Citizens and scientists: toward a gendered history of scientific practice in post-revolutionary France.

Because the French Revolution failed to produce a widely acceptable definition of citizenship, the limits of manhood suffrage in the early nineteenth century were uncertain. Social practices, in particular scientific activity, served as claims to the status of citizen. By engaging in scientific pastimes, bourgeois Frenchmen asserted that they possessed the rationality and autonomy that liberal theorists associated both with manliness and with civic capacity. However, bourgeois science was never a stable signifier of masculinity or of competence. As professional science emerged, the bourgeois amateur increasingly became the feminised object of satire rather than the sober and meritorious citizen-scientist.

Activin expression by cultured human retinal pigment epithelial cells.

PURPOSE: To determine whether human retinal pigment epithelial (hRPE) cells produce activin, a growth factor in the transforming growth factor beta family, and to characterize growth regulatory effects of activin on retinal pigment epithelium. METHODS: mRNA expression was examined using polymerase chain reaction with primers specific for the beta A and beta B chains of activin and by slot blot analysis with a probe specific for the beta A chain. Protein localization was determined immunocytochemically using antibodies specific for the beta A chain of activin and intact activin A. The effect of activin A on DNA synthesis was studied by measuring (3H) thymidine incorporation after cells were exposed to recombinant human activin A (rhA). Growth regulatory effects of rhA on hRPE cells were examined with cell growth assays. RESULTS: beta A mRNA was expressed constitutively in 8/8 cells lines tested. beta B mRNA was not expressed in any of the six cell lines tested but was expressed in human ovarian granulosa cell controls. Positive immunostaining was observed for both the beta A chain and intact activin A. (3H) thymidine incorporation was inhibited 44% (P < 0.025), 45% (P < 0.025), and 44% (P < 0.015) when RPE cells were exposed to 100 ng/ml rhA and grown in serum-free medium, medium with 0.5% serum, and 1% serum, respectively. Cell growth was inhibited 33.2% (P = 0.0001) after RPE cells were exposed to 100 ng/ml rhA for 8 days. CONCLUSIONS: These results suggest that activin A can act as an autocrine-paracrine growth regulator in RPE cells and may help control cellular growth in ocular development and proliferative eye disease.

Role of protease inhibition in myocardial preservation in prolonged hypothermic cardioplegia followed by reperfusion. Effect of aprotinin in an experimental model.

The effects of aprotinin on canine myocardium subjected to cardioplegia and global ischemia for 4 hours and then reperfused for 1 hour were investigated. Lysosomal and mitochondrial enzymes and cyclic nucleotides (adenosine cyclic monophosphate and guanosine cyclic monophosphate) were measured in coronary sinus blood. Aprotinin was given intravenously before cardiopulmonary bypass at total doses of 10 X 10(3) kallikrein units per kilogram (group A, six dogs) and 20 X 10(3) KU/kg (group B, six dogs). In group A, three dogs survived but with poor cardiac function; all dogs in group B survived and had better cardiac function. Lysosomal (N-acetyl-beta-D-glucosaminidase) and mitochondrial (aspartate aminotransferase) enzymes in coronary sinus blood at 60 minutes of reperfusion were significantly (p less than 0.05) lower in group B than in group A. In both groups, guanosine cyclic monophosphate was significantly (p less than 0.01) lower during reperfusion than before cardiopulmonary bypass; however, the values were significantly (p less than 0.05) higher in group B than in group A. Serum adenosine cyclic monophosphate was lower during reperfusion than before bypass in both groups, but it recovered during reperfusion in group B. Myocardial adenosine triphosphate was well preserved in both groups but creatine phosphate was decreased (p less than 0.01) in group A. These results suggest that aprotinin at a dose of 20 X 10(3) KU/kg may be effective in preserving myocardial viability and function after prolonged cardioplegia.

Role of two-dimensional echocardiography in the prediction of in-hospital complications after acute myocardial infarction.

