The promise of technetium-99m-based perfusion imaging agents.
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Coronary Circulation↗
Biomedical subjects
E H Botvinick
Publications and source records attributed to E H Botvinick.
"Hot spot" imaging agents for acute myocardial infarction.
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Humans↗
The scintigraphic characteristics of ventricular pre-excitation through Mahaim fibers with the use of phase analysis.
The phase image pattern of blood pool scintigrams was blindly assessed in 11 patients exhibiting conduction through Mahaim pathways, including 6 nodoventricular and 5 fasciculoventricular. These patterns were compared with the phase image findings in normal subjects, patients with left and right bundle branch block in the absence of pre-excitation and patients with pre-excitation through atrioventricular (AV) connections. In all patients with a Mahaim pathway, the site of earliest phase angle was septal or paraseptal. Phase progression was asymmetric and the pre-excited ventricle demonstrated the earliest mean ventricular phase angle in 10 of 11 patients. This pattern, and the associated ventricular phase difference, appeared to vary from that in normal subjects and in those with a septal AV connection, in whom phase progression is generally symmetric. Scintigraphic phase analysis provided localizing information and presented patterns consistent with Mahaim pathways. Although not able to differentiate among Mahaim pathway subtypes, these phase patterns differed from those in normal subjects, those with right and left lateral free wall pathways and most patients with a septal AV pathway. However, the phase pattern of patients with a Mahaim pathway may not differ from that of patients with a septal AV connection displaying an asymmetric pattern of phase progression, or those with left and right bundle branch block in the absence of pre-excitation. Objective, yet imperfect phase measurements supported these differences. Such image findings may complement the often complex electrophysiologic evaluation of patients presenting with pre-excitation.
Adult↗
ECG left anterior fascicular block reveals diverse patterns on scintigraphic phase analysis.
Left anterior fascicular block (LAFB) remains an uncertain diagnosis by scalar ECG, particularly with coexisting inferior infarction. To assess the use of phase analysis in LAFB, left ventricular phase and amplitude maps were evaluated in the 70-degree left anterior oblique projection in eight control patients and 13 patients with LAFB who met the ECG criteria of Warner et al. The left ventricular region was divided into anterior (A) and inferior (I) segments. Contraction patterns were assessed by examination of the sequence of phase angles (phi), relative contraction time of the anterior versus inferior segments was assessed from the difference between segment mean phase angles, delta phi A-I, determined from the phase histogram, and duration of contraction was assessed by histogram width. Relative stroke volume was assessed on the amplitude image. Eight control subjects had normal amplitude, contraction of the anterior before inferior segment, narrow histogram width, and a normal ECG. Among the 13 patients with ECG LAFB, seven were concordant, with phase analysis demonstrating anterior contraction delay. Two of seven patients had narrow histograms and normal amplitude, which were compatible with isolated anterior conduction delay, and five of seven patients had broad histograms and reduced anterior amplitude, compatible with anterior infarction. Phase analysis was discordant with ECG LAFB diagnosis in six patients. All showed contraction of anterior segments before inferior segments as in normal subjects. Four had broad histograms and reduced inferior amplitude, compatible with prior inferior infarction without LAFB, and two had normal phase and amplitude maps. Phase patterns appear characteristic of LAFB with or without associated infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Bundle-Branch Block↗
Value of color Doppler estimation of regurgitant volume in patients with chronic aortic insufficiency.
