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Biomedical subjects

M L Weisfeldt

Publications and source records attributed to M L Weisfeldt.

At least 55 records · Page 3Linked to original sources
PubMed1990

Observations of hemodynamics during human cardiopulmonary resuscitation.

To evaluate hemodynamics during human CPR, 32 patients with witnessed cardiac arrest were studied during manual and mechanical conventional CPR. In eight patients during manual conventional CPR, peak systolic radial artery, right atrial (RAP), and pulmonary artery pressures were found to be similar (59.8 +/- 4.3, 70.8 +/- 4.7, 71.2 +/- 8.2 mm Hg) and higher than external jugular venous pressure (33.8 +/- 1.9 mm Hg, p less than .0001). The diastolic radial artery to RAP gradient was found to be only 10.7 +/- 2.1 mm Hg. In four patients, maneuvers that avoid chest compression and thus obviate cardiac compression, i.e., rhythmic compression of the abdomen, yielded arterial pressures comparable to those generated by conventional CPR (48 +/- 6.4 vs. 52.8 +/- 3.4 mm Hg, NS). In 13 other patients during mechanical conventional CPR at constant chest compression force, radial artery pressure was higher during the first compression after ventilation as compared with subsequent chest compressions (67.5 +/- 5.0 vs. 61.9 +/- 4.8 mm Hg, p less than .007). These hemodynamic observations are similar to those reported in large dogs during CPR and support the generation of vascular pressures during CPR by an increase in intrathoracic pressure. They also suggest that despite anatomic differences, the similarity of hemodynamics in dogs and humans justifies the use of large dogs as a human model during acute resuscitation studies.

Arm↗
PubMed1990

Pharmacokinetics of recombinant human superoxide dismutase.

Superoxide dismutase (SOD) disposition was studied in order to design a rational approach for drug administration in the setting of acute myocardial infarction. Four chronically instrumented conscious dogs received the following dosage regimens of recombinant human SOD (rhSOD) on successive days: (a) 5 mg/kg left atrial (LA) bolus, (b) 5 mg/kg central vein (CV) bolus, (c) 15 mg/kg CV bolus, and (d) 5 mg/kg CV infusion over 60 min; additionally, all dogs received (e) a 5 mg/kg CV bolus under pentobarbital anesthesia. Serial serum samples were obtained after each dose and serial myocardial samples were obtained after dose (e). The serum rhSOD concentration was measured by radioimmunoassay and the data were fit to a two-compartment model. The distribution half-life was 7.8 +/- 1.7 min (mean +/- SEM), and the elimination half-life was 51.1 +/- 5.9 min; the central compartment volume of distribution (Vc) was 81 +/- 26 ml/kg and the steady-state volume of distribution was 156 +/- 20 ml/kg. The dosage regimen had no influence on clearance rates. Peak plasma concentrations (micrograms/ml) for the dosage regimens were (a) 65 +/- 28, (b) 89 +/- 19, (c) 214 +/- 61, (d) 20 +/- 5, and (e) 86 +/- 9. The peak level following continuous infusion did not occur until 50 min of infusion and was only one-fourth of the level achieved with a bolus of the same dose. Myocardial levels were less than 1% of serum levels, suggesting negligible rhSOD penetration into the myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Three-dimensional mapping of acute ischemic regions using MRI: wall thickening versus motion analysis.

