Prognostic significance of pre-transplant quality of life in allogeneic hematopoietic cell transplantation recipients.

Quality of life (QOL) is an important outcome for hematopoietic cell transplantation (HCT) recipients. Whether pre-HCT QOL adds prognostic information to patient and disease related risk factors has not been well described. We investigated the association of pre-HCT QOL with relapse, non-relapse mortality (NRM), and overall mortality after allogeneic HCT. From 2003 to 2012, the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale instrument was administered before transplantation to 409 first allogeneic HCT recipients. We examined the association of the three outcomes with (1) individual QOL domains, (2) trial outcome index (TOI) and (3) total score. In multivariable models with individual domains, functional well-being (hazard ratio (HR) 0.95, P=0.025) and additional concerns (HR 1.39, P=0.002) were associated with reduced risk of relapse, no domain was associated with NRM, and better physical well-being was associated with reduced risk of overall mortality (HR 0.97, P=0.04). TOI was not associated with relapse or NRM but was associated with reduced risk of overall mortality (HR 0.93, P=0.05). Total score was not associated with any of the three outcomes. HCT-comorbidity index score was prognostic for greater risk of relapse and mortality but not NRM. QOL assessments, particularly physical functioning and functional well-being, may provide independent prognostic information beyond standard clinical measures in allogeneic HCT recipients.

Quality of life and outcomes in patients⩾60 years of age after allogeneic hematopoietic cell transplantation.

Hematopoietic cell transplantation (HCT) has become an established standard of care for many older patients with hematologic malignancies. The effect of transplantation on the quality of life (QOL) of older patients, however, has not been well studied. We thus analyzed QOL in patients ⩾60 undergoing an allogeneic HCT compared with patients <60 years. Prospective psychometric instruments were administered to 351 patients who underwent HCT from 2003 to 2010. Psychometric data were assessed longitudinally by validated questionnaires: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), Coping Inventory and the Profile of Mood State-Short Form. Patients ⩾60 reported better social (P=0.006) and functional well-being (P=0.05) with FACT assessment, and had better total scores, (P=0.043) across all time points. When adjusted for baseline QOL scores as a covariate, social well-being remained significantly better, whereas the other scores became non-significant. With a median follow-up of 49 months, there were no significant differences in OS, relapse-free survival, relapse or chronic GVHD. This study provides further evidence that advanced age should not be a barrier in the decision to pursue allogeneic HCT. Older patients achieved comparable QOL when compared with younger patients.

Validating the positive impact of in-hospital lay care-partner support on patient survival in allogeneic BMT: a prospective study.

This prospective study validates the finding from retrospective research that having an inpatient lay care-partner (CP) is associated with better survival following allogeneic BMT. Compared with patients without a CP (n=76), patients with a CP (n=88) have significantly better OS (P=0.017) and relapse-free survival (RFS) (P=0.020). Four-year and median survivals were 42% and 36 months among patients with CPs, compared with 26% and 10 months among those without CPs. Four-year survival and median RFS were 39% and 25 months among those with CPs, compared with 23% and 7 months among those without CPs. Further, better survival and RFS were associated with CP visit duration of >3 h per day (P=0.005 and P=0.007, respectively) and with CP frequency of visits >75% of inpatient days (P=0.004 and P=0.010, respectively). A CP support program should encourage not only presence of a CP but also duration and frequency of CP visits associated with better patient survival.

Utility of the psychosocial assessment of candidates for transplantation (PACT) scale in allogeneic BMT.

The psychosocial assessment of candidates for transplantation (PACT) scale was completed before the transplant on 120 patients who underwent allogeneic transplant from November 2003 to June 2007. The PACT has eight subscales, each rated on a 5-point scale, and an initial and final rating independently based on the rater's overall impressions of the candidate's acceptability for transplant. This exploratory study assessed the clinical utility of the PACT scale for psychosocial screening in allogeneic BMT. Associations of the PACT subscales and the final rating with sixteen post transplant medical outcomes were examined using the Jonchkheere-Terpstra test, the Cochran-Armitage test or the Cox proportional hazards analysis. Significant relationships (P

Allogeneic BMT and patient eligibility based on psychosocial criteria: a survey of BMT professionals.

