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Biomedical subjects

G Wisenberg

Publications and source records attributed to G Wisenberg.

At least 19 recordsLinked to original sources
PubMed2001

Examining a canine model of stunned myocardium with Gd-DTPA-enhanced MRI.

It has previously been shown that the distribution volume of Gd-DTPA (lambda) in infarcted, canine myocardium is higher than that of normal tissue. The purpose of this study was to determine whether stunned myocardium exhibits increased lambda. Stunning was produced in beagles by means of 30 min LAD occlusion followed by 3 weeks (n = 4) reperfusion. Gd-DTPA was infused at each imaging session and lambda determined in vivo using a saturation recovery turboFLASH sequence; cine imaging was used to assess ventricular wall thickening (%WT). (201)Tl uptake was used as an independent assessment of viability. %WT data confirmed that the brief insult caused prolonged, yet reversible, regional contractile dysfunction in each animal. %WT was not significantly different from baseline values by 3 weeks post-reflow. Normal (201)Tl uptake confirmed the absence of infarction. The lambda of stunned tissue (lambda = 0.381 +/- 0.030 ml/g) was not elevated above that of normal tissue (lambda = 0.398 +/- 0.027 ml/g, P = NS), at any time point studied, in vivo. These data suggest that an increase in lambda is a specific indicator of irreversible damage.

Animals↗
PubMed2001

Gd-DTPA bolus tracking in the myocardium using T1 fast acquisition relaxation mapping (T1 FARM).

MRI methods currently used for bolus tracking in the myocardium, such as saturation recovery turbo-fast low-angle shot (FLASH) (srTFL), are limited by signal intensity (SI) saturation at high contrast agent (CA) concentrations. By using T1 fast acquisition relaxation mapping (T1 FARM), a Gd-DTPA bolus (0.075 vs. 0.025 mmol/kg) may be injected without causing saturation. This study tested the feasibility of in vivo T1 FARM bolus tracking under rest/stress conditions in seven beagles with multiple permanently occluded branches of the left anterior descending (LAD) coronary artery. Although it underestimated the myocardial perfusion reserve (MPR) measured ex vivo using radioactive microspheres (mean +/- SEM; 3.60 +/- 0.26), the MPR determined upon application of the modified Kety model (1.86 +/- 0.10) enabled distinction between normal and infarcted tissue. The partition coefficient (lambda) estimated at rest and stress using the modified Kety model underestimated ex vivo radioactive measurements in infarcted tissue (0.25 +/- 0.01 vs. 0.26 +/- 0.01 vs. 0.79 +/- 0.08 ml/g, P < 0.0001) yet was accurate in normal tissue (0.28 +/- 0.01 vs. 0.30 +/- 0.01 vs. 0.33 +/- 0.01 ml/g, P = NS). Thus, although unsuitable for myocardial viability assessment, T1 FARM bolus tracking shows potential for assessment of myocardial perfusion.

Animals↗
PubMed2001

The use of Gd-DTPA as a marker of myocardial viability in reperfused acute myocardial infarction.

At present, accurate assessment of the extent of myocardial viability after acute myocardial infarction is limited due to the spatial resolution of currently available imaging modalities. MR cardiac imaging, with its superior spatial resolution, would be used if viable and infarcted tissue could be separated based on signal intensity. In infarcted tissue, cell membrane breakdown allows the entry of the MR contrast agent Gd-DTPA which is normally extracellular. The increased space for Gd-DTPA distribution (partition coefficient, lambda) in this infarcted tissue results in increased Gd-DTPA concentration and hence increased signal intensity on T1-weighted MR images. In a canine model of ischemia/reperfusion injury, the partition coefficient in infarcted tissue increased as early as 1 min post reperfusion. lambda in infarcted tissue stayed increased over that in normal tissue for at least 8 weeks. The accuracy of contrast-enhanced MRI was confirmed by results of 201Tl SPECT and a cine MRI dobutamine wall motion study in a patient 1 week after an acute myocardial infarction. Thus, contrast-enhanced MRI shows great promise for the non-invasive determination of myocardial viability after acute myocardial infarction.

