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C B Higgins

Publications and source records attributed to C B Higgins.

At least 595 records · Page 33Linked to original sources
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Overview and methods used for the study of the cardiovascular actions of contrast materials.

Contrast materials cause numerous effects on the cardiovascular system. The major direct actions on the heart are myocardial mechanical and electrophysiological alterations. The major direct action on the peripheral circulation is vasodilation. The indirect effects, for the most part, are reflexly mediated and tend to offset the direct effects. The author reviews the various experimental models and techniques used for assessing the actions of contrast materials on the cardiovascular system. The salient findings from previous studies using various experimental models are discussed.

Animals↗
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Effects of contrast materials on left ventricular function.

The effects of intracoronary administration of contrast materials were investigated in conscious and anesthetized dogs prepared with pressure gauges or catheters in the left ventricle for measuring aortic pressure (P), LVP, and dP/dt, and dimension crystals on opposing endocardial surfaces of the LV for measuring LV dimensions and its first derivative dD/dt (velocity of contraction). All contrast materials were tested at a concentration of 370 mg I/ml. Biphasic responses were observed with monomeric contrast materials; direct effects occurred within the first 10 seconds after injection, while secondary or indirect effects (reflex?) ensued near the end of the first 10 seconds or in the second 10-second period (Higgins, 1978). The standard sodium-containing monomeric contrast material caused decreases in LV peak systolic pressure (LVSP), peak dP/dt, dP/dt at an LVP of 40 mmHg (dP/dt40), peak -dP/dt, -dP/dt at an LVP of 50 mmHg (-dP/dt50), and dD/dt (Higgins, 1978, Newell, 1979). It caused increases in LV end-systolic and end-diastolic dimension. The decreases in -dP/dt (rate of relaxation) persisted during the second 10 seconds, when the parameter of LV contractile state had increased above control levels. Similar effects were observed in the presence of regional myocardial ischemia. Monomeric ionic material with added calcium ions (Isopaque 370) caused initial and secondary increases in LVSP and indexes of LV contractile state but still produced decreases in LV relaxation rate (-dP/dt50). Standard monomeric materials caused a decline in Ca++ of coronary sinus blood concomitant with the depression in LV contractile state, while the calcium-containing material produced an increase in Ca++ in association with the enhancement in LV contractile state (Higgins, 1978). Several nonionic materials also have been tested in this preparation: metrizamide, P-297, and iopamidol. These materials had similar effects on LV function; each caused a slight increase or no change in indexes of LV contractile state and no change in LV dimensions. A new monacid dimer (P-286) with a lower sodium content than monomeric materials produced effects on LV function which were less deleterious than standard monomeric materials, but more so than the nonionic materials.

Animals↗
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Cardiovascular effects of protamine sulfate.

Rapid administration of protamine sulfate after arteriography or cardiopulmonary bypass has occasionally been associated with marked hypotension. Since it is unclear whether this is due entirely to vasodilatation or to myocardial depression in addition to vasodilatation, the authors assessed the direct myocardial and systemic circulatory effects of this drug in seven anesthetized dogs. Direct effects of protamine sulfate on global and regional myocardial function and peripheral arterial resistance were determined in the presence and absence of segmental myocardial ischemia. Effects on the myocardium were determined by intracoronary administration of protamine; effects on the systemic circulation were determined after intravenous administration. Intracoronary administration of protamine caused no significant change in left ventricular contractility in either the normal or ischemic state. Intravenous administration produced hypotension due to peripheral vasodilation.

Animals↗
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Uptake of iodinated contrast material by the ischemically damaged myocardial cell.

Computerized transmission tomography has shown differential contrast enhancement of the area of ischemic damage after intravenous administration of iodinated contrast material. The current study performed in normal dogs and dogs with two-day-old and 30-day-old myocardial infarctions was intended to determine if the iodine accumulation is intracellular. Scanning electron microscopy with energy dispersive x-ray analysis detected iodine peaks associated with the cells in areas of ischemic damage, while iodine peaks were not detected in normal myocardium. Energy spectra in the area of ischemic damage showed a significant increase in the Na+ -K+ ratio compared to normal myocardium, consistent with the loss of cellular membrane integrity in this region. Results were similar for both two- and 30-day-old infarcts. These results indicate that iodinated contrast material attaches to the membrane of enters the ischemically damaged cell, but is virtually excluded from the normal myocardial cell. It may serve as a marker of myocardial cells which have lost cellular membrane integrity after an ischemic insult.

