- Email: [email protected]
Relation between endothelial-cell activation and infection, inflammation, and infarction
THE LANCET
aldosterone and plasma renin activity (PRA) were 646 pmol/L and 2·0 ng mL⫺1 h⫺1, respectively (measured after 12 h in supine position). 4 days after enoxaparin had been discontinued, her serum concentration of aldosterone had increased to 747 pmol/L and PRA had decreased to 0·8 ng mL⫺1 h⫺1. This patient was subsequently discharged, but was readmitted 2 weeks later because of pneumonia and dehydration. Although her initial response to therapy was good, she remained immobile; after 10 days it was decided that low-dose enoxaparin was warranted. Her mean serum concentration of potassium during the week before administration of enoxaparin was 4·85 mmol/L. 2 days after rechallenge with enoxaparin serum potassium rose to 5·4 mmol/L and remained above 5 mmol/L until treatment with calcium polysterene sulphonate was started 3 days later. Her serum concentration of aldosterone before enoxaparin was 611 pmol/L and PRA was <0·2 ng mL⫺1 h⫺1. After 9 days of enoxaparin therapy, serum aldosterone remained similar (615 pmol/L) but PRA increased (1·5 ng mL⫺1 h⫺1). This case shows that low-dose, lowmolecular-weight heparin can cause clinically important hyperkalaemia even when the baseline serum concentration of potassium is well below 5 mmol/L. Heparin-induced hyperkalaemia is most likely in patients with chronic renal failure or diabetes, or during concomitant administration of drugs which affect potassium balance, such as angiotensin-converting-enzyme inhibitors.2 Previous reports indicate that low-dose unfractionated heparin has resulted in serum concentrations of potassium of more than 6 mmol/L in patients with one or more of the above risk factors.3–5 We suggest that serum potassium should be monitored in all patients during treatment with lowdose heparin, either unfractionated or of low molecular weight, particularly in those at risk of hyperkalaemia, irrespective of the initial potassium concentration. *M I Wiggam, T R O Beringer Department of Health Care for the Elderly, Royal Victoria Hospital, Belfast BT12 6BA, UK
1
2
3
4
5
Canova CR, Fischler MP, Reinhart WH. Effect of low-molecular-weight heparin on serum potassium. Lancet 1997; 349: 1447–48. Oster JR, Singer I, Fishman LM. Heparininduced aldosterone suppression and hyperkalemia. Am J Med 1995; 98: 575–86. Edes TE, Sunderajan EV. Heparin-induced hyperkalemia. Arch Intern Med 1985; 145: 1070–72. Busch EH, Ventura HO, Lavie CJ. Heparininduced hyperkalemia. South Med J 1987; 80: 1450–51. Edes TE. Heparin-induced hyperkalemia. Postgrad Med 1990; 87: 104–05.
Vol 350 • July 26, 1997
Relation between endothelial-cell activation and infection, inflammation, and infarction SIR—Patrick Vallance and colleagues (May 10, p 1391)1 postulate that acute infection or inflammation increased the risk of acute cardiovascular events by causing endothelial-cell dysfunction. The changes they describe, however, are recognised as those of endothelialcell activation. Pober2 described how stimulation of the endothelium by certain agents such as interleukin-1 resulted in a series of changes to the endothelium allowing it to participate in the inflammatory response. To emphasise that this process did not represent sublethal injury with consequent dysfunction, Pober used the term endothelial-cell activation (ECA) to describe these events, which has now become widely accepted. ECA can be induced by a wide range of agents, for example, certain bacteria, viruses, and cytokines such as interleukin-1 and tumour necrosis factor, physical and oxidative stress, oxidised low density lipoproteins, immune complexes, and B and T cell activation. It may have a central pathophysiological role in many conditions including atherosclerosis, diabetes, the systemic inflammatory response syndrome, ischaemia/ reperfusion injury, transplant rejection, and the vasculitides. The five core changes of ECA are: loss of vascular integrity; expression of leucocyte adhesion molecules;3 change in phenotype from antithrombotic to prothrombotic; cytokine production; and upregulation of HLA molecules. There are two stages of ECA. The first, endothelial-cell stimulation, or ECA type I, does not require de novo protein synthesis of gene upregulation and occurs in seconds. Effects include the retraction of endothelial cell from one another, expression of P-selectin, and release of von Willebrand factor. The second response, ECA type II, requires hours for the stimulating agent to cause an effect through gene transcription and then protein synthesis. The genes include those for E-selectin, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, proinflammatory cytokines including interleukin-6 (thus potentially regulating the acute phase response), and inducible nitric oxide synthetase. We agree with Vallance and colleagues that clinical studies in defined groups of patients are required to test the hypothesis that ECA due to acute infection or inflammation may be a risk factor for cardiovascular disease. As yet the story is incomplete, since