Animals↗
PubMed2000

Contrast-enhanced MRI for the assessment of myocardial viability after permanent coronary artery occlusion.

Previous studies in a model of ischemia/reperfusion using a constant infusion of Gd-DTPA have shown that distribution volume (lambda) is increased in infarcted myocardial tissue. This study examined this technique in the setting of permanent coronary artery occlusion. Ten beagles underwent permanent occlusion of a coronary artery for 2 days (N = 3), 1 week (N = 4), or 3 weeks (N = 3). Imaging was performed at 2 days and, depending on the length of occlusion, 1 week, 2 weeks, and 3 weeks to follow changes in lambda in vivo. At sacrifice, (201)Tl was injected and the extent of the hyperenhanced region was compared to pathology. lambda was increased in infarcted tissue by 2 days post occlusion and this increase persisted for 3 weeks. At sacrifice, lambda correlated strongly with (201)Tl uptake (r = -0.86 to -0.95, P < 0.05; i.e., lambda increased in infarcted tissue) and the size of the hyperenhanced region was comparable to pathological infarct size (slope 1.006, r = 0.96, P < 0.0001). Thus, beyond 2 days after coronary occlusion, MRI, during a constant infusion of Gd-DTPA, can assess myocardial viability regardless of the success of reperfusion. Magn Reson Med 44:309-316, 2000.

Analysis of Variance↗
PubMed2000

Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA.

This study assessed the accuracy and feasibility of magnetic resonance imaging (MRI) during a constant infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) for the determination of myocardial viability in patients with recent acute myocardial infarction (AMI). Nine patients were studied within 10 days of AMI. Rest-redistribution 201Thallium (201Tl) single photon emission computed tomography (SPECT) was used as a gold standard for viability. Using MRI, regional perfusion was assessed using dynamic imaging during a bolus injection of Gd-DTPA and viability was assessed during a continuous infusion. Finally, cine MR images were acquired at baseline, during low-dose dobutamine infusion and after recovery. To assess viability, the left ventricle was divided into 16 segments and signal intensity in corresponding MRI and redistribution SPECT segments were compared. Wall thickening index (WTI) was determined at each step during the dobutamine study. The results revealed that in five patients, reduced perfusion in infarcted regions was observed qualitatively during dynamic first pass imaging. There was a significant inverse correlation between 201Tl uptake and MRI signal intensity, i.e. infarcted tissue (low 201Tl uptake) had increased MR signal intensity. Segments were separated into normal (201Tl uptake > 90%) and infarcted (< 601%). lnfarcted MRI segments had greater signal intensity than normal segments (179 +/- 50 vs. 102 +/- 14%; P < 0.0001). WTI in normal segments increased by 18 +/- 8.5% (P < 0.0001) from baseline to 10 microg/kg per min of dobutamine while infarcted tissue WTI decreased 2.8 +/- 7.2% (P = 0.17). Thus regions of myocardium that were infarcted as defined by reduced 201Tl uptake and absent contractile reserve showed greatly increased MRI signal intensity during a constant infusion of Gd-DTPA. The use of MRI during a constant infusion of Gd-DTPA is accurate and feasible for the determination of myocardial necrosis in a clinical setting.

Adult↗
PubMed1999

Assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA: further studies at early and late periods of reperfusion.

It was previously shown in a canine model of ischemia/reperfusion injury that the partition coefficient of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) (lambda) increases in infarcted tissue. That previous study used a non-magnetic resonance imaging (MRI) method to measure lambda and only investigated reperfusion times from 2 hr to 3 weeks. This study presents evidence suggesting that lambda starts to increase as early as 1 min after reperfusion of a 2 hr occlusion and continues to rise for up to 2 hr or more; lambda stays increased as late as 8 weeks, reaching peak values at 1-11 days and subsequently decreasing. It was also demonstrated that lambda can be accurately measured in vivo using a saturation recovery turbo fast low-angle shot (FLASH) sequence. The results of this study show that MRI during a constant infusion of Gd-DTPA has great potential for the non-invasive determination of myocardial viability as early as 1 min to as late as 8 weeks following reperfusion of acute myocardial infarction.

