ABSTRACT
BACKGROUND: Appropriate utilization of vancomycin is important to attain therapeutic targets while avoiding clinical failure and the development of antimicrobial resistance. Our aim was to observe the use of vancomycin in an intensive care population, with the main focus on achievement of therapeutic serum concentrations (15-20 mg/l) and to evaluate how this was influenced by dose regimens, use of guidelines and therapeutic drug monitoring. METHODS: A prospective observational study was carried out in the intensive care units at two tertiary hospitals in Norway. Data were collected from 83 patients who received vancomycin therapy, half of these received continuous renal replacement therapy. Patients were followed for 72 h after initiation of therapy. Blood samples were drawn for analysis of trough serum concentrations. Urine was collected for calculations of creatinine clearance. Information was gathered from medical records and electronic health records. RESULTS: Less than 40% of the patients attained therapeutic trough serum concentrations during the first 3 days of therapy. Patients with augmented renal clearance had lower serum trough concentrations despite receiving higher maintenance doses and more loading doses. When trough serum concentrations were outside of therapeutic range, dose adjustments in accordance to therapeutic drug monitoring were made to less than half. CONCLUSION: The present study reveals significant challenges in the utilization of vancomycin in critically ill patients. There is a need for clearer guidelines regarding dosing and therapeutic drug monitoring of vancomycin for patient subgroups.
Subject(s)
Anti-Bacterial Agents/blood , Anti-Bacterial Agents/therapeutic use , Critical Illness , Vancomycin/blood , Vancomycin/therapeutic use , Adult , Anti-Bacterial Agents/administration & dosage , Creatinine/urine , Critical Care , Dose-Response Relationship, Drug , Drug Monitoring , Drug Resistance, Microbial , Female , Guidelines as Topic , Humans , Male , Middle Aged , Norway , Prospective Studies , Renal Replacement Therapy , Vancomycin/administration & dosageABSTRACT
The systemic physiologic changes that occur during and after brain death affect all organs suitable for transplantation. Major changes occur in the cardiovascular, pulmonary, endocrine, and immunological systems, and, if untreated may soon result in cardiovascular collapse and somatic death. Understanding these complex physiologic changes is mandatory for developing effective strategies for donor resuscitation and management in such a way that the functional integrity of potentially transplantable organs is maintained. This review elucidates these physiological changes and their consequences, and based on these consequences the rationale behind current medical management of brain-dead organ donors is discussed.
Subject(s)
Brain Death/physiopathology , Tissue Donors , Cardiovascular System/physiopathology , Endocrine System/physiopathology , Hemodynamics/physiology , Humans , Lung/physiopathology , Transplantation, HomologousABSTRACT
BACKGROUND AND OBJECTIVES: Postoperative acute renal failure predicts morbidity and mortality. We investigated the effect of nifedipine infusion on glomerular filtration rate in patients with impaired renal function undergoing cardiopulmonary bypass surgery. METHODS: Twenty patients accepted for coronary bypass and/or heart valve surgery were enrolled prospectively and randomized to nifedipine infusion or no treatment. Males and females with creatinine 150 micromol L(-1) and 130 micromol L(-1), respectively, were included. Patients with unstable angina pectoris, ejection fraction 35% and those on dialysis were excluded. Glomerular filtration rate was measured preoperatively and 48 h postoperatively. Creatinine clearance was measured preoperatively and 0-4, 20-24 and 44-48 h postoperatively. There were no statistically significant differences in patient characteristics. Biochemical markers in plasma and urine were measured before and 48 h after surgery. RESULTS: The mean +/- SD preoperative glomerular filtration rates were 32.2 +/- 11.5 and 31.4 +/- 17.0 mL min-1 per 1.73 m2 in the nifedipine and control groups (P = 0.90), respectively. There was no statistically significant change in the glomerular filtration rate or in creatinine clearance over time within or between groups. A linear mixed model showed no effect of nifedipine (P = 0.44), time (P = 0.97) or interaction of nifedipine and time (P = 0.99) on creatinine clearance. Perioperative arterial pressure was kept within predefined targets. Three patients received dialysis postoperatively, all in the control group (P = 0.21). There were no statistically significant differences between groups in changes of urinary or plasma biochemistry. CONCLUSIONS: Renal function was well preserved after cardiopulmonary bypass surgery in patients with impaired renal function when maintaining thorough intensive care surveillance. Nifedipine did not influence early postoperative renal function.
