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1.
J Biomed Mater Res A ; 67(2): 510-6, 2003 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-14566792

RESUMEN

This study investigated the local drug pharmacokinetics of intralesional drug delivery after radiofrequency ablation of the liver. We hypothesized that the tissue architecture damaged by the ablation process facilitates the drug penetration in the liver and potentially enlarges the therapeutic margin in the local treatment of cancer. The delivery rate and tissue distribution of carboplatin, an anticancer agent, released from poly(D,L-lactide-co-glycolide) implants into rat livers after radiofrequency ablation were quantified by atomic absorption spectroscopy. Results showed that carboplatin clearance through blood perfusion was significantly slower in the ablated livers, leading to a more extensive tissue retention and distribution of the drug. The concentration of Pt at the implant-tissue interface ranged from 234 to 1440 microg Pt/(g liver) in the ablated livers over 144 h versus 56 to 177 microg Pt/(g liver) in the normal tissue. The maximum penetration distance at which Pt level reached above 6 microg/g (calculated based on a reported IC90 value for carboplatin) was 8-10 mm and 4-6 mm in ablated and normal liver, respectively. Histological analysis of the necrotic lesions showed widespread destruction of tissue structure and vasculature, supporting the initial hypothesis. This study demonstrated that intralesional drug delivery could provide a sustained, elevated concentration of anticancer drug at the ablation boundary that has the potential to eliminate residual cancer cells surviving radiofrequency ablation.


Asunto(s)
Carboplatino/farmacocinética , Hígado/efectos de los fármacos , Animales , Antineoplásicos , Carboplatino/metabolismo , Hígado/lesiones , Hígado/efectos de la radiación , Ondas de Radio , Ratas
2.
Surg Endosc ; 15(2): 183-8, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11285964

RESUMEN

BACKGROUND: Laparoscopic pneumoperitoneum has been shown to decrease glomerular filtration rate (GFR) and urine volume (UV). Endothelin-1 (ET-1), a potent renal vasoconstrictor, has been implicated. The purpose of this study was to determine renal function, ET-1 gene expression, and peptide localization in kidneys subjected to CO2 pneumoperitoneum. METHODS: Experiments were performed in three groups of anesthetized Sprague-Dawley rats in which GFR and UV were measured before, during, and after insufflation. In the first group (n = 8), pneumoperitoneum (10 mmHg) was established for 30 min. The second group (n = 4) underwent a sham operation without pneumoperitoneum. In the final group (n = 4), kidneys were obtained from normal control animals without any prior surgical instrumentation. PreproET-1 (ppET-1) mRNA levels were measured by reverse transcription-polymerase chain reaction (RT-PCR). The ET-1 peptide was localized within kidneys by immunohistochemistry (IHC). RESULTS: Pneumoperitoneum caused a significant (p < 0.05) 87% decrease in GFR and a 79% decrease in UV from baseline, with a return to baseline values after desufflation. RT-PCR showed a significant (p < 0.05) increase in expression of ppET-1 mRNA in the laparoscopic group; it was 3.52 +/- 0.33 densitometric units (DU), as compared to 0.35 +/- 0.06 DU and 0.57 +/- 0.12 DU in the control and sham groups, respectively. IHC showed enhanced expression of the ET-1 peptide in the vascular endothelium and proximal tubular cells of the laparoscopic group compared to the control and sham groups. CONCLUSION: Pneumoperitoneum induces ET-1 gene and peptide upregulation in the kidney. Expression of ET-1 is increased in the renal vasculature and proximal tubular cells. The elevation of ET-1 and its localization may account for some of the renal dysfunction observed during pneumoperitoneum. This suggests that antagonism of ET-1 may be beneficial in patients with renal impairment undergoing prolonged laparoscopic procedures or in protecting allograft function during and after living donor nephrectomy.


