Biomedical subjects

E L Ritman

Publications and source records attributed to E L Ritman.

At least 19 recordsLinked to original sources

PubMed2006

Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: sequential triple biopsy studies with micro-computed tomography.

The objective of the study was to assess the time course of changes in bone mineralization and architecture using sequential triple biopsies from women with postmenopausal osteoporosis (PMO) who received long-term treatment with risedronate. Transiliac biopsies were obtained from the same subjects (n = 7) at baseline and after 3 and 5 years of treatment with 5 mg daily risedronate. Mineralization was measured using 3-dimensional (3D) micro-computed tomography (CT) with synchrotron radiation and was compared to levels in healthy premenopausal women (n = 12). Compared to the untreated PMO women at baseline, the premenopausal women had higher average mineralization (Avg-MIN) and peak mineralization (Peak-MIN) by 5.8% (P = 0.003) and 8.0% (P = 0.003), respectively, and lower ratio of low to high-mineralized bone volume (BMR-V) and surface area (BMR-S) by 73.3% (P = 0.005) and 61.7% (P = 0.003), respectively. Relative to baseline, 3 years of risedronate treatment significantly increased Avg-MIN (4.9 +/- 1.1%, P = 0.016) and Peak-MIN (6.2 +/- 1.5%, P = 0.016), and significantly decreased BMR-V (-68.4 +/- 7.3%, P = 0.016) and BMR-S (-50.2 +/- 5.7%, P = 0.016) in the PMO women. The changes were maintained at the same level when treatment was continued up to 5 years. These results are consistent with the significant reduction of turnover observed after 3 years of treatment and which was similarly maintained through 5 years of treatment. Risedronate restored the degree of mineralization and the ratios of low- to high-mineralized bone to premenopausal levels after 3 years of treatment, suggesting that treatment reduced bone turnover in PMO women to healthy premenopausal levels. Conventional micro-CT analysis further demonstrated that bone volume (BV/TV) and trabecular architecture did not change from baseline up to 5 years of treatment, suggesting that risedronate provided long-term preservation of trabecular architecture in the PMO women. Overall, risedronate provided sustained benefits on mineralization and architecture, two key determinants of bone strength, over 5 years lending support for its long-term efficacy in fracture risk reduction.

Adult↗

PubMed2004

[Minimally invasive quantitation of myocardial microvascular function using computed tomography: the blood volume-to-flow relationship].

The intramyocardial coronary microvasculature has an important role in regulating regional myocardial perfusion. Pathologic alterations of microvascular function may be present in early stages of coronary artery disease, myocardial hypertrophy, cardiomyopathy or systemic diseases such as arterial hypertension and diabetes mellitus. Fast computed tomography permits noninvasive simultaneous quantitation of regional intramyocardial blood volume and myocardial perfusion using indicator dilution principles. Our data indicate that especially the blood volume-to-flow relationship is sensitive enough to characterize and quantitate the functional impact of different pathologies along the coronary tree on microvascular function. This could be demonstrated for 1) acute impairment of microvascular function following coronary microembolization, 2) endothelial dysfunction induced by chronic hypercholesterolemia, 3) chronic epicardial non-significant stenoses, 4) physiologic maturation of the normal microvasculature and 5) quantification of heterogeneity of microvascular function. These findings, the methodological background and the concept itself are presented in this article. Application of the blood volume-to-flow relationship is not limited to fast-CT but may be used in any cross sectional imaging technique, such as MRI or echocardiography, as long as intramyocardial blood volume and perfusion can be quantitated simultaneously. This new noninvasive approach to the quantification of intramyocardial microvascular function may prove a useful adjunct to those imaging techniques that are used to noninvasively quantitate epicardial stenoses or regional wall motion abnormalities.

Animals↗

PubMed2003

Impact of coronary vasa vasorum functional structure on coronary vessel wall perfusion distribution.