Subject(s)
Acute Kidney Injury/prevention & control , Calcium Channel Blockers/pharmacology , Cardiopulmonary Bypass/adverse effects , Nifedipine/pharmacology , Renal Insufficiency/complications , Acute Kidney Injury/etiology , Aged , Aged, 80 and over , Blood Pressure/drug effects , Creatinine/blood , Creatinine/urine , Critical Care , Female , Glomerular Filtration Rate/drug effects , Humans , Infusions, Intravenous , Linear Models , Male , Middle Aged , Prospective Studies , Renal Dialysis , Time FactorsABSTRACT
This prospective, multicentre, international, observational, cohort study compared injection site pain (ISP) and injection site reactions (ISRS) between interferon beta-1b (IFNB-1b; Betaferon) 250 microg subcutaneously every other day and interferon beta-1a (IFNB-1a; Rebif) 44 microg subcutaneously three times weekly in patients with relapsing-remitting MS. Patients started treatment within 3 months before recruitment and were on full dose of therapy at inclusion. Patients self-injected IFNB and self-assessed ISP for 15 consecutive injections immediately, 30 and 60 min after injection, using a visual analogue scale diary. Study staff assessed ISRS. Of 445 patients (valid cases), approximately 90% used autoinjectors. More patients were pain-free at all timepoints with IFNB-1b than with IFNB-1a (eg, 30 min: 42.6% versus 19.7%; P<0.0001). The mean proportion of pain-free injections was greater for IFNB-1b (eg, 30 min: 79.0%) than for IFNB-1a (53.3%; P<0.0001). The proportion of patients without ISRS was greater for IFNB-1b (second visit 51.8% versus 33.8%; P<0.0001). Compared with IFNB-1a, more IFNB-1b patients either had no pain or their ISP had no influence on treatment satisfaction (76.9% versus 64.1%; P=0.006). The impact on tolerability and patient acceptability of any new IFNB product formulations would, however, have to be evaluated in comparative studies.
Subject(s)
Adjuvants, Immunologic/adverse effects , Interferon-beta/adverse effects , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Pain/chemically induced , Adjuvants, Immunologic/administration & dosage , Adult , Female , Humans , Injections, Subcutaneous , Interferon beta-1a , Interferon beta-1b , Interferon-beta/administration & dosage , Male , Pain Measurement , Patient Compliance , Prospective StudiesABSTRACT
BACKGROUND: Therapeutic hypothermia has been shown to increase survival after out-of-hospital cardiac arrest (OHCA). The trials documenting such benefit excluded patients with cardiogenic shock and only a few patients were treated with percutaneous coronary intervention prior to admission to an intensive care unit (ICU). We use therapeutic hypothermia whenever cardiac arrest patients do not wake up immediately after return of spontaneous circulation. METHODS: This paper reports the outcome of 50 OHCA patients with ventricular fibrillation admitted to a tertiary referral hospital for immediate coronary angiography and percutaneous coronary intervention when indicated. Patients were treated with intra-aortic balloon counterpulsation (IABP) (23 of 50 patients) if indicated. All patients who were still comatose were treated with therapeutic hypothermia at 32-34 degrees C for 24 h before rewarming. The end-points were survival and cerebral performance category (CPC: 1, best; 5, dead) after 6 months. RESULTS: Forty-one patients (82%) survived until 6 months. Thirty-four patients (68%) were in CPC 1 or 2, and seven (14%) were in CPC 3. Of the 23 patients treated with IABP, 14 (61%) survived with CPC 1 or 2. In patients not treated with IABP, 20 patients (74%) survived with CPC 1 or 2. Forty patients (80%) developed myocardial infarction. Percutaneous coronary intervention was performed in 36 patients (72%). CONCLUSION: In OHCA survivors who reached our hospital, the survival rate was high and the neurological outcome acceptable. Our results indicate that the use of therapeutic hypothermia is justified even in haemodynamically unstable patients and those treated with percutaneous coronary intervention.
