Annotations
subject to the disadvantages of fixed-rate pacing. The above case illustrates that this is more than of theoretical importance. Ventricular fibrillation due to pacemaker stimulus “R-onT” phenomenon has occurred during acute myocardial infarction,” during treatment with catecholamines,’ and shortly after pacemaker ins&tion.5 At these times, and probably at all times, activation of demand temporary pacemakers should be performed in the following manner. Initially, milliamperage should be at the nadir. Second, the unit should be switched on at a time other than the vulnerable interval. Last, the milliamperage should be increased until proper capture ensues. These steps, practiced routinely, will minimize such complications of pacemaker therapy. John W, Schatz, M.D. Leslie Wiener, M.D. Albert N. Brest, M.D. Division of Cardiology Jefferson Medical College 1025 Walnut St. Philadelphia, Pa. 19107
Protamine-renografin
chemical
1. Preston, T. A.: Anodal stimulation as a cause of pacemaker-induced ventricular fibrillation, AM. HEART J. 86:366, 1973. ’ 2. Shearon, L.: Personal communication. 3. Bilitch, M., Cosby, R. S., and Cafferky, E. A.: Ventricular fibrillation and competitive pacing, N. Engl. J. Med. 276:598. 1967. 4. Lemberg, L., Castellanos, A., and Berkovits, B. V.: Pacemaking on demand in A-V block. J. A. M. A. 191:12. 1965. 5. Tavel, M., and Fisch, C.: Repetitive ventricular arrhythmia resulting from artificial internal pacemaker, Circulation 30:493, 1964.
embolus
There have been several recent reviews of complications of coronary arteriography using the transfemoral approach. Several authors including Walker and co-workers,’ Judkins and Gander,’ and an annotation by Eyer,3 have noted the significant decrease in thromboembolic complications following the use of heparin prior to the initiation of arteriography. McCarty and Glasser,’ have also reported on the thrombogenicity of guidewires in the experimental animal. They also noted that heparinization seemed to decrease the tendency toward clot formation. It is of interest that Walker and coworkers’ and Eyefl both use protamine at the conclusion of a catheterization. No complications have been reported with the use of p&amine as a coagulant drug in coronary arteriography. Jaques> reported, in the Canadian MedicalAssociation Journul, on a review of protamine. The toxicity of protamine has not been promulgated extensively. He notes significantly, that p&amine, when injected rapidly, will release histamine and agglutinate platelets. Protamine can, when introduced intravenously, cause a pronounced fall in blood pressure in most animal species. Most of the actions are thought to be histamine-like in nature. These effects seem to be reduced by injecting the protamine slowly. Protamine combining with heparin in the mast cells will displace histamine and/or serotonin. Protamine first combines with exogenous heparin in the circulation and only when there is protamine in excess of the amount required for combination of the mast, cells affected. Gourin, Streaian, and Stuckey” have observed adverse effects on the electrocardiogram related to histamine release. This is probably a further reason for limiting the protamine dosage to that equivalent to heparin in the circulation. Ellison, Ominsky, and Wollman7 reported that intravenous injections of multiple doses of protamine in eight volun-
678
REFERENCES
teer subjects totaling 609 mg. per 70 kilograms produced typical symptoms of histamine release; i.e., itching, flushing, fatigue, malaise, nausea, vomiting, headache, hyperventilation, and temperature elevation. All of the subjects exhibited itching, flushing, and only one subject showed hyperventilation and temperature elevation. The intensity of these symptoms increased as the dose was increased. When titration is not done it is beet to depend on the rule of thumb that not more than 1 mg. per 109 USP units of heparin be given for neutralization. The amount should be reduced in proportion to the time which has elapsed since the last heparin administration by about 1 mg. per minute for the average patient.5 A second complicating feature is the effect of protamine on Renografin-76 (meglumine diatrizoate). Most videopatent dyes have a basic base. Renografin-76 has a pH of 7.0 to 7.6. As is common with transfemoral arteriography, frequent flushing is the rule. If, at the conclusion of the catheterization, the protamine is given intra-arterially, and the dye is withdrawn in the syringe, the dye, if not flushed out of the catheter, will then be withdrawn into the syringe with prompt clumping and a white precipitate being formed within the syringe containing the p&amine. Protamine sulfate has a pH of 3 to 4, which will cause precipitation of diatrizoic acid. It is conceivable that if this precipitate is then injected intra-arterially, a significant chemical embolus may result. It is, therefore, the purpose of this brief annotation to caution the arteriographer to be certain that his catheter is free of any radio-opaque contrast media before the injection of protamine intra-arterially. The drug may be given intravenously without difficulty, hopefully. The side effects, as noted previously, must be watched for. There does not appear to be any precaution against the intra-arterial use, and I have not been able to
November,
1975, Vol. 90, No. 5
Annotations
find significant mine.
studies on the intra-arterial
use of prota-
L. A. Iannone, 943 19th Des Moines, Iowa
M.D. Street 50314
REFERENCES
1. Walker, W. J., Mundall, S. L., et al: Systemic heparinization for femoral percutaneous coronary arteriography, N. Engl. J. Med. 288:826, 1973. 2. Judkins, M. P., and Gander, N. P.: Prevention of complications of coronary arteriography, Circulation 49:599, 1974.
