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P Rooth

Publications and source records attributed to P Rooth.

34 records · Page 2Linked to original sources
PubMed1992

Verapamil (VP) improves the outcome after renal transplantation (CRT).

Calcium antagonists (CATs) have a role in the management of certain types of renal insufficiency. These include prophylaxis against post-transplant-associated acute renal failure and cyclosporine A (CsA)-induced renal dysfunction. For the transplanted kidney, CATs may be beneficial in several settings. First, a CAT during organ procurement protects the kidney during ischemic periods. Second, CATs given perioperatively protect the kidney during reperfusion and early after transplantation. Third, CATs also offer protection against CsA nephrotoxicity.

Calcium Channel Blockers↗
PubMed1991

Improvement of cadaver renal transplantation outcomes with verapamil: a review.

Although cyclosporin A (CsA) has allowed substantial advances in organ transplantation due to its immunosuppressive properties, its use is complicated by its direct nephrotoxic effects. Initial studies with mice confirmed that CsA caused a dose-related inhibition of the subcapsular microcirculation; subsequent clinical investigations have confirmed this inhibitory effect. Efforts to circumvent CsA-induced nephrotoxicity have focused on calcium antagonists. For example, when the calcium antagonist verapamil was administered before the initiation of CsA, renal blood flow was maintained. Verapamil therapy was also associated with significantly fewer rejection episodes (3 of 22; 14%) within 4 weeks of transplantation than CsA therapy alone (10 of 18; 56%). In a current study, verapamil 10 mg was injected into the renal artery during surgery, followed by 120 mg tid orally for 14 days. This regimen reduced delayed function incidents (the need for dialysis) during the first post-transplant week. Excluding nonfunctioning kidneys and technical failures, there were no graft losses secondary to rejection in patients treated with verapamil. The beneficial effects of verapamil therapy on transplant outcome may be related to its ability to protect cells from ischemia, the selective vasodilation of the efferent arteriole, elevated CsA blood levels, and inherent immunosuppressive properties.

Administration, Oral↗
PubMed1991

Verapamil improves the outcome after cadaver renal transplantation.

Because of their favorable effects on renal hemodynamics, calcium antagonists may have a major role in the prevention and management of certain types of acute renal dysfunction. In fact, verapamil (VP) was shown to prevent cyclosporin A (CsA)-induced decreases in RBF in mice and in cadaver renal transplant (CRT) recipients. The study presented here of 59 cadaver renal transplant patients evaluates the outcome from perioperative treatment with VP (N = 30) administered intraoperatively into the renal artery (10 mg) followed by oral administration of 120 mg every 8 to 12 h for 14 days versus no drug (N = 29). Early immunosuppression included azathioprine, corticosteroids, and antilymphocyte globulin with subsequent overlapping with CsA on days 5 and 6. Actuarial graft survival at 1 yr was different when the two groups were compared (P less than 0.05). Estimated graft survival at 1 yr for VP patients was 93.3 compared with 72.4% in control patients. The improved graft survival was most striking in repeat transplants with 90% graft survival at 1 yr for VP recipients versus 37.5% for controls. Compared with controls, VP recipients had significantly improved renal parenchymal diastolic blood flow velocities on the first day after surgery (7.8 versus 5.8 cm/s). By day 7, GFR were greater with VP (44 +/- 29 mL/min) versus controls (28 +/- 22 mL/min). Of VP patients, 67% (18 of 24) had GFR greater than 30 mL/min versus 33% (9 of 26) for control patients. Similarly, on the seventh day, 77% (21 of 30) of VP patients had serum creatinines less than 2.0 mg% versus 34% (10 of 29) for controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Prevention of detrimental effect of cyclosporin A on vascular ingrowth of transplanted pancreatic islets with verapamil.

The revascularization of pancreatic islet clusters transplanted beneath the renal capsule was studied in a syngeneic mouse model. The degree of vascular ingrowth was visualized by in vivo fluorescence microscopy (fluorescein isothiocyanate-dextran) and judged by a semiquantitative method from coded video recordings. The recipients of isografts were divided into four groups, depending on their daily immunosuppressive treatment: 1) none (controls), 2) 15 mg/kg cyclosporin A (CsA), 3) 0.4 mg/kg verapamil + 15 mg/kg CsA, and 4) 20-30 mg/kg methylprednisolone. In control animals, capillary ingrowth was first demonstrated on day 6, followed by progressive vascularization up to day 34. After 6 mo, the vascular architecture was similar to that seen in normal islets in situ. CsA alone significantly decreased vascular ingrowth on day 14 compared with controls (P less than .02). Verapamil prevented the detrimental effect of CsA (P less than .01), probably by improving renal subcapsular blood flow. Methylprednisolone did not affect revascularization compared with control animals at day 14. We conclude that CsA inhibits vascular ingrowth into transplanted pancreatic islets, which is likely to have clinical implications. The prevention of CsA vascular ingrowth inhibition by a calcium antagonist indicates a possible approach to the correction of this problem, particularly when the renal capsule is used as the recipient's transplant site.

