218
patient centred;3 there is a greater emphasis on team work; and people’s expectations of health care reflect more more
those of
consumers
than of the
recipients of largesse.
In
addition, public esteem for doctors seems to have diminished, whereas that for nurses and other health workers has increased substantially. Some of these forces may lie at the heart of the changing doctor-nurse relationship but they do not satisfactorily explain it, let alone account for the problems raised. Nor do they indicate a possible way forward. To do this one must look at other issues. Any interaction between people can be construed as a game,4even the relationship between doctors and nurses.5 The following example illustrates the point. Whilst it suits doctors to have nurses carry out their requests, nurses can be affronted by feeling their autonomy is constrained, so they initiate the treatment they would have wanted anyway but collude with their medical colleagues to maintain the belief it was the doctors’ decision all along. Games can help people cope with difficult situations, especially when there is something to be gained on both sides.4 However, usually someone loses, and the worry here is that it might be the patient. Moreover, if the game no longer satisfies one or both players it can no longer continue.6 At worst, it sometimes seems that with doctors and nurses the rules have been changed, the goal posts moved, the pitch invaded, people sent off for foul play, and someone has run off with the ball. Consequently the doctor-nurse game has had to be abandoned, leaving behind an eerie silence in the stadium. The changing doctor-nurse relationship can be reduced to a single issue—"roles"/ Some doctors, and many more nurses, are no longer doing what they did, and the people involved are ignorant of, misunderstand, or misconstrue the other person’s role or, even worse, make wrong assumptions about what they should be doing. As a result, the doctor may feel that the nurse is "never there", when in fact she is making a home visit, or is always "swanning off", whereas she is actually sitting on a national committee. Conversely, the nurse may think that the doctor does not take the patient’s feelings seriously but instead concentrates on a double-blind prospective study, or ignores team-building to concentrate on
on practice can initially appear highly We are not used to it, and our education, threatening. whether before or after registration, has not encouraged it. Very importantly, we have to learn to trust as well as to understand one another. This will take time, and there will be those who will see it as an unnecessary intrusion into an already busy schedule, but with commitment all round it can happen. What will be the benefits? There is evidence that patients respond favourably both physiologically and psychologically when allowed by health professionals to assume greater control of their illness,13 and there is even the suggestion that improved team working influences health outcomes positively.l4 Interpersonal relationships have also been shown to affect mortality rates of intensive care units. is Overall, however, there has been little research into the effects of professional relationships on health outcomes; such studies are much needed.
Reflection
1. Smith L. Doctors rule, OK? Nursing Times 1987; July 2: 49-51. 2. Nichols KA. Psychological care in physical illness, Beckenham: Croom Helm, 1984. 3. McWhinney I. The need for a trasformed clinical method. In: Stewart M, Roter D, eds. Communicating with medical patients, London: Sage, 1989: 25-40. 4. Berne E. Games people play. Harmondsworth: Penguin, 1964. 5. Stein, LI. The doctor-nurse game. Arch Gen Psychiatry 1967; 16: 699-703. 6. Stein LI, Watts DT, Howell T. The doctor-nurse game revisited. N Engl J Med 1990; 332; 8: 546-49. 7. Darbyshire P. The burden of history. Nursing Times 1987; Jan 28: 32-34. 8. Schon DA. The reflective practitioner, New York: Basic Books, 1983. 9. Coles CR. Self assessment and medical audit: an educational approach. Br Med J 1989; 299: 807-08. 10. Coles CR. Making audit truly educational. Postgrad Med J (in press). 11. General Medical Council. Recommendations on the training of specialists. London: GMC, 1987. 12. Greig DNH. Team work in general practice. Tunbridge Wells: Castle House, 1988. 13. Coles CR. Diabetes education: letting the patient into the picture. Pract Diabetes 1990; 7: 110-12. 14. Schmitt MH, Williams TF. Nurse-patient collaboration and outcomes for patients. Ann Intern Med 1985; 103: 956. 15. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. An evaluation of outcome from intensive care in major medical centres. Ann Intern Med 1986; 104: 410-18.
fund-raising.
