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Biomedical subjects

S Strandgaard

Publications and source records attributed to S Strandgaard.

At least 73 records · Page 4Linked to original sources

Cerebral circulation under normal and pathologic conditions.

Autoregulation of the cerebral circulation is the regulating mechanism that keeps cerebral blood flow (CBF) constant within wide limits of arterial pressure. The lower limit is defined as the value of mean arterial pressure below which CBF decreases below the plateau, and the upper limit as the value of mean arterial pressure above which CBF increases above the plateau (60 and 150 mm Hg, respectively). Two possible mechanisms for autoregulation are discussed, myogenic response and metabolic regulation. Stimulation of the sympathetic nervous system and antagonism of the renin-angiotensin system modulate CBF autoregulation by shifting the entire curve toward higher or lower values of arterial pressure, respectively. The autoregulatory curve is shifted toward higher arterial pressures in chronic hypertension. Therefore, the tolerance to acute decreases in arterial pressure is impaired. Concomitantly, the tolerance of the brain to acute increases in arterial pressure is improved. This shift in the limits of autoregulation is due to structural and functional (hemodynamic) changes in the cerebral resistance vessels. These adaptive changes are partly reversible after chronic treatment with antihypertensive agents. The pathophysiology of autoregulation should be taken into consideration before drugs are used to decrease arterial pressure acutely.

Animals↗

Lithium clearance in chronic nephropathy.

1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption of lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium clearance data were independent of whether renal disease was of primarily glomerular or tubular origin and, further, were not influenced by long-term conventional antihypertensive treatment. 6. It is concluded that, even with a reduced kidney function, the data are compatible with the suggestion that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct). With more severe impairment the proximal tubule also becomes involved in the adjustment.

Adult↗

Cerebral blood flow and its pathophysiology in hypertension.

In chronic hypertension, the lower limit of autoregulation of cerebral blood flow (CBF) is shifted towards high blood pressure with a consequent impairment of the tolerance to acute hypotension. Despite this, antihypertensive treatment in the great majority of patients prevents stroke and the risk for treatment-induced cerebral ischemia is only real in a limited number of clinical settings such as malignant hypertension, hypertension in the elderly, and hypertension associated with acute stroke. During long-term treatment adaptive hypertensive changes in CBF autoregulation may be reversible, especially in young patients. Drugs used for emergency lowering of blood pressure may be classified into four groups according to their effect on CBF and intracranial pressure: (1) drugs with no pharmacological action in the cerebral circulation; (2) cerebral vasodilators; (3) alpha-adrenergic and ganglionic blockers; and (4) angiotensin-converting enzyme (ACE) inhibitors. Oxygen saturation in the jugular venous blood is of the order of 60% to 70% and is considerably higher than in the coronary sinus. It is hypothesized that this oxygen reserve enables the brain better than the heart to take hemodynamic advantage of pressure lowering without risking tissue ischemia. This may explain why antihypertensive treatment prevents stroke but not myocardial infarction. Acute hypertensive encephalopathy is probably caused by failure of autoregulatory vasoconstriction with focal or generalized dilatation of small arteries and arterioles. This is associated with a high CBF, dysfunction of the blood-brain barrier, and the formation of brain edema that is thought to cause the clinical symptoms.

Animals↗

Changes in glomerular filtration rate, lithium clearance and plasma protein clearances in the early phase after unilateral nephrectomy in living healthy renal transplant donors.

1. Glomerular and tubular function was studied before and 2 months after unilateral nephrectomy in 14 healthy kidney donors by measurement of the clearances of 51Cr-labelled ethylenediaminetetra-acetate, lithium, beta 2-microglobulin, albumin and immunoglobulin G. 2. The glomerular filtration rate (GFR) of the kidney that remained in the donor rose from 45 +/- 10 (mean +/- SD) to 59 +/- 10 ml/min (P less than 0.01) 5 days after contralateral nephrectomy and remained at this level through the observation period. 3. The lithium clearance (CLi) of the remaining kidney rose from 11.6 +/- 3.7 to 20.5 +/- 8.2 ml/min (P less than 0.01) and remained significantly elevated throughout the observation period. 4. Absolute proximal fluid reabsorption rate (APR), which was estimated as GFR minus CLi, was unchanged 5 days after contralateral nephrectomy, but then rose gradually to reach significantly elevated levels after 4 weeks. 5. Fractional proximal reabsorption (FPR; APR/GFR) fell from 0.75 +/- 0.06 to 0.66 +/- 0.11 (P less than 0.01) but subsequently rose to levels not significantly decreased from normal. 6. Twenty-four hour fractional clearances of beta 2-microglobulin, albumin and immunoglobulin G rose markedly on the day of nephrectomy, peaked at 2-3 days and subsequently fell to moderately elevated levels. 7. Both the CLi and the plasma protein clearance studies demonstrate that the early response of the remaining kidney to contralateral nephrectomy in man is an increase in GFR, an unchanged APR and a fall in FPR. The proximal tubules thus initially handle the increased filtrate load by passing it on to more distal nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The influence of body posture on lithium clearance.