Noncoronary vasa vasorum have been described as networks of microvessels in the wall of arteries and veins. However, we have shown, using microcomputerized tomography (micro-CT) imaging methods, that porcine coronary vasa vasorum have a tree-like branching structure similar to the vasculature in general. In this study, we elucidate functional aspects of coronary vasa vasorum perfusion territories. Three pig hearts were injected with radiopaque Microfil via the coronary sinus to fill the left anterior descending coronary arteries (LADs) retrogradely at atmospheric pressure. In three other hearts, LADs were injected antegradely at 100-mmHg pressure via the left main carotid artery. Additionally, six LADs were injected in vivo with a suspension of 100- or 300-microm-diameter microspheres before harvesting of the hearts and injection of the LADs with Microfil. All harvested LADs were scanned intact with micro-CT (20 microm cubic voxels). The spatial density of vasa vasorum (no. of vasa/mm2) was measured in 20-microm-thick cross sections (at 0.4-mm intervals). Retrogradely injected LADs showed high and uniformly distributed vasa vasorum densities in the adventitia (means +/- SE; 5.38 +/- 0.09 vs. 3.58 +/- 0.1 vasa/mm2 in antegradely prepared LADs; P < 0.001). Antegradely prepared LADs showed patchy distributed, low-vasa-vasorum-density territories especially on the myocardial side of the coronary artery wall (epicardial density: 4.29 +/- 0.13 vasa/mm2 vs. myocardial density: 2.80 +/- 0.1 vasa/mm2, P < 0.001). Microembolization reduced vasa vasorum densities significantly (100-mum-diameter microspheres: 3.26 +/- 0.07 vasa/mm2, P < 0.05; 300-microm-diameter microspheres: 2.66 +/- 0.07 vasa/mm2, P < 0.001 vs. antegrade controls) and increased the size of low-vasa-vasorum-density territories. We conclude that coronary vasa vasorum are functional endarteries not connected via a plexus. This characteristic may have a significant impact on the spatial distribution of perfusion and drainage of the coronary vessel wall.

Animals↗

PubMed2003

Time course of epiphyseal growth plate fusion in rat tibiae.

Although the rat is the most common animal model used in studying osteoporosis, it is often used inappropriately. Osteoporosis is a disease that most commonly occurs in humans long after growth plate fusion with the associated cessation of longitudinal bone growth, but there has been a question as to when or to what extent the rat growth plate fuses. To investigate this question, we used microcomputed X-ray tomography, at voxel resolutions ranging from (5.7 micro m)(3) to (11 micro m)(3), to image the proximal epiphyseal growth plates of both male (n = 19) and female (n = 15) rat tibiae, ranging in age from 2 to 25 months. The three-dimensional images were used to evaluate fusion of the epiphyseal growth plate by quantitating the amount of cancellous bone that has bridged across the growth plate. The results suggest that the time course of fusion of the epiphyseal growth plate follows a sigmoidal pattern, with 10% of the maximum number of bridges having formed by 3.9 months in the male tibiae and 5.8 months in the female tibiae, 50% of the maximum number of bridges having formed by 5.6 months in the male tibiae and 5.9 months in the female tibiae, and 90% of the total maximum of bridges have formed by 7.4 months for the males and 6.5 months for the females. The total volume of bridges per tibia at the age at which the maximum number of bridges per tibia has first formed is 0.99 mm(3)/tibia for the males and 0.40 mm(3)/tibia for the females. After the maximum number of bridges (-290 for females, -360 for males) have formed the total volume of bridges per tibia continues to increase for an additional 7.0 months in the males and 17.0 months for the females until they reach maximum values (-1.5 mm(3)/tibia for the males and -2.2 mm(3)/tibia for the females).

Aging↗

PubMed2003

Effects of implant healing time on crestal bone loss of a controlled-load dental implant.