that what is needed is better inter-professional communication. Of course it would, but how can this be made to happen? A more productive alternative would be for doctors and nurses to develop a greater sense of what has been termed "intimacy"-a relationship more rewarding than games. Put another way, health professionals should reflect on their practice.8 They should look together at what they do, learn from it, and if necessary change what they do and how they do it.9 They can make a start by describing their work to one another. Better still, they could present to their colleagues a video or audio recording of a consultation, an outpatient clinic, or a home visit. Then they need to engage in constructive criticism, in which the presenter identifies the strengths and weaknesses of his or her performance before others offer their opinion. Importantly, any negative criticism needs supporting evidence and realistic alternatives.1O Almost as a byproduct of this process of self-assessment and peer review," health professionals will get to know more about themselves and each other. Not only are they likely to come to understand their own role and that of others, but colleagues who until then had been working more or less independently could develop into a cohesive team.12 It would be trite
TOXIC EPIDERMAL NECROLYSIS— A PREMATURE REQUIEM?
to say
In 1956 Alan LyelP described four adults with a spontaneous eruption characterised by red, hot, peeling, tender skin; he called this syndrome toxic epidermal necrolysis (TEN). The condition subsequently became known as Lyell’s syndrome. The worst damage occurred in the epidermis, which showed severe necrosis; the peeling was due to either subepidermal or intra-epidermal splitting. LyelF introduced the term necrolysis to convey the idea of clinical epidermolysis with histological necrosis. A very similar syndrome was soon recognised in babies and children,3.4 but in these patients the longitudinal splitting of the epidermis always occurred just below the stratum
granulosum
and there
was
much less
epidermal
necrosis, so the term necrolysis was less appropriate. When further work showed that the syndrome in children was
always due to a circulating staphylococcal epidermolytic toxinthe disorder in this age group became known as the staphylococcal scalded skin syndrome (SSSS) to distinguish it from adult TEN. The adult syndrome is usually associated with a drug reaction or erythema multiforme; occasional cases are idiopathic or associated almost
219
lymphoma or a graft-versus-host reaction ;2 and staphylococci are very rarely responsible. Adult-type TEN associated with erythema multiforme or a drug reaction is occasionally encountered in children, unaccompanied by staphylococcal6 infection, but the two types are readily distinguished. The distinction between staphylococcal scalded skin syndrome and adult-type non-staphylococcal TEN has now been recognised by dermatologists for a decade, and the major textbooks accept the distinction. "Fitzpatrick" explicitly states that the designation toxic epidermal necrolysis excludes the staphylococcal scalded skin syndromeand "Rook" agrees that although in the past the terms have been used interchangeably, SSSS is now used for the staphylococcal induced disease and TEN is used for the adult form of unknown pathogenesis.8 Lye1l9 has now published what he calls a requiem for the term toxic epidermal necrolysis, on the grounds that his original four patients did not ultimately represent a single entity. But by 1979 he had already acknowledged that his original cases had been a mixed bag--one very rare adult SSSS, one drug-induced TEN, and two idiopathic2 (which he now believes were due to a generalised bullous fixed drug eruption, despite a negative drug history9). "The demise of TEN need occasion no regret", he declares, suggesting that the term should be replaced by "exanthematic necrolysis" or even "acute disseminated epidermal necrosis". Surely we should remind Dr Lyell of the laws relating to delayed with
infanticide. The term he fathered in 1956 may not have turned out exactly as he planned it at conception, but it has grown up to be a very useful 34-year-old. We can understand his desire for another baby neologism or two, but we cannot condone the killing of TEN. Lyell A. Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br J Dermatol 1965; 68: 355-61. 2. Lyell A. Toxic epidermal necrolysis (the scalded skin syndrome): a reappraisal. Br J Dermatol 1979; 100: 69-83. 3. Catto JVF. Toxic epidermal necrolysis occurring in a child. Br Med J 1.
1959; ii: 544. 4. Frain-Bell W, Koblenzer PJ. Two cases of toxic epidermal necrolysis. Proc R Soc Med 1959; 52: 1029. 5. Arbuthnott JP, Kent J, Lyell A, Gemmell CG. Toxic epidermal necrolysis produced by an extracellular product of Staphylococcus aureus. Br J Dermatol 1971; 85: 145-49. 6. Amon RB, Dimond RL. Toxic epidermal necrolysis: rapid differentiation between staphylococcal and drug-induced disease. Arch Dermatol 1975; 111: 1433-37. 7. Fritsch PO, Elias PM. Toxic epidermal necrolysis. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds. Dermatology in general medicine. 3rd ed. New York: McGraw-Hill, 1987: 563-67. 8. Pye RJ. Bullous eruptions. In: Rook A, Wilkinson DS, Ebling J, Champion RH, Burton JL, eds. Textbook of dermatology. 4th ed. Oxford: Blackwell, 1986: 1656-57. 9. Lyell A. Requiem for toxic epidermal necrolysis. Br J Dermatol 1990; 122: 837.