To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were measured four times at 1-week intervals: two in the supine and one in the sitting position, and one when the subject was walking around. Glomerular filtration rate was not influenced by posture changes. On the contrary, lithium clearance, which in the supine position was 30 +/- 9 ml/min (1 SD), tended to fall in the sitting position, and fell significantly to 26 +/- 5 ml/min (p less than 0.025) in walking subjects. Absolute proximal tubular reabsorption rate of fluid correspondingly rose from 83 +/- 16 to 92 +/- 15 ml/min (p less than 0.005) and sodium clearance fell from 1.52 +/- 0.81 to 1.00 +/- 0.52 ml/min (p less than 0.05) in walking subjects. Absolute distal reabsorption of sodium decreased during walking from 4052 +/- 1219 to 3449 +/- 658 mumol/min (p less than 0.025), while fractional distal reabsorption of sodium was unchanged. Our results show a rise in proximal tubular reabsorption during moderate physical activity. Hence, when renal tubular function is studied with the lithium clearance method, standardization of posture and physical activity is important. In such studies physical activity such as walking should particularly be avoided.

Adolescent↗

The incidence rate of phaeochromocytoma and Conn's syndrome in Denmark, 1977-1981.

In the years 1977 to 1981, 47 cases of phaeochromocytoma and 19 cases of aldosterone-producing adrenal adenoma (Conn's syndrome) were diagnosed in Denmark as reported to the National Register of Hospital Patients. This corresponds to an average annual incidence of phaeochromocytoma and Conn's syndrome of 1.9 and 0.8 per million inhabitants, respectively. Treatment results were evaluated from the patient's records and follow-up questionnaires. Of 30 surviving patients operated upon for phaeochromocytoma and followed-up after 18-81 months, 23 were normotensive without treatment and seven were mildly to moderately hypertensive. Of 11 patients operated upon for Conn's syndrome, follow-up data at 1-2 years were obtained in seven, of whom five were normotensive and two hypertensive. Phaeochromocytoma and Conn's syndrome are rare diseases. The results of surgical treatment are often gratifying, but not all patients remain normotensive after surgery, even in the absence of recurrence of endocrine disease.

Adolescent↗

Can differences in cerebral and coronary autoregulation and O2-extraction explain why antihypertensive treatment prevents stroke but not myocardial infarction?

It is proposed that the failure of current antihypertensive treatment to reduce the incidence of coronary heart disease in patients with hypertension is due to severe, possibly irreversible restriction of coronary vascular reserve in the deeper layers of the left ventricle. Contrary to the heart, the brain can maintain a normal oxidative metabolism when the blood pressure is lowered, by extracting more oxygen from the blood. The brain is thus better suited than the heart to take advantage of the beneficial effect of antihypertensive treatment in terms of protection against hypertensive organ damage. This hypothesis is supported by studies of cerebral and coronary autoregulation and the J-shaped relation between death from myocardial infarction and treated diastolic blood pressure now reported from a number of studies.

Cerebrovascular Circulation↗

Why does antihypertensive treatment prevent stroke but not myocardial infarction?

It is proposed that differences in autoregulatory reserve and blood oxygen extraction potential between the coronary and cerebral circulations explain why antihypertensive treatment effectively protects patients against stroke but has failed to reduce the increased incidence of myocardial infarction associated with hypertension. In the brain, oxygen extraction from the blood can be increased if blood pressure falls below the lower limit of autoregulation. In the coronary circulation, however, oxygen extraction is nearly maximum at rest, and lowering of blood pressure by antihypertensive therapy can lead to myocardial ischaemia.

Antihypertensive Agents↗

Cerebrospinal fluid creatine kinase isoenzyme BB levels do not predict the clinical outcome in patients unconscious following cardiac resuscitation.