To evaluate prospectively the prognostic value of two-dimensional echocardiography after acute myocardial infarction, two-dimensional echocardiography was performed on 61 consecutive patients who were admitted to the hospital with this condition. A left ventricular wall motion score index was derived from analysis of regional wall motion; an index of 2.0 or more within 12 hours of admission identified patients at high risk for pump failure, malignant ventricular arrhythmia or death. These complications occurred in 24 of 27 patients with an initial wall motion score index of 2.0 or more, but in only 6 of 34 with an initial index of less than 2.0 (p less than 0.0005). Of the 47 patients who were in Killip class I on admission, complications developed in 11 (79%) of the 14 with an initial index of 2.0 or more, but in only 6 (18%) of the 33 with an initial index of less than 2.0. After acute myocardial infarction, early determination of the wall motion score index by two-dimensional echocardiography is useful for identifying patients at high risk for complications and is especially valuable in the subset of patients who initially seem to be in stable condition as judged from clinical variables.

Cardiovascular hemodynamics of bicycle and handgrip exercise in normal subjects before and after administration of propranolol.

Radionuclide angiography was used to study the effects of supine and upright bicycle exercise and handgrip exercise in 17 (12 well-trained) normal subjects before (control) and immediately after the administration of propranolol (160 mg/day for 4 days). Cardiac hemodynamic values were related to position in that control left ventricular volumes and the cardiac index were greater in the supine position than in the upright at rest but resting left ventricular ejection fraction was similar in both positions. The pressure volume index was greater in the upright position than in the supine. At maximal exercise before treatment, however, similar cardiovascular hemodynamic measurements were recorded in both positions. Propranolol increased left ventricular end-diastolic volume at rest and at maximal exercise. Left ventricular end-systolic volume, however, was substantially greater only in the upright position both at rest and at maximal exercise when compared with control values. Heart rate, systolic arterial pressure, cardiac index, and pressure volume index were decreased at rest and maximal exercise after treatment with propranolol. Ejection fraction was decreased in the upright position after propranolol administration but was unchanged in the supine position. Handgrip exercise primarily increased heart rate and arterial pressure and did not affect cardiac volume, and this response was unaffected by propranolol.

Reentrant tachycardia associated with atrial synchronous pacing. Report of a case with intact ventriculoatrial conduction.

Reentrant tachycardia occurred after implantation of an atrial synchronous ventricular-inhibited pacemaker in a patient with bradycardia caused by second-degree (Mobitz II) atrioventricular block. Despite the presence of antegrade atrioventricular block, intact ventriculoatrial conduction was present at a cycle length that exceeded the atrial refractory period of the pacemaker. Consequently, a reentrant or "endless-loop" tachycardia occurred. Application of a magnet terminated the tachycardia. Because the episodes were frequent and could not be prevented by medication, the pacemaker was reprogrammed to a ventricular-inhibited mode. All candidates for atrial synchronous pacing should undergo an appropriate electrophysiologic study preoperatively.

Relationship between left ventricular morphology and postoperative cardiac function following valve replacement for mitral stenosis.

The left ventricular myocardium excised from 14 patients who had mitral stenosis and who underwent mitral valve replacement was examined, and myocardial fibrosis was quantitated in relation to cardiac function. Conventional mitral valve replacement was performed with cold potassium-induced cardioplegia associated with systemic hypothermia (28 degrees C rectal temperature) and topical cooling. All 14 patients had perivascular fibrosis; the amounts ranged from 16% to 54% of the whole tissue excised. The mean left ventricular end-diastolic volume index (LVEDVI) determined by M-mode echocardiography increased significantly (p less than 0.001) from 66.9 +/- 4.6 ml/m2 preoperatively to 79.0 +/- 2.9 ml/m2 postoperatively. The difference between preoperative and postoperative LVEDVIs was significantly correlated (p less than 0.01) to the percentage of myocardial fibrosis (r = 0.72), in that the index increased postoperatively when myocardial fibrosis was more than 35% and decreased when fibrosis was less than 35%. After mitral valve replacement, the mean ejection fraction increased when fibrosis was less than 35% of whole tissue (+0.12 +/- 0.04) and decreased when fibrosis was greater than 35% (-0.02 +/- 0.02, p less than 0.01). No measured preoperative hemodynamic parameters were predictive of prognosis. These data suggest that the degree of myocardial fibrosis is related to left ventricular performance after mitral valve replacement.

