperfusion. Intraportal PGE1 infusion reduced I/R injury and was associated with down-regulation of ICAM-1, VCAM-1, P-selectin, and E-selectin on reperfusion.

Lowered microvascular vessel wall oxygen consumption augments tissue pO2 during PgE1-induced vasodilation

Continuous infusion of intravenous prostaglandin E1 (PgE1, 2.5 mug/kg/min) was used to determine how vasodilation affects oxygen consumption of the microvascular wall and tissue pO(2) in the hamster window chamber model. While systemic measurements (mean arterial pressure and heart rate) and central blood gas measurements were not affected, PgE1 treatment caused arteriolar (64.6 +/- 25.1 microm) and venular diameter (71.9 +/- 29.5 microm) to rise to 1.15 +/- 0.21 and 1.06 +/- 0.19, respectively, relative to baseline. Arteriolar (3.2 x 10(-2) +/- 4.3 x 10(-2) nl/s) and venular flow (7.8 x 10(-3) +/- 1.1 x 10(-2)/s) increased to 1.65 +/- 0.93 and 1.32 +/- 0.72 relative to baseline. Interstitial tissue pO(2) was increased significantly from baseline (21 +/- 8 to 28 +/- 7 mmHg; P < 0.001). The arteriolar vessel wall gradient, a measure of oxygen consumption by the microvascular wall decreased from 20 +/- 6 to 16 +/- 3 mmHg (P < 0.001). The arteriolar vessel wall gradient, a measure of oxygen consumption by the vascular wall, decreased from 20 +/- 6 to 16 +/- 3 mmHg (P < 0.001). This reduction reflects a 20% decrease in oxygen consumption by the vessel wall and up to 50% when cylindrical geometry is considered. The venular vessel wall gradient decreased from 12 +/- 4 to 9 +/- 4 mmHg (P < 0.001). Thus PgE1-mediated vasodilation has a positive microvascular effect: enhancement of tissue perfusion by increasing flow and then augmentation of tissue oxygenation by reducing oxygen consumption by the microvascular wall.

Efficacy of Prostaglandin E1 in Relieving Obstruction in Coarctation of a Persistent Fifth Aortic Arch Without Opening the Ductus Arteriosus

A persistent fifth aortic arch (PFAA) with coarctation and type A interruption of the fourth arch was recognized in a 9-day-old infant. The widening of the area of coarctation in the fifth arch with prostaglandin E1 infusion without opening the ductus arteriosus is presented to document that ectopic ductal tissue constriction contributes to the development of coarctation in PFAA.

Advances in Neonatal Cardiac Surgery

After completing this article, readers should be able to: 1. Describe the developments that have allowed advances in neonatal cardiac surgery. 2. Describe the diagnostic approach to hypoplastic left heart syndrome (HLHS). 3. Delineate the preoperative management of the neonate who has HLHS. 4. Describe the original Norwood procedure and subsequent modifications. 5. Delineate the optimal therapy in the postoperative period for neonates who have a single ventricle. Advances in the surgical and medical management of children who have congenital heart disease (CHD) have led to a dramatic improvement in overall survival and reduced the long-term sequelae of open-heart surgery. With improved survival and decreased morbidity over the past 2 decades, the early complete repair of complex congenital heart problems in preterm and low-birthweight neonates has gained wider acceptance. Cardiologists and cardiothoracic surgeons now consider and perform complete neonatal repair more frequently than palliative surgery in this patient population. The treatment of hypoplastic left heart syndrome (HLHS) best illustrates the evolution of management strategies to improve survival and long-term outcome. A recent modification of the Norwood operation that involves a right ventricle-to-pulmonary artery conduit has led to much improved early postoperative stability and, in many centers, improved survival to a stage II superior cavopulmonary connection. A multidisciplinary team approach is required to provide the necessary care for this complex patient population. In 1938, Robert Gross at Children’s Hospital in Boston successfully ligated a patent ductus arteriosus, and this procedure—performed against the wishes of surgeon-in-chief William Ladd—opened the era of surgery for CHD. (1) Gross and Hufnagel performed detailed animal experiments to develop a technique for treatment of coarctation of the aorta that involves excision and end-to-end anastomosis. (2) Clarence Craaford of Stockholm, Sweden, had visited Gross to observe his experimental work, and in October 1944, Craaford and Nylin were the first to repair aortic …

Transporting newborn infants with suspected duct dependent congenital heart disease on low-dose prostaglandin E1 without routine mechanical ventilation

Aim: To evaluate the safety of transporting newborn infants with suspected duct dependent congenital heart disease (CHD) treated with prostaglandin E1 (PGE1) without routine mechanical ventilation. Methods: A retrospective population-based...

