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Biomedical subjects

L O Lerman

Publications and source records attributed to L O Lerman.

At least 37 records · Page 2Linked to original sources

Electron beam computerized tomography assessment of in vivo single kidney glomerular filtration rate and tubular dynamics during chronic partial unilateral ureteral obstruction in the pig.

PURPOSE: The assessment of hydronephrosis due to chronic partial ureteral obstruction is controversial. We determined whether a new radiographic technique for assessing kidney function, electron beam computerized tomography (CT), can detect altered renal physiology due to chronic partial ureteral obstruction. We also compared and contrasted electron beam CT with standard well tempered diuretic mercaptoacetyltriglycine (MAG-3) urography. MATERIALS ANDS METHODS: Six pigs underwent creation of unilateral partial ureteral occlusion or sham operation. Three weeks after surgery diuretic enhanced MAG-3 renal scan was done and 48 hours later contrast enhanced electron beam CT was performed. RESULTS: Mean differential function plus or minus standard error of mean of the obstructed kidney was 5.6% +/- 2.4% on MAG-3 renography. In contrast, electron beam CT revealed significantly preserved mean renal function at 24.5% +/- 2.7% (p <0.01). Electron beam CT analysis of tubular function revealed persistent glomerular filtration and filtrate flow through the proximal tubules and loop of Henle with a selective decrease in distal tubular flow, which were findings suggestive of proximal tubular sparing that were not demonstrated by nuclear renography. CONCLUSIONS: Renal function on MAG-3 renography is primarily determined by measuring kidney perfusion and tubular secretion of the isotope. In contrast, electron beam CT determines renal function via quantifying the in vivo single kidney glomerular filtration rate and by assessing renal tubular function. This study documents that electron beam CT of differential renal function is significantly different from that of MAG-3 renography. To our knowledge which of these 2 radiographic studies is most clinically applicable is unknown to date.

Animals↗

Minimally invasive evaluation of coronary microvascular function by electron beam computed tomography.

BACKGROUND: We previously demonstrated that in vivo electron-beam computed tomography (EBCT)-based indicator-dilution methods provide an estimate of intramyocardial blood volume (BV) and perfusion (F), which relate as BV=aF+b radicalF, where a characterizes the recruitable (exchange) and b the nonrecruitable (conduit) component of the myocardial microcirculation. In the present study, we compared BV and F with intracoronary Doppler ultrasound-based coronary blood flow (CBF) as a method for detecting and quantifying differential responses of these microvascular components to vasoactive drugs in normal (control) and hypercholesterolemic (HC) pigs. METHODS AND RESULTS: BV and F values were obtained from contrast-enhanced EBCT studies in 14 HC and 14 control pigs. BV, F, and CBF values were obtained at baseline (intracoronary infusion of saline) and after 5 minutes each of intracoronary infusion of adenosine (100 microgram. kg(-1). min(-1)) and nitroglycerin (40 microgram/min). BV and CBF reserves in response to adenosine were attenuated in HC pigs compared with controls (90+/-36% versus 127+/-42%, P<0.03, and 485+/-182% versus 688+/-160%, P<0.01, respectively). The relationship between BV and F showed consistently lower recruitable BV in HC versus control pigs. Nonrecruitable BV reserve in response to adenosine was attenuated in HC compared with controls (77+/-20% versus 135+/-28%, P<0.001). Our findings are consistent with HC-induced impairment of intramyocardial resistance vessel function. CONCLUSIONS: EBCT technology allows minimally invasive evaluation of intramyocardial microcirculatory function and permits assessment of microvascular BV distribution in different functional components. This method may be of value in evaluating the coronary microcirculation in pathophysiological states such as hypercholesterolemia.

Adenosine↗

Altered myocardial microvascular 3D architecture in experimental hypercholesterolemia.