We studied 16 patients with chronic aortic insufficiency to compare a method for measuring regurgitant volume with color Doppler flow mapping to stroke count ratio determined by radionuclide ventriculography and to ventricular volumes assessed by two-dimensional echocardiography. A real-time color flow map of the left ventricular was obtained from an apical two- and five-chamber view and the maximal mosaic pattern of diastolic turbulent flow was planimetered as a reflection of the maximal regurgitant volume using biplane Simpson's rule. The maximal Doppler regurgitant volume evaluated by color Doppler flow mapping correlated with the stroke count ratio measured by scintigraphy (r = 0.86, SEE = 11 cc). There were significant relationships between maximal regurgitant volume measured by color Doppler and echocardiographic left ventricular end-diastolic volume (r = 0.88), left ventricular end-systolic volume (r = 0.77), and left ventricular mass (r = 0.71). Patients with larger regurgitant volumes tended to have a larger left ventricular end-diastolic volume-to-mass ratio (r = 0.56). Thus maximal aortic regurgitant volume can be estimated noninvasively with color Doppler flow mapping. The measurement appears to relate to left ventricular morphologic changes occurring in this condition and it may prove to be useful in assessing patients with chronic aortic insufficiency and in determining their long-term management.
Adult↗
Noninvasive assessment of cardiomyopathy in normotensive diabetic patients between 20 and 50 years old.
PURPOSE: To further the understanding of diabetic heart disease, we tested the hypothesis that an asymptomatic group of normotensive diabetic patients between 20 and 50 years old had a restrictive cardiomyopathy independent of clinically significant coronary artery disease. PATIENTS AND METHODS: Quantitative two-dimensional echocardiography and stress myocardial perfusion scintigraphy were performed to detect and characterize the cardiac abnormalities in this study group comprising 88 patients with rigorously classified diabetes and 65 volunteer control subjects. RESULTS: Diabetic patients were shown to have a mildly reduced left ventricular end-diastolic volume index: 50.1 +/- 8.2 and 52.1 +/- 14.7 mL/m2 for patients with type I and type II diabetes, respectively, versus 58.9 +/- 11.7 mL/m2 for control subjects. The left ventricular diastolic filling was also impaired in diabetic patients as reflected by a lower atrial emptying index: 0.73 +/- 0.24 and 0.76 +/- 0.3 for type I and type II diabetics, respectively, compared with 1.14 +/- 0.24 for control subjects. Exercise tolerance was normal in subjects with type I diabetes and slightly reduced in subjects with type II diabetes. Only one patient developed regional ischemia on thallium exercise testing. CONCLUSION: Using a comprehensive, noninvasive approach, we have shown that asymptomatic normotensive patients with type I or type II diabetes who were between 20 and 50 years old had a restrictive cardiomyopathy characterized by mildly reduced left ventricular end-diastolic volume and altered left ventricular compliance independent of critical coronary artery disease.
Adult↗
Scintigraphic assessment of regional cardiac adrenergic innervation.
To assess the feasibility of noninvasively imaging the regional distribution of myocardial sympathetic innervation, we evaluated the distribution of sympathetic nerve endings, using 123I metaiodobenzylguanidine (MIBG), and compared this with the distribution of myocardial perfusion, using 201Tl. Twenty dogs were studied: 11 after regional denervation, and nine as controls. Regional denervation was done by left stellate ganglion removal, right stellate ganglion removal, and application of phenol to the epicardial surface. Computer-processed functional maps displayed the relative distribution of MIBG and thallium in multiple projections in vivo and excised heart slices in all animals. In six animals, dual isotope emission computed tomograms were acquired in vivo. Tissue samples taken from innervated and denervated regions of the MIBG images were analyzed for norepinephrine content to validate image findings. Normal controls showed homogeneous and parallel distributions of MIBG and thallium in the major left ventricular mass. In the left stellectomized hearts, MIBG was reduced relative to thallium in the posterior left ventricle; whereas in right stellectomized hearts, reduced MIBG was in the anterior left ventricle. Phenol-painted hearts showed a broad area of decreased MIBG extending beyond the area of phenol application. In both stellectomized and phenol-painted hearts, thallium distribution remained homogeneous and normal. Norepinephrine content was greater in regions showing normal MIBG (550 +/- 223 ng/g) compared with regions showing reduced MIBG (39 +/- 44 ng/g) (p less than 0.001), confirming regional denervation. Combined MIBG-thallium functional maps display the regional distribution of sympathetic innervation. This new ability to noninvasively map the distribution of sympathetic nerves with simultaneous comparison to regional perfusion may provide important new insights into mechanisms, whereby an imbalance in sympathetic activity may relate to clinical disorders.
