Reversible Central Apnea in an Infant with Cyanotic Heart Disease

oped by Moore et al,20 insuBlation of pigeon antigen caused a humoral response, with no evidence of cellular hypersensitivity or alteration of tissue; however, if these animals were first given BeG vaccine intravenously and then were challenged with the inhalation of the antigen, they developed the histologic changes of cellular hypersensitivity. Certain antigens, as Bice et al 21 reported with Micropolyspora loom testing in rabbits, may serve as their own immunologic adjuvant, and fonnation of granulomas in certain cases may be associated with the activity of the adjuvant. Whether talc presented by embolization, perhaps with tissue damage or adjuvant effect, causes its effect through an immunologically mediated process is unproven but it is a possibility that should be considered, in light of the variability of the extent of the parenchymal involvement, the progression of the disease beyond the time of the initial insult, and the response of the process to corticosteroid therapy. Immunologic testing, such as with macrophagic migration inhibition and lymphocytic stimulation testing, which were not done in this patient, would provide a fertile area of future investigation. ACKNOWLEDGMENT: We wish to thank Dr. William Hughes for his critical review of the manuscript.

REF'ERENCES 1 Wendt VE, Puro HE, Shapiro J, et al: Angiothrombotic pulmonary hypertension in addicts: "Blue velvet" addiction. JAMA 188:755-757, 1964 2 Puro HE, Wolf PL, Skirgaudas J, et aI: Experimental production of human "blue velvet and red devil" lesions. JAMA 197:1100-1102,1966 3 Hahn HH, Schweid AI, Beaty HN: Complications of injecting dissolved methylphenidate tablets. Arch Intern Med 123:656-659, 1969 4 Hopkins GB, Taylor DG: Pulmonary talc granulomatosis: A complication of drug abuse. Am Rev Respir Dis 101:101-104,1970 5 Lewman LV: Fatal pulmonary hypertension from intravenous injection of methylphenidate (Ritalin) tablets. Hum PathoI3:67-70, 1972 6 Arnett EN, Battle WE, Russo JV, et al: Intravenous injection of talc-containing drugs intended for oral use: A cause of pulmonary granulomatosis and pulmonary hypertension. Am J Med 60:711-718, 1976 7 Robertson CH, Reynolds RC, Wilson JE: Pulmonary hypertension and foreign body granulomas in intravenous drug abusers: Documentation by cardiac catheterization and lung biopsy. Am J Med 61:657-664,1976 8 Moskowitz RL: Talc pneumoconiosis: A treated case. Chest 58:37-41, 1970 9 Smith RH, Graf MS, Silverman JF: Successful management of drug-induced talc granulomatosis with corticosteroids. Chest 73:552-554, 1978 10 Hayes RL, Nelson B, Swartzendruber DC, et aI: Studies of the intracellular deposition of 87gallium. J Nucl Med 12:364, 1971 11 Niden AB, Mishkin FS, IChurana MML: 87Gallium citrate lung scans in interstitial lung diseases. Chest 69:266268, 1976 12 ThadepaDi H, Rambhatla Ie. Mishkin FS, et aI: Correlation of microbiologic flndings and 87gallium scans in patients with pulmonary infections. Chest 72:442-448,

CHEST, 77: 4, APRIL, 1980

1977 13 Strieder DJ, Mark EJ: Case records of the Massachusetts General Hospital. N Eng) J Med 298:327-332, 1978 14 Kinoshita F, Ushio T, Maebwa A.et aI: Scintiscanning of pulmonary diseases with 87gallium citrate. J Nucl Med 15:227-233, 1974 15 Crystal RG, Fulmer JD, Roberts WC, et aI: Idiopathic pulmonary fibrosis: Clinical, histologic, radiologic, physiologic, scintigraphic, cytologic, and biochemical aspects. Ann Intern Med 85:769-788, 1976 16 Waxman AD, Blendon JI\, Richli W, et aI: Steroid-induced suppression of gallium uptake in tumors of the central nervous system: Concise communication. J Nucl Med 19:480-482, 1978 17 Hildiclc:-Smith GY: The biology of talc. Br J Industr Med 33:217-229, 1976 18 Unanue EI\, Benacerraf B: Immunologic events in experimental hypersensitivity granulomas. Am J PathoI71:349359,1973 19 Roberts I\, Moore VL: Immunopathogenesis of hypersensitivity pneumonitis. Am Rev Respir Dis 116:1075-1090, 1977 20 Moore VL, Hensley GT, F'mk IN: An animal model of hypersensitivity pneumonitis in the rabbit. J Clin Invest 56:937-944,1975 21 Bice DE, McCarron Ie, Hoffman EO, et al: Adjuvant properties of Micropoly",ora fDeni. Int Arch Allergy Appl lmmunol55:267-274,1977

Reversible Central Apnea in an Infant with Cyanotic Heart Disease* CaTl E. Hunt. M.D.