Subject(s)
Heart Arrest/therapy , Hypothermia, Induced/methods , Aged , Coma/therapy , Coronary Angiography , Female , Follow-Up Studies , Humans , Hypothermia, Induced/mortality , Intra-Aortic Balloon Pumping/methods , Male , Middle Aged , Retrospective Studies , Shock, Cardiogenic/therapy , Survival Rate , Treatment Outcome , Ventricular Fibrillation/therapySubject(s)
Acute Kidney Injury/prevention & control , Postoperative Complications/prevention & control , Atrial Natriuretic Factor/administration & dosage , Atrial Natriuretic Factor/adverse effects , Blood Pressure/drug effects , Cardiotonic Agents/administration & dosage , Diuretics/administration & dosage , Diuretics/adverse effects , Diuretics, Osmotic/administration & dosage , Dopamine/administration & dosage , Dopamine/analogs & derivatives , Fenoldopam/administration & dosage , Furosemide/administration & dosage , Furosemide/adverse effects , Humans , Mannitol/administration & dosage , Vasodilator Agents/administration & dosageABSTRACT
Continuous renal replacement therapy (CRRT) in critically ill patients with renal failure may significantly increase drug clearance, requiring drug dosing adjustments. Drugs significantly eliminated by the kidney often undergo substantial removal during CRRT, and a supplemental dose corresponding to the amount of drug removed by CRRT should be administered. Clearance by CRRT can either be measured or estimated. The high-flux membranes used in CRRT make no filtration barrier to most drugs, and the filtrate concentration can be estimated by the unbound fraction of the drug in plasma. When adding dialysis to filtration, this approach overestimates drug clearance, and a correcting factor should be used. A method for estimating drug clearance as a function of creatinine clearance is also suggested, but it has the same limitations in overestimating drug clearance when dialysis is combined with filtration. For non-toxic drugs, doses can safely be increased 30% above actual estimates to ensure adequate dosing. For drugs with a narrow therapeutical margin, monitoring plasma concentrations are mandatory. When appropriate, the use of a readily available reference for drug dosing is recommended.
Subject(s)
Critical Illness , Hemodiafiltration , Hemofiltration , Pharmaceutical Preparations/administration & dosage , Pharmacokinetics , HumansABSTRACT
Extracorporeal membrane oxygenation is the recommended treatment for fulminant pulmonary failure due to varicella pneumonia. However, in pregnancy fetal viability during extracorporeal membrane oxygenation is generally poor resulting in either therapeutic or spontaneous abortion. The present case is to our knowledge the first report on the treatment with nitric oxide to improve oxygenation in a pregnant woman with fulminant pulmonary failure due to varicella pneumonia. Adding 20 parts per million nitric oxide to the inspiratory gas increased arterial oxygen saturation from 75 to 88%, and it could be kept at this level. Due to a vaginal bleeding, an emergency Caesarean section was performed with successful outcome for the fetus. The mother started to improve after delivery and could be weaned from nitric oxide after 5 days. We conclude that inhalation of nitric oxide may be a good alternative to extracorporeal membrane oxygenation in the treatment of fulminant pulmonary failure due to varicella pneumonia in pregnancy.
Subject(s)
Chickenpox/drug therapy , Nitric Oxide/therapeutic use , Pneumonia, Viral/drug therapy , Pregnancy Complications, Infectious/drug therapy , Respiratory Insufficiency/drug therapy , Adult , Female , Humans , Infant, Newborn , Oxygen/blood , Pregnancy , Respiratory Insufficiency/etiologyABSTRACT
BACKGROUND: In order to assess the immediate renal function after living donor transplantation, renal function was compared in eight renal allograft recipients and their living related kidney donors during the first 24 h after transplantation. METHODS: Substantial and comparable intraoperative volume loading with Ringer's acetate and mannitol was performed together with the administration of frusemide. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated by the clearances of inulin and p-aminohippurane, respectively. Tubular reabsorptive function and injury were estimated from the clearance of lithium, the fractional excretion of sodium and the urinary excretion of N-acetyl-beta-glucosaminidase. RESULTS: One hour after completion of surgery, GFR (54 +/- 7 ml/min) and ERPF (294 +/- 35 ml/min) were only 30% lower in the grafts than in the remaining donor kidneys, increasing to similar levels within 3 h. Only minor tubular dysfunction and injury were revealed in the grafted kidneys, and these tended to normalize within 24 h. CONCLUSIONS: By the present transplantation procedure comprising short ischaemia time and substantial volume expansion combined with mannitol and frusemide administration, kidneys from living donors regain nearly normal function within a few hours after transplantation.
