Renal duplex sonography: main renal artery versus hilar analysis.

OBJECTIVE: The purpose of this study was to compare the accuracy of main renal artery Doppler scanning interrogation and hilar analysis to diagnose hemodynamically significant renal artery disease. METHODS: From January 1998 to August 1999, 41 patients had renal duplex sonography with both main renal artery interrogation and hilar analysis followed by angiography. They form the basis of this review. The sample consisted of 24 men and 17 women, with a mean age of 68.9 +/- 10.2 years, who provided 80 kidneys for comparative analysis. Significant renal artery disease revealed through angiography was defined as >/= 60% diameter-reducing stenosis or occlusion. Peak systolic velocity (PSV) (in meters per second) and the presence of poststenotic turbulence (PST) were determined from main renal artery interrogation. Acceleration time (AT) (in milliseconds) was measured by means of hilar analysis. Significant renal artery stenosis was defined by a PSV of 2.0 m/s or more and a PST or an AT more than 100 ms. Sensitivity analyses of both PSV and AT were examined, and 95% CIs were computed. Receiver operating characteristic curves were used to estimate optimal values for PSV and AT. RESULTS: Angiography revealed hemodynamically significant fibromuscular dysplasia in 5 kidneys (4 patients), atherosclerotic stenosis >/= 60% in 48 kidneys (30 patients), and renal artery occlusion in 4 kidneys (4 patients). Kidneys with significant renal artery stenosis had a higher PSV (2.54 +/- 0.11 vs 1.28 +/- 0.08, P <.001) and AT (82.43 +/- 7.2 vs 30.0 +/- 2.8, P <.001) compared with those without stenosis. Compared with angiography, a PSV of 2.0 m/s or more and PST demonstrated a sensitivity of 91%, specificity of 96%, and overall accuracy of 92% for detection of significant renal artery stenosis. Two of five studies with false-negative results reflected diseased polar vessels. By contrast, AT of more than 100 ms had a sensitivity of 32%, specificity of 100%, and overall accuracy of 54%. Receiver operating characteristic curve analysis revealed a PSV of more than 1.8 m/s and an AT of 58 ms or greater as optimal values. With an AT of 58 ms or more, the sensitivity was 58%, and specificity was 96%, with an overall accuracy of 70%. There were no apparent associations between PSV or AT and type or location of renal artery lesion, serum creatinine level, or end-diastolic ratio. CONCLUSION: Main renal artery interrogation is an accurate screening test to detect significant stenosis or occlusion of the main renal artery. Hilar analysis alone does not provide sufficient sensitivity to be used as a sole screening study. Neither method detects the presence of renovascular disease associated with polar vessels.

Management of ischemic nephropathy: dialysis-free survival after surgical repair.

PURPOSE: This retrospective review describes the surgical management of consecutive patients with severe hypertension and ischemic nephropathy due to atherosclerotic renovascular disease. METHODS: From January 1987 through December 1998, a total of 590 patients underwent operative renal artery repair at our center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66 +/- 8 years) with atherosclerotic renovascular disease and preoperative serum creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in renal function was determined from glomerular filtration rates estimated from preoperative and postoperative serum creatinine. The influence of selected preoperative parameters and renal function response on time to dialysis and dialysis-free survival was determined by a proportional hazards regression model. RESULTS: In all, 83 patients underwent unilateral renal artery repair and 149 patients underwent bilateral repair, including repair to a solitary kidney in 17 cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies were performed in these patients. After surgery, there were 17 deaths (7.3%) in the hospital or within 30 days of surgery. Advanced patient age (P =.001; hazard ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure (P =.04; hazard ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations with perioperative mortality. With a change of 20% or more in EGFR being considered significant, 58% of patients had improved renal function, including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%. Follow-up death from all causes or progression to dialysis dependence demonstrated a significant and independent association with early renal function response. Both patients whose function was unchanged (P =.005; hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened (P =.03; hazard ratio, 2.2; CI [1.1, 4. 5]) remained at increased risk of death or dialysis dependence. For patients with unchanged renal function after operation, risk of death or dialysis demonstrated a significant interaction with preoperative renal function. In addition to severe preoperative renal dysfunction, diabetes mellitus demonstrated a significant and independent association with follow-up death or dialysis. CONCLUSION: Surgical correction of atherosclerotic renovascular disease can retrieve excretory renal function in selected hypertensive patients with ischemic nephropathy. Patients with improved renal function had a significant and independent increase in dialysis-free survival in comparison with patients whose function was unchanged and patients whose function was worsened after operation. These results add further evidence in support of a prospective, randomized trial designed to define the value of renal artery intervention in patients with ischemic nephropathy.

Effect of aminoguanidine on plasma nitric oxide by-products and blood flow during chronic peritoneal sepsis.

