Factors contributing to blood pressure elevation during norepinephrine and phenylephrine infusions in dogs

To examine the factors contributing to the rise in systemic blood pressure during α- and β- adrenergic stimulation, phenylephrine, an α-adrenergic agonist, and norepinephrine, an α- and β-adrenergic agonist, were infused intravenously to anesthetized dogs until mean aortic blood pressure was raised equally by 40–60 mmHg. Changes in preload were estimated by changes in left ventricular end-diastolic pressure or segment length recorded by an ultrasonic technique. By obstructing the inferior vena cava (IVC), the increase in preload could be reduced to control level during phenylephrine and norepinephrine infusions without altering peripheral resistance (mean aortic blood pressure/cardiac output). Normalization of preload reduced the pressure response by 2/3 during phenylephrine infusion and by 1/4 during norepinephrine infusion. However, after β-adrenergic blockade by propranolol, normalization of preload reduced the pressure response by 2/3 during both phenylephrine and norepinephrine infusions. Thus, during α-adrenergic stimulation, the increase in preload is a more important factor than the increase in peripheral resistance. Norepinephrine raised stroke volume by 24±5%. When the increase in stroke volume was prevented by IVC obstruction, the pressure response to norepinephrine was halved. Thus, during norepinephrine infusion the rise in stroke volume caused by β-adrenergic stimulation is as important as α-adrenergic stimulation for the pressure response.     

Mechanism of blood pressure elevation during angiotensin infusion

The mechanism of increased preload and its contribution to the rise in blood pressure during intravenous angiotensin infusion were studied in anesthetized dogs. In open-chest dogs angiotensin increased mean aortic blood pressure by 58±12 mmHg. Left ventricular end-diastolic dimension, measured as myocardial chord length (MCL) by ultrasonic technique, increased by 7±1 %. By inflating a balloon in the inferior vena cava, end-diastolic MCL was reduced to control value and the rise in mean aortic blood pressure was almost halved to 32±10 mmHg above control value. A similar preload effect was recorded in closed-chest dogs using end-diastolic left ventricular pressure as an estimate of left ventricular volume. During angiotensin infusion to the upper body only, end-diastolic MCL did not increase. When redistribution of the splanchnic blood volume was prevented, the effect of angiotensin on end-diastolic MCL was reduced to 1/3. Angiotensin reduced liver but not splenic dimension measured by ultrasonic technique. We conclude that about half of the rise in blood pressure during angiotensin infusion is due to increased end-diastolic volume caused by blood redistribution. About 2/3 of this increase in preload is due to redistribution from the splanchnic bed, mainly from the liver.     

Immunological Studies of Patients with Down's Syndrome

Abstract. Recurrent diarrhoea and weight loss in many adult patients with Down's syndrome (DS), initiated a search for malabsorption based on determination of serum IgG and IgA antibody levels to dietary antigens. The results were compared with measurements of autoantibodies and serum zinc levels. DS patients had increased IgG and IgA activities to gluten proteins, casein and ovalbumin compared with an age- and sex-matched group of other mentally retarded patients in the same institution. Intestinal biopsy was performed in six of the 38 patients; one had total and one partial villous atrophy. Serum zinc was significantly lower in DS patients (median 14.7 μmol/l, range 5.5–20 μmol/l) than in the controls (median 16.4 μmol/l, range 12.7–19.5 μmol/l). DS patients with increased IgA activity to gluten weighed less and had lower concentrations of zinc in serum than DS patients with normal IgA activity. Twenty-eight per cent of the DS patients had autoantibodies to the thyroid gland. Our results suggest intestinal malfunction in DS, perhaps related to a defect of immune regulation caused by reduced levels of zinc in serum.     

Activities of glycolytic and citric acid cycle enzymes in oral leukoplakia

abstract — Biopsies of homogeneous leukoplakias and non-involved oral mucosa were obtained from the same patient, and buccal mucosa samples were obtained from individuals free of oral mucous membrane disease. Activities of glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK), glycerol-3-phosphate dehydrogenase (G3PDH), NAD and NADP dependent isocitrate dehydrogenases (ICDH) were quantitated in microdissected specimens of the superficial third of the epithelium. ICDH (NAD) was measured photo-kinetically with the aid of a bioluminescent system. The remaining enzymes were assayed according to the techniques developed by l owry and co-workers. The activities of G6PDH and G3PDH in non-involved mucosa of leukoplakia patients were double those of mucosa from healthy controls. The activities of PK and ICDH (NAD and NADP) in these two groups of lesion-free mucosa were similar. Non-involved mucosa differed from leukoplakias with respect to the two ICDH's. In hyperorthokeratinized leukoplakias, NAD and NADP dependent ICDH activities were decreased by 59% and 37%, respectively. The values for the two ICDH's in hyperparakeratinized lesions lay between the levels of activity in noninvolved mucosa and hyperorthokeratotic leukoplakias but did not differ significantly from either.     

Angiotensin II infusion during β-adrenergic stimulation by isoproterenol. Effects on hepatic,splenic and cardiac blood volumes and on the magnitude and distribution of cardiac output in the dog

The cardiac and peripheral vascular adjustments to angiotensin II (0.1–0.2 μg kg^-1 min^-1 i.v.) during high β-adrenergic activity by a continuous isoproterenol infusion (0.2–0.3 μg kg^-1 min^-1 i.v.) were examined in anaesthetized, atropinized dogs. Hepatic, splenic and left ventricular (LV) volume changes were estimated by an ultrasonic-technique, and the blood flow distribution was measured by injecting radioactive microspheres and by electromagnetic flowmetry on the caval veins, the hepatic artery and the portal vein. During isoproterenol infusion, angiotensin II increased the systolic LV pressure by 45 ± 3 mmHg and the stroke volume by 17 ± 6 %. Concomitantly, the hepatic and splenic blood volumes declined by 29 ± 4 and 14 ± 6 ml, respectively, and the LV end-diastolic segment length increased by 3 ± 1 %. The flow through the inferior caval vein increased by 39 ± 9%, whereas the superior vena caval flow remained unchanged. The hepatic arterial flow more than doubled. Thus, at high inotropy by isoproterenol infusion, angiotensin II relocates blood from the liver and the spleen towards the heart. By activating the Frank-Starling mechanism, cardiac output is increased and conducted through the lower body, especially through the hepatic artery, because of the poor autoregulation of flow through this vessel.,     

Contributions of blood drainage from the liver,spleen and intestines to cardiac effects of aortic occlusion in the dog

By occluding the descending thoracic aorta, blood transferred from the lower to the upper part of the body increases left ventricular end-diastolic volume and maintains stroke volume despite a rise in systolic left ventricular pressure (LVP) of about 60 mmHg. Seventy percent of the blood drained stems from the splanchnic circulation. To examine which splanchnic organs contribute to the cardiac effects, selective occlusions were performed during ultrasonic measurements of spleen and liver dimensions and left ventricular myocardial chord length (MCL) in atropinized, open-chest dogs. Drainage of 15±2 ml from the spleen accounted for 18±4% of the increase in end-diastolic MCL, whereas liver dimensions remained unaltered. Similar results were obtained during aortic occlusion at high inotropy (isoproterenol infusion). it was ascertained by occlusion of the coeliac and mesenteric arteries that about 50% of the cardiac response to aortic occlusion was due to drainage from the intestines and the aorta. Liver blood volume could be reduced by combined occlusion of the aorta and portal vein or coeliac and mesentenc arteries and was sensitive to changes in pressure in the inferior vena cava, but did not contribute to the cardiac response to aortic occlusion.