RESUMO
OBJECTIVE/BACKGROUND: Fenestrated endovascular repair (FEVAR) has been used to treat complex abdominal aortic aneurysms (AAAs). The risk of renal function deterioration compared with infrarenal endovascular aortic repair (EVAR) has not been determined. METHODS: Patients with preserved renal function (estimated glomerular filtration rate [eGFR] > 45 mL/minute) enrolled in two prospective, non-randomised studies evaluating Zenith fenestrated and AAA stent grafts were matched (1:2) by propensity scores for age, sex, hypertension, diabetes, and pre-operative eGFR. Sixty-seven patients were treated by FEVAR and 134 matched controls treated by EVAR. Mean follow-up was 30 ± 20 months. Outcomes included acute kidney injury (AKI) defined by RIFLE and changes in serum creatinine (sCr), eGFR, and chronic kidney disease (CKD) staging up to 5 years. RESULTS: AKI at 1 month was similar between groups, with > 25% decline in eGFR observed in 5% of FEVAR and 9% of EVAR patients (p = .39). There were no significant differences in > 25% decline in eGFR at 2 years (FEVAR 20% vs. EVAR 20%; p > .99) or 5 years (FEVAR 27% vs. EVAR 50%; p = .50). Progression to stage IV-V CKD was similar at 2 years (FEVAR 2% vs. EVAR 3%; p > .99) and 5 years (FEVAR 7% vs. EVAR 8%; p > .99), with similar sCr and eGFR up to 5 years. During follow-up, there were more renal artery stenosis/occlusions (15/67 [22%] vs. 3/134 [2%]; p < .001) and renal related re-interventions (12/67 [18%] vs. 4/134 [3%]; p < .001) in patients treated by FEVAR. Rate of progression to renal failure requiring dialysis was low and identical in both groups (1.5% vs. 1.5%; p > .99). CONCLUSION: Aortic repair with FEVAR and EVAR was associated with similar rates of renal function deterioration in patients with preserved pre-operative renal function. Renal related re-interventions were higher following FEVAR, although net changes in renal function were similar in both groups.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Nefropatias/etiologia , Rim/fisiopatologia , Stents , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Biomarcadores/sangue , Implante de Prótese Vascular/efeitos adversos , Creatinina/sangue , Progressão da Doença , Procedimentos Endovasculares/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Nefropatias/terapia , Masculino , Estudos Prospectivos , Desenho de Prótese , Diálise Renal , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
Nephrogenic systemic fibrosis (NSF) is a debilitating disease in patients with severely diminished kidney function. Currently, no standard treatment exists but improvement has been reported after restoration of kidney function. We retrospectively studied 17 NSF patients with and without successful kidney transplantation (KTx) to evaluate the effects of KTx on NSF. Nine of the 11 KTx developed NSF pretransplant whereas two developed NSF immediately after KTx with delayed graft function. Two of the six dialysis patients had previous failed kidney transplants. Age and sex were well matched. All but one patient was dialysis dependent at the time of NSF. Median follow-up was 35 months for KTx patients and 9 months for dialysis patients. Kidney transplants achieved adequate renal function with median serum creatinine of 1.4 (0.9-2.8) mg/dL and a glomerular filtration rate of 42 (19-60) mL/min/1.73 m(2). NSF improved in 54.6% of the transplanted patients and 50% of the nontransplanted patients (p = 0.86). Two KTx patients had complete resolution of their symptoms whereas four had partial improvement. Improvement in the dialysis patients was all partial. Successful KTx did not insure improvement in NSF and in fact appeared to have no significant benefit over dialysis.
