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Currently available magnetic resonance (MR) contrast agents are not confined to the intravascular space because of their small molecular size. These agents produce peak vascular enhancement for only a short period. Conversely, blood pool agents have longer intravascular residence time and higher relaxivity. Therefore these agents provide MR angiography with flexibility, versatility, and accuracy. With blood pool agents, the timing of contrast injection becomes less significant because the optimal imaging window is in tens of minutes rather than seconds. In addition, larger anatomic regions can be imaged optimally. Preliminary evidence appears to support the notion that blood pool agents may play a diagnostic role in coronary, peripheral, and pulmonary angiography. Besides their ability to increase vascular contrast, blood pool agents provide physiologic information, including rate of entry, rate of accumulation, and rate of elimination. MR imaging with blood pool agents also have proven to be of significant value in the assessments of myocardial perfusion and microvascular permeability. In anticipation of broad clinical use, blood pool agents are currently being evaluated in human trails. Examples include gadolinium-chelate that binds in vivo to albumin to form blood pool agents and ultrasmall superparamagnetic iron oxide particles. This review discusses the applications of MR blood pool agents in the cardiovascular system. J. Magn. Reson. Imaging 2000;12:890-898., (Copyright 2000 Wiley-Liss, Inc.)

Magnetic resonance (MR) functional and perfusion imaging were employed in a canine model of coronary artery stenosis (n = 6) for the quantification of functional and perfusion deficits before and after dipyridamole administration. Left anterior descending and circumflex (LCX) coronary blood flow were measured continuously after placing Doppler flowmeters. Inversion recovery gradient echo images during the transit of MR contrast medium gadolinium-benzyloxypropionictetraacetate dimeglumine (Gd-BOPTA/Dimeg) and fast breath-hold cine MR images were acquired at baseline, during LCX stenosis in basal state, and during LCX stenosis with vasodilation (dipyridamole 0.5 mg/kg). The extent of the functional defect and perfusion defect was expressed as percent of left ventricle (LV) circumference. During stenosis (LCX flow: 62.6 +/- 5.6% of baseline) the extent of the functional defect was slightly larger than the perfusion defect (11.0 +/- 1.8% versus 6.3 +/- 1.70% of LV circumference, respectively; P < 0.01). During vasodilation the extent of the functional defect was considerably smaller than the perfusion defect (25.3 +/- 2.5% versus 35.3 +/- 3.5%; P < 0.01). Thus, the sizes of ischemic regions displayed by MR perfusion defect and functional defect differ from each other.

Purpose: To evaluate the usefulness of electron-beam computed tomography (CT) for identification of coronary artery stenoses., Materials and Methods: Coronary angiography and contrast material-enhanced, electrocardiographically triggered electron-beam CT of the heart were performed in 23 patients. With axial CT images and axial maximum intensity projection reconstructions, the coronary arteries were assessed by two observers blinded to the results of angiography., Results: Cardiac motion artifact (unsharpness) precluded evaluation of the right coronary artery (RCA) in six subjects and the left circumflex coronary artery (LCX) in one patient. With the vessels degraded by motion artifact eliminated from analysis, overall sensitivity of electron-beam CT for hemodynamically significant stenoses was 88%, and specificity was 79%. In the left anterior descending coronary artery (LAD), sensitivity was 93% and specificity was 63%; in the LCX, sensitivity was 100% and specificity was 67%; and in the RCA, sensitivity was 67% and specificity was 77%. The presence of coronary artery calcification did not have an effect on sensitivity for stenoses, but it did decrease specificity., Conclusion: Electron-beam CT angiography can depict hemodynamically significant stenoses in the LAD and LCX with a sensitivity of more than 90%. The presence of coronary artery calcification resulted in decreased specificity but no appreciable change in sensitivity.

Fast magnetic resonance (MR) imaging techniques have the capability of demonstrating regions of ischemia caused by stenosis. The size of the potentially ischemic area determines the importance of the stenosis. The purpose of this study was to determine the relative values of relaxivity-enhancing and magnetic-susceptibility MR contrast media in detecting and sizing the area at risk in dogs. Eight dogs were subjected to critical left circumflex coronary artery (LCX) stenosis. Sixty sequential inversion-recovery- and driven-equilibrium-prepared fast gradient recalled echo images were acquired during bolus administration of 0.03 mmol/kg gadodiamide or 0.4 mmol/kg sprodiamide in basal and vasodilated (dipyridamole-stress) states. The size of the area at risk was measured and compared with that measured post mortem. In the basal state, gadodiamide and sprodiamide equivalently altered the signal intensities of nonischemic myocardium and the territory of stenosed coronary artery. Dipyridamole produced a significant increase in left anterior descending coronary artery flow with a decrease in LCX flow. The hypoperfused region was observed as a low-and high-signal intensity region after administration of gadodiamide and sprodiamide, respectively. The size of the hypoperfused region was slightly smaller with gadodiamide (37.4% +/- 2.8%) and sprodiamide (34.0% +/- 2.2%) than the true area at risk measured post mortem (41.8% +/- 2.2%; p < 0.05). Dipyridamole perfusion MR imaging with relaxivity or susceptibility contrast media is a noninvasive method to identify and quantify the area at risk in the territory of a stenotic coronary artery. Changes in myocardial signal intensity on fast gradient recalled echo images reflect the augmentation of flow and volume induced with dipyridamole and are consistent with the "steal phenomenon."

