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Biomedical subjects

C L Wolfe

Publications and source records attributed to C L Wolfe.

At least 55 records · Page 3Linked to original sources

Iodine-123 phenylpentadecanoic acid myocardial scintigraphy in patients with left ventricular hypertrophy: alterations in left ventricular distribution and utilization.

Regional alterations in myocardial substrate uptake and/or utilization have been demonstrated in rats with hypertension. To determine whether alterations in left ventricular fatty acid uptake and/or utilization are present in patients with left ventricular hypertrophy (LVH), we compared the results of rest and exercise iodine-123 phenylpentadecanoic acid (IPPA) myocardial scintigraphy in 10 patients with hypertension who had concentric LVH without evidence of coronary artery disease and in 15 normal subjects. Patients with LVH had more heterogeneous left ventricular activity of IPPA compared to normal subjects after exercise but not at rest (23 +/- 8% versus 13 +/- 5% difference in maximum segmental activity at 4 minutes after exercise; p = 0.005). Although IPPA clearance was similar in both patients with LVH and normal subjects, postexercise washout in segments showing decreased initial IPPA uptake was reduced compared to washout at rest in patients with LVH (11.7 +/- 7.5% versus 21.5 +/- 8.4% at 20 minutes after injection, n = 15; p = 0.005). Exercise thallium-201 (TI-201) scintigraphy was normal in all seven patients with LVH tested. Patients with LVH showed significantly greater heterogeneity in IPPA uptake compared to TI-201 uptake immediately after exercise (25 +/- 5% versus 16 +/- 6%; p = 0.013). We conclude that (1) compared to normal subjects, patients with LVH show heterogeneous myocardial IPPA activity after exercise but not at rest; (2) postexercise washout of IPPA was decreased in segments with reduced uptake after exercise in patients with LVH; and (3) the distribution of IPPA is more heterogeneous than that of TI-201 immediately after exercise in patients with concentric LVH. The postexercise heterogeneity in IPPA uptake and delayed washout in segments with reduced initial uptake is consistent with exercise-induced myocardial ischemia in patients with LVH.

Adult↗

A model of acute regional myocardial ischemia and reperfusion in the rat.

Studies were conducted in 76 rats to describe and validate a new closed-chest in vivo model for acute ischemia and reperfusion of the left coronary artery. Radiolabeled microsphere distribution in six rat hearts confirmed a significant reduction in arteriolar flow at the center of the ischemic zone (93% reduction of total myocardial counts compared to nonischemic region, P less than 0.01) after 7 min of occlusion. Arteriolar flow returned to control values upon reperfusion. While hemodynamic parameters in 10 rats during 7 min of occlusion and 7 min of reperfusion were monitored, end diastolic pressures increased significantly (P less than 0.01) during occlusion. Finally, the utility of this rat model was demonstrated in a study of contrast enhanced magnetic resonance imaging (N = 4). Normal myocardium could not be differentiated from acutely ischemic myocardium on noncontrast-enhanced MR images. After 5 min of myocardial ischemia and following contrast administration (albumin-Gd-DTPA), the ischemic zone appeared less enhanced than normal myocardium. Upon release of the occluder the left ventricular free wall once again yielded a homogeneous signal similar to that of the normal myocardium.

Animals↗

Acute myocardial ischemia and reperfusion: MR imaging with albumin-Gd-DTPA.