Three-dimensional (3D) endocardial wall motion and thickening were compared as quantitative methods for distinguishing ischemic from non-ischemic myocardium and for their potential to map regional left ventricular (LV) function. Data were obtained by gated magnetic resonance (MR) images in seven open-chest dogs with acute ischemia. The LVs were reconstructed in 3D at end diastole (ED) and end systole (ES) with a helical coordinate system that wraps the endocardium and epicardium. Thickness and percent wall thickening were calculated by a 3D volume element method. Wall motion was calculated by the 3D displacement of the endocardium perpendicular to the wall using both fixed and floating centroids. Monastral blue nonstaining identified the ischemic regions from five anatomical slices of the LV, which corresponded to the in vivo image planes. Thickening and motion were compared at the centers of the ischemic and the remote normal zones, in addition to comparing the functional maps of the entire LV to the postmortem anatomical maps. All methods distinguished between the center of the ischemic zone and the remote normal zone; however, thickening discriminated most strongly between zones. Comparison of the 3D in vivo maps with the 3D postmortem maps showed that the sensitivity, specificity, and overall accuracy of the thickening algorithm exceeded those obtained by the wall motion algorithms with fixed or floating centroids. Thus wall thickening utilizing the 3D volume element approach is superior to 3D wall motion algorithms in distinguishing ischemic from nonischemic zones and in mapping regional function in the entire LV.

Acute Disease↗
PubMed1990

Quantification and validation of left ventricular wall thickening by a three-dimensional volume element magnetic resonance imaging approach.

We have developed a method to quantify and map regional wall thickening throughout the left ventricle (LV) with magnetic resonance imaging. In contrast to methods that measure planar wall thickness and thickening, this method uses the three-dimensional (3D) geometry of the left ventricle to calculate the perpendicular thickness of the wall. We tested this method at three levels of increasing complexity using 1) phantom studies, 2) in vivo experiments in dogs with normal cardiac function, and 3) in vivo studies in dogs during acute ischemia. Experiments were conducted in 15 open-chest dogs imaged by a 0.38 T iron core magnet. Five short-axis images at end diastole and end systole were obtained with the spin echo technique by use of the QRS as a trigger for end diastole and the second heart sound, S2, to time end systole. After acquisition of preischemic images, acute ischemia was induced by either coronary artery ligation (n = 5) or intracoronary dental rubber injection (n = 5), which produced severe transmural ischemia. By use of computer-aided contouring of the endocardial and epicardial borders, each image was divided into 16 segments with radial lines originating from the midwall centroid. A 3D volume element was defined as that generated by connecting two matched planar segments in two adjacent image planes. This defined 64 volume elements comprising the entire left ventricle. Thickness and thickening before and during ischemia were then calculated by using the planar segments and the 3D volume elements. In phantom studies, the 3D method was accurate, independent of the angle of inclination of the image plane to the phantom wall, whereas the planar method showed considerable overestimation of thickness when the image plane was oblique to the phantom wall. In the dogs before induction of ischemia, the 3D method demonstrated the well-established normal taper in end-diastolic wall thickness from 1.10 +/- 0.02 cm at the base to 1.05 +/- 0.11 cm at the apex (p less than 0.01). By contrast, the planar method did not detect the decrease in thickness toward the apex (1.13 +/- 0.07 cm at the base vs. 1.16 +/- 0.14 cm at the apex, p = NS). During acute ischemia, thickening was calculated by both methods at the center of the ischemic zone defined by Monastral blue nonstaining and compared with the preischemic values.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1990

Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers.

Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardiac events developed in 9.8% of subjects and consisted of 20 cases of new angina pectoris, 13 myocardial infarctions, and seven deaths. Events occurred in 7% of individuals with both negative 201Tl and ECG, 8% of those with either test positive, and 48% of those in whom both tests were positive (p less than 0.001). By proportional hazards analysis, age, hypertension, exercise duration, and a concordant positive ECG and 201Tl result were independent predictors of coronary events. Furthermore, those with positive ECG and 201Tl had a 3.6-fold relative risk for subsequent coronary events, independent of conventional risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Noninvasive quantification of left ventricular rotational deformation in normal humans using magnetic resonance imaging myocardial tagging.

