Biomedical subjects

H R Schelbert

Publications and source records attributed to H R Schelbert.

At least 73 records · Page 4Linked to original sources

PubMed1994

Myocardial blood flow at rest and during pharmacological vasodilation in cardiac transplants during and after successful treatment of rejection.

BACKGROUND: The relative intracoronary flow reserve has been found to be reduced during acute transplant rejection, but the effects of rejection on absolute flows at rest and during hyperemia have not been established previously. This has now become possible through noninvasive quantification of myocardial blood flow with positron emission tomography. METHODS AND RESULTS: Myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia was quantified in 10 transplant patients (group A) during an acute, biopsy-proven rejection episode and again after successful immunosuppressive treatment and in 6 transplant patients (group B) without prior rejection episode. In group A patients, MBF during rejection averaged 1.7 +/- 0.3 mL.min-1.g-1 at rest and 2.5 +/- 0.9 mL.min-1.g-1 during hyperemia; after recovery, MBF at rest had declined to 1.2 +/- 0.3 mL.-1.g-1 (P < .001) but had increased to 3.9 +/- 1.1 mL.-1.g-1 (P < .001) during hyperemia. Flows after recovery from rejection were similar to those in the group B patients (0.9 +/- 0.2 and 3.9 +/- 0.7 mL.min-1.g-1). Flow reserve in the group A patients was only 1.5 +/- 0.5 during rejection but improved to 3.4 +/- 0.9 at recovery (P < .001) and thus remained lower than in the control patients (4.5 +/- 0.7, P < .05). Minimal coronary resistance during dipyridamole vasodilation was elevated during rejection (40 +/- 11 mm Hg.mL-1.min-1.g-1); after recovery, it no longer differed from that in the group B patients (26 +/- 11 versus 22 +/- 4 mm Hg.mL-1.min-1.g-1). MBF during rejection was increased relative to cardiac work, as demonstrated by significantly higher ratios of blood flow to rate-pressure product than those at recovery and in the control patients. CONCLUSIONS: A decrease in hyperemic and an increase in resting myocardial blood flow, in excess to cardiac work, account for the previously reported reduction in coronary flow reserve. Because both alterations improve with antirejection treatment, they may reflect reversible alterations, presumably of endothelial function, local coagulation, and edema. The compromise in flow reserve and hyperemic flows may contribute to acute and chronic injury from rejection and thus provides a rationale for exercise restriction during rejection. The results further suggest a potential role for serial noninvasive flow measurements to guide immunosuppressive therapy.

Adult↗

PubMed1994

Non-invasive quantification of myocardial blood flow and flow reserve using dynamic positron emission tomography.

Positron Emission Tomography (PET) permits the non-invasive quantification of myocardial blood flow and flow reserve. This capability requires an understanding of the determinants of resting and hyperemic blood flow in order to interpret correctly quantitative findings with PET. Equally important is the knowledge of how such measurements are obtained and of their advantages and limitations. The aim of the current overview was therefore a) to review the concept of the myocardial flow reserve and b) to discuss recent animal experimental and clinical studies which have employed quantitative PET for measuring myocardial blood flow and flow reserve.

Cardiomyopathy, Hypertrophic↗

PubMed1994

Quantification of the extent and severity of perfusion defects in canine myocardium by PET polar mapping.

UNLABELLED: This study validates perfusion defect extent and severity as derived by PET polar maps in vivo against measurements derived from radiolabeled microspheres. METHODS: In seven open-chest dogs, either the left anterior descending (n = 11) or left circumflex coronary artery (n = 13) were ligated sequentially from distal to proximal. After each occlusion, gated PET images were acquired with 13N-ammonia (20 mCi) while radiolabeled microspheres were administered into the left atrium. The transaxial PET images were reoriented into left ventricular short-axis cuts, including the apex, and polar maps were generated from circumferential activity profiles. PET polar maps were then compared with polar maps derived from microspheres after normal databases for 13N-ammonia and for microspheres were established. Nitrogen-13 or microsphere activities of less than 1.5 s.d. below the mean were defined as hypoperfused. RESULTS: The extent (percent of left ventricular mass) and mean severity of the hypoperfused myocardium in the postmortem microsphere measurements ranged from 3% to 69% and 3% to 58%, respectively. The estimated extent by summed PET and by microspheres correlated by y = 4.95 + 0.95x (r = 0.91, s.e.e. = 0.085, p < 0.001) and mean severity by y = 5.52 + 0.87x (r = 0.85, s.e.e. = 0.101, p < 0.001). The extent and severity were similar for summed and gated PET studies. CONCLUSION: The current study validated a polar map approach that provides accurate, quantitative assessment of the extent and severity of myocardial perfusion defects in vivo. Gating did not yield an improved correlation between PET and microsphere measurements. Thus, ungated PET images can be used to assess accurately the extent and severity of perfusion defects.