BMT professionals were compared regarding their willingness to proceed with allogeneic BMT given select psychosocial issues. A questionnaire was sent to 660 physician members of ASBMT, 92 social work members of BMT Special Interest Group, Association of Oncology Social Work, and 626 nurse members of BMT Special Interest Group, Oncology Nursing Society; 597 responded with a response rate of 43.5%. Items included background information, followed by 17 case vignettes; each represented a different psychosocial issue to which respondents indicated whether or not they would recommend proceeding with allogeneic BMT. In every vignette, at least 10% of respondents indicated they would not proceed. In six vignettes, at least 64% indicated do not proceed: suicidal ideation (86.8%), uses addictive illicit drugs (81.7%), history of noncompliance (80.5%), no lay caregiver (69.3%), alcoholic (64.8%), and mild dementia/Alzheimer's (64.4%). In 10 vignettes, at least 73% indicated proceed. On four vignettes, professional subgroups differed in their recommendation on whether or not to proceed with allogeneic BMT. Qualitative data suggest that this decision is contingent on the perceived acuity, severity, and currency of the psychosocial issue, patient ability to comply with treatment given the issue, and its manageability as a risk factor for treatment related vulnerability and outcomes.

Endothelin-mediated constriction of prenodal lymphatic vessels in the canine forelimb.

Endothelin is a 21 amino acid peptide which is produced by the vascular endothelium and is believed to be the mediator of endothelium-dependent vasoconstriction. In the current study we assessed the ability of synthetic human endothelin-1 to affect prenodal lymphatic vessel contractility in the canine forelimb. Intralymphatic infusion of endothelin at 1.09 x 10(-9), 1.09 x 10(-8) and 1.09 x 10(-7) M significantly constricted lymphatic vessels as evidenced by dose-dependent increases in lymphatic perfusion pressure. The increase in lymphatic perfusion pressure seen during intralymphatic infusion of endothelin at 1.09 x 10(-8) M during the intra-arterial infusion of phentolamine was not significantly different from that seen prior to phentolamine, indicating that endothelin-mediated lymphatic constriction is not alpha-receptor mediated. Intra-arterial infusion of endothelin at three infusion rates significantly increased forelimb arterial, systemic and lymphatic perfusion pressures. The constriction seen when endothelin (1.09 x 10(-8) M) was infused intralymphatically in the intact lymphatic system was not significantly different from that observed when only the prenodal lymph vessel was perfused. This indicated that the lymph nodes and efferent lymph vessels do not contribute significantly to the lymphatic constriction produced by endothelin. These data are consistent with the hypothesis that endothelin may modulate lymphatic function under either normal or pathophysiological conditions.

Perfused prenodal lymphatics are constricted by prostaglandins.

Prostaglandins may contribute to the control of lymph flow by affecting lymphatic vessel contractility. We measured the pressure in perfused prenodal lymphatic vessel in the paw of the anesthetized dog as affected by administration of prostaglandins E1, E2, F2 alpha or arachidonic acid. The forelimb was perfused at constant flow with blood obtained from a femoral artery. Systemic arterial, central venous, and forelimb vascular pressures were measured. When added to the lymphatic perfusate, all of the prostaglandins and arachidonic acid caused constriction of lymphatic vessels. Perfusion of prenodal lymphatics separated from downstream nodes and vessels showed that this constriction occurred primarily in prenodal vessels. However, only prostaglandin F2 alpha caused lymphatic constriction when infused into the blood to the forelimb. Because prostaglandins are a common component of the lymph leaving an area of tissue damage, these results are compatible with the possibility that prostaglandins, by directly affecting lymphatics, help modulate lymph flow following local injury.

On-site screening for urinary Hg concentrations and correlation with glomerular and renal tubular function.

