Biomedical subjects

E M Krieger

Publications and source records attributed to E M Krieger.

At least 37 records · Page 2Linked to original sources

PubMed1999

Outcome of patients with malignant hypertension and end-stage renal failure treated by long-term hemodialysis.

Malignant hypertension is associated with high mortality and morbidity usually caused by cardiovascular events. The course and prognosis of malignant hypertension patients treated with renal replacement therapy has not been thoroughly investigated. In the present work, we compared the clinical evolution and survival of 24 end-stage renal failure malignant hypertension patients with that of a group of individually matched renal failure patients admitted to the same dialysis center during a period of 21 years. Survival rates at 1, 5 and 8 years were 87, 82 and 50% for malignant hypertension patients and 87, 75 and 65% for controls, respectively (p = 0.766, NS). Nonfatal cardiovascular complications occurred in 2 individuals of each group. The most important cause of death in both groups was cardiovascular. The frequency of fatal cardiovascular events was similar in the two groups: 64% of deaths for malignant hypertension and 71% for controls (NS). In conclusion, previous malignant hypertension did not increase the risk of patients in long-term hemodialysis in our series.

Adolescent↗

PubMed1999

Cardiac effects of persistent hemodialysis arteriovenous access in recipients of renal allograft.

In hemodialysis patients, large arteriovenous (AV) fistulas for vascular access may cause ventricular hypertrophy and high-output cardiac failure. The long-term cardiac consequences of functional AV fistulas in renal transplant patients are unclear. A precise knowledge of these consequences is important to decide if and when such fistulas should be closed in successfully transplanted patients. In this retrospective study including 61 stable renal transplant patients with adequate renal function (serum creatinine <2.0 mg/100 ml), echocardiography was performed in 39 patients with a functional AV fistula (group 1) and in 22 whose fistulas had been closed, for esthetic reasons, within 2 months postoperatively (group 2). The volume flow of the fistulas, measured in 22 randomly selected individuals of group 1, was 900 +/- 350 ml/min (range 500-1,600). Patients of group 1 were older (40 +/- 12 vs. 33 +/- 12 years, p < 0.05), had longer duration of the fistula (62 +/- 31 vs. 36 +/- 30 months, p < 0.05), higher body mass index (24 +/- 4 vs. 22 +/- 3 kg/m2, p < 0.05), systolic (154 +/- 24 vs. 138 +/- 18 mm Hg, p < 0.05) and diastolic (96 +/- 12 vs. 89 +/- 11 mm Hg, p < 0.05) blood pressure and increased left ventricular (LV) end-diastolic dimension (53 +/- 5 vs. 49 +/- 5 mm, p < 0.01). LV mass, cardiac index, ejection fraction and the proportion of patients with LV hypertrophy were comparable in the two groups. LV end-diastolic dimension was positively and independently influenced only by the presence of the AV fistula (p < 0.01) after adjusting for age, duration of the fistula, body mass index, systolic and diastolic blood pressure and the nature of the antihypertensive drugs used. In conclusion, the persistence of large, high-flow AV fistulas for prolonged periods of time had little impact on cardiac morphology and function of stable renal transplant patients with adequate renal function. The data do not support routine closure of these fistulas in all renal transplant patients.

Adult↗

PubMed1999

State-of-the-Art lecture: influence of exercise training on neurogenic control of blood pressure in spontaneously hypertensive rats.

Exercise training plays an important role in the reduction of high blood pressure. In this review, we discuss the effect of distinct intensities of exercise training on the reduction of high blood pressure in spontaneously hypertensive rats (SHR). In addition, we present some hemodynamic mechanisms and associated neural controls by which exercise training attenuates hypertension in SHR. Low-intensity exercise training is more effective in reducing high blood pressure than is high-intensity exercise training in SHR. The decrease in blood pressure is due to resting bradycardia, and in consequence, lower cardiac output. Sympathetic attenuation to the heart is the major explanation for the resting bradycardia. Recovery of the sensitivity of baroreflex control of heart rate, which is usually impaired in SHR, is an important neurogenic component involved in the benefits elicited by exercise training.

