&motations Use of the “diving reflex” for the treatment of parFxysmal supraventricular tachycardia
When an acquatic animal such as a seal or a duck dives underwater, it develops profound bradycardia and peripheral vasoconstriction. ‘-’ This “diving reflex” is initiated partly through stimulation by cold water of afferent nerve endings in the area of the mouth and nose, and partly by apnea. The efferent limb of the reflex is mediated by increased sympathetic stimulation to peripheral vessels (except to the brain and heart) and, simultaneously, intense vagal stimulation and sympathetic withdrawal to the heart. Terrestrial animals, including man, have retained a vestige of this potent reflex: in normal man, apneic submersion of the face in cold water causes a rapid drop in resting heart rate by IO to 40’%, accompanied by slight hypertension.“-’ Although apparently modest in its effects at rest, the diving reflex in man retains the potential to exert major cardiovascular changes; thus, the tachycardia of heavy dynamic exercise can be completely overridden when the diving reflex is superimposed on the exercise.e Several features of the diving reflex led to the suggestiorY that it might be a near-ideal means to treat some patients with paroxysmal supraventricular tachycardia (PSVT). The procedure is non-invasive and simple to perform, painless and inexpensive, and rapidly reversible. Patients can be instructed to treat themselves at home. Like carotid sinus massage, the diving reflex (which in man is initiated well before hypoxemia develops) produces intense vagal stimulation; but unlike carotid sinus massage and many other vagotonic maneuvers that are used to convert PSVT, it does not produce hypotension, and the danger of cerebral hypoperfusion is therefore minimized. The diving reflex can be induced as a therapeutic procedure quite easily. The patient is seated comfortably before a table, on which is placed a pan of cold water. He then takes a deep breath and, without expiring, submerges his face for up to 40 seconds. Conversion of PSVT often occurs within a few seconds, and almost always by 35 seconds. Prolonging the “dive” beyond 40 seconds is not useful in our experience, but a second trial is often successful if the.first was not satisfactory. We find it helpful to speak reassuringly to the patient throughout the procedure and to describe the progress of the trial to him; this helps avoid premature termination of the test due to anxiety and time-disorientation. The intensity of the vagal stimulation is greatest at cold temperatures,’ but some patients experience undue discomfort if the water is below 10° C. For them, and for patients for whom less intense stimulation is desired, results are often satisfactory at higher temperatures.” Clinical trials of the diving reflex in patients with PSVT have been most encouraging. Considering several published reports,n-‘z as well as information supplied by referring physicians and our own experience, we conclude that over 90% of patients with PSVT who perform the simulated diving procedure satisfactorily will convert to normal rhythm. Over half of
636
October,
1979, Vol. 98, No. 4
patients who are resistant to carotid sinus massage will nevertheless respond favorably to divingI?; and of those few patients who fail to respond to either procedure alone, many will convert to sinus rhythm when both procedures are applied simultaneously.lz Successful treatment has been accomplished in patients of all ages, including ne0nates.l’ Elderly patients are somewhat more resistant to the diving reflex than are young adults and children,‘, ‘z perhaps as a consequence of a general reduction in reflex cardiovascular responsiveness with aging.” Patients with general autonomic dysfunction similarly do not respond optimally to the diving reflexI In our experience, however, the most common reason for PSVT not to be converted to normal rhythm by the diving reflex is patient apprehension, with a resultant failure to maintain breath-holding in water for a sufficient time to activate the reflex adequately. This problem occurs in as many as onethird of patients who are treated in an emergency room with the diving reflex for the first time. Reassurance by the physician and careful explanation of the nature of the procedure is often sufficient to eliminate the problem. Patients with PSVT attributable to ischemic heart disease apparently respond as well to diving as do patients with no underlying cardiac pathology. Indeed, the diving reflex has been used successfully to convert PSVT in a patient with acute myocardial infarction and cardiogenic shock who had failed to respond to other procedures: and there is evidence to suggest that the reflex is even more potent in patients with a recent infarction than in age-matched controls.’ Patients with acute ischemic processes should generally be subjected to diving only with great caution, however, because the severe bradycardia that follows conversion during a dive can increase the chance of ventricular extrasystoles and fibrillation in with severely cold tempersusceptible patients,‘.‘. ‘I’ especially atures (which can increase stimulation of cardiac sympathetic nerves, as well as the vagi). Because occasional subjects characteristically experience transient dysrhythmias or prolonged asystole during diving, even in the absence of cardiac pathology, the first performances of the. procedure should be made under conditions of careful monitoring, and patients who respond in an aberrant manner should not be taught the procedure for use at home. Dangerous or worrisome responses are rare, however, and of over 60 patients whom we have successfully converted with the diving reflex, only one displayed an aberrant ventricular response (a ventricular couplet three seconds after resumption of sinus rhythm). Obviously, the diving reflex is useful only in the conversion of PSVT to normal rhythm, and it does not provide protection against future episodes nor should it be used to supplant prophylactic drug therapy. Some patients such as those with sick sinus syndrome and underlying second-degree or thirddegree AV block have an increased risk for experiencing prolonged asystole with diving and probably should not be
0002-8703/79/100536
+ 02$00.20/O
0 1979 The
C. V. Mosby
Co.