Of classification
of cardiomyopathies
Cardiomyopathies, just as any group of diseases, should be classified for the convenience of the clinician for communication, diagnosis, management, and study. However, for the convenience of clinicians the classification must be simple and practical. Class&ation of cardiomyopathies should stimulate the physician to consider immediately the etiology, prevention, and early recognition of the disease. This type of classification imposea no restrictions on diagnosis and care. When disease of the myocardium reaches the late stages, such as marked cardiomegaly and congestive heart failure, the disease is at a terminal state and usually at an irreversible state. Furthermore, the late states are readily recognized by the clinician, but the prognosis is extremely grave then. It is when patients are in those final stage-s of their disease that they are usually referred to the cardiologist for management. Thus, a cardiologist who practices little or no internal meclitine has little opportunity to see the initial and early stages of cardiomyopathies, i. e., when the disease is preventable and cure is most possible. Thus, it is the general practitioner, general internist or physician or family doctor who will have the opportunity to detect in patients the presence of etiologic factors that are potential producers of myocardial disease. It is the family physician who has the opportunity to detect the disease3 early. As indicated many years ago,’ infections, anemia, toxins, and many other factors2 can damage the myocardium. These etiologic factors must be avoided or at least detected early and removed. When the myocardial damage is already present, it must be recognized early so that treatment can be instituted early, long before his illness prom into congestive heart failure or any final irreversible state. Therefore, the average cardiologist does not seem to be prepared or have the opportunity to prevent, cure, or significantly ameliorate heart muscle disease. Nevertheless, he must be concerned with prevention and early treatment. The physician must recognize the existence of factors which can damage the myocardium and remove those potential etiologic factors. Fortunately, the presence of etiologic factors and the initial
American
Heart
Journal
3. Eyer, K. M.: Complications of transfemoral coronary arteriography and their prevention using heparin, AM. HEART J. 86:428, 1973. 4. McCarty, R. J., and Glasser, S. P.: Thrombogenicity of guidewires, Am. J. Cardiol. 32943, 1973. 5. Jaques, L. B.: Protamine-antagonist to heparin, Canad. Med. Assoc. J. 108:X291, 1973. 6. Gourin, A., Streaian, R., and Stuckey, J. H.: Total cardiopulmonary protamine sulfate, J. Thorac. Cardiovasc. Surg. 61 :X0, 1971. 7. Ellison, N., Ominsky, A. J., and Wollman, H.: Is protamine a clinically important anticoagulant? A negative answer, Anesthesiology 35:621, 1971.
early stages of the cardiomyopathiea are readily recognized by a simple “clinical work-up,” i. e., without the use of cardiac catheterization, cardioangiography, or other complex and unnecessary and hazardous procedures, and even before these complex procedures can reveal abnormalities. It must be remembered, however, that idiopathic hypertrophic subaortic stenosis can offer diagnostic difficulties, especially in extremely early diagnosis. Fortunately, this entity is rare, so that it is an extremely ins&n&ant pmblem in the practice of the average family physician, whereas many of the other cardiomyopathies are common. These can and should be recognixed early. The factors known to produce cardiomyopathy are readily detected 80 that they can be removed. This practice, in turn, treats or eliminates “potential” cardiomyopathy. Finally, if prevention and cure are the objectives in the management of the cardiomyopathies, then an understanding of etiology, pathogenesis, potential disease, and initial and early myocardial damage must be emphasized in training and in practice. It is for this reason that the classification previously published by us2. 3 was developed. All diseases have a cause and a beginning, and every possible effort must be exercised at all times and continuously to learn the cause of cardiomyopathy so that the myocardial disease can be prevented or detected and managed in ita incipiency. Tulane
Uniuersity
G. E. Burch, M. D. School of Medicine and Charity Hospital New Orleans, La.
REFERENCES
1. Burch, G. E. : A primer of cardiology, 4th ed., Philadelphia, 1971, Lea & Febiger. 2. Burch, G. E., and DePasquale, N. P.: Heart muscle disease, Disease-a-Month, Chicago, May, 1968, Year Book Medical Publishers, Inc. 3. Burch, G. E., and DePasquale, N. P.: Recognition and prevention of cardiomyopathy, Circulation 42:A-47, 1970.