BACKGROUND: Experimental hypercholesterolemia (HC) impairs intramyocardial microvascular function. However, whether this is associated with alterations in microvascular architecture remained unknown. Using a novel 3D micro-CT scanner, we tested the hypothesis that HC is associated with an alteration in the microvascular architecture. METHODS AND RESULTS: Pigs were euthanized after 12 weeks of either normal (n=6) or 2% HC (n=6) diet. The hearts were excised and the coronary arteries injected with a radiopaque contrast material. Myocardial samples were scanned with micro-CT, and 3D images were reconstructed with 21-microm cubic voxels. The myocardium was tomographically subdivided into subepicardium and subendocardium, and microvessels (<500 microm in diameter) were counted in situ within each region. In the subendocardium of HC pigs, the intramyocardial density of microvessels was significantly higher than in normal animals (1221.4+/-199.7 versus 758.3+/-90.8 vessels/cm(3), P:<0.05) because of an increase in the number of microvessels <200 microm in diameter (1214.4+/-199.7 versus 746. 6+/-101.5 vessels/cm(3), P:<0.05). The subepicardial vascular density was similar in both groups. CONCLUSIONS: -HC has differential effects on the spatial density of the subendocardial microvasculature that may play a role in regulation and/or spatial distribution of myocardial blood flow. This study also demonstrates the feasibility of studying myocardial microvascular architecture with micro-CT in pathophysiological states.

Animals↗

Effects of acute and chronic angiotensin receptor blockade on myocardial vascular blood volume and perfusion in a pig model of coronary microembolization.

Based on the reduction of ischemic cardiac events in clinical trials and experimental observations, inhibition of the effects of angiotensin II on coronary microcirculatory function may afford myocardial protection after injury. The immediate effects of intracoronary AT1 receptor blockade with irbesartan were examined in a pig model in the healthy myocardium and in acute ischemia induced by injection of 30-microm microspheres into the left anterior descending coronary artery (LAD). Electron-beam computed tomography was performed for in-vivo quantitative measurements of regional intramyocardial vascular blood volume (V(B)) and perfusion (F(M)), as well as left ventricular ejection fraction (LVEF) and muscle mass. Ratios of V(B) and F(M) in the anterior (LAD-supplied)/ inferior (control) myocardium were generated. At baseline, 0.2 mg/kg irbesartan injected into the LAD increased V(B) and F(M) ratios significantly by 27 +/- 8% and 51 +/- 13%, respectively. After anterior coronary microembolization, V(B) and F(M) ratios were 0.60 +/- 0.05 and 0.51 +/- 0.05, respectively, and were significantly increased by irbesartan (by 24 +/- 10% and by 36 +/- 11%, respectively). After 4 weeks of treatment with oral irbesartan (n = 7) or placebo (n = 7), an improved LVEF (56 +/- 4% v 44 +/- 4%, P = .046) was observed in irbesartan-treated animals, but no difference in LV end-diastolic volumes or muscle mass. Resting V(B) (0.95 +/- 0.06 v 0.76 +/- 0.06; P = .047) and F(M) (0.84 +/- 0.05 v 0.64 +/- 0.04; P = .016) ratios were significantly greater in irbesartan-treated animals. Using adenosine, there was a trend for higher V(B) and F(M) ratios in irbesartan- v placebo-treated animals. Therefore, in a pig model of acute myocardial ischemia, AT1 receptor blockade by irbesartan induced microvascular vasodilation and, ostensibly, conveyed myocardial protection. Long-term treatment with irbesartan resulted in moderate enhancements of resting V(B) and F(M) compared with placebo, suggesting a role for coronary microcirculatory effects of chronic AT1 receptor blockade in preserving LVEF.

Angiotensin-Converting Enzyme Inhibitors↗

Novel noninvasive techniques for studying renal function in man.

Renal artery stenosis is a major cause of renovascular hypertension in humans, and may lead to ischemic nephropathy and end-stage renal disease. The mechanisms responsible for the progressive renal functional and structural alterations have not been fully elucidated, partly because of the lack of reliable, noninvasive techniques capable of quantifying renal regional hemodynamics and function distal to a stenosis in the renal artery. Novel imaging tools now enable quantification of concurrent intrarenal (cortical and medullary) hemodynamics, segmental nephron dynamics (intratubular transit times and fluid concentrations), and renal function in the intact kidney. Fast computed tomography (CT) scanners, such as electron beam CT, allow discrimination of subtle alterations in renal perfusion and segmental nephron function consequent to changes in renal perfusion pressure, both within and below the range of renal blood flow autoregulation. This technique provides an opportunity to define intrarenal perfusion patterns and function in animals and patients with renal artery stenosis, and may provide insight into the effects of chronic unilateral or bilateral renovascular disease on both the hypoperfused and contralateral kidneys. This methodology may thereby prove to be very useful in the evaluation of renal disease in general, and the renovascular hypertensive patient in particular.

