Effects of cardiac depression and of anesthesia on the myocardial action of a cardiac glycoside.

The effects of ouabain (G-strophanthin) 20 mug/kg, on left ventricular (LV) pressure (P), diameter (D), velocity of contraction (dD/dt), and dP/dt were studied in conscious dogs instrumented with ultrasonic diameter gauges and miniature pressure gauges. The effects of ouabain were compared on separate occasions in the same dogs after cardiac depression with propranolol, 3.0 mg/kg, and also after general anesthesia with Na pentobarbital, 30 mg/kg. Maximal pressor effects were observed in the first 10 min, but maximal effects on the contractile state occurred at 30 min after ouabain. At this time, in conscious dogs, ouabain had increased LV isolength systolic pressure by 5%, LV isolength velocity by only 9%, and LV (dP/dt)/P by 21%, while end systolic diameter (ESD) decreased slightly and end diastolic diameter (EDD) and heart rate (HR) were unchanged. After anesthesia, ouabain increased LV systolic pressure by 8%, velocity 32%, (dP/dt)/P by 47%, and ESD decreased by 1.2 mm while EDD rose slightly and HR fell by 26 beats/min. Returning HR to control with atrial pacing decreased EDD 0.9 mm below control. After cardiac depression with propranolol, ouabain caused responses similar to those observed in the anesthetized dogs. Thus, the cardiac glycoside was found to exert only minor inotropic effects on the nonfailing heart of conscious dogs but far more striking inotropic responses in the anesthetized state.

Left ventricular response to severe exertion in untethered dogs.

The left ventricular response to severe exercise was studied by telemetering direct measurements of left ventricular diameter (D) and pressure (P) and aortic blood flow from healthy dogs running at speeds up to 30 mph in the field. Severe exercise increased cardiac output from 101 to 478 ml/kg per min, heart rate from 95 to 297 beats/min, stroke volume from 31 to 44 ml, left ventricular isolength (iso) systolic pressure from 120 to 186 mm Hg, left ventricular end diastolic pressure from 6 to 18 mm Hg, and left ventricular end diastolic diameter from 58.9 to 60.1 mm, while end systolic diameter decreased from 53.0 to 52.2 mm. Two indices of myocardial contractility, (dP/dt)/P increased from 37 to 92 sec(-1), while dD/dt, the velocity of myocardial fiber shortening at isolength, rose from 54 to 119 mm/sec. All of these changes were statistically significant. When, in resting dogs, heart rate was first raised to exercise levels by electrical stimulation, severe exercise subsequently increased left ventricular end diastolic diameter more profoundly, from 55.7 to 59.7 mm, while end systolic diameter remained constant and the increases in left ventricular pressure, (dP/dt)/P and velocity(iso) were roughly comparable to those occurring during exercise in spontaneous rhythm. After propranolol, 1.0 mg/kg, severe exercise resulted in significantly smaller increases in cardiac output (from 82 to 240 ml/kg), in heart rate (from 87 to 186 beats/min), in left ventricular pressure(iso) (from 122 to 150 mm Hg), in (dP/dt)/P (from 32 to 44 sec(-1)), in velocity(iso) (from 47 to 59 mm/sec), and in slightly greater increases in end diastolic diameter, from 59.8 to 62.0 mm and pressure from 8 to 22 mm Hg, while end systolic diameter did not change significantly.Thus, the left ventricle responds to severe exercise with near maximal increases in heart rate and contractility, while significant increases in end diastolic diameter (Frank-Starling mechanism) and stroke volume occur as well. When heart rate was held constant severe exercise produced similar increases in contractility but end systolic size failed to diminish and the increases in end diastolic size were greater. Beta adrenergic receptor blockade interfered with the chronotropic and particularly the inotropic response to severe exercise and while the participation of the Frank-Starling mechanism was somewhat greater, the latter was not sufficient to increase cardiac output normally.

Direct and reflex effects of nitroglycerin on coronary and left ventricular dynamics in conscious dogs.

