Esmail Koushanpour

Effects of hyperosmotic mannitol infusion on hemodynamics of dog kidney.

This study evaluated the effect of systemic infusion of hypertonic mannitol on renal hemodynamics (aortic pressure [P]-renal blood flow [RBF] relationship, glomerular filtration rate [GFR], and effective renal plasma flow [ERPF]) during 50% reduction of left kidney blood flow. Conditioned mongrel dogs anesthetized with halothane were hydrated by continuous infusion of lactated Ringers solution containing creatinine to measure GFR and p-aminohippurate (PAH), to measure ERPF. The left kidney was exposed and two hydraulic occluders were placed, one around the aorta just above the renal arteries and the other around the left renal artery. Experimental design consisted of measuring P near the left renal artery, RBF by electromagnetic flowmeter, and ERPF and GFR by clearance methods in both kidneys in response to stepwise reduction in the aortic pressure by aortic occlusion before and after 50% reduction in the left kidney blood flow. The P-RBF relationship, GFR, and ERPF thus obtained were compared with those obtained during systemic intravenous infusion of 20% mannitol for a period of 1 h. We found that 1) a transient increase occurred in RBF with step reduction of P from 80 to 60 mm Hg under control conditions; 2) reducing the RBF by 50% changed the shape of the P-RBF relationship from a convex to the P axis to a linear form with a marked shift toward the P axis; 3) infusion of mannitol, during reduced RBF, caused a significant shift of the P-RBF curve toward the RBF axis and returned the linear P-RBF relationship toward normal, but had no effect on altered yield pressure; and 4) infusion of hypertonic mannitol had slightly increased GFR and ERPF in the right (unconstricted) kidney. However, hypertonic mannitol significantly increased GFR and ERPF values in the left (constricted) kidney suggesting a beneficial effect of mannitol on ischemic kidney. The results are consistent with the hypothesis that infusion of hypertonic mannitol to ischemic kidney increases RBF, presumably by decreasing the intrarenal vascular resistance. We speculate that this compensatory response may be mediated either 1) by stimulating the release of a vasodilator substance (e.g., prostaglandins), or 2) by washing out interstitial sodium, thereby reducing the sensitivity of the renal vasculature to ischemia-induced stimulation of renin-angiotensin system. (Anesth Analg 1996;82:902-8)

Mathematical simulation of normal nephron function in rat and man

Abstract A mathematical model of the nephron was developed by writing a set of material balance equations for the flow of water, sodium and urea along the length of the nephron. The differential equations derived incorporate the geometrics of an average nephron. The parameters of these equations were calculated using the analytical solutions and the available micro-puncture data. The model yielded piecewise continuous curves for volume flow rate and sodium and urea concentration profiles emphasizing the sequential processing of the filtrate along the consecutive nephron segments. The simulation of normal function in the rat nephron agreed reasonably well with the tubular fluid to plasma ratio data for inulin, urea and sodium along the proximal and distal tubules. Assuming a linear medullary interstitial solute concentration profile, the model generated continuous curves for the luminal concentrations of sodium and urea along the descending and ascending limbs of the loop of Henle. The simulated curves were consistent with available micropuncture data for sodium and suggested a possible mechanism for the handling of urea by the nephron to account for the passive recirculation of this solute and its role in the development of the longitudinal medullary concentration gradient. The simulation of the human nephron, after making certain necessary extrapolations from the rat nephron, gave comparable curves for water, sodium and urea transport.

Partition of the Carotid Sinus Baroreceptor Response in Dogs between the Mechanical Properties of the Wall and the Receptor Elements

The purpose of this investigation was to learn what part of the carotid sinus baroreceptor response is attributable to the gross mechanical properties of the wall and what part to the receptor elements. Static pressure forcings were applied to an isolated dog carotid sinus preparation while baroreceptor nerve activity was recorded; carotid sinus deformation was measured from still photographs taken during the experiment. Pressure–nerve activity data were obtained from four dogs and pressure-deformation data from another five dogs. The average electrical power in the nerve signal was used as the measure of nerve activity, and strain-energy density, a scalar quantity, was selected as the best indicator of the mechanical state of the sinus wall. Strain-energy density was calculated by measuring the circumferential and the longitudinal strains and by estimating the corresponding stresses in accordance with a thin-walled, axially symmetric model. The pressure–nerve activity data followed an S-shaped pattern, but the pressure–strain-energy density data were linear over the pressure range of 50 to 250 mm Hg. A curve of strain-energy density vs. nerve activity constructed from these two graphs, with pressure as the parametric variable, showed a linear relationship between nerve activity and strain-energy density over the pressure range of 75 to 175 mm Hg, but the slope of the curve rapidly went to zero with increasing pressure. We concluded that the nonlinearity in the pressure–nerve activity relationship was primarily due to the inability of the receptor elements to respond to increasing wall strains.