Ammonia↗

PubMed1994

Blood flow and metabolism by PET.

Quantitative imaging capabilities, the large number of radiotracers labeled with short-lived positron-emitting isotopes, and appropriate tracer kinetic models offer a broad range of possibilities for probing different aspects of normal and diseased human myocardium. To some extent, PET has already had an impact on clinical cardiology and can decisively influence patient management. At the same time, PET offers tools for elucidating mechanisms of disease and for monitoring responses to treatment. It is also likely to offer new insights into myocardial function in normal and pathologic conditions. Although these insights may initially seem to lack clinical implications, they are likely to lead to a new hypothesis which can simultaneously be tested. The considerable range of assay techniques available with PET is likely to contribute to a more comprehensive characterization of abnormal processes. This, in turn, may lead to new therapeutic opportunities and, thus, result in a broader utilization of PET in cardiovascular disease.

Animals↗

PubMed1994

Persistent twenty-four hour SPECT thallium-201 defects, plasma thallium-201 concentrations and PET metabolic viability.

Previous studies have shown that defects on four hour thallium-201 redistribution images often exhibit late reversibility, suggesting that the thallium-201 scintigraphic assessment of myocardial viability might be influenced by delayed redistribution imaging. To assess tissue metabolic activity in segments with late thallium-201 defects, positron emission tomography (PET) with 13NH3 and 18FDG was performed in 26 coronary artery disease patients with left ventricular dysfunction undergoing twenty-four hour SPECT thallium-201 scintigraphy. In 13 patients, plasma thallium-201 levels were obtained at the time of SPECT study and integrated tracer concentrations were determined one, two, four and twenty-four hours following injection. On circumferential profile image analysis of the PET images, ischemia was defined by preserved glucose metabolism in hypoperfused myocardium while infarction was identified by concordant reductions in both perfusion and glucose metabolism. Nineteen patients had stress-redistribution SPECT studies and seven had rest-redistribution SPECT studies. Using a semi-quantitative scoring system, four experienced observers visually identified 100 fixed, 17 partially reversible and twelve completely reversible segmental SPECT thallium-201 defects. On PET, metabolic activity was identified in 51 (51%) fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) partially reversible defects (five PET ischemia, four PET normal). Of the twelve completely reversible thallium-201 defects, six (50%) were normal on PET, five (42%) had PET ischemia and one (8%) had PET infarction. The relative number of fixed thallium-201 defects with metabolic activity on PET did not depend on whether a stress or rest thallium-201 study was performed, or on whether the plasma thallium-201 integral concentration was high or low relative to mean values at any time point. Despite delayed redistribution imaging, PET imaging identifies glucose metabolic activity, and therefore residual tissue viability, in the majority of fixed twenty-four hour thallium-201 defects.

Aged↗

PubMed1994

Metabolic imaging to assess myocardial viability.

A potentially reversible impairment of contractile function in patients with chronic coronary artery disease characteristically exhibits a regional increase in glucose utilization or, more precisely, glucose extraction, as evidenced by the presence of a blood flow-glucose metabolism mismatch. The predictive accuracy of patterns of blood flow and glucose metabolism has now been established in more than 107 patients with 384 dysfunctional myocardial segments against the gold standard of myocardial viability, the functional outcome of contractile function after revascularization. According to long-term albeit retrospective follow-up studies, correlations exist between the blood flow-metabolism patterns and patient survival or cardiac morbidity. The same studies point out the high risk of patients with blood flow-metabolism mismatches and, at the same time, the considerable benefits derived from revascularization, i.e., reduced mortality and improvement in symptoms related to congestive heart failure. Imaging of the relative distribution of blood flow and of exogenous glucose utilization with PET therefore appears to be of considerable value for identifying high-risk patients as well as for stratifying patients to the most appropriate therapeutic management. This pertains especially to patients with poor left ventricular function and symptoms related to congestive heart failure. Assessment of myocardial viability in this particular patient group remains diagnostically challenging. On the other hand, as demonstrated by several investigations, blood flow metabolism imaging with 18F-deoxyglucose and PET is highly accurate in these patients for the identification of viable or reversibly dysfunctional myocardium.

