Role of citrate synthase in aldosterone-mediated sodium reabsorption

Aldosterone and other mineralocorticoids increase citrate synthase activity in the kidney and enhance renal sodium reabsorption, but it is unclear whether the increased citrate synthase activity is involved in renal sodium transport. We used the Wistar-Furth rat, an inbred strain found to be deficient in renal citrate synthase activity, as an experimental model to investigate this issue. We confirmed that renal citrate synthase activity from adrenalectomized Wistar-Furth rats was decreased compared with that from control Wistar rats (by 28%). Similarly, urinary citrate excretion was 23% lower in Wistar-Furth rats. Subnormal citrate formation in Wistar-Furth rats could not be accounted for by differences in systemic pH or circulating potassium levels. Because renal citrate synthase activity was reduced in Wistar-Furth rats, we hypothesized that renal sodium excretory responses to mineralocorticoids would be reduced as well. Four-hour sodium excretion after intraperitoneal injection of 5 microg of aldosterone was reduced by 56% in adrenalectomized Wistar rats and by 52% in adrenalectomized Wistar-Furth rats (both P<0.01 compared with vehicle injection). Similarly, the pattern of urinary sodium excretion in response to subcutaneous injections of deoxycorticosterone acetate over a 2-week period was similar in adrenalectomized Wistar and Wistar-Furth rats. In summary, acute and chronic antinatriuretic responses to mineralocorticoids are maintained in Wistar-Furth rats at the level of Wistar rats, despite the marked reduction in citrate synthase activity. These findings are not consistent with an important role for citrate synthase activity in mineralocorticoid-mediated renal sodium transport.     

Acute renal failure following cardiopulmonary bypass: a changing picture

Objective: To assess the incidence of acute renal failure (ARF) developing perioperatively in adult patients requiring cardiopulmonary bypass surgery (CPB) and to make comparisons with data from the same institution published earlier. Design: Prospective, observational. Setting: Tertiary referral centre for cardiopulmonary medicine. Patients and participants: All patients admitted to the intensive care unit (ICU) who developed ARF perioperatively necessitating continuous veno-venous haemofiltration (CVVH) during the 24 months January 1997–December 1998. Interventions: None. Measurements and results: Of 2337 adult patients undergoing cardiac surgery, 47 (2.0 %) needed CVVH. Patients were excluded from analysis who underwent cardiac transplantation (n = 4), pericardial surgery (n = 3) or insertion of a left ventricular assist device (n = 1). Of the remaining 39, 21 patients died in ICU (53.8 % mortality). Relatively more non-survivors suffered from diabetes, hypertension and preoperative renal dysfunction. A previous report from our Unit revealed that, in 1989–90, 2.7 % of all patients undergoing CPB required CVVH with an in-hospital mortality of 83 %. The current study population were older (65.3 vs 56.0 years in 1990), and more severely ill as evidenced by a higher percentage of patients requiring redo (30 % vs 8.6 % in 1990) and emergency (50 % vs 25.7 % in 1990) surgery. Conclusions: The need for CVVH following CPB may be diminishing despite increased risk factors. ARF-associated mortality in these circumstances is falling. Received: 10 September 1999 Final revision received: 18 January 2000 Accepted: 15 February 2000     

The effects of beam shape on the ability to predict changes in vessel size from Doppler signal power

Theory suggests that, under certain ideal circumstances, the power of a Doppler signal is proportional to the size of the vessel from which it is recorded and can, therefore, be used to assess the scale of any changes in vessel size that occur during clinical recordings of cerebral blood flow. However, the relationship between signal power and vessel size depends on the intensity of the incident beam being uniform across the vessel. This is unlikely to be the case for cerebral vessels insonated by commercial transducers. A model was used to estimate the signal power received from vessels insonated by a beam passing through a homogeneous medium, and also by beams passing through each of five samples of temporal bone. In each case, the effects of initial vessel size and various changes in cross-sectional area were investigated for different vessel positions in the beam. The results for the beam paths through bone predict that the power change arising from a change in vessel cross-sectional area is between 5% and 75% smaller than that occurring in a uniform beam. If these results are representative of those arising for an in vivo change in middle cerebral artery size, then the potential magnitude of the error illustrates the caution that may need to be applied when interpreting changes in Doppler signal power.     