Na+-Ca2+ EXCHANGER AND CARDIAC CONTRACTION For the mammalian heart to beat at its normal rate the cellular processes that control contraction must function at remarkable speed with the potential to proceed even faster when the body is confronted by fear or disease. Ultimately muscle fibre shortening must be mediated by changes in the concentration of intracellular free calcium (Ca2 +). In cardiac tissue, excitation-contraction coupling is thought to involve the influx of Ca2 + channels in the plasma membrane (sarcolemma) to include Ca2 + release from the
pool stored in sarcoplasmic reticulum.’ However, this picture is too simple and overlooks the contributions that stem from changes in membrane voltage brought about by of other ions such as sodium. In this context the Na +-Ca2 + exchanger has lately aroused great interest. This protein uses the influx of Na + into the cell to extrude Ca2 +, in a ratio of three Nay to one Ca2 +, thereby generating an inward electrical current. But under certain conditions the direction of flow can be reversed-Ca2 + enters and Na + is extruded, so creating a net outward current.2 Whilst the existence of this exchanger has been recognised for some time, the alterations in free Ca2 + that it effects were thought to occur too slowly for it to have a role in the initiation of contraction. New work that has identified the exchanger as a rapid inward transporter of Ca2 + may alter this view. Leblanc and Hume3have shown that cardiac contraction is preceded by the entry of Na + through Na+ channels. As a result the Na+-Ca2+ exchanger is activated in its reverse mode to expel Na + and permit Ca2 + to enter the cell. The resulting rise in Ca2 + provokes further Ca2 + release from intracellular stores, but the overall rise in Na + required for this sequence of events to occur cannot be achieved in the time available. The only way the model will fit the physiological facts is for the entering Na + to be prevented from diffusing widely into the cytoplasm so that the local concentration rises sharply close to the inside of the sarcolemma. Although proof of this mechanism is lacking the notion may not be far-fetched: changes in the local concentrations of ions could be more important for normal cellular function and prevent the cell from being exposed to enormous fluctuations in overall electrolyte concentrations. Some data4 have emerged to substantiate this suggestion with respect to Ca2 +, and the development of fluorescent dyes sensitive to changes in free Na + may eventually help to show regional intracellular variations. These studies, although already challenged,5 give the Na + -Ca2 + exchanger a central role in the early events controlling contraction. More evidence has emerged that its role changes during the cardiac cycle. The findings of Bridge and co-workers6 in guineapig ventricular myocytes seem to suggest that both the Ca2 + admitted into the cell and that released from stores is ultimately extruded via the movements
Na+-Ca2+ exchanger. Thus,
as
repolarisation proceeds
and membrane voltage falls back, the exchanger is changing its operational direction and relaxation occurs. The findings also underline the primary role of Na + influx in the excitation-contraction process in cardiac muscle, and the Na + -Ca2 + exchanger assumes an important position in the control of intracellular Ca2+ in this tissue. These observations may be clinically relevant. The inotropic effects of cardiac glycosides have been attributedto the rise in Na +, which would stimulate Na + -Ca2 + exchange and consequently Ca2 + -induced Ca2 + release. The negative inotropic effects of some antiarrhythmic agents could be ascribed to their ability to block Na + channels, thereby reducing the Na + available to promote contraction.8 1. Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 1983; 245: C1-14. 2. Kimura J, Noma A, Irisawa H. Na-Ca exchange current in mammalian heart cells. Nature 1986; 319: 596-97. 3. Leblanc N, Hume JR. Sodium current-induced release of calcium from cardiac sarcoplasmic reticulum. Science 1990; 248: 372-76. 4. Erne P, Hermsmeyer K. Intracellular vascular muscle Ca2+ modulation in genetic hypertension. Hypertension 1989; 14: 145-51.
patient centred;3 there is a greater emphasis on team work; and people’s expectations of health care reflect more more
those of
consumers
than of the
recipients of largesse.
