Jaundice, the circulation and the kidney.

(Fig. 1) Cholemia per se (i.e. independent of parenchymal liver damage) causes a profound disturbance of systemic hemodynamics. This includes decrease in total peripheral vascular resistance, and possible impairment of left ventricular performance. These, in turn, lead to a decrease in effective blood volume, a tendency to hemorrhagic shock and prerenal failure. Early in the course of cholemia , the natriuretic effects of bile salts in the circulation may aggravate the hypovolemia. In marked contrast to the decrease in total peripheral vascular resistance, the regional vascular beds of the kidney and the brain constrict during cholemia . The combined effect of cholemia may thus lead to redistribution of cardiac output away from the kidney and the brain. When parenchymal liver damage complicates obstructive jaundice, the tendency to arterial hypotension is aggravated. The overall interrelationship between jaundice and circulatory homeostasis is depicted in figure 1.

Concentration and composition of plasma proteins in wild mammals.

Total protein concentrations from a variety of wild mammalian species were measured by the Lowry and Biuret techniques and compared with results obtained or derived by refractometry. Values obtained with the Lowry method were the highest and certain derived refractometry results, the lowest. It is suggested that the Biuret method provides the most acceptable values but that care should be exercised in using the correct standard. The percentage composition of plasma from 22 species of wild mammals is also presented and the observations discussed with relation to methodology and A/G ratio.

Effect of peroral administration of sotalol on the hemodynamics of the baboon.

We investigated the effect of oral administration of sotalol on coronary and renal blood flow and other hemodynamic parameters of the baboon. Measurements were made in anesthetized baboons under basal conditions and during the intravenous infusion of isoproterenol at rates of 0.5, 1.0, 2.0 microgram. min-1 in an experimental (n = 20) and a control (n = 6) group. Subsequently, sotalol (dose 1-4 mg.kg-1, mean 2.25 mg.kg-1) or placebo was administered. After 2 h the procedure was repeated. Measurements included renal (RBF) and coronary (COR BF) blood flow, cardiac output (CO), heart rate (HR), stroke volume (SV), left ventricular systolic pressure (LVSP), maximum positive dP/dt (dP/dt max), aortic diastolic (APD) and mean (APM) pressures, heart rate-left ventricular systolic pressure product (RPP), and left ventricular stroke work index (LVSWI). RBF and COR BF were determined indirectly from the rate of 133 Xe clearance. In the control group, changes before and after the administration of placebo did not differ significantly for all parameters. In the experimental group, changes after sotalol administration were significantly lower for COR BF, CO, HR, LVSP, dP/dt max, APD, APM and RPP, but were not significantly different for RBF, SV and LVSWI. Beta-blockade had no effect on RBF. The reduction in COR BF was associated with a reduction in RPP (myocardial oxygen consumption). However, the oxygen supply-demand relationship was maintained. Decrease in CO was largely due to reduction in HR since SV (and LVSWI) were unaffected by Beta-blockade.

Oestrogen-induced bone marrow aplasia in a dog.

A case of oestrogen toxicity in the dog is described. The bone marrow was primarily affected with resultant non-regenerative anaemia, leukocytosis followed by leukopaenia, and thrombocytopaenia. Endometritis, toxaemia and disseminate intravascular coagulation were complicating factors. The case terminated fatally intensive therapy.

The effect of dopamine on renal cortical blood flow in baboons with experimentally induced obstructive jaundice.

The effect of dopamine hydrochloride on renal blood flow in bile duct ligated baboons was assessed using the 133Xe washout technique. Intrarenal infusions of dopamine in different concentrations did not significantly increase renal cortical blood flow. On the contrary, over the lower dose range, the normal dopamine-induced renal vasodilatation was abolished in the jaundiced state. An in vitro experiment that measured the perfusion pressure of an isolated rabbit kidney perfused with normal and jaundiced baboon plasma confirmed the in vivo results. These observations suggest that dopamine would not be of value in treating the renal failure that may develop in patients with obstructive jaundice.

Impaired skeletal muscle vasomotor response to infused noradrenaline in baboons with obstructive jaundice.

1. We have measured muscle blood flow by a 133Xe clearance technique, and its response to noradrenaline in baboons before and 2 weeks after ligation of the bile ducts when they were jaundiced. 2. In the normal baboons, the response to noradrenaline was a dose-dependent decrease in muscle blood flow. 3. Bile-duct ligation caused no significant alteration in skeletal muscle blood flow but the response to noradrenaline in the jaundiced baboons was significantly attenuated. This effect was not observed in four sham-operated baboons.