Assuntos
Transplante de Rim/métodos , Dermopatia Fibrosante Nefrogênica/terapia , Adulto , Idoso , Creatinina/sangue , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIMS: Patients with renovascular hypertension (RVH) exhibit elevated urinary mtDNA copy numbers, considered to constitute surrogate markers of renal mitochondrial injury. The modest success of percutaneous transluminal renal angioplasty (PTRA) in restoring renal function in RVH has been postulated to be partly attributable to acute reperfusion injury. We hypothesized that mitoprotection during revascularization would ameliorate PTRA-induced renal mitochondrial injury, reflected in elevated urinary mtDNA copy numbers and improve blood pressure and functional outcomes 3 months later. METHODS: We prospectively measured urinary copy number of the mtDNA genes COX3 and ND1 using qPCR in RVH patients before and 24 hrs after PTRA, performed during IV infusion of vehicle (n = 8) or the mitoprotective drug elamipretide (ELAM, 0.05 mg/kg/h, n = 6). Five healthy volunteers (HV) served as controls. Urinary mtDNA levels were also assessed in RVH and normal pigs (n = 7 each), in which renal mitochondrial structure and density were studied ex-vivo. RESULTS: Baseline urinary mtDNA levels were elevated in all RVH patients vs HV and directly correlated with serum creatinine levels. An increase in urinary mtDNA 24 hours after PTRA was blunted in PTRA+ELAM vs PTRA+Placebo. Furthermore, 3-months after PTRA, systolic blood pressure decreased and estimated glomerular filtration rate increased only in ELAM-treated subjects. In RVH pigs, mitochondrial damage was observed using electron microscopy in tubular cells and elevated urinary mtDNA levels correlated inversely with renal mitochondrial density. CONCLUSIONS: PTRA leads to an acute rise in urinary mtDNA, reflecting renal mitochondrial injury that in turn inhibits renal recovery. Mitoprotection might minimize PTRA-associated mitochondrial injury and improve renal outcomes after revascularization.
Assuntos
DNA Mitocondrial/metabolismo , Hipertensão Renovascular/metabolismo , Rim/metabolismo , Mitocôndrias/metabolismo , Animais , Variações do Número de Cópias de DNA , Feminino , Humanos , Hipertensão/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Circulação Renal/fisiologia , SuínosRESUMO
Thirteen patients with hypertension and normal renal function received nitrendipine, a calcium entry blocker. Nitrendipine did not modify renal blood flow (RBF) or glomerular filtration rate (GFR), decreased mean arterial pressure (MAP) and total peripheral resistance, and did not significantly change cardiac output. Individual RBF changes did not correlate with MAP or cardiac output modifications. Mean arterial pressure changes were inversely correlated with basal renin levels and directly associated with age. Plasma catecholamines and plasma renin activity increased, but plasma aldosterone and plasma volume did not change significantly. However, the greater decrements of MAP tended to be associated with the greater increases in plasma volume. Data show that long-term calcium entry blockade by nitrendipine does not modify RBF or GFR despite the decreased renal perfusion pressure. Further, nitrendipine may be more effective in older patients and the presence of low renin.
Assuntos
Líquidos Corporais/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Rim/efeitos dos fármacos , Nifedipino/análogos & derivados , Adulto , Idoso , Aldosterona/sangue , Volume Sanguíneo/efeitos dos fármacos , Catecolaminas/sangue , Eletrólitos/sangue , Feminino , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêutico , Nitrendipino , Renina/sangueRESUMO
Although surgical repair of renal artery stenosis occasionally improves renal function, it is not yet known when revascularization is indicated for that reason. We report the results observed in a patient with renovascular hypertension and additional stenosis in the contralateral kidney whose renal function deteriorated on repeated occasions during antihypertensive therapy. Renal hemodynamic studies during sodium nitroprusside infusion showed severely impaired autoregulation of blood flow, and glomerular filtration rate was corrected after revascularization of the contralateral kidney alone. After surgery, normal BPs were tolerated without loss of function. These findings demonstrate a specific clinical indication for renal revascularization to preserve kidney function.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Renovascular/tratamento farmacológico , Obstrução da Artéria Renal/cirurgia , Feminino , Humanos , Hipertensão Renovascular/cirurgia , Pessoa de Meia-IdadeRESUMO
Hypertension develops in most patients after transplantation when immunosuppression is based on cyclosporine and prednisone. The pathogenesis appears to be multifactorial but involves rapidly rising vasoconstrictor tone in renal and systemic vascular beds. Much of this tone reflects abnormal vascular function, characterized by impaired prostacyclin and EDRF effects, in conjunction with increased vasoconstriction due to endothelin and possibly other factors. Effective management of the transplant recipient depends on preventing excessive vasoconstriction, usually with calcium channel blocking agents.