Diversity of responses of renal cortical and medullary blood flow to vasoconstrictors in conscious rabbits

The medullary microcirculation receives only about 10% of total renal blood flow, but plays a critical role in long-term arterial pressure regulation, so we need to better understand its regulation. Although there is evidence that circulating and locally acting hormones can differentially affect cortical and medullary blood flow in anaesthetized animals, there is little information from studies in conscious animals. This study is aimed (i) to develop a method for chronic measurement of cortical and medullary blood flow in conscious rabbits, and (ii) to test whether renal cortical and medullary blood flow can be differentially affected by intravenous (i.v.) infusions of various vasoconstrictor hormones in conscious rabbits. At preliminary operations, rabbits were equipped with single-fibre laser-Doppler flowprobes in the (left) renal cortex and medulla, and Transonic flowprobes for measuring cardiac output and renal blood flow. Intravenous angiotensin II (300 ng kg(-1) min(-1)), [Phe2,Ile3,Orn8]-vasopressin (30 ng kg(-1) min(-1)), noradrenaline (300 ng kg(-1) min(-1)), endothelin-1 (20 ng kg(-1) min(-1)) and N G-nitro-L-arginine (10 mg kg(-1)) increased mean arterial pressure (by 10-45% of baseline) and reduced heart rate (by 16-35%) and cardiac output (by 16-45%). Consistent with previous observations in anaesthetized rabbits, all treatments except [Phe2,Ile3, Orn8]-vasopressin reduced renal blood flow (13-63%) and cortical blood flow (16-47%), but medullary blood flow was significantly reduced only by [Phe2,Ile3,Orn8]-vasopressin (41%) and N G-nitro-L-arginine (42%). The diversity of these responses of cortical and medullary blood flow to i.v. infusions of vasoconstrictors provides further evidence for physiological roles of circulating and local hormones in the differential regulation of regional kidney blood flow.     

Risk factors for syncope in a community-based sample (the Framingham Heart Study)

The epidemiology of syncope has not been well described. Prior studies have examined risk factors for syncope in hospital-based or other acute or long-term care settings. To determine risk factors for syncope in a community-based sample, we performed a nested case-control study. We examined reports of syncope in Framingham Heart Study participants who underwent routine clinic visits from 1971 to 1990. For each syncope case (n = 543) 2 controls were matched for age, sex, and examination period. Mean age of subjects was 67 years (range 25 to 95); 59% were women. History of stroke or transient ischemic attack, history of myocardial infarction, high blood pressure, use of antihypertensive medication, use of other cardiac medication, smoking, alcohol intake, body mass index, systolic blood pressure, diastolic blood pressure, heart rate, atrial fibrillation, PR interval prolongation, interventricular block, and diabetes or elevated glucose level were examined as potential predictors. Using conditional logistic regression analysis, the predictors of syncope included a history of stroke or transient ischemic attack (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.62 to 4.04), use of cardiac medication (OR 1.67, 95% CI 1.21 to 2. 30), and high blood pressure (OR 1.46, 95% CI 1.14 to 1.88). Lower body mass index was marginally associated with syncope (OR per 4 kg/m(2) decrement 1.10, 95% CI 0.99 to 1.22), as were increased alcohol intake (OR per 5 oz/week 1.11, 95% CI 0.99 to 1.26), and diabetes or an elevated glucose level (OR 1.29, 95% CI 0.96 to 1.75). To our knowledge, this study represents the first community-based study of risk factors for syncope.     

Diagnostic dilemma

In those issues in which our regular Case of the Month does not appear, The Green Journal will present a Diagnostic Dilemma-an electrocardiogram or radiograph, or both, with a brief case history-as a challenge for our readers to solve. The correct answer appears on page 742. If you would like to contribute a Diagnostic Dilemma, please submit a high-quality copy of the ECG or radiograph with a brief synopsis (<250 words) of the case to editorial office of the American Journal of Medicine.     

Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia

The effect of traumatic lumbar puncture at the time of initial diagnostic workup on treatment outcome in children with newly diagnosed acute lymphoblastic leukemia (ALL) was investigated. The findings of the first 2 lumbar punctures performed on 546 patients with newly diagnosed ALL treated on 2 consecutive front-line studies (1984-1991) at St Jude Children's Research Hospital were retrospectively reviewed. Lumbar punctures were performed at the time of diagnosis and again for the instillation of first intrathecal chemotherapy. The event-free survival (EFS) experience for patients with 1 cerebrospinal fluid (CSF) sample contaminated with blast cells was worse than that for patients with no contaminated CSF samples (P =.026); that of patients with 2 consecutive contaminated CSF samples was particularly poor (5-year EFS = 46 +/- 9%). In a Cox multiple regression analysis, the strongest prognostic indicator was 2 consecutive contaminated CSF samples, with a hazard ratio of 2.39 (95% confidence interval, 1. 36-4.20). These data indicate that contamination of CSF with circulating leukemic blast cells during diagnostic lumbar puncture can adversely affect the treatment outcome of children with ALL and is an indication to intensify intrathecal therapy.