1243
SIR,-Dr Watts and colleagues demonstrate the importance of
lipid-lowering intervention in coronary artery disease. One important issue is what proportion of patients with a myocardial infarction have their plasma lipid values measured and how long after the event? Lipid measurement and management after coronary bypass has been disappointing.’ Is it a similar story for myocardial infarction? We have done a retrospective audit on patients aged less than 70 over the six months between July 1,1991,and Dec31,1991. There were 77 admissions; 74 case-notes were available. The average age was 59 years; 55 patients were male; 15 patients had ischaemic heart disease, and 13 died during the period of study, 9 from cardiac causes. Of the 61 survivors, 39 (64%) had had their plasma lipids
guanidinosuccinic acid are the most abundant.l-4 Whether these substances are responsible for the clinical features of uraemia is questionable. Methylguanidine has a diuretic and natriuretic action at doses achieving plasma concentrations found in uraemia.55 Structurally it resembles the side chain of the nitric oxide (NO) synthase inhibitor L-NG-methylarginine (L-NMMA) (figure) and could act as an NO inhibitor in vivo, directly or through chain elongation after interaction with other circulating species. However, there are no reports of these substances having a pressor action. We have examined the effect of bolus intravenous methylguanidine (05 mmol/kg) injection on arterial blood pressure in anaesthetised
checked: When lipids measured On admission On admission and repeated up to 3 Up to 6 wk after MI 6 wk to 3 mo after MI 3 mo to 6 mo after MI
mo
No 11 (28%) 5 (13 % ) 8 (21%) 11 (28%) 4 (10%)
later
Of the 22
patients for whom no lipid values were documented possible explanations include lipid values known before myocardial infarction (5), transfer and follow-up at regional cardiothoracic unit (3), or no hospital follow-up appointment made, discharged to general practitioners, patient aged more than 65, no apparent reason (10). From our group of patients only 4 had normal total cholesterol concentration (less than 5.2 mmol/1), the remaining 35 having borderline or abnormal values (mean 6-68 mmol/1). Only 4 patients were on lipid-lowering medication; 1 was referred to the regional lipid clinic but the other 30 were given dietary advice. Triglyceride values were documented where formal requests had been made to the laboratory; all patients with a total cholesterol above 6-5 rnmol/1 had fasting triglyceride values measured. Although it is encouraging to see nearly two-thirds of patients having plasma lipid values checked post-infarction, some were still being overlooked on admission and at outpatient follow-up (though perhaps subsequently identified by astute general practitioners). There was no uniformity about when lipid measurements were done. Total cholesterol falls after an acute myocardial infarction but for 24 hours.2,3 If measurements are done on admission or the morning (when blood is taken for cardiac enzymes anyway), they will reflect the pre-infarct lipid state, so that dietary and lifestyle advice can be given at a time when patients are especially not
next
receptive. have prompted a policy at this hospital of lipid admission. A non-fasting total cholesterol is the first investigation requested; any dietary advice is implemented before discharge. Lipid-lowering should not be taken in isolation, equal attention to all modifiable risk factors being necessary.
These
fmdings
measurement on
Departments of Endocrinology and
SANDEEP GUPTA RICHARD J. FRANKEL MALCOLM J. BOYD
Cardiology,
Frimley Park Hospital, Frimley GU16 5UJ, UK
1. Hoad NA. Searching for hyperlipidaemia in patients with coronary artery bypass grafts. Lancet 1989; i: 968-69. 2. Fyfe T, Baxter RH, Cockran KM, et al. Plasma lipid changes afer myocardial infarction. Lancet 1971; ii: 997-1001. 3. Ryder REJ, Hayes TM, Mulligan IP, et al. How soon after myocardial infarction should plasma lipid values be assessed? Br Med J 1984; 289: 1651-53.
Structures of
and conscious
uraemia
SIR,—The presence of circulating "toxins" in patients with renal failure and their relation
to
protein catabolism and the
pathophysiology of uraemia have been subjects of intensive research and speculation for many years.’ The suggestion by Dr Vallance and colleagues (March 7, p 572) that derivatives of arginine might accumulate to produce a biological effect in these patients is
intriguing.
