Endurance Exercise in the Presence of Heart Disease

in 17 of 40 (42 percent) who received doxapram infusions for greater than six hours, no tachyphylaxis developed between six and 48 hours. As our patient had no apparent reversible cause for her repeated failures to wean, and since the patients symptoms very closely paralleled those seen in primary alveolar hypoventilation, we empirically used doxapram. As evident from Figure 1, the change was dramatic, and the use of doxapram obviated the need to reintubate the patient. Moreover, a "recruitment" phenomenon was observed wherein each successive use of doxapram resulted in a sustained increase in respiratory rate which persisted after discontinuance of the drug. This same phenomenon has been observed when doxapram was used to facilitate weaning in brain-damaged patients. 13 We could find no previous reports where doxapram had been used to assist weaning from mechanical ventilation in adults. Nor has newly developed central hypoventilation been identified as an impediment to weaning in the literature to date. Fahey and Hydes6 study identified a subgroup of COPD patients who were "won't breathers" and C02 retainers and who, in addition, had a depressed ventilatory drive relative to nonretainers ("pink puffers"). Our patient had an amplification of this depressed ventilatory drive for reasons which remain unclear. We suspect that this condition exists in other patients requiring prolonged mechanical ventilation and may contribute to their failure to wean. It may remain unrecognized when masked by the other factors which impair weaning outlined above. Further investigations are needed to support the existence and frequency of this problem and the potential benefits of treatment with doxapram. ACKNOWLEDGMENT: The authors gratefully acknowledge the assistance of Mrs. Martha Rhodes and Shirley Haake in the preparation of this manuscript. REFERENCES

1 Tobin MJ, Perez W, Guenther SM, Semmes BJ, Mador MJ, Allen SJ, et al. The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation. Am Rev Respir Dis 1986; 134:1111-18 2 Cohen CA, Zagelbaum G, Gross D, Roussos C, Macklem PT. Clinical manifestations of inspiratory muscle fatigue. Am J Med 1982; 78:308-16 3 Hughes RL, Davison R. Limitations of exercise reconditioning in COLD. Chest 1983; 83:241-49 4 Zwillich CW, Pierson DJ, Hofeldt FD, Lufkin EG, Wei! JV, Ventilatory control in myxedema and hypothyroidism. N Eng! J Med 1975; 292:662-65 5 Javaheri SJ, Shore NS, Rose B, Kazemi H. Compensatory hypoventilation in metabolic alkalosis. Chest 1982; 81:296-01 6 Fahey PJ, Hyde Rw. "Won't breathe" vs" can't breathe," detection of depressed ventilatory drive in patients with obstructive pulmonary disease. Chest 1983; 84:19-25 7 Aubier M, Murciano D, Lecocguic Y, Vires N, Jacquenes Y, Squara P, et al. Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure. N Eng! J Med 1985; 313:420-24 8 Ward JW. Franko BV. A new centrally acting agent (AHR-619) with marked respiratory stimulating, presssor, and "awakening" effects. Fed Proc 1962; 21:325 9 Burki NK. Ventilatory effects of doxapram in conscious human subjects. Chest 1984; 85:600-04

10 Ohi M, Nakashima M, Heki S, Kato M, Sagawa Y. Doxapram hydrochloride in the treatment of acute exacerbation of chronic respiratory failure. Chest 1978; 74:453-54 11 Houser WC, Schlueter DP. Prolonged doxapram infusion in obesity-hypoventilation syndrome. JAMA 1978; 239:340-41 12 Lugliani R, Whipp BJ, Wasserman K. Doxapram hydrochloride: a respiratory stimulant for patients with primary alveolar hypoventilation. Chest 1979; 76:414-19 13 Gilbert J, Rice WH, Johnston J. Possible doxapram reversal of ventilator dependence in a brain damaged patient. Crit Care Med 1985; 13:605-06 14 Freeman J. The effectiveness of doxapram administration in hastening arousal following general anesthesia in outpatients. AANA-J 1986; 54:16-20 15 Moser KM, Luchsinger PC, Adamson JS, McMahon SM, Schlueter DP, Spivack M, et al. Respiratory stimulation with intravenous doxapram in respiratory failure. N Eng! J Med 1973; 288:427-31

Endurance Exercise in the Presence of Heart Disease lbmela S. Douglas, M.D.;* Alison Sigler; M.D.;* Mary L. O'Toole, Ph.D.;t and W Douglas B. Hiller; M.D.t