3-Iodobenzylguanidine↗
Response of myocardial metabolites to graded regional ischemia: 31P NMR spectroscopy of porcine myocardium in vivo.
The changes in myocardial high energy phosphates and pH during regional ischemia, and their potential role in mediating functional abnormalities, is unclear. To determine the degree of regional blood flow reduction required to induce changes in high energy phosphates and pH, and to correlate these metabolic changes with alterations in blood flow, 31P nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional blood flow and phosphate compounds were made during various steady-state degrees of regional ischemia in which subendocardial blood flow was reduced by as much as 80%. ATP did not fall over the total range of graded ischemia, while phosphocreatine (PCr), inorganic phosphate (Pi), and pH all changed progressively after blood flow was reduced below 50% of normal. The ratio of PCr/Pi (a measure of the energy reserve of the myocardium) was strongly correlated to subendocardial blood flow (r = 0.94) and declined by 25% when blood flow was reduced by only 21% below normal. These findings indicate that PCr/Pi is a sensitive marker of ischemia and support the hypothesis that the in vivo energy status of the myocardium is closely coupled to myocardial blood flow.
Adenosine Triphosphate↗
Blood pool scintigraphy.
Scintigraphic techniques offer a variety of computer aided analytic methods for the assessment of ventricular size and function. They are objective, quantitative, and reproducible, and contribute to the clinical evaluation of all forms of cardiac disease. In some cases complementary to other methods, the scintigraphic assessment of ventricular function is often unique in the valuable clinical data which they supply.
Cardiac Output↗
In vivo alterations of high-energy phosphates and intracellular pH during reversible ischemia in pigs: a 31P magnetic resonance spectroscopy study.
Phosphorus-31 magnetic resonance spectroscopy was used to study the relationship between metabolic and functional alterations during acute regional ischemia in vivo. Phosphocreatine, adenosine triphosphate (ATP), inorganic phosphate, and intracellular pH (pHi) were monitored in 11 pigs at 2-minute intervals during 4 and 20 minutes of acute left anterior descending coronary artery occlusion followed by 20 minutes of reperfusion. In a parallel series of experiments, segment shortening was continuously monitored by sonomicrometry during the early ischemic period. Segment shortening decreased precipitously after coronary occlusion, and systolic expansion was noted within 30 seconds. Phosphocreatine levels decreased rapidly and reached a minimum value of 44 +/- 13% (mean +/- SE) of the control value by 20 minutes of ischemia. Ischemia-induced reduction of ATP was small and not statistically significant. Inorganic phosphate increased rapidly to a peak level of 158 +/- 9% of the control value by 4 minutes of ischemia. Intracellular pH decreased 0.76 +/- 0.04 units during the initial 10 minutes of ischemia and subsequently stabilized. After reperfusion, phosphocreatine, inorganic phosphate, and pHi recovery occurred within 4 minutes and was similar in the 4- and 20- minute ischemia groups. These results indicate that the changes in high-energy phosphates and pHi observed during both 4 and 20 minutes of coronary occlusion are rapidly reversible. The temporal course of metabolic and functional alterations during early ischemia suggests that if these are causally related the decline in contractility is mediated by an increase in inorganic phosphate, a decrease in pHi, or both rather than by loss of ATP.
Adenosine Triphosphate↗
Segmental evaluation of left ventricular wall motion after myocardial infarction: magnetic resonance imaging versus echocardiography.
