In vitro hemocompatibility studies of drug-loaded poly-(L-lactic acid) fibers.

Our objective was to evaluate the hemocompatibility of biodegradable stent fibers, employing a closed-loop circulation system filled with human blood. We also investigated the effects of the anti-inflammatory and anti-proliferative drugs curcumin and paclitaxel, incorporated into stent fibers. Fresh whole blood was circulated in four parallel closed-loop systems: the empty tube circuit (control) and tubes containing either a PLLA fiber coil (PLLA), a curcumin-loaded PLLA coil (C-PLLA) or a paclitaxel-loaded PLLA coil (P-PLLA). The influence of PLLA fiber, alone or loaded with drug incorporated during melt-extrusion, on leukocyte and platelet adhesion and activation was determined by flow cytometry. The effects of blood flow and fiber properties on cell deposition were assessed by scanning electron microscopy (SEM). The flow cytometry results clearly demonstrated that PLLA triggers blood cell activation at the site of deployment, as shown by increases in CD11b, CD62P and leukocyte-platelet aggregates, compared to controls. Curcumin and paclitaxel treatments both significantly reduced leukocyte and platelet activation and adhesion to PLLA fibers, as shown by flow cytometry and SEM. Activated leukocytes and platelets revealed significantly lower CD11b and CD62P receptor binding for C-PLLA compared with PLLA alone, and slightly lower for P-PLLA. Reductions in platelet-leukocyte aggregates were observed as well. In addition, there was less leukocyte and platelet adhesion to C-PLLA, compared with PLLA fiber controls, as shown by SEM. A continuous linear thrombus, composed of platelets, leukocytes, red blood cells and fibrin was occasionally detected along the line of tangency between the coil and the tube wall. Flow separation and eddying, proximal and distal to the line of tangency of coil and tube, is thought to contribute to this deposit. Curcumin was more effective than paclitaxel in reducing leukocyte and platelet activation and adhesion to PLLA stent fibers in this setting. However there was evidence of paclitaxel degeneration during melt extrusion that may have inhibited its effectiveness. Incorporation of the anti-inflammatory and anti-proliferative drug curcumin into bioresorbable stent fibers is proposed to prevent thrombosis and in-stent restenosis.

Aprotinin but not epsilon-aminocaproic acid decreases interleukin-10 after cardiac surgery with extracorporeal circulation: randomized, double-blind, placebo-controlled study in patients receiving aprotinin and epsilon-aminocaproic acid.

BACKGROUND: Extracorporeal circulation induces a systemic inflammatory response, which may adversely affect organ function. One manifestation of this response is increased fibrinolysis. Antifibrinolytic drugs such as aprotinin and epsilon-aminocaproic acid have been effective in reducing fibrinolysis and blood loss after extracorporeal circulation; however, the effects of antifibrinolytic drugs on proinflammatory and anti-inflammatory mediators are not known. This study examined the effects of aprotinin and epsilon-aminocaproic acid on plasma levels of proinflammatory [interleukin-6 (IL-6)] and anti-inflammatory [interleukin-10 (IL-10)] cytokines during and after extracorporeal circulation. METHODS AND RESULTS: Seventy-two patients undergoing coronary artery bypass grafting with extracorporeal circulation were randomly assigned in a double-blind study to receive high-dose aprotinin, epsilon-aminocaproic acid, or saline placebo. Plasma levels of IL-6 and IL-10 were measured at 5 time points before, during, and after extracorporeal circulation. In all 3 groups, both IL-6 and IL-10 rose significantly after institution of extracorporeal circulation and remained elevated through the first postoperative day. Compared with saline, aprotinin significantly reduced IL-10 (P=0.02) and peak IL-6 (P=0.02) after extracorporeal circulation. In contrast, none of the reductions in IL-6 and IL-10 by epsilon-aminocaproic acid achieved statistical significance. Both aprotinin and epsilon-aminocaproic acid decreased blood loss compared with saline, but there was no significant difference in the number of patients receiving blood products among the treatment groups. CONCLUSIONS: These data suggest that aprotinin and epsilon-aminocaproic acid differ in their effects on the inflammatory response to extracorporeal circulation. Aprotinin but not epsilon-aminocaproic acid appears to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6 and IL-10. Further studies will be required to determine if these cytokine alterations translate to changes in clinical outcomes.