The utility of a macromolecular, intravascular contrast agent, albumin-gadolinium diethylenetriaminepentaacetic acid (DTPA), for the differentiation of acutely ischemic and reperfused myocardium on magnetic resonance (MR) images was investigated. Regional, reversible myocardial ischemia was produced in rats and confirmed. After reperfusion, flow to the compromised myocardial segment returned to baseline. Normal myocardium could not be differentiated from ischemic myocardium on nonenhanced MR images (n = 12). After 5 minutes of myocardial ischemia and after administration of albumin-Gd-DTPA, the ischemic zone involving the free wall of the left ventricle was characterized by the absence of significant enhancement. Normal myocardium appeared homogeneously enhanced (by 145%). This pattern persisted for up to 1 hour of myocardial ischemia. In six rats that underwent myocardial reperfusion after 5 minutes of ischemia, the normal and reperfused myocardium became isointense. Radiotracer studies with albumin-Gd-153-DTPA confirmed the decreased distribution of contrast agent to the ischemic myocardium, possibly due to decreased blood pool or a blocked primary delivery system in the ischemic myocardium.

Animals↗

Noninvasive evaluation of pulmonary artery pressure during exercise by saline-enhanced Doppler echocardiography in chronic pulmonary disease.

To determine the feasibility of noninvasive determination of right ventricular systolic pressure (RVSP) during a graded-exercise protocol, saline contrast-enhanced Doppler echocardiography of tricuspid insufficiency was performed in 36 patients with chronic lung disease and 12 normal controls. In the patients with chronic pulmonary disease, symptom-limited, incremental supine bicycle exercise and pulse oximetry were performed on and off high-flow oxygen. Technically adequate Doppler studies were initially obtained in 20 patients (56%) at rest and 14 (39%) on exercise; these numbers increased to 33 (92%) and 32 (89%), respectively, after enhancement with agitated saline (both p less than 0.001). In 10 patients with chronic lung disease who had simultaneous hemodynamic monitoring during exercise, the correlation between Doppler and catheter measurements of pulmonary artery systolic pressure was close (r = 0.98). Among controls, RVSP increased from 22 +/- 4 at rest (mean +/- SD) to 31 +/- 7 mm Hg at peak exercise. In patients with chronic lung disease, RVSP increased from 46 +/- 20 to 83 +/- 30 mm Hg (both p less than 0.001 vs. controls). Despite normal resting values for RVSP in 28% of study patients, nearly all showed abnormal increases in RVSP during supine bicycle exercise. Increases in RVSP during exercise were greatest in patients who showed oxyhemoglobin desaturation. The short-term administration of oxygen significantly blunted the increase in RVSP during exercise. Saline contrast-enhanced Doppler evaluation of tricuspid insufficiency seems a potentially valuable noninvasive method of determining the exercise response of RVSP in patients with chronic pulmonary disease.

Adult↗

Assessment of myocardial salvage after ischemia and reperfusion using magnetic resonance imaging and spectroscopy.

To test the hypothesis that contrast-enhanced magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) can differentiate reversible from irreversible myocardial injury, these modalities were used to study ischemia and reperfusion in a rat model. The presence of ischemia and reperfusion were confirmed with radiolabeled microspheres (n = 6). Groups of animals were subjected to either 16 (n = 17), 30 (n = 14), 60 (n = 11), or 90 (n = 14) minutes of left coronary artery (LCA) occlusion and 60 minutes reperfusion. After albumin-gadolinium (Gd)-DTPA injection, contrast-enhanced, T1-weighted, spin-echo proton images were acquired at baseline and every 16 minutes during LCA occlusion and reperfusion. In separate experiments, 31phosphorus (31P) spectra were acquired at similar time points during ischemia and reperfusion. After 16 minutes occlusion, normally perfused myocardium enhanced significantly compared with ischemic myocardium on MRI (104 +/- 7.9% vs. 61 +/- 11.0%, p less than 0.05, n = 5, mean +/- SEM, % of baseline value). MRS showed reduced phosphocreatine (PCr) and adenosine triphosphate (ATP) (58.8 +/- 2.4%, p less than or equal to 0.01; 81.4 +/- 2.4, p less than or equal to 0.01, n = 12). After 16 or 30 minutes ischemia, reflow resulted in uniform MRI signal intensity of the ischemic zone compared with normal myocardium (93.5 +/- 11.3 vs. 80.9 +/- 7.0, p = NS, n = 11, % of baseline value at 30 minutes reperfusion) and PCr recovery on MRS (94.3 +/- 4.0%, p = NS, n = 20, % baseline value at 30 minutes reflow). After 60 and 90 minutes ischemia, reflow resulted in marked enhancement of reperfused compared with normal myocardium on MRI (254.0 +/- 30.0 vs. 78.3 +/- 9.2, p less than or equal to 0.01, n = 10) and no recovery of PCr on MRS (64.1 +/- 3.0, p = NS, n = 14). Triphenyltetrazolium chloride (TTC) staining revealed transmural myocardial infarction (MI) in all hearts subjected to 60 or 90 minutes ischemia and reflow, and small nontransmural MIs in only 2/11 hearts subjected to 16 or 30 minutes ischemia and reperfusion. Thus, 1) MRI with albumin-Gd-DTPA is useful for identifying myocardial ischemia by enhancing the contrast between normally perfused and ischemic myocardia; 2) MRI with albumin-Gd-DTPA is useful for identifying reperfusion after myocardial ischemia; and 3) after reperfusion, reversible can be distinguished from irreversible myocardial injury by characteristic findings on MRI and MRS.