Annotations
treated routinely with the procedure. Transiently, severe bradycardia might present a potential hazard in patients receiving propranolol as well, although to date we have encountered no problem in several such individuals. Finally, patients with the permanent or chronic form of reciprocating AV junctional tachycardia, whose PSVT responds poorly to vagal stimulation, are not good candidates for the diving reflex, of course. For most acute episodes of vagoresponsive PSVT, however, the diving reflex offers a safe, simple, and useful mode of treatment that deserves a place in the standard therapeutic approach to the syndjvJme. Kern Wildenthal, M.D., Ph.D. James M. Atkins, M.D. Pauline and Adolph Weinberger Laboratory for Cardiopulmonary Research Depts. of Internal Medicine & Physiology University of Texas Health Science Center at Dallas Dallas, Texas 75235
6.
7.
a.
9.
1975.
10.
11.
REFERENCES
I. 2.
3.
4.
5.
12.
Anderson? H. T.: Physiological adaptations in diving vertebrates, Physiol. Rev. 46:202, 1966. Yonce, L. R., and Folkow, B.: The integration of the cardiovascular response to diving, AM. HEART J. 79:1, 1970. Strauss, M. B.: Physiological aspects of mammalian breath-hold diving: a review, Aerospace Med. 41:1362, 1970. Wolf, S., Schneider, R. A., and Groover, M. E. Further studies on the circulatory and metabolic alterations of the oxygen-conserving (diving) reflex in man, Trans. Assoc. Am. Physicians 78:242, 1965. Moore, T. O., Lin, Y. C., Lally, D. A., and Hong, S. K.:
Sulfinpyrazone
after myocardial
+ 02.$00.20/O
0 1979 The
C. V. Mosby
13. 14.
15.
16.
Whitman, V., and Zakeosian, G. M.: The diving reflex in termination of supraventricular tachycardia in childhood, J. Pediatr. 89:1032, 1976. Whitman, V., Friedman, Z., Berman, W., and Maisels, M. J.: Supraventricular tachycardia in newborn infants: an approach to therapy, J. Pediatr. 91:304, 1977. Mathew, P. K.: Treatment of paroxysmal atria1 tachycardia by diving reflex, Lancet 1:510, 1978. Wildenthal, K.: Treatment of paroxysmal atria1 tachycardia by diving reflex, Lancet 1:1042, 1978. Grilhn, B., Pickering T. G., Sleight, P., and Pete, R.: Effect of age and high blood pressure on baroreflex sensitivity in man, Circ. Res. 29:424, 1971. Bennett, T., Hosking, D. J., and Hampton, J. R.: Cardiovascular reflex responses to apnoeic face immersion and mental stress in diabetic subjects, Cardiovasc. Res. 10:192, 1976. Condry, P., Jain, A., Marshall, R., and Bowyer, A.: Ventricular tachycardia caused by the diving reflex, Lancet 2:,l263, 1975.