Animals↗
PubMed1989

Prevention of acute cyclosporine-induced renal blood flow inhibition and improved immunosuppression with verapamil.

Pretreatment with calcium antagonists such as verapamil (VP) and isradipine prevents CsA-induced decrease in renal microcirculation in mice. Recently, in posttransplant cadaver renal transplant (CRT) recipients, we demonstrated a CsA-induced 70% reduction in renal parenchymal diastolic blood flow velocity (PDBFV). Using duplex Doppler scanning, this randomized study of forty CRT patients examines the effect of pretreatment with VP on renal blood flow velocity and posttransplant function. Patients with initially low PDBFV (less than 8.0 cm/sec) who received VP therapy prior to administration of CsA experienced prompt restoration of flow, and continued to improve during CsA administration. With CsA alone, PDBFV diminished from 8.9 +/- 2.4 (SD) to 5.3 +/- 2.7 cm/sec (P less than 0.002). Although blood CsA levels were significantly higher at 1, 4, and 7 days (68, 184, and 235 ng/ml, respectively), after CsA induction, during VP treatment than in control patients (39, 105, and 156 ng/ml, respectively) (P less than 0.001), with the same daily doses of CsA, serum creatinines at day 7 were lower during VP treatment (1.28 +/- 0.44 vs. 1.66 +/- 0.44 mg%) than in controls (P less than 0.01). When the glomerular filtration rate was less than 45 ml/min on day 1. VP-treated patients showed greater improvement in GFR at day 7 by 34.1 +/- 10.9 ml/min compared with the 18 +/- 13 ml/min in controls (P less than 0.02). Only 3 of the 22 VP patients had rejection episodes within 4 weeks, versus 10 of the 18 recipients randomized to no drug (P less than 0.005). We conclude that VP is beneficial in CRT because it improves renal blood flow characteristics and prevents CsA-induced inhibition of blood flow. VP also ameliorates CsA-induced acute nephrotoxicity, and is associated with improved immunosuppression and fewer early rejections.

Cyclosporins↗
PubMed1988

Protection against cyclosporine-induced impairment of renal microcirculation by verapamil in mice.

Fluorescence microscopy was used to examine the effect of cyclosporine (CsA) infusion on renal subcapsular (cortical) blood flow in 53 living mice, using FITC-dextran (MW: 156,000) as a fluorescent marker. CsA (8-19 mg/kg body weight) given i.v. for 1 min induced complete inhibition of blood flow. A complete standstill of flow was also obtained during a continuous infusion with a rate of 0.8-2 mg/kg/min. With lower infusion rates (0.15-0.23 mg/kg/min), blood flow was partially impaired. In all experiments, the decrease in flow occurred after a 15-25 min delay, suggesting a CsA metabolite or exhaustion of a protective mechanism as the causative agent. Pretreatment with an alpha-blocking agent, phentolamine (1.0 mg/kg), did not prevent the CsA-induced inhibition of blood flow. In contrast, pretreatment with a calcium antagonist, verapamil (0.3-0.4 mg/kg), prevented the impairment of blood flow at low (0.15-0.23 mg/kg/min), and partially at higher (0.8-2.4 mg/kg/min) rates of CsA infusion. Clinical studies are warranted to explore the role of calcium antagonists in the prevention of posttransplant acute cyclosporine-induced nephrotoxicity.

Animals↗
PubMed1988

In vivo fluorescence microscopy of kidney subcapsular blood flow in mice. Effects of cyclosporine, (NVA2)-cyclosporine, and isradipine, a new calcium antagonist.

The subcapsular kidney microcirculation in mice was observed through a fluorescence microscope, recorded on videotape, and examined for response to infusions of cyclosporine A (CsA) and cyclosporine G (CsG). Coded video recordings were evaluated by a semiquantitative method. CsA infusion (1.6 +/- 0.4 mg/kg/min) induced a nearly complete inhibition of the subcapsular blood flow. At lower infusion rates (0.46 +/- 0.2 mg/kg/min), the blood flow inhibition was less pronounced. CsG infusions at corresponding rates induced significantly less inhibition. Pretreatment with a new calcium antagonist, isradipine (18-20 micrograms/kg bwt), completely prevented the CsA-induced impairment of subcapsular microcirculation. The calcium antagonist, however, did not improve blood flow when administered after induction of inhibition by CsA (16.8 +/- 2.5 mg/kg), emphasizing the importance of pretreatment. This study suggests hypoperfusion due to vasoconstriction as an important pathophysiologic mechanism for CsA-induced nephrotoxicity. CsG, when given at corresponding rates, induced less inhibition of the blood flow. Pretreatment with a calcium antagonist, isradipine, completely prevented a CsA-induced inhibition of blood flow, suggesting a potential value in the prevention of CsA-induced nephrotoxicity.