Albumins↗

Cine magnetic resonance imaging: tomographic analysis of left ventricular function.

Cine magnetic resonance imaging has the attributes that enable its use as a method for quantitating the three-dimensional functional geometry of the ventricles. The completely noninvasive nature of this technique is advantageous for sequential studies needed to monitor evolution of cardiac disease and response to therapy. This article reviews the authors' experiences with this technique for the evaluation of left ventricular and valvular function.

Aortic Valve Insufficiency↗

Determination of buffering capacity of rat myocardium during ischemia.

To determine the buffering capacity of ischemic rat myocardium, lactate production was altered by glycogen depletion prior to total global ischemia. Lactate production was monitored by 1H-NMR spectroscopy in perfused rat hearts and determined by enzymatic assay of freeze-clamped tissue extracts. Intracellular pH was measured by 31P-NMR spectroscopy. The relationship between total lactate produced and pH varied considerably, depending on the final pH reached. At pH greater than 6.4 this relationship is linear with a total buffering capacity (delta lactate/delta pH) of 25 mumol H+/g wet weight per pH unit. At lower pH values (pH less than 6.4), the total buffering capacity increases progressively. Since ischemia is invariably accompanied by ATP and phosphocreatine (PCr) hydrolysis, the proton production/consumption during high-energy phosphate hydrolysis must be considered when evaluating the intrinsic buffering capacity of the myocardium against proton loads produced by lactate production from glucose and glycogen. Schemes are presented which allow an estimation of the contribution of ATP and PCr hydrolysis and the buffering by the CO2/HCO3- system during ischemia. At pH greater than 6.4, the majority (about 60%) of buffering is due to hydrolysis of adenosine triphosphate, phosphocreatine in the heart, and neutralization of sodium bicarbonate in the perfusate. At pH less than 6.4 an increasing proportion of cardiac buffering is from intrinsic cardiac buffers, most likely from intracellular proteins. After correction for these contributions to the observed total cardiac buffering capacity, the intrinsic buffering capacity of the myocardium can be accounted for by a high capacity (170 mumol/g wet weight) but low pKa (5.2) buffering system.

Adenosine Triphosphate↗

Iodine 123-phenylpentadecanoic acid myocardial scintigraphy: usefulness in the identification of myocardial ischemia.