The effects of intravenous and sublingual glyceryl trinitrate (nitroglycerin), 40 mug/kg, were studied on coronary blood flow and resistance, left ventricular (LV) pressures (P) and diameters (D), rate of change of pressure (dP/dt), (dP/dt)/P, and on the velocity (V) of myocardial fiber shortening in conscious dogs. Nitroglycerin i.v. caused substantial coronary vasodilatation prior to any changes in systemic hemodynamics. Mean coronary flow increased by a maximum of 47 ml/min and coronary sinus P(o2) rose from 16 to 26 mm Hg while pressure and diameter began to fall, and heart rate began to rise. After the maximal fall in mean arterial pressure (-26 mm Hg), a secondary peak in coronary flow occurred which was associated with increases in heart rate (100 beats/min), (dP/dt)/P (22%), and isolength V (12%). Beta blockade prevented the reflex increases in contractility but only a part of the reflex tachycardia; the remainder was prevented by cholinergic blockade. Maintaining heart rate constant minimized the decreases in LV D and increases in contractility. When the reflex inotropic and chronotropic effects were prevented by a combination of atrial pacing and beta blockade the early coronary vasodilatation was unaltered, but the later coronary vasodilatation was minimized. Thus i.v. nitroglycerin in the conscious dog exerts a potent direct coronary vasodilating action and also a secondary coronary vasodilation caused by reflex increases in contractility and heart rate. The decreases in diameter are largely the result of tachycardia. Sublingual nitroglycerin produced directionally similar, but quantitatively lesser effects on coronary flow and resistance, LV D, LV P, and contractility.

Alterations in the baroreceptor reflex in conscious dogs with heart failure.

The effectiveness of the baroreceptor reflex in conscious dogs with experimental cardiac hypertrophy and heart failure was compared with that in a group of normal conscious dogs. Cardiac hypertrophy and heart failure were produced by tricuspid avulsion and progressive pulmonary stenosis. The sensitivity of the baroreceptor reflex to transient hypertension was assessed by determining the slope of the regression line relating the prolongation of the R-R interval to the rise in systolic arterial pressure during the transient elevation of arterial pressure induced by an intravenous injection of 1-phenylephrine. The mean slope averaged 22.4+/-2.3 msec/nm Hg in 16 normal animals. 23.1 +/-1.5 in five sham-operated animals, and was significantly reduced to 8.3 +/-0.8 in 10 dogs with hypertrophy alone (P < 0.001), and to 3.3+/-0.5 in nine dogs with heart failure (P < 0.001). The response to baroreceptor hypotension was compared during bilateral carotid artery occlusion (BCO) in six normal and six heart failure dogs previously instrumented with Doppler flow transducers on the superior mesenteric and renal arteries. During BCO, in normal dogs arterial pressure increased 52+/-4 mm Hg, heart rate 33+/-2 beats/min, mesenteric resistance 0.17+/-0.03 mm Hg/ml per min, and renal resistance 0.37+/-0.10 mm Hg/ml per min. In the heart failure group all of these variables increased significantly less (P < 0.01); arterial pressure rose 25 +/-3 mm Hg, heart rate 13 +/-4 beats/min, mesenteric resistance 0.04+/-0.007 mm Hg/ml per min, and renal resistance 0.18+/-0.09 mm Hg/ml per min.Thus, in heart failure, all measured systemic and regional circulatory adjustments consequent to baroreceptor hypo- and hypertension are markedly attenuated. This study demonstrates a profound derangement of a major cardiovascular control mechanism in experimental heart failure.

The peripheral vascular response to severe exercise in untethered dogs before and after complete heart block.

The peripheral vascular response to severe exercise was studied in 11 healthy conscious dogs instrumented with Doppler ultrasonic flow probes on the mesenteric, renal, and iliac arteries, and miniature pressure gauges in the aorta. The response to severe exercise was restudied in six of these dogs after recovery from a second operation producing complete heart block by the injection of formalin into the atrioventricular (AV) node. Three of these dogs also exercised while their ventricles were paced at rates of 100/min and 200/min. The untethered normal dogs ran at speeds of 15-25 miles/hr behind a mobile recording unit for a distance averaging 1.5 miles, while continuous measurements of arterial blood pressure and blood flow were telemetered and recorded on magnetic tape. Severe exercise in normal dogs increased heart rate from 84 to 259/min, arterial pressure from 89 to 140 mm Hg, flow resistance in the mesenteric and renal beds by 59 and 52% respectively, and iliac blood flow 479% above control, while mesenteric and renal blood flows remained constant and iliac resistance decreased by 73%. In dogs with complete AV block, severe exercise at speeds of 10-18 miles/hr increased heart rate from 47 to 78/min, mean arterial pressure from 81 to 89 mm Hg, iliac flow 224%, resistance in the renal bed by 273%, and mesenteric bed by 222% while it decreased blood flow in mesenteric and renal beds by 61 and 65% respectively, and iliac resistance by 62%. A similar response occurred during exercise with pacing at 100/min, but when paced at 200/min a more normal exercise response reappeared. Thus, in normal dogs the peripheral vascular response to severe exercise involved increases in heart rate, arterial pressure and visceral resistance but visceral blood flow did not decrease. In dogs with heart block, where the ability to increase heart rate is severely compromised, compensatory reduction of mesenteric and renal blood flows occurred.