Five-year experience with temporary pacemaker therapy in the coronary care unit.

The clinical course of 1,022 consecutive patients who received a temporary transvenous pacemaker in the coronary care unit during a 5-year period between January 1976 and January 1981 was reviewed. The route of pacemaker insertion was identified in 942 patients (92.2%) and included antecubital vein cutdown in 606 patients (59.3%), subclavian venipuncture in 177 patients (17.3%), right internal jugular venipuncture in 111 patients (10.9%), and femoral venipuncture in 48 patients (4.7%). Pacemaker-related complications occurred in 140 instances (13.7% morbidity), without associated mortality. The most common complication was the development of a new pericardial rub (54 patients, 5.3%). The right internal jugular approach was associated with the lowest complication rate. On the basis of these findings, it is our practice to insert temporary pacemakers via the right internal jugular or subclavian route.

Detection of intracellular anoxia and its relationship to onset of hemodynamic dysfunction and ST-segment elevation in the intact dog heart.

The temporal relationships among onset of cellular anoxia after coronary artery occlusion, contractile dysfunction, and electrocardiographic ischemia were studied in dogs with an intact circulation. Nicotinamide adenine dinucleotide (NADH) fluorescence was used to detect intracellular anoxia, using a fiber-optic method. Paired NADH concentrations from ischemic (394 +/- 10 mumol/g) and normoxic (285 +/- 11 mumol/g) regions of the heart were obtained, and the differences (delta[NADH]) were correlated with compensated fluorescence (r = 0.76, P less than 0.01). Onset of fluorescence occurred 1 to 2 sec after coronary artery occlusion, followed by hemodynamic (5 sec) and electrocardiographic (13 sec) changes. These data indicate that intracellular anoxia, with alterations in redox potential, is not synchronous with the onset of contractile failure and provide indirect support for intracellular acidosis as the likely mediator of contractile failure.

Preservation of oxidative phosphorylation by lidocaine in ischemic and reperfused myocardium.

The effect of lidocaine (2 mg/kg bolus, 0.04 mg/kg per min infusion) on ischemic and reperfused myocardial respiration was assessed in 32 dogs, using indices of mitochondrial respiration (ADP:O ratio, state 3 and state 4 respiration, and respiratory control index). Heart rate, left ventricular (LV) pressure, LV dp/dt, cardiac index, epicardial ST segment, and regional myocardial blood flow, using 9 +/- 1 micron radiospheres, were measured after 40 min of constriction of the anterior descending coronary artery (N = 16) and after 20 min of reperfusion (N = 16). Results showed that lidocaine increased state 3 respiration and respiratory control in reperfused myocardium (P less than 0.05) with both glutamate and succinate-rotenone as substrate. It is concluded that lidocaine improves postischemic mitochondrial oxidative phosphorylation independent of altered hemodynamics or change in myocardial blood flow.

Protective effect of lidocaine during regional myocardial ischemia: an altered pathophysiologic response assessed by NADH fluorescence.