Purpose: To monitor with fast gradient-echo magnetic resonance (MR) imaging the dynamics of gadolinium benzyloxypropionictetraacetate (gadobenate) dimeglumine on myocardial signal intensity in dogs with critical left circumflex coronary artery stenosis., Materials and Methods: Fast gradient-echo MR images were acquired in a short axis of the left ventricle. Two bolus injections of 0.05 mmol/kg gadobenate dimeglumine were administered in the basal state after stenosis and after infusion of 0.5 mg/kg dipyridamole., Results: In the basal state, there was an equivalent increase in signal intensity of normal and hypoperfused myocardium during the first pass. Dipyridamole increased left anterior descending flow (287% +/- 36; P < .05) and decreased left circumflex flow (65% +/- 14; P < .05). The magnitude of signal intensity increase during the second bolus in the hypoperfused region was less than that of normal myocardium (P < .05). Contrast-enhanced images showed the hypoperfused region as smaller than the postmortem measurement (43.8% +/- 3.3; P < .05)., Conclusion: Contrast-enhanced fast MR imaging in the vasodilated state allows detection of hypoperfused myocardium in the presence of critical coronary stenosis.

Brief episodes of myocardial ischemia are known to cause reversible depression of regional myocardial contraction after reperfusion. One of the mechanisms of this persistent regional dysfunction has been proposed to be depletion of high-energy phosphate compounds. Eight cats were prepared with a reversible snare occluder around the left anterior descending artery (LAD); a surface coil sutured to the epicardial surface over the LAD territory for measurement of 31-phosphorus (31P) magnetic resonance spectroscopy (MRS) spectra; and a pair of ultrasonic crystals implanted in the mid-myocardium for measurement of regional segment length shortening. The baseline value of percent segment length shortening (%SS) was 12.8 +/- 1.4%. Increased afterload did not significantly alter high-energy phosphate levels or %SS. All animals exhibited passive systolic bulging during occlusion (-8.4 +/- 3.6% systolic shortening) as well as reduced phosphocreatine (PRc, 30 +/- 3% of control) and increased inorganic phosphorus (Pi) (239 +/- 18%), but there was no change in adenosine triphosphate (ATP). During reflow, %SS did not completely recover (4.0 +/- 2.9%, P less than .05 versus baseline). PCr and Pi returned to control levels during the first 30 minutes of reperfusion. Increased afterload had no significant effect on high-energy phosphates or %SS in stunned hearts. These findings indicate a lack of correlation between recovery of high-energy phosphate stores and regional myocardial contractility in stunned myocardium. High-energy phosphate reserves are preserved in stunned myocardium and are unlikely to be a direct cause of myocardial dysfunction.

The current study used cine magnetic resonance imaging to determine the effect of increasing severity of valvular regurgitation on systolic wall stress and to demonstrate that wall stress was disproportionately increased in relation to the severity of regurgitation in patients with myocardial disease. A total of 39 patients with predominantly mitral (n = 22) or aortic (n = 17) regurgitation with (n = 13) and without (n = 26) myocardial disease and 10 normal volunteers were examined with cine magnetic resonance imaging (MRI) at 1.5 T. Left ventricular (LV) cardiac output (CO) and peak systolic (PS) wall stress (WS) and end-systolic (ES) WS were calculated from blood pressure recordings, carotid pulse tracings, and wall thickness (h) and diameter (D) measurements obtained from cine MRI. Patients were classified into three degrees of severity according to their LV regurgitant volume (RV). Myocardial disease was defined by an ejection fraction (EF) of less than 40%. Mean LV EF was 61 +/- 3% in normal volunteers, 64 +/- 3% in patients with regurgitation, and 25 +/- 2% in patients with myocardial disease. LV CO was directly related to RV in patients without myocardial disease, whereas it was disproportionately low in relation to RV in patients with myocardial disease. PS WS was significantly higher in severe mitral and/or aortic regurgitation compared with moderate, mild, and no mitral and/or aortic regurgitation. Compared with the degree of regurgitation, PS WS was disproportionately higher in patients with myocardial disease. Thus LV CO and WS rise progressively with increasing severity of regurgitation. Disproportionately high systolic WS relative to RV indicates the presence of myocardial disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina is characterized by brief periods of ischemia followed by reperfusion; the cumulative effect of these episodes on energetics of the myocardium has not been fully elucidated. This study used an in vivo feline model for the assessment of high-energy phosphate compounds during brief sequential periods of ischemia and reperfusion. Nine adult, open-chest, anesthetized cats were prepared with a reversible occluder around the proximal left anterior descending artery and a 1.2-cm-inside diameter coil sutured on the myocardial surface in the distribution of the left anterior descending coronary artery. Levels of PCr, Pi, and ATP (beta-phosphate signal) were measured by 31P MRS in a GE CSI 2-T NMR spectrometer/imager. Measurements were obtained during a control period and during three successive occlusion-deocclusion periods of roughly 12 and 20 min' duration, respectively. The last deocclusion period was observed for 60 min. Electron microscopy was performed in two animals. PCr declined (P less than 0.01) rapidly following each occlusion to 51 +/- 5.2% (occlusion 1), 53 +/- 5.8% (occlusion 2), and 48 +/- 5.7% (occlusion 3) of the control value by 6 min. Pi rose (P less than 0.01) with the three sequential occlusions to 253 +/- 46, 288 +/- 57, and 277 +/- 46%, respectively. PCr and Pi returned to baseline promptly with reperfusion, while ATP showed a gradual decline throughout the experiment, decreasing to 77 +/- 7.2% of control at the end of the last reperfusion (P less than 0.05). Although PCr returned to baseline during reperfusion, ATP did not, suggesting a reduction in the nucleotide pool. These findings indicate that the repeated episodes of ischemia, which are insufficient to produce necrosis, can have an effect on myocardial high-energy phosphate metabolism as evidenced by mild depletion of ATP.