Pressure-Heart Rate Relationship in Intact and After Stepwise Elimination of Three Major Baroreflex loops in Dogs

Systemic arterial blood pressure (BP)-heart rate (HR) relationship (the pressor test) is often used as an index of baroreflex. We evaluated this index by simultaneously comparing BP-HR, right carotid sinus pressure (CSP)-nerve action potentials (NAP), and NAP-HR relationships in dogs anesthetized with pentobarbital. BP was increased or decreased stepwise by intravenous (IV) infusions of phenylephrine or sodium nitroprusside, respectively. In nine dogs BP-HR and CSP-NAP relationships were measured and NAP-HR relationship was constructed before and after sequential and stepwise sectioning of the left aortic depressor nerve (LADN), the right aortic depressor nerve (RADN), and blockade of the left carotid sinus nerve (BLK) with 1% lidocaine. We found that HR was a negative sigmoidal function of BP in intact dogs. Linear slope of this relationship was significantly reduced after sectioning of LADN and RADN, but returned toward baseline after BLK. NAP was a positive sigmoidal function of CSP in intact dogs. Linear slope of this relationship was significantly depressed after sectioning of LADN and RADN. However, after BLK, the slope surpassed control, suggesting the existence of a central communication between the two carotid sinuses. HR was a negative function of NAP in intact dogs. However, as the other baroreflex feedback loops were eliminated, the slope of the NAP-HR relationship approached zero indicating that a closed integrated parallel feedback system is required for reflex regulation of HR. Our findings suggest that under normal conditions the pressor test is a valid index for baroreceptor function, but its use may not be warranted in chronic pathological states, such as atherosclerosis and hypertension. However, in contrast to the present acute experimental model, chronic pathological processes may not develop in sequence, and baroreceptor function on the affected site may not be completely eliminated from the baroreceptor loop such as performed in this study. (Anesth Analg 1996;83:965-74)

Local versus central effect of halothane on carotid sinus baroreceptor function.

Depressive effect of halothane on carotid sinus baroreceptor function may be due to direct local action, action in the CNS, or both. Paris of dogs were anesthetized with pentobarbital and ventilated with oxygen. The carotid sinus of the recipient dog was isolated and perfused with blood from the common carotid artery of the donor dog. Blood from the recipient sinus was returned through its external carotid to the donor common carotid. Thus, both carotid sinuses of the donor and the contralateral carotid sinus of the recipient dog received uninterrupted circulation. Carotid sinus nerve action potentials and lingual artery pressure of the isolated recipient sinus were recorded before and during steady state end-tidal halothane concentrations of 0, 0.5, 1.0, 1.5, 2.0, and 2.5% in oxygen, given randomly first to the donor dog (to evaluate direct local effect) and then to the recipient dog (to determine central effect). The dog not given halothane received pentobarbital. Plots of normalized nerve activity versus halothane concentrations showed approximately zero slope when the donor was given halothane but showed significant decrease in nerve activity when the recipient was given halothane. Halothane appears to have no direct local effect but causes depression of baroreceptor nerve activity, possibly via CNS inhibition of sympathetic efferents to the carotid sinus.

Regulation of Renal Blood Flow and Glomerular Filtration Rate

In the preceding chapter we learned that the process of passive filtration at the glomerulus delivers a copious volume of virtually protein-free plasma to the proximal tubule for further processing. Since major alterations in the volume of plasma filtered at the glomerulus per minute, namely, the glomerular filtration rate (GFR), would have a profound effect on the subsequent tubular processing of this filtrate, there must be some intrinsic mechanisms whereby GFR is carefully controlled. In this chapter we briefly review some of the experiments that have led to the current concept of renal autoregulation and the intrinsic control of renal blood flow (RBF), including the possible role of the juxtaglomerular apparatus. In addition to these mechanisms, the roles of the intrarenal production of renin-angiotensin and prostaglandin in autoregulation and renal regulation of volume and composition of body fluids are also discussed. Finally, we conclude with a discussion of the extrinsic control of the renal circulation.

Mechanism of Concentration and Dilution of Urine

In Chapter 9, while discussing the sequential processing of the filtrate along Henle’s loop, we alluded to the role of this nephron segment in concentrating and diluting the urine. In this chapter we consider the principle of countercurrent multiplication and the evidence for its application to the kidney. We then examine the mechanism of concentration and dilution of urine, the measurement of the ability of the kidney to concentrate urine, and finally the action of some selective diuretics and their potential therapeutic effects. We begin with a comprehensive presentation of the structural organization of the renal medulla.