Assuntos
Hipertensão/etiologia , Transplante de Fígado , Complicações Pós-Operatórias , Adulto , Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Terapia de Imunossupressão/efeitos adversos , Labetalol/uso terapêutico , Masculino , Infecções Oportunistas/etiologia , Cuidados Pós-Operatórios , Prednisona/uso terapêuticoRESUMO
Studies of normotensive offspring of hypertensive parents offer the potential to identify inherited abnormalities that contribute to essential hypertension. We compared renal and systemic hemodynamic responses to saline infusion between normotensive sons of two hypertensive parents (SOHT) and sons of two normotensive parents (SONT) selected from the general population of Rochester, Minn. Hemodynamic measurements were performed after a week of low sodium intake (10 meq/day) and were repeated after a week of high sodium intake (200 meq/day). Despite being in the normotensive range, blood pressures in SOHT were higher than those in SONT during low sodium (124 +/- 3/85 +/- 3 versus 118 +/- 2/71 +/- 2 mm Hg, p less than 0.01) and high sodium (122 +/- 3/80 +/- 3 versus 112 +/- 2/70 +/- 2 mm Hg, p less than 0.05) conditions. Higher pressures in SOHT were associated with elevated systemic and renal vascular resistance. After a high sodium diet, renal vascular resistance in SOHT rose further during acute saline infusion, whereas systemic vascular resistance did not change. After a low sodium diet, this renal vasoconstrictor response to saline infusion in SOHT was not present, and renal vascular resistance fell to levels not different from SONT. Plasma renin activity, aldosterone, and atrial natriuretic peptide did not differ between SONT and SOHT. Circulating levels of norepinephrine were higher in SOHT. These data demonstrate a renal vasoconstrictor response to saline infusion in normotensive SOHT, which depends on prior sodium intake. This alteration in renal hemodynamics may represent an inherited abnormality related to the development of hypertension.
Assuntos
Hipertensão/genética , Circulação Renal/efeitos dos fármacos , Sódio/farmacologia , Adulto , Vasos Sanguíneos/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Dieta Hipossódica , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Cloreto de Sódio/farmacologia , Resistência Vascular/efeitos dos fármacosRESUMO
Interpretation of results obtained with angiotensin-converting enzyme inhibition in hypertensive patients has been obscured by the possibility of nonangiotensin-mediated mechanisms, particularly rats, we have compared the effects of converting enzyme inhibition (CEI) by oral captopril administration to those of dextrose. In this setting of constant angiotensin II levels, any apparent effects of CEI must be mediated by a nonangiotensin-related mechanism. Angiotensin II infusion at 30 ng/min increased mean blood pressure by an average of 22 mm Hg. Following 7 days of CEI, effective blockade of converting enzyme was established both by a 10-fold elevation of vasodepressor sensitivity to exogenous bradykinin and a markedly decreased plasma converting enzyme activity. On the ninth day of angiotensin II infusion, mean arterial pressure, heart rate, and plasma renin activity were not different between CEI and dextrose-treated groups. Similarly, blockade of angiotensin II by saralasin induced a comparable fall in blood pressure in both groups. Metabolic studies also revealed no long-term differences in water and food intake, weight change, or sodium and potassium metabolisms. These findings suggest that, in the continued presence of angiotensin II, there is no detectable hemodynamic or metabolic effect of chronic converting enzyme inhibition, and therefore that bradykinin plays little or no role in its long-term antihypertensive action.
Assuntos
Angiotensina II/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Prolina/análogos & derivados , Animais , Bradicinina/metabolismo , Bradicinina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Infusões Intra-Arteriais , Masculino , Potássio/metabolismo , Ratos , Saralasina/farmacologia , Sódio/metabolismoRESUMO
To assess the interaction between adrenergic activity and blood pressure regulation in patients with chronic renal failure, plasma norepinephrine (NE) and plasma renin activity (PRA) were measured before and after vigorous ultrafiltration. The significance of PRA was further assessed by angiotensin blockade with saralasin. Two patterns of response were defined: nine patients had low levels of PRA before and after hemodialysis. These patients showed a net fall in norepinephrine and no angiotensin dependence of any time. Failure to stimulate either PRA or norepinephrine was also observed during periods of marked hypotension. Seven other patients had higher PRA, which rose during hemodialysis. This was associated with an increase in NE and postdialysis angiotensin dependence. Patients experiencing hypotension in this group showed a sharp rise in NE, suggesting baroceptor-mediated adrenergic stimulation. In all patients sustaining hypotension during therapy, postdialysis PRA was closely correlated with NE. These results indicate that hemodialysis mobilizes the renin-angiotensin system to maintain hypertension in a greater proportion of dialysis patients than previously supposed and that impaired renin release following hypotension may represent uremic autonomic dysfunction.