Animals↗

PubMed1999

Cardiopulmonary reflex impairment in experimental diabetes in rats.

The aim of the present study was to evaluate the sensitivity of the cardiopulmonary receptors in experimental diabetes induced by streptozotocin by the use of 2 different methods: (1) administration of increasing doses of serotonin to analyze peak changes of arterial pressure and heart rate for each given dose in conscious intact normal and diabetic rats; (2) expanding blood volume with the use of dextran (6%) to produce similar increases in left ventricular end-diastolic pressure to quantify the arterial pressure, heart rate, and renal sympathetic nerve activity in sinoaortic, denervated, anesthetized normal and diabetic rats. Blood samples were collected to measure blood glucose. Diabetic rats showed hyperglycemia (22+/-0. 7 versus 7+/-0.2 mmol/L), reduced body weight (226+/-12 versus 260+/-4 g) and heart rate (294+/-14 versus 350+/-10 bpm), and similar arterial pressure (104+/-4 versus 113+/-4 mm Hg) when compared with control rats. Serotonin induced significant bradycardia and hypotension, which were similar and proportional to the dose injected in both groups. Mean arterial pressure and heart rate decreases in response to volume overload were significantly lower in diabetic than in control rats. The reflex reduction of the renal sympathetic nerve activity as expressed by percentage changes in nerve activity in response to increasing left end-diastolic pressure was abolished in diabetic animals (1.9+/-0.8% versus -14+/-4%/mm Hg in controls). These results showed an impairment of cardiopulmonary reflex control of circulation in diabetes during acute volume expansion. The normal responses to serotonin administration indicated that the cardiopulmonary reflex is still preserved in diabetic rats.

Animals↗

PubMed1999

Comparison of three methods for the determination of baroreflex sensitivity in conscious rats.

Baroreflex sensitivity was studied in the same group of conscious rats using vasoactive drugs (phenylephrine and sodium nitroprusside) administered by three different approaches: 1) bolus injection, 2) steady-state (blood pressure (BP) changes produced in steps), 3) ramp infusion (30 s, brief infusion). The heart rate (HR) responses were evaluated by the mean index (mean ratio of all HR changes and mean arterial pressure (MAP) changes), by linear regression and by the logistic method (maximum gain of the sigmoid curve by a logistic function). The experiments were performed on three consecutive days. Basal MAP and resting HR were similar on all days of the study. Bradycardic responses evaluated by the mean index (-1.5 +/- 0.2, -2.1 +/- 0.2 and -1.6 +/- 0.2 bpm/mmHg) and linear regression (-1.8 +/- 0.3, -1.4 +/- 0.3 and -1.7 +/- 0.2 bpm/mmHg) were similar for all three approaches used to change blood pressure. The tachycardic responses to decreases of MAP were similar when evaluated by linear regression (-3.9 +/- 0.8, -2.1 +/- 0.7 and -3.8 +/- 0.4 bpm/mmHg). However, the tachycardic mean index (-3.1 +/- 0.4, -6.6 +/- 1 and -3.6 +/- 0.5 bpm/mmHg) was higher when assessed by the steady-state method. The average gain evaluated by logistic function (-3.5 +/- 0.6, -7.6 +/- 1.3 and -3.8 +/- 0.4 bpm/mmHg) was similar to the reflex tachycardic values, but different from the bradycardic values. Since different ways to change BP may alter the afferent baroreceptor function, the MAP changes obtained during short periods of time (up to 30 s: bolus and ramp infusion) are more appropriate to prevent the acute resetting. Assessment of the baroreflex sensitivity by mean index and linear regression permits a separate analysis of gain for reflex bradycardia and reflex tachycardia. Although two values of baroreflex sensitivity cannot be evaluated by a single symmetric logistic function, this method has the advantage of better comparing the baroreflex sensitivity of animals with different basal blood pressures.

Analysis of Variance↗

PubMed1998

Plasma kinetics of chylomicron-like emulsion in renal transplant patients receiving cyclosporin-based immunosuppression.