Asunto(s)
Endotelina-1/genética , Neumoperitoneo Artificial/efectos adversos , ARN Mensajero/metabolismo , Insuficiencia Renal/etiología , Animales , Secuencia de Bases , Pruebas de Función Renal , Laparoscopía/métodos , Masculino , Modelos Animales , Datos de Secuencia Molecular , Neumoperitoneo Artificial/métodos , Probabilidad , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/fisiopatología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo , Regulación hacia Arriba
3.
Transplantation ; 71(2): 211-6, 2001 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-11213061

RESUMEN

BACKGROUND: Utilization of organs subjected to ischemia/reperfusion (I/R) injury could expand the donor pool. Endothelin (ET) is implicated in renal I/R injury. Therefore, our study compared the effectiveness of pre- and postischemic administration of the ET receptor antagonist, Tezosentan, in preserving renal function. METHODS: In a rat model, a kidney was subjected to 45 min of ischemia along with a contralateral nephrectomy. After 24 hr of reperfusion, renal function was assessed by serum creatinine (Scr), inulin clearance (glomerular filtration rate; GFR), and histology. ET-1 peptide expression was localized using immunohistochemistry. Three groups were studied: I/R untreated (n=17), I/R pretreated (n=11), and I/R posttreated (n=13) with Tezosentan (15 mg/kg, i.v.). RESULTS: Tezosentan significantly decreased (P<0.05) the rise in Scr from I/R injury (2.0+/-0.4 mg/dl, before and 2.9+/-0.4 mg/dl, after treatment) compared with untreated animals (4.2+/-0.4 mg/dl). GFR was significantly increased (P<0.05) from 0.13+/-0.03 ml/min (untreated animals) to 0.74+/-0.16 and 0.47+/-0.14 ml/min (pre- and posttreated animals). Untreated animals had significant cortical acute tubular necrosis, which was almost completely prevented by pretreatment with Tezosentan and markedly reduced by posttreatment. Increased ET-1 peptide expression was noted in the renal vasculature and in the cortical tubular epithelium of kidneys exposed to I/R. CONCLUSIONS: The purpose of this study was to optimize the function of kidneys exposed to I/R injury. Pretreatment as well as posttreatment with Tezosentan successfully decreased Scr, increased GFR, and maintained renal architecture in kidneys after ischemia. Therefore, ET receptor antagonists may be useful to preserve renal function in the transplantation setting.


Asunto(s)
Antagonistas de los Receptores de Endotelina , Isquemia/tratamiento farmacológico , Riñón/irrigación sanguínea , Riñón/fisiología , Piridinas/farmacología , Tetrazoles/farmacología , Animales , Endotelina-1/análisis , Tasa de Filtración Glomerular/efectos de los fármacos , Inmunohistoquímica , Riñón/química , Necrosis Tubular Aguda/prevención & control , Masculino , Piridinas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacos , Daño por Reperfusión/prevención & control , Tetrazoles/administración & dosificación , Factores de Tiempo
4.
J Surg Res ; 85(1): 101-8, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10383845

RESUMEN

BACKGROUND: Prolonged cold ischemia time (CIT) can lead to posttransplant renal dysfunction; however, the pathophysiology remains unclear. Endothelin (ET), a potent vasoconstrictive peptide, may play a role in this injury. The purpose of this study was to determine if cold ischemia could induce renal ET-1 gene upregulation and to localize ET-1 peptide expression in the hypothermic kidney. MATERIALS AND METHODS: Kidneys from Lewis rats were perfused with Viaspan, harvested, and stored at 4 degrees C for varying periods of CIT: 0, 6, 24, and 48 h. Preproendothelin-1 (ppET-1) gene upregulation was measured using a reverse-transcription polymerase-chain reaction. ET-1 peptide expression was localized using immunohistochemistry. RESULTS: Control kidneys (0 h CIT) had 0. 56 +/- 0.22 DU of ppET-1 mRNA. After 6 h of CIT, a 2.3-fold increase in this level was noted. Following 24 h of CIT, ppET-1 mRNA was significantly upregulated to 1.96 +/- 0.38 DU (P < 0.05). Immunohistochemistry revealed typical vascular ET-1 staining in control kidneys. At 6 h of CIT, a significant increase in the expression of ET-1 was noted in the peritubular capillaries and vasa recta. After 24 h, intense staining for ET-1 was seen in the medullary collecting ducts. After 48 h of CIT, early cellular necrosis was present along with global decreases in ET-1 expression and ppET-1 mRNA levels. CONCLUSIONS: This study demonstrates that 24 h of cold preservation can induce significant upregulation of the renal ET-1 gene and increase expression of the ET-1 peptide localized to both vascular endothelial and tubular epithelial surfaces of the kidney. Consequently, prolonged cold ischemia prior to transplantation may lead to delayed renal function following revascularization via endothelin-induced vasoconstriction and/or tubular impairment.