Assuntos
Hipertensão/fisiopatologia , Falência Renal Crônica/fisiopatologia , Norepinefrina/sangue , Diálise Renal , Renina/sangue , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Volume Sanguíneo , Humanos , Hipotensão/fisiopatologia , Pessoa de Meia-Idade , Saralasina/farmacologiaRESUMO
The antihypertensive, hemodynamic, and humoral effects of the new converting-enzyme inhibitor enalapril (MK-421) were assessed by sequential studies during 3 months of uninterrupted treatment (20 mg twice daily) in 10 hypertensive patients. Six achieved good blood pressure (mean arterial pressure) control with enalapril alone (from 126 +/- 7.0 mm Hg pretreatment to 105 +/- 1.6 mm Hg at 3 months, p less than 0.05). The other four required the addition of diuretics (hydrochlorothiazide 25 mg orally twice daily) at different stages of follow-up, with resultant blood pressure control (128 +/- 9.6 mm Hg pretreatment to 113 +/- 1.9 mm Hg at 2 months after the addition of diuretics). Neither the acute nor long-term blood pressure response could be predicted from the pretreatment levels of plasma renin activity. The blood pressure reduction during enalapril therapy was characterized by a decrease in total peripheral resistance (53 +/- 2.5 U X M2 pretreatment to 38 +/- 3.0 U X M2 at 3 months, p less than 0.05) with no significant change in cardiac output or heart rate. This lack of reflex tachycardia could not be ascribed to baroceptor dysfunction since the response to head-up tilt (the increase in diastolic blood pressure, in heart rate, and in plasma catecholamines) was normal and not significantly different from pretreatment response. Average blood volume did not change (91% +/- 4.3% of normal in the pretreatment period to 93% +/- 2.9% after 3 months of therapy, p = NS) despite the significant lowering of arterial pressure with enalapril alone (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos/uso terapêutico , Dipeptídeos/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Adulto , Idoso , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Volume Sanguíneo/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Dipeptídeos/farmacologia , Quimioterapia Combinada , Enalapril , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidroclorotiazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resistência Vascular/efeitos dos fármacosRESUMO
Cyclosporine induces hypertension and wide-spread vasoconstriction after transplantation in addition to reducing kidney function. We studied hemodynamic, renal, and hormonal effects of monotherapy with nifedipine XL (n = 37) in liver transplant recipients within a year after transplant (median, 4.4 months). Systemic hemodynamics were determined with thoracic electrical bioimpedance. Blood pressure before therapy was 172 +/- 4/108 +/- 2 mm Hg. Sixty-four percent of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall in systemic vascular resistance index (2427 +/- 245 dyne.s.cm-5.m-2 in responders versus 2905 +/- 281 in nonresponders, P < .01). Despite the fall in systemic vascular resistance, glomerular filtration rates were not changed during nifedipine therapy, as measured by both creatinine and iothalamate clearances. Urinary prostacyclin (6-ketoprostaglandin F1 alpha) was suppressed below normal from 2468 +/- 323 ng/d before transplant to 1103 +/- 99 ng/d (P < .01) after transplant and did not change during nifedipine therapy. Urinary thromboxane B2 and plasma renin activity also fell after transplant and remained low during nifedipine. These data demonstrate that nifedipine can reverse systemic vasoconstriction associated with hypertension after transplantation. Systemic effects were not transmitted to the kidney sufficiently to improve glomerular filtration rate or reverse hormonal changes within the kidney. Hence, vascular and functional regulation of the kidney was dissociated from the systemic circulation during nifedipine administration after transplantation.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Ciclosporina/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , 6-Cetoprostaglandina F1 alfa/urina , Adolescente , Adulto , Idoso , Débito Cardíaco/efeitos dos fármacos , Diástole/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Hipertensão/fisiopatologia , Transplante de Fígado/imunologia , Transplante de Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , Renina/sangue , Sístole/efeitos dos fármacos , Tromboxano B2/urina , Resistência Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacosRESUMO
To better define the intrarenal hemodynamic effects of angiotensin in human renovascular hypertension, 10 patients underwent renal hemodynamic and functional measurements before and during infusion of a competitive angiotensin analog, [Sar1, Thr8] AII. Eight had technically satisfactory split function studies. Despite a fall in mean arterial pressure (132 +/- 6 to 121 +/- 6 mm Hg, p less than 0.05) and humoral changes consistent with angiotensin-mediated hypertension, the intrarenal effects of this analog were commonly those of an angiotensin agonist, producing vasoconstriction and sodium retention. This was quantitatively greatest in the contralateral kidney, whose preinfusion sodium excretion (86 +/- 30 microEq/min vs 25 +/- 9 microEq/min, p less than 0.02) and glomerular filtration rate (76 +/- 7 ml/min vs 41 +/- 7 ml/min, p less than 0.01) were higher than the stenotic kidney. In some cases, an increase in renal blood flow and rise in sodium excretion were evident during angiotensin blockade, suggesting a tonic intrarenal action of angiotensin. Although renin vein renin values differed markedly between the stenotic and contralateral kidney (ratio = 2.05 +/- 0.30), relative changes in effective renal plasma flow were correlated (r = 0.84: p less than 0.01) during infusion of this analog. These results underscore the differences in sensitivities between vascular beds to the effects of angiotensin II and the major role of the contralateral kidney in renal function and sodium homeostasis in human renovascular hypertension.