Animals↗

Enhanced coronary vasoconstriction to oxidative stress product, 8-epi-prostaglandinF2 alpha, in experimental hypercholesterolemia.

OBJECTIVES: The F2-isoprostanes are a family of novel prostaglandin isomers and a stable product of in vivo oxidative stress. 8-epi-prostaglandinF2 alpha, a member of this isoprostane family, is a vasoconstrictor and its local release may contribute to the abnormal vasomotor tone associated with hypercholesterolemia. We therefore aimed to outline the role of 8-epi-prostaglandinF2 alpha as a coronary vasoconstrictor in experimental hypercholesterolemia. METHODS AND RESULTS: Pigs were randomized to two experimental groups (each n = 9): normal (N) and high cholesterol (HC) diet. To determine the vasoconstrictive effects of 8-epi-prostaglandinF2 alpha in vitro, doses from 10(-9) to 10(-5) M were used to constrict coronary epicardial rings. Plasma total and LDL cholesterol levels were significantly higher in the HC group compared with the N group (P < 0.005) as were plasma 8-epi-prostaglandinF2 alpha levels (P < 0.001). 8-epi-prostaglandinF2 alpha immunoreactivity was present in the vessel wall in both groups. Normal vessels with intact endothelium (n = 8 rings) contracted to 8-epi-prostaglandinF2 alpha (maximal contraction 15.5 +/- 8.74%). In the HC group, rings with intact endothelium had a greater contractile response to 8-epi-prostaglandinF2 alpha compared to normals (72.3 +/- 7.9%; n = 8; P < 0.0001). This was reversed by preincubation with NOR-3, a NO donor (maximal contraction 6.7 +/- 1.56%; n = 5; P < 0.0001). Enhanced contraction in normal vessels occurred with endothelial denudation (98.4 +/- 3.56%; n = 6; P < 0.0001) and with preincubation of the endothelium-intact rings with L-NMMA (N-monomethyl-L-arginine), an NO synthase inhibitor (85.5 +/- 10.3%, n = 6, P < 0.001). The enhanced contraction seen with hypercholesterolemia did not occur with other prostanoid vasoconstrictors. CONCLUSION: Experimental hypercholesterolemia leads to a significant increase in 8-epi-prostaglandinF2 alpha levels in addition to enhanced 8-epi-prostaglandinF2 alpha-induced coronary vasoconstriction, in vitro. These findings support a role for the F2-isoprostanes in the regulation of coronary vasomotor tone in pathophysiologic states.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

The development of x-ray imaging to study renal function.

The well-established role of the kidney in control of blood volume and ultimately arterial blood pressure has been underscored by the demonstration of alterations in renal hemodynamics and function recognized as responsible for these and other regulatory mechanisms. Nevertheless, the spatial complexity of intrarenal structure and function has made evident the need to study these separately in different regions of the intact kidney. Because of the introduction of x-rays, assessment of renal function has indeed been one of their attractive applications. However, despite the appeal of their noninvasiveness, several limitations confounded the different x-ray techniques used, most of which remained unresolved until the development of computed tomography. Furthermore, the development of fast imaging, which allows repetitive analysis of the same region of interest during the transit of contrast medium, holds a great potential to estimate intrarenal distribution of blood flow and the dynamic characteristics of tubular fluid flow in individual nephron segments. This latter assessment requires the administration of filterable x-ray contrast medium, which is cleared from the plasma almost exclusively by glomerular filtration, and the generation of contrast dilution curves. A historical review of the development and progress of the various x-ray techniques used will help understand the past and present of x-ray imaging, and will make it easier to envision the importance of their future roles in the study of renal physiology and pathophysiology.

