Annotations
D. B., Steed, G. R., Thorne, M. G., Jones, S., Guerrier, C. J., Eraut, C. D., McHugh, P. M., Chowdhury, N. R., Jafary, M. H., and Wallace, T. J.: Acute myocardial infarction: Home and hospital treatment, Br. Med. J. 3:334, 1971. 3. Hampton, J. R., Morris, G. K., and Mason, C.: Survey of
general practitioners' attitudes to management of patients with heart attacks, Br. Med. J. 4:146, 1975. Hayes, M. J , Morris, G. K., and Hampton, J. R.: Comparison of mobilisati0n after two and nine days in uncomplicated myocardial infarction, Br. Med. J. 3:10, 1974.
Of the conduction system and myocardial function
Physicians, as well as physiologists, fail to realize t h a t the time course of contraction of all portions of the myocardium is extremely important for efficient and effective emptying of the ventricle. For example, if the outflow tract of the right or left ventricle were to contract first in the cardiac cycle, the outlet of the ventricles would be sphincterally partially closed to some degree, thus impairing outflow and emptying o f bloodl But, this does not occur in normal hearts because the electric impulse which initiates ventricular contraction is delivered to the septal and apical regions of the heart first and to the bases last. The order of activation of t h e myocardium depends upon the anatomic distribution and function of the conduction tissue of the heart. Thus, the order of ventricular myocardial contraction is predetermined by the order of ventricular myocardial depolarization or electric activation. The order of electric activation is genetically and developmentally determined in utero. When this is entirely normal, ventricular .myocardial pumping function is normal and orderly in its time course. We h a v e found two normal patterns of order of time course of ventricular activation or depolarization displayed in the spatial vectorcardiogram. 1 When the order of electric activation or time course Of depolarization of the myocardium is disordered, ventricular contraction becomes disordered and, in turn, myocardial function is disturbed. The ventricle becomes less efficient and less effective, which can lead to clinically recognizable diseased cardiac states. For example, with R B B B and LBBB the order of ventricular myocardial contraction is definitely abnormal. It is even more abnormal or more disordered when disease of the Purkinje network or arborization block or defective intraventricular conduction (defective I.V.C.) is present. The order is abnormal when artificial pacemakers are driving the heart. Such disturbance in the order of ventricular
depolarization could conceivably occur on a congenital basis with abnormal anatomic distribution or function of the Purkinje network, or because of anatomic or morphologic disease, a n d / o r on a purely functional basis, or in therapy as with the use of a pacemaker. This would lead to dysfunction of the myocardial and systolic ven~ricular contraction and ejection. In fact. such a mechanism could readily explain the development of subaortic or subpulmonic {crista supraventricularis hypertrophy) hypertrophic obstruction. If these outflow tract areas were depolarized early in the cardiac cycle, "work" hypertrophy would occur initially and myocardial degeneration or disease would develop later. Such disordered activation could produce t h e hemodynamlc manifestations described for ventricular outflow obstruction due to hypertrophic subaortic stenosis or crista supraventricularis hypertrophy. One can readily imagine the multitude of myocardial dysfunctional states t h a t could follow different disturbances in the order of electric activation of the myocardium regardless of the conceivable causes, i.e.. genetic, developmental, morphologic, therapeutic, a n d / o r functional. It is impressive how orderly the time course of electric activation is in people. all predetermined by development, morphology, and function.
G. E. Burch, M.D. Tulane University School of Medicine and Charity Hospital New Orleans, La. REFERENCE 1.
Burch. G. E.. Abildskov. J. A.. and Cronvich. J. A.: Studies of the spatial vectorcardiogram in normal man. Circulation 7"558, 1953.