some mechanisms of ECA have only been observed in vitro or in animal models. The diverse effects of ECA have been shown to share a common intracellular control mechanism through the activation of the transcription factor nuclear factor B(NF-B). Some of the antiinflammatory effects of glucocorticoids4 and aspirin,5 the same agents that Vallance et al say give protection against temporary ECA, have been shown to act through the inhibition of NF-B. As a transcriptional activator of the genes of ECA, NF-B itself is an ideal target. Fundamental approaches to switching off NF-B are being explored. *Beverley J Hunt, Karen M Jurd Department of Haematology, St Thomas’ Hospital, London SE1 7EH, UK
1
2
3
4 5
Vallance P, Collier J, Bhagat K. Infection, inflammation and infarction: does acute endothelial cell dysfunction provide a link? Lancet 1997; 349: 1391–92. Pober JS. Cytokine-mediated activation of vascular endothelium. Am J Pathol 1988; 133: 426–33. Adams DH, Shaw S. Leucocyte-endothelial interactions and regulation of leucocyte migration. Lancet 1994; 343: 831–36. Marx J. How the glucocorticoids suppress immunity. Science 1995; 270: 232–33. Kopp E, Ghosh S. Inhibition of NF-B by sodium salicylate and aspirin. Science 1994; 265: 956–59.
SIR—Patrick Vallance and colleagues 1 suggest a link between the clinical symptoms of cardiovascular disease, such as angina, and endothelial-cell dysfunction, focusing on the loss of control of vasodilation mediated by substances such as nitric oxide. They briefly ask how might inflammation or infection alter the risk associated with atheroma, including the alteration of clotting factors such as fibrinogen. We believe that the alternative aspect of the physiology of the endothelium—ie, its role in thrombosis and haemostasis—is of equal, if not greater, importance. In addition to its vasomotor function, the endothelial cell is important in the regulation of blood clotting, for example, the production of prostacyclin, coagulation factor V, tissue plasminogen activator, and von Willebrand factor. Furthermore, the endothelial cell membrane component, thrombomodulin, affects the biology of thrombin and the anticoagulant protein C.2 In addition to fibrinogen, some endothelial products have prognostic value in cardiovascular disease and stroke. Epidemiological studies indicate that increased concentrations of tissue plasminogen activator and von Willebrand factor both predict adverse cardiovascular
293
THE LANCET
outcomes (stroke and myocardial infarction).3 Although von Willebrand factor is regarded mainly as a specific marker of endothelial-cell damage, it is also an acute phase reactant (providing a link with infection), and is increased by risk factors such as smoking. By virtue of binding sites/epitopes for platelet membrane components gpIIb/IIIa and gpIb, and matrix constituents such as collagen and vitronectin, von Willebrand factor has the capacity to promote platelet aggregation and platelet adhesion to the subendothelium.4 Increased concentrations of soluble thrombomodulin in patients with ischaemic heart disease and peripheral arterial disease also imply loss of vascular integrity, and its failure to respond to proinflammatory cytokines provide an interesting contrast to von Willebrand factor. Loss of membranebound anticoagulant thrombomodulin and the appearance of fragmented, inactive, soluble thrombomodulin in the plasma is also likely to promote thrombus formation by increasing the half life of thrombin and reducing the activity of protein C.4,5 Although loss of vasomotor control by the endothelium can certainly carry with it undesirable clinical consequences, most patients with cardiovascular disease will die prematurely or suffer increased morbidity or arterial surgery, as a result of loss of haemostasis—ie, of thrombosis. We suggest that the measurement of markers such as von Willebrand factor and soluble thrombomodulin to assess endothelialcell damage is likely to provide valuable new tools for vascular biologists and clinicians with an interest in cardiovascular disease. *Andrew D Blann, Gregory Y H Lip Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, The City Hospital, Birmingham B18 7QH, UK
1
2
3
4
5
Vallance P, Collier J, Bhagat K. Infection, inflammation and infarction: does acute endothelial dysfunction provide a link. Lancet 1997; 349: 1391–92. Pearson JD. Vessel wall interactions regulating thrombosis. Br Med Bull 1994; 50: 776–88. Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo J, for the ECAT. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635–41. Blann AD, Taberner DA. A reliable marker of endothelial cell dysfunction: does it exist? Br J Haematol 1995; 90: 244–48. Boffa MC. Considering cellular thrombomodulin distribution and its modulating factors can facilitate the use of plasma thrombomodulin as a reliable endothelial marker. Haemostasis 1996; 26 (suppl 4): 233–43.