The present study was undertaken to define the effects of left ventricular hypertrophy on postischemic recovery of myocardial performance and high energy phosphate metabolism. Hemodynamics and 31P-magnetic resonance spectra were monitored simultaneously in the isolated Langendorff-perfused rat heart during 30 minutes of ischemia and 30 minutes of reperfusion. Left ventricular hypertrophy was produced by either suprarenal aortic constriction or chronic thyroxine administration. In chronic pressure overload hypertrophy, minimal coronary resistance was significantly higher (p less than 0.001) and the loss of purine nucleosides in the coronary effluent during early reperfusion significantly larger (p less than 0.001) compared with both normal hearts and thyroxine-induced hypertrophied hearts. Postischemic recovery of the baseline values for left ventricular developed pressure and phosphorylation potential was 43 +/- 4% and 82 +/- 4%, respectively, in chronic pressure overload hypertrophied hearts; 86 +/- 4% and 91 +/- 3%, respectively, in normal hearts (chronic pressure overload hypertrophy versus normal hearts, p less than 0.001 and p less than 0.05); and 100 +/- 4% and 98 +/- 2%, respectively, in thyroxine-induced hypertrophied hearts (normal hearts versus thyroxine-induced hypertrophied hearts, p less than 0.05 and p less than 0.05). Recovery after reperfusion was not related to intracellular pH, ATP, phosphocreatine, or inorganic phosphate levels during ischemia. Also, recovery was not related to developed pressure or oxygen consumption before ischemia. However, recovery was inversely related to coronary resistance and directly related to coronary flow before ischemia. Thus, functional and/or anatomic alterations of the coronary vascular bed and a greater loss of purine nucleosides during reperfusion are likely responsible for the attenuated compensatory response to ischemia and reperfusion in left ventricular hypertrophy induced by chronic pressure overload. On the other hand, the excess muscle mass per se does not seem to alter recovery, since thyroxine-induced myocardial hypertrophied hearts responded at least as well as normal hearts.

Computerized tomographic abnormalities have been observed within hours after coronary occlusion. It has not been determined whether these CT changes are always indicative of irreversible myocardial damage or whether they can be produced by reversible myocardial injury. Accordingly, in the current study, the circumflex coronary arteries of 16 dogs were occluded for 20 minutes (reversible injury) or 40 minutes (irreversible injury) and then reperfused. The animals were sacrificed 24 hours later. Ten minutes prior to sacrifice, eight of the dogs received contrast material intravenously. The electron microscopic changes in the 20-minute occlusion group consisted of reversible damage, while those in the 40-minute group were irreversible. Two of the animals in the 20-minute group showed slightly decreased X-ray density of the infarct in the absence of contrast media, but none showed contrast enhancement of the infarct in the presence of contrast media. All the animals in the 40-minute group showed decreased X-ray density, and all animals that received contrast media had contrast enhancement of the area of ischemic damage. The results of the current study suggest that the decreased X-ray density of the area of ischemic damage on CT scans is due to cellular edema and may be observed in reversible myocardial injury, while delayed contrast enhancement is only associated with, and is indicative of, irreversible myocardial injury.

Acute myocardial infarctions were produced in 11 dogs by ligation of the left anterior descending coronary artery. Twenty-four hours after ligation, 0.35 millimoles per kilogram of Gd-DTPA was injected intravenously, followed by cardiectomy either 90 seconds (3 dogs) or 5 minutes (5 dogs) later. The remaining 3 dogs had cardiectomy without injection of Gd-DTPA at 24 hours after coronary occlusion. The 3 dogs that did not receive Gd-DTPA had longer T1 and T2 relaxation times in infarcted myocardium than in normal myocardium, as measured by a 10.7-MHz magnetic resonance (MR) spectrometer. The T1 and T2 relaxation times of normal myocardium at 90 seconds postinjection of Gd-DTPA were significantly shorter (p less than 0.05) than those of the normal myocardium of animals that did not receive Gd-DTPA. At five minutes postinjection, significantly (p less than 0.01) greater T1 shortening was exhibited in the infarcted myocardium compared with adjacent normal myocardium in the dogs injected with Gd-DTPA. Thus, Gd-DTPA has differential and time-varying effects on relaxation times of normal and infarcted myocardium.

The treatment of ischemic heart disease is dependent upon defining the physiologic significance of coronary arterial stenoses demonstrated on coronary arteriograms. Accordingly, physiologic--angiographic correlates were studied in 12 anesthetized dogs prepared with an electromagnetic flowmeter and micrometer-controlled occluder on the circumflex coronary artery, a pair of sonic crystals in the myocardium within the distribution of the circumflex artery, and a catheter in the thoracic aorta. Measurement of arterial diameters on coronary arteriograms was made to define the minimum percent stenosis that caused: (1) decrease in resting coronary blood flow (CBFr); decline in the peak level of coronary blood flow (CBF) produced by intense vasodilatation induced by intracoronary infusion of ATP (CBFATP); and (3) segmental left ventricular (LV) dysfunction. CBFR decreased at an average stenosis of 80.45 +/- 9.13% (SD) (percent reduction in luminal diameter), while CBFATP declined at a stenosis of 31.83 +/- 5.64%. Segmental LV dysfunction was observed at a stenosis of 85.92 +/- 9.83%. In all dogs, the initial stenosis causing decline in CBFATP was a less than or equal to 40% reduction in luminal diameter. The results of this study indicate that coronary arterial stenoses of 40% or less may be hemodynamically significant under situations of augmented CBF. On the other hand, regional contractile function at rest is preserved up to stenosis in excess of 80%.

The effects of intracoronary administration of contrast materials on regional and global left ventricular (LV) function and coronary sinus osmolality were assessed in six anesthetized dogs with segmental myocardial ischemia produced by critical stenosis of the circumflex coronary artery. Effects caused by Renografin (sodium meglumine diatrizoate), two new low osmolality contrast agents (Hexabrix and Hexabrix with added calcium ions), and metrizamide were evaluated. In a nonischemic state, Renografin produced an early (0-10 seconds) decrease in LV contractility followed by a late (10-20 seconds) rebound augmentation in contractility. In the presence of regional ischemia, there are prolongation of the depression of the myocardial contractile state. The monoacid dimer, Hexabrix, demonstrated a similar biphasic response, although the initial depression of myocardial contractility was significantly less than that observed with Renografin. Hexabrix with added calcium ions and metrizamide produced only augmentation in global and regional parameters of LV contractile function. This lack of depressant effects was also observed in the ischemic state. Renografin caused a significantly greater increase in coronary sinus osmolality (Tp) as compared with Hexabrix, Hexabrix-Ca++, and metrizamide. The increases in osmolality in response to the latter three contrast agents were statistically indistinguishable.