Epimembranous nephropathy
It is usually easy for the physician to diagnose the nephrotic syndrome: massive proteinuria, hypoalbuminemia, edema, and frequently though not always, hypercholesterolemia, form a complex t h a t in most cases can hardly be overlooked;
American Heart Journal
hypertension may or may n o t be present. Much more difficult, however, is the important problem of the subspecies of nephrosis the doctor is dealing with. Certainly, the "minimal" lesion or lipoid variety is most commonly seen in children, the
809
Annotations
mesangiocapillary form is most common in adolescence, and "epimembranous riephropathy" (EN) is most common in adults. 1 But exceptions to these rules are so frequent t h a t one is easily led astray by them. In fact, epimembranous nephropathy happens in all age groups. Furthermore, it is of more than academic interest to establish a precise histologic diagnosis, for the prognosis and treatment are rather different for these varieties. ~ Nothing short of a renal biopsy can establish with certainty the precise diagnosis in such cases. The tissue obtained by biopsy will show, when submitted to special stains, the underlying pathology, ~ namely the presence of "granular" deposits of immunoglobulin G (IgG) and complement on the epithelial surface of the glomerular basement surface; these deposits tend to be separated by spikes emanating from the basement membrane: at a later stage, they are englobed in what appears to be a thickened basement membrane. Hence. the correct term for the disease is "epimembranous nephropathy," albeit because this term is easier to distinguish from membranoproliferative nephropathy. Electronm~croscopy and immunofluorescence study of the tissue brings out all these features in greater detail. The etiology of EN is obscure. Indeed. in the vast majority of cases no cause can be found; however, in many patients such a "cause" can be determined: heavy metal intoxications. some viral diseases (especially hepatitis virus B). administration of some drugs, e.g., Tridion, gold, penicillamin, etc. ~Thus, ironically some drugs that can cause EN are the ones used to combat the very maladies that in themselves may cause EN; rheumatoid arthritis, syphilis, malaria, etc. Thus as the reader sees. the causes of EN are multiple; diabetes, sarcoidosis, lupus, and other collagen diseases also join the ranks of occasional culprits. Much more ominous is the bizarre "associatiofi" of EN with lymphomas, carcinomas2 etc. What's more. *the nephrotic syndrome can appear in a patient with well-established malignancy, concomitantly with the inchoate stage of malignancy, or, in some cases antecede it by weeks or even months. Hence. the wise physician should not be satisfied with the diagnosis of EN but is bound to search carefully for possible underlying or evolving lymphoma, etc. Fortunately, the removal of a "cause" when this is known frequently leads to the removal or at least remission of the renal "complication." Yet such remissions occasionally happen in cryptogenetic eases also. and even without treatment; this makes it quite difficult s gauge the prognosis in any individual person. Nonetheless, it is generally accepted that E N is a serious disorder, usually leading to renal failure and death after
several years of duration. ~ Hence, the importance Of treatment. The general measures of low salt diet, abundant protein intake, and diuretics suffice in many patients, at least to alleviate the condition. In a significant proportion of patients, however, this therapeutic armamentarium is insufficient. Most nephrologists are very skeptical about the value of corticosteroids; some, however, do find them quite efficacious. 1 Evermore contentious fs the role of cyclophosphamide; we are convinced of its usefulness as an adjuvant of steroids. 1 On the other hand, dipyridamole is still sub judice. The latest arrival into the field of therapeutic agents is indomethacine2 Its definite role will be awaited with impatience by those physicians who care for patients afflicted with EN.
Mardoqueo L Salomon, M.D. Attending Physician Arthur C. Logan Memorial Hospital Flower Fifth Avenue Hospital Clinical Professor of Medicine and Attending Physician New York Medical College Metropolitan Medical Center Conrad Hsu, Ph.D. Professor of Microbiology Columbia University College of Physicians and Surgeons Victor Tchertkoff, M . D . Director of Laboratories Metropolitan Hospital Professor of Pathology New York Medical College New York, N. Y. REFERENCES 1. 2.
3.
4. 5.
Salomon, M. I., Hsu, K., and Tchertkoff, V.: Membranous nephropathy: An overview, J. Am. Geriatr. Soc. 23:535, 1975: Pollak, V. E., Pirani, C. L., and Clyne, D. H.: The natural history of membranous glomerulopathy, in KincaidSmith, P., Mathew, T., and Becker, E. L., editors, Glomerulonephritis, New York, 1973, John Wiley & Sons, Inc., Publishers, p. 423. Heptinstall, R. H.: Pathology of membranous glomerulonephritis, i n Kincaid-Smith, P., Mathew, T., and Becker, E. L., editors, Glonlerulonephritis, New York, i973, John Wiley & Sons, Inc., Publishers, p. 415. Lewis, M. B., Loughridge, L. W., and Phillips, T. M.: Immunologic studies in nephrotic syndrome associated with extrarenal malignant disease, Lancet H:134, 1971. Simon, N. M.: Indomethacin treatment of refractory nephrotic syndrome, Kidney Int. 8:420, 1975.