Animals↗
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1982 Memorial Award Paper. Detection of regional myocardial dysfunction during ischemia with computerized tomography: documentation and physiologic basis.

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.

Animals↗
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A comparison of peak-to-peak pulmonary transit time determined by digital intravenous angiography with standard dye-dilution techniques in anesthetized dogs.

To evaluate the relationship between mean pulmonary transit time and peak-to-peak transit time by digital intravenous angiography six dogs were assessed during either isoproterenol or phenylephrine infusion. Acutely anesthetized dogs were instrumented with catheters in the pulmonary artery, left atrium, and carotid artery. An injection catheter was placed in the inferior vena cava, and contrast injections were made with a power injector (30 cc/second for 1 second of Renografin 76). Peak-to-peak transit times (pulmonary artery-left atrial time) were derived from videodensitometric time-absorption curves. Mean transit time was calculated from the usual optical densitometric analyses of green dye injected first in the pulmonary artery and then in the left atrium (sampled in a carotid artery). Peak-to-peak times averaged 3.6% greater than mean transit time (4.39 +/- 1.76 seconds vs. 4.24 +/- 1.82 seconds, P less than .05), though they correlated well with green dye values (r = .97; y = .97 x +.44). It was concluded that peak-to-peak transit times are excellent approximates of standard dye-dilution mean transit times and may simplify calculations of the pulmonary circulation when videodensitometric or radionuclide techniques are utilized.

Anesthesia↗
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Physiologic--angiographic correlates of coronary arterial stenoses in resting and intensely vasodilated states.

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%.

Adenosine Triphosphate↗
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Computerized tomographic (CT) appearance of the myocardium after reversible and irreversible ischemic injury.

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.

Animals↗
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Intrarenal backflow during retrograde pyelography with graded intrapelvic pressure. A radiologic study.

Intrarenal backflow (IRB)--a form of pyelorenal backflow where contrast material appears in the renal parenchyma during retrograde pyelography--seems to be the same phenomenon as intrarenal reflux (IRR), sometimes observed during micturating cystography in children or animals with vesicoureteral reflux. Retrograde pyelography experiments were performed on baby pigs to study the relationship between renal pelvic pressure and IRB. Intrapelvic pressure was raised to 30-35 mm Hg (moderate) or 70-75 mm Hg (high) for 5 minutes. IRB developed in only four of 12 kidneys at moderate pressure but in all six kidneys at high pressure. Similar experiments were conducted on kidneys which had been rendered temporarily ischemic prior to retrograde pyelography. Twenty-seven kidneys were so studied 30 minutes after a 30- or 60-minute period of ischemia. With moderate and high pressure retrograde pyelography, all kidneys developed IRB. The most intense and widespread IRB occurred after 60 minutes of ischemia and at high pressure. IRB localized to the upper pole most frequently but was also observed in other portions of the kidney. The effect of IRB upon renal blood flow (RBF) was determined with electromagnetic flow probes during the same experiments. IRB caused a 16% mean decrease in RBF at moderate pressures and a 57% mean decrease in RBF at high pressures and was independent of preceding ischemia. It is concluded that both raised intrapelvic pressure and preceding renal ischemia are important factors determining the degree of IRB during retrograde pyelography and that backflow itself causes decreased RBF.

Animals↗
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Quantitation of size of myocardial infarctions by computerized transmission tomography. Comparison with hot-spot and cold-spot radionuclide scans.