1he plll'pOllle of this report is to present the ftndinp in a neonate with tetralogy of Fallot and a history of prolonged sleep-related apnea requiring resuscitation. At a baseUne arterial oxygen preIBUI'e of 46 mm JII, his preopentive responses to carbon dioDde dnring nonREM sleep (26.1 and 26.6 mI/kg/min/mm JIg of alveolar carbon dIoDde tension [PAC02 D were identical to those reported in near-miss sodden infant death syndrome. Following a systemic-pulmonary arterial shunt, the arterial satnntlon reached 95 percent, and no fnrtber apnea oc:c:urred. 1he prompt nonnalization of the response to carbon dioxide folowing SUIIery (75.1 and 75.4 mI/kg/min/mm JIg of PACOJ indicates that, unlike infanes with the sudden infant death syndrome, a low sensitivity to carbon dioxide In Infanes with cyanotic heart disease may be dependent on hypoxemia and, thns, reversible. are now being identified in whom prolonged I nfants sleep-related apnea is associated with an abnormality in central carbon dioxide responsiveness. Patients with central hypoventilation syndrome, for example, have essentially no ventilatory sensitivity to carbon di-

c::.

-From the Department of Pediatrics, Children's Memorial Hospital and Northwestern University, Chicalo. by the Sprague Foundation and grant Supported in RR-05475-14 the National Institutes of Health. Reprint reqU88t8: Dr. Hunt, Children', Memorial Hos¢tal, 2300 Children', Plaza. Chicago 60614

REVERSIBLE CENTRAL APNEA 585

oxide, 1 and a low ventilatory response to carbon dioxide has been identified in infants at risk for the sudden infant death syndrome.t The purpose of this brief report is to present tbe Bndings in an infant with tetralogy of Fallot who, similar to the infants with near-miss sudden infant death syndrome, had prolonged sleep-related apnea associated with an impaired ventilatory response to breathing carbon dioxide during non-REM sleep; however, unlike the infants with near-miss sudden infant death syndrome, his prolonged sleep-related apnea and diminished sensitivity to carbon dioxide promptly normalized as soon as arterial oxygenation was improved by a palliative shunt. CASE REPoRT

The patient is a full-term male infant who was admitted to Children's Memorial Hospital, Chicago, at two days of age for evaluation of cyanosis and multiple dysmorphic features. Cardiac catheterization established the diagnosis of tetralogy of Fallot, with arterial saturations of 82 to 87 percent. A systemic-pulmonary arterial shunt was not required, and the patient was discharged at 12 days of age. Chromosomal studies obtained during this admission subsequently revealed a 4q+ syndrome. The patient was readmitted four days later with a history of being found apneic and cyanotic at home and requiring mouth-to-mouth resuscitation. On admission the sample of arterial blood (with patient breathing air) revealed a pH of 7.43, arterial carbon dioxide tension of 28 mm Hg, arterial oxygen pressure (Pa0 2 ) of 46 mm Hg. He was mildly cyanotic at rest. Several episodes of apnea and increased cyanosis occurred following admission, some of which did require resuscitation efforts. A right pulmonary arterial-ascending aortic anastomosis was performed when the patient was 26 days old. Following surgery, he was acyanotic, had an arterial saturation of approximately 95 percent, and had no further clinical abnonnalities of respiratory control. Steady-state carbon dioxide response tests with 5 percent carbon dioxide were obtained four and five days prior to the shunt procedure and were repeated at 8 and 13 days after surgery. Our methods used to measure the alveolar carbon dioxide tension (PAC0 2 ) , tidal volume (TV), and minute ventilation 'VE have been described previously.l,a All measurements were obtained during intervals of sleep when the breathing pattern was slow and regular and there was no spontaneous muscular activity or eye movements suggestive of active (REM) sleep. The ventilatory response to breathing carbon dioxide was expressed as the change in minute ventiper millimeter of mercury of increase in endlation (~'VE) tidal PAC0 2 (mllkg/min/mm Hg of PAC0 2 ) . The ventilatory measurements during non-REM sleep are summarized in Table 1. Compared to normal values,2,. respiratory frequency was elevated and PAC0 2 was decreased prior to surgery. Although respiratory frequency, TV, and 'VE were not significantly different following surgery, the PAC0 2 was now higher than normal, Since there was no acid-base imbalance before surgery and no reason after surgery for an increase in production of carbon dioxide, the higher PACO~ occurring after surgery is assumed to be secondary to a-decrease in alveolar dead space. The two ventilatory responses to steady state carbon dioxide breathing obtained before surgery were identical at 26.1 and 26.6 mllkg/min/mm Hg of PAC0 2 (Fig 1). Following