The universally accepted concept of delay-loaded dental implants has recently been challenged. This study hypothesizes that early loading (decreased implant healing time) leads to increased bone formation and decreased crestal bone loss. We used 17 minipigs to study implants under a controlled load, with non-loaded implants for comparison. Radiographic and histological assessments were made of the osseointegrated bone changes for 3 healing times (between implant insertion and loading), following 5 months of loading. The effect of loading on crestal bone loss depended on the healing time. Early loading preserved the most crestal bone. Delayed loading had significantly more crestal bone loss compared with the non-loaded controls (2.4 mm vs. 0.64 mm; P < 0.05). The histological assessment and biomechanical analyses of the healing bone suggested that loading and bioactivities of osteoblasts exert a synergistic effect on osseointegration that is likely to support the hypothesis that early loading produces more favorable osseointegration.

Alveolar Bone Loss↗

PubMed2003

Measurement of gene expression following cryogenic mu-CT scanning of human iliac crest biopsies.

An important consideration in interpreting indices of gene expression in human bone is relating mRNA levels to functional endpoints such as bone architecture. In the present study, a method was developed for quantitative measurement of gene expression and bone morphology in the same specimen. Three-dimensional images of iliac crest bone biopsies from healthy premenopausal women were obtained using a novel high resolution cryogenic mu-CT scanner. RNA was isolated from the biopsies and mRNA levels were measured for genes related to bone metabolism. The gene expression profile and variability of expression within iliac crest biopsies of women was similar to human osteoblastic cell lines and rat long bones. mRNA for alkaline phosphatase, bone matrix proteins, and selected cytokines and cytokine receptors were consistently detected in biopsies. As previously shown in rat bone, there was a tight correlation between mRNA levels for type 1 collagen and osteonectin, a weaker correlation between type 1 collagen and osteocalcin and no correlation between bone matrix proteins and alkaline phosphatase. The relative abundance of the mRNA for the three most prevalent transforming growth factor-beta (TGF-beta) isoforms in bone (TGF-beta(1)>> TGF-beta(3)> TGF-beta(2)) was the same as the known abundance of the corresponding TGF-beta peptides in bone matrix. The results demonstrate the feasibility of analyzing the three-dimensional architecture of a bone biopsy using cryogenic mu-CT imaging and then measuring expression of genes related to bone cell function within the same specimen following RNA extraction and analysis.

Journal Article↗

PubMed2001

Quantitative assessment of the rat intrahepatic biliary system by three-dimensional reconstruction.

The anatomical details of the biliary tree architecture of normal rats and rats in whom selective proliferation was induced by feeding alpha-naphthylisothiocyanate (ANIT) were reconstructed in three dimension using a microscopic-computed tomography scanner. The intrahepatic biliary tree was filled with a silicone polymer through the common bile duct and each liver lobe embedded in Bioplastic; specimens were then scanned by a microscopic-computed tomography scanner and modified Feldkamp cone beam backprojection algorithm applied to generate three-dimensional images. Quantitative analysis of bile duct geometry was performed using a customized software program. The diameter of the bile duct segments of normal and ANIT-fed rats progressively decreased with increasing length of the biliary tree. Diameter of bile ducts from ANIT-fed rats (range, 21 to 264 microm) was similar to that of normal rats (22 to 279 microm). In contrast, the number of bile duct segments along the major branch reproducibly doubled, the length of the bile duct segments decreased twofold, and the length of the biliary tree remained unchanged after ANIT feeding. Moreover, the total volume of the biliary tree of ANIT-fed rats was significantly greater (855 microl) than in normal rats (47 microl). Compared with normal rats, the total surface area of the biliary tree increased 26 times after ANIT-induced bile duct proliferation. Taken together, these observations quantitate the anatomical remodeling after selective cholangiocyte proliferation and strongly suggest that the proliferative process involves sprouting of new side branches. Our results may be relevant to the mechanisms by which ducts proliferate in response to hepatic injury and to the hypercholeresis that occurs after experimentally induced bile duct proliferation.

1-Naphthylisothiocyanate↗

PubMed2001

Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia.