Extent of carotid sinus regulation of the myocardial contractile state in conscious dogs.

The effects of bilateral carotid artery occlusion (BCO) and carotid sinus nerve stimulation (CSNS) on left ventricular (LV) pressure (P), diameter (D), velocity of contraction (V), rate of change of pressure (dP/dt), and cardiac output were studied in conscious dogs instrumented with ultrasonic diameter gauges, miniature pressure gauges, and aortic electromagnetic flow transducers. The effects of BCO and CSNS were also studied after automatic blockade and were compared to similar alterations in pressure produced by norepinephrine, methoxamine, and nitroglycerin. When heart rate was maintained constant with atrial stimulation, BCO had little effect on ventricular contractility, increasing isolength systolic pressure (LV P(iso)) by 36% while isolength velocity of myocardial shortening (V(iso)) decreased by 12% and (dP/dt)/P fell by 8%. These effects could be explained largely by vasoconstriction, since elevating systolic pressure with methoxamine produced similar results, while norepinephrine increased V(iso) by 36% and (dP/dt)/P by 56%. CSNS produced directionally opposite results from BCO; it decreased P(iso) by 15%, V(iso) increased by 11%, while (dP/dt)/P remained almost constant. These effects may be explained largely by vasodilatation since reducing systolic pressure to the same level with nitroglycerin produced similar results. When peripheral vasoconstriction was minimized by phenoxybenzamine pretreatment. BCO produced a slight positive inotropic effect (P(iso) increased by 8%, V(iso) by 4%, and (dp/dt)/P by 10%), while CSNS produced a slight negative inotropic effect (P(iso) decreased by 3%, V(iso) decreased by 5%, and (dP/dt)/P by 7%).Thus, in the normal, healthy, conscious dog, the carotid sinuses exert relatively little control of the inotropic state of the left ventricle; moreover, this small inotropic action is masked by the more powerful effects on peripheral resistance.

Extent of regulation of the heart's contractile state in the conscious dog by alteration in the frequency of contraction.

The effects of alterations in the frequency of contraction over the range from 94 to 220/min on left ventricular pressure, diameter, and dP/dt were studied in 10 dogs instrumented with ultrasonic diameter ganges and miniature pressure gauges. The same dogs were studied on separate days in the conscious state, after general anesthesia with pentobarbital Na, 30 mg/kg, and in the conscious state after pretreatment with propranolol, 3 mg/kg. End diastolic diameter was maintained constant during alterations in frequency by infusing saline intravenously. The maximum increases in peak dP/dt and dP/dt/P in the conscious state were 14 and 10%, respectively. After anesthesia, raising the frequency of contraction from 122 to 220/min caused maximum increases in peak dP/dt and dP/dt/P of 36 and 30%, respectively. In the conscious state after cardiac depression by propranolol, the maximum increases in peak dP/dt and dP/dt/P were 23 and 23%, respectively. Thus, increasing the frequency of contraction of the normal heart of the conscious dog causes only a slight inotropic effect, but this effect is significantly greater in the presence of myocardial depression produced by anesthesia with pentobarbital Na or in the conscious animal after a myocardial-depressing dose of propranolol.

Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media.

