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Biomedical subjects

R B Cross

Publications and source records attributed to R B Cross.

At least 19 recordsLinked to original sources

Aortic wall stress profile after repair of coarctation of the aorta. It is related to subsequent true aneurysm formation?

UNLABELLED: True aneurysm formation at the site of coarctation repair has been increasingly recognized after synthetic patch aortoplasty. A mathematical model was developed to determine the aortic wall stress profile after coarctation repair with this technique. METHODS: A two-dimensional nonlinear mathematical model and a three-dimensional finite element model were developed for different physiologic, geometric, and materials properties variables, which were incorporated into an idealized coarctation repair. RESULTS: The models demonstrated that the major variable affecting stress levels in the aortic wall after coarctation repair was the patch geometry. If the patch was allowed to balloon out, the aortic wall stress increased out of proportion to the increase in aortic diameter because of nonlinear effects. The maximal aortic wall stress concentration occurred opposite the patch. Patch stiffness was also an important variable, with a lower stiffness (subclavian flap repair) leading to a higher aortic wall stress for the same patch geometry as a synthetic patch repair. Inferences: Development of true aneurysms after coarctation repair by synthetic patch aortoplasty is likely to result from excessive aortic wall stress due to patch geometry.

Aorta↗

Cardiovascular effects of parathyroid hormone in conscious sheep.

The cardiovascular effects of the synthetic amino terminal fragment of parathyroid hormone, PTH(1-34), were studied in intact conscious sheep. Physiological doses of bovine (b) PTH(1-34), 0.188, 0.376, 0.56 and 0.75 micrograms kg-1 h-1 were infused in random order into conscious sheep for periods of 1 h each. Isotonic saline was infused as a control. Mean arterial blood pressure (MABP) decreased from 99.2 +/- 1.2 mmHg during the control infusion to 88.9 +/- 1.4 mmHg during infusion of the highest dose of PTH. Heart rate (HR) increased from 81.6 +/- 7.3 beats min-1 during the control infusion to 142.3 +/- 14.0 beats min-1 at the highest PTH dose and plasma renin activity (PRA) increased from 0.33 +/- 0.15 ng ml-1 h-1 to 1.54 +/- 0.46 ng ml-1 h-1. Cardiac output (CO), calculated by an indirect method, increased to 176 +/- 28% of the control values. The changes in all four parameters were dose dependent. Renal blood flow (RBF) increased during the PTH infusion period.

Animals↗

Comparison of a single-injection technique and inulin clearance for determining glomerular filtration rate in the sheep.

Glomerular filtration rate (GFR) was assessed over a 2 h period by the clearance of inulin (Cin) and in the subsequent 2 h period by a single-injection technique using radiolabelled sodium iothalamate (Ciot) or chromium-EDTA (CEDTA). Regression analysis yielded a significant correlation (P less than 0.05) between the standard clearance technique and the single-injection method, with the relationship Ciot = -10.67 + 1.25Cin with a significant correlation coefficient of r = 0.71 (P less than 0.02). There was better agreement between clearance values of inulin measured on successive days than between values determined by the single-injection technique on successive days. Cin remains the method of choice in sheep.

Animals↗

A simple field test for assessing salt balance in heat-stressed miners.

A simple colorimetric test for urinary chloride (Fantus test) corrected for urine specific gravity (measured by refractometry) enabled 24-hour urinary sodium excretion rates to be predicted accurately from a single spot sample of urine. In 29 acclimatized miners working in an environment in excess of 40 degrees C, salt-conserving mechanisms, involving renin and aldosterone, were not active until the urinary sodium excretion rate fell below 50 mmol/24 h. A predicted sodium excretion rate greater than 50 mmol/24 h indicates that dietary sodium supplementation is not necessary.

Adult↗

The effects of two calcium antagonists (nifedipine and verapamil) on renal function in sheep.

The effects of the calcium antagonists, nifedipine and verapamil, were measured in five conscious Merino ewes at a dose rate of 0.5 microgram min-1 kg-1 for 60 min. Nifedipine caused a significant fall in mean arterial blood pressure (MABP) and central venous pressure (CVP) and an increase in heart rate (HR). There was no significant effect on renal vascular resistance (RVR) but, with the fall in MABP, renal plasma flow (RPF) decreased. There was a significant rise in glomerular filtration rate (GFR) and a small rise in filtration fraction (FF). Solute excretion, urine osmolality and solute-free water reabsorption (Tc, H2O) increased and urine flow (V) decreased. Plasma potassium (PK) and osmolality (Posm) decreased. Verapamil produced a similar fall in MABP and also had similar effects on the other parameters, except that in this case RVR was significantly reduced and there were significant increases in RPF and GFR. The rise in GFR which occurred regardless of the change in RPF, can account for the increase in solute excretion, although an effect of the calcium antagonists on tubular function cannot be excluded.

