Evidence for post-cleavage fertilization among mosaics in Habrobracon juglandis.

Habrobracon females homozygous for the mutant ebony produce about 5% mosaic progeny among fertilized eggs. The present experiment demonstrates by means of a test-cross method that in the production of these mosaics only one pronucleus is involved, and that this nucleus cleaves before union of one of its daughter nuclei with the sperm nucleus.

The interrelation of renin and iron binding capacity.

When rats are subjected to hypoxia, an increase in serum angiotensinogen concentration occurs which is accompanied by the appearance of serum erythropoietin (EP) during the first 24 h. Subsequent increases in EP reach maximum values 24 to 48 h after increases in packed cell volume (PCV) and serum renin levels. The current experiments were designed to determine if a decrease in iron stores is the stimulus for renin production when rats are rapidly expanding their red cell volume in a hypoxic environment. Young rats fed McCall's low iron diet were paired with rats fed the same diet supplemented with ferric citrate (6 g/kg diet). After two weeks at ambient pressure, they were subjected to hypoxia (0.48 atm) for 1 to 10 days. After 5 days at the reduced pressure, a fraction of the rats on the low iron diet were fed the iron-supplemented diet. At the time of sacrifice, serum was assayed for total iron binding capacity (TIBC) and renin. Rats that were fed the low iron diet showed an increase in TIBC, an increase in serum renin and a positive correlation between serum renin and TIBC. Rats that were fed a normal iron diet under the same conditions had lower TIBC, lower serum renin and no correlation between serum renin and TIBC. When low iron diet rats were supplemented with iron, TIBC and serum renin decreased. These experiments may have a clinical counterpart. The total iron binding capacity, renin and angiotensinogen were measured in the serum of women during the first 19 weeks of pregnancy. Women during early pregnancy showed an increase in TIBC, an increase of renin and angiotensinogen in the serum and a positive correlation between TIBC and renin concentration. It is suggested that the increased concentration of renin in the serum of women during the first 19 weeks of pregnancy and in the serum of rats that are rapidly expanding their red cell volume are related to a decrease in iron stores.

Biochemical and dynamic responses to single and repeated doses of methyldopa and propranolol during dynamic physical activity.

Our purpose was to describe changes in potassium disposition with antirenin antihypertensives during dynamic physical activity in normal subjects receiving methyldopa and propranolol. Before the study, 2 hr after dosing and coincident with immediate preexercise on treadmill (at graded increases of exercise), and 2 hr after exercise, blood was sampled for determination of potassium, renin, aldosterone, and catecholamine levels. Blood pressure and heart rate were measured. The results demonstrate no greater increase in potassium after single or multiple doses of methyldopa than after placebo. After the first dose of propranolol there was a greater rise in potassium over that with placebo, but it was not observed after multiple doses, which may be related to the low doses. There were minor, but significant, changes in norepinephrine, renin, and systolic pressure with multiple-dose methyldopa and in renin, heart rate, and systolic and diastolic pressure with propranolol. Overall, the adrenergic responses to exercise win methyldopa and propranolol were biochemically altered rather than functionally impaired. The latter is related to dose and the underlying age and state of health of our subjects. Methyldopa (or clonidine) may be useful in patients with hypertension who exercise and are predisposed to pertubations in potassium disposition.

Dynamic and biochemical responses to single and repeated doses of clonidine during dynamic physical activity.

Beta-adrenoceptor blockade increases serum K, which may be related to renin inhibition, hypoaldosteronism, and exercise-induced skeletal muscle release of serum K. We report on the dynamic and biochemical response to clonidine (C) after single (S) 0.2-mg and repeated (R) 0.1-mg bid doses of C to six normal subjects at rest, 2 hr after dosing and immediately before dynamic physical activity (DPA) on a treadmill, and at peak activity and 2 hr after DPA. Blood pressure (BP), heart rate (HR), plasma renin concentration (PRC), aldosterone (ALD), serum K, epinephrine (E), and norepinephrine (NE) were measured in standing subjects before and 2 hr after placebo or C (S or R), at peak DPA, and 2 hr after exercise. K, BP, and HR were also determined during all stages of DPA. Results show a parallel rise in K at peak over rest after C (S or R) and after placebo. NE, E, and PRC decreased after 1 wk of C (P less than 0.01), but the fall of ALD was only slight. The fall in NE at rest suggested a relationship to the decrease in systolic BP and rate pressure product after 1 wk on C. With DPA there is a normal yet smaller increase in systolic BP and also a smaller rise in HR with S- and R-dose C. There is no adverse rise in K in C-treated subjects during DPA.