Asunto(s)
Frío , Criopreservación , Endotelinas/genética , Regulación de la Expresión Génica/fisiología , Isquemia/genética , Riñón/fisiología , Preservación de Órganos , Animales , Endotelina-1/metabolismo , Inmunohistoquímica , Masculino , Precursores de Proteínas/genética , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas Lew , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Distribución Tisular/fisiología
5.
Am J Med Sci ; 317(4): 215-21, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10210355

RESUMEN

Although hyperlipidemia has been associated with the progression of glomerulosclerosis, little attention has been directed toward the use of lipid-lowering agents in altering diabetic nephropathy. We tested the hypothesis that lovastatin and the combination of lovastatin and enalapril would preserve renal function in streptozotocin-induced diabetic Wistar rats. Five groups of animals were studied: group 1, nondiabetic (n = 10); group 2, diabetic, insulin only (n = 12); group 3, lovastatin, (15 mg/kg/day, n = 13); group 4, enalapril, (50 mg/L drinking water, n = 10) and group 5, lovastatin plus enalapril, (n = 14). After 8 weeks of treatment, glomerular filtration rate (GFR, insulin clearance) was measured in anesthetized animals. The diabetic group was characterized by a GFR of 0.18 +/- 0.03 ml/min/g of kidney weight (gKW), a blood glucose level of 441 +/- 36 mg/dL, plasma cholesterol and triglyceride levels of 64 +/- 6.0 and 103 +/- 26.0 mg/dL. Lovastatin preserved GFR, 0.52 +/- 0.06 ml/min/gKW compared with the diabetic control subjects (P < 0.05). Enalapril also maintained GFR (0.42 +/- 0.06 ml/min/gKW, P < 0.05). In the lovastatin plus enalapril group, GFR (0.62 +/- 0.05 ml/min/gKW) was greater than in the enalapril group (P < 0.05), but was not different from the lovastatin group. Plasma lipid levels were not altered in any of the groups. Assessment of the kidneys by histology after treatment showed that the mesangial matrix injury score was better in the lovastatin, enalapril, and lovastatin plus enalapril groups compared with the diabetic group (P < 0.05). Lovastatin, enalapril, and lovastatin plus enalapril abrogated the decline in GFR and glomerular injury in diabetic rats. Lovastatin's direct renal protective effect seems to be independent of its lipid-lowering properties.


Asunto(s)
Anticolesterolemiantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Tasa de Filtración Glomerular/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Riñón/efectos de los fármacos , Lovastatina/farmacología , Animales , Antihipertensivos/farmacología , Colesterol/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/fisiopatología , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/fisiopatología , Quimioterapia Combinada , Enalapril/farmacología , Riñón/patología , Riñón/fisiopatología , Pruebas de Función Renal , Masculino , Ratas , Ratas Wistar , Triglicéridos/sangre
6.
Kidney Int ; 55(3): 1011-8, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10027938

RESUMEN

BACKGROUND: Endothelin (ET), a potent vasoconstrictor, is known to play a role in ischemic acute renal failure. Although preproET-1 (ppET-1) mRNA is known to be up-regulated following ischemia/reperfusion injury, it has not been determined which component of the injury (ischemia or reperfusion) leads to initial gene up-regulation. Likewise, although ET-1 peptide expression has been localized in the normal kidney, its expression pattern in the ischemic kidney has not been determined. Therefore, the purpose of this study was twofold: (a) to determine whether ischemia alone or ischemia plus reperfusion is required for the up-regulation of ppET-1 mRNA to occur, and (b) to localize ET-1 peptide expression following ischemia in the rat kidney to clarify better the role of ET in the pathophysiology of ischemia-induced acute renal failure. METHODS: Male Lewis rats underwent clamping of the right renal vascular pedicle for either 30 minutes of ischemia (group 1), 60 minutes of ischemia (group 2), 30 minutes of ischemia followed by 30 minutes of reperfusion (group 3), or 60 minutes of ischemia followed by three hours of reperfusion (group 4). The contralateral kidney acted as a control. ppET-1 mRNA up-regulation and ET-1 peptide expression were examined using the reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Reverse transcription-polymerase chain reaction yielded a control (nonischemic) value of 0.6 +/- 0.2 densitometric units (DU) of ppET-1 mRNA in the kidney. Group 1 levels (30 min of ischemia alone) were 1.8 +/- 0.4 DU, a threefold increase (P < 0.05). Group 2 levels (60 min of ischemia alone) increased almost six times above baseline, 3.5 +/- 0.2 DU (P < 0.01), whereas both group 3 and group 4 (ischemia plus reperfusion) did not experience any further significant increases in mRNA levels (1.9 +/- 0.4 DU and 2.8 +/- 0.6 DU, respectively) beyond levels in group 1 or 2 animals subjected to similar ischemic periods. ET-1 peptide expression in the ischemic kidneys was significantly increased over controls and was clearly localized to the endothelium of the peritubular capillary network of the kidney. CONCLUSIONS: Initial ET-1 gene up-regulation in the kidney occurs secondary to ischemia, but reperfusion most likely contributes to sustaining this up-regulation. The marked increase of ET-1 in the peritubular capillary network suggests that ET-induced vasoconstriction may have a pathophysiological role in ischemic acute tubular necrosis.