Animals↗

Validation of minimally invasive measurement of myocardial perfusion using electron beam computed tomography and application in human volunteers.

OBJECTIVES: To measure myocardial perfusion using an estimate of intramyocardial vascular volume obtained by electron beam computed tomography (EBCT) in an animal model; to assess the feasibility and validity of measuring regional myocardial perfusion in human volunteers using the techniques developed and validated in the animal studies. METHODS: Measurements of myocardial perfusion with EBCT employing intravenous contrast injections were compared with radioactive microsphere measurements (flow 57 to 346 ml/100 g/min) in seven closed chest dogs. Fourteen human volunteers then underwent EBCT scans using intravenous contrast injections. RESULTS: Mean (SEM) global intramyocardial vascular volume by EBCT was 7.6 (1.1)%. The correlation between global EBCT (y) and microsphere (x) perfusion was y = 0.59x + 15.56 (r = 0.86) before, and y = 0.72x + 6. 06 (r = 0.88) after correcting for intramyocardial vascular volume. Regional perfusion correlation was y = 0.75x + 23.84 (r = 0.82). Corresponding improvements in agreement between the two techniques were also seen using Bland-Altman plots. In the human subjects, mean resting global myocardial flow was 98 (6) ml/100 g/min, with homogeneous flow across all regions. In 10 of these subjects, perfusion was studied during coronary vasodilatation using intravenous adenosine. Global flow increased from 93 (5) ml/100 g/min at rest to 250 (19) ml/100 g/min during adenosine (p < 0.001), with an average perfusion reserve ratio of 2.8 (0.2). Similar changes in regional perfusion were observed and were uniform throughout all regions, with a mean regional perfusion reserve ratio of 2.8 (0.3). CONCLUSIONS: Accounting for intramyocardial vascular volume improves the accuracy of EBCT measurements of myocardial perfusion when using intravenous contrast injections. The feasibility of providing accurate measurements of global and regional myocardial perfusion and perfusion reserve in people using this minimally invasive technique has also been demonstrated.

Adenosine↗

Coronary endothelial function is preserved with chronic endothelin receptor antagonism in experimental hypercholesterolemia in vitro.

Hypercholesterolemia is associated with increased circulating and tissue endothelin-1 immunoreactivity, decreased nitric oxide (NO) activity, and altered endothelial function. We tested the hypothesis that chronic endothelin receptor antagonism preserves endothelial function and increases NO in experimental porcine hypercholesterolemia. Pigs were randomized to 3 groups: Group 1, a 2% high-cholesterol (HC) diet alone (n=7); group 2, RO-48-5695, a combined endothelin receptor antagonist, and an HC diet (n=8); and group 3, ABT-627, a selective endothelin-A receptor antagonist, and an HC diet (n=8). Coronary epicardial and arteriolar endothelial function was determined by a dose-response relaxation to bradykinin (10(-11) to 10(-6) mol/L), in all groups and in pigs maintained on a normal diet. Plasma total oxidized products of NO (NO(x)) were determined by chemiluminescence at baseline and after 12 weeks. Bradykinin-stimulated coronary epicardial and arteriolar relaxation in group 1 was attenuated compared with normal-diet controls. This relaxation was normalized with endothelin receptor antagonism. Plasma NO(x) decreased after 12 weeks in group 1 (-74.8+/-5.5%). This decrease was attenuated in the endothelin receptor antagonist groups (group 2, -28.2+/-15.0%; group 3, -38.9+/-20.6%). Chronic endothelin receptor antagonism preserves coronary endothelial function and increases NO in hypercholesterolemia. This study supports a role of endothelin-1 in the regulation of NO activity and suggests a possible therapeutic role for endothelin receptor antagonists in hypercholesterolemia.

Animals↗

In vivo renal vascular and tubular function in experimental hypercholesterolemia.