Subject(s)
Kidney Transplantation , Kidney/physiopathology , Living Donors , Acetylglucosaminidase/urine , Adult , Diuresis/physiology , Glomerular Filtration Rate/physiology , Humans , Middle Aged , Natriuresis/physiology , Postoperative Period , Renal Circulation/physiology , Time FactorsABSTRACT
Pulmonate snails that experience extreme variations in gas tensions and temperatures possess extracellular, high-molecular mass ( approximately 1.7 x 10(6) Da) hemoglobins (Hbs) that are little known as regards oxygenation and allosteric characteristics. Biomphalaria glabrata hemolymph exhibits a high O2 affinity (half-saturation O2 tension = 6.1 mmHg; pH 7.7, 25 degreesC), pronounced Bohr effect (Bohr factor = -0.5), and pH-dependent cooperativity (Hill's cooperativity coefficient at half-saturation = 1.1-2.0). Divalent cations increase O2 affinity, Ca2+ exerting greater effect than Mg2+. Analyses in terms of the Monod-Wyman-Changeux model indicate novel O2 affinity control mechanisms. In contrast to vertebrate Hb, where organic phosphates and protons lower affinity via decreased O2 association equilibrium constant of Hb in low-affinity state (KT), and to extracellular annelid Hbs, where protons and cations primarily modulate O2 association equilibrium constant of Hb in high-affinity state (KR), in B. glabrata Hb, the Bohr effect is mediated predominantly via KR and the cation effect via KT, reflecting preferential, oxygenation-linked proton binding to oxygenated Hb and cation binding to deoxygenated Hb. CO2 has no specific (pH independent) effect. Nonlinear van't Hoff plots show temperature dependence of the overall heats of oxygenation, indicating oxy-deoxy heat capacity differences. The findings are related to possible physiological significance in pond habitats.
Subject(s)
Biomphalaria/metabolism , Hemoglobins/metabolism , Oxygen/blood , Allosteric Regulation/physiology , Animals , Dialysis , Hemoglobins/chemistry , Hemolymph/metabolism , SpectrophotometryABSTRACT
In the management of adult respiratory distress syndrome pressure limited mechanical ventilation may protect the lungs from overdistention injury. Unacceptable hypoxia may be avoided by adding nitric oxide to the inspiratory gas, and thus make pressure limited ventilation easier to perform. There exists no consensus about an acceptable lower limit of SaO2, and in the present case we gave preference to pressure limitation at the cost of oxygenation. A young woman with severe adult respiratory distress syndrome was set on pressure limited mechanical ventilation with peak pressures of 35-38 cm H2O, PEEP of 10-12 cm H2O, and FiO2 of 0.95 with 20 ppm nitric oxide. SaO2 varied between 75 and 85%, and cardiac output ranged between 5.2 and 7.5 L min-1. Oxygen consumption was in the upper normal range, and she did not became acidotic. After 3 days, she started to improve. In conclusion, it seems that hypoxia might be well tolerated as long as the circulation is not compromised. It might prove beneficial to accept some hypoxia to avoid ventilator induced lung damage.
Subject(s)
Hypoxia/physiopathology , Nitric Oxide/therapeutic use , Respiration, Artificial , Respiratory Distress Syndrome/drug therapy , Adult , Air Pressure , Cardiac Output/drug effects , Cardiac Output/physiology , Female , Humans , Lung Injury , Oxygen/blood , Oxygen Consumption/genetics , Oxygen Consumption/physiology , Positive-Pressure Respiration , Respiration, Artificial/adverse effectsABSTRACT
To examine the effect of atrial natriuretic factor (ANF) on renin release induced by renal hypotension, experiments were performed in seven barbiturateanaesthetized dogs with denervated kidneys. Renin release induced by renal arterial constriction to 55 mmHg was measured before and during intrarenal infusion of ANF (200 ng min-1 kg-1 body weight). Before ANF infusion, renal arterial constriction increased renin release from 0.2 +/- 0.1 to 21.8 +/- 3.3 micrograms angiotensin I min-1 (p < 0.05). During ANF infusion renal arterial constriction increased renin release as much as before from 0.8 +/- 0.6 to 23.7 +/- 4.6 micrograms angiotensin I min-1 (p < 0.05). Although ANF increased glomerular filtration rate from 33.9 +/- 4.2 to 43.4 +/- 5.6 ml min-1 (p < 0.05) and sodium excretion from 72 +/- 22 to 567 +/- 112 mumol min-1 (p < 0.05) at normal renal perfusion pressure, ANF was without effect on glomerular filtration rate and sodium excretion during renal arterial constriction. The present study shows that ANF is not an inhibitor of renin release induced by renal arterial constriction in anaesthetized dogs with denervated kidneys. Our findings indicate that ANF does not influence renin release induced by the haemodynamic mechanism.