56& CARL E. HUNT

Table l-Yendlaaory Meauremene. duriq Non-REM Sleep· Before Shunt·· After Shunt** ,-----A------.. ~

21 Days

Data

22 Days

34 Days

39 Days

Respiratory frequency, breaths per minute

44

39

43

48

End-tidal PAC01, mm Hg

27

27

42

43

TV, ml/kg]

4.4

6.8

4.7

3.9

VE , ml/kg/mint

195

265

200

185

•Although never simultaneous with these measurements, capillary pH determined on these days ranged from 7.36 to 7.41. **Aortic-pulmonary shunt performed at age of 26 days. tBody temperature and pressure, saturated. surgery, the responses of the two carbon dioxide slopes were also identical, but significantly increased to 75.2 and 75.4 ml/kg/min/mm Hg of PAC0 2 • For all four carbon dioxide responses obtained, the correlation coefficient ( r) for the regression line obtained was greater than or equal to 0.93. DISCUSSION

Patients with cyanotic congenital heart disease are known to have impaired ventilatory responses to hypoxia." Following corrective surgery and normalization of arterial saturation, hypoxic ventilatory responses have 400

__ BEFORE SHUNT -

AFTER SHUNT

300

~VE

(ml/kg/min) 200

100

o

1

2

6.

3

4

5

6

PAC02 (nunHg)

1. Change in minute ventilation (~VE) vs change in end-tidal PAC0 2 (aPAC0 2 ) in response to steady-state breathing of 5 percent carbon dioxide. Postoperative values obtained are within normal range. 2 , . For each individual carbon dioxide response test, r ~ 0.93. FiGURE

CHEST, 77: 4, APRIL, 1980

returned to normal levels within a few weeks. In contrast to hypoxic responses, very little information is available regarding hypercapnic ventilatory responses in patients with cyanotic congenital heart disease. Although normal carbon dioxide responses have been reported in adults following correction of tetralogy of Fallot,8 no preoperative measurements of carbon dioxide responsiveness are available. The clinical abnormalities of respiratory control that were exhibited by this infant were similar to those reported in infants with prolonged sleep-related apnea requiring repeated resuscitation and thus prompted us to assess hypercapnic ventilatory response. The preoperative values for carbon dioxide response obtained were significantly lower than in normal infants at the same agefo and were in fact identical to those reported in infants with near-miss sudden infant death syndrome." however, unlike the infants with aborted sudden infant death syndrome, our patient did not have a normal arterial oxygen saturation initially and did demonstrate a normal carbon dioxide response once arterial oxygenation was improved. It is known that the responsiveness to carbon dioxide can be affected by the level of oxygenation; 7 for example, in normal infants the ventilatory response to breathing carbon dioxide is significantly less when breathing 15 percent oxygen than when breathing air. a The diminished carbon dioxide response in our patient in the presence of hypoxemia and the prompt normalization of the carbon dioxide response following the shunt indicate that the initial low carbon dioxide response was dependent on hypoxemia and was not related to any inherent abnormality in ventilatory control. In summary, symptomatic apnea may occur as a consequence of an hypoxemiCHiependent decrease in neural inspiratory drive. In hypoxemic patients, therefore, diminished responsiveness to carbon dioxide cannot be Interpreted unless PaOI is known.