To assess relative capabilities of magnetic resonance (MR) imaging and two-dimensional echocardiography (2DE) for evaluating regional contractile dysfunction in the left ventricle after a myocardial infarction, results from 22 concurrent MR (orthogonal-transaxial, ECG-gated, multiphasic, single-spin echo) and 2DE examinations were compared. By means of the same 11-segment LV description, MR and 2DE examinations were independently scored segment by segment for residual wall motion (point scores: 2 = normal, 1 = hypokinesia, 0 = akinesia, and -1 = dyskinesia). Significant correlation between MR and 2DE scoring was found throughout most of the left anterior descending (LAD) distribution, but right coronary artery (RCA) distribution (i.e., middle-posterior segment not well seen) could not be fully evaluated by MR imaging. When cumulative scores for the 10 segments mutually evaluated were used to derive measures of global residual LV function (i.e., score quotient [SQ] = accumulated points divided by 20 total possible points), MR SQ correlated well overall with both 2DE SQ (r = 0.82; p less than 0.05) and ejection fraction (EF) from ventriculography (r = 0.86, p less than 0.05 vs r = 0.88, p less than 0.05 for 2DE SQ compared with EF). MR evaluation of segmental wall motion was relatively stronger in the LAD distribution (MR SQ compared with 2DE SQ: r = 0.86, p less than 0.05; MR SQ compared with EF: r = 0.96, p less than 0.05) than in the RCA distribution (r = 0.06, p greater than or equal to 0.05 and r = 0.62, p greater than or equal to 0.05, respectively). For 2DE, regional variations were not as evident (2DE SQ compared with EF: r = 0.90, p less than 0.05 for LAD and r = 0.81, p less than 0.05 for RCA). For segmental evaluation of wall motion after myocardial infarction, MR imaging (transaxial, multiphasic) appears to be comparable to 2DE overall but superior in LAD distribution and inferior in RCA distribution.
Adult↗
Estimation of the functional and anatomic extent of myocardial infarction using magnetic resonance imaging.
This study assesses magnetic resonance (MR) imaging for the evaluation of both the functional and anatomic extent of damage to the left ventricle (LV) from myocardial infarction (MI). This was accomplished by blinded region-of-interest analysis of 36 MR examinations (orthogonal-transaxial, electrocardiographically-gated, multiphasic, single spin-echo) for determination of ejection fraction (EF) and relative MI volume (i.e., percent of total LV myocardial volume). Comparison of the results was then made with a measure of global residual LV function (i.e., score quotient or SQ) derived from segmental scoring of LV wall motion on a two-dimensional echocardiogram (Echo) and with an EF value from a left ventriculogram (LVG), both performed relatively concurrently with MR. Significant (p less than 0.01) overall correlations were noted between MR-EF and both Echo-SQ (r = 0.56) and LVG-EF (r = 0.78), and these relationships were relatively stronger when MI was located in the right coronary artery (RCA) than when it was found in the left anterior descending (LAD) distribution (e.g., MR-EF compared with LVG-EF: r = 0.87, p less than 0.05 for RCA; and r = 0.48, p = NS for LAD). The best expression of relative MI volume appeared to be based upon absolute volume of regionally-thinned LV wall multiplied by a correction factor for its residual contractility and then the addition of a volume correcting for the amount of regional wall thinning by necrosis (i.e., "total-Fxn" MI volume).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Nuclear magnetic resonance imaging-guided phosphorus-31 spectroscopy of the human heart.
Phosphorus-31 nuclear magnetic resonance spectroscopy can determine the status of high energy phosphates in vivo. However, its application to human cardiac studies requires precise spatial localization without significant contamination from other tissues. Using image-selected in-vivo spectroscopy (ISIS), a technique that allows three-dimensional localization of the volume of interest, 12 subjects were studied to determine the feasibility and reproducibility of phosphorus-31 spectroscopy of the human heart. Nuclear magnetic resonance imaging was performed using a commercial 1.5 tesla system to define the volume of interest. Phosphorus-31 spectra were obtained from the septum and anteroapical region of the left ventricle in 10 studies. Relative peak heights and areas were determined for high energy phosphates. The mean phosphocreatine to adenosine triphosphate ratio was 1.33 +/- 0.19 by height analysis and 1.23 +/- 0.27 by area analysis. Duplicate measurements in four subjects showed a reproducibility of less than or equal to 10% in three of the subjects. All spectra showed significant signal contribution from the 2,3 diphosphoglycerate in chamber red cells without evidence of skeletal muscle contamination. These results demonstrate the feasibility of image-guided phosphorus-31 spectroscopy for human cardiac studies and indicate the potential of this technique to study metabolic disturbances in human myocardial disease.