infarction
membranes. Its deposition seems to be affected little by anticoagulants such as heparin or warfarin, a fact which may explain the ineffectiveness of these agents after myocardial infarction. Sulfinpyrazone is a uricosuric agent and it was noted that it restored, after several weeks’ administration, shortened platejet survival to normal in gouty subjects with thromboembolic disorders3 It also prolongs platelet survival m rabbits, a species with very low serum uric acid levels, which led Mustard and associates4 to suppose that its antiplatelet action was independent of its uricosuric effects. Although the drug inhibits platelet aggregation in the test tube, the concentrations required seem to be higher than those likely to be attained with in viva use.5 However, inhibition of collageninduced aggregation has been shown in viv~,~ and the small but statistically significant prolongation of bleeding time demonstrable with careful study after only two days’ administration to healthy volunteers suggests that in therapeutic dosage it does indeed have some inhibitory effect on the interaction between platelets and vascular endothelium.’ Although the Anturane Reinfarction Trial Research Group
The recent report of a reduction in sudden deaths after myocardial mfarction in patients treated with sulfinpyrazone’ is at first sight rather surprising. Indeed, the title of the study, the Anturane Reinfarction Trial, suggests that the investigators were expecting the antithrombotic effects of sulfinpyrazone to protect their patients from further myocardial infarction, but this has not yet been demonstrated. However, myocardial infarction is not always attributable to occlusive thrombosis within the coronary arteries and it is worth considering other possible explanations for the reduction in sudden deaths. It has been suggested that the drug reduced the rate of platelet/fibrin emboli within the coronary vasculature and in so doing prevented the development of fatal cardiac arrhythmias.* This seems to be a tenable hypothesis since, as we shall see, sulfinpyrazone has been shown to affect both platelets and also fibrin, which are the main components of so-called “white thrombus.” White thrombus forms in areas of high blood flow rate and shear stress and may occur within the arterial circulation and also on the surfaces of foreign materials such as artificial heart valves and dialyser
0002-8703/79/100537
Effects of temperature, immersion, and ambient pressure on human apneic bradycardia, J. Appl. Physiol. 33:36, 1972. Bergman, S. A., Campbell, J. K., and Wildenthal, K.: “Diving reflex” in man: its relations to isometric and dynamic exercise, J. Appl. Physiol. 33:27, 1972. Gooden. B. A., , Holdstock. G.. and Ham&on. J. R.: The magnitude of the bradycardia’induced by face immersion in patients convalescing from myocardial infarction, Cardiovas. Res. 12:239, 1978. Wildenthal, K., Atkins, J. M., Leshin, S. J., and Skelton, C. L.: The diving reflex used to treat paroxysmal atria1 tachycardia, Lancet 1:12, 1975. Pickerma. T.. and Bolton-Maeas. P.: Treatment of paroxysmal supraventricular tacxycardia, Lancet 1:340,
Co.
American
Heart
Journal
537
When an acquatic animal such as a seal or a duck dives underwater, it develops profound bradycardia and peripheral vasoconstriction. ‘-’ This “diving reflex” is initiated partly through stimulation by cold water of afferent nerve endings in the area of the mouth and nose, and partly by apnea. The efferent limb of the reflex is mediated by increased sympathetic stimulation to peripheral vessels (except to the brain and heart) and, simultaneously, intense vagal stimulation and sympathetic withdrawal to the heart. Terrestrial animals, including man, have retained a vestige of this potent reflex: in normal man, apneic submersion of the face in cold water causes a rapid drop in resting heart rate by IO to 40’%, accompanied by slight hypertension.“-’ Although apparently modest in its effects at rest, the diving reflex in man retains the potential to exert major cardiovascular changes; thus, the tachycardia of heavy dynamic exercise can be completely overridden when the diving reflex is superimposed on the exercise.e Several features of the diving reflex led to the suggestiorY that it might be a near-ideal means to treat some patients with paroxysmal supraventricular tachycardia (PSVT). The procedure is non-invasive and simple to perform, painless and inexpensive, and rapidly reversible. Patients can be instructed to treat themselves at home. Like carotid sinus massage, the diving reflex (which in man is initiated well before hypoxemia develops) produces intense vagal stimulation; but unlike carotid sinus massage and many other vagotonic maneuvers that are used to convert PSVT, it does not produce hypotension, and the danger of cerebral hypoperfusion is therefore minimized. The diving reflex can be induced as a therapeutic procedure quite easily. The patient is seated comfortably before a table, on which is placed a pan of cold water. He then takes a deep breath and, without expiring, submerges his face for up to 40 seconds. Conversion of PSVT often occurs within a few seconds, and almost always by 35 seconds. Prolonging the “dive” beyond 40 seconds is not useful in our experience, but a second trial is often successful if the.first was not satisfactory. We find it helpful to speak reassuringly to the patient throughout the procedure and to describe the progress of the trial to him; this helps avoid premature termination of the test due to anxiety and time-disorientation. The intensity of the vagal stimulation is greatest at cold temperatures,’ but some patients experience undue discomfort if the water is below 10° C. For them, and for patients for whom less intense stimulation is desired, results are often satisfactory at higher temperatures.” Clinical trials of the diving reflex in patients with PSVT have been most encouraging. Considering several published reports,n-‘z as well as information supplied by referring physicians and our own experience, we conclude that over 90% of patients with PSVT who perform the simulated diving procedure satisfactorily will convert to normal rhythm. Over half of