BACKGROUND: Because ischemically injured myocardium is frequently composed of viable and nonviable portions, a method to discriminate the two is useful for clinical management. METHODS AND RESULTS: Ischemically injured myocardium was characterized with extracellular nonspecific (Gd-DTPA) and necrosis-specific (mesoporphyrin) MR contrast media in rats. Relaxation rates (R1) were measured on day 1 and day 2 by inversion-recovery echoplanar imaging. Spin-echo imaging was used to define contrast-enhanced regions and regional wall thickening. Gadolinium concentration, area at risk, and infarct size were measured at postmortem examination. DeltaR1 ratio (DeltaR1(myocardium)/DeltaR1(blood)) after administration of Gd-DTPA was greater in ischemically injured myocardium (1.20+/-0.15) than in normal myocardium (0.47+/-0.05, P<0.05), which was attributed to differences in gadolinium concentration and water content. The Gd-DTPA-enhanced region on day 2 was larger (32.8+/-0.9%) than true infarction as demonstrated by triphenyltetrazolium chloride (TTC) (24.6+/-1.4%, P<0.001, r=0.21). Bland-Altman analysis revealed that the Gd-DTPA-enhanced region overestimated true infarct size by 7.8+/-5.9%. On the other hand, the mesoporphyrin-enhanced region (26.9+/-1.8%, P=NS, r=0.87) and true infarct size were identical. The difference in the areas demarcated by the 2 agents is the peri-infarction. Systolic and diastolic MR images revealed no wall thickening in the mesoporphyrin-enhanced region (0.3+/-3.3%) but reduced thickening in the Gd-DTPA-enhanced rim (8.5+/-5.5%, P<0.05). CONCLUSIONS: The Gd-DTPA-enhanced region encompasses both viable and nonviable portions of the ischemically injured myocardium. The Gd-DTPA-enhanced area overestimated infarct size, but the mesoporphyrin-enhanced area matched true infarct size. The salvageable peri-infarction zone can be characterized with double-contrast-enhanced and functional MR imaging; the mismatched area of enhancement between the 2 agents shows residual wall thickening.

Sequential magnetic resonance monitoring of pulmonary flow with endovascular stents placed across the pulmonary valve in growing Swine.

BACKGROUND: Patients with endovascular stent implantation for the treatment of right ventricular outflow tract obstruction are often left with incomplete relief of the obstruction and significant pulmonary regurgitation. A noninvasive and reproducible method for monitoring such patients is desirable. MRI in the presence of a stent, however, has to overcome the problem of potential metallic artifacts. METHODS AND RESULTS: Under x-ray fluoroscopic guidance, endovascular nitinol stents were placed across the pulmonary valve in 6 young pigs to induce pulmonary regurgitation. Five additional pigs served as controls. Initial MRI was performed after 2 days (13.5+/-1.8 kg) and follow-up after 3 months (32+/-2.9 kg). Pulmonary flow volumes and regurgitant fraction were quantified by velocity-encoded cine (VEC) MRI through (VEC-TS) and distal to (VEC-DS) the stent. VEC-TS was compared with VEC-DS and volumetric measurements of left and right ventricular stroke volumes provided by cine MRI ("gold standard"). Antegrade and retrograde pulmonary flow volumes by VEC-TS were slightly but significantly less than those with VEC-DS and cine MRI. Excellent correlations (r>0.97) for phasic pulmonary flow volumes as measured by VEC-TS and VEC-DS were shown. Pulmonary regurgitant fraction increased from 32.8+/-15% to 49.6+/-17% (P<0.05) over the course of 3 months with VEC-TS. CONCLUSIONS: MRI demonstrates the progression of pulmonary regurgitation in growing swine. VEC MRI has the ability to quantify pulmonary blood flow inside the lumen of nitinol stents. MRI appears to be ideally suited for monitoring patients with endovascular nitinol stents in the pulmonary artery or pulmonary valve position.

Magnetic resonance-based assessment of global coronary flow and flow reserve and its relation to left ventricular functional parameters: a comparison with positron emission tomography.

BACKGROUND: Measurement of coronary sinus blood flow (CSF) by phase-contrast magnetic resonance (PC-MR) imaging at rest and during hyperemia may allow noninvasive assessment of global coronary hemodynamics. METHODS AND RESULTS: Sixteen healthy volunteers (age, 22 to 32 years) were examined with MR and PET in random order within 1 to 2 days. At rest and during hyperemia (dipyridamole 0.56 mg/kg), CSF was measured by a cine PC-MR technique (temporal resolution, 40 ms; spatial resolution, 1.25x0.8 mm(2)), and myocardial blood flow (MBF) was measured by [(13)N]NH(3) PET. PET and MR agreed closely for coronary flow reserve (CFR; mean difference, 2.2+/-14.7%; Bland-Altman method). CSF divided by either total left ventricular mass or an estimate of drained myocardium (LVM(drain)) correlated highly with PET flow data (r=0.93 and 0.95, respectively) and with measures of oxygen demand, ie, heart rate, afterload-corrected fiber shortening, and peak systolic stress determined by MR (overall correlation coefficients, 0.81 and 0.87, respectively, multivariate analysis). CSF/LVM(drain) did not differ significantly from PET-derived MBF (difference, 3.6+/-16.6%). In orthotopic heart transplant recipients (n=9), CFR was reduced and blood supply-demand relationships at rest were shifted toward higher flows (P<0.0001). CONCLUSIONS: This integrated MR approach allows comprehensive assessment of autoregulated and hyperemic coronary flow and is suitable for serial measurements in patients. In transplanted hearts, elevated resting flow is the major cause of reduced CFR.