Asunto(s)
Endotelina-1/genética , Endotelina-1/metabolismo , Riñón/irrigación sanguínea , Riñón/lesiones , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Animales , Secuencia de Bases , Capilares/metabolismo , Cartilla de ADN/genética , Endotelinas/genética , Endotelio Vascular/metabolismo , Inmunohistoquímica , Riñón/metabolismo , Necrosis Tubular Aguda/etiología , Necrosis Tubular Aguda/genética , Necrosis Tubular Aguda/metabolismo , Masculino , Precursores de Proteínas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas Lew , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba
7.
J Endourol ; 12(2): 193-7, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9607449

RESUMEN

Prolonged pneumoperitoneum during laparoscopic surgery has been associated with oliguria in clinical experimental studies. Although the pathophysiology of this oliguria is thought to be renal parenchymal and venous compression, the role of the potent vasoconstrictor endothelin (ET) has not been studied. The purpose of this study was to investigate the effect of pneumoperitoneum on endothelin release and renal function in a canine model. Two groups of dogs were studied during pneumoperitoneum (Group 1, N = 7) or isolated left renal vein compression (Group 2, N = 6). Urine and plasma samples were collected for urine output, glomerular filtration rate (GFR), urine sodium, and plasma endothelin measurements. In Group 1, GFR fell significantly (p < 0.05) by 49% from a control of 0.88 +/- 0.12 mL/min per gram of kidney weight. Urine volume fell by 79% (p < 0.05) from a control value of 0.014 +/- 0.003 mL/min/gkw. Sodium excretion was decreased by 88%. Sodium reabsorption was significantly enhanced during pneumoperitoneum (99.56 +/- 0.15% v 98.44 +/- 0.25%). Arterial plasma ET concentrations were elevated by 8% during the first 20 minutes of pneumoperitoneum (30.8 +/- 3.6 v 33.3 +/- 3.4 pg/mL; p < 0.05). In Group 2, left renal vein compression resulted in a 31% decrease (p < 0.05) in GFR in the left kidney and a 25% decrease in the right kidney. Urine volume fell by 67% in the left kidney and 40% in the right. Renal venous ET concentrations also increased after renal vein compression. Although the mechanism by which oliguria occurs during pneumoperitoneum is not fully understood, the ET concentration was elevated. Because ET can decrease RBF, GFR, and sodium excretion, it may contribute to the oliguria observed during long periods of pneumoperitoneum.


Asunto(s)
Abdomen/fisiopatología , Endotelinas/metabolismo , Neumoperitoneo/fisiopatología , Animales , Perros , Endotelinas/sangre , Riñón/fisiopatología , Ligadura , Neumoperitoneo/metabolismo , Presión , Venas Renales
8.
Urology ; 50(5): 812-7, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9372901