Assuntos
Angiotensina II/análogos & derivados , Hipertensão Renovascular/fisiopatologia , Rim/efeitos dos fármacos , Obstrução da Artéria Renal/fisiopatologia , Adulto , Idoso , Angiotensina II/administração & dosagem , Angiotensina II/farmacologia , Pressão Sanguínea , Feminino , Humanos , Infusões Intra-Arteriais , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Sódio/metabolismoRESUMO
Two sets of studies were performed in 13 patients with proved adrenal pheochromocytoma to test the hypothesis that the sympathetic nervous system (SNS) is active and might contribute to the hypertensive state. Similar studies were performed in 15 additional patients considered to have essential hypertension. In the first set, 13 patients with pheochromocytoma were subjected to head-up tilt to assess the activity of the SNS. This maneuver decreased diastolic blood pressure in only two; heart rate increased appropriately in all except one. Changes in plasma norepinephrine (NE) were variable and did not correlate with changes in blood pressure (BP) and heart rate (HR). In the second set, 10 patients with pheochromocytoma were given a single oral dose of clonidine (0.3 mg) to evaluate what role, if any, the SNS might contribute to the hypertensive state. Fifteen patients with essential hypertension were studied similarly for comparison. Clonidine produced significant decreases in BP and HR but left plasma renin activity unchanged in both groups. In essential hypertension, the cardiovascular responses were accompanied by significant reductions in plasma NE. By contrast, plasma NE was unchanged in patients with pheochromocytoma, despite similar reductions in BP and HR. These results suggest that the sympathetic reflexes are intact in pheochromocytoma, and that much of the hypertension associated with these tumors may be related to increased sympathetic activity.
Assuntos
Neoplasias das Glândulas Suprarrenais/fisiopatologia , Pressão Sanguínea , Hipertensão/fisiopatologia , Feocromocitoma/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Clonidina/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Norepinefrina/sangue , Postura , Renina/sangue , Sistema Nervoso Simpático/fisiopatologiaRESUMO
Sixteen patients with refractory hypertension were submitted to vigorous sodium depletion while cardiovascular homeostasis was monitored with measurements of hormonal and hemodynamic parameters and repeat saralasin tests. This regimen resulted in a negative sodium balance by an average of 300 mEq. The loss of sodium closely correlated to the decrease of body weight (r = 0.70, p less than 0.005). Blood pressure (BP) decreased from 176/166 +/- 8/3 to 155/109 +/-6/3 mm Hg. There was a significant correlation between percent increments in plasma renin activity (PRA) and the rise in plasma norepinephrine (r = 0.68, p less than 0.05) and a close negative correlation between percent increase in PRA and the ratio of fall in mean blood pressure (MAP) per unit of weight loss (r = -0.73, p less than 0.005). Thus, patients with the least percent increase in PRA demonstrated the greatest fall in BP per unit of weight loss, indicating that relative rather than absolute elevation of renin may be the factor limiting antihypertensive efficacy of sodium depletion. Sodium depletion induced increase in peripheral resistance and decrease in cardiac output, both mostly attributable to relative hyperreninemia. Indeed, the adverse hemodynamic changes were reversed by angiotensin inhibition, during which BP normalized. It is concluded that vigorous sodium depletion complemented by angiotensin blockade or suppression with sympatholytic agents improves management of otherwise refractory hypertension.