It has been postulated that rotation of the left ventricular apex with respect to the base is a component of normal systolic function in humans, but it has been difficult to measure it noninvasively. Tagging is a new magnetic resonance imaging technique that labels specific areas of myocardium by selective radio-frequency excitation of narrow planes orthogonal to the imaging plane before acquiring an image. Tags appear as black lines and persist in myocardium for 400-500 msec and, if applied at end diastole, will move with the myocardium through systole. Tagging was used to noninvasively quantify left ventricular torsion and circumferential-longitudinal shear (shearCL) in humans. Eight normal volunteers, aged 24-38 years, were imaged in a 0.38-T iron-core resistive magnet. Five short-axis left ventricular images, positioned to encompass the entire left ventricle (LV), were obtained separately at end systole. Four equiangular radial tags had been applied at end diastole, intersecting the myocardium at eight locations. We calculated the difference in angular displacement of each epicardial and endocardial tag point (a tag point being where the tag crossed the epicardium or endocardium) at end systole from the systolic position of the corresponding tag point on the basal plane. This value was called the torsion angle. From this, shearCL, the angle inscribed on the epicardial or endocardial surface between the systolic tag position, the corresponding basal tag position, and its projection onto the slice of interest could be calculated at 32 points in the left ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Excitation-contraction coupling in postischemic myocardium. Does failure of activator Ca2+ transients underlie stunning?

To elucidate the mechanism of contractile dysfunction in postischemic ("stunned") myocardium, time-resolved measurements of intracellular free Ca2+ concentration ([Ca2+]i) were made using gated 19F nuclear magnetic resonance in seven perfused ferret hearts loaded with the fluorinated Ca2+ indicator 5F-BAPTA. Left ventricular developed pressure decreased to 65 +/- 3% (mean +/- SEM) of control after 15 minutes of global ischemia at 37 degrees C. In stunned myocardium, diastolic [Ca2+]i (0.24 +/- 0.03 microM) was not changed from control (0.18 +/- 0.03 microM, p greater than 0.10), but peak [Ca2+]i (1.03 +/- 0.13 microM) was paradoxically higher than that in control (0.61 +/- 0.06 microM, p less than 0.02). The slope of the relation between developed pressure and Ca2+ transient amplitude in stunned myocardium was significantly lower than that in control (p less than 0.05), even after normalization by maximal Ca2(+)-activated pressure. These results indicate that contractile failure in stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to the previously identified decrease in maximal Ca2(+)-activated force; failure of activator Ca2+ delivery cannot be implicated. The increase in the amplitude of Ca2+ transients would require that more ATP be spent in Ca2+ sequestration; thus, decreased efficiency of energy utilization in stunned myocardium would result.

Animals↗
PubMed1990

Recombinant soluble CR1 suppressed complement activation, inflammation, and necrosis associated with reperfusion of ischemic myocardium.

In summary, conversion of wild-type CR1 to a soluble form (sCR1) creates a potent inhibitor of complement activation by both the classical and alternative pathways by inhibiting the C3/C5 convertases. In the rat reperfusion infarct model, sCR1 significantly suppresses complement activation at the endothelial surface of capillaries and venules. This suppression of complement activation is accompanied by reduced accumulation of leukocytes within the infarct zone, perhaps because of reduction of the generation of C5a, which promotes expression of leukocyte adhesion receptors and leukocyte chemotaxis. In addition, formation of the C5b-9 attack complex, which may contribute to direct endothelial injury, was suppressed by sCR1. The inhibition of complement activation and leukocyte infiltration by sCR1 explains the observed significant reduction in myocardial necrosis after ischemia and reperfusion. These studies have identified sCR1 as a potential agent for therapeutic intervention in diseases associated with complement-dependent tissue injury.

Amino Acid Sequence↗
PubMed1989

Measurement and characterization of postischemic free radical generation in the isolated perfused heart.