Coronary Circulation↗

PubMed1994

Evaluation of the effect of glucose ingestion and kinetic model configurations of FDG in the normal liver.

UNLABELLED: The liver plays an important role in glucose homeostasis. PET studies with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) of the liver (e.g., in neoplasms) require an understanding of the effects of dietary conditions on hepatic FDG uptake. METHODS: Twenty studies were performed on 10 normal volunteers (ages 24 +/- 4) after fasting 4 to 19 hr and again after oral consumption of 100 g of dextrose to investigate tracer kinetic model configurations of FDG in the normal liver and to evaluate the impact of oral glucose on liver in normal subjects. Dynamic PET images were acquired for about 1 hr using a Siemens/CTI 931 tomograph. RESULTS: A three-compartment model with an input function delay time parameter was the statistically preferred model configuration. The model estimated transport rate constant from plasma to liver, K1, increased significantly (p < 0.05) from 0.864 +/- 0.136 ml/min/g in fasting studies to 1.058 +/- 0.269 ml/min/g in postglucose studies. Glucose loading also significantly increased (p < 0.01) the rate constant for FDG phosphorylation, k3, from 0.005 +/- 0.003 min-1 in fasting studies to 0.013 +/- 0.007 min-1 in postglucose administration and, consequently, significantly increased both the phosphorylation fraction (k3/(k2 + k3)) and the influx constant (K1k3/(k2 + k3)). No significant differences in the liver-to-plasma transport rate constant, k2, dephosphorylation constant, k4, or distribution volume of FDG (K1/(k2 + k3)) were observed. CONCLUSION: Dynamic FDG-PET studies can be used to evaluate kinetics of liver glucose metabolism. The results indicate that dietary conditions have a significant effect on hepatic FDG kinetics. Because of the higher net FDG uptake by normal liver after glucose loading, fasting conditions are preferred for FDG liver tumor studies to increase the tumor-to-background contrast.

Administration, Oral↗

PubMed1993

Assessment of the effects of dobutamine on myocardial blood flow and oxidative metabolism in normal human subjects using nitrogen-13 ammonia and carbon-11 acetate.

The dual purposes of this study with positron emission tomography were to measure the effects of dobutamine on myocardial blood flow and oxidative metabolism, and to compare carbon-11 (C-11) acetate versus nitrogen-13 (N-13) ammonia in quantitating flow in normal subjects. Flow was quantitated with N-13 ammonia at rest and at peak dobutamine infusion (40 micrograms/kg/min) in 21 subjects. In 11 subjects, oxidative metabolism was also estimated at rest and peak dobutamine infusion using the clearance rate of C-11 acetate, k mono (min-1). A 2-compartment kinetic model was applied to the early phase of the C-11 acetate data to estimate flow. The rest and peak dobutamine rate-pressure products were 7,318 +/- 1,102 and 19,937 +/- 3,964 beats/min/mm Hg, respectively, and correlated well (r = 0.77) with rest and peak dobutamine flows of 0.77 +/- 0.14 and 2.25 ml/min/g determined using N-13 ammonia as a flow tracer. Rest and dobutamine flows estimated with C-11 acetate were highly correlated with those determined with N-13 ammonia (r = 0.92). k mono increased from 0.05 +/- 0.01 to 0.18 +/- 0.02 min-1, and correlated highly with the increase in flows (r = 0.91) and rate-pressure products (r = 0.94). Thus, the increase in cardiac demand associated with dobutamine is highly correlated with an increase in supply and oxidative metabolism. C-11 acetate is a unique tracer that can be used to image both flow and metabolism simultaneously.

Adult↗

PubMed1993

Metabolism in non-ischemic myocardium during coronary artery occlusion and reperfusion.