679
subject to the disadvantages of fixed-rate pacing. The above case illustrates that this is more than of theoretical importance. Ventricular fibrillation due to pacemaker stimulus “R-onT” phenomenon has occurred during acute myocardial infarction,” during treatment with catecholamines,’ and shortly after pacemaker ins&tion.5 At these times, and probably at all times, activation of demand temporary pacemakers should be performed in the following manner. Initially, milliamperage should be at the nadir. Second, the unit should be switched on at a time other than the vulnerable interval. Last, the milliamperage should be increased until proper capture ensues. These steps, practiced routinely, will minimize such complications of pacemaker therapy. John W, Schatz, M.D. Leslie Wiener, M.D. Albert N. Brest, M.D. Division of Cardiology Jefferson Medical College 1025 Walnut St. Philadelphia, Pa. 19107
Protamine-renografin
chemical
1. Preston, T. A.: Anodal stimulation as a cause of pacemaker-induced ventricular fibrillation, AM. HEART J. 86:366, 1973. ’ 2. Shearon, L.: Personal communication. 3. Bilitch, M., Cosby, R. S., and Cafferky, E. A.: Ventricular fibrillation and competitive pacing, N. Engl. J. Med. 276:598. 1967. 4. Lemberg, L., Castellanos, A., and Berkovits, B. V.: Pacemaking on demand in A-V block. J. A. M. A. 191:12. 1965. 5. Tavel, M., and Fisch, C.: Repetitive ventricular arrhythmia resulting from artificial internal pacemaker, Circulation 30:493, 1964.
embolus
There have been several recent reviews of complications of coronary arteriography using the transfemoral approach. Several authors including Walker and co-workers,’ Judkins and Gander,’ and an annotation by Eyer,3 have noted the significant decrease in thromboembolic complications following the use of heparin prior to the initiation of arteriography. McCarty and Glasser,’ have also reported on the thrombogenicity of guidewires in the experimental animal. They also noted that heparinization seemed to decrease the tendency toward clot formation. It is of interest that Walker and coworkers’ and Eyefl both use protamine at the conclusion of a catheterization. No complications have been reported with the use of p&amine as a coagulant drug in coronary arteriography. Jaques> reported, in the Canadian MedicalAssociation Journul, on a review of protamine. The toxicity of protamine has not been promulgated extensively. He notes significantly, that p&amine, when injected rapidly, will release histamine and agglutinate platelets. Protamine can, when introduced intravenously, cause a pronounced fall in blood pressure in most animal species. Most of the actions are thought to be histamine-like in nature. These effects seem to be reduced by injecting the protamine slowly. Protamine combining with heparin in the mast cells will displace histamine and/or serotonin. Protamine first combines with exogenous heparin in the circulation and only when there is protamine in excess of the amount required for combination of the mast, cells affected. Gourin, Streaian, and Stuckey” have observed adverse effects on the electrocardiogram related to histamine release. This is probably a further reason for limiting the protamine dosage to that equivalent to heparin in the circulation. Ellison, Ominsky, and Wollman7 reported that intravenous injections of multiple doses of protamine in eight volun-
678
REFERENCES
teer subjects totaling 609 mg. per 70 kilograms produced typical symptoms of histamine release; i.e., itching, flushing, fatigue, malaise, nausea, vomiting, headache, hyperventilation, and temperature elevation. All of the subjects exhibited itching, flushing, and only one subject showed hyperventilation and temperature elevation. The intensity of these symptoms increased as the dose was increased. When titration is not done it is beet to depend on the rule of thumb that not more than 1 mg. per 109 USP units of heparin be given for neutralization. The amount should be reduced in proportion to the time which has elapsed since the last heparin administration by about 1 mg. per minute for the average patient.5 A second complicating feature is the effect of protamine on Renografin-76 (meglumine diatrizoate). Most videopatent dyes have a basic base. Renografin-76 has a pH of 7.0 to 7.6. As is common with transfemoral arteriography, frequent flushing is the rule. If, at the conclusion of the catheterization, the protamine is given intra-arterially, and the dye is withdrawn in the syringe, the dye, if not flushed out of the catheter, will then be withdrawn into the syringe with prompt clumping and a white precipitate being formed within the syringe containing the p&amine. Protamine sulfate has a pH of 3 to 4, which will cause precipitation of diatrizoic acid. It is conceivable that if this precipitate is then injected intra-arterially, a significant chemical embolus may result. It is, therefore, the purpose of this brief annotation to caution the arteriographer to be certain that his catheter is free of any radio-opaque contrast media before the injection of protamine intra-arterially. The drug may be given intravenously without difficulty, hopefully. The side effects, as noted previously, must be watched for. There does not appear to be any precaution against the intra-arterial use, and I have not been able to
November,
1975, Vol. 90, No. 5
Annotations
find significant mine.
studies on the intra-arterial
use of prota-
L. A. Iannone, 943 19th Des Moines, Iowa
M.D. Street 50314
REFERENCES
1. Walker, W. J., Mundall, S. L., et al: Systemic heparinization for femoral percutaneous coronary arteriography, N. Engl. J. Med. 288:826, 1973. 2. Judkins, M. P., and Gander, N. P.: Prevention of complications of coronary arteriography, Circulation 49:599, 1974.