We hypothesized that plasma nitric oxide (NO), generated via inducible NO synthase (iNOS) or endothelial constitutive NO synthase and measured via its by-products NO2- and NO3- (NO2- + NO3- = NOx) would increase and remain elevated during chronic peritoneal sepsis. We further hypothesized that treatment with aminoguanidine (AG; 50 mg/kg), a selective iNOS inhibitor, would decrease NO production and alter blood flow. Sprague Dawley rats were randomized to septic and nonseptic groups. Septic rats received an intraperitoneal cecal slurry (200 mg of cecal material/5 mL 5% dextrose-H2O/kg); control rats received sterile 5% dextrose-H2O (5 mL/kg) only. Plasma NOx and hemodynamics were measured 0, 4, 12, 24, and 48 h after sepsis or sham induction. We also examined the effect of AG, an iNOS inhibitor, on plasma NOx levels and tissue blood flow at 24 h. Septic rats uniformly displayed signs of sepsis, including lethargy, piloerection, and diarrhea. NOx levels were significantly elevated compared with controls at 4, 12, 24, and 48 h (p < or = .05). Septic rats also demonstrated hypotension (t = 12, 24, and 48 h) and tachycardia (t = 4, 12, 24, and 48 h). The infusion of AG (50 mg/kg intravenously for 30 min) at 24 h significantly decreased plasma NOx in septic animals. Plasma NOx concentrations returned to basal levels by 90 min after infusion of AG. In addition, blood flow studies demonstrated that AG treatment in nonseptic rats resulted in a significant decrease in blood flow to the stomach, skin, and adipose tissue, whereas AG infusion did not significantly alter the regional perfusion profile in septic animals. Furthermore, treatment with AG did not significantly alter mean arterial pressure in either group; however, nonseptic animals exhibited a decrease in stroke volume, and septic animals demonstrated an increase in heart rate. In contrast to the rise and fall of NOx levels in endotoxemia, this study demonstrates that the initial rise is sustained during 48 h of peritoneal sepsis. This sustained increase in NOx levels in this model correlated with the observable signs of systemic infection and may relate to enhanced iNOS activity. AG infusion demonstrated variable effects on regional tissue blood flow profiles in septic and nonseptic animals and attenuated the increase in plasma NOx levels in septic animals, an index of iNOS activity.

Adenosine receptor antagonism affects regional resting vascular resistance during rat peritoneal sepsis.

BACKGROUND: To identify vascular beds where endogenous adenosine plays a significant role as a mediator of resting perfusion alterations associated with sepsis, we tested the hypothesis that adenosine receptor blockade would cause differential regional increases in vascular resistance during intraperitoneal (ip) sepsis in the rat. MATERIALS AND METHODS: Rats (250-350 g) were catheterized and randomized to septic or nonseptic groups. Sepsis was induced with an ip injection of cecal slurry (150 mg/kg in D5W; 5 ml/kg), and baseline hemodynamics, cardiac output (CO), and blood flows (microspheres) were measured 24 h later. Animals then received the adenosine receptor antagonist 8-phenyltheophylline (8-PTH; 10 mM, 1.5 ml/kg), its vehicle (1.5 ml/kg), or normal saline (1.5 ml/kg), iv, and measurements were repeated. RESULTS: Septic animals treated with 8-PTH had a significant increase in skeletal muscle, hepatic portal, and cerebral vascular resistance with concomitant decreases in CO when compared with vehicle at 1 min. No significant resistance changes were observed in the renal, adipose, or coronary vasculatures. Adenosine receptor blockade caused a significant increase in +dP/dt and -dP/dt during sepsis, indicating that the reduced CO was not secondary to myocardial depression. CONCLUSIONS: These data suggest that adenosine receptor-mediated actions during sepsis affect vascular beds selectively and indicate a significant role for adenosine in resting perfusion redistribution in sepsis.

Evidence that adenosine contributes to maintenance of hepatosplanchnic blood flow during peritoneal sepsis in rats.

Sepsis induced derangements in hepatosplanchnic perfusion can contribute to organ damage and death. Adenosine, a common and potent metabolic vasodilator, has not been evaluated as a mechanism for maintenance of blood flow during sepsis. We tested the hypothesis that adenosine receptor blockade would cause a decrease in hepatosplanchnic blood flow during intraperitoneal (i.p.) sepsis in the rat. Rats (250-350 g) were catheterized for hemodynamic and blood flow measurements with tracer microspheres. Sepsis was induced with an i.p. injection of cecal material (150 mg/kg in D5W; 5 mL/kg), and baseline measurements were taken 24 h later. Animals then received either the adenosine receptor antagonist 8-PTH (10 mM, 1.5 mL/kg), its vehicle (1.5 mL/kg) or normal saline (1.5 mL/kg), intravenously, and measurements were repeated 1 and 10 min later. There was a significant increase in hepatosplanchnic portal resistance in septic animals given 8-PTH, with no change in mean arterial blood pressure (MAP) or heart rate. Regionally, there was a significant decrease in gastric, small intestinal, cecal, and pancreatic blood flow when compared with vehicle. Adenosine receptor blockade caused a significant reduction in hepatosplanchnic blood flow during sepsis, suggesting that maintenance of splanchnic blood flow during sepsis involves receptor mediated adenosine actions.