294
Tick toxicant SIR—Steven Schutzer (June 7, p 1668)1 describes how exposure to Lyme disease can be kept to a minimum by recognition and avoidance of high-risk areas. I have observed deer trails, the nearby stream, the ground cover and wooded area, the bird seed in feeders, and the tell-tale signs of white-footed mice in the 2-acre plot on which my house stands. As you know, Monmouth County, New Jersey, is a high-risk area. Avoidance is a possible solution. Prevention was what I was hoping for. If white-footed mice are the predominant maintenance and reservoir for Borrelia burgdorferi, would a tick toxicant, placed in mouse-nesting material and housed in a biodegradable cardboard tube which could be deployed where mice reside, suffice? Such a product was developed by Harvard Medical School. Its active ingredient is permethrin and it is commercially available (Eco Health Inc, Boston, MA, USA). This product is designed to eliminate spring nymphal ticks and summer hatched larval ticks. If individual home owners use this product it may solve their problem. If a community effort were made, perhaps our county could enjoy the outdoors again. Ellyse Stanislow Pacific Institute of Oriental Medicine, New York, New York 10010, USA
1
Schutzer SE. Reduction of Lyme disease exposure by recognition and avoidance of high-risk areas. Lancet 1997; 349: 1668.
Different criteria for pharmacological and surgical treatment of hypertension S IR —The goal of antihypertensive therapy is to reduce cardiovascular risk. Since excessive lowering of blood pressure may actually increase the frequency of cardiovascular complications, the adage in pharmacological treatment of hypertension is to start with low doses and to increase doses only after a long time to avoid rapid lowering of blood pressure. By contrast, a rapid fall in blood pressure after surgical treatment of renovascular hypertension—a disease which in twothirds of patients is caused by atherosclerotic disease—is viewed as a success of this operation. At present, there are no guidelines for the management of this postoperative lowering of blood pressure.
We report a 48-year-old man with a history of severe hypertension (210/124 mm Hg). Despite antihypertensive treatment, his blood pressure remained high (190/114 mm Hg). A left renalartery stenosis was diagnosed and surgical treatment was planned. On the day of surgery, antihypertensives were stopped and a renal-artery reconstruction with a femoral-artery patch was carried out. During surgery, blood pressure was kept stable at 160/80 mm Hg, and fluids and dopamine were administered guided by arterial blood pressure and filling pressures, obtained by a pulmonary artery catheter. This treatment, aimed at preventing a rapid fall in blood pressure, was continued after the operation during his stay in the intensive-care unit. In the first 24 h after surgery, his blood pressure was about 140/70 mm Hg, and his heart rate (sinus rhythm) was stable. No abnormalities were found on physical and neurological examination. 1 day after surgery, he was transferred to the nursing ward. 4 h later, a right-sided hemiparesis with aphasia was diagnosed, at which time his blood pressure was 144/70 mm Hg. Computed-tomography scanning showed an extensive cerebral infarction of the left arteria cerebri media area. Doppler scanning revealed a total occlusion of the left internal carotid artery. His neurological condition did not improve in the following weeks and he had to be transferred to a nursing home. In this group of atherosclerotic patients, the rapid fall in blood pressure after renovascular surgery can have risks, as described above. It is remarkable that no attention is paid to the “go low, go slow” approach in the lowering of blood pressure by renovascular surgery, especially since this type of surgery is meant to prevent cerebrovascular events. Guidelines are needed, first for preoperative diagnostic procedures (Duplex imaging) to identify patients at high risk of this complication, and second for treatment of blood pressure to prevent adverse cerebral outcomes. Furthermore, should we not aim for long-term pharmaceutical normalisation of blood pressure before surgery or, if this is inappropriate, consider long-term treatment to increase blood pressure after surgery in order to lower blood pressure more gradually and thereby keep to a minimum the risk of cerebrovascular events? *J J M Ligtenberg, A R J Girbes Intensive Care and Respiratory Unit and Surgical Intensive Care Unit, Groningen University Hospital, PO Box 30-001, NL-9700 RB Groningen, Netherlands
1
Oparil S. Arterial hypertension. In:
Vol 350 • July 26, 1997