Hypercholesterolemia (HC) is often associated with impaired peripheral and coronary vascular responses to endothelium-dependent vasodilators, which are probably due to low bioavailability of nitric oxide. To examine the effect of HC on renal vascular and tubular function, 22 domestic pigs were studied after being fed a 12-week normal (n=11) or HC (n=11) diet. Renal regional perfusion and intratubular contrast media concentration in each nephron segment (representing fluid reabsorption) were quantified in vivo with electron-beam computed tomography before and after a suprarenal infusion of either acetylcholine (6 pigs of each diet) or sodium nitroprusside (SNP; 5 pigs of each diet). An increase in cortical perfusion, observed in normal pigs with acetylcholine (+35+/-6%, P=0. 002) and SNP (+12+/-4%, P=0.005), was blunted in the HC group (+8. 8+/-4.0, P=0.01, and -4.6+/-4.0%, P=0.1, respectively, P=0.003 and P=0.005 compared with normal) as was an increase in medullary perfusion (+58+/-21 in normal versus +24+/-11% in HC, P=0.04). A decrease in the intratubular contrast media concentration in the distal tubule and collecting duct of normal pigs was observed in all tubular segments (and was significantly enhanced in the proximal tubule and Henle's loop) in the HC group, which was associated with increased sodium excretion. The tubular and renal excretory responses to SNP were similar between the groups. In conclusion, early experimental HC in the pig attenuates renal perfusion response to both endothelium-dependent and -independent vasodilators possibly because of decreased bioavailability or decreased vascular responsiveness to nitric oxide. This vascular impairment may play a role in maladjusted renovascular responses and contribute to renal damage in later stages of atherosclerosis.

Acetylcholine↗

Noninvasive evaluation of a novel swine model of renal artery stenosis.

Intrarenal hemodynamics and excretory function distal to renal artery stenosis are difficult to quantify noninvasively. In this study, a swine model of chronic unilateral renal artery stenosis, achieved by implantation of an intravascular device that leads to a gradual and progressive luminal area narrowing, was developed and evaluated. Bilateral cortical and medullary volumes, blood flows, and segmental tubular dynamics were assessed in the intact kidneys of seven pigs using electron-beam computerized tomography before and 1 mo after implantation of the device. Within 1 mo, a 66% angiographic stenosis was significantly correlated with a 25% increase in BP. The volume and blood flow were markedly lower in the stenotic compared with the contralateral kidney and cortex, while the medulla exhibited minimal changes. In the stenotic kidney, intratubular contrast content has decreased in all nephron segments, especially in the distal tubule, where it correlated with an increase in serum creatinine and stenosis severity. In the contralateral kidney, dilution of proximal tubular fluid correlated with the increase in BP, likely due to pressure-natriuresis. In conclusion, the swine model closely resembles human renovascular hypertension. In the stenotic kidney, the hemodynamic impairment of the cortex is dissociated from the relatively preserved renal medulla, and the earliest effect on excretory function is observed in the distal nephron, where the fall in the amount of fluid reaching that segment is directly proportional to the renal arterial compromise. Electron-beam computerized tomography shows promise to noninvasively quantify, follow-up, and study changes in concurrent, in vivo intrarenal hemodynamics and segmental tubular function in renovascular hypertension.

Animals↗

Cardiac production of angiotensin II and its pharmacologic inhibition: effects on the coronary circulation.

Angiotensin II (AII), produced systemically as well as locally in the heart, affects the coronary circulation, as do consequences of its pharmacologic inhibition. AII is a powerful vasoconstrictor directly acting on vascular smooth muscle cells, modulating sympathetic innervation and calcium ion influx, and releasing other vasoconstrictor factors. In addition to these immediate actions, AII has longer-term biologic actions that influence cardiac endothelial function, vascular smooth muscle cell phenotype expression, and fibroblast proliferation. Moreover, the production of AII is interrelated with the vasodilator substances bradykinin, nitric oxide, and prostaglandins E2 and I2 (prostacyclin). Circulating hormonal actions of AII include fluid retention, direct vasoconstriction, and sympathetic neuromodulation, all resulting in increased left ventricular preload and afterload. Because of these local and hormonal characteristics, AII can immediately affect the myocardial balance of metabolic demand and supply and long term can induce structural vascular and myocardial alterations. Pharmacologic inhibition of AII production likely conveys myocardial and vascular protection in situations of acute myocardial oxygen debt. In the long term, inhibition of AII may attenuate structural changes in the coronary microcirculation related to various cardiomyopathies or acute tissue injury, and direct antiatherogenic effects may also occur.