In this study, we tested the hypothesis that myocardial ischemia induced by exercise in patients is associated with diminished metabolism and/or delayed clearance of an intravenously injected fatty acid, iodine 123-labeled phenylpentadecanoic acid (IPPA). Fifteen normal volunteers and 18 patients with significant coronary heart disease (CHD) received IPPA during exercise. In the patients with CHD, radionuclide ventriculograms were also obtained during exercise. The normal volunteers had relatively uniform initial left ventricular segmental IPPA activity after exercise and uniform IPPA clearance in the interval from 4 to 20 min immediately after exercise. In contrast, the patients with CHD had increased initial left ventricular segmental IPPA activity (63%, p less than .001) and delayed IPPA clearance (44%, p less than .01) in segments supplied by significantly narrowed coronary arteries. Based on analysis with the mean values +/- 1 SD for initial IPPA activity, clearance, or both in normal volunteers, the sensitivity and specificity of exercise IPPA scintigraphy for detecting CHD were 89% and 67%, respectively; when +/- 2 SD differences from the mean values in the normal volunteers were considered, the sensitivity and specificity were 72% and 100%, respectively. Among the total of 27 noninfarcted left ventricular segments supplied by significantly narrowed coronary arteries in the study patients, 26 (96%) had an abnormality (mean +/- 1 SD) of either initial IPPA activity or clearance compared with corresponding segments in the normal volunteers and/or with other left ventricular segments in the same image that were not supplied by significantly narrowed coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Determination of left ventricular mass using single-photon emission computed tomography.

To test the hypothesis that single-photon emission computed tomography (SPECT) could actually determine left ventricular LV mass in humans, SPECT measurements of LV mass were compared with LV mass determined by cineangiography in 12 patients with normal coronary arteries and LV function. Repeat SPECT determinations of LV mass were carried out in 5 patients. Projection images of the left ventricle were acquired after intravenous injection of thallium-201 (TI-201) using a rotating gamma camera. Transverse sections were reconstructed by filtered backprojection. The boundary of LV uptake of TI-201 in each transverse section was defined using a 3-dimensional threshold detector. Scintigraphic LV mass (total number of voxels demonstrating LV TI-201 uptake X voxel volume X specific gravity of myocardium) was compared with angiographic LV mass. There was good correlation between LV mass determined by SPECT and that determined by cineangiography. Mean angiographic LV mass was 208 +/- 45 g (+/- standard deviation). Mean SPECT LV mass was 204 +/- 42 g. Linear regression analysis revealed the following relation: SPECT LV mass = 0.76 X angiographic LV mass + 46.1 (r = 0.82, root-mean-square deviation from regression = 24.7). The SPECT values of LV mass varied an average of 10.4 +/- 4.6% (+/- standard deviation) in the 5 patients in whom 2 determinations were made. Thus, SPECT of TI-201 can accurately measure LV mass in humans.

Heart Ventricles↗

Acute hemodynamic and electrophysiologic effects of propranolol in patients receiving diltiazem.

Because the combined use of a beta-adrenergic blocking agent and a calcium antagonist may be beneficial in some patients with severe angina, the acute hemodynamic and electrophysiologic effects of intravenous propranolol in the presence and absence of oral diltiazem treatment was studied. In 22 patients (11 men, 11 women, mean age 50 years), 12 receiving diltiazem (mean 243 mg/day, range 180 to 360) and 10 not receiving diltiazem, hemodynamic and electrophysiologic variables were measured before and 5 minutes after intravenous propranolol (0.1 mg/kg). Cardiac index (by thermodilution) and left ventricular (LV) peak dP/dt fell and LV end-diastolic pressure increased similarly in both groups. Mean systemic arterial pressure was unchanged. Coronary sinus blood flow (by thermodilution) decreased slightly in patients receiving diltiazem and was unchanged in those not receiving it. Propranolol caused a similar reduction in heart rate and increase in atrio-His conduction in both groups. Thus, when intravenous propranolol is given to patients with normal or only mildly depressed LV systolic function, the hemodynamic and electrophysiologic effects are similar in those receiving and not receiving oral diltiazem.

Benzazepines↗

Tomographic gated blood pool radionuclide ventriculography: analysis of wall motion and left ventricular volumes in patients with coronary artery disease.