At the American Dental Association 1985 and 1986 Annual Sessions, an on-site screening for mercury was conducted as part of the Health Screening Program (HSP) to identify dentists having elevated urinary mercury concentrations. The data generated from this study were used to examine the relationship between elevated urinary mercury exposure and kidney dysfunction. Kidney dysfunction was assessed by measurement of serum and urine beta 2 microglobulin concentrations, serum creatinine, and creatinine clearance. The mean values found for urinary mercury were 5.8 micrograms Hg/L and 7.6 micrograms Hg/L for 1985 and 1986, respectively. Urinary mercury concentrations for this population were found to fall within the range of not detected to 115 micrograms Hg/L. Of the total number of participants assayed in 1985 and 1986, roughly 10 percent of the sample exhibited elevated mercury concentrations above 20 micrograms Hg/L. An analysis of the clinical markers indicated no clear relationship between elevated urinary mercury concentrations and kidney dysfunction. In addition to mercury testing, all dentists who participated in the 1985 and 1986 HSP were issued a questionnaire soliciting information as to their professional exposure. Those participants who were identified as having elevated urinary mercury concentrations in the 1985 HSP were issued a followup questionnaire that addressed psychological and neuropsychological symptoms. From these questionnaires three significant relationships were found. These relationships were associated with mercury/amalgam handling and skin contact, the number of amalgams placed by the dentist, and the number of hours of practice per week. The reported absence of a clear relationship between urinary mercury concentrations and potential kidney dysfunction is in agreement with other findings at the mercury concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Constriction of perfused lymphatics by acetylcholine, bradykinin and histamine.

We have previously reported that perfused lymphatic vessels in the canine forelimb constrict in response to increased sympathetic nerve activity or local infusions of endogenous vasoconstrictor substances. In the present study we have assessed the effects of three endogenous vasodilators; acetylcholine, bradykinin and histamine on lymphatic vessel contractility. Each one of these agents, when infused intralymphatically, produced lymphatic constriction as evidenced by significant increases in lymphatic perfusion pressure. The threshold concentrations which produced lymphatic constriction were between 10(-6) and 10(-5) molar for acetylcholine and bradykinin and between 10(-5) and 10(-4) molar for histamine. Surgical exclusion of the lymph nodes and efferent lymph vessels from the perfused tissue did not significantly affect the observed response, indicating that the response occurs predominately in the prenodal segments of the lymphatic system. Infusion of acetylcholine and bradykinin into the arterial supply to the forelimb did not significantly alter lymphatic perfusion pressure, unlike the response seen when catecholamines are infused intra-arterially. Histamine displayed an unusual property in that it constricts lymph vessels upon initial administration but was thereafter completely ineffective. Constriction of lymphatic vessels by substances which are potent vasodilators clearly indicates that significant functional differences exist in endothelial cell/smooth muscle relationships between blood vessels and lymph vessels.

The inflammatory actions of platelet activating factor are blocked by levorotatory terbutaline.

Platelet activating factor (PAF), a potent vasoactive lipid, may play an important role in the inflammatory process. In this study, we infused PAF intra-arterially to characterize its edematogenic potency in the canine forelimb. We have also assessed the ability of the beta 2-receptor agonist l-terbutaline to block PAF-mediated edema formation. The infusion of PAF at .25 micrograms/min, .5 micrograms/min and 1 micrograms/min increased forelimb arterial pressures and, at the two higher dosages, significantly decreased systemic arterial pressure. PAF infusions increased transvascular fluid and macromolecular flux as indicated by significant increases in skin lymph flow, protein concentration and protein transport. The intra-arterial infusion of l-terbutaline at 1 micrograms/min significantly decreased forelimb arterial pressures but did not affect small vein pressure, systemic pressure or forelimb lymph parameters. The subsequent infusion of PAF at .5 micrograms/min, during the continued infusion of l-terbutaline, failed to significantly affect forelimb lymph parameters. These data indicate that PAF is significantly more potent as an edematogenic agent in the forelimb than histamine or bradykinin. Furthermore, the blockade of PAF-mediated edema formation by l-terbutaline suggests that beta 2-receptor agonists may be capable of antagonizing the inflammatory actions of a wide variety of putative inflammatory mediators.

Neurokinin A and B: potent vasodilators in the canine forelimb.

Neurokinin A and neurokinin B may play a role in control of the peripheral circulation in either physiological or pathophysiological conditions. We have infused these peptides intra-arterially at three infusion rates each to assess their actions on vascular pressures, blood flows and total and segmental resistances in skin and skeletal muscle in the canine forelimb. Neurokinin A infusions (.01, .1, and 1 micrograms/min) decreased total forelimb resistance; transiently, 26% and 57%, respectively. The decrease in resistance was equally distributed between the skin and skeletal muscle circulations and was manifest in both large artery and small vessel resistances. Systemic and forelimb arterial pressures were decreased in a dose-dependent manner. Neurokinin B infusions (.5, 1 and 5 micrograms/min) decreased total forelimb resistance 29%, 31%, and 52%, respectively. The decrease in resistance was equally distributed between the skin and skeletal muscle circulations and was the result of decreases in both large artery and small vessel resistances. Systemic and forelimb arterial pressures were decreased in a dose-dependent manner. The potent effect of neurokinins on vascular resistance and their concentration in perivascular nerves innervating the resistance vessels of the circulation suggests a potential role for these neuropeptides in circulatory control.