In
addition, public esteem for doctors seems to have diminished, whereas that for nurses and other health workers has increased substantially. Some of these forces may lie at the heart of the changing doctor-nurse relationship but they do not satisfactorily explain it, let alone account for the problems raised. Nor do they indicate a possible way forward. To do this one must look at other issues. Any interaction between people can be construed as a game,4even the relationship between doctors and nurses.5 The following example illustrates the point. Whilst it suits doctors to have nurses carry out their requests, nurses can be affronted by feeling their autonomy is constrained, so they initiate the treatment they would have wanted anyway but collude with their medical colleagues to maintain the belief it was the doctors’ decision all along. Games can help people cope with difficult situations, especially when there is something to be gained on both sides.4 However, usually someone loses, and the worry here is that it might be the patient. Moreover, if the game no longer satisfies one or both players it can no longer continue.6 At worst, it sometimes seems that with doctors and nurses the rules have been changed, the goal posts moved, the pitch invaded, people sent off for foul play, and someone has run off with the ball. Consequently the doctor-nurse game has had to be abandoned, leaving behind an eerie silence in the stadium. The changing doctor-nurse relationship can be reduced to a single issue—"roles"/ Some doctors, and many more nurses, are no longer doing what they did, and the people involved are ignorant of, misunderstand, or misconstrue the other person’s role or, even worse, make wrong assumptions about what they should be doing. As a result, the doctor may feel that the nurse is "never there", when in fact she is making a home visit, or is always "swanning off", whereas she is actually sitting on a national committee. Conversely, the nurse may think that the doctor does not take the patient’s feelings seriously but instead concentrates on a double-blind prospective study, or ignores team-building to concentrate on
on practice can initially appear highly We are not used to it, and our education, threatening. whether before or after registration, has not encouraged it. Very importantly, we have to learn to trust as well as to understand one another. This will take time, and there will be those who will see it as an unnecessary intrusion into an already busy schedule, but with commitment all round it can happen. What will be the benefits? There is evidence that patients respond favourably both physiologically and psychologically when allowed by health professionals to assume greater control of their illness,13 and there is even the suggestion that improved team working influences health outcomes positively.l4 Interpersonal relationships have also been shown to affect mortality rates of intensive care units. is Overall, however, there has been little research into the effects of professional relationships on health outcomes; such studies are much needed.
Reflection
1. Smith L. Doctors rule, OK? Nursing Times 1987; July 2: 49-51. 2. Nichols KA. Psychological care in physical illness, Beckenham: Croom Helm, 1984. 3. McWhinney I. The need for a trasformed clinical method. In: Stewart M, Roter D, eds. Communicating with medical patients, London: Sage, 1989: 25-40. 4. Berne E. Games people play. Harmondsworth: Penguin, 1964. 5. Stein, LI. The doctor-nurse game. Arch Gen Psychiatry 1967; 16: 699-703. 6. Stein LI, Watts DT, Howell T. The doctor-nurse game revisited. N Engl J Med 1990; 332; 8: 546-49. 7. Darbyshire P. The burden of history. Nursing Times 1987; Jan 28: 32-34. 8. Schon DA. The reflective practitioner, New York: Basic Books, 1983. 9. Coles CR. Self assessment and medical audit: an educational approach. Br Med J 1989; 299: 807-08. 10. Coles CR. Making audit truly educational. Postgrad Med J (in press). 11. General Medical Council. Recommendations on the training of specialists. London: GMC, 1987. 12. Greig DNH. Team work in general practice. Tunbridge Wells: Castle House, 1988. 13. Coles CR. Diabetes education: letting the patient into the picture. Pract Diabetes 1990; 7: 110-12. 14. Schmitt MH, Williams TF. Nurse-patient collaboration and outcomes for patients. Ann Intern Med 1985; 103: 956. 15. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. An evaluation of outcome from intensive care in major medical centres. Ann Intern Med 1986; 104: 410-18.
fund-raising.