636
October,
1979, Vol. 98, No. 4
patients who are resistant to carotid sinus massage will nevertheless respond favorably to divingI?; and of those few patients who fail to respond to either procedure alone, many will convert to sinus rhythm when both procedures are applied simultaneously.lz Successful treatment has been accomplished in patients of all ages, including ne0nates.l’ Elderly patients are somewhat more resistant to the diving reflex than are young adults and children,‘, ‘z perhaps as a consequence of a general reduction in reflex cardiovascular responsiveness with aging.” Patients with general autonomic dysfunction similarly do not respond optimally to the diving reflexI In our experience, however, the most common reason for PSVT not to be converted to normal rhythm by the diving reflex is patient apprehension, with a resultant failure to maintain breath-holding in water for a sufficient time to activate the reflex adequately. This problem occurs in as many as onethird of patients who are treated in an emergency room with the diving reflex for the first time. Reassurance by the physician and careful explanation of the nature of the procedure is often sufficient to eliminate the problem. Patients with PSVT attributable to ischemic heart disease apparently respond as well to diving as do patients with no underlying cardiac pathology. Indeed, the diving reflex has been used successfully to convert PSVT in a patient with acute myocardial infarction and cardiogenic shock who had failed to respond to other procedures: and there is evidence to suggest that the reflex is even more potent in patients with a recent infarction than in age-matched controls.’ Patients with acute ischemic processes should generally be subjected to diving only with great caution, however, because the severe bradycardia that follows conversion during a dive can increase the chance of ventricular extrasystoles and fibrillation in with severely cold tempersusceptible patients,‘.‘. ‘I’ especially atures (which can increase stimulation of cardiac sympathetic nerves, as well as the vagi). Because occasional subjects characteristically experience transient dysrhythmias or prolonged asystole during diving, even in the absence of cardiac pathology, the first performances of the. procedure should be made under conditions of careful monitoring, and patients who respond in an aberrant manner should not be taught the procedure for use at home. Dangerous or worrisome responses are rare, however, and of over 60 patients whom we have successfully converted with the diving reflex, only one displayed an aberrant ventricular response (a ventricular couplet three seconds after resumption of sinus rhythm). Obviously, the diving reflex is useful only in the conversion of PSVT to normal rhythm, and it does not provide protection against future episodes nor should it be used to supplant prophylactic drug therapy. Some patients such as those with sick sinus syndrome and underlying second-degree or thirddegree AV block have an increased risk for experiencing prolonged asystole with diving and probably should not be
0002-8703/79/100536
+ 02$00.20/O
0 1979 The
C. V. Mosby
Co.
Annotations
treated routinely with the procedure. Transiently, severe bradycardia might present a potential hazard in patients receiving propranolol as well, although to date we have encountered no problem in several such individuals. Finally, patients with the permanent or chronic form of reciprocating AV junctional tachycardia, whose PSVT responds poorly to vagal stimulation, are not good candidates for the diving reflex, of course. For most acute episodes of vagoresponsive PSVT, however, the diving reflex offers a safe, simple, and useful mode of treatment that deserves a place in the standard therapeutic approach to the syndjvJme. Kern Wildenthal, M.D., Ph.D. James M. Atkins, M.D. Pauline and Adolph Weinberger Laboratory for Cardiopulmonary Research Depts. of Internal Medicine & Physiology University of Texas Health Science Center at Dallas Dallas, Texas 75235
6.
7.
a.
9.
1975.
10.
11.
REFERENCES
I. 2.
3.
4.
5.
12.
Anderson? H. T.: Physiological adaptations in diving vertebrates, Physiol. Rev. 46:202, 1966. Yonce, L. R., and Folkow, B.: The integration of the cardiovascular response to diving, AM. HEART J. 79:1, 1970. Strauss, M. B.: Physiological aspects of mammalian breath-hold diving: a review, Aerospace Med. 41:1362, 1970. Wolf, S., Schneider, R. A., and Groover, M. E. Further studies on the circulatory and metabolic alterations of the oxygen-conserving (diving) reflex in man, Trans. Assoc. Am. Physicians 78:242, 1965. Moore, T. O., Lin, Y. C., Lally, D. A., and Hong, S. K.:
Sulfinpyrazone
after myocardial
+ 02.$00.20/O
0 1979 The
C. V. Mosby
13. 14.