The use of lepirudin for anticoagulation in patients with heparin-induced thrombocytopenia during major vascular surgery.

The method of anticoagulation in patients undergoing major vascular surgery with a history of heparin-induced thrombocytopenia (HIT) is controversial. We present two cases in which a bolus only technique using recombinant hirudin (Lepirudin or Refludan) was used successfully in patients with HIT scheduled for vascular surgery.

Remifentanil versus meperidine for monitored anesthesia care: a comparison study in older patients undergoing ambulatory colonoscopy.

UNLABELLED: Colonoscopy is one of the most frequently performed outpatient procedures in the United States. This study was designed to test the hypothesis that a remifentanil infusion would be superior to boluses of meperidine in older patients undergoing ambulatory colonoscopy. One hundred ASA physical status I-IV patients undergoing colonoscopy were randomized in this double-blinded study to receive either remifentanil infusions (n = 49) or titrated boluses of meperidine (n = 51). Patient tolerance was assessed using physiologic variables and side effects associated with opioid analgesia. Verbal pain/anxiety and patient/operator satisfaction were also assessed. As a group, the physiologic characteristics demonstrated no significant differences in the response to the colonoscopy procedure. Although the patient and operator satisfaction surveys were similar between groups, the incidences of tachycardia, hypotension, and nausea were less and the adjusted verbal pain and anxiety scores were more in the Remifentanil group compared with the Meperidine group. This study demonstrates that remifentanil and meperidine were equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider. The differences in the pharmakinetics of remifentanil and meperidine most likely account for the differences noted between the two treatment groups. IMPLICATIONS: Remifentanil infusions and meperidine boluses are equally well tolerated in older patients undergoing ambulatory colonoscopy when administered by an anesthesia provider.

Esophageal Doppler monitor determinations of cardiac output and preload during cardiac operations.

BACKGROUND: Perioperative management of cardiac surgical patients frequently mandates measurements of cardiac output and left ventricular filling. This study compared cardiac output and left ventricular filling measured by pulmonary artery (PA) catheter and esophageal Doppler monitor (EDM). METHODS: Thirty-four patients undergoing coronary artery bypass grafting were prepared by implanting a PA catheter, an EDM, and a transit-time ultrasonic flow probe around the ascending aorta. In 20 patients, left ventricular end-diastolic short-axis area (EDA) was measured by transesophageal echocardiography. At five time points, cardiac output was measured from the flow probe, the EDM, and the PA catheter (by thermodilution), and left ventricular filling was assessed from the PA catheter (as PA diastolic pressure), the EDM (corrected flow time), and the EDA. For cardiac output, concordance correlations relating EDM to flow probe and PA catheter to flow probe were calculated, transformed (Fisher's z transformation), and compared by Student's t test. For left ventricular filling, regression coefficients were created between corrected flow time and EDA and between PA diastolic pressure and EDA. Spearman correlations were compared by Wilcoxon rank sum test. RESULTS: The EDM and the PA catheter exhibited similar relationships to the flow probe (concordance correlations, 0.55 +/- 0.35 [mean +/- standard deviation] and 0.49 +/- 0.34, respectively; p = 0.088). The correlation between corrected flow time and EDA was better than the correlation between PA diastolic pressure and EDA (concordance correlations, 0.49 +/- 0.55 versus 0.10 +/- 0.43, respectively; p < 0.01). CONCLUSIONS: These data suggest that the EDM may offer a less invasive technique for evaluating cardiac output and a more accurate estimate for preload compared with the PA catheter.

D-Dimer formation during cardiac and noncardiac thoracic surgery.

