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Biomedical subjects

M L Weisfeldt

Publications and source records attributed to M L Weisfeldt.

At least 19 recordsLinked to original sources
PubMed1992

Direct measurement of myocardial free radical generation in an in vivo model: effects of postischemic reperfusion and treatment with human recombinant superoxide dismutase.

OBJECTIVES: The purpose of this study was to determine whether postischemic reperfusion of the heart in living rabbits induces a burst of oxygen free radical generation that can be attenuated by recombinant human superoxide dismutase administered at the moment of reflow. BACKGROUND: This phenomenon was previously demonstrated in crystalloid perfused, globally ischemic rabbit hearts. METHODS: Thirty-two open chest rabbits were assigned to one of four groups of eight animals each: Group I (control animals), no coronary artery occlusion; Group II, 30 min of circumflex marginal coronary artery occlusion without reperfusion; Group III, 30 min of coronary occlusion followed by 60 s of reperfusion, and Group IV, 30 min of coronary occlusion followed by treatment with recombinant human superoxide dismutase (a 20-mg/kg body weight bolus 90 s before reperfusion and a 0.17-mg/kg infusion during 60 s of reperfusion). Full thickness biopsy specimens taken from the ischemic region were then rapidly freeze clamped and electron paramagnetic resonance spectroscopy was performed at 77 degrees K. RESULTS: Three radical signals similar to those previously identified in the isolated, crystalloid perfused rabbit heart were observed: an isotropic signal with g = 2.004 suggestive of a semiquinone, an anisotropic signal with g parallel = 2.033 and g perpendicular = 2.005 suggestive of an oxygen-centered alkyl peroxy radical, and a triplet with g = 2.000 and aN = 24 G suggestive of a nitrogen-centered radical. In addition, a fourth signal consistent with an iron-sulfur center was seen. The oxygen-centered free radical concentration during normal perfusion (Group I) was 1.8 +/- 0.8 mumol compared with 4.4 +/- 0.9 mumol after 30 min of regional ischemia without reperfusion (Group II) and 13.0 +/- 2.5 mumol after 60 s of reperfusion (Group III) (p < 0.05 among all three groups). In contrast, superoxide dismutase treated-rabbits (Group IV) demonstrated a peak oxygen radical concentration of only 5.9 +/- 1.2 mumol (p < 0.05 vs. Group III). CONCLUSIONS: This study demonstrates that reperfusion after regional myocardial ischemia in the intact rabbit is associated with a burst of oxygen-centered free radicals. The magnitude of this burst is greater than that seen after a comparable duration of global ischemia in the isolated, buffer-perfused rabbit heart preparation and is significantly reduced by superoxide dismutase administration begun just before reflow.

Animals↗
PubMed1992

Dissociation between left ventricular untwisting and filling. Accentuation by catecholamines.

BACKGROUND: Efficient early diastolic filling is essential for normal cardiac function. Diastolic suction, as evidenced by a decreasing left ventricular pressure during early filling, could result from restoring forces (the release of potential energy stored during systolic deformation) dependent on myofilament relaxation. Although these restoring forces have been envisioned within individual myofibers, recent studies suggest that gross fiber rearrangement involving the connective tissue network occurs easy in diastole. This may lead to the release of potential energy stored during systole and suction-aided filling. METHODS AND RESULTS: To establish precisely the timing and extent of restoration of the systolic torsional deformation of the left ventricle with respect to early filling at baseline and with enhanced relaxation, we studied untwisting during control conditions and with catecholamine stimulation. Using noninvasive and nondestructive magnetic resonance tagging, torsional deformation of the left ventricle was measured at 20-msec intervals in 10 open-chest, atrially paced dogs, starting at aortic valve closure. Eight equiangular tags intersected the epicardium and endocardium in three short-axis imaging planes (base, mid, and apex). From the intersection points, epicardial and endocardial circumferential chord and arc lengths were measured and angular twist of mid and apical levels with respect to the base (maximal torsion and its reversal, untwisting) was calculated. Echo-Doppler provided timing of aortic valve closure and of mitral valve opening. Zero torsion was defined at end diastole. Torsion at the apical level reversed rapidly between its maximum and the time immediately after mitral valve opening: from 7.0 +/- 5.8 degrees to 3.2 +/- 5.4 degrees and 12.0 +/- 8.5 degrees to 6.9 +/- 7.8 degrees (mean +/- SD, both p less than 0.01) at the epicardium and endocardium, respectively. During the same period, no significant circumferential segment length changes occurred. As expected, after mitral valve opening, filling resulted in significant circumferential segment lengthening, whereas further reversal of torsion was small and nonsignificant. During dobutamine infusion, torsion at end systole was greater and reversal during isovolumic relaxation was much more rapid and greater in extent (p less than 0.01). Torsion reversed from 11.5 +/- 4.3 degrees to 5.7 +/- 4.8 degrees and 17.4 +/- 6.4 degrees to 6.9 +/- 7.7 degrees at epicardium and endocardium. CONCLUSIONS: Untwisting occurs principally during isovolumic relaxation before filling and is markedly enhanced in speed and magnitude by catecholamines. This partial return of the left ventricle to its preejection configuration before mitral valve opening could represent an important mechanism for the release of potential energy stored in elastic elements during the systolic deformation. These myocardial restoring forces would be markedly enhanced by physiological changes consequent to catecholamines such as during exercise, offsetting the concomitant shortening of the filling period.