15.
16.
Whitman, V., and Zakeosian, G. M.: The diving reflex in termination of supraventricular tachycardia in childhood, J. Pediatr. 89:1032, 1976. Whitman, V., Friedman, Z., Berman, W., and Maisels, M. J.: Supraventricular tachycardia in newborn infants: an approach to therapy, J. Pediatr. 91:304, 1977. Mathew, P. K.: Treatment of paroxysmal atria1 tachycardia by diving reflex, Lancet 1:510, 1978. Wildenthal, K.: Treatment of paroxysmal atria1 tachycardia by diving reflex, Lancet 1:1042, 1978. Grilhn, B., Pickering T. G., Sleight, P., and Pete, R.: Effect of age and high blood pressure on baroreflex sensitivity in man, Circ. Res. 29:424, 1971. Bennett, T., Hosking, D. J., and Hampton, J. R.: Cardiovascular reflex responses to apnoeic face immersion and mental stress in diabetic subjects, Cardiovasc. Res. 10:192, 1976. Condry, P., Jain, A., Marshall, R., and Bowyer, A.: Ventricular tachycardia caused by the diving reflex, Lancet 2:,l263, 1975.
infarction
membranes. Its deposition seems to be affected little by anticoagulants such as heparin or warfarin, a fact which may explain the ineffectiveness of these agents after myocardial infarction. Sulfinpyrazone is a uricosuric agent and it was noted that it restored, after several weeks’ administration, shortened platejet survival to normal in gouty subjects with thromboembolic disorders3 It also prolongs platelet survival m rabbits, a species with very low serum uric acid levels, which led Mustard and associates4 to suppose that its antiplatelet action was independent of its uricosuric effects. Although the drug inhibits platelet aggregation in the test tube, the concentrations required seem to be higher than those likely to be attained with in viva use.5 However, inhibition of collageninduced aggregation has been shown in viv~,~ and the small but statistically significant prolongation of bleeding time demonstrable with careful study after only two days’ administration to healthy volunteers suggests that in therapeutic dosage it does indeed have some inhibitory effect on the interaction between platelets and vascular endothelium.’ Although the Anturane Reinfarction Trial Research Group
The recent report of a reduction in sudden deaths after myocardial mfarction in patients treated with sulfinpyrazone’ is at first sight rather surprising. Indeed, the title of the study, the Anturane Reinfarction Trial, suggests that the investigators were expecting the antithrombotic effects of sulfinpyrazone to protect their patients from further myocardial infarction, but this has not yet been demonstrated. However, myocardial infarction is not always attributable to occlusive thrombosis within the coronary arteries and it is worth considering other possible explanations for the reduction in sudden deaths. It has been suggested that the drug reduced the rate of platelet/fibrin emboli within the coronary vasculature and in so doing prevented the development of fatal cardiac arrhythmias.* This seems to be a tenable hypothesis since, as we shall see, sulfinpyrazone has been shown to affect both platelets and also fibrin, which are the main components of so-called “white thrombus.” White thrombus forms in areas of high blood flow rate and shear stress and may occur within the arterial circulation and also on the surfaces of foreign materials such as artificial heart valves and dialyser
0002-8703/79/100537
Effects of temperature, immersion, and ambient pressure on human apneic bradycardia, J. Appl. Physiol. 33:36, 1972. Bergman, S. A., Campbell, J. K., and Wildenthal, K.: “Diving reflex” in man: its relations to isometric and dynamic exercise, J. Appl. Physiol. 33:27, 1972. Gooden. B. A., , Holdstock. G.. and Ham&on. J. R.: The magnitude of the bradycardia’induced by face immersion in patients convalescing from myocardial infarction, Cardiovas. Res. 12:239, 1978. Wildenthal, K., Atkins, J. M., Leshin, S. J., and Skelton, C. L.: The diving reflex used to treat paroxysmal atria1 tachycardia, Lancet 1:12, 1975. Pickerma. T.. and Bolton-Maeas. P.: Treatment of paroxysmal supraventricular tacxycardia, Lancet 1:340,
Co.
American
Heart
Journal
537