The systemic hemodynamic and myocardial effects of potent vasodilators administered directly into the left coronary artery were determined and compared with the actions of contrast material in 10 anesthetized dogs in the normal state and in the presence of segmental myocardial ischemia. Contrast material (Renografin 76) caused systemic hypotension, rise in left ventricular diastolic pressure and decreases in LV dp/dt and dp/dt/LVP in both states. Doses of ATP (7.2 microgram/kg and 20 microgram/kg/min) which are maximally effective in augmenting coronary blood flow caused only mild arterial hypotension and minimal inotropic effects in both states. Nitroglycerin (3 microgram/kg and 10 microgram/kg/min) induced no inotropic effects but slightly greater arterial hypotension than ATP in both states. On the other hand, papaverine HCl (300 microgram/kg and 800 microgram/kg/min) induced profound increases in LV dp/dt and dp/dt/LVP, decreases in LVEDP and arterial hypotension in the non-ischemic state. In the presence of segmental ischemia, papaverine HCl caused significantly less increases in LV dp/dt and dp/dt/LVP, paradoxical increases in LVEDP in 5 dogs and ventricular fibrillation in 3 dogs. Thus, maximally effective vasodilatory doses of ATP causes only small alterations in hemodynamics and myocardial contractile state of the normal and ischemic heart. Similar doses of papaverine induce profound positive inotropic effects which are apparently deleterious to the ischemic heart.

Central cardiovascular anatomy and function have been evaluated with intravenous digital subtraction angiography (DSA). The subtraction techniques used for studying the left ventricle (LV) were mask mode, time interval difference and functional subtraction. Aside from contrast enhancement, a major use of digital fluoroscopy for cardiac applications has been computer-assisted quantitative analysis of LV dimensions and function. Left ventricular volumes and wall thickness determined from DSA studies have correlated closely with direct left ventriculograms and sonocardiometry measurements in patients and animals, respectively. Measurements of segmental LV contraction with DSA correlated closely with direct left ventriculography in normal patients and patients with coronary artery disease. The sensitivity of intravenous DSA for detecting significant coronary artery disease was increased by performing DSA immediately after increasing the myocardial oxygen demands by atrial pacing. The advantages and disadvantages of DSA in relation to other semi-or non-invasive imaging modalities are discussed.

Using multigated radionuclide ventriculography (RNV), the left ventricular (LV) phase histogram (PH) was used to quantitate LV synchrony at rest and at submaximal and maximal supine exercise in 10 normal and 10 coronary (CAD) patients. Each LV PH was obtained by masking the phase image with an LV region, generated semiautomatically and modified if necessary to minimize ambiguity of LV delineation. The shape and spread of each histogram was characterized by its standard deviation (SD) and skewness (SK). Normals had a tight resting PH with slight negative skewness (SD = 9.06 +/- 0.22 (mean +/- SEM; SK = -0.53 +/- 0.05). CAD patients had a wider resting PH with a larger SD and a significantly more positive skewness reflecting greater contractile asynchrony (SD = 16.53 +/- 2.26; SK = 0.35 +/- 0.22). With exercise the PH distribution for the normals remained tight (SD = 8.1 +/- 0.24) while SK changed little (SK = -0.29 +/- 0.04). In contradistinction, with exercise CAD patients markedly increased the spread of their LV PH (SD = 27.42 +/- 3.77) and increased the number of late pixels (SK = 0.75 +/- 0.15). It is concluded that quantitative PH analysis is a useful adjunct for the analysis of regional asynergy during resting or exercise radionuclide left ventriculography.

Prospectively ECG-gated and nongated computed tomography (CT) can be used to assess global and regional left ventricular (LV) function and to measure myocardial infarct (MI) size. In the current study, CT was used to assess the effects of coronary occlusion and reperfusion in 16 dogs. Ten dogs were subjected to permanent occlusion of the proximal left anterior descending coronary artery and 6 dogs were reperfused after a 2-hour period of total coronary occlusion. Gated scans were used to quantitate the extent of wall thickening in the ischemic zone and to assess changes in mid-LV cross-sectional chamber area at end-diastole and end-systole. Nongated scans were used to estimate the size of the initial perfusion defect during contrast injection shortly after coronary occlusion and the size of the MI as indicated by delayed enhancement of the infarct 10 to 30 minutes after cessation of contrast administration. Neither group showed significant changes in end-diastolic chamber area during acute occlusion or 3 days later. Both groups showed a significant deterioration in percent change in chamber area both early after coronary occlusion and 3 days later; however, in the permanent occlusion group, percent wall thickening in the ischemic zone decreased from 46.2 +/- 16.5% (mean +/- standard deviation) to 1.6 +/- 9.0% during acute occlusion (p less than 0.01) and thickening remained depressed 3 days later (2.4 +/- 10.1%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Using equilibrium radionuclide angiography, we evaluated the ejection time (ET), peak ejection rate (PER), and time to peak ejection rate (TTp) at test and during supine bicycle exercise in 39 subjects, divided into three groups: group 1 = 13 normal subjects; group 2 = 10 patients with a previous infarction (MI); and group 3 = 16 patients with coronary disease without a previous MI. Normal subjects had greater ejection fractions and PERs than the other two groups at rest or peak exercise (p less than 0.05). PER was no more useful than ejection fraction in identifying cardiac dysfunction at either rest or exercise. The time of its occurrence varied with the group studied, and was slightly but significantly later in systole in groups 2 and 3 when compared to normals (p less than 0.05), though substantial overlap between groups occurred. During exercise, absolute ET shortened in all groups, but actually increased as a function of the R-R interval. The time to peak ejection rate (normalized for the R-R interval) was greater in the noninfarct group (group 3) patients (p less than 0.05) when compared to the group 1 or group 2 individuals at peak exercise. In conclusion, equilibrium radionuclide angiography is a useful technique for the quantification and characterization of events during systole, and is capable of providing information on the timing of events during ejection. Tardokinesis, or the delay of ventricular ejection, is not seen in the response of global indices of left ventricular function to exercise stress. While global early systolic indexes may not detect regional dyssynchrony, their timing during stress may occasionally aid in discerning the presence of cardiac dysfunction.