Subject(s)
Atrial Natriuretic Factor/pharmacology , Hypotension/physiopathology , Renal Artery , Renin/metabolism , Angiotensin I/analysis , Animals , Constriction , Denervation , Dogs , Female , Glomerular Filtration Rate , Hypotension/etiology , Kidney/innervation , Male , NatriuresisABSTRACT
A 40-year-old woman with transplanted lungs developed life threatening hyperkalaemia (6.8 mmol L-1) during high dose treatment with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia. Trimethoprim has an amiloride-like effect on the distal nephron and may thus induce hyperkalaemia, particularly if other contributing factors coexist. The present patient was also treated with the angiotensin-converting enzyme (ACE) inhibitor enalapril, and the combination of ACE-inhibition and potassium-sparing diuretics is known to induce hyperkalaemia. Hyperkalaemia was probably induced by the combination of ACE-inhibitor and trimethoprim, and this combination may be as dangerous as the combination of ACE-inhibitors with other potassium-sparing diuretics.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/adverse effects , Anti-Infective Agents/adverse effects , Enalapril/adverse effects , Hyperkalemia/chemically induced , Lung Transplantation , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , Adult , Fatal Outcome , Female , HumansABSTRACT
The amount of blood lost during liposuction with the "dry" or classic "wet" techniques has been a cause for concern. In the present study 26 consecutive patients who underwent syringe-assisted liposuction with the "superwet" or "tumescent" technique had their blood loss recorded prospectively. The mean (SD) volume aspirated was 2448 (1368) ml and the mean (SD) drop in haemoglobin concentration was 11 (7) g/l. The haemoglobin concentration was measured in both the fluid and the fat fraction of the aspirate, and the mean (SD) amount of whole blood was 16.5 (9.3) ml/litre of aspirate. The present study shows that blood loss is considerably reduced when the "super-wet" or "tumescent" technique is used, compared with the reported amount lost by authors who used the "dry" or classic "wet" techniques.
Subject(s)
Blood Loss, Surgical , Epinephrine , Lipectomy/adverse effects , Lipectomy/methods , Adult , Anesthesia, General , Anesthesia, Local , Blood Loss, Surgical/prevention & control , Hemoglobinometry , Humans , Middle AgedABSTRACT
Liposuction, like many other plastic surgical procedures, is often performed under local anesthesia. Drug toxicity is the most serious complication and the factor that limits the use of this form of anesthesia. Toxic effects are related to the peak concentration in plasma and depend on the type of local anesthetic, the drug concentration, total dose, site of injection, injection speed, and whether vasoconstrictors are used or not. This study evaluates the use of large volumes of subcutaneously injected 0.1% lidocaine with epinephrine 1:1,000,000 as the local anesthetic procedure in 12 patients undergoing suction-assisted lipectomy of the abdomen, flanks, and/or lower extremities. A total dose of 1260 to 2880 mg lidocaine corresponding to 10.5 to 34.4 mg/kg was administered with an injection speed of 60 to 78 ml/min. The peak concentration of lidocaine varied between 0.9 and 3.6 micrograms/ml and occurred between 6 and 12 hours postoperatively. For the given dose range, a linear correlation (r = 0.83) was found between the total dose of lidocaine and the peak concentration in plasma. A dose increase of 1 mg/kg raised the peak concentration approximately 0.1 microgram/ml. Our data clearly demonstrate that when using pH-adjusted 0.1% lidocaine with epinephrine subcutaneously for suction-assisted lipectomy, lidocaine can be administrated safely in significantly higher doses than recommended. When such high doses are used, the patient probably should be observed for at least 18 hours postoperatively.