Of classification
of cardiomyopathies
Cardiomyopathies, just as any group of diseases, should be classified for the convenience of the clinician for communication, diagnosis, management, and study. However, for the convenience of clinicians the classification must be simple and practical. Class&ation of cardiomyopathies should stimulate the physician to consider immediately the etiology, prevention, and early recognition of the disease. This type of classification imposea no restrictions on diagnosis and care. When disease of the myocardium reaches the late stages, such as marked cardiomegaly and congestive heart failure, the disease is at a terminal state and usually at an irreversible state. Furthermore, the late states are readily recognized by the clinician, but the prognosis is extremely grave then. It is when patients are in those final stage-s of their disease that they are usually referred to the cardiologist for management. Thus, a cardiologist who practices little or no internal meclitine has little opportunity to see the initial and early stages of cardiomyopathies, i. e., when the disease is preventable and cure is most possible. Thus, it is the general practitioner, general internist or physician or family doctor who will have the opportunity to detect in patients the presence of etiologic factors that are potential producers of myocardial disease. It is the family physician who has the opportunity to detect the disease3 early. As indicated many years ago,’ infections, anemia, toxins, and many other factors2 can damage the myocardium. These etiologic factors must be avoided or at least detected early and removed. When the myocardial damage is already present, it must be recognized early so that treatment can be instituted early, long before his illness prom into congestive heart failure or any final irreversible state. Therefore, the average cardiologist does not seem to be prepared or have the opportunity to prevent, cure, or significantly ameliorate heart muscle disease. Nevertheless, he must be concerned with prevention and early treatment. The physician must recognize the existence of factors which can damage the myocardium and remove those potential etiologic factors. Fortunately, the presence of etiologic factors and the initial
American
Heart
Journal
3. Eyer, K. M.: Complications of transfemoral coronary arteriography and their prevention using heparin, AM. HEART J. 86:428, 1973. 4. McCarty, R. J., and Glasser, S. P.: Thrombogenicity of guidewires, Am. J. Cardiol. 32943, 1973. 5. Jaques, L. B.: Protamine-antagonist to heparin, Canad. Med. Assoc. J. 108:X291, 1973. 6. Gourin, A., Streaian, R., and Stuckey, J. H.: Total cardiopulmonary protamine sulfate, J. Thorac. Cardiovasc. Surg. 61 :X0, 1971. 7. Ellison, N., Ominsky, A. J., and Wollman, H.: Is protamine a clinically important anticoagulant? A negative answer, Anesthesiology 35:621, 1971.
early stages of the cardiomyopathiea are readily recognized by a simple “clinical work-up,” i. e., without the use of cardiac catheterization, cardioangiography, or other complex and unnecessary and hazardous procedures, and even before these complex procedures can reveal abnormalities. It must be remembered, however, that idiopathic hypertrophic subaortic stenosis can offer diagnostic difficulties, especially in extremely early diagnosis. Fortunately, this entity is rare, so that it is an extremely ins&n&ant pmblem in the practice of the average family physician, whereas many of the other cardiomyopathies are common. These can and should be recognixed early. The factors known to produce cardiomyopathy are readily detected 80 that they can be removed. This practice, in turn, treats or eliminates “potential” cardiomyopathy. Finally, if prevention and cure are the objectives in the management of the cardiomyopathies, then an understanding of etiology, pathogenesis, potential disease, and initial and early myocardial damage must be emphasized in training and in practice. It is for this reason that the classification previously published by us2. 3 was developed. All diseases have a cause and a beginning, and every possible effort must be exercised at all times and continuously to learn the cause of cardiomyopathy so that the myocardial disease can be prevented or detected and managed in ita incipiency. Tulane
Uniuersity
G. E. Burch, M. D. School of Medicine and Charity Hospital New Orleans, La.
REFERENCES
1. Burch, G. E. : A primer of cardiology, 4th ed., Philadelphia, 1971, Lea & Febiger. 2. Burch, G. E., and DePasquale, N. P.: Heart muscle disease, Disease-a-Month, Chicago, May, 1968, Year Book Medical Publishers, Inc. 3. Burch, G. E., and DePasquale, N. P.: Recognition and prevention of cardiomyopathy, Circulation 42:A-47, 1970.
679