Little data exist about the relationship between changes in cardiac end-diastolic pressure and changes in pulmonary blood volume. To assess this relationship, we studied 11 patients with coronary heart disease during atrial pacing in an attempt to produce multiple pressure-volume points. During catheterization, we obtained Millar pressure recordings of end-diastolic pressure along with equilibrium radionuclide angiograms. Cardiac output, ejection fraction, and pulmonary blood volume were obtained by means of recently validated radionuclide techniques. During pacing, substantial changes in pulmonary blood volume occurred only with marked increase in end-diastolic pressure volume (greater than or equal to 15 mm Hg) and rarely exceeded 15% of control pulmonary blood volume. Cardiac output did not change, while ejection fraction declined during pacing. There was a fair correlation between the absolute change in pulmonary activity (or pulmonary blood volume) or the percentage of change in pulmonary activity over the control value with end-diastolic pressure when all the data points were evaluated (n = 74, r greater than 0.70). However, the scatter in the data precluded making accurate estimates of pressure changes from changes in radionuclide volume changes. We conclude that large changes in cardiac filling pressure must occur during atrial pacing, where cardiac output does not change, before visible pulmonary blood volume changes occur. This may limit the extrapolation of presumed pressure changes from known pulmonary blood volume when changes are small.

The effects of intracoronary administration of contrast materials on regional and global left ventricular (LV) function were assessed in anesthetized dogs with segmental myocardial ischemia produced by critical stenosis of the circumflex coronary artery. Effects caused by sodium meglumine diatrizoate (R76), sodium meglumine calcium metrizoate (ISO), and metrizamide were evaluated. In the nonischemic state R76 produced an early (0-10 seconds) decrease in LV contractility followed by a late (10-20 seconds) positive inotropic effect. In the presence of regional ischemia there was prolongation of the negative inotropic effect. ISO produced only positive inotropic effects without significant differences between responses in the nonischemic and ischemic states. Metrizamide produced almost no alterations in LV function.

Differential uptake of iodine containing radiographic contrast medium (I) in myocardial infarcts compared with normal mycardium has been detected by computerized transmission tomography (CTT). In this study the histologic and cellular distribution of I in ischemically damaged canine myocardium after intravenous administration of contrast material was examined by the use of scanning electron microscopy and energy dispersive X-ray microanalysis of fresh frozen cryosections. Analysis of individual cells in 6-mu thick sections mounted on carbon substrates showed that I was detectable in the ischemically damaged but not the normal myocardial cells. A decline in the potassium-to-sodium ratio confirmed the loss of membrane integrity in the ischemically damaged cells that accumulated I. These results indicate that I enters ischemically damaged but not normal myocardial cells suggesting that CTT scans after intravenous administration of contrast material may be capable of defining the area of the myocardium in which cells have lost membrane integrity after an ischemic injury.

Cardiac anatomy was defined by gated nuclear magnetic resonance (NMR) imaging at a magnetic field strength of 3.5 kGauss in eight normal subjects and 10 patients with chronic myocardial infarctions. Multisectional imaging was performed with the spin-echo technique and encompassed most of the left ventricle in an imaging time of 5 to 12 min. In all subjects internal cardiac structure was well delineated without the use of any type of contrast medium. The myocardial wall-blood interface was sharply defined, resulting in visualization of trabeculations, papillary muscle, and chordal structures in both ventricles. In patients with ischemic heart disease, the extent of postinfarctional wall thinning, aneurysms, and mural thrombi were depicted on NMR images. Images obtained with the second spin-echo (delay time = 56 msec) demonstrated high signal intensity in regions of the left ventricular chamber adjacent to the site of aneurysms or infarctions; this finding suggested stasis of blood in a region of akinesis or dyskinesis. The results of this study show that gated NMR is feasible as a technique for imaging the human heart and is capable of demonstrating a variety of left ventricular abnormalities associated with chronic myocardial infarction. NMR is a completely noninvasive technique for clinical imaging of the cardiovascular system.

Proton magnetic resonance (MR) spectroscopy with homonuclear editing was used to assess lactate accumulation in ischemic and anoxic hearts perfused according to the Langendorff method. An increase in the lactate signal was observed after 5 minutes of ischemia and after 10 to 20 minutes of anoxia. This study demonstrates that proton MR spectroscopy can be used to monitor the time course of MR-visible lactate levels in ischemic and anoxic isolated rat hearts.

In the canine model there exist major differences in the velocity-displacement relationships of systolic contraction between normal and ischemic myocardium. These differences are noninvasively measurable in vivo from video recordings of the fluoroscopic image of the heart, and can be detected within the time period of one cardiac cycle. Velocity data is plotted against the corresponding wall displacement on orthogonal axes (phase-space), producing characteristic loops which give an immediate visual indication of myocardial dysfunction.