Blood flow and metabolism in non-ischemic myocardium were studied at baseline and during occlusion and reperfusion of the left anterior descending coronary artery in closed chest dogs using positron emission tomography. Myocardial blood flow (MBF) and oxygen consumption (MVO2) in non-ischemic tissue were each increased by 28% relative to the rate pressure product during occlusion, consistent with increased work to compensate for the dyskinetic segment. MVO2 in non-ischemic sectors remained elevated relative to the rate pressure product early (1-2 h) post-reperfusion, 21% above baseline, but subsequently normalized. When sectors with normal blood flow during occlusion were divided into sectors adjacent to and remote from the risk zone, MBF in the 2 sector groups was similar at all times, but metabolic differences were found. MVO2 was depressed by 15% in adjacent relative to remote sectors 1 day post-reperfusion, with a concomitant 62% increase in glucose metabolic rate; relative increases in glucose metabolism were found only when glucose metabolism was low in remote myocardium, suggesting a decreased suppressibility of glucose metabolism in adjacent myocardium. The kinetics of (1-11C] palmitate were also altered in adjacent sectors, consistent with a small increase in esterification relative to oxidation of long chain fatty acids. Thus, sectors adjacent to ischemic segments show metabolic changes similar to those seen in reversibly injured post-ischemic tissue, despite normal blood flow during occlusion.

Animals↗

PubMed1993

Factors affecting myocardial 2-[F-18]fluoro-2-deoxy-D-glucose uptake in positron emission tomography studies of normal humans.

The goal of this study was to identify the anatomic and physiologic factors affecting left ventricular myocardial 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) uptake and myocardial glucose utilization rates (MRGlc) in normal humans. Eighteen healthy male volunteers were studied in the fasting state (4-19 h) and 16 after oral glucose loading (100 g dextrose) with positron emission tomography (PET) and FDG. Substrate and hormone concentrations were measured in each study. The kinetics of myocardial FDG uptake were evaluated using both a three-compartment model and Patlak graphical analysis. Systolic blood pressures and rate pressure products were similar in the fasting and postglucose states. MRGlc averaged 0.24 +/- 0.17 mumol/min/g in fasting subjects and rose to 0.69 +/- 0.11 mumol/min/g after glucose loading. Phosphorylation rate constant, k3, and MRGlc were linearly related (P < 0.001). Increases in MRGlc following glucose loading were correlated with plasma glucose, insulin and free fatty acid concentrations, ratios of insulin to glucagon levels, and influx rate constants of FDG. Glucose loading improved the diagnostic image quality due to more rapid clearance of tracer from blood and higher myocardial FDG uptake. When MRGlc, glucose and insulin concentrations, and insulin to glucagon ratios exceeded 0.2 mumol/min/g, 100 mg/dl, 19 microU/ml, and 0.2 microU/pg, respectively, myocardial uptake of FDG was always adequate for diagnostic use. FDG image quality and MRGlc were similar after relatively short (6 +/- 2 h) and overnight (16 +/- 2 h) fasting. Significant (P < 0.05) regional heterogeneity of myocardial FDG uptake and MRGlc was observed in both the fasting and the postglucose studies. MRGlc and FDG uptake values in the posterolateral wall were higher than those in the anterior wall and septum. Thus, both 6-h and overnight fasts resulted in similarly low myocardial glucose utilization rates. While MRGlc and myocardial FDG uptake depended on plasma glucose, free fatty acid, and insulin concentrations, the results also suggest an additional dependency on plasma glucagon levels. Regional heterogeneities in myocardial FDG uptake and MRGlc are evident and independent of the subjects' dietary state. These regional heterogeneities need to be considered in studies of patients with cardiac disease.

Adult↗

PubMed1993

Blood flow-dependent uptake of indium-111 monoclonal antimyosin antibody in canine acute myocardial infarction.