The use of planar radionuclide ventriculography to evaluate global and segmental ventricular function is limited by the superimposition of structures in some projections and the gross segmental resolution of the planar technique. Preliminary reports have suggested the feasibility of tomographic gated radionuclide ventriculography with rotating detector systems. This study tested the hypotheses that 1) tomographic radionuclide ventriculography detects segmental dysfunction at rest not identified with multiview planar studies and single plane contrast ventriculography, and 2) ventricular volumes and ejection fraction calculated from these studies provide data similar to those obtained with angiography and planar radionuclide ventriculography. Gated blood pool tomograms were acquired over 180 degrees at 15 frames per cardiac cycle during the initial 90% of the cardiac cycle. Compared with the multiview planar technique tomographic ventriculography showed an increased sensitivity for detecting left ventricular segments with significant coronary artery stenosis (97 versus 74%, p less than 0.025) without any loss in specificity. Compared with both planar radionuclide and contrast ventriculography, tomographic radionuclide ventriculography also detected more noninfarcted left ventricular segments supplied by stenosed coronary arteries (81 versus 39 and 32%, respectively, p less than 0.01). Tomographic radionuclide ventriculographic measurements of left ventricular volumes and ejection fraction showed close correlations with angiographic and planar radionuclide determinations. Gated blood pool tomography is a sensitive method for the evaluation of segmental wall motion and an accurate method for the measurement of global left ventricular volumes and ejection fraction.

Adult↗

Measurement of myocardial infarction fraction using single photon emission computed tomography.

Although infarct size correlates generally with prognosis after acute myocardial infarction, an absolute measure of infarct size may have differing prognostic significance depending on absolute left ventricular mass. To test the hypothesis that single photon emission computed tomography can accurately measure myocardial infarct size as a percent of total left ventricular mass ("infarction fraction"), thallium-201 and technetium-99m pyrophosphate tomograms were acquired in 21 dogs 24 to 48 hours after fixed occlusion of the left anterior descending or circumflex coronary artery. Pathologic infarct weight was measured as the myocardial mass that showed no staining with triphenyltetrazolium chloride. Scintigraphic infarct mass by technetium-99m pyrophosphate was calculated from the total number of left ventricular volume elements (voxels) demonstrating technetium-99m pyrophosphate uptake X voxel dimension [( 0.476 cm]3) X specific gravity of myocardium (1.05 g/cm3). Scintigraphic left ventricular mass was calculated in a similar fashion using an overlay of the thallium-201 and technetium-99m pyrophosphate scans. The "infarction fraction" was calculated as: infarction fraction = infarct mass/left ventricular mass. There was good correlation between single photon emission computed tomography and pathologic measurements of infarct mass (technetium-99m pyrophosphate mass = 1.01 X pathologic infarct mass + 0.96; r = 0.98), left ventricular mass (single photon emission computed tomographic left ventricular mass = 0.60 X pathologic left ventricular mass + 37.4; r = 0.86) and "infarction fraction" (single photon emission computed tomographic infarction fraction = 1.09 X pathologic infarction fraction - 1.7; r = 0.94).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Quantification of myocardial infarction: a comparison of single photon-emission computed tomography with pyrophosphate to serial plasma MB-creatine kinase measurements.

Single photon-emission computed tomography (SPECT) with 99mTc-pyrophosphate (PPi) has been shown to estimate size of myocardial infarction accurately in animals. We tested the hypothesis that SPECT with 99mTc-PPi and blood pool subtraction can provide prompt and accurate estimates of size of myocardial infarction in patients. SPECT estimates are potentially available early after the onset of infarction and should correlate with estimates of infarct size calculated from serial measurements of plasma MB-creatine kinase (CK) activity. Thirty-three patients with acute myocardial infarction and 16 control patients without acute myocardial infarction were studied. Eleven of the patients had transmural anterior myocardial infarction, 16 had transmural inferior myocardial infarction, and six had nontransmural myocardial infarction. SPECT was performed with a commercially available rotating gamma camera. Identical projection images of the distribution of 99mTc-PPi and the ungated cardiac blood pool were acquired sequentially over 180 degrees. Reconstructed sections were color coded and superimposed for purposes of localization of infarct. Areas of increased PPi uptake within myocardial infarcts were thresholded at 65% of peak activity. The blood pool was thresholded at 50% and subtracted to determine the endocardial border for the left ventricle. Myocardial infarcts ranged in size from 1 to 126 gram equivalents (geq) MB-CK. The correlation of MB-CK estimates of size of infarct with size determined by SPECT (both in geq) was good (r = .89 with a regression line of y = 13.1 + 1.5x).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Measurement of myocardial infarct size by technetium pyrophosphate single-photon tomography.