aldosterone and plasma renin activity (PRA) were 646 pmol/L and 2·0 ng mL⫺1 h⫺1, respectively (measured after 12 h in supine position). 4 days after enoxaparin had been discontinued, her serum concentration of aldosterone had increased to 747 pmol/L and PRA had decreased to 0·8 ng mL⫺1 h⫺1. This patient was subsequently discharged, but was readmitted 2 weeks later because of pneumonia and dehydration. Although her initial response to therapy was good, she remained immobile; after 10 days it was decided that low-dose enoxaparin was warranted. Her mean serum concentration of potassium during the week before administration of enoxaparin was 4·85 mmol/L. 2 days after rechallenge with enoxaparin serum potassium rose to 5·4 mmol/L and remained above 5 mmol/L until treatment with calcium polysterene sulphonate was started 3 days later. Her serum concentration of aldosterone before enoxaparin was 611 pmol/L and PRA was <0·2 ng mL⫺1 h⫺1. After 9 days of enoxaparin therapy, serum aldosterone remained similar (615 pmol/L) but PRA increased (1·5 ng mL⫺1 h⫺1). This case shows that low-dose, lowmolecular-weight heparin can cause clinically important hyperkalaemia even when the baseline serum concentration of potassium is well below 5 mmol/L. Heparin-induced hyperkalaemia is most likely in patients with chronic renal failure or diabetes, or during concomitant administration of drugs which affect potassium balance, such as angiotensin-converting-enzyme inhibitors.2 Previous reports indicate that low-dose unfractionated heparin has resulted in serum concentrations of potassium of more than 6 mmol/L in patients with one or more of the above risk factors.3–5 We suggest that serum potassium should be monitored in all patients during treatment with lowdose heparin, either unfractionated or of low molecular weight, particularly in those at risk of hyperkalaemia, irrespective of the initial potassium concentration. *M I Wiggam, T R O Beringer Department of Health Care for the Elderly, Royal Victoria Hospital, Belfast BT12 6BA, UK
1
2
3
4
5
Canova CR, Fischler MP, Reinhart WH. Effect of low-molecular-weight heparin on serum potassium. Lancet 1997; 349: 1447–48. Oster JR, Singer I, Fishman LM. Heparininduced aldosterone suppression and hyperkalemia. Am J Med 1995; 98: 575–86. Edes TE, Sunderajan EV. Heparin-induced hyperkalemia. Arch Intern Med 1985; 145: 1070–72. Busch EH, Ventura HO, Lavie CJ. Heparininduced hyperkalemia. South Med J 1987; 80: 1450–51. Edes TE. Heparin-induced hyperkalemia. Postgrad Med 1990; 87: 104–05.
Vol 350 • July 26, 1997
Relation between endothelial-cell activation and infection, inflammation, and infarction SIR—Patrick Vallance and colleagues (May 10, p 1391)1 postulate that acute infection or inflammation increased the risk of acute cardiovascular events by causing endothelial-cell dysfunction. The changes they describe, however, are recognised as those of endothelialcell activation. Pober2 described how stimulation of the endothelium by certain agents such as interleukin-1 resulted in a series of changes to the endothelium allowing it to participate in the inflammatory response. To emphasise that this process did not represent sublethal injury with consequent dysfunction, Pober used the term endothelial-cell activation (ECA) to describe these events, which has now become widely accepted. ECA can be induced by a wide range of agents, for example, certain bacteria, viruses, and cytokines such as interleukin-1 and tumour necrosis factor, physical and oxidative stress, oxidised low density lipoproteins, immune complexes, and B and T cell activation. It may have a central pathophysiological role in many conditions including atherosclerosis, diabetes, the systemic inflammatory response syndrome, ischaemia/ reperfusion injury, transplant rejection, and the vasculitides. The five core changes of ECA are: loss of vascular integrity; expression of leucocyte adhesion molecules;3 change in phenotype from antithrombotic to prothrombotic; cytokine production; and upregulation of HLA molecules. There are two stages of ECA. The first, endothelial-cell stimulation, or ECA type I, does not require de novo protein synthesis of gene upregulation and occurs in seconds. Effects include the retraction of endothelial cell from one another, expression of P-selectin, and release of von Willebrand factor. The second response, ECA type II, requires hours for the stimulating agent to cause an effect through gene transcription and then protein synthesis. The genes include those for E-selectin, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, proinflammatory cytokines including interleukin-6 (thus potentially regulating the acute phase response), and inducible nitric oxide synthetase. We agree with Vallance and colleagues that clinical studies in defined groups of patients are required to test the hypothesis that ECA due to acute infection or inflammation may be a risk factor for cardiovascular disease. As yet the story is incomplete, since