Animals↗
PubMed1998

Noninvasive assessment of pharmaceutical intervention during myocardial ischemia-reperfusion in a canine model using two-dimensional 31P chemical shift imaging.

The metabolic effects during myocardial ischemia and sustained reperfusion of the antianginal agents diltiazem (n = 10) and propranolol (n = 10) were monitored with noninvasive phosphorus nuclear magnetic resonance spectroscopy to establish any correlation between metabolic changes and infarct size. Spectroscopy followed changes in high-energy phosphate concentrations and myocardial intracellular pH during 2 h of left anterior descending coronary artery occlusion and 3 subsequent weeks of reperfusion, in a closed chest canine infarct model. Gadolinium-DTPA enhanced magnetic resonance imaging was used to assess the extent of myocardial injury (infarct size). Microspheres were used to document the zone at risk and the success of reperfusion. Whereas diltiazem appeared to reduce the derangement in high-energy phosphates during coronary occlusion, there was no significant change in infarct size when compared with a previously studied control group. Propranolol, which produced a lesser decline in pH during occlusion and smaller pH changes during early reperfusion, was associated with a significant reduction in the degree of tissue necrosis (compared with controls). There was an inverse correlation (r = -0.51) between the change in myocardial pH (occlusion end to immediate reperfusion) and the recovery index (an index of myocardial salvage). By 1 h into reperfusion, there was a stronger inverse correlation between pH and infarct size (r = -0.75), implying a protective effect of delaying pH recovery during early reperfusion and indicating the potential use of this parameter as a predictor of tissue viability.

Adenosine Triphosphate↗
PubMed1997

Myocardial infarction in a canine model monitored by two-dimensional 31P chemical shift spectroscopic imaging.

We have developed a closed chest animal model that allows noninvasive monitoring of cardiac high energy phosphate metabolism before, during, and for at least 3 weeks after a myocardial infarction. Ten beagles underwent 2 h of coronary occlusion followed by 3 weeks of reperfusion. Myocardial high energy phosphates from 12-ml voxels were noninvasively tracked using 31P two-dimensional chemical shift imaging. Gadolinium enhanced 1H MRI identified the zone at risk, and radioactive microspheres assessed regional blood flow and partition coefficients. Occlusion of the left anterior descending coronary artery produced infarcts that were 13.7+/-8.8% (mean+/-SD) of the left ventricular volume. Rapid changes in the phosphocreatine and inorganic phosphate levels were observed during occlusion, whereas adenosine triphosphate levels decreased more slowly. All metabolites recovered to base-line levels 2 weeks after occluder release. Multiple inorganic phosphate peaks in the infarct voxel spectra indicated that more than one metabolically compromised tissue zone developed during occlusion and reperfusion. Microsphere data indicating three distinct blood flow zones during ischemia and reperfusion (<0.3, 0.3-0.75, and >0.75 ml/min/g) supported the grouping of pH values into three distinct metabolic distributions.

Adenosine Triphosphate↗
PubMed1997

Controlled reperfusion after myocardial ischemia in a canine model monitored by two-dimensional phosphorus 31 chemical shift spectroscopic imaging.

Phosphorus 31 magnetic resonance spectroscopy at 2 T was used to monitor high-energy phosphate metabolism over a 3-week period in a canine model of myocardial infarction and reperfusion. Twenty animals were divided into two groups: group 1 (n = 11) received intravenous nitroglycerin beginning at the onset of coronary occlusion; group 2 (n = 9) received a 105-minute infusion of superoxide dismutase (SOD) beginning at the onset of reperfusion. A metabolic protective effect was observed (vs controls) with both agents, manifested by a reduction in the degree of pH decline from baseline values and preservation of the adenosine triphosphate/total phosphate ratio during occlusion and reperfusion. Further, both treatments, compared with controls, produced a lower infarct/zone at risk ratio: controls, 1.5 +/- 1.2; nitroglycerin, 0.52 +/- 0.50; and SOD, 0.64 +/- 0.40. The technique of 31P magnetic resonance spectroscopy demonstrated its use for the noninvasive assessment of myocardial metabolism in response to therapeutic intervention.