Electron paramagnetic resonance spectroscopy has been applied to measure radical generation in the postischemic heart; however, there is controversy regarding the methods used and the conclusion as to whether radicals are generated. In order to resolve this controversy, direct and spin trapping measurements of the time course and mechanisms of radical generation were performed in isolated perfused rabbit hearts. In reperfused tissue, 3 prominent radical signals are observed: A, isotropic g = 2.004 suggestive of a semiquinone; B, anisotropic g parallel = 2.033 and g perpendicular = 2.005 suggestive of ROO.; and C, a triplet g = 2.000 and aN = 24 G suggestive of a nitrogen centered radical. B and C, however, are highly labile and disappear at temperatures probably encountered in some previous studies. In normally perfused hearts, A is observed with only small amounts of B and C. During ischemia, B and C increase reaching a maximum after 45 min while A decreases. On reflow with oxygenated perfusate all 3 signals increase. With varying duration of ischemia and reflow, peak signal intensities occurred after 15 s of reflow following 30 min of ischemia. Reperfusion with superoxide dismutase, deferoxamine, or mannitol abolished the reperfusion increase of B. Measurements performed with the spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) demonstrated a similar time course of radical generation with prominent DMPO-OH and DMPO-R signals peaking between 10 and 20 s of reflow. Superoxide dismutase and deferoxamine also quenched these signals. Thus, .O2- derived .OH, R., and ROO. radicals are generated in postischemic myocardium. While the experimental techniques used can result in loss of intrinsic radicals and generation of extraneous radicals, with proper care and controls valid measurements of free radicals in biological tissues can be performed.

Animals↗
PubMed1989

Clinical management of acute myocardial infarction.

There is increasing evidence that angiography and revascularization soon after thrombolytic therapy offer no benefit over expectant medical therapy. Rather, intervention should be held in reserve for those patients in whom ischemia recurs. The hospital management of acute myocardial infarction, beginning when the patient is admitted to the coronary care unit, is discussed.

Angioplasty, Balloon↗
PubMed1989

Calcium-antagonist receptors in the atrial tissue of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is characterized by a nondilated, hypertrophied left ventricle in the absence of any overt cause. A possible role of adrenergic innervation or of cellular calcium regulation is suggested by the presence of hyperdynamic left ventricular function and by the clinical and symptomatic improvement seen in patients treated with beta-receptor antagonists or calcium antagonists. Therefore, we measured the density of calcium-antagonist receptors and beta-adrenoceptors in the atrial myocardium of 16 patients with hypertrophic cardiomyopathy and 19 patients with various other cardiac disorders. For comparison, we also measured the number of voltage-sensitive sodium channels. Calcium-antagonist binding sites, measured as the amount of dihydropyridine bound to atrial tissue, were increased by 33 percent in patients with hypertrophic cardiomyopathy (mean [+/- SD], 397 +/- 104 fmol per milligram of protein in patients with hypertrophic cardiomyopathy, as compared with 299 +/- 108 in patients with other cardiac disorders; P less than 0.01). The densities of saxitoxin-binding sites on voltage-sensitive sodium channels and beta-adrenoceptors were the same in the two groups, although the density of beta-adrenoceptors was higher in atrial samples from patients receiving beta-receptor antagonists (165 +/- 86 fmol per milligram of protein [patients receiving beta-blockers] vs. 85 +/- 60 [patients not receiving beta-blockers]; P less than 0.04). The increase in the number of calcium-antagonist receptors in hypertrophic cardiomyopathy suggests that abnormal calcium fluxes through voltage-sensitive calcium channels may play a pathophysiologic part in the disease.

Adolescent↗
PubMed1989

Aortic diameter and pressure-flow sequence identify mechanism of blood flow during external chest compression in dogs.