Ventricular fibrillation induced by a unipolar implanted pacemaker (cathodal stimulation)
In 1973 Preston stated in this journal1: "A search of the literature showed that every documented episode of pace-
810
maker-induced ventricular tachycardia/fibrillation in humans has been with a bipolar electrode system. The association of
December, 1976, Vol. 92, No. 6
D. B., Steed, G. R., Thorne, M. G., Jones, S., Guerrier, C. J., Eraut, C. D., McHugh, P. M., Chowdhury, N. R., Jafary, M. H., and Wallace, T. J.: Acute myocardial infarction: Home and hospital treatment, Br. Med. J. 3:334, 1971. 3. Hampton, J. R., Morris, G. K., and Mason, C.: Survey of
general practitioners' attitudes to management of patients with heart attacks, Br. Med. J. 4:146, 1975. Hayes, M. J , Morris, G. K., and Hampton, J. R.: Comparison of mobilisati0n after two and nine days in uncomplicated myocardial infarction, Br. Med. J. 3:10, 1974.
Of the conduction system and myocardial function
Physicians, as well as physiologists, fail to realize t h a t the time course of contraction of all portions of the myocardium is extremely important for efficient and effective emptying of the ventricle. For example, if the outflow tract of the right or left ventricle were to contract first in the cardiac cycle, the outlet of the ventricles would be sphincterally partially closed to some degree, thus impairing outflow and emptying o f bloodl But, this does not occur in normal hearts because the electric impulse which initiates ventricular contraction is delivered to the septal and apical regions of the heart first and to the bases last. The order of activation of t h e myocardium depends upon the anatomic distribution and function of the conduction tissue of the heart. Thus, the order of ventricular myocardial contraction is predetermined by the order of ventricular myocardial depolarization or electric activation. The order of electric activation is genetically and developmentally determined in utero. When this is entirely normal, ventricular .myocardial pumping function is normal and orderly in its time course. We h a v e found two normal patterns of order of time course of ventricular activation or depolarization displayed in the spatial vectorcardiogram. 1 When the order of electric activation or time course Of depolarization of the myocardium is disordered, ventricular contraction becomes disordered and, in turn, myocardial function is disturbed. The ventricle becomes less efficient and less effective, which can lead to clinically recognizable diseased cardiac states. For example, with R B B B and LBBB the order of ventricular myocardial contraction is definitely abnormal. It is even more abnormal or more disordered when disease of the Purkinje network or arborization block or defective intraventricular conduction (defective I.V.C.) is present. The order is abnormal when artificial pacemakers are driving the heart. Such disturbance in the order of ventricular
depolarization could conceivably occur on a congenital basis with abnormal anatomic distribution or function of the Purkinje network, or because of anatomic or morphologic disease, a n d / o r on a purely functional basis, or in therapy as with the use of a pacemaker. This would lead to dysfunction of the myocardial and systolic ven~ricular contraction and ejection. In fact. such a mechanism could readily explain the development of subaortic or subpulmonic {crista supraventricularis hypertrophy) hypertrophic obstruction. If these outflow tract areas were depolarized early in the cardiac cycle, "work" hypertrophy would occur initially and myocardial degeneration or disease would develop later. Such disordered activation could produce t h e hemodynamlc manifestations described for ventricular outflow obstruction due to hypertrophic subaortic stenosis or crista supraventricularis hypertrophy. One can readily imagine the multitude of myocardial dysfunctional states t h a t could follow different disturbances in the order of electric activation of the myocardium regardless of the conceivable causes, i.e.. genetic, developmental, morphologic, therapeutic, a n d / o r functional. It is impressive how orderly the time course of electric activation is in people. all predetermined by development, morphology, and function.
G. E. Burch, M.D. Tulane University School of Medicine and Charity Hospital New Orleans, La. REFERENCE 1.
Burch. G. E.. Abildskov. J. A.. and Cronvich. J. A.: Studies of the spatial vectorcardiogram in normal man. Circulation 7"558, 1953.