The current study evaluated the ability to quantitate the volume of myocardial infarctions when they are outlined by intravenously administered contrast media in the myocardial perfusion phase and in the phase of delayed contrast enhancement of the infarct. Quantitation by contrast media was assessed from computerized transmission tomography (CTT) scans of the ex situ heart and compared with quantitation by technetium-99m (99mTc)pyrophosphate (99mTc PYP) and thallium-201 (201Tl) scans of the same ex situ hearts. True volume was defined by histochemical morphometry. CTT during the contrast perfusion phase uniformly underestimated infarct size but had a good correlation with true volume (r = 0.87). CTT during enhancement phase correlated closely with true volume (r = 0.98) and most precisely measured true size (y = 1.06 X 0.23). The 99mTc PYP scan overestimated infarct volume (predictive overestimation of 6 to 199%) but had a good correlation with true volume (r = 0.87). 201Tl underestimated infarct volume but correlated well with true volume (r = 0.94). Thus, quantitation of infarct volume from CTT scans performed during either the perfusion or infarct enhancement phase after intravenous contrast media provides a good estimate of true infarct volume. Delineation of the infarct by contrast media in the ex situ heart is more precise during the phase of delayed enhancement of the infarct.

Animals↗
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Digital intravenous ventriculography. Comparison of volumes from mask-mode and nonsubtracted images with thermodilution and sonocardiometric measurements.

Left ventricular volumes calculated from mask-mode (MM) images obtained by digital intravenous ventriculography (DIV) were compared with volumes determined from direct contrast images (CV), thermodilution and sonomicrometer measurements in six anesthetized dogs in which volumes were varied by isoproterenol and phenylephrine infusions. Short and long axis sonomicrometer crystals allowed continuous measurement of cardiac size and function. The MM and CV ejection fractions and volumes correlated well with each other (r greater than or equal to 0.96) through the MM volumes consistently underestimated the CV volumes by 12 +/- 3%. Analyzing each dog individually, both CV and MM volumes and ejection fractions correlated well with sonomicrometer results. In addition CV and MM estimates of stroke volume correlated well (r greater than or equal to 0.91) with the thermodilution values, although the CV values exceeded the thermodilution value by 17 +/- 4%. We conclude that MM analysis of left ventricular function correlates well with standard measures of cardiac dimensional changes and agrees with, though underestimates, the simultaneous nonsubtracted contrast ventriculographic images.

Animals↗
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A comparison of the effects of intravenous and direct left ventricular contrast injections on left ventricular function.

Digital intravenous ventriculography (DIV) has become increasingly recognized as a useful and reliable approach for evaluating left ventricular (LV) performance. While it might be assumed that the hemodynamic changes caused by intravenous injection of contrast media are less than those caused by direct LV injection, these responses have not actually been compared. Accordingly, the hemodynamic effects of IV and direct LV contrast injections were compared in eight anesthetized dogs instrumented with two pairs of ultrasonic dimension crystals, one to measure LV endocardial segment length and one to measure LV internal dimension, and a LV high-fidelity pressure catheter. The alterations in LV dimension and pressure were similar using both injection techniques, though they were less marked with IV injection. Both routes of injection caused a significant decline in LV pressure (P less than 0.05) which was greatest at 30 seconds after injection, and a significant (P less than 0.05) increase in end-diastolic dimension (which was greatest between 10-30 seconds) and extent of change in LV diameter (P less than 0.01). The afterload reducing effects of the contrast media increased the rate of LV segment length shortening slightly after LV injection but not with IV injection. These data demonstrate no important differences in the hemodynamic response to IV and LV injection of contrast media. The induced hemodynamic changes after IV administration were relatively small in magnitude and transient in duration and probably not sufficient to obviate quantitative analysis of LV dimensions and function by digital intravenous angiography.

Animals↗
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Perfluoroctylbromide. Acute hemodynamic effects, in pigs, of intravenous administration compared with the standard ionic contrast media.

Perfluoroctylbromide (PFOB) is a relatively new noniodinated contrast media that, after intravenous administration, produces prolonged opacification of the blood pool and subsequently selectively enhances the liver and spleen on computed tomography. There has been concern regarding the hemodynamic effect of this agent but little actual knowledge exists in this regard. Accordingly, the acute transient hemodynamic effects of PFOB emulsion were evaluated in five pigs and compared with the standard ionic contrast agent meglumine sodium diatrizoate (Renografin-76). Left ventricular (LV) pressure, internal diameter, and wall thickness were monitored during the alternate intravenous administration of 930 mg/ml PFOB and 370 mg/ml R-76 at a rate of 20 mls/second for a total volume of 1 ml/kg body weight. Renografin-76 caused a significant decrease in LV pressure and dp/dt (rate of change of LV pressure), and an increase in LV end-systolic diameter and a decrease in LV end-diastolic wall thickness. PFOB caused no change in LV pressure and dimensions. Thus, rapid intravenous administration of PFOB does not induce significant acute alterations in left ventricular pressure, dp/dt, dimension, or wall thickness.