Renovascular hypersensitivity to noradrenaline in dietary-induced hypercholesterolaemia in baboons.

1. Using the xenon-133 washout technique, the renovascular response to intrarenal infusions of 3 and 30 mumol/min noradrenaline in four baboons with dietary-induced hypercholesterolaemia was measured. 2. The degree of reduction in cortical blood flow rate during an intrarenal infusion of 3 mumol/min noradrenaline in the four hypercholesterolaemic baboons was not significantly different from that in normocholesterolaemic baboons. However, a significant difference in the degree of reduction in cortical blood flow rate was found with the 30 mumol/min noradrenaline infusion (P less than 0.05). 3. The mean arterial blood pressure of the four animals was significantly higher (P less than 0.001) than the mean blood pressure in baboons used in this laboratory for other experiments. 4. These results have shown that baboons with dietary-induced hypercholesterolaemia have an enhanced renovascular sensitivity to exogenous noradrenaline. However, the possibility that this enhanced sensitivity was due to the associated hypertension cannot be excluded.

Renal blood flow in obstructive jaundice: an experimental study in baboons.

1. The distribution of intrarenal blood flow has been measured using the 133Xe-washout technique in thirteen baboons 2 weeks after ligation of the common bile duct. 2. In comparison with eight sham-operated baboons, there was a signifigant decrease in the percentage distribution of blood to the cortex, although the rate of flow was unchanged. These changes were accompanied by a significantly increased flow rate and percentage distribution of flow through the juxtameduallary circulation. 3. In a further five baboons treated in the same way, various doses of noradrenaline were infused into the renal artery. In these animals there was an enhanced pressor response to noradrenaline, and this effect was completely abolished by an alpha-adrenoreceptor blocking agent (phenoxybenzamine). The beta-adrenoceptor blocking drug (propranolol) had no such effect. 4. This enhanced response was not seen when noradrenaline was infused into three sham-operated baboons. 5. These observations suggest that the alterations in renal perfusion in obstructive jaundice may be due to an increase renovascular sensitivity to circulating catecholamines and an enhanced alpha-adrenoceptor activity.

Observations on plasma creatine phosphokinase activity in dogs.

Plasma creatine phosphokinase (PCPK) activity was determined in 14 clinically normal adult pedigree dogs of various breeds with an activated enzyme assay medium. PCPK levels were not significantly influenced by the time of sampling, body mass or eating, but there was a significant correlation (P is less than 0.05) between PCPK levels and moderate physical activity. The mean enzyme activity was 22.9 iu/litre at 30 degrees C. The PCPK levels are 10 times greater than those obtained by other authors with the non-activated enzyme assay method.

Renovascular resistance and noradrenaline.

Stimulation of the renal nerves can cause cortical vasoconstriction either by direct activation of vascular smooth muscle or by the generation of angiotensin II following renin release from the juxtaglomerular cells. High doses ( greater than 5 mug/min) of the renal neurotransmitter noradrenaline (NA) infused into the renal artery of the baboon causes cortical vasoconstriction. This NA-induced vasoconstriction is significantly reduced (P less than 0.001) by SQ20881, an inhibitor of converting enzyme, and by saralasin, a competitive inhibitor of angiotensin II. These results suggest that NA stimulates the renin-angiotensin mechanism. The further addition of the alpha-adrenergic blocking agent, phenoxybenzamine, to the NA-SQ20881 or NA-saralasin infusate completely abolishes NA-induced cortical vasoconstriction. These results suggest that NA-induced cortical vasoconstriction in the kidney is mediated by activation of both the renin-angiotensin system and alpha-adrenergic receptors.

The effect of noradrenaline, adrenergic blocking agents, and tyramine on the intrarenal distribution of blood flow in the baboon.

The intrarenal distribution of blood flow in the baboon was measured using the 133xenon clearance technique, and dose-response curves for the various components of renal blood flow were determined during intra-arterial infusions of noradrenaline; the alpha-adrenergic blocking agent, phenoxybenzamine; the beta-adrenergic blocking agent, propranolol; and tyramine which causes the release of endogenous NA. High doses of noradrenaline reduced flow in the outer cortex; this effect was attenuated by phenoxybenzamine, but not by propranolol. Tyramine had no effect. These r results suggest that there are alpha-adrenergic receptors in the resistance vessels of the kidney but are inconsistent with an important role for NA-mediated autonomic control of renal blood flow.