UNLABELLED: The ability to make therapeutic decisions regarding excessive fibrinolysis in the perioperative period is limited by the lack of availability of a near site monitor of fibrinolysis. We investigated the use of a latex agglutination D-dimer assay to detect perioperative fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. We studied 27 patients who underwent thoracic surgery requiring cardiopulmonary bypass (CPB; coronary artery bypass grafting, n = 12; valvular surgery, n = 15) and a cohort of 20 patients who underwent noncardiac thoracic surgical procedures not requiring CPB. The purpose of this investigation was to determine the relationship among alterations in the latex agglutination D-dimer assay, use of extracorporeal circulation, type of cardiac surgical procedure, and mediastinal and/or chest tube drainage (cardiac surgery only) in patients undergoing thoracic surgery. Perioperative D-dimer levels, measured by latex agglutination, had significant (P < or = 0.05) intragroup changes among patients undergoing cardiac surgery (requiring CPB) and the cohort of patients who underwent noncardiac thoracic surgery without CPB. Although intraoperative D-dimer levels were not increased in patients undergoing noncardiac thoracic surgery, postoperative levels were significantly (P < 0.05) increased (compared with preinduction). In cardiac surgery patients requiring CPB, intraoperative D-dimer formation was significantly (P < or = 0.05) increased but did not demonstrate any intragroup (coronary artery bypass grafting versus valvular surgery) differences. Finally, D-dimer levels were not associated with postoperative mediastinal and/or chest tube accumulative drainage measured at intervals up to 48 h postoperatively in patients undergoing cardiac surgery requiring CPB. Our study indicates that the latex agglutination D-dimer assay can detect excessive fibrinolysis perioperatively, and that extracorporeal circulation can significantly influence the pattern of D-dimer formation in patients undergoing thoracic surgery. IMPLICATIONS: We assessed the ability of a readily available D-dimer assay to detect excessive fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. The findings demonstrate that the assay used in this investigation reflected variable amounts of fibrinolysis in patients undergoing both types of thoracic surgery.

Near-site monitoring of the antiplatelet drug abciximab using the Hemodyne analyzer and modified thrombelastograph.

OBJECTIVE: This investigation examines the hypothesis that the antiplatelet effect of abciximab and its reversal can be monitored using the Hemodyne (Hemodyne, Inc, Midlothian, VA) analyzer and modified Thrombelastograph (Haemoscope, Skokie, IL). DESIGN: In vitro dose-response and reversal study. SETTING: Anesthesia Research (Dallas, TX) and Special Studies Coagulation Laboratories (Washington, DC). PARTICIPANTS: Nine healthy volunteers. INTERVENTIONS: The addition of increasing concentrations of abciximab, 0 to 10 microg/mL, and purified fibrinogen, 50 to 400 mg/dL. The reversal of abciximab, 4 microg/mL, with the addition of fresh platelet-rich plasma (PRP) sufficient to increase the platelet concentration by approximately 10%. MEASUREMENTS AND MAIN RESULTS: Platelet aggregation and platelet contractile force using the Hemodyne analyzer were used as platelet-specific measurements. The Thrombelastograph maximum amplitude (MA) for platelets (MA(PLT)) was calculated by subtracting the MA from a platelet-poor plasma (PPP) sample (MA(ppp)) determined in one thromboelastography well from that of whole-blood MA (MA(WB)) run simultaneously in the second thromboelastography well. The addition of abciximab, 0 to 10 microg/mL, resulted in significant concentration-dependent reductions in platelet aggregation (p < 0.001), platelet contractile force (p < 0.001), and MA(PLT) (p < 0.001). Platelet contractile force (p < 0.03) and MA(PLT) (p < 0.05) were significantly more responsive than MA(WB) to the effect of abciximab, 4 microg/mL, and its reversal with the addition of fresh PRP. Purified fibrinogen concentration directly correlated with thromboelastography MA (r(s) = 0.97; p < 0.001), yet had no effect on platelet contractile force. The addition of abciximab had no measurable influence on the MA(ppp). CONCLUSION: This in vitro study suggests that the Hemodyne analyzer and modified Thrombelastograph might be clinically useful methods to monitor the platelet inhibitory effects of agents such as abciximab.

Does the duration of cardiopulmonary bypass or aortic cross-clamp, in the absence of blood and/or blood product administration, influence the IL-6 response to cardiac surgery?

