Intra-arterial Vasodilator Infusion Research Articles

Delayed cerebral ischemia and therapeutic approaches after subarachnoid hemorrhage

Delayed cerebral ischemia after subarachnoid hemorrhage is one of the most important causes of mortality and poor functional outcome in patients. Initially, the etiology and treatment of delayed cerebral ischemia focused primarily on cerebral vasospasm. However, recent studies have detected that depolarization, microcirculation, and autoregulation disorder, which spreads together with cerebral vasospasm, also play a role in the etiology. The main treatment strategies in the prevention and treatment of delayed cerebral ischemia are the regulation of blood pressure and the use of calcium channel blockers, especially nimodipine. The main step in the early diagnosis and treatment of the disease is to monitor the neurological clinical status. In addition to transcranial Doppler ultrasonography, computed tomography, or magnetic resonance imaging angiography, continuous electroencephalography and invasive brain multimodal examination may be required in the follow-up period of the disease. In addition to blood pressure regulation, optimization of cardiac output, endovascular interventions, angioplasty, and/or intra-arterial vasodilator infusion are other treatment methods. This review aimed to evaluate delayed cerebral ischemia, one of the most important complications of subarachnoid hemorrhage, in the light of current literature.

Predictors of response to intra-arterial vasodilatory therapy of non-occlusive mesenteric ischemia in patients with severe shock: results from a prospective observational study

BackgroundNon-occlusive mesenteric ischemia (NOMI) is a life-threatening condition occurring in patients with shock and is characterized by vasoconstriction of the mesenteric arteries leading to intestinal ischemia and multi-organ failure. Although minimal invasive local intra-arterial infusion of vasodilators into the mesenteric circulation has been suggested as a therapeutic option in NOMI, current knowledge is based on retrospective case series and it remains unclear which patients might benefit. Here, we prospectively analyzed predictors of response to intra-arterial therapy in patients with NOMI.MethodsThis is a prospective single-center observational study to analyze improvement of ischemia (indicated by reduction of blood lactate > 2 mmol/l from baseline after 24 h, primary endpoint) and 28-day mortality (key secondary endpoint) in patients with NOMI undergoing intra-arterial vasodilatory therapy. Predictors of response to therapy concerning primary and key secondary endpoint were identified using a) clinical parameters as well as b) data from 2D-perfusion angiography and c) experimental biomarkers of intestinal injury.ResultsA total of 42 patients were included into this study. At inclusion patients had severe shock, indicated by high doses of norepinephrine (NE) (median (interquartile range (IQR)) 0.37 (0.21–0.60) μg/kg/min), elevated lactate concentrations (9.2 (5.2–13) mmol/l) and multi-organ failure. Patients showed a continuous reduction of lactate following intra-arterial prostaglandin infusion (baseline: (9.2 (5.2–13) mmol/l vs. 24 h: 4.4 (2.5–9.1) mmol/l, p < 0.001) with 22 patients (52.4%) reaching a lactate reduction > 2 mmol/l at 24 h following intervention. Initial higher lactate concentrations and lower NE doses at baseline were independent predictors of an improvement of ischemia. 28-day mortality was 59% in patients with a reduction of lactate > 2 mmol/l 24 h after inclusion, while it was 85% in all other patients (hazard ratio 0.409; 95% CI, 0.14–0.631, p = 0.005).ConclusionsA reduction of lactate concentrations was observed following implementation of intra-arterial therapy, and lactate reduction was associated with better survival. Our findings concerning outcome predictors in NOMI patients undergoing intra-arterial prostaglandin therapy might help designing a randomized controlled trial to further investigate this therapeutic approach.Trial registration Retrospectively registered on January 22, 2020, at clinicaltrials.gov (REPERFUSE, NCT04235634), https://clinicaltrials.gov/ct2/show/NCT04235634?cond=NOMI&draw=2&rank=1.

Evaluation of Intra-Arterial Nimodipine Therapy in Post-Subarachnoid Hemorrhage Refractory Cerebral Vasospasm

Background: Cerebral vasospasm is a major cause of morbidity and mortality in patients with subarachnoid hemorrhage. Vasospasm is managed with triple H and vasodilators but sometimes, patients do not respond. Intra-arterial vasodilator infusion has been shown to improve outcome in such patients. In this study, we try to evaluate the efficacy of intra-arterial nimodipine therapy in 43 patients of post-aneurysmal subarachnoid hemorrhage refractory cerebral vasospasm.

