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Biomedical subjects

M Hofmann

Publications and source records attributed to M Hofmann.

At least 253 records · Page 14Linked to original sources

Lateralization of spatial preference in the female rat.

Female rat pups were either left undisturbed in infancy and raised in lab cages or were handled in infancy and raised in enriched environments. In adulthood, animals underwent brain surgery consisting of: 1) a right neocortical ablation, 2) a left neocortical ablation, 3) a sham operation, or 4) no surgery. After recovering, they were tested for the initial direction of movement (left or right) in the open field. Nonhandled intact females were biased to move leftward indicating an asymmetrical brain organization. The intact handled-enriched group was unbiased. The right and left lesions caused the animals to move ipsilateral to the lesion, but there was no difference in the magnitude or response in either early experience group. Thus, early experience in the female rat has a different effect then in the male, and the nature of the brain organization in the two sexes is markedly different.

Animals↗

Intracoronary thrombolysis in acute myocardial infarction: an attempt to quantitate its effect by comparison of enzymatic estimate of myocardial necrosis with left ventricular ejection fraction.

The quantity of myocardium was estimated that can be salvaged by reperfusion of acute transmural myocardial infarction (MI). Serial analysis of serum creatine kinase (CK) activity was carried out in 41 consecutive patients with acute MI who underwent intracoronary thrombolysis. Enzymatic estimate of MI size was calculated using an average (method A) and an individually determined elimination constant (method B). Left ventricular ejection fraction 4 weeks after successful thrombolysis (cineangiogram) correlated inversely with MI size (method A: r = -0.85, method B: r = -0.76; both p less than 0.001). Patients with recanalization within 4 hours after the onset of symptoms were assembled in group A1 (n = 13, early reperfusion), and patients with successful recanalization after 4 hours in group A2 (n = 16, late reperfusion). Group B consisted of 12 patients without reperfusion. MI size in group A1 was 21 CK-g-Eq (method A) and 23 CK-g-Eq (method B), in group A2 50 CK-g-Eq (method A) and 54 CK-g-Eq (method B), and in group B 73 CK-g-Eq (method A) and 63 CK-g-Eq (method B). Mean values in group A1 were lower than in group A2 and group B (p less than 0.05). It is concluded that MI size was significantly reduced to about one third after early reperfusion as compared with no reperfusion. In contrast, MI size was not significantly reduced after late reperfusion.

Adult↗

Handling in infancy, brain laterality and muricide in rats.

Rats were handled for the first 20 days of life or were not disturbed. Between 21 and 50 days approximately half of each group was reared in enriched environments while the remainder was group reared in laboratory cages. When adult, four males from each litter received a right neocortical ablation, a left ablation, a sham operation, or no surgery. They were tested for mouse killing between 9-12 months of age. Intact non-handled controls without enrichment experience had a 96% incidence of muricide. Handling and enrichment treatments independently and additively reduced the rate of mouse killing in animals with intact brains. There was no evidence of brain laterality for animals which received no extra stimulation in early life. In contrast, the brains of handled animals were lateralized, with the left lesion group having a higher killing response than the right. Non-lesioned handled rats had approximately the same level of muricide as those with a right hemisphere lesion, leading to the inference that in the intact brain the left hemisphere inhibits the killing response of the right.

Aggression↗

Thrombolysis in acute experimental myocardial infarction.

Lysis of thrombi by intracoronary application of streptokinase has become a new therapeutic approach in patients with acute myocardial infarction. To simulate the clinical situation of myocardial infarction a new experimental model was developed, which was based on a thrombotic coronary occlusion at the site of a high degree stenosis created by a constrictor. In 20 dogs, two ligations 15 mm apart were prepared at the left anterior descending or circumflex coronary artery. After closure of the distal ligation, 2 IU of thrombin was injected through a catheter directly in front of the proximal ligation. The catheter was withdrawn and the proximal ligation was closed. Occlusion time ranged from 1 to 6 hours. At 1, 2, 4 and 6 hours after occlusion, streptokinase was infused for 1 hour (100,000 IU in 200 ml of saline solution) into the left main coronary artery. Hemodynamic variables and coronary blood flow to the ischemic and normal myocardial areas were recorded continuously. Myocardial perfusion was measured six times with tracer microspheres. Reinstatement of blood flow, as well as normalization of myocardial perfusion in the ischemic area, was achieved by streptokinase at 5 minutes after 1 hour of occlusion, 8 minutes after 2 hours, 15 minutes after 4 hours, and 30 minutes after 6 hours; no hyperemic flow occurred. Postmortem staining of infarct size revealed more than 50% of viable myocardium in the perfusion area of the thrombotic vessel even after 6 hours of occlusion. Hemorrhage occurred only after 6 hours of occlusion and was limited to the central area of necrosis in the subendocardial layer. Serious reperfusion arrhythmias occurred only after 1 and 2 hours of occlusion and seemed to be independent of the mode of reperfusion; however, the total number of episodes of ventricular fibrillation after reperfusion was probably decreased compared with that after sudden and hyperemic reflow.