Echocardiographic Source of Early Anterior Systolic Motion in Late Systolic: Mitral Valve Prolapse· Nicholoa Z. Kerin, M.D.;·· WaldemtJr J. WtJinczul:, M.D., F.C.C.P.;t

Philip N. CII6CDI1e, MD., F.C.C.P.;t John Schalrer, D.O.;§ and Meloyn Rubenfire. M.D.;I! wUh technictJl aai&ttmce of Fran PenJino

The ecbocardlognpble features of patients with ....... chnte mitral valve have revaled the combination of 8D early systoUc movement of the mitral valve and late systolie prolapse. CrosHecflonai eehoeardiognpId and angIopaphfc studies showed that the early systolic anterior motion produced by the preleDCe of • 8aO scallop of the 8Dterlor mitrallea8et In the left ventrlcalar

w.

outftow tract.

E

chocar diogra phic study for the diagnosis of mitral valve prolapse was initially described by Shah and Gramiak. 1 With this abnormality the most speciflc echocardiographic change in mitral valve motion occurs in systole. At the beginning of systole, the mitral valve m0tion may be normal, but in midsystole, there is a posterior and downward bucJding throughout late systole. l o• Early anterior systolic mitral valve movement, with rapid recovery reminiscent of systolic anterior motion in idiopathic hypertrophic subaortic stenosis, fo is rarely seen in prolapsing mitral valve," This early systolic anterior motion is not exaggerated by the administration of amyl nitrite or Valsalva's maneuver.s The present report is concerned with a case characterized by an early systolic anterior motion and a late systolic prolapse. The shape and motion of the mitral 1eaHets were examined by cross-sectional echocardiographic and angiographic studies.

llEFERENCES

CASEREPOBT

1 Hunt CE, Matalon SV, Thompson TR, et al. Central hypoventilation syndrome: experience with bilateral pluenic nerve pacing in three neonates. Am Rev Resph Dis 1978; 118:23-8 2 Shannon OC, Kelly DH, O'Connell K. Abnormal regulation of ventilation in infants at risk for sudden-infant-death syndrome. N Engl J Medl977; 297:747-50 3 Rigatto H. Respiratory control and apnea in the oewbom infant. Crit Care Med 1977; 5:2-9 4 Frantz 10, Adler SM, Thach BT, Taeusch HW. Maturational effects on respiratory responses to carbon dioxide in premature infants. J Appl Physiol 1976; 41:41-5 5 Blesa MI, Lahiri S, Phil D, RaahIdnd WJ, Fishman AP. Normalization of the blunted ventilatory response to acute hypoxia in congenital cyanotic heart disease. N Eng} J Med 1977; 296:237-41 6 Sorensen SC, Severinghaus JW. Respiratory insensitivity to acute hypoxia persisting after correction of tetralogy of FaIIot. J Appl Physioll968; 25:221-3 7 Motoyama EK, Almirall JJ. Milic-EmiIi J. A new analysis of the interaction of hypoxia and hypercapnia on breathing. Chest 1978; 73( suppl2) :263-6

Since 1971, a 46-year-old woman had been known to have mitral valve prolapse. For nine months, she complained of increasing paroxysmal nocturnal dyspnea and "three-piDow orthopnea. The patient denied having a history of rheumatic heart disease, syphilis, or hypertension. One of her children had a patent ductus arteriosus. Physical eumiDation showed an apparently healthy woman with blood pressure of 100/65 DUD Hg and normal

CHEST, 77: 4, APRil, 1980

II

·From the Noninvasive Laboratory, Section of Cardiovascular Medicine. Qepartment of Medicine, and the Sectioa of Diagnostic Radiology, Department of Radiology, Sinai Hospit81 of Detroit; aDd die Department of Medicine, Wayne State University, Detroit. "Director, Noninvasive Laboratory, and Assistant Professor of Medicine. tAssociate Chief, Section of CardJovascular Diseases, and Associate Professor of Medicine. tChief. Section of Diagnostic Radiology, andAssistant Clinical Professor. §Fellow. Section of Cardiovascular Diseases. IIChief, Section of Cardiovascular Diseases, and Associate Professor of Medicine. Reprint requsatl: Dr. Kerin, SitwJi HOIJlIltJl of DeftoiI, Detroit

48234

ECHOCARDIOGRAPHIC SOURCE OF WLY AmRIOR SYSTOUC lIonOIL 587