OBJECTIVE: Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. METHODS: Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. RESULTS: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93+/-6%) and Group 2 (89+/-7%) but impaired in Group 3 (71+/-11%; P<0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88+/-2.45 per-mm(2)) and Group 3 (4.50+/-1.37 per-mm(2)) compared to Group 1 (2.97+/-1.37 per-mm(2); P<0.05 vs. Group 2 and 3). CONCLUSION: This study demonstrates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vasorum neovascularization in the initial stage of atherosclerotic vascular disease.

Analysis of Variance↗

PubMed2001

Coronary microvascular functional reserve: quantification of long-term changes with electron-beam CT preliminary results in a porcine model.

PURPOSE: To evaluate the ability of electron-beam computed tomography (CT) to help quantify long-term changes in coronary microvascular functional reserve in a porcine model. MATERIALS AND METHODS: Electron-beam CT-based intramyocardial blood volume and perfusion and Doppler ultrasonography (US)-based intracoronary blood flow were obtained in 13 pigs at baseline and again 3 months later. Measurements were obtained at rest and after the administration of adenosine. The short-term variation during 30 minutes of electron-beam CT measurements was assessed in nine additional pigs. RESULTS: Short-term variation of blood volume and perfusion averaged 8% and 9%, respectively, and was similar for both weight groups at rest and after adenosine administration. At rest, intracoronary blood flow, blood volume, and perfusion remained unchanged from baseline to follow-up. Long-term increases (percentage change with adenosine relative to that at rest) in blood volume and perfusion reserves were consistent with increasing intracoronary blood flow reserves. Despite these long-term changes in intracoronary blood flow, blood volume, and perfusion, the blood volume-to-perfusion relationship suggests a similar blood volume distribution among different microvascular functional components in normal porcine myocardium at both weight groups. CONCLUSION: Electron-beam CT may be of value for quantifying long-term changes in intramyocardial microvascular function.

Animals↗

PubMed2001

Noninvasive measurement of concurrent single-kidney perfusion, glomerular filtration, and tubular function.

To assess the reliability of electron beam computed tomography (EBCT), measurements of single-kidney renal blood flow (RBF), glomerular filtration rate (GFR), and intratubular contrast medium concentration (ITC) of radiographic contrast media were quantified in anesthetized pigs before and after acetylcholine-induced vasodilation and diuresis. EBCT measurements were compared with those obtained with intravascular Doppler and inulin clearance. The capability of EBCT to detect chronic changes in single-kidney function was evaluated in pigs with unilateral renal artery stenosis, and their long-term reproducibility in normal pigs was studied repeatedly at 1-mo intervals. EBCT-RBF (ml/min) correlated with Doppler-RBF as RBF(EBCT) = 45 + 1.07 * RBF(Doppler), r = 0.81. EBCT-GFR (ml/min) correlated with inulin clearance as GFR(EBCT) = 11.7 + 1.02 * GFR(inulin), r = 0.80. During vasodilation, RBF and GFR increased, whereas ITC decreased along the nephron. In renal artery stenosis, single-kidney GFR decreased linearly with the degree of stenosis, and ITC increased along the nephron, indicating increased fluid reabsorption. EBCT-RBF, GFR, and ITC were similar among repeated measurements. This approach might be invaluable for simultaneous quantification of regional hemodynamics and function in the intact kidneys, in a manner potentially applicable to humans.

Animals↗

PubMed2001

Measurement and display of regional myocardial motion during post infarct treatment.

Quantitative assessment of 3-D regional heart motion has significant potential to provide more specific diagnosis of cardiac malfunction than currently possible. Using functional parametric mapping, regional myocardial motion during a cardiac cycle can be color-mapped onto a deformable heart model to provide better understanding of the structure-to-function relationships in the myocardium, including regional patterns of akinesis or dyskinesis associated with ischemia or infarction. In this study, 3-D reconstructions of human hearts were obtained from Electron-Beam Computed Tomography [1] (EB-CT), comparing stages of treatment after myocardial infarction.

Computer Simulation↗

PubMed2001

Corporeal structural and vascular micro architecture with X-ray micro computerized tomography in normal and diabetic rabbits: histopathological correlation.