that what is needed is better inter-professional communication. Of course it would, but how can this be made to happen? A more productive alternative would be for doctors and nurses to develop a greater sense of what has been termed "intimacy"-a relationship more rewarding than games. Put another way, health professionals should reflect on their practice.8 They should look together at what they do, learn from it, and if necessary change what they do and how they do it.9 They can make a start by describing their work to one another. Better still, they could present to their colleagues a video or audio recording of a consultation, an outpatient clinic, or a home visit. Then they need to engage in constructive criticism, in which the presenter identifies the strengths and weaknesses of his or her performance before others offer their opinion. Importantly, any negative criticism needs supporting evidence and realistic alternatives.1O Almost as a byproduct of this process of self-assessment and peer review," health professionals will get to know more about themselves and each other. Not only are they likely to come to understand their own role and that of others, but colleagues who until then had been working more or less independently could develop into a cohesive team.12 It would be trite
TOXIC EPIDERMAL NECROLYSIS— A PREMATURE REQUIEM?
to say
In 1956 Alan LyelP described four adults with a spontaneous eruption characterised by red, hot, peeling, tender skin; he called this syndrome toxic epidermal necrolysis (TEN). The condition subsequently became known as Lyell’s syndrome. The worst damage occurred in the epidermis, which showed severe necrosis; the peeling was due to either subepidermal or intra-epidermal splitting. LyelF introduced the term necrolysis to convey the idea of clinical epidermolysis with histological necrosis. A very similar syndrome was soon recognised in babies and children,3.4 but in these patients the longitudinal splitting of the epidermis always occurred just below the stratum
granulosum
and there
was
much less
epidermal
necrosis, so the term necrolysis was less appropriate. When further work showed that the syndrome in children was
always due to a circulating staphylococcal epidermolytic toxinthe disorder in this age group became known as the staphylococcal scalded skin syndrome (SSSS) to distinguish it from adult TEN. The adult syndrome is usually associated with a drug reaction or erythema multiforme; occasional cases are idiopathic or associated almost
219
lymphoma or a graft-versus-host reaction ;2 and staphylococci are very rarely responsible. Adult-type TEN associated with erythema multiforme or a drug reaction is occasionally encountered in children, unaccompanied by staphylococcal6 infection, but the two types are readily distinguished. The distinction between staphylococcal scalded skin syndrome and adult-type non-staphylococcal TEN has now been recognised by dermatologists for a decade, and the major textbooks accept the distinction. "Fitzpatrick" explicitly states that the designation toxic epidermal necrolysis excludes the staphylococcal scalded skin syndromeand "Rook" agrees that although in the past the terms have been used interchangeably, SSSS is now used for the staphylococcal induced disease and TEN is used for the adult form of unknown pathogenesis.8 Lye1l9 has now published what he calls a requiem for the term toxic epidermal necrolysis, on the grounds that his original four patients did not ultimately represent a single entity. But by 1979 he had already acknowledged that his original cases had been a mixed bag--one very rare adult SSSS, one drug-induced TEN, and two idiopathic2 (which he now believes were due to a generalised bullous fixed drug eruption, despite a negative drug history9). "The demise of TEN need occasion no regret", he declares, suggesting that the term should be replaced by "exanthematic necrolysis" or even "acute disseminated epidermal necrosis". Surely we should remind Dr Lyell of the laws relating to delayed with
infanticide. The term he fathered in 1956 may not have turned out exactly as he planned it at conception, but it has grown up to be a very useful 34-year-old. We can understand his desire for another baby neologism or two, but we cannot condone the killing of TEN. Lyell A. Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br J Dermatol 1965; 68: 355-61. 2. Lyell A. Toxic epidermal necrolysis (the scalded skin syndrome): a reappraisal. Br J Dermatol 1979; 100: 69-83. 3. Catto JVF. Toxic epidermal necrolysis occurring in a child. Br Med J 1.
1959; ii: 544. 4. Frain-Bell W, Koblenzer PJ. Two cases of toxic epidermal necrolysis. Proc R Soc Med 1959; 52: 1029. 5. Arbuthnott JP, Kent J, Lyell A, Gemmell CG. Toxic epidermal necrolysis produced by an extracellular product of Staphylococcus aureus. Br J Dermatol 1971; 85: 145-49. 6. Amon RB, Dimond RL. Toxic epidermal necrolysis: rapid differentiation between staphylococcal and drug-induced disease. Arch Dermatol 1975; 111: 1433-37. 7. Fritsch PO, Elias PM. Toxic epidermal necrolysis. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds. Dermatology in general medicine. 3rd ed. New York: McGraw-Hill, 1987: 563-67. 8. Pye RJ. Bullous eruptions. In: Rook A, Wilkinson DS, Ebling J, Champion RH, Burton JL, eds. Textbook of dermatology. 4th ed. Oxford: Blackwell, 1986: 1656-57. 9. Lyell A. Requiem for toxic epidermal necrolysis. Br J Dermatol 1990; 122: 837.