It has recently been claimed that an increase in creatine kinase isoenzyme BB(CK-BB) in cerebrospinal fluid (CSF) is well correlated with the cerebral outcome in patients resuscitated after cardiac arrest. Twenty-one such patients consecutively admitted from outside this hospital participated in the study. The patients were divided into two groups: 6 survivors and 15 nonsurvivors. The median CSF-CK-BB value was 5 U/L among nonsurvivors and below detection limit among survivors (NS). However, the predictive value of a positive test is limited, since only 6 of 15 nonsurvivors (40%) had an increase in CSF-CK-BB (predictive value of positive test = 67%). The predictive value of a negative test is limited, since 3 of 6 survivors (50%) showed no rise in CSF-CK-BB (predictive value of negative test = 25%). No relationship between cerebral dysfunction and CSF-CK-BB values was revealed. Thus, CSF-CK-BB does not predict the clinical outcome in patients resuscitated after cardiac arrest.

Creatine Kinase↗

The renal handling of sodium and water is not affected by the standard-dose cisplatin treatment for testicular cancer.

Renal clearances of 51Cr-EDTA, lithium, sodium and potassium were measured before and after each of four consecutive treatment series with cisplatin in 15 men with testicular cancer. Since lithium is reabsorbed like sodium and water in the proximal tubules, but not reabsorbed to any measurable degree in the remainder of the nephron, lithium clearance equals the amount of fluid delivered from the end of the proximal straight segment to the thin descending limb of the loop of Henle. From the clearances of lithium and sodium, distal tubular reabsorption can be calculated. Lithium clearance and all other parameters of glomerular filtration and renal sodium handling remained normal throughout the study (with the exception of a fall in fractional sodium excretion after the first treatment series). Plasma magnesium declined during all four treatment periods, signifying renal magnesium wasting.

Adult↗

Hypertension in renal allograft recipients may be conveyed by cadaveric kidneys from donors with subarachnoid haemorrhage.

Evidence for hypertension was sought retrospectively in the necropsy records of 37 cadaveric kidney donors who had died of subarachnoid haemorrhage and 41 donors who had died of head injury, cerebral tumour, or (in a few instances) other causes. Mean relative heart weight in the donors with subarachnoid haemorrhage was 0.58 (1 SD = 0.09)% and in the other donors 0.52 (0.09)% (p less than 0.01), a difference unexplained by any factor other than a comparatively higher blood pressure in the donors who had died of subarachnoid haemorrhage. Blood pressure was analysed over 72 months after renal transplantation in 23 recipients with normal or near normal graft function and no evidence of chronic rejection or graft artery stenosis. Twelve patients who had received kidneys from donors with subarachnoid haemorrhage had consistently higher systolic blood pressures (p less than 0.004) and needed more antihypertensive treatment (p less than 0.0004) than the 11 recipients of kidneys from donors who had died of head injury or cerebral tumour. These observations suggest that cadaveric kidneys from donors dying of subarachnoid haemorrhage may induce or sustain hypertension after transplantation.

Adult↗

Effects of sulindac and naproxen in patients with chronic glomerular disease.

Eight patients with chronic glomerulonephritis were treated with either naproxen or sulindac in an open randomized study to observe their effects on the urinary excretion of prostaglandins and renal function. Both drugs were given for 7 days. Naproxen caused a decrease (p less than 0.01) of 80% in prostaglandin PGE2 and decrease (p less than 0.01) of 55% in prostaglandin PGF2 alpha. Sulindac caused a decrease (p = 0.01) of 37% in PGE2 and a decrease (p less than 0.05) in PGF2 alpha of 13%. The decrease in urinary excretion of prostaglandins were greater (p less than 0.05) during the naproxen treatment. Naproxen caused a decrease (p less than 0.05) in 24-hour creatinine clearance of 14 ml/min, an increase (p less than 0.05) in plasma urea of 1.0 mmol/l, an increase (p less than 0.05) in plasma potassium of 0.4 mmol/l and a decrease (p less than 0.01) in 24-hour urinary excretion of albumin of 11 mumol. Sulindac did not change any of these parameters significantly. In conclusion, sulindac affects renal prostaglandin synthesis to a significantly minor degree than naproxen and contrary to naproxen it does not influence the renal function in patients with chronic glomerular disease.

Adult↗