OBJECTIVES: The relation of myocardial blood flow and indium-111 (111In) antimyosin antibody uptake was studied by inducing myocardial infarction in 18 dogs, 8 with closed chest left anterior descending artery balloon occlusion for 3 h followed by reperfusion (group A) and 10 dogs with open chest left anterior descending artery ligation (without reperfusion, group B). BACKGROUND: The relation of antimyosin uptake to myocardial injury has been documented. However, its relation to tracer delivery by myocardial blood flow has not been studied and has been assumed to be independent. METHODS: Indium-111 antimyosin antibody, 2 mCi, was injected 20 min after reperfusion and 3 h after coronary artery ligation in groups A and B, respectively. Regional blood flows were determined by radiolabeled microspheres during occlusion and 24 h later in both groups. On day 2, dogs were killed after risk zone delineation with gentian violet. The heart was excised and stained with triphenyltetrazolium chloride solution and graded for increasing severity of tissue injury based on extent of staining. Microsphere activity and 111In antimyosin activity were measured in control tissue (grade 1), noninfarct tissue at risk (grade 2), mixed tissue (grade 3), infarct tissue (grade 4) and hemorrhagic infarct tissue (grade 5, present only in group A dogs). Count activity was normalized to that of the mean value in control tissue (grade 1) and expressed as a ratio of activity. RESULTS: Indium-111 antimyosin activity was high in triphenyltetrazolium chloride grade 4 tissue in both groups but was attenuated in grade 4 tissue in group B dogs (10.6 +/- 5.1 vs. 5.0 +/- 4.5; p < 0.05 group A vs. group B), which had lower blood flow on day 2 (0.51 +/- 0.36 vs. 0.23 vs. 0.22; p < 0.01). Normalizing 111In antimyosin activity for blood flow on day 2 resulted in equivalent 111In antimyosin uptake for infarct tissue (32.6 +/- 21.6 vs. 36.6 +/- 29.8 for group A vs. group B; p = NS). CONCLUSIONS: Thus, 111In antimyosin uptake is a specific marker of necrotic tissue with a high signal ratio in reperfused tissue. However, its uptake is dependent on residual blood flow in the infarct territory. Indium-111 antimyosin could potentially serve as a suitable tracer for infarct sizing if myocardial blood flow in the same region were factored simultaneously.

Animals↗

PubMed1993

Use of nonionic or low osmolar contrast agents in cardiovascular procedures. American College of Cardiology Cardiovascular Imaging Committee.

Low osmolar contrast agents produce less adverse electrophysiologic and hemodynamic alterations during cardiac catheterization. The nonionic agents probably reduce the risk of provoking myocardial ischemia during coronary arteriography or ventriculography. Patients also report less subjective sensation of discomfort during administration of low osmolar agents for cardiovascular procedures. However, nonionic agents have not been proved to reduce the incidence of several serious complications of cardiac catheterization, including acute renal failure and anaphylactoid reaction. Although evidence is inconclusive, there may be an increased risk of thromboembolic complications during cardiac catheterization when certain low osmolar nonionic agents are administered. Nonionic contrast agents have not been definitely proved to reduce the risk of death after cardiac catheterization.

Cardiac Catheterization↗

PubMed1993

Quantification and parametric imaging of renal cortical blood flow in vivo based on Patlak graphical analysis.

Patlak graphical analysis was applied to quantify renal cortical blood flow with N-13 ammonia and dynamic positron emission tomography. Measurements were made in a swine model of kidney transplantation with a wide range of normal and abnormal renal blood flows (N = 57 studies) and in 20 healthy human volunteers (N = 45 studies). Estimates of renal cortical blood flow by the Patlak method were compared to those from a two-compartment model for N-13 ammonia. In addition, estimates of renal cortical blood flow by the N-13 ammonia PET approach were compared in 10 normal human volunteers to estimates by the metabolically inert, freely diffusible O-15 water and a one-compartment model. Patlak graphical analysis estimates of renal cortical blood flow correlated linearly with the standard two-compartment model in pigs (y = -0.05 + 1.01x, r = 0.99) and in humans (y = 0.57 + 0.88x, r = 0.93). Estimates of renal cortical blood flow by O-15 water in human volunteers were also linearly correlated with those by N-13 ammonia and the Patlak graphical analysis (y = 0.71 + 0.84x, r = 0.86). Renal cortical blood flow estimates were highly reproducible both with N-13 ammonia and O-15 water measurements in humans. It is concluded that the Patlak graphical analysis with N-13 ammonia dynamic positron emission tomograpic imaging renders accurate and reproducible estimates of renal cortical blood flow. Moreover, the graphical analysis approach is 1,000 times faster than the standard model fitting approach and suitable for generating parametric images of renal blood flow in the clinical setting.

