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Biomedical subjects

W F Finn

Publications and source records attributed to W F Finn.

47 records · Page 3Linked to original sources
PubMed1976

Effect of prostaglandin synthetase inhibitors on renal blood flow in the rat.

Using a small-diameter electromagnetic flow transducer, the effect on the autoregulation of renal blood flow (RBF) of two structurally different prostaglandin synthetase inhibitors, indomethacin, 4 mg/kg BW, and meclofenamate, 5 mg/kg BW, was studied in nondiuretic rats anesthetized with either the oxybarbiturate, sodium pentobarbital, or the thiobarbiturate, Inactin. Regardless of the anesthetic agent, RBF remained relatively constant above a perfusion pressure of 105 mmHg. Treatment with either indomethacin or meclofenamate had no measurable effect on the autoregulatory response. Each agent, however, resulted in an increase in the renal vascular response to exogenous angiotensin II, an effect consistent with prostaglandin synthetase inhibition. Base-line RBF was significantly reduced by indomethacin or meclofenamate only in those animals that had previously received angiotensin. These results support the hypothesis that, in th rat, autoregulation of RBF occurs independently of prostaglandin activity, but that a relationship does exist between the renal vascular actions of angiotensin II and prostaglandins.

Angiotensin II↗
PubMed1975

Autoregulation of blood flow in the rat kidney.

We present evidence showing that renal blood flow (RBF) in the anesthetized nondiuretic rat can be measured reliably and accurately using a noncannulating flow transducer and an electromagnetic flowmeter. In vitro calibration yielded a linear relationship (r=0.998) between flowmeter output voltage and blood flow rates from 0.2 to 10.3 ml/min. Excellent agreement was observed between simultaneous determinations of RBF by the flowmeter and the PAH clearance technique. Glomerular filtration rate and RBF for a kidney with a flow transducer around its renal artery did not differ significantly from corresponding values for the undisturbed contralateral kidney. The relationship of mean RBF with steady-state variations in perfusion pressure was evaluated in 13 nondiuretic rats. RBF averaged 6 ml/min.g kidney wt at arterial pressures (AP) above 100 mmHg. A high degree of autoregulatory efficiency was observed when mean AP varied between 105 and 145 mmHg. Over this pressure range RBF changed only 3% as changes in intrarenal vascular resistance and AP were directly related (r=0.994). Below 95-105 mmHg RBF decreased in a curvilinear fashion with the concavity toward the pressure axis.

Aminohippuric Acids↗
PubMed1975

Pathogenesis of acute renal failure following temporary renal ischemia in the rat.

In this study, we characterized the sequence of several intrarenal events and evaluated their relative importance in the pathogenesis of unilateral oliguric acute renal failure induced experimentally in rats by complete occlusion of a renal artery for 1 hour. Kidneys were studied prior to occlusion and 1-3 hours and 22-26 hours after release of the temporary occlusion. Renal blood flow measured by an electromagnetic flow transducer was reduced to 40-50% of control during both postocclusion periods. Flow of tubular fluid was markedly reduced, and the damaged kidneys were oliguric. Proximal and distal convolutions were filled with fluid and dilated 1-3 hours after occlusion; their pressures were greatly heterogeneous and were elevated, on the average, to 31 and 16 mm Hg, respectively. Glomerular capillary pressure at this time was normal or slightly increased. Histological sections showed extensive tubular obstruction. We conclude that initially the oliguria is primarily due to intraluminal obstruction in the absence of predominant increases in preglomerular vascular resistance. Observations at 22-26 hours after occlusion indicated acute tubular necrosis. Moreover, the combined involvement of preglomerular vasoconstriction, presisting tubular obstruction, and passive backflow of tubular fluid appeared to be important in the maintenance of the oliguria. Glomerular capillary, proximal intratubular, and peritubular capillary hydrostatic pressures were reduced below control values. After acute volume expansion, the reduced pressures and renal blood flow were reversed, yet the experimental kidneys remained oliguric. Thus, it is clear that tubular obstruction is a significant factor responsible for both the genesis and the maintenance of oliguria in this experimental model of ischemia-induced acute renal failure.

Acute Kidney Injury↗
PubMed1974

Nephron stop-flow pressure response to obstruction for 24 hours in the rat kidney.

Complete ureteral ligation of 24-h duration significantly reduced stop-flow and estimated glomerular capillary pressures in nephrons accessible to micropuncture in obstructed kidneys. In kidneys without ureteral obstruction, a similar response occurred in single tubules blocked for 24 h without affecting nearby unblocked tubules. Thus, the response to tubular obstruction occurs on an individual nephron basis and results from constriction of individual afferent arterioles. The mechanism leading to the response is unknown, but a feedback mechanism operating through the juxtaglomerular apparatus of individual nephrons is an attractive possibility.

Animals↗
PubMedDate not supplied

FK506 nephrotoxicity.

Tacolimus (FK506) is a potent immunosuppressive agent with significant nephrotoxic properties. FK506 is complexed with an intracellular binding protein FKBP-12. Both the immunosuppressive and nephrotoxic effects may be linked to the inhibitory effect of this complex on calcineurin. The initial phase of FK506 nephrotoxicity is associated with a reduction in renal blood flow and glomerular filtration rate. More significant microvascular injury may follow with endothelial damage. Tubular epithelial cell vacuolation, atrophy and micocalcification may be associated with the development of irreversible interstitial fibrosis. At times, mesangial cell proliferation adds to the glomerular abnormalities. These effects may be mediated by the inhibitory effect on calcineurin and its role in regulating cellular calcium channels. FK506 stimulates several inflammatory cytokines, such as transforming growth factor-beta, with potential deleterious effects. Also abnormalities in the reninangiotensin system, endothelin, renal prostaglandins, adrenergic receptors may all play a role in the nephrotoxic effects.

Calcineurin↗
PubMedDate not supplied

Urinary biomarkers: recommendations of the Joint European/United States Workshop for future research.

The session concluded on a positive note with enthusiasm on the part of participates to become involved in one of the proposed joint protocols. Left to be answered was whether or not individual urinary biomarkers can be tailored to be disease specific or will there always be a need for a panel of biomarkers to insure interpretable results? It was agreed that proposals for three studies would be prepared. The first study will take advantage of the fact that field studies are currently being organized by both European and American groups. European scientists are working with the World Health Organization to investigate lead exposure in a region of China. At the same time, scientists in the United States are implementing a surveillance program in a population exposed to lead and other heavy metals in Kellogg, Idaho. These efforts provide an excellent opportunity for the sharing of samples and the study of a biomarkers panel that would contain both standard and candidate biomarkers. It was agreed that the parties interested in participating would alert the workshop organizers. The second study will expand upon a protocol developed by Dr. Debroe that has as its subjects non-transplant patients being treated with cyclosporine. An additional complimentary study of tacrolimus (FK-506) nephrotoxicity will also be developed. This protocol will be designed to follow the loss of renal function with a urinary biomarkers panel. The third study will follow the lead of Dr. Safirstein who urged the consideration of Cisplatin nephrotoxicity as a singular model for analyzing the usefulness of various biomarkers as measures of both acute and chronic nephrotoxicity.

Biomarkers↗