Assuntos
Pressão Sanguínea , Dieta Hipossódica , Hipertensão/fisiopatologia , Renina/sangue , Adulto , Peso Corporal , Feminino , Hemodinâmica , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Norepinefrina/fisiologia , Saralasina/farmacologia , Sódio/fisiologia , Simpatolíticos/farmacologiaRESUMO
The antihypertensive effects of nitrendipine were evaluated in 12 subjects with hypertension, one of whom could not tolerate the drug for more than 3 days; hence hemodynamics were studied in the 11 subjects who were treated for 2 wk. In one patient taking 40 mg twice a day, blood pressure reduction was associated with a hemodynamic pattern of hyperkinetic circulation. Of the other 10 subjects, all of whom were taking 20 mg twice a day, two did not respond, but 8 had significant reduction in mean arterial pressure (136 +/- 4.3 to 106 +/- 3.2 mm Hg) resulting from a decrease in total peripheral resistance (52 +/- 3.7 to 35 +/- 2.6 U X m2). Changes in cardiac output, heart rate, and cardiopulmonary volume varied widely among subjects, such that average changes did not attain significance. Heart rate and cardiopulmonary volume, however, changed in the same direction, which suggests that the alterations in both were related to the degree of reflex sympathetic stimulation induced by nitrendipine. Plasma renin activity (PRA) increased during treatment (2.6 +/- 1.0 to 9.3 +/- 4.1 ng/ml/hr), whereas the increase in plasma aldosterone (PA) levels did not attain significance (13.7 +/- 1.6 to 21.5 +/- 4.5 ng/dl). As a result, PA/PRA decreased (16.1 +/- 4.9 to 9.4 +/- 2.6). These results suggest that calcium entry blockade might have interfered with steroidogenesis, thus blunting the effect of increased PRA. Finally, blood pressure response to nitrendipine in the whole group correlated inversely with pretreatment PRA (r = -0.88), suggesting greater activity of the drug in low-renin hypertension.
Assuntos
Anti-Hipertensivos/farmacologia , Hemodinâmica/efeitos dos fármacos , Nifedipino/análogos & derivados , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Volume Sanguíneo/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Nifedipino/efeitos adversos , Nifedipino/farmacologia , Nitrendipino , Sistema Renina-Angiotensina/efeitos dos fármacos , Taquicardia/induzido quimicamenteRESUMO
In orthostatic intolerance, the patient develops symptoms while standing that are relieved when the patient assumes a supine position. Different degrees of orthostatic intolerance exist, but not a system of grading severity. We have developed a system that grades the severity of orthostatic intolerance by the three-pronged criteria of the rapidity of development and the severity of orthostatic symptoms, the ability of the subject to withstand orthostatic stresses, and the degree of interference with daily living. In this article, this system is presented, and one disorder, postural tachycardia syndrome (POTS), is examined in some detail.
Assuntos
Hipotensão Ortostática/fisiopatologia , Postura/fisiologia , Taquicardia/fisiopatologia , Humanos , Hipotensão Ortostática/terapia , Síndrome , Taquicardia/terapiaRESUMO
Changes in blood pressure, renal function, and fluid balance were studied in 12 patients receiving intravenous recombinant interleukin-2 (IL-2) (100,000 units/kg every eight hours) over five days for treatment of metastatic melanoma and renal and colorectal cancers. The IL-2 regimen produced progressive hypotension, azotemia, and sodium avidity (fractional excretion of sodium = 0.20 +/- 0.07 percent) despite massive fluid administration (mean: 18.4 liter per five days) and weight gain (mean: 4.0 kg). Plasma renin activity rose. Hypoalbuminemia developed rapidly (3.6 +/- 0.1 g/dl to 2.2 +/- 0.1 g/dl, p less than 0.01) with widespread edema formation despite normal central venous pressures. Hematocrit did not change during the IL-2 period, consistent with a "capillary-leak." Hemodynamic and renal functional changes reversed after the IL-2 regimen was discontinued, but hypoalbuminemia and elevated urinary n-acetyl-glucosaminidase levels persisted after six days. These studies demonstrate widespread hemodynamic and vascular effects of IL-2 administration that limit its safe use and suggest a possible role for the lymphokine in mediating cardiovascular instability under other circumstances, such as endotoxic shock.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Creatinina/sangue , Interleucina-2/efeitos adversos , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Adulto , Neoplasias do Colo/sangue , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/urina , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Interleucina-2/administração & dosagem , Interleucina-2/uso terapêutico , Neoplasias Renais/sangue , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/urina , Masculino , Melanoma/sangue , Melanoma/tratamento farmacológico , Melanoma/urina , Pessoa de Meia-Idade , Sódio/urinaRESUMO
Thirty-three hypertensive patients with a wide range of renal function were studied during initiation of angiotensin-converting enzyme inhibition with captopril to evaluate changes in potassium levels concomitant with reduction of aldosterone excretion. Ten patients (Group I) with low levels of plasma renin activity had no change in either aldosterone excretion or potassium during the first week of therapy. Twenty-three other patients (Group II) had decreased aldosterone excretion of an average of 63 percent, often reversing secondary hyperaldosteronism. This was associated with a rise in serum potassium from 3.6 +/- 0.1 to 4.4 +/- 0.1 mEq/liter (p less than 0.001). Serum potassium levels during captopril therapy were inversely related to glomerular filtration rate (creatinine clearance) and transiently exceeded 6.0 mEq/liter in markedly azotemic subjects. Despite rising potassium levels, nine patients had reduced aldosterone excretion to subnormal levels, sometimes for many months. During initiation of converting-enzyme inhibition, potassium-sparing agents and supplements should be discontinued and serum potassium levels should be monitored closely, particularly in patients with imparied renal function.