BACKGROUND: Atherosclerotic cardiovascular disease is prevalent among renal transplant patients. Increase in serum total cholesterol, low-density lipoprotein, and very low-density lipoprotein is common in those patients. Alterations in chylomicron metabolism, however, are also related to atherogenesis and were not studied in renal transplant. HYPOTHESIS: The aim of this study was to evaluate chylomicron metabolism in renal transplant recipients receiving cyclosporin-based immunosuppression. We determined the plasma kinetics of triglyceride-rich emulsions labeled with [3H]triolein and [14C]cholesteryl oleate that are known to mimic the chylomicron metabolism when injected into the blood stream. METHODS: Fourteen renal transplant recipients with normal renal function (10 men, 4 women, aged 40 +/- 6.1 years) and 17 age- and gender-matched healthy controls received bolus injections of the chylomicron-like emulsion. Plasma samples were then taken at regular intervals during 60 min. Disappearance curves of the labels and the respective fractional clearance rates (FCR) were calculated in order to measure lipolysis and chylomicron remnant removal from the plasma. RESULTS: Fasting serum lipid levels did not differ in the two groups. The difference between Median FCR of [3H]triolein emulsion in renal transplant patients and that obtained in the controls (0.07 vs. 0.11 min-1, NS) was not statistically significant. Median FCR of [14C]cholesteryl oleate also did not differ between the groups (patients: 0.044; controls: 0.046, NS). CONCLUSION: These results indicate that neither chylomicron lipolysis nor remnant removal are affected in stable renal transplant patients treated with cyclosporin-based immunosuppression.

Adult↗

PubMed1998

Lack of effect of a single oral dose of cyclosporine on systemic blood pressure and on forearm blood flow and vascular resistance in humans.

The acute hemodynamic effect of cyclosporine in man is controversial. A randomized, double blind, placebo-controlled, cross-over study was undertaken to evaluate the effect of a single oral dose of cyclosporine (20 mg/kg body weight) on mean blood pressure (MBP), heart rate (HR), forearm blood flow (FBF), and vascular resistance (FVR) in 16 healthy adult subjects. Subjects were studied twice, with an intervening period of 2 weeks, before and after the administration of either cyclosporine or the vehicle olive oil. Blood pressure was measured on brachial and digital arteries. After 30 min of rest, basal measurements were obtained and individuals were randomly assigned to receive either cyclosporine or the vehicle, and the same measurements were repeated 2 h later. Mean whole blood levels of cyclosporine were 1542+/-387 ng/mL (range 1000 to 2550) 2 h after the administration of a single oral dose of cyclosporine. Cyclosporine did not cause any significant change in the hemodynamic parameters when compared with vehicle. Pre- and post-cyclosporine data were as follows (means +/-/SD): MBP (determined by Finapres on the digital artery), 92+/-10 v 95+/-11 mm Hg; HR, 66+/-10 v 68+/-11 beats/min; FBF, 3.90+/-1.3 v 3.8+/-1.8 mL/ 100 mL/min; and FVR, 28+/-9 v 33 +/-18 units, respectively. For the vehicle the results were: MBP, 94+/-9 v 94+/-9; HR, 67+/-9v 67 /-11; FBF, 3.3+/-1.6 v 3.2+/-2.0; FVR, 35+/-14 v 37+/-15, respectively. These figures did not differ from those obtained with the auscultatory method applied to the brachial artery among 10 selected subjects studied with Finapres. In conclusion, we found no evidence that at supratherapeutic doses cyclosporine causes acute increase in blood pressure or peripheral vasoconstriction in humans.

Administration, Oral↗

PubMed1998

Chronic AT1 receptor blockade alters aortic nerve activity in hypertension.