RESUMEN

OBJECTIVES: Patients with reduced renal mass are at increased risk of developing renal failure. A remnant kidney model has been used to study the hemodynamic and structural changes that occur. We recently reported that the lipid-lowering agent lovastatin preserves renal function in this model. The purpose of the present study was to determine the specific effects of lovastation on the renal microcirculation of rats with reduced renal mass. METHODS: We used the rat hydronephrotic kidney preparation with a 5/6 partial nephrectomy. This model allows direct visualization of preglomerular and postglomerular vessels using videomicroscopy. The diameters and vascular responses to acetylcholine and angiotensin II of the interlobular, afferent, and efferent vessels were determined in two groups of animals with renal mass reduction: 15 rats with no lovastatin treatment and 18 rats treated with oral lovastatin (15 mg/kg body weight/day) for 2 weeks. RESULTS: In the lovastatin-treated rats, the baseline efferent vessel diameter was smaller by 21% (P < 0.05), but the interlobular and afferent vessel baseline diameters were not different from those in the untreated rats. Serum creatinine levels were lower in the treated rats (1.5 +/- 0.1 versus 2.0 +/- 0.2 mg/dL, P < 0.05), but serum lipids were not different. In the lovastatin-treated rats, vascular reactivity to acetylcholine was enhanced in the afferent and decreased in the efferent vessels. CONCLUSIONS: In this renal ablation model, lovastatin preserved renal function as measured by serum creatinine without lowering plasma lipid levels. Lovastatin treatment resulted in smaller efferent vessel diameters. Lovastatin also increased the vasodilatory response to acetylcholine in the afferent vessels. Together, these preglomerular and postglomerular changes would increase the single-nephron glomerular filtration rate. The renal protective effect of lovastatin may be due to these vasoactive effects on the renal microcirculation.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Lovastatina/farmacología , Animales , Hidronefrosis/fisiopatología , Riñón/patología , Microcirculación/efectos de los fármacos , Ratas
9.
Urology ; 48(6): 862-7, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8973668

RESUMEN

OBJECTIVES: Patients with renal mass reduction of more than 50% are at increased risk for progressive renal failure. Lipid-lowering agents have been shown to preserve renal function in various models of chronic renal failure. This study was performed to evaluate the hemodynamic effects of lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in the remnant kidney model. METHODS: Two groups of animals were studied. Group 1 (n = 9) served as controls and group 2 (n = 14) received lovastatin, 15 mg/kg/day orally, for 2 weeks after renal ablation. Glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, ultrasonic flow probe), and 24-hour protein excretion were measured in anesthetized rats. RESULTS: Two weeks after renal ablation, GFR was 0.28 +/- 0.09 mL/min/gkw (gram kidney weight) in group 1, whereas in group 2, lovastatin preserved GFR at 0.58 +/- 0.3 mL/min/gkw (P < 0.05). RBF in group 1 was 1.2 +/- 0.2 mL/min/gkw and increased to 2.1 +/- 0.4 mL/min/gkw in group 2 (P < 0.05), representing a 43% increase. Protein excretion decreased significantly to 13 +/- 1.7 mg/24 hr in group 2. The lovastatin-treated group had a lower serum cholesterol (59 +/- 3 mg/dL versus 71 +/- 2 mg/dL, P < 0.05), but serum triglyceride levels were not different between the two groups. CONCLUSIONS: Lovastatin preserves renal function in a renal ablation model after 2 weeks of treatment. It specifically increased total RBF. Therefore, in addition to its known cholesterol lowering effect, lovastatin also has the direct renal hemodynamic effect of increasing RBF and maintaining GFR.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Riñón/efectos de los fármacos , Riñón/fisiopatología , Lovastatina/farmacología , Nefrectomía , Animales , Hemodinámica/efectos de los fármacos , Masculino , Ratas , Ratas Wistar
10.
J Urol ; 156(1): 249-52, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8648816

RESUMEN

PURPOSE: Lovastatin, an HMG-CoA reductase inhibitor, has been shown to preserve renal function in models of chronic renal failure. We determined the effect of lovastatin on renal function and hemodynamics in normal nonpathologic kidneys in a rodent model. MATERIALS AND METHODS: Renal function was measured in anesthetized (Inactin) control rats (n = 13) and lovastatin-treated rats (15 mg./kg./day, 3 weeks, orally, n = 17). Renal blood flow was measured with an ultrasonic flowprobe, and glomerular filtration rate was measured by inulin clearance. The effect of lovastatin on pre- and postglomerular vessel diameters was also observed in a hydronephrotic kidney preparation by videomicroscopy. RESULTS: Lovastatin significantly increased (p < 0.05) renal blood flow and glomerular filtration rate by 17% (3.4 +/- 0.2 ml./min./gram kidney weight (gKW) versus 2.9 +/- 0.2 ml./min./gKW) and 49% (0.67 +/- 0.04 ml./min./gKW versus 0.45 +/- 0.06 ml./min./gKW). The increase in renal blood flow was mediated by preglomerular vasodilation (expressed as percent increase from baseline diameter, n = 20), 25% in the interlobular artery and 20% in the afferent arteriole (p < 0.05). CONCLUSIONS: In addition to its known lipid-lowering properties, lovastatin has a direct renal hemodynamic effect, increasing renal blood flow and glomerular filtration rate in normal nonpathologic kidneys. Lovastatin's selective preglomerular vasodilation may account for the observed increase in renal blood flow and glomerular filtration rate. Accordingly, this additional hemodynamic effect may be useful in preserving renal function in models of chronic renal failure.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Lovastatina/farmacología , Circulación Renal/efectos de los fármacos , Animales , Hemodinámica/efectos de los fármacos , Masculino , Ratas , Ratas Wistar
13.
J Urol ; 155(1): 350-4, 1996 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7490885