Na+-Ca2+ EXCHANGER AND CARDIAC CONTRACTION For the mammalian heart to beat at its normal rate the cellular processes that control contraction must function at remarkable speed with the potential to proceed even faster when the body is confronted by fear or disease. Ultimately muscle fibre shortening must be mediated by changes in the concentration of intracellular free calcium (Ca2 +). In cardiac tissue, excitation-contraction coupling is thought to involve the influx of Ca2 + channels in the plasma membrane (sarcolemma) to include Ca2 + release from the
pool stored in sarcoplasmic reticulum.’ However, this picture is too simple and overlooks the contributions that stem from changes in membrane voltage brought about by of other ions such as sodium. In this context the Na +-Ca2 + exchanger has lately aroused great interest. This protein uses the influx of Na + into the cell to extrude Ca2 +, in a ratio of three Nay to one Ca2 +, thereby generating an inward electrical current. But under certain conditions the direction of flow can be reversed-Ca2 + enters and Na + is extruded, so creating a net outward current.2 Whilst the existence of this exchanger has been recognised for some time, the alterations in free Ca2 + that it effects were thought to occur too slowly for it to have a role in the initiation of contraction. New work that has identified the exchanger as a rapid inward transporter of Ca2 + may alter this view. Leblanc and Hume3have shown that cardiac contraction is preceded by the entry of Na + through Na+ channels. As a result the Na+-Ca2+ exchanger is activated in its reverse mode to expel Na + and permit Ca2 + to enter the cell. The resulting rise in Ca2 + provokes further Ca2 + release from intracellular stores, but the overall rise in Na + required for this sequence of events to occur cannot be achieved in the time available. The only way the model will fit the physiological facts is for the entering Na + to be prevented from diffusing widely into the cytoplasm so that the local concentration rises sharply close to the inside of the sarcolemma. Although proof of this mechanism is lacking the notion may not be far-fetched: changes in the local concentrations of ions could be more important for normal cellular function and prevent the cell from being exposed to enormous fluctuations in overall electrolyte concentrations. Some data4 have emerged to substantiate this suggestion with respect to Ca2 +, and the development of fluorescent dyes sensitive to changes in free Na + may eventually help to show regional intracellular variations. These studies, although already challenged,5 give the Na + -Ca2 + exchanger a central role in the early events controlling contraction. More evidence has emerged that its role changes during the cardiac cycle. The findings of Bridge and co-workers6 in guineapig ventricular myocytes seem to suggest that both the Ca2 + admitted into the cell and that released from stores is ultimately extruded via the movements
Na+-Ca2+ exchanger. Thus,
as
repolarisation proceeds
and membrane voltage falls back, the exchanger is changing its operational direction and relaxation occurs. The findings also underline the primary role of Na + influx in the excitation-contraction process in cardiac muscle, and the Na + -Ca2 + exchanger assumes an important position in the control of intracellular Ca2+ in this tissue. These observations may be clinically relevant. The inotropic effects of cardiac glycosides have been attributedto the rise in Na +, which would stimulate Na + -Ca2 + exchange and consequently Ca2 + -induced Ca2 + release. The negative inotropic effects of some antiarrhythmic agents could be ascribed to their ability to block Na + channels, thereby reducing the Na + available to promote contraction.8 1. Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 1983; 245: C1-14. 2. Kimura J, Noma A, Irisawa H. Na-Ca exchange current in mammalian heart cells. Nature 1986; 319: 596-97. 3. Leblanc N, Hume JR. Sodium current-induced release of calcium from cardiac sarcoplasmic reticulum. Science 1990; 248: 372-76. 4. Erne P, Hermsmeyer K. Intracellular vascular muscle Ca2+ modulation in genetic hypertension. Hypertension 1989; 14: 145-51.