In the chronic phase of coarctation hypertension (CH) we have shown both reduction in baroreceptor sensitivity (Hypertension. 1992;19[suppl II]:II-198-II-201.) and normalization of the depressed baroreceptor reflex control of heart rate, even with the persistence of hypertension in losartan-treated animals (Am J Physiol. 1995;269:H812-H818). In the present study we analyzed the effects of angiotensin II blockade on afferent aortic nerve activity of CH and sham-operated groups treated chronically with vehicle or losartan (10 mg/kg per day p.o.). CH was induced by subdiaphragmatic aortic coarctation, and the treatments lasted 8 days (4 control and 4 experimental days). Aortic pressure (conscious rats) and aortic nerve activity simultaneous to pressure (anesthetized rats) were recorded on the fourth day of the experimental period. Losartan-treated rats showed reduced tail pressure (104+/-3 versus 117+/-3 mm Hg in the vehicle group). In both groups, aortic coarctation caused a significant increase in pressure (25% and 28%, respectively) and a depression of the aortic nerve activity/pressure relationship when compared with sham-operated coarcted animals. In the physiological range of pressure changes, the depression was significantly smaller after losartan treatment (3.30+/-0.33 versus 2.18+/-0.37%/mm Hg in the losartan- and vehicle-treated CH groups, respectively, versus 5.05+/-0.33%/mm Hg in the sham-operated vehicle-treated group). Angiotensin type 1 (AT1) receptor blockade was also accompanied by reduced variability of the afferent discharge. The data suggested that apart from its pressure effect, angiotensin II acts at AT1 receptors to decrease the sensitivity of aortic afferents during physiological (+/-10 mm Hg) increases and decreases in pressure. Thus, angiotensin II may contribute to reductions of baroreceptor gain in chronic hypertension.

Afferent Pathways↗

PubMed1998

Baroreflex control of sympathetic activity in experimental hypertension.

The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD) and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100%) was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

Animals↗

PubMed1998

Role of arterial baroreceptor function on cardiovascular adjustments to acute and chronic dynamic exercise.

Our series of experiments in rats, and other data of the literature, indicate that the arterial baroreceptors are actively involved in the reflex control of circulation during acute and chronic exercise. Although heart rate increases simultaneously with arterial blood pressure during an acute bout of dynamic exercise, the gain of the baroreflex bradycardia remains unchanged. Moreover, the more pronounced increase in mean arterial pressure during all exercise period observed in sino-aortic denervated rats, compared to sham-operated rats, suggests that the arterial baroreflex restrains the increase in blood pressure during dynamic exercise. However, the arterial baroreflex seems to have no influence on the development of exercise tachycardia. Exercise training can affect baroreflex bradycardia and tachycardia in the opposite direction, since decreased baroreflex bradycardia is observed despite increased baroreflex tachycardia. Since the increased baroreflex tachycardia may be attributed to an increased sensitivity of the afferent pathway of the baroreceptors, the attenuation of the baroreflex bradycardia is probably due to an impairment of the efferent pathway of the reflex. Finally, the decreased tonic sympathetic nerve activity produced by exercise training can be considered as one of the mechanisms involved in the attenuation of hypertension induced by exercise training.

Animals↗

PubMed1997

Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension. Irbesartan Multicenter Investigators.

In this double-blind, randomized study, an antihypertensive regimen based on irbesartan, an angiotensin II receptor antagonist, reduced systolic and diastolic blood pressure by 40/30 mm Hg at week 12 in patients with severe hypertension; this reduction was at least equivalent to that of a regimen using enalapril up to 40 mg. The irbesartan-based regimen had a better tolerability profile with fewer adverse events (55% vs 64%) and significantly less cough (2.5% vs 13.1%, p = 0.007).

Angiotensin II↗

PubMed1997

In vivo adaptive responses of the aorta to hypertension and aging.