RESUMEN

PURPOSE: The purpose of this study was to characterize the hemodynamic changes in the contralateral testis during acute spermatic cord torsion in anesthetized rats. MATERIALS AND METHODS: We used videomicroscopy to examine the microcirculation of the contralateral testis following acute torsion. Specifically, we examined the effect on vasomotion, a rhythmic dilation and constriction of the arterioles that is involved in fluid and nutrient exchange and modulation of local vascular resistance. In a separate set of experiments, blood flow in the contralateral internal spermatic artery was measured with an ultrasonic flow probe during acute torsion. RESULTS: Following 720 degrees torsion, the amplitude of vasomotion in the contralateral testis increased 121% (29.0 +/- 3.9% versus 13.0 +/- 1.7%) compared with controls. Blood flow in the contralateral internal spermatic artery decreased 43% after 2 hours' torsion. CONCLUSIONS: Acute spermatic cord torsion altered the microcirculation by increasing the amplitude of vasomotion and decreased total blood flow to the opposite testis. Because the hydraulic resistance of a blood vessel exhibiting vasomotion is always less than a vessel with the same average but static diameter, the observed microcirculatory changes may be an adaptive response to preserve local flow in the presence of decreased total flow. The long-term consequences of these changes in the microcirculation may affect testicular function and ultimately fertility.


Asunto(s)
Torsión del Cordón Espermático/fisiopatología , Testículo/irrigación sanguínea , Enfermedad Aguda , Animales , Arterias/fisiología , Arteriolas/fisiología , Masculino , Microscopía por Video , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/fisiología , Vasoconstricción/fisiología , Vasodilatación/fisiología
14.
Urology ; 46(4): 559-61, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7571229

RESUMEN

OBJECTIVES: To evaluate the effectiveness of percutaneous endoscopy of the tunica vaginalis for identifying testicular torsion in a rodent model. METHODS: One testis was randomly selected in 10 Wistar rats weighing 500 to 600 g. Following 2 hours of 720 degree torsion, bilateral percutaneous endoscopy of the tunica vaginalis was performed by a blinded investigator utilizing a 70 degree cystoscope lens through a single midline 3 to 4 mm scrotal cutdown incision. RESULTS: Using this technique, the blinded investigator was able to identify the torsed testis rapidly in every case, which was distinguished by its cyanotic color and by the size and color of the testicular surface vessels. CONCLUSIONS: Tunica vaginoscopy is a simple, accurate, rapidly performed, minimally invasive, diagnostic technique in this experimental model of testicular torsion.


Asunto(s)
Torsión del Cordón Espermático/diagnóstico , Animales , Endoscopía , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar
15.
Urology ; 46(3): 438-42, 1995 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7660528

RESUMEN

OBJECTIVES: To define the role of endothelium-derived relaxing factor (EDRF) in the regulation of renal hemodynamics in the hydronephrotic kidney. METHODS: Experiments were performed in control rats and in rats that had undergone unilateral ureteral ligation 6 weeks before. Renal blood flow was monitored before and after inhibition of EDRF synthesis in the control and hydronephrotic animals. Videomicroscopy was also performed in hydronephrotic animals to observe directly the effect of inhibition of EDRF synthesis on the renal microcirculation. RESULTS: Inhibition of EDRF synthesis resulted in a 61% decrease in renal blood flow in the control animals compared with only a 27% decrease for the hydronephrotic animals. The videomicroscopy studies demonstrated that inhibition of EDRF synthesis results in significant vasoconstriction of the preglomerular and postglomerular resistance vessels. CONCLUSIONS: Although EDRF continues to play a significant role in the maintenance of renal blood flow in the chronically obstructed kidney, EDRF synthesis by the renal vascular endothelium may be reduced in this setting, contributing to ischemic renal atrophy.