PURPOSE: The pathophysiology of diabetes mellitus induced erectile dysfunction is poorly understood. In patients with diffuse venous leakage structural changes in the corpora cavernosa have correlated with failure of the veno-occlusive mechanism. Three-dimensional (D) micro computerized tomography (CT) has proved to be an important imaging technique for the intact kidney, heart, liver and bone. We examined control and diabetic rabbit penises by 3-D micro CT and quantified any structural changes. MATERIALS AND METHODS: Male white New Zealand rabbits were treated with alloxan to induce diabetes or used as normal controls. Via aortic access at laparotomy the penile vascular tree was vasodilated with papaverine and perfused with radiopaque silicone rubber. X-ray micro CT was then performed at 21 microm. resolution and images were analyzed in 3-D using custom software. RESULTS: Nine diabetic rabbits with blood glucose greater than 400 mg./dl. and 9 control animals were used for micro CT analysis. Significant decreases (p <0.05) were observed in the mean sinusoidal and vascular volume fraction plus or minus standard error of mean of the corpus cavernosum in the diabetic (323.7 +/- 43.1 mm.3 and 37.9 +/- 2.0%, respectively) and control (510.1 +/- 47.4 mm.3 and 53.1 +/- 3.80%, respectively) groups. Also, the mean left and right cavernous artery luminal cross-sectional area in diabetics (0.15 +/- 0.02 and 0.16 +/- 0.01 mm.2, respectively) versus controls (0.2 +/- 0.01 and 0.2 +/- 0.01 mm.2, respectively) was significantly decreased (p <0.05). Furthermore, the mean left and right total cavernous artery luminal volume in diabetics (0.4 +/- 0.07 and 0.4 +/- 0.09 mm.3, respectively) versus controls (1.0 +/- 0.13 and 0.9 +/- 0.11 mm.3, respectively) was significantly decreased (p <0.05). CONCLUSIONS: Diabetic rabbit penises showed a significant decrease in corporeal vascular volume as well as decreased cavernous artery diameter and luminal volume compared to controls. This finding correlated well with the mean decrease in trabecular smooth muscle in control and severely diabetic rabbits on histopathological studies (42.2% +/- 1.5% versus 35.8% +/- 1.5%). This combination of potential arterial insufficiency as well as an increase in diffuse connective tissue may contribute to the overall pathophysiology of diabetic erectile dysfunction. These results suggest that 3-D x-ray micro CT with molecular analysis may be a powerful tool for examining the pathophysiology of diabetic erectile dysfunction.

Angiography↗

PubMed2001

An integrated approach to assess structure-to-function relationships in the skeleton.

In general, the disciplines of biomechanics, morphology, densitometry, biochemistry, cell biology and molecular biology have advanced independently of one another. In spite of this fragmentation, there have been incremental increases in our understanding of the organization, mechanical properties, growth, remodeling and repair of the tissues comprising the skeleton. As a practical application, this increased knowledge has greatly improved our capabilities for early diagnosis of bone loss and has proven similarly useful in determining the efficacy of interventions to prevent osteoporosis. This approach, however, has been much less successful in countering several other important musculoskeletal disorders, including arthritis. In the immediate future, a major emphasis will be placed on tissue regeneration (engineering) to restore lost mechanical function to a compromised skeleton. To accomplish this goal, it will be necessary to employ much more sophisticated approaches toward evaluating the structure-to-function relationships, ones which will include integration of the respective contributions of gene expression, cell number and activity, matrix composition and architecture to achieve adequate tissue function.

Journal Article↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

The effect of collateral flow and myocardial viability on the distribution of technetium-99m sestamibi in a closed-chest model of coronary occlusion and reperfusion.