Angiotensin II↗

Quantitative evaluation of regional myocardial perfusion using fast X-ray computed tomography.

Clinical quantitation of regional myocardial perfusion using a minimally invasive and easily applied technique could allow for ready quantitation of the functional significance of coronary disease, allow for further understanding of flow reserve in various cardiomyopathic and hemodynamic overload (pressure versus volume) conditions, and possibly provide basic information needed regarding the development and clinical significance of coronary collateral vessels and diseases of the myocardial microcirculation. Electron beam CT (EBCT) is a unique cardiac imaging modality that allows for rapid acquisition tomographic slices of the heart with excellent spatial resolution. It has been demonstrated to provide accurate measurements of cardiac anatomy, biventricular function, myocardial mass, and estimates of mural atherosclerotic plaque burden via quantification of coronary calcium. The application of classical indicator techniques for use by fast x-ray computed tomography techniques such as electron beam CT has been shown to allow quantitative analysis of regional myocardial perfusion throughout the myocardium. Initial studies using central intravenous contrast injection in experimental animals showed a close correlation of regional myocardial perfusion as quantitated by electron beam CT with measurements using radiolabeled microspheres at resting and moderately increased flow states. At high flow states, however, electron beam CT significantly underestimated absolute myocardial perfusion and thus myocardial flow reserve. Using another fast CT device, the Dynamic Spatial Reconstructor (DSR), concepts of intramyocardial vascular blood volume and its relation to myocardial flow have been established. By adapting these concepts to electron beam CT scanning and accounting for the increase in intramyocardial vascular blood volume at vasodilatation, the ability to correctly quantitate perfusion states up to approximately 400 mL.min-1. 100 g-1 using central intravenous contrast administration was demonstrated. This implies that studies can be done with intravenous injection methods for characterization of regional myocardial perfusion up to the normal flow reserve of approximately 4:1. Important physiologic and clinical abnormalities in flow reserve generally result in a ratio < 3:1. Electron beam CT offers the capability to quantitate regional myocardial perfusion in both the clinical and research setting. Of particular interest is the ability to provide quantitative regional myocardial perfusion which can be coupled to the evaluation of cardiac anatomy and function as well as mural coronary atherosclerotic calcium burden during the same scanning session. Thus, electron beam CT has the potential to become a valuable, minimally invasive clinical tool for comprehensive analysis of cardiac function and coronary status.

Cardiomyopathies↗

Perfusion pressure dependency of in vivo renal tubular dynamics.

To examine whether changes in renal perfusion pressure (RPP) within the range of autoregulation induce detectable changes in tubular dynamics in an entire nephron population of the intact kidney, we measured, using electron beam computed tomography (EBCT), transit times (TT, s) and intratubular concentration (%) of filterable contrast media in various nephron segments simultaneously with renal regional perfusion. In seven dogs (group A) this was performed at the upper and lower limits of autoregulation (RPP = 130 and 95 mmHg, respectively) while group B (n = 5) served as control. In group A alone, a decrease in RPP led to an increase in TT by 40%, 68%, and 32% in the proximal tubules, ascending limb of Henle's loop, and distal tubules, respectively, in association with an increase in intratubular concentration (+ 50%, 80%, and 42%, respectively). Papillary perfusion decreased, whereas perfusion of the adjacent, outlying inner medulla increased. The decrease in papillary perfusion correlated positively with the concurrent change in sodium excretion (R = 0.81). This study demonstrates that changes in RPP within the autoregulatory range elicit changes of tubular sodium reabsorption mainly in proximal, distal, and ascending tubules, in which most of the nephrons participate. These tubular changes are associated with an alteration of perfusion circumscribed to two areas of the inner renal medulla.

Animals↗

The relationship between renal cortical volume and predisposition to hypertension.