Phosphorus-31 magnetic resonance spectroscopy (MRS) was used to monitor regional changes in high-energy phosphorus compounds and intracellular pH during 60 min of acute regional ischemia (acute occlusion of left anterior descending artery) and reperfusion in open-chest cats using a 1.2-cm two-turn coil sutured to the myocardium. During the 60-min ischemic phase, phosphocreatine (PCr) intensity was reduced to 47 +/- 4.9% (mean +/- SE) of control (p less than 0.01) by 15 min postocclusion while adenosine triphosphate (ATP) intensity decreased more slowly with the decrease (66 +/- 5.6%) achieving significance (p less than 0.05) only at 60 min postocclusion. Inorganic phosphate (Pi) increased to a maximum of 397 +/- 42% of control (p less than 0.01) while the pH decreased progressively from 7.36 +/- 0.02 to 6.02 +/- 0.14 (p less than 0.01). After release of occlusion PCr intensity recovered to 86 +/- 12% of the initial control value at 15 min postreperfusion but showed a subsequent downward trend to 79 +/- 8.8%. The ATP did not recover but tended to decline further during reperfusion. The Pi intensity decreased to 260 +/- 38% of control while the pH increased to 7.01 +/- 0.23 by 15 min postreperfusion. Thus, the reperfused irreversibly injured myocardium is characterized by persistent depletion of PCr and ATP and elevation of Pi. Phosphorus-31 MRS provides a nondestructive method for characterizing the reperfused irreversibly damaged myocardium.

To assess regional ventricular wall thickening, we studied 8 open-chest dogs using digital intravenous ventriculography at a control stage, after subtotal and total coronary occlusion, and then after isoproterenol administration. In 3 dogs, 2 pairs of myocardial thickness crystals were implanted. Correlations of measures of wall thickness and percentage of wall thickening with crystal measures were excellent at the base (r greater than or equal to 0.97) and near the apex (r greater than or equal to 0.97). Four areas of the inferoapical wall muscle were measured: the base, mid-wall, distal wall, and apex. Four chamber dimensions were also examined: the long axis, base decreased with ischemia. At completion occlusion, it was -24.6 +/- 6% at the base, -27.3 +/- 5% at the mid-wall, -27.1 +/- 5% at the distal wall, and -24.7 +/- 5% at the apex. Percent thickening decreased with occlusion, although greater at the base and mid-wall than at the distal wall and apex. With isoproterenol, end-diastolic thickness increased only at the apex, with little change at the base, distal wall, and mid-wall. Percent thickening increased. In general, ischemia produced increases in end-diastolic hemichords with little change in the long axis. Isoproterenol reduced the hemichords, although the long axis did not change. We conclude the digital intravenous ventriculograms can be used to assess changes in wall thickness with high degrees of accuracy. Asymmetric thickening occurred at rest, with ischemia and with inotropic stimulation, being greatest at the apex and least at the base.

Nine adult rats underwent occlusion of the left coronary artery (LCA) to assess the ability of a manganese chelate of N, N'-Bis (pyridoxal-5-phosphate) ethylenediamine-N, N'-diacetic acid (Mn-DPDP), to delineate acute myocardial ischemia. Hemodynamic effects of the contrast medium were tested in the isolated rat heart. Gated transaxial images of the heart at the mid-ventricular level were obtained using a 2 Tesla magnet. A TE of 20 msec and a TR of 1 R-R interval (approximately 250 msec) were used. Images were taken prior to injection of 400 mumol/kg of Mn-DPDP, 2 minutes after injection, and then at 15 minute intervals for one hour. The time between LCA occlusion and injection of contrast averaged 95 minutes. The signal intensity (SI) of normal myocardium was increased by 125 +/- 9% immediately after injection, and did not significantly vary over one hour. SI of ischemic myocardium increased by only 16 +/- 14% immediately after injection, gradually rising to 44 +/- 13% after one hour. Visual discrimination between normal and ischemic myocardium was obtained throughout the study. The percent contrast between normal and ischemic myocardium was 47.2 +/- 6% at 2 minutes after injection, gradually decreasing to a final value of 31.3 +/- 4%. No hemodynamic effects were produced in the isolated heart using concentrations in the perfusate several-fold higher than those expected to be produced by the intravenous injection of 400 mumol/kg Mn-DPDP. Mn-DPDP shows the potential for delineation of the jeopardy area resulting from coronary occlusion for at least one hour after injection of the agent.

We studied 90 patients with congestive myocardial disease documented at cardiac catheterization (46 idiopathic, 39 ischemic, and 5 hypertensive) who underwent M-mode and two-dimensional echocardiograms every 2-3 months for up to 7 years (mean 3.4 +/- 1.6 years, +/- 1 S.D.). All had angiographic evidence of severe left ventricular dysfunction (left ventricular ejection fraction less than 40%), and were on a variety of inotropic, diuretic, and vasodilating drugs. Only 9 were ingesting anticoagulants (5 warfarin and 4 aspirin), those on warfarin had documented pulmonary emboli or deep venous thrombosis. All but 4 patients were in normal sinus rhythm. Only one subject in this group was found to have a myocardial (left ventricular) thrombus. Postmortem examinations of 27 patients confirmed the ultrasound data. Thus, we conclude that cardiac thrombi are unusual in patients with congestive cardiomyopathies and rarely develop over the course of the illness even in the absence of chronic anticoagulation.

Dysprosium diethylenetriamine-pentaacetic acid-bis (methylamide) (DTPA-BMA), a new nonionic contrast medium for magnetic resonance (MR) imaging, produces signal loss on T2-weighted images because of induced magnetic field gradients. The potential of this agent to delineate myocardial ischemia was investigated in 10 rats with acute (30 minutes) occlusion of the left coronary artery. T2-weighted MR images were acquired before and for 1 hour after intravenous administration of 1 mmol/kg of Dy-DTPA-BMA. Before administration of the contrast medium, signal intensity (SI) in the ischemic region was significantly greater than that in the normal myocardium; however, the borders of the ischemic region were not consistently distinct. The contrast medium caused marked decrease in SI of normal myocardium (18% +/- 3% of the control value), only slight decrease in the jeopardized region (76% +/- 6% of the control value), and no discernible effects on heart rate or blood pressure. Substantial contrast between normal and ischemic myocardium persisted for 1 hour. Moderate signal loss was observed in skeletal muscle. Dy-DTPA-BMA has the potential to demarcate the myocardial area in jeopardy as a region of high signal intensity because it erases signal preferentially in the normal myocardium.