Myocardial uptake of technetium-99m sestamibi at low coronary flow rates overestimates blood flow, but the relative impact of flow and viability on 99mTc-sestamibi kinetics is unclear. The objective of this study was to determine the effect of myocardial viability and the degree of collateral blood flow on the uptake and retention of 99mTc-sestamibi by examining three animal models of coronary occlusion and reperfusion, each reflecting a different state of viability and collateral blood flow. Three closed-chest animal models were studied: canine (high collateral flow, preserved viability), porcine (low collateral flow, absent viability) and porcine with slowly occlusive coronary stents producing infarction and enhanced collateral blood flow (high collateral flow, absent viability). There were seven dogs, seven pigs and six pigs, respectively, in each animal model. Animals from all three models were subjected to a 40-min total left anterior descending artery (LAD) occlusion followed by 2 h of reperfusion. 99mTc-sestamibi and radiolabelled microspheres were injected during LAD occlusion 10 min prior to reperfusion. Animals were sacrificed after 2 h of reperfusion flow. Ex situ heart slice imaging to determine risk area was followed by viability staining to determine infarct size. Slices were subsequently sectioned into equally sized radial segments and placed in a gamma well counter. Risk area as determined by ex situ 99mTc-sestamibi imaging was not significantly different by model. Pathological infarct size differed significantly by model [canine = 1%+/-1% of the left ventricle (LV); porcine = 13%+/-8% LV; porcine with stent = 14%+/-7% LV; P = 0.002)]. Collateral blood flow by microspheres during occlusion tended to differ among models (overall P = 0.08), with the canine and porcine with stent models having relatively high flow rates compared with the acute porcine model. 99mTc-sestamibi activity correlated with microsphere blood flow in all three models, with r values for individual animals (n = 20) ranging from 0.86 to 0.96 (all P<0.0001). There was a significant difference in the regression line intercepts (P<0.0001) and slopes (P<0.01) among the three models comparing 99mTc-sestamibi uptake with myocardial blood flow. 99mTc-sestamibi uptake overestimated blood flow to a greater extent in the canine model (high flow with viability) than in the porcine model (low flow, absent viability). Despite enhanced collateral flow, there was significantly less overestimation of flow in the porcine stent model (high flow, absent viability). In conclusion, at low flow rates 99mTc-sestamibi activity overestimates myocardial blood flow. This effect is most pronounced in myocardium with significant collateral flow and preserved viability, consistent with over-extraction or redistribution of the tracer. The effect is markedly decreased in non-viable myocardium regardless of blood flow.

Animals↗

PubMed2000

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↗

PubMed2000

A systematic analysis of factors which may impact upon tomographic perfusion imaging measurements: implications for the use of Tc-99m sestamibi in acute myocardial infarction.

BACKGROUND: The use of acute Tc-99m sestamibi imaging has provided a valuable methodology to assess myocardium at risk and collateral blood flow. OBJECTIVE: The purpose of this study was to determine the impact of physical, physiologic, and reconstruction factors on the extent and severity of Tc-99m sestamibi images in a porcine model of coronary occlusion and reperfusion. METHODS AND RESULTS: Eleven pigs underwent 40 min of coronary occlusion using a balloon catheter followed by reperfusion. Radiolabeled microspheres were injected during occlusion for blood flow determination and 20-30 mCi of Tc-99m sestamibi was injected intravenously for cardiac imaging. Each animal underwent four modes of gamma camera imaging: a cardiac and respiratory gated SPECT study, an ungated SPECT study, a post-mortem SPECT study and an ex-situ study where the heart was sliced into five short axis slices and directly imaged. All animals had extensive wall motion abnormalities at the time of imaging. Myocardial risk area by ex-situ imaging was 32 +/- 9% LV and did not significantly change with the addition of a chest cavity and tomographic reconstruction (post-mortem and gated imaging) or cardiac and respiratory motion (ungated imaging). Defect severity was significantly underestimated with the addition of a chest cavity and tomographic reconstruction but was unaltered by cardiac and respiratory motion. CONCLUSIONS: The assessment of risk area acutely by SPECT Tc-99m sestamibi imaging is unaffected by cardiac motion obviating the necessity for gated imaging. Estimated defect severity (which has been used as a measure of collateral flow) is significantly reduced by the chest wall and tomographic acquisition and reconstruction suggesting a role for scatter and attenuation algorithms for this measure.

Animals↗