Evaluation of right ventricular early diastolic filling by cine nuclear magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

Numerous studies have established abnormalities in systolic and diastolic function of the left ventricle in hypertrophic cardiomyopathy. A consistent feature of this disease is reduced diastolic function of the left ventricle, but little information is available regarding right ventricular function in this disease. Cine nuclear magnetic resonance (NMR) imaging has been found to be effective for measuring right ventricular volumes and therefore was used to assess early diastolic filling of the right ventricle in patients with hypertrophic cardiomyopathy. Right ventricular time-volume curves were obtained from cine NMR images in 10 patients with hypertrophic cardiomyopathy and 8 normal subjects. Right ventricular volume was calculated with use of Simpson's algorithm at approximately 18 phases of the cardiac cycle and, from the curve, peak filling rate and filling fraction during the first third of diastole were determined. In patients with hypertrophic cardiomyopathy, peak filling rate tended to be less (176 +/- 46 vs. 305 +/- 50 ml/s, p less than 0.01) and filling fraction decreased (39.5 +/- 13.8 vs. 74.5 +/- 13.3%, p less than 0.01) in comparison with values in normal subjects. Thus, analysis of right ventricular time-volume curves obtained by using cine NMR imaging demonstrated diastolic dysfunction of the right ventricle in hypertrophic cardiomyopathy.

Evaluation of pulmonary blood supply by nuclear magnetic resonance imaging in patients with pulmonary atresia.

Nuclear magnetic resonance (NMR) imaging defines the blood pool without the need for contrast medium. Consequently, it may be useful for defining the pulmonary circulation in patients with pulmonary atresia, in whom opacification of these vessels can be problematic. Ten patients with pulmonary atresia were evaluated by gated NMR imaging. The morphology of the right ventricular outflow tract, the size and the course of the central pulmonary vessels and the source of the collateral supply to the lung were assessed. Central pulmonary arteries were identified and measured in 9 of the 10 patients. One patient had no detectable central pulmonary arteries. Angiography confirmed the NMR findings in all but two patients, in whom NMR scanning visualized a main pulmonary artery that was not seen on angiography. Collateral arteries arising from the aorta or the arch vessels, as well as intracardiac malformations and aortic arch anomalies, were identified in all 10 patients. In six patients with palliative surgery, NMR imaging correctly demonstrated all patent shunts. Nuclear magnetic resonance imaging appears to be an effective noninvasive technique for evaluating patients with pulmonary atresia. However, tomographic thickness and spatial resolution are still limiting factors for this technique in infants.

Delineation of acute myocardial infarction with dysprosium DTPA-BMA: influence of dose of magnetic susceptibility contrast medium.