The primary determinant of prognosis after acute myocardial infarction (AMI) is the size of the acute infarct. The present study evaluates 46 patients with different infarct distributions and sizes to test the hypothesis that single photon emission computed tomography with technetium-99m pyrophosphate (Tc-99m-PPi) and blood pool overlay allows measurements of AMI size that provide insight into prognosis irrespective of infarct location. Identical Tc-99m-PPi and ungated blood pool projections were acquired over 180 degrees with a rotating gamma camera. Reconstructed sections were color-coded and superimposed for purposes of infarct localization. Areas of increased pyrophosphate uptake within myocardial infarcts were thresholded at 65% of peak activity. The blood pool was thresholded at 50% and subtracted so as to determine an endocardial border for the left ventricle. Using this method, myocardial infarcts weighed 2.5 to 81.2 g. The correlation of infarct mass with prognosis showed that patients without previous AMI and with acute infarcts that weighed more than 40 g had an increased frequency of death and congestive heart failure (p less than 0.001). The correlation of measured infarct mass with peak serum creatine kinase level was significant (r = 0.83, p less than 0.001; y = 0.015x + 13.20). The correlation coefficients for anterior, inferior and nontransmural AMI were not significantly different from those for the entire group. In conclusion, tomographically determined infarct mass data correlate with subsequent clinical prognosis, and Tc-99m-PPi tomography with blood pool overlay is a safe and effective means of sizing infarcts in patients with AMI.

Adult↗

Measurement of infarct size in acute canine myocardial infarction by single-photon emission computed tomography with technetium-99m pyrophosphate.

The location and extent of myocardial infarction (MI) are important predictors of patient course. The current study tests the hypothesis that MI size could be measured accurately using rotating gamma camera single-photon emission computed tomography ( SPECT ) and technetium-99m pyrophosphate (PPi) and that the accuracy of these measurements was independent of MI location and transmural or nontransmural distribution. SPECT was performed in 38 dogs 48 hours after ligation of the left anterior descending coronary artery (14 dogs) or left circumflex coronary artery (LC) (24 dogs) at the mid-level or below. Projection images were corrected for center-of-rotation and field nonuniformity and processed with a 1-dimensional low-pass filter to diminish rib activity. Sixteen 0.5-cm-thick transverse sections, including the entire left ventricle, were reconstructed by filtered backprojection , low-pass filtered, contrast enhanced and processed with a 3-dimensional boundary enhancement operator. The boundary of PPi uptake in each slice was marked automatically using an algorithm that combined a directional derivative and a threshold, and required continuity of the boundary in 3 dimensions. The total number of volume elements that showed abnormal tracer uptake were summed, corrected to absolute volume, and multiplied by the specific weight of cardiac muscle. Scintigraphic MI weight was compared with pathologic MI weight. There was an excellent correlation between scintigraphic and pathologic MI weight. The poorer correlation for nontransmural compared with transmural MIs is most likely a function of size alone, since MIs that weighed less than 10 g (n = 12, range 1.3 to 9.5 g), both transmural and nontransmural, showed a similar correlation: S = 1.07 X P + 0.56 (r = 0.81, standard error of the slope = 0.245).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