Adenosine Triphosphate↗
Substrate regulation of the nucleotide pool during regional ischaemia and reperfusion in an isolated rat heart preparation: a phosphorus-31 magnetic resonance spectroscopy analysis.
Isolated rat heart preparations were studied to characterise the alterations in high energy phosphates that occur during reversible regional ischaemia and to determine whether pyruvate, as the sole exogenous energy substrate, would attenuate the ischaemia induced depletion of the nucleotide pool when compared with glucose. Using phosphorus-31 magnetic resonance spectroscopy baseline concentrations of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH were compared with values during 30 min of left coronary artery occlusion followed by 30 min of reperfusion. These variables were related to changes in developed pressure, coronary flow, and oxygen consumption. In addition, the total nucleotide pool was evaluated by biochemical analysis of myocardial tissue extracts and coronary effluent. The ischaemic region was characterised by a dye staining technique and cross sectional echocardiographic measurements of regional myocardial wall thinning. In both glucose and pyruvate perfused groups, coronary flow and oxygen consumption decreased to 50-60% of control within 1 min of ischaemia and returned to baseline values with reflow. Developed pressure decreased to 50(9) and 74(8)% (mean(SEM] of control after 30 min of ischaemia in glucose and pyruvate perfused groups respectively. Reperfusion resulted in complete recovery of developed pressure in hearts perfused with pyruvate but not in the glucose group. Glucose perfused hearts had a greater decrease in intracellular pH during ischaemia (7.07(0.01) to 6.36(0.1] than pyruvate perfused hearts (7.06(0.02) to 6.83(0.04]. Reperfusion resulted in a rapid return to baseline intracellular pH in both groups. During ischaemia, adenosine triphosphate values decreased to a greater degree in glucose than in pyruvate perfused hearts (57(4) and 79(5)% of baseline respectively). Thirty minutes of reperfusion did not significantly improve adenosine triphosphate concentrations in either group. Phosphocreatine concentrations decreased to 52(7) and 75(6)% of baseline in glucose and pyruvate perfused groups respectively after the ischaemic period. Reperfusion resulted in normalisation of phosphocreatine values in the pyruvate but not in the glucose perfused group. Biochemical analysis of myocardial tissue extracts confirmed the spectroscopy data and showed that pyruvate inhibits the efflux of adenine nucleotide derivatives. Tissue concentrations of adenosine monophosphate were three times greater and adenosine 50% less after 30 min of ischaemia in the pyruvate perfused group.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Breast attenuation artifacts in Tl-201 scintigraphy.
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Breast↗
Improvement in myocardial performance without a decrease in high-energy phosphate metabolites after isoproterenol in Syrian cardiomyopathic hamsters.