Sepsis alters myocardial and plasma concentrations of endothelin and nitric oxide in rats.

Cardiovascular derangements during sepsis may arise from a mismatch between endothelin (ET) and nitric oxide (NO). We hypothesized that progression of chronic peritoneal sepsis would affect cardiac performance and would modulate the concentrations of NO and ET in the heart and plasma. Male Sprague-Dawley rats (340-390 g) were catheterized and made septic with a cecal slurry (200 mg/kg: i.p.). Heart rate, mean arterial pressure, and plasma ET and nitrite/nitrate (NOX) were determined at 0, 4, 8, 12, 24, and 48 h after induction of sepsis. Septic rats were found to have tachycardia at 48 h following induction of sepsis. Mean arterial pressure and pulse pressure were not altered in septic and non-septic rats. In a separate series of experiments, the function of isolated hearts from septic and non-septic rats was assessed at preload pressures of 2, 5, and 10 mmHg. Sepsis produced a significant decrease in rates of pressure development and relaxation (+/-dP/dt) at 24 and 48 h as compared to the hearts of non-septic rats. In septic rats, plasma concentrations of ET were significantly increased at t = 4, 8, 12 h as compared to basal values, and at 12 h as compared to non-septic rats, and returned to basal levels at 24 and 48 h. In contrast, circulating NO levels did not become elevated until t = 8 h and remained elevated throughout the remaining times. In the left ventricle, the concentration of ET was found to be significantly increased both in septic and non-septic rats at 4 and 8 h as compared to t = 0 h. In the left ventricles of non-septic rats, ET levels returned to baseline values at 12 h, while in septic rats, the concentration of ET remained significantly elevated until 12 h. In septic rats, left ventricular NO levels were found to be significantly increased at t = 12 h. It appeared that induction of sepsis contributed to an imbalance in the plasma concentration of ET and NO 12 h after the induction of sepsis. However, a similar imbalance was not observed in the left ventricle. It is concluded from these observations that peritoneal sepsis in a chronic rat model produced a divergence of plasma NO and ET levels. This suggests a homeostatic imbalance between vasoactive mediators, i.e. ET and NO, could contribute to the cardiovascular derangements that occur during sepsis.

Steroid hormone alterations following induction of chronic intraperitoneal sepsis in male rats.

The influence of sepsis on male reproductive function in chronic animal models has not been extensively investigated. On the basis of earlier clinical studies, it was hypothesized that chronic intraperitoneal (i.p.) sepsis in rats would modulate the circulating levels of steroid reproductive hormones. Male Sprague-Dawley rats (300-375 g) were randomized to septic and nonseptic groups. Sepsis was induced with cecal slurry (200 mg/kg/5 mL 5% dextrose in water (D5W); i.p.) in septic rats, while nonseptic rats received only sterile D5W. The rats (n = 8-12) were catheterized to measure systemic hemodynamics and to collect blood at 0, 12, 24, and 48 h after induction of sepsis/sham sepsis. A separate group of normal rats was included to serve as an unoperated control group. The plasma concentration of corticosterone, progesterone, and testosterone in serum was determined using radioimmunoassay. The heart rate was significantly increased at t = 12, 24, and 48 h following induction of sepsis. However, septic rats did not display any significant alterations in the mean arterial pressure and pulse pressure. Basal circulating concentrations of serum corticosterone, progesterone, and testosterone were 356 +/- 124 ng/mL, 2.37 +/- 1.03 ng/mL, and 1.88 +/- .29 ng/mL, respectively, in the unoperated rats. At t = 0 h there was a significant increase in the levels of corticosterone in septic rats and in the levels of progesterone in both septic and nonseptic rats. The elevations in the concentrations of corticosterone and progesterone returned to basal values after 24 and 48 h. The septic animals had significantly decreased levels of testosterone at t = 24 and 48 h as compared with basal values and nonseptic groups. Our model of sepsis produced a time-dependent decrease in levels of testosterone, an end product of male steroidogenesis. This, along with unchanged levels of corticosterone and progesterone at 24 and 48 h following sepsis, indicates that separate mechanisms for steroidogenesis regulating synthesis of these steroid hormones (progesterone and testosterone) occur with sepsis. It is concluded that in our chronic septic rat model, induction of i.p. sepsis produced dysfunction in steroidogenesis, which selectively affected the synthesis of testosterone.