some mechanisms of ECA have only been observed in vitro or in animal models. The diverse effects of ECA have been shown to share a common intracellular control mechanism through the activation of the transcription factor nuclear factor B(NF-B). Some of the antiinflammatory effects of glucocorticoids4 and aspirin,5 the same agents that Vallance et al say give protection against temporary ECA, have been shown to act through the inhibition of NF-B. As a transcriptional activator of the genes of ECA, NF-B itself is an ideal target. Fundamental approaches to switching off NF-B are being explored. *Beverley J Hunt, Karen M Jurd Department of Haematology, St Thomas’ Hospital, London SE1 7EH, UK
1
2
3
4 5
Vallance P, Collier J, Bhagat K. Infection, inflammation and infarction: does acute endothelial cell dysfunction provide a link? Lancet 1997; 349: 1391–92. Pober JS. Cytokine-mediated activation of vascular endothelium. Am J Pathol 1988; 133: 426–33. Adams DH, Shaw S. Leucocyte-endothelial interactions and regulation of leucocyte migration. Lancet 1994; 343: 831–36. Marx J. How the glucocorticoids suppress immunity. Science 1995; 270: 232–33. Kopp E, Ghosh S. Inhibition of NF-B by sodium salicylate and aspirin. Science 1994; 265: 956–59.
SIR—Patrick Vallance and colleagues 1 suggest a link between the clinical symptoms of cardiovascular disease, such as angina, and endothelial-cell dysfunction, focusing on the loss of control of vasodilation mediated by substances such as nitric oxide. They briefly ask how might inflammation or infection alter the risk associated with atheroma, including the alteration of clotting factors such as fibrinogen. We believe that the alternative aspect of the physiology of the endothelium—ie, its role in thrombosis and haemostasis—is of equal, if not greater, importance. In addition to its vasomotor function, the endothelial cell is important in the regulation of blood clotting, for example, the production of prostacyclin, coagulation factor V, tissue plasminogen activator, and von Willebrand factor. Furthermore, the endothelial cell membrane component, thrombomodulin, affects the biology of thrombin and the anticoagulant protein C.2 In addition to fibrinogen, some endothelial products have prognostic value in cardiovascular disease and stroke. Epidemiological studies indicate that increased concentrations of tissue plasminogen activator and von Willebrand factor both predict adverse cardiovascular
293
THE LANCET
outcomes (stroke and myocardial infarction).3 Although von Willebrand factor is regarded mainly as a specific marker of endothelial-cell damage, it is also an acute phase reactant (providing a link with infection), and is increased by risk factors such as smoking. By virtue of binding sites/epitopes for platelet membrane components gpIIb/IIIa and gpIb, and matrix constituents such as collagen and vitronectin, von Willebrand factor has the capacity to promote platelet aggregation and platelet adhesion to the subendothelium.4 Increased concentrations of soluble thrombomodulin in patients with ischaemic heart disease and peripheral arterial disease also imply loss of vascular integrity, and its failure to respond to proinflammatory cytokines provide an interesting contrast to von Willebrand factor. Loss of membranebound anticoagulant thrombomodulin and the appearance of fragmented, inactive, soluble thrombomodulin in the plasma is also likely to promote thrombus formation by increasing the half life of thrombin and reducing the activity of protein C.4,5 Although loss of vasomotor control by the endothelium can certainly carry with it undesirable clinical consequences, most patients with cardiovascular disease will die prematurely or suffer increased morbidity or arterial surgery, as a result of loss of haemostasis—ie, of thrombosis. We suggest that the measurement of markers such as von Willebrand factor and soluble thrombomodulin to assess endothelialcell damage is likely to provide valuable new tools for vascular biologists and clinicians with an interest in cardiovascular disease. *Andrew D Blann, Gregory Y H Lip Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, The City Hospital, Birmingham B18 7QH, UK
1
2
3
4
5
Vallance P, Collier J, Bhagat K. Infection, inflammation and infarction: does acute endothelial dysfunction provide a link. Lancet 1997; 349: 1391–92. Pearson JD. Vessel wall interactions regulating thrombosis. Br Med Bull 1994; 50: 776–88. Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo J, for the ECAT. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635–41. Blann AD, Taberner DA. A reliable marker of endothelial cell dysfunction: does it exist? Br J Haematol 1995; 90: 244–48. Boffa MC. Considering cellular thrombomodulin distribution and its modulating factors can facilitate the use of plasma thrombomodulin as a reliable endothelial marker. Haemostasis 1996; 26 (suppl 4): 233–43.