To determine the effect of isoproterenol on cardiac energetics and function in an animal preparation of cardiomyopathy, we studied Langendorff perfused hearts from Syrian cardiomyopathic hamsters. High-energy phosphate metabolites (phosphocreatine [PCr], ATP, inorganic phosphate [Pi]) and intracellular pH (pHi) were measured by 31P nuclear magnetic resonance spectroscopy and correlated with left ventricular developed pressure, coronary flow, and O2 consumption before and during a 10(-6)M infusion of isoproterenol. Total intracellular calcium was also determined by atomic absorption spectroscopy with the use of potassium ethylenediamine tetra-acetate cobaltate as a marker for extracellular space. In cardiomyopathic hamsters, isoproterenol infusion increased mean developed pressure by 300% (p less than .005 compared with control; n = 5), O2 consumption eightfold (p less than .0005), and PCr by 40% (p less than .05). PCr/Pi ratio, which is analogous to phosphorylation potential, improved 100% (p = .05). In normal hamsters, isoproterenol infusion resulted in an 83% increase in developed pressure (p less than .001) and a 25% increase in O2 consumption (NS). However, mean PCr and PCr/Pi decreased by 30% and 50%, respectively (p less than .05 for both), during isoproterenol infusion. pHi decreased in normal animals (p less than .01), but tended to improve in diseased animals (NS) during isoproterenol infusion. Freeze-clamp measurements of phosphate metabolites correlated well with the nuclear magnetic resonance data. Intracellular calcium increased from 0.0102 +/- 0.002 to 0.144 +/- 0.030 mumol/ml heart water in normal hamsters during isoproterenol infusion. Cardiomyopathic hamsters had a markedly elevated baseline calcium content of 60.82 +/- 5.85 mumol/ml heart water due to the presence of dystrophic calcification.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Analysis of thallium-201 "washout" from parametric color coded images.
We developed a parametric washout image which color codes regional washout, and blindly compared enhanced perfusion images in multiple projections with regional washout graphs and images in 25 patients. Washout images permitted true spatial and anatomic assessment of regions viewed en face as well as those seen in tangent, making possible the exclusion of non-coronary irregularities and permitting evaluation of washout over the apparent cavity. "Cavitary" washout was abnormal in 10 of 12 patients with apparent cavitary dilation on the post stress image, but in none without this finding. The distribution and rotation of washout abnormalities seen over the cavity when viewed en face, and the long delay between the termination of stress and post-exercise image acquisition, suggest that apparent cavitary dilation is often related to improved visibility of the 201T1 deficient blood pool due to relative ischemia of the overlying myocardial wall.
Color↗
Hemodynamic and clinical evaluation of piroximone, a new inotrope-vasodilator agent, in severe congestive heart failure.
To assess the potential utility of piroximone (MDL-19,205), an investigational inotrope-vasodilator agent, in severe heart failure, 15 patients with severe left ventricular failure refractory to conventional agents were enrolled in an acute hemodynamic study. After incremental intravenous dosing (mean total dose 1.8 +/- 0.4 mg/kg body weight), cardiac index increased (1.7 +/- 0.3 to 2.6 +/- 0.6 liters/min per m2; p less than 0.001) and left ventricular filling pressure decreased (25 +/- 7 to 19 +/- 7 mm Hg; p less than 0.001). Also decreasing significantly were right atrial pressure (13 +/- 6 to 7 +/- 5 mm Hg; p less than 0.005) and systemic vascular resistance (1,633 +/- 394 to 1,183 +/- 278 dynes.s.cm-5; p less than 0.001). Heart rate and mean arterial pressure did not change, whereas stroke work index increased significantly (13.3 +/- 4.3 to 21.6 +/- 7.3 g.m/m2; p less than 0.005). The increase in stroke work index with a concomitant decrease in left ventricular filling pressure indicates an improvement in systolic performance after treatment with piroximone. Similar responses were obtained after incremental doses of piroximone in oral solution. After oral doses of piroximone tablets, cardiac index also increased significantly (2.1 +/- 0.6 to 2.4 +/- 0.5 liters/min per m2; p less than 0.05), although this magnitude of increase was comparatively low. In a subgroup of 10 patients who underwent equilibrium gated radionuclide blood pool scintigraphy before and after intravenous piroximone, end-diastolic volume index tended to increase (106 +/- 42 to 132 +/- 60 ml/m2; p = 0.07), whereas left ventricular filling pressure decreased significantly (26 +/- 8 to 19 +/- 9 mm Hg; p less than 0.01).
Aged↗