Animals↗

Hypotension-induced hypokalaemia in sheep.

Plasma K+ was measured in Merino ewes during 50-90 min periods of hypotension induced by sodium nitroprusside, isoprenaline, verapamil or nifedipine. Doses were adjusted to produce falls in systemic blood pressure of approximately 20 mmHg. All of these drugs caused decreases in plasma K+ which could not be attributed to increased urinary excretion of K+. In all cases plasma renin activity increased during the hypotension. Plasma aldosterone concentration which was measured in some sodium nitroprusside experiments also increased during the hypotension. However, enhancement of the plasma renin activity and plasma aldosterone concentration responses by prior sodium depletion of the sheep by furosemide administration or suppression of the plasma renin activity and plasma aldosterone concentration responses by prior salt loading did not influence the magnitude of the hypotension-induced hypokalaemia.

Adrenergic beta-Agonists↗

A cardiac specific analog of angiotensin I potentiated by converting enzyme inhibition.

[1-Sarcosine, 7-Alanine] angiotensin I [( 1-Sar, 7-Ala] AI) and closely related analogs were tested for inotropic activity in the isolated cat heart, and for pressor activity in the intact conscious sheep both before and during converting enzyme inhibition (CEI). [1-Sar, 7-Ala] AI exhibited potent inotropic activity but was only weakly pressor. [1-Sar] AI, [1-Sar, 5-Val] AI, [1-Sar, 7-alpha MeAla] AI [1-Sar, 5-Val, 7-NMeAla] AI and [1-Sar, 5-Val, 7-Sar] were all potent agonists in both preparations. The action of [1-Sar, 7-Ala] AI was potentiated by CEI in both the isolated heart and the intact sheep. The activity of the remaining analogs was either partially or completely blocked by CEI. The activity of all analogs was inhibited by AII receptor blockade. These data indicate that the nature of the substitution in position 7 determines the affinity of the analog for converting enzyme. The [7-Ala] substitution appears to decrease the effect of the analog upon vascular receptors.

Angiotensin I↗

Effects of facial cooling during exercise at high temperature.

Healthy men and women were exercised on a cycle ergometer in a hot environment (46 degrees C). Cold air (5 degrees C) was blown onto the face either as a jet from the tube directed towards the nose or being introduced under a face mask. There was a subjective feeling of increased comfort although the temperature under the mask decreased to only 28 degrees C-32 degrees C. Facial cooling did not cause any changes in either blood pressure or heart rate. It is concluded that this degree of facial cooling does not invoke the previously described peripheral vasconstriction which could inhibit further heat loss.

Adult↗

Converting-enzyme inhibition and 1-sarcosine-8-isoleucine-angiotensin II: effects on renal function in the dehydrated sheep.

The effect of a converting-enzyme inhibitor (captopril) was studied in nine conscious dehydrated Merino ewes. Captopril (4 mg I.V. over 40 min) caused significant decreases in mean arterial blood pressure (M.A.B.P.), renal vascular resistance (R.V.R.) and filtration fraction, and increases in urine flow (V), sodium excretion, glomerular filtration rate (G.F.R.), renal plasma flow, solute clearance (Cosm), solute-free water reabsorption (TC, H2O) and plasma renin activity (P.R.A.). None of these effects was observed when captopril was similarly administered to sheep pretreated with angiotensin II (AII) receptor blocker, 1-sarcosine-8-isoleucine-AII (sarileucin). It is concluded that the effects of captopril were probably not due to bradykinin potentiation but rather to decreased levels of circulating AII. The effect of sarileucin itself was complex. It effectively blocked the pressor response to administered AII, but it also had an AII-like effect indicated by a rise in R.V.R., and decreases in V, G.F.R., Cosm and TC, H2O. This apparent mixture of AII agonist and antagonist properties probably accounts for the absence of any change in M.A.B.P. or P.R.A. during sarileucin administration.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Mechanisms of escape from sodium retention during angiotensin II hypertension.

This study examined the role of increased renal arterial pressure (RAP) in renal escape from the chronic Na-retaining effects of angiotensin II (ANG II). When RAP was allowed to increase during ANG II infusion (5 ng X kg-1 X min-1), urinary Na excretion (UNaV) decreased transiently on the first day but there was no significant change in Na iothalamate space or cumulative Na balance when ANG II infusion was continued for 6 days. Mean arterial pressure (MAP) rose from 100 +/- 3 to 132 +/- 2 mmHg after 3 days and remained near that level for the next 5 days of ANG II infusion. When RAP was prevented from rising with a servo-controlled aortic occluder, UNaV remained below control even after 6 days of ANG II infusion, cumulative Na balance increased by 210 +/- 37 meq, and Na iothalamate space rose by 1,158 +/- 244 ml. MAP did not plateau when RAP was servo-controlled during ANG II infusion but continued to rise and after 6 days averaged 157 +/- 3 mmHg. In three of the eight dogs in which RAP was servo-controlled during ANG II infusion, Na and water retention became so severe that MAP increased to 165-180 mmHg and pulmonary edema developed within 4-6 days. These data suggest that a rise in RAP is essential in allowing the kidneys to escape from the chronic Na-retaining actions of ANG II and in attaining Na balance and a stable level of MAP without severe volume expansion.