Asunto(s)
Hidronefrosis/fisiopatología , Óxido Nítrico/fisiología , Circulación Renal/fisiología , Acetilcolina/farmacología , Animales , Arginina/análogos & derivados , Arginina/farmacología , Enfermedad Crónica , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Masculino , Microcirculación/efectos de los fármacos , Microscopía por Video , Óxido Nítrico/biosíntesis , Nitroarginina , Ratas , Ratas Wistar , Circulación Renal/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasoconstricción/fisiología
16.
Am J Physiol ; 268(2 Pt 2): F302-8, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7864170

RESUMEN

The effect of dietary protein on renal function and on renal microvascular reactivity to angiotensin II was determined in rats fed a high-protein diet (40% protein), a low-protein diet (6% protein), or a normal diet (23% protein). Inulin clearance was higher in high-protein-fed rats (n = 7) than in rats fed a low-protein diet (n = 7), 0.88 +/- 0.14 (means +/- SE) vs. 0.54 +/- 0.07 ml.min-1.g kidney wt-1 (P < 0.05). We also used videomicroscopy to assess the effect of angiotensin II on the renal microcirculation in a hydronephrotic kidney preparation. The afferent and efferent arterioles constricted to angiotensin II and norepinephrine in both high- and low-protein-fed rats; this constriction was diminished to angiotensin II but not to norepinephrine, in rats fed a high-protein diet (-24.3 +/- 4.5, -20.2 +/- 4.2%) compared with rats fed a low-protein diet (-39 +/- 5.1, -39.1 +/- 5.7%). The vasoconstrictor responses to angiotensin II in rats fed a high-protein diet and a normal diet were significantly greater following inhibition of angiotensin II formation with captopril but not in low-protein-fed rats. The apparent high-endogenous level of angiotensin II among rats fed a high-protein diet may account for the diminished reactivity to exogenous angiotensin II. Thus alterations in intrinsic vascular reactivity to angiotensin II are not responsible for the altered hemodynamics associated with dietary protein.


Asunto(s)
Angiotensina II/farmacología , Proteínas en la Dieta/farmacología , Circulación Renal/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Captopril/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Masculino , Microcirculación/efectos de los fármacos , Microscopía por Video , Norepinefrina/farmacología , Ratas , Ratas Wistar , Vasodilatadores/farmacología
17.
Cleve Clin J Med ; 61(5): 356-62, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7955308

RESUMEN

BACKGROUND: The renal circulation plays a central role in regulating blood pressure and glomerular filtration. OBJECTIVE: To examine the effects of the various classes of antihypertensive agents on the renal microcirculation. SUMMARY: Peripheral vascular resistance is generally increased in hypertension, and the microcirculation makes the major contribution to resistance. In the kidney, the preglomerular and postglomerular vessels constrict to protect the glomerular capillary from increased hydrostatic pressure, further increasing peripheral resistance. Because the renal microcirculation adjusts to maintain glomerular filtration and blood flow, antihypertensive agents that can normalize the pressure and blood flow in these vessels may help prevent the long-term consequences of hypertension. Angiotensin-converting enzyme inhibitors directly affect preglomerular and postglomerular resistance, but they further decrease postglomerular resistance. Calcium antagonists selectively decrease preglomerular resistance. The diuretics, vasodilators, alpha blockers, and beta blockers may also cause changes in preglomerular and postglomerular resistance; however, compensatory reflex responses may mitigate their direct effects. CONCLUSION: Some antihypertensive agents have unique actions on the renal microcirculation that better maintain renal function. A basic understanding of the physiologic action of these agents on the microcirculation may help in their selection.


Asunto(s)
Antihipertensivos/farmacología , Hipertensión/tratamiento farmacológico , Circulación Renal/efectos de los fármacos , Antihipertensivos/uso terapéutico , Humanos , Microcirculación/efectos de los fármacos , Microcirculación/fisiología , Circulación Renal/fisiología
18.
Cleve Clin J Med ; 61(3): 179-85, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-8026061

RESUMEN

BACKGROUND: In the kidney, the afferent and efferent arterioles normally constrict or dilate in response to changes in systemic blood pressure to maintain glomerular filtration while protecting the glomerulus from excessive pressure. In diabetes mellitus and hypertension, the two most common causes of kidney failure, sustained hypertension within the glomerulus damages the glomerular membrane and eventually results in loss of kidney function. SUMMARY: Techniques developed in the last 10 years allow direct study of the glomerulus and the glomerular circulation. In both diabetes and hypertension, the afferent vessels may dilate, resulting in excessive pressure in the glomerulus. Calcium antagonists, angiotensin-converting enzyme inhibitors, and cyclosporine have direct effects on the preglomerular and postglomerular vessels, and the afferent and efferent arterioles may respond differently to the same agent. CONCLUSIONS: Techniques for studying afferent and efferent arteriolar changes and glomerular filtration rate may provide important insights into the actions of drugs and into renal diseases. Clinicians are beginning to be able to select drugs that have desired effects on the renal microcirculation.