294
Tick toxicant SIR—Steven Schutzer (June 7, p 1668)1 describes how exposure to Lyme disease can be kept to a minimum by recognition and avoidance of high-risk areas. I have observed deer trails, the nearby stream, the ground cover and wooded area, the bird seed in feeders, and the tell-tale signs of white-footed mice in the 2-acre plot on which my house stands. As you know, Monmouth County, New Jersey, is a high-risk area. Avoidance is a possible solution. Prevention was what I was hoping for. If white-footed mice are the predominant maintenance and reservoir for Borrelia burgdorferi, would a tick toxicant, placed in mouse-nesting material and housed in a biodegradable cardboard tube which could be deployed where mice reside, suffice? Such a product was developed by Harvard Medical School. Its active ingredient is permethrin and it is commercially available (Eco Health Inc, Boston, MA, USA). This product is designed to eliminate spring nymphal ticks and summer hatched larval ticks. If individual home owners use this product it may solve their problem. If a community effort were made, perhaps our county could enjoy the outdoors again. Ellyse Stanislow Pacific Institute of Oriental Medicine, New York, New York 10010, USA
1
Schutzer SE. Reduction of Lyme disease exposure by recognition and avoidance of high-risk areas. Lancet 1997; 349: 1668.
Different criteria for pharmacological and surgical treatment of hypertension S IR —The goal of antihypertensive therapy is to reduce cardiovascular risk. Since excessive lowering of blood pressure may actually increase the frequency of cardiovascular complications, the adage in pharmacological treatment of hypertension is to start with low doses and to increase doses only after a long time to avoid rapid lowering of blood pressure. By contrast, a rapid fall in blood pressure after surgical treatment of renovascular hypertension—a disease which in twothirds of patients is caused by atherosclerotic disease—is viewed as a success of this operation. At present, there are no guidelines for the management of this postoperative lowering of blood pressure.
We report a 48-year-old man with a history of severe hypertension (210/124 mm Hg). Despite antihypertensive treatment, his blood pressure remained high (190/114 mm Hg). A left renalartery stenosis was diagnosed and surgical treatment was planned. On the day of surgery, antihypertensives were stopped and a renal-artery reconstruction with a femoral-artery patch was carried out. During surgery, blood pressure was kept stable at 160/80 mm Hg, and fluids and dopamine were administered guided by arterial blood pressure and filling pressures, obtained by a pulmonary artery catheter. This treatment, aimed at preventing a rapid fall in blood pressure, was continued after the operation during his stay in the intensive-care unit. In the first 24 h after surgery, his blood pressure was about 140/70 mm Hg, and his heart rate (sinus rhythm) was stable. No abnormalities were found on physical and neurological examination. 1 day after surgery, he was transferred to the nursing ward. 4 h later, a right-sided hemiparesis with aphasia was diagnosed, at which time his blood pressure was 144/70 mm Hg. Computed-tomography scanning showed an extensive cerebral infarction of the left arteria cerebri media area. Doppler scanning revealed a total occlusion of the left internal carotid artery. His neurological condition did not improve in the following weeks and he had to be transferred to a nursing home. In this group of atherosclerotic patients, the rapid fall in blood pressure after renovascular surgery can have risks, as described above. It is remarkable that no attention is paid to the “go low, go slow” approach in the lowering of blood pressure by renovascular surgery, especially since this type of surgery is meant to prevent cerebrovascular events. Guidelines are needed, first for preoperative diagnostic procedures (Duplex imaging) to identify patients at high risk of this complication, and second for treatment of blood pressure to prevent adverse cerebral outcomes. Furthermore, should we not aim for long-term pharmaceutical normalisation of blood pressure before surgery or, if this is inappropriate, consider long-term treatment to increase blood pressure after surgery in order to lower blood pressure more gradually and thereby keep to a minimum the risk of cerebrovascular events? *J J M Ligtenberg, A R J Girbes Intensive Care and Respiratory Unit and Surgical Intensive Care Unit, Groningen University Hospital, PO Box 30-001, NL-9700 RB Groningen, Netherlands
1
Oparil S. Arterial hypertension. In:
Vol 350 • July 26, 1997