Adolescent↗

PubMed1993

Consideration of measurements of myocardial blood flow with positron-emission tomography.

The available data suggest that the different approaches permit the noninvasive quantification of regional myocardial blood flow in humans with comparable degrees of accuracy. Much of this accuracy depends on how carefully such measurements are performed and on the attention paid to detail when quantitative information is derived from the serially acquired PET images. Although absolute values for estimated flow may differ among laboratories and among techniques, consistency in analysis of data is of utmost importance. Yet, the choice of a specific measurement approach is often determined by practical considerations specific to a given laboratory. Factors are availability of a given tracer, ease of synthesis, proximity of the cyclotron to the scanner, instrument performance, as well as the type of studies performed in the same laboratory in other organs and associated needs for a given tracer. On the other hand, it is clear that the technology for quantifying blood flow in human myocardium has reached a point at which it can be applied routinely and reliably for the study of coronary circulatory physiology and pathophysiology of the human heart. What remains less certain at present is to what extent such quantitative approaches will augment the accuracy with which coronary artery disease can be diagnosed and characterized, and the effects of therapy monitored. However, it is clear that these novel approaches are likely to offer new insights into the pathophysiology of other than apparent coronary artery disease, as exemplified by the initial observations in patients with syndrome-X or hypertrophic cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Regional myocardial blood flow and glucose utilization in symptomatic patients with hypertrophic cardiomyopathy.

BACKGROUND: Previous studies suggested the presence of myocardial ischemia in symptomatic patients with hypertrophic cardiomyopathy. Positron emission tomography, a technique that can identify metabolic consequences of ischemia in coronary artery disease, permits the noninvasive measurements of regional myocardial blood flow and glucose metabolism. This new quantitative imaging approach should therefore be suitable for detecting a possible enhancement of glucose utilization in myocardium of patients with hypertrophic cardiomyopathy and thus may help to elucidate the pathomechanism of ischemia in this disease. METHODS AND RESULTS: In 13 symptomatic patients with hypertrophic cardiomyopathy, myocardial blood flow and glucose utilization were measured with intravenous N-13-ammonia and F-18 deoxyglucose at rest and, in four patients, again during supine bicycle exercise. At rest, blood flow was significantly lower in hypertrophied than in normal myocardium (0.78 +/- 0.19 versus 0.99 +/- 0.13 mL.min-1.g-1, p < 0.025), whereas rates of glucose utilization were similar (0.88 +/- 0.31 versus 0.87 +/- 0.35 mumol.min-1.g-1). With exercise, blood flow and glucose utilization failed to increase in hypertrophic and normal segments but became more heterogeneously distributed throughout the left ventricular myocardium. Blood flow-metabolism mismatches indicative of myocardial ischemia were noted in three patients at rest and in three of the four patients during exercise and were due to reduced flow in the presence of maintained glucose uptake. The discordance between flow and glucose metabolism in hypertrophied myocardium was significantly more prominent in younger than in older patients. CONCLUSIONS: Normal or even elevated rates of glucose utilization and the presence of diminished blood flow in hypertrophied relative to normal myocardium suggest the presence of myocardial ischemia in symptomatic hypertrophic cardiomyopathy. The age dependence of blood flow metabolism disparity suggests differences in the underlying pathophysiology or severity of disease.

Adult↗

PubMed1993

Influence of age and hemodynamics on myocardial blood flow and flow reserve.