Stereospecificity of the anti-inflammatory actions of terbutaline.

Intra-arterial infusion of a racemic mixture of the beta 2-agonist terbutaline blocks histamine-mediated increases in lymph flow and protein concentration in the canine forelimb. In the current study we have assessed the relative anti-inflammatory potencies of the purified stereoisomers of terbutaline. Infusion of histamine (4 micrograms base/min) increased lymph flow, protein concentration and protein transport. The intra-arterial infusion of 1-terbutaline (1 microgram/min) significantly decreased forelimb arterial pressures and prevented any changes in lymph parameters due to subsequent histamine infusion. Intra-arterial infusion of d-terbutaline (1 microgram/min) did not significantly affect forelimb vascular pressures but subsequent to histamine administration, lymph parameters increased similar to that seen with histamine alone. Infusion of a high dose of d-terbutaline (100 micrograms/min) slightly decreased forelimb arterial pressures but failed to inhibit histamine-mediated increases in lymph parameters. Infusion of 1-terbutaline alone (1 microgram/min) significantly decreased forelimb arterial pressures, lymph flow and protein transport and slightly but significantly increased lymph protein concentration. These data indicate that the beta 2-agonistic and anti-inflammatory properties of terbutaline are confined solely to the levorotatory enantiomer.

Anti-inflammatory actions of enprofylline, a modified xanthine, in the canine forelimb.

It has been previously reported that enprofylline (3-propyl xanthine) prevents histamine-mediated edema formation in the guinea pig lung. To further assess the potential anti-inflammatory effects of enprofylline, we infused it intra-arterially into the canine forelimb before and during a local intra-arterial infusion of histamine (4 micrograms/min) while monitoring forelimb skin lymph parameters. Infusion of enprofylline at 2 mg/min significantly decreased forelimb arterial pressures and increased heart rate and pulse pressure. Subsequent infusion of histamine caused a further reduction in forelimb arterial pressures and an increase in lymph flow, protein concentration, and protein transport similar to that seen with the infusion of histamine alone. Infusion of enprofylline at 5 mg/min decreased forelimb arterial pressures and systemic pressure. Subsequent histamine infusion further reduced forelimb arterial pressures, but the increase in lymph parameters was markedly attenuated. Enprofylline infused at 10 mg/min also decreased forelimb arterial and systemic pressures, but subsequent histamine infusion was essentially without effect on lymph parameters. To assess the role of catecholamines in enprofylline-mediated attenuation of histamine edema formation, we infused enprofylline at 5 mg/min in the presence of a beta 2-receptor blockade produced by the intra-arterial infusion of ICI 118551. The effects of enprofylline and histamine on vascular pressures were similar to those seen in the absence of beta 2-receptor blockade, but lymph flow, protein concentration, and protein transport increased similar to that seen with histamine alone. These data indicate that enprofylline is capable of attenuating histamine-induced increases in microvascular permeability, but this action of enprofylline is of an indirect nature, mediated through the release of catecholamines.

Bradykinin-mediated edema formation is blocked by levorotatory but not dextrorotatory terbutaline.

The ability of the purified stereoisomers of the beta 2-receptor agonist terbutaline to block bradykinin-mediated increases in lymph flow and protein concentration was assessed in the canine forelimb perfused at constant arterial flow. Intra-arterial infusion of bradykinin (2 micrograms/min, n = 8) decreased forelimb arterial pressures but did not affect skin small vein pressure or systemic pressure. Lymph flow, protein concentration and protein transport were significantly increased. Intra-arterial infusion of 1-terbutaline (1 microgram/min, n = 9) decreased forelimb arterial pressures and systemic pressure but did not affect lymph parameters. Subsequent infusion of bradykinin during the continued infusion of 1-terbutaline failed to alter forelimb lymph parameters. Intra-arterial infusion of d-terbutaline (1 microgram/min, n = 11) did not alter vascular pressures or lymph parameters. Subsequent infusion of bradykinin during the continued infusion of d-terbutaline decreased forelimb arterial pressures and significantly increased lymph flow, protein concentration and protein transport. Intra-arterial infusion of a high dose (100 micrograms/min, n = 9) of d-terbutaline significantly decreased forelimb arterial pressure but was likewise ineffective in blocking the increases in lymph parameters produced by subsequent bradykinin infusion. These data indicate that the beta 2-receptor agonistic and anti-permeability actions of terbutaline are found solely in the levorotatory enantiomer.