Cardiopulmonary Effects of Intravenous Prostaglandin E1 during Experimental One-Lung Ventilation

One-lung ventilation greatly improves operating conditions during thoracic surgery. Serious disadvantages of one-lung ventilation are hypoxaemia and increased pulmonary vascular resistance. Prostaglandins, like prostaglandin I2 (PGI2), are potent pulmonary vasodilators but may also influence venous admixture and systemic circulation. Since the lung is capable of extensive degradation of prostaglandin E1 (PGE1) but not of PGI2, PGE1 might affect systemic circulation to a lesser degree. Hence, we studied the effects of intravenous PGE1 on systemic and pulmonary circulation and on oxygenation during one-lung ventilation. Lateral thoracotomy and cross-clamping of the left main stem bronchus was performed in twelve anaesthetised and ventilated pigs. Animals were cannulated with arterial, central venous and fast response thermodilution pulmonary artery catheters for haemodynamic measurements. PGE1 was administered with infusion rates of 25, 50, and 100 ng x kg (-1) x min (-1) during one-lung ventilation. All doses of PGE1 significantly decreased pulmonary vascular resistance and mean pulmonary artery pressure. However, a comparable significant reduction in systemic vascular resistance and mean arterial pressure was found. Arterial oxygen tension and venous admixture showed a slight but significant deterioration. Oxygen delivery remained unchanged or increased since the cardiac index increased. During one-lung ventilation in the pig, infusion of PGE1 significantly decreased pulmonary vascular resistance and pulmonary artery pressure but failed to achieve selective pulmonary vasodilation.

Arterial complications of thoracic outlet syndrome

Objective: Arterial vascular complications resulting from thoracic outlet compression, although rare, can be substantial and potentially limb threatening. These complications are due to compressions at the thoracic outlet, the treatment of which continues to be a dilemma. The objective of the present study was to review our experience with this problem with particular reference to its management.Methods: We performed a retrospective study of 12 years and retrieved data from the medical records department of Nizam’s Institute of Medical Sciences, Hyderabad, India. A retrospective review identified 35 patients (age range 15–50 years). In 31 patients, the vasculopathy was caused by a cervical rib, soft tissue anomalies (n = 31), and an elongated transverse process (n = 4). Evaluation included assessment with colour duplex and arteriography with positional maneuvers. Thirty‐two patients presented with a fixed pulse deficit, 22 patients had palpable mass and 15 patients had distal embolization.Results: In 31 patients with cervical rib, the rib was excised via a supraclavicular approach, Scalenectomy was performed and the arterial pathology was repaired on its merit, usually by a vein graft replacement or bypass. The elongated process was excised in the other four patients. Twelve patients required thrombectomy of the distal arteries and a bypass procedure (with a vein/prosthetic graft) was performed in 14 patients. Dorsal sympathectomy, as an adjunct, was carried out in 10 patients. In view of their advanced distal disease, four patients were given prostaglandin therapy. Short‐term follow up of 2 years showed good results.Conclusion: Our results show that simple excision of the cervical rib with scalenectomy via supraclavicular approach, together with arterial reconstruction (if required) is adequate for arterial vascular complications resulting from thoracic outlet compression. Patients with severe distal disease may require other adjunct procedures like dorsal sympathectomy or prostaglandin infusions along with proximal reconstruction.

Renal hemodynamic responses to intrarenal infusion of acetylcholine: Comparison with effects of PGE2 and NO donor

Acetylcholine (Ach) could serve as a selective renal medullary vasodilator in studies of the mechanism of arterial pressure regulation; however, effects of intramedullary Ach infusion were disparate. In anesthetized rats, the total renal blood flow (RBF) was measured by renal artery probe, and local perfusion of the cortex (CBF), outer medulla (OMBF) and inner medulla (IMBF) as laser-Doppler (l-D) flux. Renal artery infusion of Ach (60-150 microg/kg/h) significantly increased RBF by 17% and l-D parameters by 7-14%, without affecting arterial blood pressure (BP); the responses were prevented by inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME). Intramedullary Ach (180 microg/kg/h) significantly increased OMBF by 9% and IMBF by 7% but also RBF and CBF (both 9%). Carbamylcholine (Cch, 15 or 30-60 microg/kg/h), a stable Ach analog, increased CBF, OMBF, and IMBF by 5-8%; there was no dose dependency and, as with Ach, no preferential effect on medullary perfusion. Intramedullary infusion of prostaglandin E(2) (PGE2) (15 microg/kg/h), and S-nitroso-N-acetyl-D,L penicillamine (SNAP), an NO donor (15-30 mg/kg/h), significantly and substantially increased OMBF and IMBF only. Ach increased perfusion of all kidney zones by an NO-dependent mechanism. Infusion of Ach or Cch into the renal medullary interstitium failed to affect preferentially the medullary perfusion, in contrast to the well-demonstrable selective effects of PGE2 and SNAP. The reason was probably the Ach's dual opposed action, vasoconstrictor and vasorelaxant, on the intrarenal vasculature.