Metabolism of arginine (via the urea cycle) and creatinine leads to the production of the so-called uraemic toxins (guanidino compounds), of which methlyguanidine and
L-NMMA.
but found no change. There are several NO all based on arginine;6 presumably the full aminoacid structure is required for binding at the enzyme’s active site. Thus, it is likely that other methylguanidine derivatives, such as cimetidine and meobentine, which do not have the a-aminoacid structure, would also lack NO synthase inhibitor activity. If circulating endogenous inhibitors of NO production are important in the pathophysiology of uraemia, it seems paradoxical that L-NMMA can amelioriate the platelet defect and bleeding tendency associated with uraemia.7 Moreover, a relative deficiency of circulating arginine is not a consistent finding in renal failure.8 rats
synthase inhibitors,
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London W12
G. TAYLOR
Institute of Urology and Nephrology, UCMH Medical School, Middlesex Hospital, London W1 N 8AA, UK
R. UNWIN
Department of Clinical Pharmacology, Royal Postgraduate Medical School
M. WILKINS
Department of Paediatric Nephrology, Medical Faculty I, University of Naples, Naples, Italy
G. CAPASSO
May RC, Kelly RA, Mitch WE. Pathophysiology of uraemia. In: Brenner BM, Rector FC, eds. The kidney. Philadelphia: Saunders, 1991: 1997-2018. 2. Onta Y, Tsubakihara Y, Ando A, et al. Effect of arginine or creatinine administration on the urinary excretion of methylguanidine. Nephron 1978; 22: 328-36. 3. Yokozawa T, Fujitsuka N, Oura H. Studies on the precursor of methylguanidine in rats with renal failure. Nephron 1991; 58: 90-94. 4. Nakamura K, Ienaga K, Yokozawa T, et al. Production of methylguanidine from creatinine via creatol by active oxygen species: analyses of the catabolism in vivo. Nephron 1991; 58: 42-46. 5 Henneman H, Bloemertz B, Heidland A. Studies on natriuretic properties of methylguanidine. Res Exp Med 1972; 158: 58-65. 6. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991; 43: 109-42. 7. Remuzzi G, Penco N, Zoja C, et al. Role of endothelium-derived nitric oxide in the bleeding tendency of uremia. J Clin Invest 1990; 86: 1768-71. 8. De Deyn P, Marescau B, Lornoy W, et al. Guanindino compounds in uremic dialyzed patients. Clin Chim Acta 1986; 157: 143-50. 1.
Arginine derivatives and
methylguanidine and
SIR,-Dr Watts and colleagues demonstrate the importance of
lipid-lowering intervention in coronary artery disease. One important issue is what proportion of patients with a myocardial infarction have their plasma lipid values measured and how long after the event? Lipid measurement and management after coronary bypass has been disappointing.’ Is it a similar story for myocardial infarction? We have done a retrospective audit on patients aged less than 70 over the six months between July 1,1991,and Dec31,1991. There were 77 admissions; 74 case-notes were available. The average age was 59 years; 55 patients were male; 15 patients had ischaemic heart disease, and 13 died during the period of study, 9 from cardiac causes. Of the 61 survivors, 39 (64%) had had their plasma lipids
guanidinosuccinic acid are the most abundant.l-4 Whether these substances are responsible for the clinical features of uraemia is questionable. Methylguanidine has a diuretic and natriuretic action at doses achieving plasma concentrations found in uraemia.55 Structurally it resembles the side chain of the nitric oxide (NO) synthase inhibitor L-NG-methylarginine (L-NMMA) (figure) and could act as an NO inhibitor in vivo, directly or through chain elongation after interaction with other circulating species. However, there are no reports of these substances having a pressor action. We have examined the effect of bolus intravenous methylguanidine (05 mmol/kg) injection on arterial blood pressure in anaesthetised
checked: When lipids measured On admission On admission and repeated up to 3 Up to 6 wk after MI 6 wk to 3 mo after MI 3 mo to 6 mo after MI
mo
No 11 (28%) 5 (13 % ) 8 (21%) 11 (28%) 4 (10%)
later
Of the 22
patients for whom no lipid values were documented possible explanations include lipid values known before myocardial infarction (5), transfer and follow-up at regional cardiothoracic unit (3), or no hospital follow-up appointment made, discharged to general practitioners, patient aged more than 65, no apparent reason (10). From our group of patients only 4 had normal total cholesterol concentration (less than 5.2 mmol/1), the remaining 35 having borderline or abnormal values (mean 6-68 mmol/1). Only 4 patients were on lipid-lowering medication; 1 was referred to the regional lipid clinic but the other 30 were given dietary advice. Triglyceride values were documented where formal requests had been made to the laboratory; all patients with a total cholesterol above 6-5 rnmol/1 had fasting triglyceride values measured. Although it is encouraging to see nearly two-thirds of patients having plasma lipid values checked post-infarction, some were still being overlooked on admission and at outpatient follow-up (though perhaps subsequently identified by astute general practitioners). There was no uniformity about when lipid measurements were done. Total cholesterol falls after an acute myocardial infarction but for 24 hours.2,3 If measurements are done on admission or the morning (when blood is taken for cardiac enzymes anyway), they will reflect the pre-infarct lipid state, so that dietary and lifestyle advice can be given at a time when patients are especially not
next
receptive. have prompted a policy at this hospital of lipid admission. A non-fasting total cholesterol is the first investigation requested; any dietary advice is implemented before discharge. Lipid-lowering should not be taken in isolation, equal attention to all modifiable risk factors being necessary.