Current Treatment Options in Cardiovascular Medicine: Update on Reversible Cerebral Vasoconstriction Syndrome

To describe advances in the diagnosis and management of reversible cerebral vasoconstriction syndrome (RCVS), a group of conditions with reversible multifocal narrowing of intracranial arteries. Over the last decade, multiple cohort studies have characterized RCVS and distinguished it from primary angiitis of the central nervous system and aneurysmal subarachnoid hemorrhage. Onset with recurrent thunderclap headaches (TCH) occurs in 85–90% of patients; most authors believe that RCVS and primary TCH are similar conditions. Rare cases with concurrent takotsubo cardiomyopathy or extracranial artery narrowing have been published. Stroke and brain edema can develop in up to 40% of inpatients; however, the discharge and 10-year outcome is invariably benign. Pregnancy-associated RCVS may have worse outcome. The pathophysiology remains relatively unknown. There is no specific treatment. Management involves pain relief and removal of identified vasoconstrictive factors. Calcium-channel blockers may help to relieve headaches. Glucocorticoids are associated with significantly worse outcome. The role of intra-arterial vasodilator infusion remains uncertain. The recently developed “RCVS2 score” enables accurate bedside diagnosis with up to 99% specificity and 90% sensitivity, obviating the need for invasive tests such as lumbar puncture, brain biopsy and catheter angiography to exclude mimics or confirm the diagnosis. RCVS can now be accurately diagnosed using clinical and imaging features available upon presentation. Advances in knowledge about the risk factors, prognosis, and potential harmful effects of certain therapeutic strategies, are expected to optimize the management of this increasingly well recognized syndrome.

Local Intra-arterial Vasodilator Infusion in Non-Occlusive Mesenteric Ischemia Significantly Increases Survival Rate

PurposeTo investigate the outcome of local intra-arterial papaverine infusion therapy in patients with non-occlusive mesenteric ischemia (NOMI), and factors influencing survival, in comparison with a conservative approach.MethodsFrom 2013 to 2019, patients with NOMI confirmed by imaging were included in a retrospective two-center study. According to different in-house standard procedures, patients were treated in each center either conservatively or interventionally by a standardized local infusion of intra-arterial papaverine into the splanchnic arteries. Thirty-day mortality and factors influencing the outcome, such as different demographics and laboratories, were compared between groups using Kaplan–Meier survival analysis and Cox regression, respectively.ResultsA total of 66 patients with NOMI were included, with n = 35 treated interventionally (21 males, mean age 67.7 ± 12.3 years) and n = 31 treated conservatively (18 females, mean age 71.6 ± 9.6 years). There was a significant difference in 30-day mortality between the interventional (65.7%; 12/35 survived) and the conservative group (96.8%; 1/31 survived) (hazard ratio 2.44; P = 0.005). Thresholds associated with a worse outcome of interventional therapy are > 7.68 mmol/l for lactate, < 7.31 for pH and < − 4.55 for base excess.ConclusionLocal intra-arterial papaverine infusion therapy in patients with NOMI significantly increases survival rate in comparison with conservative treatment. High lactate levels, low pH and high base excess, and high demand for catecholamines are associated with a poor outcome.Level of EvidenceLevel III.

Morphological changes of intracranial pressure quantifies vasodilatory effect of verapamil to treat cerebral vasospasm

IntroductionAfter aneurysmal subarachnoid hemorrhage (SAH), both proximal and distal cerebral vasospasm can contribute to the development of delayed cerebral ischemia. Intra-arterial (IA) vasodilators are a mainstay of treatment for distal...

Delayed Ischemic Neurologic Deficit after Aneurysmal Subarachnoid Hemorrhage.