Behavior of life-shortening genes in genetic mosaics of Drosophila melanogaster.

Genetic mosaics of two life-shortening (adult lethal) genes in Drosophila melanogaster were analyzed with respect to the location and extent of external tissues which exhibited the life-shortening genotype. It was hoped by this method to localize the site of action of each gene. For one mutant, AL 2, no correlation was found between the site of the adult lethal genotype and the adult life span of the mosaic fly. However, there was a direct correlation between the total amount of tissue exhibiting the adult lethal genotype and length of adult life. For the other mutant, AL 4, a more direct correlation could be made between location of adult lethal tissue and a shortened adult life span. Its focus was oriented toward the cephalic region. Like AL 2, it exhibited a direct correlation between total adult lethal tissue and length of adult life. The importance of this method of genetic analysis for the understanding of the action of life-shortening genes is discussed.

Sensitivity to vasovagal maneuvers in normal children and adults.

In 15 male and 15 female healthy subjects who were 10 to 48 years of age, we studied alterations in heart rate and finger blood flow in response to the cold pressor test and four strong vasovagal maneuvers: diving response (apneic facial exposure to an ice water bag), Valsalva maneuver (forced expiration against a column of mercury to 40 to 50 mm Hg), unilateral carotid sinus massage, and oculocardiac reflex (inflation of a Honan balloon against one eye). Peripheral vasoconstriction as a consequence of the diving response paralleled the vasoconstriction from the cold pressor test, but it preceded the bradycardia that resulted from the diving response maneuver. In contrast, the rate of finger blood flow was high during the bradycardia that followed stage 4 of the Valsalva maneuver. Changes in heart rate correlated with age for the diving response, the Valsalva maneuver, and the oculocardiac reflex. Changes in heart rate and finger blood flow were not dependent on sex. The change in heart rate noted with the diving response was significantly correlated with that noted with the Valsalva maneuver and the oculocardiac reflex. Changes in finger blood flow did not correlate with changes in heart rate for any maneuver. This study provides a response profile of relative sensitivities to strong vasovagal maneuvers in normal children and adults.

Effect of an angiotensin-converting enzyme inhibitor on blood pressure and erythropoiesis in rats.

Positive correlation between systolic blood pressure and plasma renin substrate was demonstrated in Wistar-Kyoto rats when plasma renin substrate was reduced to within a range of 18 and 88% of control values with varying amounts of ramipril. When ramipril was given in amounts that had a maximum effect on systolic blood pressure, marked changes in erythropoietin, reticulocyte count and hematocrit % were observed. Consistent blood pressure-lowering effect was evident for several weeks after ramipril withdrawal. Furthermore, blood pressure obtained 3 days after the rats were taken off ramipril correlated positively with the hematocrit % measured while the rats were still on ramipril (r = 0.83; P less than 0.001). Mean blood volume of 17 rats receiving ramipril was similar to that of the 10 control rats. Plasma and renal renin substrate were highly and positively correlated (r = 0.86; P less than 0.001). Inasmuch as plasma renin substrate is rate-limiting for angiotensin I, it may reflect intrarenal AII and prove to be a useful clinical assessment of converting enzyme inhibition. The increased levels of renin, renin substrate and packed cell volume seen in rats fed Purina basal diet (10% fat) as compared with rats fed Purina lab chow (4.5% fat), support the working hypothesis that intrarenal angiotensin II controls both blood pressure and erythropoiesis.

Aspiration pneumonitis. Prevention and treatment.