To investigate the dynamic behavior of the aorta of freely moving rats during the maintenance of hypertension, a longitudinal study was performed in renal hypertensive (Goldblatt 1 kidney, 1 clip) rats aged 3, 6, and 9 mo in which hypertension was maintained for 1, 3, and 6 mo, respectively. The pulsatile caliber of the thoracic aorta was measured (electrolytic strain gauge chronically implanted) simultaneously with aortic pressure under basal conditions and during transient changes of blood pressure. Aortic thickness was determined postmortem by morphometry. Establishment of hypertension (179 +/- 5 mmHg) by increasing the stress developed by the aorta caused increases in the resting values of caliber (20%), thickness (21%), and strain (95%); the maintenance of hypertension for a 6-mo period caused a further increase in thickness (58% vs. age-matched normotensive aortas) but not in aortic caliber and strain, the subsequent alterations of which were due only to growth/aging. Although different calibers, thicknesses, and dynamic strains were presented, the stress-strain relationship during transient blood pressure changes was similar for all hypertensive and normotensive groups with the exception of renal hypertensive rats aged 6 mo, which presented a steeper relationship (a large transitory increase in aortic distensibility was observed at that age). Dynamic adaptive responses of the aorta to hypertension compensate for geometric changes in such a way as to maintain a near-constant distensibility. It was concluded that, in contrast to the extrathoracic vessels, the adaptive responses of the aorta to hypertension were directed to maintain its compliance without changing the distensibility and stress-strain relationship, contributing to partially counterbalance the increased pressure and the decreased compliance of the more peripheral components of the arterial tree.

Acclimatization↗

PubMed1997

Low-intensity exercise training decreases cardiac output and hypertension in spontaneously hypertensive rats.

The decrease in cardiac sympathetic tone and heart rate after low-intensity exercise training may have hemodynamic consequences in spontaneously hypertensive rats (SHR). The effects of exercise training of low and high intensity on resting blood pressure, cardiac output, and total peripheral resistance were studied in sedentary (n = 17), low- (n = 17), and high-intensity exercise-trained (n = 17) SHR. Exercise training was performed on a treadmill for 60 min, 5 times per week for 18 weeks, at 55% or 85% maximum oxygen uptake. Blood pressure was evaluated by a cannula inserted into the carotid artery, and cardiac output was evaluated by a microprobe placed around the ascending aorta. Low-intensity exercise-trained rats had a significantly lower mean blood pressure than sedentary and high-intensity exercise-trained rats (160 +/- 4 vs. 175 +/- 3 and 173 +/- 2 mmHg, respectively). Cardiac index (20 +/- 1 vs. 24 +/- 1 and 24 +/- 1 ml.min-1 x 100 g-1, respectively) and heart rate (332 +/- 6 vs. 372 +/- 14 and 345 +/- 9 beats/min, respectively) were significantly lower in low-intensity exercise-trained rats than in sedentary and high-intensity exercise-trained rats. No significant difference was observed in stroke volume index and total peripheral resistance index in all groups studied. In conclusion, low-intensity, but not high-intensity, exercise training decreases heart rate and cardiac output and, consequently, attenuates hypertension in SHR.

Animals↗

PubMed1997

Lipid metabolism alterations in normotensive subjects with positive family history of hypertension.

Metabolic abnormalities are usually reported in hypertensive patients. These metabolic alterations seem to begin in childhood. The young offspring of hypertensive parents have not been studied thoroughly for metabolic alterations. The aim of this study was to examine the level of total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, uric acid, glycemia, aldosterone, and plasma renin activity in a population of 42 young, slender normotensive subjects with positive family history of hypertension (FH+) or negative family history of hypertension (FH-). Measurements were made in 20 young normotensive subjects (age 21.1+/-2.2 years, 11 males, 15 white, 5 oriental, body mass index of 22.1+/-2.3 kg/m2) with FH+ and 22 young normotensive subjects (age 19.9+/-1.4 years, 17 males, 17 white, 5 oriental, body mass index of 22.1+/-2.3 kg/m2) with FH-. The total cholesterol (4.47+/-0.8 versus 3.95+/-0.6 mmol/L), LDL cholesterol (2.74+/-0.63 versus 2.36+/-0.61 mmol/L), VLDL cholesterol (0.5+/-0.25 versus 0.35+/-0.09 mmol/L), and triglycerides (2.52+/-1.26 versus 1.76+/-0.5 mmol/L) were significantly elevated (P<.05) in the FH+ group compared with the FH- group. The total cholesterol/HDL cholesterol ratio was significantly higher in the group with a positive family history of hypertension (3.75+/-0.02 versus 3.11+/-0.02, P<.05). Glycemia was slightly elevated in the FH+ group (2.16+/-0.29 mmol/L) but was not significantly different from that of the FH- group (2+/-0.2 mmol/L). Uric acid, plasma renin activity, and aldosterone were similar in both groups. We conclude that young, slender normotensive subjects with a positive history of hypertension show alterations in lipid metabolism, suggesting a positive correlation between lipid metabolism and hypertension heredity.