Trimethaphan-induced hypotension: effect on renal function

This study was designed to evaluate the effects of trimethaphan-induced hypotension on renal function in healthy young patients undergoing maxillofacial surgery. Anaesthesia was induced with thiopentone and was maintained with halothane 1.5-2.0 per cent in oxygen. Each patient served as his own control, and data were analyzed using the paired t-test. Trimethaphan was infused at a rate of 45-52 [xg-kg-lmin-1 for an average hypotensive period of 53 ± 4 (mean ± SEM) minutes to reduce the mean arterial pressure (MAP) to 49 ± 2 torr. Endogenous creatinine clearance, urinary Po2, sodium reabsorption rate (TNa), and serum and urine osmolalities were determined before, during and after arterial hypotension with trimethaphan. Urine flow averaged 2.9 ± 1 ml/min during the period of hypotension. Endogenous creatinine clearance and TNa were significantly decreased (p < 0.05) in the hypotensive period. These values returned to normal levels within one hour upon discontinuation of trimethaphan and restoration of blood pressure. We found no statistical difference in urine Po2, and serum and urine osmolalities during control, hypotensive and recovery periods. These results suggest that medullary renal tissue oxygenation, an index of tissue viability, may have remained adequate despite a significant reduction in endogenous creatinine clearance during the hypotensive period. Furthermore, it appears that the effect of trimethaphan-induced hypotension on renal function is similar to the sodium nitro-prusside-induced hypotension in man which we have reported previously.RésuméCette étude aé6lé entreprise dans le but d’évaluer le retentissement de l’hypotension produite par le trimetaphan (TMP) sur la fonction résale de jeunes adultes en bon état subissant une intervention maxillo-faciale. L’anesthésie a été induite au thiopentone et maintenue à l’halothane 1.5-2.0 pour cent dans l’oxygène. Chaque patient était son propre contrôle et les données ont été analysées avec le test de Student. Le TMP a été perfusé#x00E9; à la vitesse de 45-52ing-kg--min-1 pour une durée moyenne d’hypotension de 53 ± 4 (moyenne ± SEM) minutes de façbaisser la pression artérielle moyenne à 49 ± 2 torr. La clairance de Iacréatinine endogène, la Po2 urinaire, la vitesse de réabsorbtion au sodium (TNa) et l’osmolalité urinaire et sérique ont été déterminées avant, pendant et après l’hypotension au TMP. Le débit urinaire était en moyenne de 2.9 ± 1 ml/min pendant la période d’hypotension. La clairance de la créatinine endogène et laT Na se sont abaissées de facçon significative (P < 0.05) pendant la péiiode hypotensive. II n’y a eu de différence significative dans la P02 urinaire et les osmolalités sérique et urinaire pendant la période de contrôle, d’hypotension et de recouvrement. Ces résultats suggèrent que l’index de viabilité du tissus rénal qu’est I’oxygénation médullaire pourrait être adéquat malgré une baisse significative de la clairance de la créatinine endogène pendant la période hypotensive. De plus, il semble que le retentissement de l’hypotension produite par le TMP sur la fonction résale est identique à celle produite chez 1’homme par le nitroprussiate de soude.

Mathematical simulation of the body fluid regulating system in dog

Abstract A mathematical model of body fluid volume and osmolality regulation was developed which incorporated the major nonlinearities of fluid assimilation, exchange, distribution and excretion. The non-linear differential equations define compartmental material balances for water, urea, sodium, protein and antidiuretic hormone (ADH). The parameters of these equations were calculated using analytical solutions and available steady-state experimental data. The model was used to simulate the renal response to five input forcings: (1) intraesophageal water infusion; (2) water ingestion; (3) intravenous ADH injection; (4) intravenous water infusion; and (5) intermittent water loading. The model yielded continuous simulation curves which agreed reasonably well with the available transient and steady-state experimental data. The model predicted that stimulating volume receptors via changes in left atrial pressure accounts for only 15–20% of changes in ADH secretion rate, whereas stimulation of the osmotic receptors via changes in plasma osmolality accounts for the remaining 80–85% of changes. Thus, it appears that regulation of ADH secretion is largely dependent upon plasma osmolality during forcings which do not appreciably alter the cardiovascular blood volume.

Effect of Mean Pressure Levels on the Dynamic Response Characteristics of the Carotid Sinus Baroceptor Process in Dog

The purpose of this investigation was to delineate the effect of imposed mean pressure levels on the open-loop dynamic response characteristics of the carotid sinus baroceptors in dogs. The experimental design consisted of measuring the intrasinus pressure and the gross baroceptor nerve activity while forcing the isolated sinus with sinusoidal pulse pressures, with peak-to-peak amplitude of 50 mm Hg, superimposed on mean pressures of 75, 125, 175, and 225 mm Hg at frequencies of 0.5, 1, 2, 3, 4, 5, 7, 10, 15 and 20 Hz. With this forcing protocol, we were able to divide the traditional sigmoidal pressurenerve activity relationship into three piecewise linear segments whose input-output (transfer) functions could then be determined by conventional linear system analysis. We found that (a) at each mean pressure level, the transfer function relating nerve activity, N(s), to forcing pressure, P(s), was second order and of the form, N(s)/P(s) = ¿(1 + ßs + ¿s2), and (b) the coefficients ¿, ß, and ¿ were all quadratic functions of the mean pressure level, P¿ Incorporating the equations for each coefficient as a function of mean pressure into the transfer function yielded the nonlinear differential equation, N(t) = k¿(P¿) [(P(t) - P¿) + ß(P¿) (dp(t)/dt) + ¿(P¿) (d2P(t)/dt2)], which describes the dynamic response of the carotid sinus baroceptor nerve, N(t), over the entire pressure range, P(t), studied.