The effects of intracoronary injection of two nonionic contrast media (iohexol and metrizamide) on myocardial contraction and chemical composition of coronary sinus (CS) blood were compared with those caused by the standard ionic contrast material for coronary angiography, sodium meglumine diatrizoate (R76), in 14 anesthetized dogs. The effects of each agent on regional contractility were compared in the normal state and in the presence of a critical coronary artery stenosis. The three contrast media produced equivalent decreases in hematocrit and sodium (both NS), but R76 caused a greater increase in CS osmolality (p less than 0.02). R76 caused a significant decrease in CS potassium and ionized calcium (both p less than 0.001), but neither nonionic contrast medium caused a significant change in either potassium or calcium. In the normal state, R76 caused initial transient (less than 10 seconds) increases in both end-diastolic (p less than 0.006) and end-systolic segment length (p less than 0.02) and a decrease in rate of change of segment length (dL/dt) (p less than 0.002). The nonionic agents caused a mild increase in dL/dt (p less than 0.04) and a decrease in end-systolic segment length (p less than 0.03); both returned to control levels within 1 minute. In the presence of a stenosis, R76 caused a more severe and prolonged increase in end-diastolic and end-systolic segment lengths (p less than 0.03) and a decrease in dL/dt (p less than 0.002), which did not return to control within 2 minutes. The effects of the nonionic agents were similar in both normal and diseased states. We conclude that nonionic contrast media produce fewer alterations than ionic contrast media in coronary sinus blood chemistry and myocardial contractile state. The effect of ionic contrast media on regional contraction is accentuated in the presence of coronary artery stenosis.

An unusual case of an acquired coronary-to-bronchial artery communication is presented. Collateral flow to the lung was provided by the right coronary circulation following obstruction of pulmonary blood flow by chronic pulmonary emboli. A coronary steal phenomenon may have caused an exacerbation of cardiac symptoms by further reducing already compromised coronary blood flow in a patient with atherosclerotic coronary artery disease.

Cardiac-gated magnetic resonance (MR) imaging was performed in rats to determine the effects of manganese ethylenediaminetetraphosphonate (TP). Ten normal rats received Mn-TP in a dose of 50 mumol/kg through a tail-vein injection. Spin-echo MR images were obtained before and every 10 minutes after Mn-TP injection for 1 hour. Cardiac signal intensity (SI) increased more than 70% after Mn-TP injection and remained nearly unchanged 1 hour after injection. Myocardial T1 was 517 +/- 49 msec in eight control rats and 282 +/- 61 msec (P less than .001) in six rats 81 +/- 0 minutes after injection. Nine rats underwent occlusion of the left anterior descending coronary artery prior to MR imaging. Images were obtained before and 15, 30, and 60 minutes after Mn-TP injection. In normal myocardium, SI increased up to 82% and remained elevated for 1 hour. In ischemic myocardium, SI rose 11%, leading to a marked contrast between the two tissue zones. T1 was also different in the two regions: In normal tissue, it was 206 msec +/- 54; in ischemic tissue, 338 +/- 82 (P less than .001). With T1-weighted MR imaging, Mn-TP showed a potential for delineating the jeopardized area after acute myocardial ischemia.

Several different paramagnetic contrast agents have been investigated for use in myocardial MR imaging. Gd-DTPA, the most extensively studied agent, has been shown to improve the conspicuity of acute myocardial infarcts on MR images in experimental animals and humans. However, this agent is limited as a marker of perfusion because of its rapid elimination by renal excretion and equilibration within the extracellular fluid space. Future investigation of Gd-DTPA as a myocardial perfusion agent may involve rapid-scanning techniques to define time-dependent accumulation of the contrast agent in normal and ischemic myocardium during the first pass after IV injection. Nondiffusable paramagnetic agents and agents with prolonged retention in myocardium are being studied actively, but further tests of toxicity and metabolism are needed before clinical trials. Additional macromolecular-bound metal chelates will be tested in the future. It is hoped that these agents will allow detection of the jeopardized region of myocardium in the setting of acute ischemia, before the onset of myocardial edema.

Cross-sectional imaging techniques have the potential for measuring left ventricular (LV) wall thickness (WTh) dynamics. This proposition was assessed in a canine experimental model, using prospectively gated computed tomography (CT) scans before and after occlusion of a coronary artery. Gated CT scans detected loss of wall thickening in the LV anterior segment immediately after occlusion of the left anterior descending coronary artery in two dogs. After demonstrating the feasibility of using gated CT scans to demonstrate ischemic functional abnormalities by monitoring wall thickness changes, we assessed the relationship between regional wall thickening dynamics and coronary blood flow in eight anesthetized dogs. Graded circumflex (Cx) coronary artery stenosis (CAS) was produced while sonomicrometer crystals continuously recorded LV WTh and extent of wall thickening (EWTh) in the anterior descending and the Cx distributions. The first significant change in EWTh in the ischemic segment occurred at 33% decrease in CBF (P less than .05) which corresponded to an 80% CAS. At 33% decrease in CBF, there was a concomitant increase in EWTh in the normal segment. In conclusion, we have demonstrated the feasibility of using gated CT to detect myocardial ischemia by monitoring WTh dynamics. Physiologic studies document a close relationship between regional wall thickening dynamics and coronary blood flow and should provide a basis for interpretation of dynamic cross-sectional images of the left ventricle in ischemic heart disease.