UNLABELLED: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response characterized by release of proinflammatory cytokines, including interleukin 6 (IL-6). Recent reports suggest that plasma IL-6 is increased after CPB. Previous studies evaluating the influence of duration of CPB and/or aortic cross-clamp time on the release of IL-6 are conflicting. Infusion of blood and blood products during these studies may have influenced plasma concentrations of proinflammatory cytokines by inducing host cell (monocyte) activation and IL-6 release. The purpose of our investigation was to determine, in an environment free from blood and/or blood product administration, the influence of duration of CPB and/or aortic cross-clamp on the magnitude of the IL-6 response in patients undergoing cardiac surgery. We prospectively evaluated plasma IL-6 levels preinduction (T0) and at sternal closure in 16 patients undergoing CPB (coronary artery bypass grafting, n = 9; valvular cardiac surgery, n = 7) to determine whether there is a correlation between the absolute increase in IL-6 and the duration of CPB or aortic cross-clamp time. None of the patients received blood and/or blood products during the study to control for the introduction of additional activated cells and soluble mediators, including IL-6. The results demonstrate that the magnitude of the IL-6 response to CPB is positively correlated with the duration of CPB but not with duration of aortic cross-clamp. It seems that induction of IL-6 release is part of a normal response to CPB and does not depend on activation of host cells during prolonged aortic cross-clamp. The activation or presence of inflammatory cytokines associated with administration of blood and/or blood products could have influenced previously published investigations relating the influence of duration of CPB and/or aortic cross-clamp time to the magnitude of the IL-6 response. IMPLICATIONS: This study found a positive correlation between the magnitude of the interleukin 6 response to cardiopulmonary bypass and duration of cardiopulmonary bypass (but not duration of aortic cross-clamp) when measurements were made in the absence of blood/blood product transfusion. Future studies evaluating strategies to reduce cytokine responses to cardiopulmonary bypass should therefore control for cardiopulmonary bypass duration.

A method for the quantitative assessment of platelet-induced clot retraction and clot strength in fresh and stored platelets.

BACKGROUND AND OBJECTIVES: The changes that occur in platelets as they undergo storage have been documented by aggregometry as well as by flow cytometry. However, one of the most essential platelet functions, the induction of clot retraction, has not been quantitatively assessed in stored platelets. We describe two potentially useful methods, platelet-induced clot retraction and clot strength, to assess effect of storage of platelets in blood banks or of platelet preparations subjected to freezing or freeze-drying. These methods have previously been developed for bedside monitoring of patients receiving c7E3 (Reopro(R)). MATERIALS AND METHODS: Platelet-induced clot retraction (PICR) and clot strength were measured with the Hemodyne and Thromboelastograph, respectively. Paired Study: Fresh platelet concentrates (n = 3) were obtained from leukapheresis donors and divided into two equal units; one unit was tested within 4 h of collection and the other stored for 5 days at 22 degrees C in a platelet incubator and tested. Unpaired Study: Fresh platelet concentrates (n = 15) were obtained from leukapheresis donors and tested within 4 h of collection and compared to outdated platelets (n = 30; random or single donor) that had been stored for 5 days at 22 degrees C in a platelet incubator. Alternative Preservation Methods: Lyophilized platelets, platelets chilled to 4 degrees C, platelets frozen at -70 degrees C in 5% dimethyl sulfoxide (DMSO) or in the absence of a cryoprotectant. RESULTS: Paired Study: Stored platelets demonstrated an increase in PICR; the difference was not significant (p = 0.55). There was no difference in clot strength between fresh and outdated platelets (p = 0.90). Unpaired Study: When compared to fresh platelets, stored platelets demonstrated a 2-fold higher PICR (p = 0.0011). On the other hand, there was no difference in the time to onset of PICR (p = 0.08) and there was no difference in clot strength between fresh and outdated platelets (p = 0.14). Alternate Preservation Methods: In contrast, PICR and clot strength were reduced in platelets frozen at -70 degrees C in 5% DMSO and absent in lyophilized platelets, in platelets frozen at -70 degrees C in the absence of cryoprotectants or stored at 4 degrees C. CONCLUSION: The data indicate that the ability of platelets to induce clot retraction and to enhance clot strength is not altered by storage, despite functional abnormalities in aggregation and agglutination. These data suggest that quantitative measurements of PICR and clot strength may be simple, useful tools for assessing the function of stored platelet concentrates, platelets that have undergone freezing or exposure to alternative buffers and for evaluating platelet functions relevant to PICR.

A modified thromboelastographic method for monitoring c7E3 Fab in heparinized patients.