Adenosine Triphosphate↗
PubMed1996

The determination of myocardial viability using Gd-DTPA in a canine model of acute myocardial ischemia and reperfusion.

The partition coefficient of Gd-DTPA was thought to vary with the amount of cellular membrane damage after an acute myocardial infarction. The relationship between the partition coefficient of Gd-DTPA (lambda) and the uptake of 201Tl (as a marker of tissue viability) was studied 2 h to 3 weeks after reperfusion of a 2-h occlusion to the left anterior descending coronary artery in a canine model. Gd-DTPA was infused as a bolus followed by a prolonged constant infusion, and this infusion protocol was optimized such that the concentration of Gd-DTPA was directly related to lambda. After this infusion, MR images of excised hearts showed regions of increased signal intensity corresponding to increased Gd-DTPA concentration. At all time points, lambda and 201Tl uptake were strongly negatively correlated indicating that lambda is an accurate indicator of myocardial viability. Furthermore, lambda in the infarcted regions was increased relative to normal regions after 2 h of reperfusion and stayed elevated up to 3 weeks. At all time points, lambda in the infarcted and normal regions were significantly different. As well, this data showed a trend that lambda in infarcted regions decreased monotonically from 1 day to 3 weeks. This trend was confirmed with MR imaging by examining the change in signal intensity of in vivo images from 4 days to 3 weeks in two animals. These results suggest that MRI with Gd-DTPA could be used to measure the extent of myocardial damage after an acute myocardial infarction.

Animals↗
PubMed1993

Techniques for the measurement of the local myocardial extraction efficiency for inert diffusible contrast agents such as gadopentate dimeglumine.

We have previously shown that the concentration of Gd-DTPA as a function of time ([Gd-DTPA]t(t)) in the myocardium following an intravenous bolus injection of Gd-DTPA can be modeled using the Modified Kety Equation. Fitting this model to measurements of [Gd-DTPA]t(t) in a region of myocardium would allow the determination of myocardial distribution volume (lambda) and the product of flow (F) and extraction efficiency (E), i.e., FE. Thus, to measure F, E must be known. We describe here techniques developed to measure local values of E in normal and diseased myocardium. These techniques are valid for any inert diffusible MR contrast agent.

Animals↗
PubMed1993

Measurement of the extraction efficiency and distribution volume for Gd-DTPA in normal and diseased canine myocardium.

We have previously shown that the myocardial Gd-DTPA concentration ([Gd-DTPA]t(t)) after a bolus injection of Gd-DTPA can be predicted by the Modified Kety Equation (MKE). If [Gd-DTPA]t(t) can be determined by MRI and the data fit to the MKE, then the distribution volume (lambda) of Gd-DTPA and the myocardial flow (F) times the extraction efficiency (E), i.e., the FE product, can be determined. Therefore F can only be quantified if E is known. We measured the global E in vivo in normal canine myocardium, and measured E and lambda, in vitro, locally in normal, acute ischemic (n = 5; coronary artery occlusion < 4 h), infarcted (n = 4; coronary artery occlusion, 6 days) and reperfused (n = 4; coronary artery occlusion 2 h, and reperfusion 2 h and 6 days) myocardium. Results indicate that E differs with F and with individuals and consequently, F cannot be quantified using the MKE unless the local E is also determined in vivo.

Animals↗
PubMed1992

Quantification of myocardial blood flow and extracellular volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic disease.