Epimembranous nephropathy
It is usually easy for the physician to diagnose the nephrotic syndrome: massive proteinuria, hypoalbuminemia, edema, and frequently though not always, hypercholesterolemia, form a complex t h a t in most cases can hardly be overlooked;
American Heart Journal
hypertension may or may n o t be present. Much more difficult, however, is the important problem of the subspecies of nephrosis the doctor is dealing with. Certainly, the "minimal" lesion or lipoid variety is most commonly seen in children, the
809
Annotations
mesangiocapillary form is most common in adolescence, and "epimembranous riephropathy" (EN) is most common in adults. 1 But exceptions to these rules are so frequent t h a t one is easily led astray by them. In fact, epimembranous nephropathy happens in all age groups. Furthermore, it is of more than academic interest to establish a precise histologic diagnosis, for the prognosis and treatment are rather different for these varieties. ~ Nothing short of a renal biopsy can establish with certainty the precise diagnosis in such cases. The tissue obtained by biopsy will show, when submitted to special stains, the underlying pathology, ~ namely the presence of "granular" deposits of immunoglobulin G (IgG) and complement on the epithelial surface of the glomerular basement surface; these deposits tend to be separated by spikes emanating from the basement membrane: at a later stage, they are englobed in what appears to be a thickened basement membrane. Hence. the correct term for the disease is "epimembranous nephropathy," albeit because this term is easier to distinguish from membranoproliferative nephropathy. Electronm~croscopy and immunofluorescence study of the tissue brings out all these features in greater detail. The etiology of EN is obscure. Indeed. in the vast majority of cases no cause can be found; however, in many patients such a "cause" can be determined: heavy metal intoxications. some viral diseases (especially hepatitis virus B). administration of some drugs, e.g., Tridion, gold, penicillamin, etc. ~Thus, ironically some drugs that can cause EN are the ones used to combat the very maladies that in themselves may cause EN; rheumatoid arthritis, syphilis, malaria, etc. Thus as the reader sees. the causes of EN are multiple; diabetes, sarcoidosis, lupus, and other collagen diseases also join the ranks of occasional culprits. Much more ominous is the bizarre "associatiofi" of EN with lymphomas, carcinomas2 etc. What's more. *the nephrotic syndrome can appear in a patient with well-established malignancy, concomitantly with the inchoate stage of malignancy, or, in some cases antecede it by weeks or even months. Hence. the wise physician should not be satisfied with the diagnosis of EN but is bound to search carefully for possible underlying or evolving lymphoma, etc. Fortunately, the removal of a "cause" when this is known frequently leads to the removal or at least remission of the renal "complication." Yet such remissions occasionally happen in cryptogenetic eases also. and even without treatment; this makes it quite difficult s gauge the prognosis in any individual person. Nonetheless, it is generally accepted that E N is a serious disorder, usually leading to renal failure and death after
several years of duration. ~ Hence, the importance Of treatment. The general measures of low salt diet, abundant protein intake, and diuretics suffice in many patients, at least to alleviate the condition. In a significant proportion of patients, however, this therapeutic armamentarium is insufficient. Most nephrologists are very skeptical about the value of corticosteroids; some, however, do find them quite efficacious. 1 Evermore contentious fs the role of cyclophosphamide; we are convinced of its usefulness as an adjuvant of steroids. 1 On the other hand, dipyridamole is still sub judice. The latest arrival into the field of therapeutic agents is indomethacine2 Its definite role will be awaited with impatience by those physicians who care for patients afflicted with EN.
Mardoqueo L Salomon, M.D. Attending Physician Arthur C. Logan Memorial Hospital Flower Fifth Avenue Hospital Clinical Professor of Medicine and Attending Physician New York Medical College Metropolitan Medical Center Conrad Hsu, Ph.D. Professor of Microbiology Columbia University College of Physicians and Surgeons Victor Tchertkoff, M . D . Director of Laboratories Metropolitan Hospital Professor of Pathology New York Medical College New York, N. Y. REFERENCES 1. 2.
3.
4. 5.
Salomon, M. I., Hsu, K., and Tchertkoff, V.: Membranous nephropathy: An overview, J. Am. Geriatr. Soc. 23:535, 1975: Pollak, V. E., Pirani, C. L., and Clyne, D. H.: The natural history of membranous glomerulopathy, in KincaidSmith, P., Mathew, T., and Becker, E. L., editors, Glomerulonephritis, New York, 1973, John Wiley & Sons, Inc., Publishers, p. 423. Heptinstall, R. H.: Pathology of membranous glomerulonephritis, i n Kincaid-Smith, P., Mathew, T., and Becker, E. L., editors, Glonlerulonephritis, New York, i973, John Wiley & Sons, Inc., Publishers, p. 415. Lewis, M. B., Loughridge, L. W., and Phillips, T. M.: Immunologic studies in nephrotic syndrome associated with extrarenal malignant disease, Lancet H:134, 1971. Simon, N. M.: Indomethacin treatment of refractory nephrotic syndrome, Kidney Int. 8:420, 1975.
Ventricular fibrillation induced by a unipolar implanted pacemaker (cathodal stimulation)
In 1973 Preston stated in this journal1: "A search of the literature showed that every documented episode of pace-
810
maker-induced ventricular tachycardia/fibrillation in humans has been with a bipolar electrode system. The association of
December, 1976, Vol. 92, No. 6