Studies were undertaken to determine the effects of lidocaine on ischemic myocardium, which was induced by coronary artery constriction in open-chested dogs. A real-time epicardial fluorescent technique to detect in vivo-reduced nicotinamide adenine dinucleotide (NADH) during 60 seconds of ischemia was used. Blood flow of ischemic myocardium was measured by using radioactive microspheres of 9 +/- 1 micrometers (mean +/- SE) and was compared with that of normal myocardium, shown by injection of alpha-zurine blue dye. Lidocaine effectively reduced peak NADH fluorescence by 18.6%, from 93.9 +/- 7.2 to 76.4 +/-4.1 mV (p less than 0.005). Lidocaine delayed the onset of fluorescence (2.2 +/- 0.2 versus 1.3 +/- 0.1 s p less than 0.002) and facilitated the recovery from ischemia (38.4 +/- 2.9 versus 54.8 +/- 2.9 s p less than 0.001). Increase in NADH concentration during ischemia correlated (r=0.76, p less than 0.006) with ischemic fluorescence. These findings were independent of altered hemodynamics or change in myocardial blood flow. Results indicate that lidocaine provides myocardial cellular protection during transient ischemia; there is an altered NADH fluorescent response to coronary artery occlusion.

Beneficial effects of multidose coronary artery washout during elective cardiac arrest and cardiopulmonary bypass: biochemical and hemodynamic evaluation.

Coronary artery washout with buffered saline (pH 7.4) during 60 and 120 minutes of elective cardiac arrest was studied in dogs during moderate hypothermic cardiopulmonary bypass. Compared with results in a group undergoing simple ischemic arrest, significantly greater myocardial adenosine triphosphate concentrations were present at 90 and 120 minutes of cardiac arrest in the coronary artery washout group. After 60 minutes of aortic cross-clamping and 60 minutes of reperfusion, left ventricular function was significantly superior in the coronary artery washout group. Coronary artery washout during the period of aortic cross-clamping preserves dynamic myocardial performance during reperfusion and is an important principle of myocardial protection during elective cardiac arrest.

Lidocaine-induced reduction in size of experimental myocardial infarction.

In anesthetized open chest dogs, the effects of therapeutic doses of lidocaine on myocardial cell respiration, creatine kinase depletion, left ventricular stroke work and cardiac necrosis were assessed. The dogs were subjected to 40 minutes of occlusion of the left anterior descending coronary artery, followed by 5 hours of reperfusion. Group I (12 dogs) had infusion of saline solution; group II (8 dogs) had infusion of 0.2 mg/kg per min of lidocaine (serum level 16.8 +/- 1.4 microgram/ml); group III (5 dogs) had infusion of 0.04 mg/kg per min or lidocaine (serum level 3.6 micrograms/ml). Ischemic regional myocardial blood flow (measured by 9 micrometer spheres of strontium-85) was 6.34 +/- 1.62 ml/100 mg per min in group I, 1.48 +/- 0.59 in group II (p < 0.05) and 1.32 +/- 0.50 in group III (p < 0.05). Oxygen consumed during conversion of adenosine diphosphate to adenosine triphosphate in mitochondria from control and lidocaine-treated ischemic tissue was depressed (p < 0.05) and correlated (r = 0.63) with creatine kinase depletion. Left ventricular stroke work was not significantly different among the three groups. Infarct size (in percent of left ventricular weight) was 12.6 +/- 2.0 for group I, 4.8 +/- 1.2 for group II (p < 0.01) and 4.8 +/- 2.5 for group III (p < 0.05). The data suggest that the reduction of myocardial infarct size by lidocaine was not dependent on enhanced myocardial blood flow and was independent of left ventricular stroke work.

Failure of interventions to maintain mitochondrial function in ischemic myocardium.

The purpose of this study was to investigate whether pyruvate (2.5 mmol/kg), the combination of glucose (3.9 mmol/kg) and insulin (0.13 unit/kg) with potassium (9.27 meq/kg), or sodium dichloroacetate (120 mg/kg) infused for 15 minutes before and 20 minutes after ligation of the left anterior descending coronary arterv in anesthetized dogs restricted the depression in mitochondrial respiratory function induced by ischemia. Myocardial blood flow after ligation in the three groups was o.2 ml/min per gram or less in ischemic subendocardium and was similar to that in saline-infused controls that had also undergone coronary artery ligation. The depressions induced in mitochondrial respiratory control index and state 3 respiration by ischemia in the subendocardium and subepicardium of the three treatment groups, when compared with corresponding nonischemic tissue, were not significantly improved from the control values. It was concluded that these three interventions fail to preserve mitochondrial respiration in ischemic myocardium.