Aldosterone↗

Aspects of renal vascular organization and early vascular tubular relations of the marsupial Isoodon obesulus.

Renal vascular tubular relationships were studied in the marsupial Isoodon obesulus (the common brown bandicoot). The microcirculation was filled with colored silicone rubber by intra-arterial injection of the intact kidney. Nephrons were defined by the injection of silicone rubber of a contrasting color into the space of Bowman's capsule in thick, cleared slices of renal tissue. The details of the vascular tubular relationship in this marsupial are strikingly similar to relationships previously described in true mammalian kidneys. An unusual feature is a wide (600mu) glomerulus-free zone at the outer cortex. This zone contains the proximal and distal convoluted tubules of the most superficial cortical nephrons and is perfused by efferent vessels from glomeruli in superficial strata of the cortex.

Animals↗

The effects of an angiotensin blocker (saralasin) on kidney function in dehydrated sheep.

Saralasin, an angiotensin II analogue and receptor blocker, was infused at 7 and 15 micrograms . min-1 into dehydrated conscious Merino ewes. This caused mean arterial blood pressure, cardiac output, heart rate and renal vascular resistance to fall, and central venous pressure to rise. Renal plasma flow was unaffected but there were significant reductions in glomerular filtration rate, filtration fraction, urine flow, sodium and potassium excretion, solute clearance and solute-free water reabsorption. It is suggested that saralasin produced these effects by inhibiting endogenous angiotensin II activity, and in particular by causing a reduction in renal post-glomerular resistance. This in turn caused a fall in glomerular filtration rate and filtration fraction. While saralasin might have had effects on renal tubular function and perhaps on vasopressin secretion, the observed effects on renal function can be explained by the decrease in glomerular filtration rate and filtration fraction.

Angiotensin II↗

The effect of carbonic anhydrase inhibition on bicarbonate reabsorption.

Renal reabsorption of bicarbonate was studied in Merino ewes during carbonic anhydrase inhibition. Bicarbonate reabsorption was directly proportional to plasma bicarbonate concentration. No tubular maximum for bicarbonate was demonstrated. Elevation of arterial PCO2 or depression of arterial pH caused slight increases in bicarbonate reabsorption. The data suggest that bicarbonate is reabsorbed by 2 distinct processes. The quantitatively more significant process may involve ionic reabsorption of bicarbonate secondary to Na+ reabsorption and a relatively minor part of bicarbonate reabsorption may be secondary to H+ secretion.

Acetazolamide↗

The effect of vasopressin upon the excretion of calcium by the sheep.

Vasopressin (140 muU/min) was infused intravenously into 12 conscious merino ewes for 2 hr. Urine flow rate and free water clearance were consistently reduced. There was no effect upon renal plasma flow, glomerular filtration rate or the rate of excretion of sodium, potassium, magnesium, chloride or phosphate. Although all animals received 75 mmol calcium chloride into the rumen on the previous day, five commenced the experiment with calcium excretion rates of less than 1 mumol/min. In these, vasopressin further decreased calcium excretion. In seven animals with calcium excretion rates between 2 and 20 mumol/min vasopressin had no effect upon either total calcium or free ionized calcium excretion rate.

Animals↗

The acute effects of intravenous infusion of parathyroid hormone on urine, plasma and saliva in the sheep.

Following an intravenous loading injection of 75 U.S.P. Units of Para-Thor-Mone (Eli Lilly and Co), seven conscious, non-pregnant, non-lactating Merino ewes were infused with a maintenance dose of the hormone at a rate of 4-75 U.S.P. units/min for 2 hr. The classical hypercalcaemia and hypophosphataemia of the non-ruminant was observed, but the hypercalcaemi- was only small. Plasma potassium concentration decreases, while there were no changes in plasma sodium, chloride or mangesium. The classical phosphaturic effect of the hormone was not observed, only trace amounts of phosphate being exreted throughout the experiment. Urinary excretion of calcium and magnesium decreased, urine flow and urinary excretion of sodium, potassium, chloride, bicarbonate and urine pH increased. Glomerular filtration rate was unaffected, but renal plasma flow increased. The concentration and secretion rate of salivary phosphate increased markedly. Changes in the other important salivary electrolytes (sodium, potassium, chloride, bicarbonate and hydrogen ion) also occurred, but it was difficult to separate primary from secondary effects of the hormone. Saliva flow rate increased transiently following hormone injection, but the effect was not sustained by the maintenance infusion.

Animals↗