Aortic flow and pressure relations and aortic diameter were examined during sinus rhythm, internal cardiac massage, vest cardiopulmonary resuscitation, conventional manual cardiopulmonary resuscitation and high impulse manual cardiopulmonary resuscitation in 14 anesthetized large dogs. During sinus rhythm and during internal cardiac massage, ascending aortic flow and pressure increased simultaneously and the rise in ascending aorta pressure preceded the rise in descending aortic pressure by (mean +/- SEM) 28 +/- 4 and 30 +/- 1 ms, respectively. In contrast, during vest, conventional and high impulse cardiopulmonary resuscitation, ascending aortic flow lagged behind the initial rise in aortic pressure by 40 +/- 4 to 46 +/- 4 ms and ascending and descending aortic pressure increased simultaneously (p less than 0.001 for each external compression mode versus sinus rhythm and internal massage). The ratio of pulse pressure to stroke volume increased by an order of magnitude during all modes of external chest compression (p less than 0.001 versus sinus rhythm and internal massage) and aortic diameter decreased during vest and high impulse cardiopulmonary resuscitation (p less than 0.05 versus sinus rhythm and internal massage). The hemodynamics of external chest compression depart from the normal physiologic sequence of stroke volume-induced increase in aortic pressure and diameter. The rise in aortic pressure precedes flow into the aorta, stroke volume does not fully account for pulse pressure, and aortic diameter decreases during chest compression. These data support the hypothesis that blood flow is due to fluctuations in intrathoracic pressure for high impulse as well as vest and conventional cardiopulmonary resuscitation.

Animals↗
PubMed1989

Comparison of prehospital conventional and simultaneous compression-ventilation cardiopulmonary resuscitation.

Nine hundred ninety-four patients were enrolled in a field trial in which ambulance crews were randomly assigned to use simultaneous compression-ventilation (SC-V) CPR or conventional CPR procedures in the prehospital setting. Survival to hospital admission and to discharge was superior in the conventional CPR group vs. the experimental group (p less than .01). In a subset of adult cases whose causes of arrest were nontraumatic, survivor rates still favored the conventional CPR group: 33.5% of 337 vs. 22.5% of 365 (p less than .001). In limited cases where cardiac arrest was due to other heart disease, was vascular in origin or secondary to other natural diseases or from hypertensive cardiovascular disease, or when ECG on arrival was an agonal rhythm, survival was better (but not statistically significantly) in the experimental group. There were no statistically significant differences in the Glasgow coma scores between surviving patients in either group at 24 h post-hospital admission or discharge. It is concluded that survival in the SC-V CPR group was lower, likely reflecting a deleterious effect of the experimental technique of resuscitation. Also noted was that 14% of the control patients and 6% of the experimental patients survived with manual CPR alone.

Adolescent↗
PubMed1989

Dependence of left ventricular twist-radial shortening relations on cardiac cycle phase.

Cardiac models have proposed tight coupling between the systolic twisting motion of the left ventricle about its longitudinal axis and muscle shortening. Whether a similar relationship holds during diastole is unknown. The present study determined the dynamic twist-radial shortening relationship throughout the cardiac cycle in six in situ canine left ventricles. Radiopaque markers (15-26) were implanted throughout the myocardial midwall in six canine left ventricles. Three-dimensional marker location was determined by computer analysis of biplane cineradiograms (60 frames/s), and the results were transformed to cardiac cylindrical coordinates. Mean chamber twist was defined as the gradient along the long axis of circumferential rotation relative to end diastole. Changes in chamber dimension were indexed by average radial shortening, normalized to span from 0 at end diastole to 1.0 at end systole. During systole, ventricular twist and radial shortening were linearly related with an average slope of -0.058 radians (r = 0.99). However, during early diastolic relaxation there was substantial untwist (48 +/- 20% of total) despite only an approximately 15% increase in mean radial dimension resulting in a much steeper twist-percent shortening relationship (-0.24 radians, r = 0.96). During most of the remainder of diastolic filling, the twist-shortening relation was shallower (-0.02, r = 0.91) than the corresponding systolic relation (P less than 0.05). Thus the twist-radial shortening relation depends on the phase of the cardiac cycle. These data suggest that models of chamber mechanics that incorporate twisting motion need to account for the matrix surrounding the muscles in addition to the shortening and lengthening of the muscle fibers.

Animals↗
PubMed1989

Circulatory assistance by intrathoracic pressure variations: optimization and mechanisms studied by a mathematical model in relation to experimental data.