The monoclonal antibody, c7E3 Fab, binds to the platelet surface fibrinogen receptor (GPIIb/IIIa), inhibiting platelet aggregation and clot retraction. We performed an in vitro study to assess the ability of a modification of the thromboelastograph (MTEG) to detect inhibition of clot strength by c7E3 Fab and its reversal with platelet-rich plasma (PRP). In the modified assay (MTEG), thrombin was added to whole blood (WB) and platelet-poor plasma (PPP) and the resultant maximum amplitude (MA) was measured, MAWB and MAPPP, respectively. Anticoagulated blood samples from 17 patients scheduled for cardiac surgery were collected for a dose response (Part I; n = 5) and c7E3 Fab reversal (Part II; n = 12) study. Clot strength was reduced in a dose-dependent manner by c7E3 Fab. Ecteola cellulose effectively reversed the effect of heparin on the thrombin time and the addition of PRP significantly increased the MAWB (P < 0.0001) and MAWP-PPP (P < 0.0001). Subtracting the MAPPP from MAWB significantly magnified the response of MA to the addition of c7E3 Fab (P = 0.002) and its reversal with PRP (P = 0.005). This in vitro study indicates that the MTEG is a responsive assay demonstrating that inhibition by the antiplatelet c7E3 Fab is reversible with PRP.

Heparin ablates force development during platelet mediated clot retraction.

Although snake venom enzymes such as reptilase do not cause viscous metamorphosis, platelet secretion or clot retraction; when batroxobin and calcium are added to citrated blood significant platelet force development occurs. When this batroxobin-calcium system was applied to the study of platelet function during cardiopulmonary bypass (CPB), force development was found to be completely inhibited. After heparin reversal by protamine sulfate, significant recovery of force occurred. The present investigation was performed to evaluate the role of heparin in reducing force development during CPB. At concentrations above 0.10 U/ml, heparin totally suppressed force development in normal plasma. Addition of protamine sulfate to heparinized plasma caused complete recovery of force development. These concentrations of heparin had little effect on platelet aggregation by ADP or collagen. Possible direct effects of heparin on fibrin assembly and structure were studied by adding varying amounts of heparin to plasma and then inducing clot formation with batroxobin. At 1 U/ml, heparin reduced the size of fibrin fibers by 33%. Higher heparin concentrations had no additional effect. These results indicate that heparin may be responsible for a significant component of the decreased platelet force noted during cardiopulmonary bypass. To test whether heparin's effect could be due to suppression of thrombin activity, the effects of the antithrombin hirudin on force development were measured. Hirudin also inhibited force development in a concentration dependent manner. Thus, heparin's reduction of platelet force development may be due, at least in part, to suppression of thrombin activity.

Reductions in platelet force development by cardiopulmonary bypass are associated with hemorrhage.

Quantitative assessment of platelet dysfunction after cardiopulmonary bypass (CPB) and prediction of excessive microvascular bleeding remain elusive goals. We used a sensitive instrument capable of simultaneously measuring the force generated by platelets during plasma clot retraction and global clot strength. We hypothesized that CPB would significantly reduce these two variables. Platelet-rich plasma was obtained from eight patients undergoing aortocoronary revascularization prior to induction, after 90 min of CPB, and after protamine administration. Platelet force development was measured using a standardized technique that controlled for platelet number and permitted clot formation in the presence of heparin. Despite the presence of a measurable elastic modulus, platelet force development during bypass was abolished. Peak platelet force development after CPB was significantly lower than before CPB (5255 +/- 955 dynes vs 11,600 +/- 780 dynes, P = 0.01). The percent recovery (after/before bypass) of peak platelet force development inversely correlated with tube thoracostomy drainage during the first 24 h after placement (rs = -0.71, P = 0.048). This study demonstrates that CPB has dramatic effects on platelet force development. The correlation between the percent recovery of peak platelet force development and blood loss supports the clinical relevance of this measurement.

Quantitative assessment of platelet function and clot structure in patients with severe coronary artery disease.