Adult↗

PubMed1997

Hemodynamics of chemoreflex activation in unanesthetized rats.

Experiments were performed on unanesthetized rats (n=6) to determine the systemic hemodynamics during chemoreflex activation by intravenous KCN. Rats chronically instrumented with ultrasonic flow probes in the ascendant aorta were submitted to KCN injections (30 microg/kg) before and after sequential administration of the autonomic blockers atropine and propranolol. In the control period KCN injections produced a 60% reduction in heart rate (HR) and a 46% elevation in blood pressure (BP), while cardiac output (CO) decreased 76%, stroke volume (SV) decreased 40%, and calculated total peripheral resistance (TPR) increased 900%. Atropine administration increased resting HR, whereas no change was observed in CO or BP. Chemoreflex-induced bradycardia was markedly attenuated (26%), and the pressor response was potentiated (59%) after atropine administration. CO and TPR responses were both attenuated after atropine administration (68% and 718%, respectively). Sequential administration of propranolol decreased HR but did not change the cardiovascular responses to KCN injections compared with the responses observed after atropine administration. In conclusion, CO is greatly reduced during KCN-evoked chemoreflex. Besides the intense bradycardia, a decrease in SV contributed to this reduction. Bradycardic response was most dependent on the cardiac parasympathetic activation, and the reduction in SV was probably most dependent on the increased cardiac afterload due to the sudden increase in BP.

Animals↗

PubMed1997

Acute and chronic effects of exercise on baroreflexes in spontaneously hypertensive rats.

We studied the effects of acute and chronic exercise on the arterial baroreflex and chemosensitive cardiopulmonary baroreflex (CCB) in spontaneously hypertensive rats (SHR). Arterial baroreflex and CCB were evaluated in normotensive rats (NR, n=11) and SHR (n=5) at rest and after 30 minutes of an acute bout of exercise (45 minutes at 50% of VO2max). In addition, these baroreflexes were evaluated in sedentary (n=5) and exercise-trained (n=9) SHR. Exercise training was performed on a motor treadmill, 5 days/week, during 60 minutes, at 50% of VO2max. Baroreflex bradycardia and tachycardia, analyzed by baroreflex sensitivity index (delta heart rate/delta mean arterial pressure), were significantly lower in SHR than in NR (0.7+/-0.1 versus 2.0+/-0.1 and 1.8+/-0.2 versus 3.4+/-0.1 beats per minute [bpm]/mm Hg, respectively). During the recovery period from acute exercise, baroreflex bradycardia was significantly higher than at rest only in SHR (1.7+/-0.1 versus 0.7+/-0.1 bpm/mm Hg). Hypotension and bradycardia induced by CCB stimulation (5-hydroxytryptamine, I.V.) were similar between SHR and NR, and an acute exercise bout did not change these responses. Exercise training markedly improved baroreflex bradycardia and tachycardia in SHR (1.9+/-0.1 versus 0.7+/-0.1 and 2.9+/-0.1 versus 1.8+/-0.2 bpm/mm Hg, respectively). Exercise-trained rats had greater bradycardiac (118+/-26 versus 14+/-2 and 209+/-30 versus 19+/-5 bpm to 1 and 2 microg/kg 5-HT, respectively) and hypotensive (30+/-6 versus 15+/-3 and 45+/-7 versus 17+/-2 mm Hg to 1 and 2 microg/kg 5-hydroxytryptamine, respectively) responses to CCB stimulation. In conclusion, an acute bout of exercise increases baroreflex bradycardia in SHR, and exercise training attenuates hypertension concomitant with improved arterial baroreflex and CCB sensitivity in SHR.