Effect of betamethasone on mitochondrial oxidative phosphorylation in ischemic canine myocardium.

Hemodynamics and myocardial blood flow were studied in 14 anesthetized open-chest dogs that were subjected to coronary artery occlusion followed by reperfusion. In six dogs, betamethasone was given intravenously 30 minutes before occlusion. During reperfusion, a significant increase in myocardial blood flow in nonischemic tissue was observed in the betamethasone group as compared with control (P less than 0.05). Also, the increase in myocardial blood flow in steroid-treated nonischemic tissues during reperfusion was significantly greater (P less than 0.05) than that measured in ischemic tissues in the same group. However, betamethasone failed to protect mitochondrial respiration from ischemic damage. Respiratory control indices in ischemic tissues were significantly depressed, compared with those in nonischemic tissues, even in betamethasone-treated dogs, and the degree of depression was the same in the ischemic tissues of control and treated dogs. These data suggest that betamethasone was not effective in preserving mitochondrial function in ischemia but that it increased myocardial blood flow in nonischemic tissue.

Effect of magnesium in cardioplegic solution upon hypothermic ischemic myocardial mitochondria.

Twelve anesthetized mongrel dogs were subjected to systemic hypothermia and potassium-induced cardioplegia for 60 minutes with or without magnesium-1-aspartate. The effect of magnesium was assessed by indices of mitochondrial oxidative phosphorylation. Cardiac arrest was induced by potassium (20 mEq per liter) (6 dogs) or potassium (20 mEq per liter)- magnesium (8 mM per liter). The heart was reperfused for ten minutes following arrest. Dogs were supported by standard cardiopulmonary bypass with hypothermia at 20 degrees C of myocardial temperature. Mitochondria were isolated from the endocardium, the epicardium of the left ventricle and the ventricular septum. ADP: 0 ratio and state 3 respiration were well maintained in both groups following 60 minutes of ischemic arrest and 10 minutes of reperfusion. Magnesium suppressed the non-phosphorylated oxygen consumption of mitochondria, therefore, respiratory control index was signficantly enhanced in the group of potassium-magnesium-1-aspartate cardioplegia. These data suggest that magnesium protects functional capacity of mitochondrial phosphorylation in the myocardium from ischemia.

Myocardial respiration and edema following hypothermic cardioplegia and anoxic arrest.

The effects of 1 and 2 hours of hypothermic anoxic arrest and cardioplegia induced by Mg-lidocaine, K-Mg, or K on left ventricular mitochondrial respiratory function, blood flow, and edema were studied in 41 mongrel dogs. Mitochondrial respiration was assessed by the indices of oxidative phosphorylation. Myocardial temperature recorded in ventricular septum was kept at 20 degrees C during ischemic arrest and 10 minutes of reperfusion. Cardioplegic solutions did not influence noncoronary blood flow during cross-clamping of the aorta. Mitochondrial respiratory function remained at control levels after 1 hour of ischemia induced by hypothermic anoxic arrest or by Mg-lidocaine or K-Mg hypothermic cardioplegia. Mitochondrial state 3 respiration after 2 hours of anoxic arrest was significantly higher in Mg-lidocaine cardioplegia than in anoxic arrest (p less than 0.05), but myocardial edema was equivalent in both groups. Mg in the cardioplegic solution suppressed mitochondrial nonphosphorylating oxygen consumption. These data suggest that mitochondrial function after 1 hour of ischemic arrest at 20 degrees C and 10 minutes of reperfusion is not significantly depressed, but at 2 hours of ischemic arrest, mitochondrial respiration is significantly impaired. However, hypothermic Mg-lidocaine cardioplegia appears to be more effective in sustaining myocardial respiration than does simple hypothermic anoxic arrest when the anoxic period is extended to 2 hours.