BACKGROUND: Aging is associated with changes of the systolic blood pressure that may increase cardiac work and myocardial blood flow at rest and reduce the myocardial flow reserve. This might be misinterpreted as age-related impairment of the coronary vasodilator capacity. METHODS AND RESULTS: Myocardial blood flow was quantified at rest and after administration of intravenous dipyridamole in 40 healthy volunteers (12 women and 28 men) with 13N-ammonia and positron emission tomography. Eighteen of the normal subjects were less than and 22 were older than 50 years (31 +/- 9 versus 64 +/- 9 years). The resting rate-pressure product was lower in the younger than in the older subjects (6895 +/- 1070 versus 8634 +/- 1890; P < 0.01). Myocardial blood flow at rest averaged 0.76 +/- 0.17 mL.min-1.g-1 in the younger volunteers and 0.92 +/- 0.25 mL.min-1.g-1 in the older volunteers (P < 0.05). Hyperemic blood flows did not differ between younger and older subjects (3.0 +/- 0.8 versus 2.7 +/- 0.6 mL.min-1.g-1; P = NS); however, minimal coronary resistance was higher in the older subjects. Corrected for indexes of coronary driving pressure, hyperemic flow was lower in older than in younger normal subjects. The higher resting blood flows combined with similar hyperemic flows resulted in a lower myocardial flow reserve in the older than in the younger normal subjects (4.1 +/- 0.9 versus 3.0 +/- 0.70; P < 0.0001). The flow reserve was more closely correlated with resting than with hyperemic blood flows. CONCLUSIONS: Aging does not alter significantly dipyridamole-induced hyperemic flows; although coronary vascular resistance after dipyridamole was somewhat increased in older subjects. The gradual decline of the myocardial blood flow reserve correlates with an age-related increase of baseline myocardial work and blood flow. These findings suggest that the reduced flow reserve with age is primarily due to increased cardiac work and blood flow at rest rather than to an abnormal vasodilator capacity.

Adult↗

PubMed1993

A refined method for quantification of myocardial oxygen consumption rate using mean transit time with carbon-11-acetate and dynamic PET.

The utility of the mean transit time equation was investigated for estimation of the myocardial clearance rate constant of 11C-acetate, which is proportional to myocardial oxygen consumption rates. The mean transit time approach was also employed to generate parametric images of the clearance rate constant of 11C-acetate with dynamic PET imaging in 20 normal human studies. Input function delays and cutoff errors due to the truncation of the myocardial tissue time-activity curve at a finite time were corrected. The clearance rate constants estimated by mean transit time correlated well with the estimates by conventional monoexponential fitting (15 min (truncation time): Y = 0.01 + 0.94X, correlated coefficient (r) = 0.99; 16 min: Y = 0.03 + 0.94X, r = 0.98; 20 min: Y = 0.03 + 0.84X, r = 0.99). The clearance rate constants estimated by the mean transit time approach also correlated well (r = 0.94) with the measured rate-pressure products. The quality and noise level of parametric images of the clearance rate constants generated by mean transit time are improved over those generated by monoexponential fitting. Additional advantages of the mean transit time approach compared to the standard monoexponential fitting method for estimating myocardial clearance rate constant of 11C-acetate include ease of input function delay correction, less sensitivity to the shape of the input function and elimination of subjective data selection of the linear portion of the clearance data on a semilog plot. Thus, this approach is expected to facilitate objective quantitative analysis of indices of myocardial oxygen consumption.

Acetates↗

PubMed1993

A simplified method for quantification of myocardial blood flow using nitrogen-13-ammonia and dynamic PET.

The utility of Patlak graphical analysis was investigated for quantification of regional myocardial blood flow (MBF) and for generating parametric images of MBF with 13N-ammonia and dynamic PET imaging in dogs and humans. MBF was estimated by a two-compartment model fit of the initial 2 min of the kinetic data and by Patlak graphical analysis of the initial 2, 3, or 4 min of data. In 11 dog studies, MBF by compartmental model fitting linearly correlated with MBF by microspheres (correlation coefficient (r) = 0.99, slope = 0.92) and by Patlak graphical analysis (r = 0.99, slope = 0.90). In 10 normal human studies, MBF obtained by the Patlak graphical analysis agreed well with MBF obtained by the compartmental model fitting (r = 0.96, slope = 1.04). Good agreement of the MBF estimates was also observed in 10 coronary artery disease patient studies (r = 0.96). Patlak graphical analysis permitted generation of parametric images of MBF. The parametric images of MBF, in units of ml/min/g, are of good image quality and have relatively low noise levels. We conclude that regional MBF can be noninvasively and conveniently measured with dynamic 13N-ammonia PET using either a two-compartment model or Patlak graphical analysis. MBF parametric images generated with the Patlak graphical analysis both map the distribution and quantitate the magnitude of myocardial perfusion abnormalities.

Adult↗