The hemodynamic effects of phasic variations in intrathoracic pressure (ITP) timed to the cardiac cycle were predicted by a mathematical model and were compared with data from canine experimental studies. The model was used to predict the hemodynamic effects of changing the onset of the ITP rise relative to the start of cardiac systole, as well as the hemodynamic effects of changes in the duration and amplitude of the ITP rise. The predictions of the model were compared with hemodynamic data from seven anesthetized dogs. Cardiac function was depressed with large doses of verapamil and propranolol, and the hearts were atrioventricular sequentially paced at a rate of 72 beats/min. Phasic ITP variations were generated by a perithoracic vest and were electronically timed to the cardiac cycle. The model predicted, and the experimental data confirmed, that phasic intrathoracic pressure variations generated by vest inflation, timed to the cardiac cycle, can augment both peak and mean aortic flow. The following predictions of the model were also confirmed by the experimental data: 1) Maximum flow augmentation occurs when the onset of the ITP rise is simultaneous with the onset of left ventricular isovolumic contraction, and the ITP rise has a duration of 400 msec. 2) The magnitude of the flow augmentation is a function of the amplitude of the ITP rise. The experimental data showed that there was little further flow augmentation when the ITP rise was greater than 30-40 mm Hg. 3) The magnitude of flow augmentation was inversely proportional to the peak left ventricular elastance (Emax). The best fit between the measured and predicted flow augmentations was obtained for an assumed Emax of 0.5 mm Hg/ml, while Emax measurements in three dogs, using a volume conductance catheter and transient vena caval occlusion, yielded values of 0.4-1.6 mm Hg/ml. Thus, both the mathematical model and canine experiments showed that relatively low-amplitude ITP variations, rising synchronously with the onset of cardiac systole and having an optimal duration, assist the failing heart by augmentation of aortic flow. The degree of cardiac assistance decreases if the ITP variations do not rise synchronously with the onset of systole, or if their duration is not optimal. Thus, properly applied ITP variations may be used as an efficient, noninvasive method to temporarily assist the failing heart.

Animals↗
PubMed1989

Alterations in calcium antagonist receptors and sodium-calcium exchange in cardiomyopathic hamster tissues.

The Syrian cardiomyopathic (CM) hamster (BIO 14.6) develops a progressive cardiomyopathy characterized by cellular necrosis, hypertrophy, and, eventually, cardiac dilatation and congestive heart failure. Several lines of evidence implicate cellular calcium overload as an important etiologic factor. We previously reported an increased number of receptors for calcium antagonist drugs, which block voltage-dependent calcium channels, in heart, skeletal muscle, and brain tissue of these hamsters in the early necrotic stage of the disease. To better characterize the pathophysiological significance of this abnormality we evaluated calcium antagonist receptor binding and Na+-Ca2+ exchange in CM and control hamsters at different stages of disease as documented by quantitative histopathologic assessment. In CM hamsters as young as 10 days, an age previously thought to be before the onset of disease, we identified cardiac myocyte hypertrophy, a twofold increase in calcium antagonist receptor binding in heart and brain, and a 50% increase in skeletal muscle. Overt histological lesions were present in skeletal muscle at 25 days and in heart between 28-30 days. The size of cardiac lesions increased over time and changed from necrotic foci with cellular infiltration to fibrotic or calcified lesions by 360 days. Myocardial cellular hypertrophy persisted through the late stages of the disease (360 days), but increased calcium antagonist binding was present in heart only to 6 months of age, in skeletal muscle to 90 days, and in brain to 30 days. Na+-Ca2+ exchange in heart was normal until 15 days and then increased by 400% at 30 days suggesting that this augmentation might be a secondary response to the earlier increase in calcium antagonist receptors. At 360 days cardiac Na+-Ca2+ exchange was decreased by 50%, likely reflecting progressive cardiac damage. The increase in calcium antagonist receptors in CM animals as young as 10 days supports the hypothesis that abnormalities in voltage-dependent calcium channels play a role in the pathophysiology of CM hamsters.

Animals↗