Constriction of lymphatics by catecholamines, carotid occlusion, or hemorrhage.

Regulation of lymphatics by sympathetic nerves or hormones seems probable. To elucidate this, we perfused a lymphatic vessel in the paw of the anesthetized dog while measuring lymphatic perfusion pressure. We studied the effects of norepinephrine, epinephrine, hemorrhage, and carotid occlusion on lymphatic pressure. Blood was pumped to the forelimb via the brachial artery. Cannulas were placed to measure systemic, central venous, and forelimb vascular pressures. Catecholamines, whether added to the lymphatic perfusate or infused into the forelimb arterial blood, and bilateral carotid occlusion significantly increased lymphatic perfusion pressure. Perfusion of prenodal lymphatics disconnected from downstream vessels and nodes indicated that this increase occurred primarily in prenodal lymph vessels. Hemorrhagic hypotension to 55 mmHg did not affect lymphatic pressure but reduction to 35 mmHg did. The increase in lymphatic pressure produced by epinephrine and norepinephrine was blocked by phentolamine. Increased lymphatic perfusion pressure subsequent to exogenous catecholamines, severe hemorrhagic hypotension, or bilateral carotid occlusion supports the possibility that lymphatic function is modulated by adrenergic mechanisms in physiological and/or pathophysiological states.

Effects of bolus injections of leukotrienes and norepinephrine on forelimb vascular and lymphatic pressures.

Leukotrienes, lypoxygenase metabolites of arachadonic acid, have been reported to be potent vasoconstrictors in some organs. This study was undertaken to delineate the actions of leukotrienes on both vascular and lymphatic vessels in the canine forelimb. Bolus intra-arterial injections of 1 microgram and 10 micrograms of leukotriene B4, C4, and D4 and 1 microgram of norepinephrine were made into forelimbs perfused at constant flow. Norepinephrine significantly increased systemic, forelimb perfusion and small artery pressures. Lymphatic pressure was significantly increased from a control of 6.6 mmHg to a peak of 14.4 mmHg. Leukotriene B4 in either dosage, did not significantly affect vascular or lymphatic pressures. Leukotriene C4 (1 microgram or 10 micrograms) significantly increased systemic and forelimb arterial pressures but did not alter lymphatic pressure. Leukotriene D4 (1 microgram) significantly increased small artery pressure. Leukotriene D4 (10 micrograms) increased systemic and forelimb arterial pressures. Neither dosage of leukotriene D4 significantly affected lymphatic pressure. Repeat injection of norepinephrine after completion of all leukotriene injections again markedly increased systemic, forelimb arterial and lymphatic pressures. These data indicate that leukotrienes exhibit only mild constrictor effects on forelimb blood vessels and do not significantly affect forelimb prenodal lymphatic vessels.

Aminophylline attenuates the edemogenic actions of histamine in the canine forelimb.

Xanthines have been employed clinically to treat asthma and related pulmonary conditions because of their bronchodilator properties. In addition, xanthines have been reported to block and/or attenuate the increase in microvascular permeability to macromolecules produced by some putative inflammatory mediators. In order to more completely assess the anti-inflammatory capabilities of xanthines, we have infused aminophylline intra-arterially in the canine forelimb prior to and during a local intra-arterial infusion of histamine. Forelimb prenodal lymph flow, protein concentration and protein transport were used as indices of transvascular fluid and protein flux. Infusion of histamine (4 micrograms/min) significantly decreased forelimb arterial pressures and increased lymph flow, protein concentration and protein transport. Aminophylline infusion (10 mg/min) decreased forelimb arterial pressures but did not affect lymph parameters. Histamine infusion during infusion of aminophylline increased lymph parameters but the increases were markedly less than with histamine infusion alone. Infusion of aminophylline (20 mg/min) decreased forelimb arterial pressures and systemic pressure. Subsequent histamine infusion resulted in small but significant increases in lymph parameters. These data indicate that aminophylline infusion can blunt the ability of subsequently administered histamine to increase microvascular permeability as evidenced by the attenuation of the increases in lymph flow, protein concentration and protein transport.