Recognizing the factors that predispose patients to aspiration and identifying the patients who are susceptible to aspiration are the first steps in preventing aspiration pneumonitis. These steps should be followed by pharmacologic and physiologic management. Mechanical ventilatory support, bronchoscopy when indicated, and aggressive fluid management are essential when aspiration does occur.

Effect of a renin-system inhibitor on blood-vessel adaptation in spontaneously hypertensive rats.

We tested the hypothesis that a metabolic error may be the triggering mechanism which leads to blood-vessel hypertrophy and hypertension. Young spontaneously hypertensive rats (SHR) were fed a moderately high salt diet to exacerbate the purported metabolic error. Haematocrit values and rubidium transport were measured as evidence of renal ATP deficiency and blood-vessel adaptation. The renin system was inhibited in two groups of SHR by giving them enalapril to determine whether angiotensin II was involved in blood-vessel adaptation. Spontaneously hypertensive rats fed the moderately high salt diet had higher haematocrit values than normotensive rats fed the same diet or SHR fed Purina rat food, suggesting a renal ATP deficiency. Spontaneously hypertensive rats had higher Na+,K+-ATPase activity in thoracic aorta after 60 min incubation than a similar group given enalapril (P less than 0.001), suggesting blood-vessel adaptation. Possibly, angiotensin II within the vasa vasorum stimulates hypertrophy which, according to the Folkow hypothesis, leads to higher blood pressure, but may concomitantly increase the respiratory chain units which provide ATP for renal function and ion transport.

Blood pressure control and erythrocytosis in rats: theory and observations.

We compared some of our latest experiments on blood pressure control and erythrocytosis in spontaneously hypertensive rats with Gaar's computer-simulated studies, which suggest that erythrocytosis is a key to understanding the hemodynamic changes in hypertension. We tested two of Gaar's several predictions: (i) peripheral vascular resistance decreases when the feedback control of erythrocytosis is blocked and (ii) in primary hypertension, blood volume is increased slightly. We also studied the interrelation of systolic blood pressure and plasma renin substrate in spontaneously hypertensive rats, and the effect of diet on renin, blood pressure, and erythrocytosis. Our data showed that (i) on a percentage basis the renin system supports blood pressure essentially in the same manner in normal and hypertensive rats, (ii) peripheral vascular resistance decreased when erythrocytosis was partially blocked by feeding a low-iron diet, (iii) blood volume was similar in normal and hypertensive rats, and (iv) dextrin stimulates plasma renin, packed cell volume, and blood pressure in hypertensive rats. We conclude that blood pressure and erythrocytosis are interrelated, that the combined data of stimulated and experimental studies support the notion that primary hypertension is a blood-vessel adaptation in response to a renal energy need that may require additional oxygen.

Lack of global vagal propensity in patients with oculocardiac reflex.

BACKGROUND: Profound bradycardia during ophthalmic surgery is a rare but potentially serious event. Little is known about the predictability of the oculocardiac reflex. METHODS: Four vagotonic maneuvers were performed on six patients who had profound oculocardiac reflex (3- to 10-second asystole) during eye surgery, the results of which were compared with 30 previously studied control subjects. Electrocardiographs were monitored during the following vagotonic maneuvers: diving response (apneic facial immersion), Valsalva maneuver, ocular compression, and carotid sinus massage. RESULTS: The degree of heart rate slowing as a result of diving response, Valsalva maneuver, and, notably, ocular compression did not differ when these patients were compared with the 30 previously studied control subjects. Carotid sinus massage produced significantly (P = 0.01) more bradycardia in the six patients (mean +/- standard deviation, -24% +/- 6%) than in the 30 control subjects (-12% +/- 7%). The heart rate response to pressure on the eyes did not correlate with prior intraoperative oculocardiac reflex. CONCLUSION: The discrepancy in heart rate sensitivity between surgical extraocular muscle tension and ocular compression may be due to different sensory receptors and brain stem processing for the trigeminally mediated oculocardiac reflex. Carotid sinus massage may help predict low heart rates during eye surgery.