OBJECTIVES: The contrast enhancement of acutely infarcted myocardium produced by the nonionic magnetic susceptibility-enhancing agent dysprosium diethylenetriamine pentaacetic acid-bis-methylamide (DyDTPA-BMA [S-043 Injection]) was assessed in the current study to establish the lowest dose that would yield optimal contrast between normal and acutely infarcted myocardium. BACKGROUND: Magnetic susceptibility contrast agents enhance differences between normal and ischemic tissue by reducing the signal of the normally perfused tissue to which they distribute. METHODS: Acute myocardial infarctions were produced by ligation of the left coronary artery. At 3 to 4 h after occlusion, a dose of 0.1, 0.3 or 0.5 mmol/kg of DyDTPA-BMA was injected intravenously into eight rats each in group 1, 2 or 3, respectively; a fourth group of seven rats served as a control group. Nuclear magnetic resonance (NMR) transverse relaxation time (T2)-weighted images (electrocardiographically gated to every 5th beat, echo delay time [TE] = 60 ms) were acquired before and for 1 h after administration of contrast agent. RESULTS: Images obtained before the injection of contrast agent showed moderate differences in signal intensity between normal and infarcted myocardium (p < 0.05). The contrast enhancement and the duration of delineation between infarcted and normal myocardium produced by this agent were dose dependent. At doses of 0.1, 0.3 and 0.5 mmol/kg, DyDTPA-BMA produced signal loss in normal myocardium: 63 +/- 5%, 41 +/- 4% and 28 +/- 4% of the baseline values, respectively, without any significant reduction in signal intensity of the infarcted region. The reduction in signal of normal myocardium and delineation of the infarct persisted for 5 min at a dose of 0.1 mmol/kg, for 20 min at a dose of 0.3 mmol/kg and for 40 min at a dose of 0.5 mmol/kg. No change in signal intensity or signal intensity ratio between normal and infarcted myocardium was observed in the control group during the same observation period. CONCLUSIONS: These results suggest that low doses of this agent, comparable to those of longitudinal relaxation time (T1)-enhancing agents, can delineate acutely infarcted myocardium. A dose of 0.3 mmol/kg of DyDTPA-BMA (S-043 Injection) provides reasonably persistent demarcation of acute myocardial infarction. Because this dose dramatically suppresses the NMR signal of normal myocardium, it shows the infarcted region as a region of high intensity (bright spot) on NMR images.

Computed tomography of the heart: evaluation of anatomy and function.

Diseases of the heart and blood vessels represent one of the most challenging problems for advanced diagnostic imaging systems. Computed tomographic scanning is potentially an ideal cardiac imaging modality since it is a cross-sectional imaging method with very high resolution. Currently available computed tomographic scanners have exposure speeds of 1 to 5 seconds, which are inadequate for the majority of cardiovascular imaging applications. Nevertheless, a variety of limited computed tomographic scanning techniques have been successfully performed in selected patient subgroups. These methods require the administration of contrast medium injected or infused into a peripheral vein, combined with either dynamic computed tomographic scanning or some form of electrocardiographic gated computed tomography. The newer conventional computed tomographic scanners can display anatomic structures in the heart and great vessels with considerable fidelity and provide not only cross-sectional displays but also, by means of computer manipulation, any selected reconstructed images in oblique, coronal or sagittal projections. Feasibility studies indicate improved accuracy of computed tomographic measurements of cardiac chamber volumes. Physiologic measurements include estimation of shunt flows and cardiac output and analysis of myocardial wall thickening. The full potential of computed tomography should be reached once fast, multiple slice, computed tomographic scanners using scanning electron beam techniques become available. The prototype CVCT (cine computed tomographic C-100 scanner) designed at the University of California, San Francisco, is now undergoing evaluation. This instrument images up to eight contiguous slices at the rate of 16 to 24 images/s. The computed tomographic scanner specifically designed for cardiac imaging should extend the utility of computed tomography in the evaluation of cardiac diseases and the study of cardiovascular physiology.

Measurement of ventricular volumes in the dog by nuclear magnetic resonance imaging.

Nuclear magnetic resonance (NMR) imaging is a new, noninvasive approach for imaging the cardiovascular system. Being a three-dimensional technique, NMR imaging has the capability of measuring volumes without the need for assumptions regarding ventricular geometry. In this study, the technique was validated in 19 excised dog hearts, filled with silicone-rubber, imaged using a multislice spin-echo sequence. The volume of the cavity in each slice was calculated from the number of pixels outlined for each slice multiplied by the pixel volume. Ventricular volumes measured by NMR imaging were highly correlated with cast volumes measured by water displacement: right ventricle (RV):RVNMR = 1.05 RVcast - 1.62; r = 0.99, SEE = 0.96 ml; left ventricle (LV):LVNMR = 0.98 LVcast + 0.35, r = 0.98, SEE = 1.48 ml. After validation in casts, NMR imaging volumes were measured in eight living dogs using a multiphasic gated technique to obtain images at 5, 105, 205, 305 and 405 ms after the QRS complex. Cardiac output (CO) and stroke volume (SV) measured by NMR imaging were significantly correlated with thermodilution (TD) measurements (CONMR = 0.63 COTD + 0.51 liters/min; r = 0.78, SEE = 0.57 liters/min; SVNMR = 0.67 SVTD + 1.95 ml; SEE = 5.58 ml). Right and left stroke volumes were closely related (LVSVNMR = 0.9 RVSVNMR + 1.75; r = 0.94, SEE = 4.32 ml), with the slope and intercept of the regression line showing no difference from 1 and 0, respectively. However, volumes determined by NMR imaging underestimated the thermodilution measurements, presumably reflecting the inability to obtain a true systolic image with the present sampling rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive evaluation of global left ventricular function with use of cine nuclear magnetic resonance.