Animals↗

PubMed1997

Early elevation of lipoprotein(a) levels in chronic renal insufficiency.

Serum lipoprotein(a) [Lp(a)] concentrations in chronic renal failure patients were investigated in relation to the degree of renal insufficiency, treatment by maintenance hemodialysis, and correction of uremia by renal transplantation with or without cyclosporin immunosuppression. Fast serum levels of Lp(a) (mg/100 mL) were determined in 34 chronic renal failure patients not in need of maintenance dialysis (16 with serum creatinine 2.0-4.0 mg/100 mL; 18 with serum creatinine higher than 4.0 mg/100 mL), 40 patients treated by hemodialysis, 55 successful renal transplant recipients (28 under cyclosporin treatment and 27 receiving no cyclosporin), and 34 healthy controls. Age and sex distributions were similar among groups. Pregnant women; non-White individuals; subjects with obesity, diabetes, nephrotic syndrome, and hepatic and thyroid diseases; and those treated with oral contraceptives or lipid-lowering drugs were excluded from the study. Compared to controls, median Lp(a) was increased in nondialyzed renal failure patients (11 vs. 47.5 p < 0.001) and this was the only lipid abnormally observed in the group. There was no significant difference in Lp(a) levels between nondialized renal failure patients with serum creatinine 2.0-4.0 and > 4.0 mg/100 mL (47 vs. 49, NS). Moreover, Pearson correlation coefficient (r = 0.01, NS) showed that Lp(a) values were not related to serum creatinine in nondialyzed patients, In hemodialysis subjects Lp(a) concentrations (median = 29) were intermediate between those observed in nondialyzed patients and controls but the differences were not significant. Lp(a) levels in renal transplant patients treated with cyclosporin (median = 6) and not receiving cyclosporin (median = 13) were similar and did not differ from controls. Serum Lp(a) increases and attains maximum levels with mild/moderate reduction in renal function, and does not seem to change through late renal failure stages or in relation to the introduction of maintenance hemodialysis treatment. Correction of uremia by successful renal transplant caused normalization of Lp(a) levels regardless of the use of cyclosporin. Increased Lp(a) levels may be the earliest and more consistent lipid alteration seen in predialysis renal failure.

Adult↗

PubMed1996

Viscoelastic mechanisms of aortic baroreceptor resetting to hypotension and to hypertension.

Viscoelastic and electrophysiological mechanisms have been implicated in the resetting of baroreceptors in hypertension, but resetting in response to hypotension has been less studied. To evaluate the temporal relationship between viscoelastic mechanisms and acute resetting, we examined the "in vivo" behavior of aortic caliber and aortic baroreceptor activity during step changes in pressure. Fifteen-minute hemorrhage in Wistar rats produced stable hypotension (30 mmHg) and viscoelastic contraction (111 +/- 14.2 microns systolic caliber; P < 0.01). Integrated aortic activity fell to 19.8 +/- 3.9% of control (P < 0.001) after 3 s of hypotension but recovered to 64 +/- 4.1% 15 min later (P < 0.01 from 3 s). Recovery of baroreceptor activity was linearly correlated to viscoelastic contraction (r = 0.963; P < 0.0001). Thirty-minute phenylephrine infusion (1.0-4.0 micrograms/min) produced stable hypertension (30 mmHg) and viscoelastic dilation (211 +/- 37.0 microns systolic caliber). Integrated aortic activity increased to 218.0 +/- 18% of control values (P < 0.001) 30 s after hypertension and was reduced to 164.0 +/- 12.0% (P < 0.001 from 3 s) within 30 min. Reduction of baroreceptor activity correlated linearly with viscoelastic relaxation (r = 0.963; P < 0.0001). The results indicate that in the in vivo rat aorta, viscoelastic mechanisms parallel and may contribute to the baroreceptor resetting during hypotension and hypertension.

Animals↗