Animals↗

Uptake of l-Ascorbate by Intact Spinach Chloroplasts.

Uptake of l-[1-(14)C]ascorbate by intact ascorbate-free spinach (Spinacia oleracea L. cv Vital(r)) chloroplasts has been investigated using the technique of silicone oil filtering. Rates greater than 100 micromoles per milligram chlorophyll per hour (external concentration, 10 millimolar) of ascorbate transport were observed. Ascorbate uptake into the sorbitol-impermeable space (stroma) followed the Michaelis-Menten-type characteristic for substrate saturation. A K(m) of 18 to 40 millimolar was determined. Transport of ascorbate across the chloroplast envelope resulted in an equilibrium of the ascorbate concentrations between stroma and medium. A pH optimum of 7.0 to 7.5 and the lack of alkalization of the medium upon ascorbate uptake suggest that only the monovalent ascorbate anion is able to cross the chloroplast envelope. The activation energy of ascorbate uptake was determined to be 65.8 kilojoules (16 kilocalories) per mole (8 to 20 degrees C). Interference of ascorbate transport with substrates of the phosphate or dicarboxylate translocator could not be detected, but didehydroascorbate was a competitive inhibitor. Preloading of chloroplasts with didehydroascorbate resulted in an increase of V(max) but did not change the K(m) for ascorbate. Millimolar concentrations of the sulfhydryl reagent p-chloromercuriphenyl sulfonate inhibited ascorbate uptake. The data are interpreted in terms of ascorbate uptake into chloroplasts by the mechanism of facilitated diffusion mediated by a specific translocator.

Journal Article↗

Noninvasive assessment of myocardial contractility in asymptomatic patients with sever aortic regurgitation and normal left ventricular ejection fraction at rest.

In 14 asymptomatic patients with isolated aortic insufficiency the slope k of the end-systolic pressure-volume relation was determined noninvasively with equilibrium radionuclide angiography. The results were compared with changes in left ventricular ejection fraction during maximal physical stress. Nine normal volunteers served as a control group. Patients with aortic insufficiency did not differ significantly from the control group with respect to left ventricular ejection fraction at rest (aortic insufficiency 62 + 8 percent, control 65 +/- 6; probability [p] = not significant [NS]), physical work capacity (aortic insufficiency 113 +/- 32 watts, control 117 +/- 25; p = NS) or age (aortic insufficiency 40 +/- 10 years, control 47 +/- 7; p = NS). The slope (k) of the end-systolic pressure-volume relation was found to be significantly lower in the group with aortic insufficiency (3.1 +/- 1.1) than in the control group (4.1 +/- 0.5; p less than 0.05). Patients with aortic insufficiency could be classified into two subgroups with respect to the slope k. In subgroup A (n = 7) the slope fell within the normal range (4.0 +/- 0.6) as defined by the control group, and the left ventricular exercise reserve was normal (6 percent +/- 1). In subgroup B (n = 7) the slope was significantly lower (2.2 +/- 0.6, p less than 0.01), indicating depressed myocardial contractility, and all patients experienced left ventricular dysfunction during exercise (left ventricular exercise reserve -5 +/- 5 percent). Thus, noninvasive determination of the end-systolic pressure-volume relation identified two subsets of asymptomatic patients with aortic insufficiency, one with impaired myocardial contractility and normal left ventricular exercise reserve and a second group with depressed myocardial contractility and left ventricular dysfunction during exercise. Therefore, an abnormal baseline contractile state in asymptomatic patients with aortic insufficiency may be uncovered by noninvasive determination of the end-systolic pressure-volume relation or by assessing the left ventricular exercise reserve. Serial studies in a larger group of patients undergoing surgical correction of the valve lesion are indicated to determine whether this information will be helpful in evaluating when to operate on asymptomatic patients with aortic insufficiency.

Adult↗

Intracoronary thrombolysis in acute myocardial infarction: duration of ischemia as a major determinant of late results after recanalization.