Delayed ischemic neurologic deficit (DIND) is the main preventable cause of poor outcomes in aneurysmal subarachnoid hemorrhage (SAH) patients. Of 50% of survivors from a SAH, approximately 30% of patients will present clinical vasospasm (VS). The cornerstone of the DIND management comprises prevention and early identification. Several diagnostic methods have been proposed differing in efficacy, invasiveness, and costs. Serial neurological examination is the most reliable method to detect a new neurological deficit. On the other hand, comatose patients require advanced monitoring methods which identify changes in the microcirculatory environment, brain autoregulation, and spreading depolarization. Multimodality monitoring with continuous electroencephalography, microdialysis, and intracranial pressure monitoring represents altogether the current state-of-art technology for the intensive care of SAH patients. Moreover, advances in genetic biomarkers to predict clinical VS have shown consistent accuracy which may in the near future allow the early prediction of DIND through a simple blood test. Several clinical trials have tested drugs with theoretical effects on DIND prevention or treatment. Nevertheless, nimodipine remains the Holy Grail in the prevention of clinical VS. Among rescue therapies, the endovascular treatment through intra-arterial vasodilator (verapamil or nicardipine) infusion is the most employed method for DIND reversal; however, there is no good quality evidence comparing results of intra-arterial infusion of vasodilators versus balloon angioplasty. Although we have addressed the most refined technology in the management of SAH and DIND, the clinical experience and strict follow-up in neurointensive care will be determinant for favorable long-term outcomes.

Management of delayed cerebral ischemia after subarachnoid hemorrhage

For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization. Prevention of DCI primarily relies on nimodipine administration and optimization of blood volume and cardiac performance. Neurological monitoring is essential for early DCI detection and intervention. Serial clinical examination combined with intermittent transcranial Doppler ultrasonography and CT angiography (with or without perfusion) is the most commonly used monitoring paradigm, and usually suffices in good grade patients. By contrast, poor grade patients (WFNS grades 4 and 5) require more advanced monitoring because stupor and coma reduce sensitivity to the effects of ischemia. Greater reliance on CT perfusion imaging, continuous electroencephalography, and invasive brain multimodality monitoring are potential strategies to improve situational awareness as it relates to detecting DCI. Pharmacologically-induced hypertension combined with volume is the established first-line therapy for DCI; a good clinical response with reversal of the presenting deficit occurs in 70 % of patients. Medically refractory DCI, defined as failure to respond adequately to these measures, should trigger step-wise escalation of rescue therapy. Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated. This review provides an overview of current state-of-the-art care for DCI management.

Is intra arterial nimodipine really beneficial in vasospasm following aneurysmal subarachnoid haemorrhage?

Object/Background: Vasospasm is a common cause of mortality and morbidity following rupture of intracranial aneurysm. Hemodynamic therapy instituted in these patients in the past has been replaced by direct manipulation of the spastic vessels by angioplasty and intra-arterial infusion of vasodilators. However, no case control studies exist proving its superiority. The purpose of our study was to compare the efficacy of intra-arterial nimodipine (IAN) to that of hemodynamic therapy in patients with vasospasm following aSAH. Material and methods: Fifty-three patients who developed vasospasm following aSAH were included in the study. IAN was instilled in addition to hemodynamic therapy in 39 patients and 14 patients (who refused to give consent for IAN) were continued on hemodynamic therapy alone and served as controls. The response to IAN was studied on angiogram. The clinical response was assessed in both the groups at regular intervals. IAN was repeated if necessary. The outcome (GOS) at discharge and at 3 months after discharge was compared. Results: Thirty-six (92.3%) out of 39 patients showed immediate angiographic reversal of vasospasm.28 of them showed clinical response, of which only 11 had lasting response. 11(28.2%) of 39 patients who received IAN had a good outcome at discharge and 23(58.9%) had a favourable outcome at 3 months follow up. In those who received hemodynamic therapy alone, 4 out of 14(28.6%) patients had a good outcome at discharge and 8 (57.1%) a favourable outcome at 3 months. Conclusions: Angiographic reversal of vasospasm is seen in majority of the patients following IAN. However, this does not necessarily translate into a long lasting clinical response. The final outcome in patients who received hemodynamic therapy is comparable to those who received additional IAN. IAN does not appear to provide a major added advantage over the conventional hemodynamic therapy.