The prothrombotic state of patients with coronary artery disease (CAD) can be attributed partially to platelet activity. Management of such patients is hindered by a lack of techniques to assess hemostatic function. This study used a sensitive technique to monitor platelet function by measuring platelet force development during clot retraction. This technique allowed simultaneous measurement of clot elastic modulus on the same sample. Fibrin mass-length ratio (mu), fibrinopeptide A, D-Dimer, von Willebrand's factor, thromboxane A2, platelet aggregation studies, and bleeding times also were performed. Fourteen patients with CAD were compared with 10 healthy volunteers. Despite more than 95% suppression of thromboxane B2 and prolongation bleeding times in patients taking aspirin, force development remained significantly elevated over healthy control patients (8,279 +/- 476 dynes versus 4,857 +/- 380 dynes, p < 0.0006). Patients not taking aspirin had normal bleeding times and force development of 19,110 +/- 3,700 dynes. Clot elastic moduli were enhanced in patients with CAD whether taking or not taking aspirin. Adenosine diphosphate and ristocetin-induced platelet aggregation were insensitive to the effect of aspirin in patients with CAD. Fibrinopeptide A, von Willebrand's factor, and D-Dimer levels were significantly elevated, and fibrin mass-length ratios were significantly larger in patients with CAD. Therefore, despite aspirin therapy, patients with severe CAD have evidence of persistent platelet activation and rigid clot structure. Monitoring of platelet force development may prove useful in delineating enhanced platelet function.

Effect of dietary calcium supplementation on blood pressure and calciotropic hormones in mineralocorticoid-salt hypertension.

In order to determine the effect of dietary calcium supplementation on blood pressure and calciotropic hormones, we studied two groups (n = 12 each) of mineralocorticoid [deoxycorticosterone (DOC)]-salt hypertensive rats, one receiving a normal-calcium diet (0.6% calcium, as calcium carbonate) and the other a high-calcium diet (2.5% calcium), over an 8-week period. Dietary calcium supplementation significantly attenuated the rise in blood pressure. Serum ionized calcium concentrations were significantly decreased from baseline levels in both groups but tended to be higher among the calcium-supplemented rats. Serum concentrations of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25-D) were significantly higher in the DOC-salt rats than in normotensive rats fed normal rat chow [PTH: 49 +/- 4 versus 15 +/- 0.9 pg/ml (means +/- s.e.m.); 1,25-D: 108 +/- 7 versus 73 +/- 13 pg/ml, in DOC-salt and normotensive rats, respectively]. In the DOC-salt rats, dietary calcium supplementation did not significantly lower the elevated serum concentration of PTH (from 49 +/- 4 to 40 +/- 4 pg/ml; NS), but did significantly reduce that of 1,25-D (from 108 +/- 7 to 66 +/- 8 pg/ml; P less than 0.01). Since 1,25-D may increase vascular smooth muscle calcium uptake, dietary calcium supplementation may lower blood pressure in DOC-salt hypertension, in part, by suppressing 1,25-D.

Systemic and regional hemodynamic effects of dietary calcium supplementation in mineralocorticoid hypertension.

This study was undertaken to determine the systemic and regional hemodynamic effects of long-term dietary calcium supplementation in mineralocorticoid (DOC)-salt hypertension. Systemic and regional hemodynamic measurements were determined by the radioactive microsphere technique in conscious and unrestrained rats (kidneys intact) with DOC-salt-induced hypertension that were pair-fed either a normal calcium (0.6% by weight, n = 12) or a calcium-supplemented (high-calcium) diet (2.5% by weight, n = 12). After 7 to 8 weeks, there were no differences in weight, heart rate, or cardiac output between the two groups. In contrast, the high-calcium rats had a significantly lower mean blood pressure (125 +/- 4 mm Hg, mean +/- SEM) than the normal calcium rats (143 +/- 5 mm Hg); this finding appeared to result predominantly from a reduction in total peripheral resistance. The high-calcium rats had a higher renal blood flow (7.8 +/- 0.5% vs. 6.2 +/- 0.4% cardiac output; p less than 0.05) and lower renal (14.3 +/- 1 vs. 19.3 +/- 2 mm Hg/min/ml/g tissue; p less than 0.05) and jejunal vascular resistance than did the normal calcium rats. Two additional identical groups of normal calcium-and high-calcium-DOC-salt rats (n = 12 each) were also studied. In these rats, serum-ionized calcium decreased significantly (p less than 0.05) from baseline in both groups. Urinary sodium increased in both groups but did not differ significantly. In conclusion, dietary calcium supplementation attenuates the rise in peripheral vascular resistance that accompanies DOC-salt hypertension. This attenuated resistance appears to be relatively selective and is noted particularly in the renal vasculature.