Previous reports have validated the accuracy of nuclear magnetic resonance (NMR) imaging for quantitating ventricular volumes and myocardial mass. In this study, a new rapid NMR imaging method, cine NMR imaging, was used to compare left ventricular volumes determined from the transverse plane and short-axis plane in healthy volunteers and patients with dilated cardiomyopathy. With use of the short-axis plane, left ventricular mass at end-systole and end-diastole were determined and left ventricular systolic wall thickening at three different levels was assessed. For validation in the current study, cine NMR imaging and two-dimensional echocardiographic measurements of left ventricular volumes were correlated. Left ventricular volumes of the normal volunteers (end-systolic volume = 34 +/- 3.8 ml, end-diastolic volume = 90.4 +/- 7.2 ml) and patients with cardiomyopathy (end-systolic volume = 173 +/- 28.3 ml, end-diastolic volume = 219.5 +/- 29.6 ml) obtained in the transverse plane were nearly identical to those obtained in the short-axis plane (normal volunteers, end-systolic volume = 30.3 +/- 3.5 ml, end-diastolic volume = 84.7 +/- 7.0 ml and patients with cardiomyopathy, end-systolic volume = 179.1 +/- 27.8 ml, end-diastolic volume = 227 +/- 30.9 ml) and correlated highly (r = 0.91) with volumes obtained by two-dimensional echocardiography. Assessment of left ventricular mass over a broad range using cine NMR imaging in a short-axis plane was identical at end-systole (normal volunteers, 117 +/- 10 g; patients with cardiomyopathy, 202 +/- 20 g) and end-diastole (normal volunteers, 115 +/- 10 g; patients with cardiomyopathy, 194 +/- 21 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of severity of myocardial injury on distribution of macromolecules: extravascular versus intravascular gadolinium-based magnetic resonance contrast agents.

OBJECTIVES: This study sought to 1) compare the distribution of extravascular (573 Da) and intravascular (92 kDa) magnetic resonance (MR) contrast agents in reperfused infarcted myocardium, and 2) investigate the effect of injury severity on these distribution patterns. BACKGROUND: Myocardial distribution of low and high molecular weight contrast agents depends on vascular permeability, diffusive/convective transport within the interstitium and accessibility of the intracellular compartment (cellular integrity). METHODS: To vary the severity of myocardial injury, 72 rats were subjected to 20, 30, 45 or 75 min (n = 18, respectively) of coronary artery occlusion. After 2 h of reflow, the animals received either 0.05 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (Gd-DTPA-BMA) (n = 24), (Gd-DTPA)30-albumin (n = 24) or saline (control group, n = 24). Three minutes after injection, the hearts were excised and imaged (spin-echo imaging parameters: repetition time 300 ms, echo time 8 ms, 2-tesla system), followed by triphenyltetrazolium chloride staining for infarct detection and sizing. RESULTS: Histomorphometric and MR infarct size (expressed as percent of slice surface) correlated well: r = 0.96 for Gd-DTPA-BMA; r = 0.95 for (Gd-DTPA)30-albumin. On Gd-DTPA-BMA-enhanced images, reperfused myocardial infarctions were homogeneously enhanced. The ratio of signal intensity of infarcted/ normal myocardium increased with increasing duration of ischemia (overall p < 0.0001, analysis of variance [ANOVA]), indicating an increase in the distribution volume of Gd-DTPA-BMA in postischemic myocardium. On (Gd-DTPA)30-albumin-enhanced images, reperfused infarctions consisted of a bright border zone and a less enhanced central core. The extent of the core increased with increasing duration of ischemia (overall p value < 0.0001, ANOVA). CONCLUSIONS: At 2 h of reperfusion, the distribution of MR contrast agents in postischemic myocardium is 1) specific for extravascular and intravascular agents, and 2) modulated by the duration of ischemia.