To define the effect of duration of myocardial ischemia on the late results after successful thrombolysis in patients with acute transmural myocardial infarction, data on 39 patients treated with intracoronary infusion of streptokinase were analyzed. Patients with successful recanalization of infarct vessel and a time lag between onset of symptoms and reperfusion less than 4 hours were assembled in group A1 (n = 15), and patients with successful recanalization but a time lag of more than 4 hours (n = 17) in group A2. Group B consisted of 7 patients with unsuccessful thrombolysis. Coronary anatomy, left ventricular volume, ejection fraction, and regional ejection fraction of infarct area were determined before and 4 weeks after thrombolysis with cineangiography. Serum creatine kinase activity was serially measured. Before intervention, the groups were comparable with regard to age, Killip class, localization of infarction, incidence of previous infarction, Gensini score of coronary anatomy, left ventricular volume, ejection fraction, regional ejection fraction of infarct area, and serum creatine kinase activity. Four weeks after the intervention, patients in group A1 had a higher ejection fraction (59%) and regional ejection fraction of infarct area (39%) than patients in group A2 (ejection fraction: 49%, p less than 0.05; regional ejection fraction: 26%, p less than 0.05) and group B (ejection fraction: 44%, p less than 0.05; regional ejection fraction: 25%, p = 0.05). Peak serum creatine kinase activity measured during the acute illness was lower in group A1 (764 U/liter) than in group A2 (1,580 U/liter, p less than 0.05) and group B (2,106 U/liter, p less than 0.05). Thus, contraction of infarct area was improved and enzymatic estimate of infarct size was reduced after early as compared with late reperfusion in patients with acute myocardial infarction.

Aged↗

Native collaterals in the development of collateral circulation after chronic coronary stenosis in mongrel dogs.

The response of native collateral circulation to chronic stenosis of the left circumflex coronary artery (LCx) was studied in 17 mongrel dogs. Stenosis restricted reactive hyperemia of the LCx without affecting resting flow. Regional myocardial blood flow was measured by the tracer microsphere technique. Coronary collateral blood flow to the LCx was determined during maximal reactive hyperemia of the left anterior descending branch before and 5 weeks after implantation of a fixed LCx stenosis in the open-chest preparation. The protective effect of collaterals was tested by LCx ligation 5 weeks after implantation of stenosis. Presence of acute myocardial infarction was determined by nitroblue tetrazolium staining. Eleven dogs had a myocardial infarction (group A), but six dogs showed no evidence of infarction at autopsy (group B). In group A, collateral flow and minimal coronary resistance of the LCx bed changed little after LCx stenosis, from 12 to 15 ml/min/100 g and from 10.5 to 10.0 mm Hg/ml/min/100 g, respectively (both p less than 0.05). In contrast, collateral flow in group B increased from 22 to 102 ml/min/100 g (p less than 0.05), and minimal coronary resistance of the LCx bed decreased from 4.8 to 1.4 mm Hg/ml/min/100 g (p less than 0.01). Group A had lower native collateral flow (p less than 0.05) and higher native minimal coronary resistance of the LCx bed than group B (p less than 0.05). Postobstructive LCx pressure correlated well with blood flow data. The LCx risk region was of comparable size in groups A and B, 36.4% vs 39.0% of total left ventricle (p greater than 0.05). Two responses of collateral circulation to chronic stenosis were documented: lack of collateral growth in group A, but significant collateral growth in group B. The natural variation of collateral circulation was the major determinant of the different responses that were important with stenosis of a major coronary artery.

Animals↗

Thrombolysis in acute myocardial infarction using intracoronary streptokinase: assessment by thallium-201 scintigraphy.

Twenty-one patients with acute myocardial infarction, admitted to the hospital within 4 hours after the onset of symptoms, were studied by seven-pinhole thallium-201 scintigraphy before and 1 hour and 24 hours after intracoronary fibrinolysis using streptokinase. The size of the thallium-201 perfusion defect was assessed from myocardial cross sections reconstructed from the original seven-pinhole data and expressed as a fraction of left ventricular circumference. Recanalization was achieved in 16 patients within 3.9 +/- 1.6 hours after onset of symptoms (group A). In these patients, the size of the perfusion defect had decreased from 36 +/- 17% to 19% +/- 15% (p less than 0.001) at 24 hours. No significant change was detected by redistribution at 1 hour after the intervention. In five patients, intracoronary fibrinolysis was unsuccessful, and the vessel remained occluded (group B). The thallium-201 perfusion defect affected 40 +/- 15% of the left ventricular circumference before the intervention; it remained virtually unchanged at 1 hour (37 +/- 16%) and at 24 hours (41 +/- 15%) after fibrinolysis. The perfusion defect was most reduced in patients with extensive collaterals supplying the ischemic area or with subtotal occlusion of the affected coronary artery. We conclude that successful intracoronary fibrinolysis may reduce the size of the thallium-201 perfusion defect in many patients with acute myocardial infarction. One important factor in the final result may be the presence of residual coronary flow supplied by extensive collaterals or by subtotal occlusion of the affected coronary artery when reperfusion is achieved around 4 hours after the onset of symptoms.

Adult↗