Animals↗
PubMed1987

Vital microscopy of islet blood flow: catecholamine effects in normal and ob/ob mice.

The pancreatic microcirculation in noninbred ob/ob mice and normal controls was visualized in a fluorescence microscope and examined for responses to intravenous infusions of epinephrine or norepinephrine. Evaluations of coded video recordings revealed a smooth dose-response relationship and validated a semiquantitative method of analysis. In ob/ob mice the islet microcirculation was markedly and reversibly inhibited by 0.14-4 micrograms of epinephrine X min-1 X kg body wt-1; the flow was almost totally stopped at the highest infusion rates. Capillary flow in the exocrine pancreas appeared unaffected, except for some inhibition at 4.0 micrograms X min-1 X kg-1. Norepinephrine was less potent an inhibitor of islet blood flow. Normal lean mice exhibited minor responses to 1-11.3 micrograms of epinephrine X min-1 X kg-1; in most cases there was no visible effect. It is concluded that there is a selective regulation of blood flow through the endocrine portion of the pancreas and that the islet microcirculation is hypersensitive to catecholamines in noninbred ob/ob mice. A defective inhibitory influence from the brain may play a role in the development of excessive hyperinsulinemia in ob/ob mice.

Animals↗
PubMed1987

Treatment of rats with hCG induces inflammation-like changes in the testicular microcirculation.

Adult rats were injected subcutaneously with 50 i.u. hCG and vascular permeability was compared to that in saline-treated control rats by two independent methods. At 4 h after hCG treatment the rats were injected intra-arterially (i.a.) with FITC-labelled macromolecular dextran (Mr 150,000) and the testicular microcirculation was studied in vivo by using a fluorescence microscope. Other rats were injected i.a. with a suspension of colloidal carbon and the location of leaking blood vessels was recorded in sections from the testes by light and electron microscopy. In hCG-treated animals leucocytes were found adhering to the endothelium in post-capillary venules and in these venular segments dextran was leaking into the interstitium. Carbon particles were deposited in the walls of post-capillary venules and leucocytes migrated through open interendothelial cell gaps in hCG-treated animals. In control animals leucocyte adhesion and migration were not observed, the injected dextran remained in the circulation and the blood vessels were not labelled by carbon. It is suggested that the hCG-induced increase in testicular interstitial fluid volume, like the tissue oedema in inflammation, is caused by a leucocyte-mediated increase in venular permeability.

Animals↗
PubMed1986

Testicular microcirculation in the rat studied by videophotometric capillaroscopy, fluorescence microscopy and laser Doppler flowmetry.

Testicular capillary blood flow was studied in rats using laser Doppler flowmetry, in vivo fluorescence microscopy and videophotometric capillaroscopy. All the methods revealed rhythmical oscillations in testicular microcirculation with a periodicity of 4-10 c.p.m. In arterioles, capillaries and small post-capillary vessels, periods of continuous blood flow alternated with periods of no or very low flow. No visible leakage of dextran-150 was observed from the testicular blood vessels. Four, 8 and 16 h after an s.c. injection of 200 IU hCG the blood flow was continuous and there was leakage of dextran-150 from the microvessels to the interstitial tissue. Twenty-four and 32 h after hCG the blood flow pattern was again rhythmical, and at 32 h there was no leakage of dextran-150. This suggests that hCG induces changes in blood flow and transvascular fluid exchange in the testis, perhaps by altering smooth muscle activity at the arteriolar-level.

Animals↗
PubMed1985

In vivo fluorescence microscopy of blood flow in mouse pancreatic islets: adrenergic effects in lean and obese-hyperglycemic mice.

The microcirculation in the islets of Langerhans was examined by fluorescence microscopy in living mice injected with fluorescent dextran. The islet capillary network was denser and more tortuously arranged in obese-hyperglycemic (ob/ob) mice than in lean controls. Injection of norepinephrine (0.5-4.0 micrograms/kg body wt) immediately led to a pronounced inhibition of islet blood flow in ob/ob mice. In experiments with lean mice less striking effects were seen. With as high a dose as 20 micrograms norepinephrine/kg body wt only a slight retardation and very brief stop of the flow occurred. The inhibition in ob/ob mice was blocked by phentolamine, indicating that the norepinephrine-induced inhibition was mediated by alpha-adrenoceptors. The alpha-2-adrenoceptor agonist, clonidine, had no effect on islet blood flow, suggesting that the effect of norepinephrine was due to alpha-1-adrenoceptor stimulation. It is concluded that in the living animal norepinephrine inhibits insulin secretion from the pancreas by a twofold mechanism involving inhibition of exocytosis (alpha-2-receptors on the beta-cells) as well as retardation of blood flow (alpha-1-receptors on blood vessels).

Animals↗