Constriction of canine prenodal lymphatic vessels following the intra-arterial injection of vasoactive agents and hemorrhage.

In the forelimbs of anesthetized dogs, perfused at constant arterial inflow, we measured the pressure in a prenodal lymphatic vessel before and following arterial hemorrhage to a mean systemic arterial pressure of approximately 55 mmHg. We also made bolus intra-arterial injections of 1 microgram epinephrine and arginine vasopressin or 20 micrograms dopamine, prostaglandin F2 alpha and tyramine. Hemorrhage and all vasoactive substances significantly increased forelimb perfusion pressure and skin small artery pressure. Skin small vein pressure was significantly decreased by hemorrhage or injection of epinephrine, dopamine or tyramine, but was not significantly altered by arginine vasopressin or prostaglandin F2 alpha. Mean systemic arterial pressure was decreased by hemorrhage, increased by arginine vasopressin, tyramine and prostaglandin F2 alpha but remained unchanged following the injection of either epinephrine or dopamine. Lymphatic pressure was significantly increased following hemorrhage or the injection of all vasoactive agents. The increase seen with tyramine was small but consistent and thus statistically significant. These data indicate that the prenodal lymphatic vessels of the canine forelimb actively constrict in response to the neural and/or hormonal consequences of arterial hemorrhage or the introduction of exogenous vasoactive substances into the arterial blood supply to the forelimb. The results of the current study support the possibility that lymphatic function, through activation of lymphatic smooth muscle, is subject to neural and/or hormonal regulation in certain physiological and/or pathophysiological states.

Evidence for constriction of canine prenodal lymphatic vessels by vasoactive agents and carotid occlusion.

We measured pressure in a prenodal lymphatic in the canine forelimb during constant flow pump-perfusion of the brachial artery. We made bolus i.a. injections of 1.0 micrograms angiotensin II, norepinephrine, bombesin, or bradykinin, 20 micrograms 5-hydroxytryptamine (5HT), or occluded the carotid arteries. Norepinephrine, 5HT, or carotid occlusion produced regular rises in forelimb perfusion pressure and in lymphatic pressure. Angiotensin II increased forelimb arterial pressures but increased lymphatic pressure in only four experiments. Bombesin increased artery pressures but did not affect lymphatic pressure. Small vein pressure was increased by carotid occlusion, 5HT and norepinephrine. Increases in lymphatic pressure were coincident with increases in vein pressure but no related in magnitude. Bradykinin decreased forelimb arterial and venous pressures but did not affect lymphatic pressure. Either active constriction of lymphatic vessels or passive compression by movements of adjacent blood vessels could increase lymphatic pressure. These data do not preclude a passive component of pressure rise in the lymphatics nor do they support the concept. We conclude that active constriction of prenodal lymphatic vessels in the dog forelimb can occur in response to circulating vasoactive agents and bilateral carotid occlusion.

Response of the forelimb vasculature to vasoactive agents: effects of ouabain.

The effect of the local intra-arterial infusion of ouabain (11.8 micrograms/min.) on the response of the forelimb to vasoactive agents was examined. In seven dogs, bolus injections of CaCl2, MgSO4, KCl, norepinephrine, adenosine, acetylcholine, PGE1 and saline were made into the forelimb perfused at constant flow before and three times during ouabain infusion. Ouabain blocked potassium vasodilation and changed the response to CaCl2 from vasoconstriction to vasodilation. The response of the forelimb to the other vasoactive agents was initially unaffected by ouabain but with time the forelimb vasculature became less sensitive to all agents studied. These changes were not seen in a series of 5 saline infused control animals. In a third series of animals steady-state dose responses to CaCl2, Ca-gluconate and KCl were explored by infusing solutions intrabrachially at three dosages. Before ouabain, forelimb resistance increased as a function of Ca++ and decreased as a function of K+. Ouabain completely blocked potassium vasodilation and on the average blocked Ca++ vasoconstriction although a number of animals evidenced vasodilation to Ca++ during ouabain infusion. These data indicate that K+ vasodilation is Na+, K+-ATPase dependent and that Na+, K+-ATPase inhibition unmasks a vasodilatory action of locally applied Ca++.