Myocardial infarct size determined by computed transmission tomography in canine infarcts of various ages and in the presence of coronary reperfusion.

Thirty-one dogs underwent in vivo scanning with computed transmission tomography; 15 dogs were studied within 7 days (mean 4) after coronary occlusion, 10 dogs 21 to 25 days (mean 28) after occlusion and 6 dogs 4 days after coronary reperfusion of a 2 to 3 hour coronary ligation. Ungated scans (1 cm in depth) of the left ventricle were obtained from apex to base to determine infarct size. In all animals with documented (postmortem) infarction (n = 26), contrast medium caused delayed enhancement of the entire infarct or the periphery of the infarct. Infarct size was calculated from scans showing contrast enhancement of the infarct. Infarct size was also determined from the postmortem heart using histochemical morphometry (nitroblue tetrazolium) and then compared with infarct size derived from tomography using the outer margin of the contrast-enhanced periphery of the infarct as the border of the infarct. Infarct size calculated by the tomographic technique (excluding the animals without an infarct) correlated well with infarct size determined at autopsy (r = 0.90, p less than 0.001). The tomographic estimate (18.2 +/- 11.3 g) of infarct size was similar to autopsy values (18.6 +/- 11.8 g, p = NS). Thus, ungated computed transmission tomographic imaging of the heart can reliably estimate infarct size in a variety of potential clinical circumstances, particularly when the area of rim enhancement of the infarct is included within the presumed infarct region.

Nuclear magnetic resonance imaging of the palliative operation for hypoplastic left heart syndrome.

Electrocardiographic-gated nuclear magnetic resonance (NMR) imaging has been shown to be effective for the evaluation of congenital heart disease, particularly in supracardiac regions. This study evaluated the postoperative status after a stage I palliative operation (Norwood procedure) for hypoplastic left heart syndrome. The NMR images from three patients were compared with those of angiography and depicted all components of the reconstructed supracardiac and intracardiac anatomy after this operation. Nonobstructive anastomosis of the main pulmonary artery to the proximal aorta was clearly demonstrated in each patient. The caliber of the central or branch pulmonary artery, patency and caliber of the systemic to pulmonary artery shunt and the size of the atrial communication were also depicted in each patient and these findings corresponded with angiographic results. The results suggest that NMR imaging is effective for assessing the results of initial palliative surgery for hypoplastic left heart syndrome, which seems to be important for managing patients before subsequent definitive surgery.

Effects of nicardipine, a calcium antagonist, on myocardial salvage and high energy phosphate stores in reperfused myocardial injury.

The current study determined the effectiveness of nicardipine, a 1,4-dihydropyridine calcium antagonist, in preserving reperfused myocardium in a cat model of temporary coronary occlusion and ascertained if replenishment of myocardial phosphate stores during reperfusion as defined by phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy was indicative of salvage. Twenty open chest, anesthetized cats were studied with use of a snare ligature around the proximal left anterior descending coronary artery, with a coil sutured to the epicardial surface overlying the distribution of the artery. Peak areas of phosphocreatine, inorganic phosphate and adenosine triphosphate (ATP) NMR signals were measured during 1 h of occlusion followed by 1.5 h of reperfusion. Infarct size and jeopardy area were determined in vitro by simultaneous infusion of phthalocyanine blue dye and triphenyltetrazolium chloride into the aorta and the left anterior descending coronary artery, respectively, after 5 h of myocardial reperfusion. Nicardipine-treated and control groups had similar jeopardy area values (41.2 +/- 1.6% versus 47.4 +/- 3.1% of the left ventricle), but infarct area was significantly reduced in the nicardipine-treated group (3.2 +/- 1.1% versus 24.9 +/- 7.5% of jeopardy area, p less than 0.01). High energy phosphate compounds remained markedly altered during reperfusion in both groups. No significant improvement in phosphocreatine or inorganic phosphate recovery was observed in animals pretreated with nicardipine despite an 87% reduction in infarct size. Myocardial ATP was greater during reperfusion in the nicardipine-treated compared with the control group (average over initial 90 min of reperfusion 58 +/- 6% versus 46 +/- 3% of baseline values, p less than 0.05), suggesting improved recovery of ATP. However, the measured levels of high energy phosphate compounds during reperfusion and their ratios did not correlate with infarct size and thus were not predictive of myocardial salvage.