In order to clarify the relationship between coronary artery disease (including myocardial infarction) and image contrast in gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced MRI it was decided to model the myocardial tissue distribution and clearance of Gd-DTPA using the modified Kety equation. Using a canine model, myocardial tissue Gd-DTPA concentrations ([Gd-DTPA]m) were measured 1 or 5 min after a bolus injection of Gd-DTPA or immediately after the end of a constant infusion of Gd-DTPA in a total of 35 dogs. It was found that within 5 min of a bolus injection [Gd-DTPA]m is determined primarily by myocardial blood flow (MBF) and after about 10 min primarily by myocardial extracellular volumes (MECV). This study suggests that repeat, rapid (every 2-4 s) measurements of myocardial T1 relaxation rates following the bolus injection of Gd-DTPA are required to calculate MBF (i.e., myocardial tissue perfusion) and MECV.

Animals↗
PubMed1992

Effects of dipyridamole infusion on human renal function observed using technetium-99m-DTPA.

Our observation that a prolonged dipyridamole infusion reduced or eliminated blood clearance of Gd-DTPA in dogs led us to investigate if dipyridamole, infused intravenously at rates comparable to those used in thallium myocardial perfusion tests, would alter renal filtration in humans. Renal filtration was assessed using a bolus injection of 10 mCi of 99mTc-DTPA in five males (19-63 yr old) with normal serum urea and creatinine. Twenty minutes following the bolus injection a 10-min intravenous infusion of either dipyridamole (0.14 mg/kg/min) or saline sham was given. Four to 10 min following the start of the dipyridamole infusion, a paradoxical rise in counts in the kidney region of interest was observed and persisted for 10 to 27 min. During this time, a 13% to 52% (mean +/- s.d., 40% +/- 16%, p less than 0.007) reduction in the exponential slope defining the clearance of counts from the cardiac region of interest occurred (implying a reduction of glomerular filtration rate), mean heart rate increased 27 +/- 5 bpm, p less than 0.002 and mean diastolic pressure decreased 12.9 +/- 6.4 mmHg, p less than 0.028. This finding indicates that renal clearance of tracers such as thallium or contrast agents such as Gd-DTPA is reduced during dipyridamole infusion.

Adult↗
PubMed1991

Left atrial bacterial mural endocarditis.

An unusual case of Staphylococcus aureus endocarditis confined to the mural left atrium is presented. Echocardiographic studies revealed a 1.5 x 2.0-cm vegetation mimicking a myxoma situated in the path of a mitral regurgitant jet on a color Doppler test. Emboli to upper and lower extremities and brain complicated the patient's preoperative course. Surgical excision and pathologic examination confirmed this rare occurrence.

Diagnosis, Differential↗
PubMed1989

Sustained effect of and lack of development of tolerance to controlled-release isosorbide-5-mononitrate in chronic stable angina pectoris.

Tolerance has been shown to develop when nitrate preparations are used in such a manner as to produce plasma levels within the therapeutic range continuously over a 24-hour period. However, a period of reduced or low nitrate plasma levels of a few hours per day may limit or completely prevent tolerance development. In 18 patients with chronic stable angina pectoris, a single 60-mg daily dose of a controlled-release preparation of isosorbide-5-mononitrate (ISMN) was compared with the administration of 30 mg, 4 times daily, of immediate-release isosorbide dinitrate (ISDN) in a double-blind, randomized, placebo-controlled, crossover study. The comparisons were carried out on the first day of therapy and after 11 to 14 days of continuous therapy to assess the duration of effectiveness and the development of tolerance. On short-term therapy, both drugs produced a significant improvement in treadmill walking times to moderate angina in comparison with placebo. The values for ISMN were 87 +/- 99 seconds (23%) at 12:30 P.M., 72 +/- 91 seconds (19%) at 5 P.M. and 51 +/- 81 seconds (13%) at 8:30 P.M. For ISDN, the respective values were 71 +/- 83 seconds (19%), 89 +/- 98 seconds (24%) and 79 +/- 87 seconds (21%). There were no significant differences between drugs. Plasma nitrate levels for each drug paralleled the improvements in exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