Animals↗
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Specific enhancement of intra-abdominal abscesses with perfluoroctylbromide for CT imaging.

Perfluoroctylbromide (PFOB), a radiopaque reticuloendothelial system contrast media for computed tomography, has been shown to accumulate in macrophages. In the current study PFOB was tested in rabbits as an abscess imaging agent. Two abscesses were induced in each of 24 rabbits, one in the liver and the other in the peritoneal cavity. CT of the rabbit abdomen was performed four days later, two days after the administration of 5 gm/Kg of PFOB to 12 of these rabbits. The average enhancement of the wall of liver abscesses was by 140 Hounsfield units (HU) relative to the enhanced liver and peritoneal abscesses by 135 HU relative to the control group. This enhancement was secondary to the intense accumulation of PFOB filled macrophages in the abscess wall. In those rabbits where the liver abscess ruptured, the edges of the peritoneal collections enhanced by 147 HU. Regions of inflammation prior to liquifaction enhanced considerably. These areas could not be detected in the animals not receiving PFOB. Though the liquified center of liver abscesses could be seen in the absence of PFOB, none of the peritoneal abscesses could be detected in the animals not receiving PFOB. In contradistinction, all peritoneal abscesses enhanced considerably following PFOB allowing their prospective localization. In conclusion, PFOB accumulates in abscess walls and areas of inflammation producing marked CT enhancement of liver and peritoneal abscess collections. This enhancement allowed the differentiation of peritoneal abscess collections from adjacent bowel.

Abscess↗
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Cardiotolerance of iohexol. Survey of experimental evidence.

The risk of significant complications from contrast media is greatest in angiocardiography. Contrast media effects on central cardiovascular function include electrophysiologic effects such as bradycardia, hypotension, and ventricular arrhythmias; hemodynamic effects such as hypotension and blood flow changes; and metabolic effects such as transient hypocalcemia. Differences between ionic and nonionic media are less obvious in clinical studies but become apparent in carefully controlled animal experiments. Evidence indicates that nonionic media have less propensity to cause ventricular arrhythmias and bradycardia than ionic media. In addition, nonionic agents do not adversely affect left ventricular regional function and produced no negative inotropic effects in the presence of coronary stenosis. Unlike ionic diatrizoate, nonionic iohexol did not significantly interact with the calcium blocker, verapamil. Iohexol also produced no increase in lung water or in femoral blood flow, while diatrizoate produced increases in both. It is concluded that iohexol has fewer and less severe negative effects on central cardiovascular function than standard ionic media.

Angiocardiography↗
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Comparison of an ionic with a nonionic contrast agent for cardiac angiography. Results of a multicenter trial.

Ionic contrast agents currently used in cardiac angiography are well tolerated but have certain negative effects. In a five-center study of 273 patients undergoing cardiac catheterization, safety and efficacy of the new nonionic contrast agent, iohexol, were compared with that of the standard ionic material, sodium methylglucamine diatrizoate. Contrast injections were made into the left ventricle and left and right coronary arteries in all patients. Left ventricular, systemic arterial and pulmonary capillary wedge pressures, and electrocardiogram lead II were recorded for 2 minutes. Following the first right and first left coronary injection, systemic arterial pressure and electrocardiographic recordings were made for 1 minute. After each subsequent coronary injection, recordings were made for 20 seconds. Both agents were found to be safe and both provided good diagnostic information. Iohexol was seen to cause both less marked overall hemodynamic alterations and a lower incidence of significant changes in pressure and heart rate. Iohexol may have an important role in coronary angiography and left ventriculography, particularly in high-risk patients, because of its lesser effect on heart rate and blood pressure.

Adult↗