These
fmdings
measurement on
Departments of Endocrinology and
SANDEEP GUPTA RICHARD J. FRANKEL MALCOLM J. BOYD
Cardiology,
Frimley Park Hospital, Frimley GU16 5UJ, UK
1. Hoad NA. Searching for hyperlipidaemia in patients with coronary artery bypass grafts. Lancet 1989; i: 968-69. 2. Fyfe T, Baxter RH, Cockran KM, et al. Plasma lipid changes afer myocardial infarction. Lancet 1971; ii: 997-1001. 3. Ryder REJ, Hayes TM, Mulligan IP, et al. How soon after myocardial infarction should plasma lipid values be assessed? Br Med J 1984; 289: 1651-53.
Structures of
and conscious
uraemia
SIR,—The presence of circulating "toxins" in patients with renal failure and their relation
to
protein catabolism and the
pathophysiology of uraemia have been subjects of intensive research and speculation for many years.’ The suggestion by Dr Vallance and colleagues (March 7, p 572) that derivatives of arginine might accumulate to produce a biological effect in these patients is
intriguing.
Metabolism of arginine (via the urea cycle) and creatinine leads to the production of the so-called uraemic toxins (guanidino compounds), of which methlyguanidine and
L-NMMA.
but found no change. There are several NO all based on arginine;6 presumably the full aminoacid structure is required for binding at the enzyme’s active site. Thus, it is likely that other methylguanidine derivatives, such as cimetidine and meobentine, which do not have the a-aminoacid structure, would also lack NO synthase inhibitor activity. If circulating endogenous inhibitors of NO production are important in the pathophysiology of uraemia, it seems paradoxical that L-NMMA can amelioriate the platelet defect and bleeding tendency associated with uraemia.7 Moreover, a relative deficiency of circulating arginine is not a consistent finding in renal failure.8 rats
synthase inhibitors,
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London W12
G. TAYLOR
Institute of Urology and Nephrology, UCMH Medical School, Middlesex Hospital, London W1 N 8AA, UK
R. UNWIN
Department of Clinical Pharmacology, Royal Postgraduate Medical School
M. WILKINS
Department of Paediatric Nephrology, Medical Faculty I, University of Naples, Naples, Italy
G. CAPASSO
May RC, Kelly RA, Mitch WE. Pathophysiology of uraemia. In: Brenner BM, Rector FC, eds. The kidney. Philadelphia: Saunders, 1991: 1997-2018. 2. Onta Y, Tsubakihara Y, Ando A, et al. Effect of arginine or creatinine administration on the urinary excretion of methylguanidine. Nephron 1978; 22: 328-36. 3. Yokozawa T, Fujitsuka N, Oura H. Studies on the precursor of methylguanidine in rats with renal failure. Nephron 1991; 58: 90-94. 4. Nakamura K, Ienaga K, Yokozawa T, et al. Production of methylguanidine from creatinine via creatol by active oxygen species: analyses of the catabolism in vivo. Nephron 1991; 58: 42-46. 5 Henneman H, Bloemertz B, Heidland A. Studies on natriuretic properties of methylguanidine. Res Exp Med 1972; 158: 58-65. 6. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991; 43: 109-42. 7. Remuzzi G, Penco N, Zoja C, et al. Role of endothelium-derived nitric oxide in the bleeding tendency of uremia. J Clin Invest 1990; 86: 1768-71. 8. De Deyn P, Marescau B, Lornoy W, et al. Guanindino compounds in uremic dialyzed patients. Clin Chim Acta 1986; 157: 143-50. 1.
Arginine derivatives and
methylguanidine and