Animals↗
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↗
PubMed1979

Regional cardiac dilatation after acute myocardial infarction: recognition by two-dimensional echocardiography.

To assess the early topographic changes after acute transmural myocardial infarction, we studied 28 patients during the first two weeks after infarction by serial two-dimensional echocardiography. Regional end-diastolic segment lengths and wall thicknesses for anterior and posterior left ventricular walls were calculated. Eight patients showed infarct expansion, with disproportionate dilatation and transmural thinning in the infarcted zone, that was significantly different (P less than 0.005) from changes in non-infarcted regions. This regional expansion led to an overall left ventricular dilatation in these eight patients of 25 per cent compared to 5 per cent in the 20 patients without infarct expansion. Although the eight patients with regional expansion did not have significantly higher peak creatine kinase or Killip classification, they had a significantly greater eight-week mortality (four of eight versus none of 20, P less than 0.004). Thus, regional cardiac dilatation may be an early, lethal consequence of transmural infarcts, and appears to be an important mechanism of acute cardiac dilatation after myocardial infarction.

Acute Disease↗
PubMed1979

Pathologic basis of thallium-201 scintigraphic defects in patients with fatal myocardial injury.

Using a quantitative, computer-aided circumferential profile technique, we have shown that thallium-201 scintigrams with large defects can identify a group of patients with a high mortality after acute myocardial infarction. To determine whether high-risk thallium scintigrams predict poor survival because of a critical loss of myocardium, we correlated infarct size in 24 autopsied patients with the extent of thallium defect in three views. Of 13 patients with large defects (computer score greater than or equal to 7.0) eight (62%) had greater than 25% loss of left ventricular (LV) myocardium, but five (38%) had smaller infarcts (4--24% of LV myocardium), suggesting that part of the scintigraphic defect was related to ischemia without necrosis. Eight of the nine patients with loss greater than or equal to 25% LV myocardium had large defects. In 10 of 11 patients with small defects (computer score less than 7.0), infarcts involved less than 20% of LV myocardium. Although scintigrams with large defects predicted a critical loss of myocardium in over 60% of our patients, they included an important second group, in which the scintigraphic defect appeared to reflect a small infarct and a large surrounding area of reversibly ischemic myocardium.

Adult↗
PubMed1979

Influence of aging on left ventricular hemodynamics and stiffness in beagles.

We studied the influence of aging on the contractile performance, stiffness, and contraction time of the canine left ventricle. Eight young (27 +/- 2.5 months, mean +/- SE) and seven old (128 +/- 20.5 months) beagles were placed on complete cardiopulmonary bypass, the arterial pressure was adjusted to 80 mm Hg, and the heart contracted isovolumically at a paced rate of 120 beats/min. Diastolic pressure-volume curves were established for each unpaced left ventricle at the beginning of each experiment, and the volume at the knee of the curve was used during the subsequent data collection when the heart was paced. Stiffness was measured with a sinusoidal forcing function, which imposed a sinusoidal displacement of 1 ml at 20 Hz into a balloon placed in the left ventricle. In each ventricle, stiffness was related linearly to pressure during the cardiac cycle, and was greater for any given pressure in the older beagles. Contraction duration was prolonged in the older dogs. In an additional seven old beagles during right heart bypass time, and duration of contraction were longer than in seven young beagles. Aging of the beagle heart is associated with an increase in left ventricular systolic and diastolic stiffness and prolonged duration of contraction.

Aging↗