It has been proposed that a reduction in the number of nephrons is a renal abnormality that plays an important role in the pathogenesis of essential hypertension. The objective of this study was to determine whether renal cortical volume, used as a measure of the number of nephrons, is lower in normotensive subjects with a familial predisposition to develop essential hypertension than in subjects who lack this predisposition. For this purpose, we measured renal cortical volume using electron beam computed tomography in 26 white offspring to two hypertensive parents (OHT; 14 women, 12 men) and 27 white offspring of two normotensive parents (ONT; 13 women, 14 men) who were stabilized on a high sodium diet for 3 days (200 mmol/day). In women, mean age was significantly greater in OHT than ONT (46.1 +/- 4.9 [standard deviation] v 41.8 +/- 5.1 years, respectively, P = .04)In men, means for age and weight were greater in OHT than ONT (age: 47.1 +/- 7.7 v 37.9 +/- 8.1 years, P < .01; weight: 90.2 +/- 10.7 v 81.1 +/- 9.4 kg, P = .03.) In women, mean total cortical volume did not differ significantly between OHT and ONT (156 +/- 33.3 v 166 +/- 30.9 cc, P = .80). After adjustment for interindividual differences in age, mean total cortical volume remained not significantly different in OHT than ONT (160 +/- 29.0 v 162 +/- 32.4 cc, P = .83). In men, mean total cortical volume was significantly greater in OHT than ONT (210 +/- 33.6 v 180 +/- 20.0 cc, P = .01). After adjustment for interindividual differences in age, mean total cortical volume remained significantly greater in OHT than ONT (207 +/- 33.2 v 182 +/- 19.8 cc, P = .02). After adjustment for interindividual differences in body weight, mean total cortical volume did not differ significantly between OHT and ONT (201 +/- 21.7 v 187 +/- 20. cc, P = .09). The results of this study do not support the hypothesis that a decrease in renal cortical volume, as a result of a decrease in number of nephrons, is a characteristic of white women or men with a familial predisposition to develop essential hypertension.

Adult↗

Computed tomography-derived intrarenal blood flow in renovascular and essential hypertension.

The effect of renal artery stenosis on intrarenal perfusion and volume in renovascular hypertensive patients is unclear. Alterations in these attributes may ultimately be involved in deterioration of renal function. We measured whole kidney, cortical, and medullary perfusion and volume with electron beam computed tomography (EBCT) in 33 hypertensive patients, with well-preserved renal function, scheduled for renal angiography. EBCT-derived whole kidney perfusion was lower in patients with atherosclerotic renal artery stenosis (RAS; N = 20) than in fibromuscular dysplasia (FMD; N = 10) or essential hypertension (N = 28; P < 0.05), as was cortical perfusion (2.44 +/- 0.16 vs. 3.26 +/- 0.17 and 3.07 +/- 0.09 ml/min/cc tissue, respectively, P < 0.005), but medullary perfusion was similar. Whole kidney, cortical, and medullary perfusion correlated inversely with degree of stenosis in FMD, but not in atherosclerotic RAS. Renal volumes were similar. These results demonstrate that, in contrast to patients with FMD, in patients with atherosclerotic RAS the decrease in cortical perfusion is not directly related to the degree of stenosis in the main renal artery. Factors other than the stenosis itself may play a role in the pathophysiology of atherosclerotic RAS and associated renal failure.

Adult↗

Reproducibility of human kidney perfusion and volume determinations with electron beam computed tomography.

RATIONALE AND OBJECTIVES: Alterations in whole kidney, cortical, and medullary perfusion and volume play a pivotal role in various physiologic and pathophysiologic processes. Electron-beam computed tomography (EBCT) provides accurate measurements of these traits in animals, but their reproducibility in humans has not been established. METHODS: Perfusion, volume, and flow measurements were obtained by EBCT in eight healthy human volunteers under controlled conditions on two consecutive days. RESULTS: Mean values for whole kidney, cortical, and medullary perfusion and volume obtained with EBCT were similar in scan 1 and scan 2 (P > 0.1), and correlated highly. Coefficients of variation for the repeated measurements usually were less than 10%. Values obtained for renal regional perfusion and volume agreed with previously reported values. CONCLUSIONS: Electron-beam computed tomography estimates of single whole kidney, cortical, and medullary perfusions and volumes are highly reproducible in normal humans, and may be useful to advance understanding of renal involvement in human disease.

Adult↗