Asunto(s)
Enfermedades Renales/fisiopatología , Glomérulos Renales/irrigación sanguínea , Circulación Renal , Animales , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/terapia , Microcirculación , Ratas , Circulación Renal/efectos de los fármacos
19.
Anesth Analg ; 78(4): 682-6, 1994 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-7907847

RESUMEN

We assessed the effects of succinylcholine and vecuronium on renal function and on the renal microcirculation in a rodent model. Vecuronium (0.02 mg/kg followed by 0.2 mg.kg-1 x h-1) caused a significant decrease of 16.1% +/- 3.87% in inulin clearance from 0.92 +/- 0.07 to 0.71 +/- 0.05 mL.min-1 x gKW-1 (gram of kidney weight), and a decrease in para-aminohippuric acid clearance by 21.6% +/- 4.69% from 1.58 +/- 0.26 to 1.31 +/- 0.20 mL.min-1 x gKW-1 (P < 0.05), whereas succinylcholine (0.45 mg/kg followed by 2 mg.kg-1 x h-1) altered neither. The effect of these muscle relaxants was also determined on the renal microcirculation in separate experiments using videomicroscopy. Succinylcholine (n = 10; 10(-10) to 10(-6) M) and its parent compound, acetylcholine (n = 10, 10(-10) to 10(-6) M) used as a control, caused a significant vasodilation from baseline diameter in the interlobular, afferent, and efferent arterioles. The vasodilation caused by succinylcholine was significantly less than that observed with acetylcholine. Atropine blocked the response to succinylcholine, indicating the latter has a muscarinic effect. In contrast, vecuronium caused a significant, selective vasoconstriction from baseline diameter in the preglomerular vessels, but not in the postglomerular vessels. The vasoconstriction caused by vecuronium was significantly different than the vasodilation caused by succinylcholine. The preglomerular vasoconstriction observed with vecuronium may contribute to the decrease in renal plasma flow and glomerular filtration rate observed experimentally. The choice of a neuromuscular blocking drug can therefore have the potential to influence renal function by altering the renal microcirculation.


Asunto(s)
Riñón/irrigación sanguínea , Succinilcolina/farmacología , Bromuro de Vecuronio/farmacología , Animales , Tasa de Filtración Glomerular/efectos de los fármacos , Microcirculación/efectos de los fármacos , Ratas , Ratas Wistar
20.
J Assist Reprod Genet ; 11(1): 42-8, 1994 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7949835

RESUMEN

PURPOSE: Having observed that sperm from the chronically obstructed caput epididymis fertilize poorly in vitro, we investigated the effect of partial zona dissection (PZD) on fertilization in a murine model of unilateral proximal epididymal obstruction. Cleavage rates were compared for zona-intact oocytes and PZD oocytes incubated with sperm from the following epididymal segments: the obstructed caput, the contralateral nonobstructed caput, the contralateral cauda, and a sperm-free preparation to control for parthenogenesis. RESULTS: Unilateral epididymal obstruction resulted in significantly higher sperm counts in the obstructed caput compared to the nonobstructed caput, although there was no difference in motility. Cleavage rates for ova incubated with sperm from the obstructed caput and the nonobstructed caput were uniformly poor and did not differ significantly from those for the sperm-free controls. Cauda sperm fertilized significantly better than all other sperm groups (P < 0.05). Partial zona dissection did not improve cleavage rates in any group. CONCLUSION: We conclude that sperm from the chronically obstructed caput epididymis, like sperm from the normal caput, are unable to fertilize ova, and PZD does not enhance this poor fertilizing capacity. Furthermore, the finding that PZD does not improve the fertilizing capacity of the presumably mature cauda sperm in our mouse model suggests that any beneficial effect of PZD may be strain-specific.


Asunto(s)
Epidídimo/citología , Capacitación Espermática/fisiología , Espermatozoides/citología , Espermatozoides/fisiología , Zona Pelúcida/fisiología , Animales , Epidídimo/fisiología , Femenino , Masculino , Ratones , Microcirugia , Oocitos/citología , Oocitos/fisiología , Interacciones Espermatozoide-Óvulo/fisiología
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