Subject(s)
Anesthesia, Local , Epinephrine , Lidocaine , Lipectomy , Adult , Epinephrine/administration & dosage , Female , Humans , Injections, Subcutaneous , Lidocaine/administration & dosage , Lidocaine/blood , Middle AgedABSTRACT
The relationship between angiotensin II and renal prostaglandins, and their interactions in controlling renal blood flow (RBF) and glomerular filtration rate (GFR) were investigated in 18 anaesthetized dogs with acutely denervated kidneys. Intrarenal angiotensin II infusion increased renal PGE2 release (veno-arterial concentration difference times renal plasma flow) from 1.7 +/- 0.9 to 9.1 +/- 0.4 and 6-keto-PGF1 alpha release from 0.1 +/- 0.1 to 5.3 +/- 2.1 pmol min-1. An angiotensin II induced reduction in RBF of 20% did not measurably change GFR whereas a 30% reduction reduced GFR by 18 +/- 8%. Blockade of prostaglandin synthesis approximately doubled the vasoconstrictory action of angiotensin II, and all reductions in RBF were accompanied by parallel reductions in GFR. When prostaglandin release was stimulated by infusion of arachidonic acid (46.8 +/- 13.3 and 15.9 +/- 5.4 pmol min-1 for PGE2, and 6-keto-PGF1 alpha, respectively), angiotensin II did not change prostaglandin release, but had similar effects on the relationship between RBF and GFR as during control. In an ureteral occlusion model with stopped glomerular filtration measurements of ureteral pressure and intrarenal venous pressure permitted calculations of afferent and efferent vascular resistances. Until RBF was reduced by 25-30% angiotensin II increased both afferent and efferent resistances almost equally, keeping the ureteral pressure constant. At greater reductions in RBF, afferent resistance increased more than the efferent leading to reductions in ureteral pressure. This pattern was not changed by blockade of prostaglandin synthesis indicating no influence of prostaglandins on the distribution of afferent and efferent vascular resistances during angiotensin II infusion. In this ureteral occlusion model glomerular effects of angiotensin II will not be detected, and it might well be that the shift from an effect predominantly on RBF to a combined effect on both RBF and GFR induced by inhibition of prostaglandin synthesis is located to the glomerulus. We therefore postulate that renal prostaglandins attenuate the effects of angiotensin II on glomerular surface area and the filtration barrier, and not on the afferent arterioles as previously suggested.
Subject(s)
Angiotensin II/pharmacology , Glomerular Filtration Rate/drug effects , Kidney/metabolism , Prostaglandins/metabolism , Renal Circulation/drug effects , Animals , Blood Proteins/analysis , Constriction, Pathologic , Dogs , Female , Indomethacin/pharmacology , Male , Pressure , Ureter/physiopathology , Vascular Resistance/drug effectsABSTRACT
Blood loss during liposuction has been a concern when more than 1500 mL of material are removed during one session. Several authors have claimed that blood loss is dramatically reduced when the targeted area is infiltrated with large amounts of dilute lidocaine with epinephrine ("tumescent" or "superwet" technique). Using this technique, 25 consecutive cases in which the liposuction aspirate was expected to be 1000 mL or more were investigated with pre- and postoperative measurements of hemoglobin. In addition, hemoglobin was also measured in the fluid fraction of the aspirate. The mean +/- SD aspirated volume was 1658 +/- 518 mL and the mean +/- SD fall in postoperative hemoglobin was 0.7 +/- 0.6 g/100 mL (5.4% +/- 4.9%). The mean amount of blood per liter of aspirate was calculated to be 10.5 +/- 5.2 mL. These results clearly demonstrate that the blood loss when using the tumescent or superwet technique is dramatically reduced compared with the dry or classical "wet" technique.
Subject(s)
Blood Loss, Surgical/prevention & control , Epinephrine/administration & dosage , Lidocaine/administration & dosage , Lipectomy/methods , Adult , Blood Volume , Hemoglobins/analysis , HumansABSTRACT
Controlled mandatory ventilation with positive end-expiratory pressure (PEEP) reduces renal sodium excretion. To examine whether atrial natriuretic factor (ANF) is involved in the renal response to alterations in end-expiratory pressure in hypervolemic dogs, experiments were performed on anesthetized dogs with increased blood volume. Changing from PEEP to zero end-expiratory pressure (ZEEP) increased sodium excretion by 145 +/- 61 from 310 +/- 61 mumol/min and increased plasma immunoreactive (ir) ANF by 104 +/- 27 from 136 +/- 21 pg/ml. Changing from ZEEP to PEEP reduced sodium excretion by 136 +/- 36 mumol/min and reduced plasma irANF by 98 +/- 22 pg/ml. To examine a possible causal relationship, ANF (6 ng.min-1.kg body wt-1) was infused intravenously during PEEP to raise plasma irANF to the same level as during ZEEP. Sodium excretion increased by 80 +/- 36 from 290 +/- 78 mumol/min as plasma irANF increased by 96 +/- 28 from 148 +/- 28 pg/ml. We conclude that alterations in end-expiratory pressure lead to great changes in plasma irANF and sodium excretion in dogs with increased blood volume. Comparison of the effects of altering end-expiratory pressure and infusing ANF indicates that a substantial part of the changes in sodium excretion during variations in end-expiratory pressure can be attributed to changes in plasma irANF.