Intra-arterial vasodilator therapy for parainfectious cerebral vasospasm

Cerebrovascular complications of bacterial meningitis may include vasculitis, vasospasm or vasoconstriction, delayed cerebral infarction, venous and arterial thrombosis, intracranial aneurysm formation. The role of invasive endovascular therapies has not been well studied for infectious vasospasm, which can lead to dire neurologic consequences. We present 2 patients who were diagnosed with bacterial meningitis. Brain MRI showed areas of acute ischemia. Neurologic worsening was seen in both patients despite aggressive medical management. Follow-up imaging demonstrated significant narrowing of the intracranial vessels with associated new scattered infarcts. Both patients underwent targeted intra-arterial vasodilator infusion with angiographically improved vessel caliber and distal flow. The neurological exam subsequently stabilized in both cases. Follow-up radiographic images demonstrated no further ischemia in one of the 2 patients. Vasculopathy and vasospasm causing delayed ischemic neurologic deficit is a rare, but severe complication of acute meningitis. It can be a significant predictor of poor prognosis, and the disease may progress despite aggressive medical therapy. Although frequently used in subarachnoid hemorrhage-related vasospasm, to our knowledge, this is the first report of endovascular vasodilator treatment as adjunctive intervention in patients with meningitis associated vasculopathy.

Reversible Cerebral Vasoconstriction Syndromes: What the Cardiologist Should Know

Over the past decade, the reversible cerebral vasoconstriction syndromes (RCVS) have emerged as a group of conditions with easily recognizable clinical-angiographic features and a usually benign prognosis. The RCVS affect young individuals, mostly women, and the majority present with recurrent, severe, 'thunderclap' headaches. Vascular imaging studies show dynamic and reversible narrowing and dilatation of multiple intracerebral arteries. Brain imaging usually shows no parenchymal lesions, however, approximately one-third of patients develop ischemic or hemorrhagic strokes or reversible brain edema. The etiopathogenesis of this syndrome remains unclear. It has been associated with diverse conditions such as pregnancy, vasoconstrictive drug use, and neurovascular procedures. Recent studies characterizing RCVS have made it relatively easy to exclude mimics such as aneurysmal subarachnoid hemorrhage and primary angiitis of the central nervous system. There is no proven treatment, although calcium channel blockers may help to reduce the intensity of headaches. Empiric glucocorticoid treatment should be avoided. Since most patients do well with simple observation alone, invasive strategies such as pharmacologically-induced hypertension, balloon angioplasty, and direct intra-arterial vasodilator infusion should be reserved for patients showing clear clinical progression.

Transient Locked-in Syndrome and Basilar Artery Vasospasm

Cerebral vasospasm is the main cause of neurological mortality and morbidity following subarachnoid hemorrhage. Basilar artery vasospasm (BAVS) is associated with a high morbidity and may have multiple clinical presentations. We report the case of a 43 years-old man with BAVS presenting as a reversible locked-in syndrome (LIS) after stopping sedation. The symptoms were successfully managed by intra-arterial infusion of vasodilators and balloon angioplasty. Magnetic resonance imaging did not reveal any brainstem lesion 48 h after the complication, demonstrating a hemodynamic mechanism. LIS can reveal BAVS. Its diagnosis relies on clinical examination. In this case, rapid neuro-interventional treatment permitted reversal of symptoms. This could not have been possible under sedation.

Safety of early endovascular catheterization and intervention through extracranial-intracranial bypass grafts

The goal of this study was to demonstrate feasibility and evaluate technical aspects of early endovascular access through extracranial-intracranial (EC-IC) bypass grafts. Patients undergoing endovascular interventions through the graft in the acute postoperative period following EC-IC bypass are presented. Results, complications, and technical nuances are reviewed. Fourteen endovascular procedures were performed in 5 patients after EC-IC bypass for ruptured aneurysms in 4 patients and posterior circulation ischemia in 1 patient. In 2 patients, a saphenous vein graft (SVG) was used to bypass the common carotid artery (CCA) to the middle cerebral artery (MCA). One patient underwent a superficial temporal artery (STA)-MCA bypass, and in 2 other patients the STA stump was connected to the intracranial circulation via an interposition SVG. The interval from surgery to endovascular intervention spanned 2-18 days; the indication was intracranial vasospasm in all patients. One case involved angioplasty of the proximal anastomosis on postoperative Day 14. All other interventions entailed proximal access through the bypass conduit for intraarterial infusion of vasodilators. Significant vasospasm of the STA itself was encountered in 2 patients during endovascular manipulation, and it was treated with intraarterial nitroglycerin. There were no cases of anastomotic disruption. Endovascular catheterization and intervention involving a recent EC-IC bypass is feasible. The main limitation in this series was catheter-induced vasospasm involving the STA. A vein graft may be the more appropriate option in patients with subarachnoid hemorrhage who may require subsequent endovascular intervention for vasospasm.