The purposes of this study were to evaluate the effects of acute myocardial ischemia with reperfusion on T1 (spin-lattice) nuclear magnetic resonance (NMR) relaxation times in a canine model and correlate these changes with bulk myocardial water content (%H2O). In 15 dogs the left anterior descending coronary artery was occluded for either 40 minutes (n = 5), 1 hour (n = 5), or 2 hours (n = 5). In 15 additional dogs, matched occlusion periods were followed by 3 hours of reperfusion. T1 of tissue from normal and ischemic myocardium was measured in vitro with a 2.5 kg NMR spectrometer. In the reperfusion animals, the 2-hour group showed significant increases in %H2O and T1 when the ischemic segment of myocardium was evaluated (both p less than 0.01). All but one animal in the 1-hour (reperfusion) group showed increases in both %H2O or T1 in the ischemic segment of myocardium when compared to control segments. The mean values from the ischemic myocardium in the 1-hour group were significantly higher than the values from the matched control segment for %H2O (p less than 0.05) and T1 (p less than 0.05). In the group undergoing 40 minutes of ischemia followed by 3 hours of reperfusion, neither %H2O nor T1 changed significantly. In the nonreperfused animals, neither T1 nor %H2O content increased significantly after 40 minutes. Significant increases were seen in the 1-hour (p less than 0.05) and 2-hour groups (without reperfusion) (p less than 0.01). In addition, the 2-hour occlusion followed by reperfusion animals had significantly greater T1 relaxation times and %H2O than control ischemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Using a new computed tomographic (CT) scanner design that uses a rapidly moving focused electron beam, 50-ms CT scans were obtained at 2 axial levels simultaneously through the hearts of 6 dogs in order to analyze left ventricular (LV) wall thickness and cross-sectional chamber area after acute occlusion of the left anterior descending coronary artery (LAD). Ten or fifteen 50-ms CT scans (rate of 17 scans/s through the middle of the left ventricle were performed in 1 second (cine acquisition) during intravenous administration of contrast medium at rest, 60 seconds after acute occlusion of the LAD, and 60 seconds after release of the occlusion. The percent extent of systolic wall thickening of the potentially ischemic anterior segment was 37 +/- 15% (+/- standard deviation) in the control state and -5 +/- 6.5% during LAD occlusion (p less than 0.01). There was no significant difference in the percent change in LV luminal area from end-diastole to end-systole between the control state (50 +/- 19%) compared with LAD occlusion (47 +/- 21%). There were no significant differences in the extent of systolic wall thickening or LV luminal area between the control state and 60 seconds after release of occlusion. The alterations in regional myocardial function during acute ischemia are characterized by wall thinning during systole in the jeopardized segment and no significant change in global LV function. These features can be assessed by cine computed tomography during a solitary heart cycle.

The potential role of computerized transmission tomography (CTT) in the detection and quantitation of acute myocardial ischemic damage was assessed in 42 excised canine hearts at 2 hours, 8 hours, and 48 hours after coronary occlusion. The CTT scan detected by myocardial damage that was 2-48 hours old each time the presence of regional ischemia was confirmed by histochemical straining or epicardial electrocardiographic mapping. Intravenous administration of contrast material enhanced the x-ray attenuation of areas of ischemic damage of 8 and 48 hours duration compared with normal myocardium, but enhanced only normal myocardium in those of 2 hours duration. Volumetric estimation of the extent of damage from the CTT scans in dogs with ischemia of 48 hours duration showed a close linear relationship with the morphometric volume in the absence of contrast material. Quantitation of the area of ischemic damage from the CTT scan after contrast administration resulted in substantial underestimation of the volume of damaged tissue.

Digital i.v. ventriculography in conjunction with rapid atrial pacing was used to assess the effects of ischemic stress on global and regional function in 22 patients referred for cardiac catheterization (5 had normal coronary arteries and 17 had greater than 70% diameter reduction of at least 1 major coronary artery). End-diastolic, end-systolic and stroke volume indexes and the ejection fraction were determined by an area-length technique from the mask mode images before and after pacing. In addition, segmental responses were quantitated using a radial shortening method. Subjects with normal coronary arteries showed no overall change in the postpacing volume or ejection fraction indexes. Coronary patients showed no overall change in postpacing end-diastolic volume (86 +/- 25 ml/m2 at control vs 90 +/- 31 ml/m2 after pacing, difference not significant), but there was a significant increase in end-systolic volume (25 +/- 15 ml/m2 at control vs 32 +/- 18 ml/m2 after pacing, p less than 0.005) and a decrease in ejection fraction (72 +/- 11% at rest vs 64 +/- 18% after pacing, p less than 0.025). Furthermore, quantitative deterioration in wall motion was seen in 14 of 17 coronary patients (82%) and in none of the normal patients. Analysis of segmental wall motion was the most sensitive diagnostic variable. A combination of atrial pacing stress testing and digital i.v. ventriculography is useful in detecting functionally significant coronary disease through quantitation of global and regional dysfunction which does not require arterial cannulation.

The incidence of significant arrhythmias and ST segment changes during barium enema examination (BE) was evaluated by Holter monitoring of 58 unselected patients over the age of 60 years. Forty percent of the group developed new significant arrhythmias of which the most common were frequent and/or multifocal premature ventricular contractions. Seven percent demonstrated ST segment depression. Administration of glucagon did not diminish the incidence of arrhythmias. Predictive factors for ECG abnormalities were advancing age, abnormal pre-BE-ECG, and pre-BE orthostatic hypotension. Analysis of arhythmias and response to phywiologic tension. Analysis of arrhythmias and response to physiologic manoeuvres suggested that the abnormalities were related to increased sympathetic tone which may be intensified by hypovolaemia resulting from routine bowel preparation.