Subject(s)
Atrial Natriuretic Factor/blood , Blood Volume/physiology , Natriuresis/physiology , Positive-Pressure Respiration , Animals , Atrial Natriuretic Factor/metabolism , Dogs , Female , Hemodynamics/physiology , Kidney/physiology , Male , Positive-Pressure Respiration/adverse effects , Renin/bloodABSTRACT
The present study on six anaesthetized dogs investigates the influences of two different vasodilators, bradykinin and papaverine, on the relationship between autoregulation of renal blood flow and glomerular filtration rate, sodium excretion and renin release. At control conditions renal blood flow and glomerular filtration rate was autoregulated to the same levels of renal arterial pressure, 55 +/- 3 and 58 +/- 3 mmHg, respectively. Renin release increased from 0.3 +/- 0.1 to 22 +/- 4 micrograms AI min-1, and sodium excretion decreased from 99 +/- 29 to 4.6 +/- 3.3 mumol min-1 when renal arterial pressure was reduced from 122 +/- 6 to 44 +/- 2 mmHg. Infusion of bradykinin (50 ng kg-1 min-1) increased renal blood flow by 50% at control blood pressure without changing glomerular filtration rate, and both renal blood flow and glomerular filtration rate autoregulated to the same pressure levels as during control. Sodium excretion increased threefold at control renal arterial pressure, but was unchanged at low renal arterial pressure. Bradykinin did not change renin release neither at control nor low renal arterial pressure. Papaverine infusion at a rate of 4 mg min-1 increased renal blood flow 50% without changing glomerular filtration rate. The lower pressure limits of renal blood flow and glomerular filtration rate autoregulation were increased to 94 +/- 6 and 93 +/- 6 mmHg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Bradykinin/pharmacology , Kidney/metabolism , Papaverine/pharmacology , Renin/metabolism , Anesthesia , Animals , Blood Pressure/drug effects , Dogs , Female , Glomerular Filtration Rate/drug effects , Kidney/drug effects , Male , Renal Circulation/drug effects , Sodium/urine , Sodium Chloride/metabolismABSTRACT
This study on 19 anaesthetized dogs had two objectives. The first was to compare the potencies of PGE2 and PGI2 as stimulators of renin release and demonstrate their dependency on activation of intrarenal mechanisms for renin release. The second objective was to demonstrate that ethacrynic acid (ECA) increases renin release not as a stimulator, but by activating intrarenal mechanisms. After inhibiting renal prostaglandin synthesis by indomethacin, PGE2 and PGI2 infused into the aorta proximal to the renal arteries exerted no significant effects on renin release, but increased renin release during ureteral occlusion. At equimolar infusion rates, PGI2 increased renin release twice as much as PGE2, but this difference in potency may reflect differences in degradation since 86% of PGE2 and 29% of PGI2 (measured as 6-keto-PGF1 alpha) were degraded during one passage through the kidney. By infusing PGF2 at 8 nmol min-1 and PGI2 at 2 nmol min-1 renin release increased equally and the prostaglandin outputs increased to the same levels as during ureteral occlusion before indomethacin administration. ECA did not increase renin release after indomethacin administration. However, infusion of PGE2 during continuous ECA administration increased renin release in a dose-dependent manner similar to the experiments performed during ureteral occlusion. We conclude that PGI2 and PGE2 in the amounts synthesized in the kidney seem to be equally important stimulators of renin release but their relative potencies cannot be determined because the site of degradation is uncertain. Renin release is enhanced by intrarenal mechanisms activated by ECA infusion or ureteral occlusion, which both cause autoregulatory vasodilation and reduce NaCl reabsorption at the macula densa.