Aneurysmal Subarachnoid Hemorrhage: An Overview for the Practicing Neurologist

Subarachnoid hemorrhage (SAH) accounts for ~5% of strokes, but causes high rates of morbidity and mortality and occurs at a relatively young age. The rupture of an intracranial aneurysm is the leading cause of nontraumatic SAH and will be the subject of this review. Rebleeding remains the most imminent danger until the aneurysm is secured (i.e., excluded from the cerebral circulation). Therefore, prompt aneurysm treatment is crucial to minimize this risk. Endovascular occlusion of the aneurysm with coils has been shown to be associated with better short- and long-term outcomes than surgical clipping in select patients. Yet, angiographic surveillance is necessary after endovascular treatment and retreatment with additional coiling may be required. Delayed cerebral vasospasm is the leading cause of brain damage once the aneurysm has been treated. Hemodynamic augmentation therapy remains the mainstay of medical treatment, but various agents are being tested as means to prevent or ameliorate vasospasm, including magnesium sulfate, statins, and an endothelin antagonist. Medically refractory vasospasm demands angioplasty of the affected vessel or intraarterial infusion of vasodilators. In this review, the authors provide an overview of the diagnosis and management of aneurysmal SAH with an emphasis on these main topics.

Improvement in Angiographic Cerebral Vasospasm after Intra-Arterial Verapamil Administration

Endovascular options for therapy for patients with vasospasm after SAH include angioplasty and intra-arterial vasodilator infusion. Preliminary studies of the effects of the calcium channel antagonist verapamil on angiographic vasospasm have yielded mixed and/or qualitative results. In this study, improvement in angiographic vasospasm after intra-arterial verapamil administration is demonstrated with quantitative, blinded methods. This retrospective observational case series includes 12 patients with vasospasm after SAH who collectively received 16 treatments with intra-arterial verapamil during a 2-year period at our institution. The exclusion criterion was concurrent treatment with angioplasty. Blinded reviewers quantitatively evaluated angiograms from each patient and/or treatment after presentation with SAH and before and after intra-arterial treatment of vasospasm. Patients were treated with intra-arterial verapamil for vasospasm 9 ± 4 days after SAH with a range from 1 to 16 days. For the 34 arterial distributions treated, the segment with the worst angiographic vasospasm from each arterial distribution averaged 51 ± 13% stenosis, which improved to 29 ± 18% stenosis (P < .001). There was no significant difference in treatment effect in proximal arterial segments, which may be amenable to angioplasty, compared with distal segments (P > .05). There was no significant difference in treatment effect in arterial segments previously subjected to angioplasty compared with other segments (P > .05). Intra-arterially administered verapamil improves angiographic vasospasm after SAH when administered at 10 ± 3 mg per arterial distribution. Optimal dose, infusion rate, and retreatment interval remain to be determined. Randomized controlled trials are needed to prove efficacy in the treatment of clinical vasospasm.

Procedural predictors of delayed cerebral infarction after intra-arterial vasodilator infusion for vasospasm following aneurysmal subarachnoid hemorrhage

The goals of this study were to identify predictors of delayed cerebral infarction in aneurysmal SAH after intra-arterial (IA) vasodilator infusion and to select proper parameters for treatment success. Forty-three patients qualified for review. Cerebral infarction was determined by DWI within 1 week of angiographic vasospasm. Infarction developed in 18 of the 43 patients (41.9%) after IA vasodilator infusion and was associated with a high degree of proximal vessel residual narrowing and angiographic cerebral circulation time (CCT) prolongation at the end of IA vasodilator infusion (p < 0.001). A high degree of proximal residual narrowing (p = 0.018; odds ratio = 1.071; 95% confidence interval [CI] 1.012-1.123) and CCT prolongation at the end of the procedure (p = 0.007; odds ratio = 2.203; 95% CI 1.254-4.232) were found to be predictors of infarction by multivariate analysis. Furthermore, receiver operating characteristic (ROC) curves showed that both variables predicted the development of infarction (proximal vessel residual narrowing, area under the ROC curve [AUC], 0.828; CCT, AUC, 0.866). When proximal vessel narrowing of >30% or a CCT of >7 s by final angiography during IA vasodilator infusion were used as a threshold, the negative predictive value for infarction was 88.9% (95% CI 65.3-98.6%), and when narrowing was >30% and CCT was >7 s, the probability of subsequent cerebral infarction was 100% (95% CI 71.7-100%). Angiographic CCT and residual narrowing at the end of IA vasodilator infusion were found to predict the subsequent occurrence of cerebral infarction. The authors suggest that residual narrowing of 30% and a CCT of 7 s could be used as a minimum indicator of IA vasodilator infusion endpoints.