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Captopril/uso terapêutico , Hiperpotassemia/induzido quimicamente , Antagonistas de Receptores de Mineralocorticoides , Prolina/análogos & derivados , Uremia/tratamento farmacológico , Adolescente , Adulto , Idoso , Aldosterona/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão Renovascular/sangue , Hipertensão Renovascular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Renina/sangueRESUMO
Changes in regional hemodynamics and function of the kidney during inhibition of angiotensin converting enzyme were studied in 25 patients with renovascular hypertension. A variety of patterns were observed depending upon (1) the activity of the renin-angiotensin system and concomitant administration of diuretics, and (2) the presence of bilateral renal artery stenosis. Increase in blood flow, glomerular filtration rate and sodium excretion during angiotensin blockade, in some instances, indicated tonic renal vasoconstriction before therapy. Release of the kidney from these effects may explain, in part, the sustained effectiveness of converting enzyme inhibition in chronic congestive heart failure. When compared with blood pressure reduction due to nitroprusside administration, initial captopril therapy in patients with unilateral stenosis produced a selective decrease in glomerular filtration, despite well-preserved renal blood flow. These results confirm the importance of efferent arteriolar vasoconstriction due to angiotensin II in man. Experimental studies demonstrate that angiotensin may become critical to sustaining glomerular filtration rate in the presence of stenosis during vasodilation. In patients with bilateral stenosis, this effect produces a syndrome of functional renal insufficiency. Taken together, these data demonstrate an intrarenal action of angiotensin II in human renovascular hypertension and underscore the importance of evaluating the functional impact of changes in regional hemodynamics.
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Captopril/uso terapêutico , Hipertensão Renovascular/tratamento farmacológico , Rim/irrigação sanguínea , Prolina/análogos & derivados , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Animais , Cães , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/fisiopatologia , Rim/efeitos dos fármacos , Masculino , Natriurese/efeitos dos fármacos , Nitroprussiato/uso terapêutico , Obstrução da Artéria Renal/complicações , Circulação Renal/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacosRESUMO
In a prospective study of 80 patients with primary aldosteronism (70 with adenoma and 10 with hyperplasia), "refractory" hypertension, hyperkinetic circulation, and hypovolemia were frequent occurrences. We found that measurements of serum potassium concentration and plasma renin activity were inadequate screening tests because of high rates of false-positive and false-negative results. The demonstration of excessive aldosterone production after three days of salt loading provided the best sensitivity (96 percent) and specificity (93 percent) in identifying patients with primary aldosteronism. Severe, persistent hypokalemia, increased plasma 18-hydroxycorticosterone values, and an anomalous postural decrease in the plasma aldosterone concentration, when present, provided the best indicators of the presence of an adenoma. Of three localizing procedures (selective adrenal venography, adrenal computed tomographic scan, and adrenal venous sampling for plasma aldosterone concentration) the measurement of adrenal venous plasma aldosterone concentration yielded 100 percent accuracy. These results indicate a wider clinical spectrum in primary aldosteronism than previously described. They also show that nonsuppressible aldosterone production is its most important diagnostic hallmark and the single best diagnostic screening procedure, and that adrenal venous sampling for plasma aldosterone concentration remains the most precise technique for identification and localization of tumors.