CONTROVERSIES IN THE ENDOVASCULAR MANAGEMENT OF CEREBRAL VASOSPASM AFTER INTRACRANIAL ANEURYSM RUPTURE AND FUTURE DIRECTIONS FOR THERAPEUTIC APPROACHES

Cerebral vasospasm is one of the leading causes of morbidity and mortality after aneurysmal subarachnoid hemorrhage. Despite maximal medical therapy, however, up to 15% of patients surviving the ictus of subarachnoid hemorrhage experience stroke or death from vasospasm. For those cases of vasospasm that are refractory to medical treatment, endovascular techniques are frequently used, including balloon angioplasty with or without intra-arterial infusion of vasodilators, combined endovascular modalities, and aortic balloon devices. In this article, we review each of these therapies and their expanding role in the management of this condition. Moving forward, rigorous prospective outcome assessments after endovascular treatment of cerebral vasospasm are necessary to clearly delineate the efficacy and indications for these techniques.

Cerebral vasospasm in subarachnoid hemorrhage

The treatment of vasospasm after subarachnoid hemorrhage remains a formidable challenge. The prompt recognition of this complication is essential to prevent ischemic damage. Initial orders should include adequate fluid and sodium supplementation to avoid volume depletion. Prophylactic hypervolemia is not effective in reducing the incidence of vasospasm and may be deleterious. Oral nimodipine (60 mg every 4 hours for 21 days) should be started on admission because it protects against delayed ischemic damage. Increasing blood flow velocities on serial transcranial Doppler studies are reliable indicators of early development of vasospasm. When symptomatic vasospasm occurs, hemodynamic augmentation therapy should be instituted. Crystalloids and colloids may be used to promote hypervolemia. Colloids may provide additional benefit by producing hemodilution. However, the rheological benefits of hemodilution may be offset by reduced oxygen carrying capacity when hematocrit drops below 28%. Hypertension may be induced by administering inotropic drugs and, in certain cases, cardiac output optimization using dobutamine also is necessary. When aggressive medical therapy fails to reverse ischemic deficits, prompt endovascular intervention is indicated. Focal vasospasm of larger vessels may be effectively treated with angioplasty and the benefits of this procedure are durable. Diffuse vasospasm involving smaller arterial branches may be treated with intra-arterial infusion of vasodilators, such as papaverine, verapamil, or nicardipine. Unfortunately, these dilatory effects tend to be short-lasting. In refractory cases, hypothermia may be considered, although value of this strategy remains largely unexplored.

The renal response to ureteral obstruction: a model for the study of factors which influence glomerular filtration pressure.

Abstract The relationship of glomerular filtration pressure to filtration rate has been examined under various experimental conditions in the rat. Unilateral ureteral obstruction, of 24 hours' duration, produces a marked reduction in filtration rate, measured after release of occlusion. This excretory lesion is associated with a reduction in glomerular filtration pressure. The relationship between filtration rate and pressure after release of obstruction closely resembles that observed in the normal kidney in which perfusion pressure is reduced by aortic constriction. The data indicate that the reduction in filtration pressure is the sole factor responsible for excretory failure after ureteral obstruction and that this lesion is characterized by an increase in preglomerular arteriolar resistance. This conclusion is supported by the observation that the intraarterial infusion of vasodilators, papaverine and acetylcholine, markedly augments filtration rate and pressure in the affected kidney. The effect of volume expansion with mannitol or albumin solutions has been studied in this lesion. Both produce a rapid and marked increase in filtration rate and pressure after release of obstruction. The effect of mannitol on filtration pressure appears to be manifest only in the free flow state, not when mannitol is given after ureteral clamping. This suggests that the action of mannitol is mediated by an intrarenal feedback mechanism responsive to changes in sodium delivery to the distal nephron. Although the precise mechanism involved in the pathogenesis of decreased filtration pressure after unilateral ureteral obstruction remains undefined, this appears to offer a simple and useful model for the study of physiologic and pathologic factors which affect glomerular filtration pressure.