Although patients with heart disease have successfully completed marathon runs, the immediate cardiac effects of similar and greater distance endurance exercise competition are unknown. Two such cases are presented, demonstrating that vigorous exercise and extreme levels of fitness are not precluded in the cardiac patient. (Chut 1989; 95:697-99)

patient chooses to exercise at all, the activity I f isa cardiac usually moderate in intensity and duration, and

noncompetitive. However, patients who have undergone coronary bypass grafting or myocardial infarction or who have hypertrophic cardiomyopathy have successfully completed endurance racing events such as marathons.,.,.. While such exercise is pursued by a select few, the physician has limited scientific knowledge to draw upon in advising the increasingly common, aspiring cardiac patient-athlete. Accordingly, we studied the immediate cardiac effects of endurance exercise competition in two patients with different forms of heart disease, one following myocardial infarction and bypass grafting, and one following receipt of a cardiac transplant. CASE REPORTS CASE

1

At age 48, this previously healthy white man began experiencing progressive, exertional angina, culminating in an anterior myocardial infarction. Treadmill exercise stress test was positive and cardiac catheterization showed a 100 percent obstruction in the proximal left anterior descending coronary artery, with collateral flow provided by the right coronary artery. There were 50 percent lesions in both the first diagonal and the first circumflex marginal arteries. The right coronary artery was small but had a mid-90 percent From the *Cardiovascular Section, Hospital of the University of Pennsylvania, Philadelphia, and tthe Baptist Memorial Hospital, Campbell Clinic, University of Tennessee, Memphis. Reprint requests: Dr: D
897

Table 1-Buulta at Pre-race Baseline, within 10 minutes of&ce Finiah, and After 24 Hours of Recovery M-Mode Echocardiogram PtNo 1 (2.4 mi swim, Pre-race Finish Recovery

BP

HR

112 mi bike, 26.2 mi run) 120180 41 135190 69 105180 71

2 (1.5k swim, 40k bike, 10k run) Pre-race 140/150 92 1801105 104 Finish Recovery 100'100 86

Doppler LV Filling Velocities

LVDd (em)

LVDs (em)

PWI'd (em)

PWfs (em)

FS (%)

Early (crnls)

Late (cm/s)

Early/ Late

5.4 5.1 4.7

3.1 3.0 3.0

1.3 1.2 1.1

2.0 2.1 2.0

43 41 35

79 66 62

57 62 50

1.4 1.1 1.2

5.2 3.0 5.2

2.6 1.2 2.8

.8 1.5 .9

1.8 2.5 1.6

50 60 46

107 63

64

35

1.8 1.3 2.1

80

30

LVDd, LVDs =left ventricular diameter at end-diastole and end systole; PWI'd, PWfs =posterior wall thickness at end diastole and end systole; FS =fractional shortening. obstruction. The patient underwent uneventful single vessel coronary bypass grafting. Five years following surgery, he competed in the Hawaii Ironman Triathlon Race (2.4 mile swim, 112 mile bike, 26.2 mile run), for which be trained 30 hours per week. His training regimen consisted of weekly averages of six miles of swimming (38 minlmi pace; range three to eight mi!wk), 200 miles of cycling (20 mph pace; range 150 to 300 mi!wk) and 70 miles of running (7'3CY' minlmi pace; range 60 to 68 mi!wk). Little or no interval or high intensity training was included. On a bicycle exercise test, be achieved a maximal workload of 19 METS, with an estimated maximal oxygen consumption {Vo1 max) of 66.5 ml!kglmin. At the time of the triathlon, be was asymptomatic and taking no medications. Baseline physical examination revealed a grade 216 blowing apical systolic murmur. Resting M-mode and two dimensional ecbocardiogram showed a top normal sized left ventricle with concentric hypertrophy. He had anteroapical hypokinesis but an overall normal ejection fraction (Thble 1). His ECG showed left atrial abnormality, left ventricular hypertrophy, and a loss of precordial R wave voltage consistent with an anterior scar. He successfully completed the triathlon in 14 hours and six minutes. At the finish line, he was without chest pain or excessive dyspnea or fatigue. His physical examination, echocardiogram, Doppler, and ECG were essentially unchanged from baseline (Thble 1). Serum electrolyte values showed increases inK, CPK, and LDH (Table 2). Recovery studies obtained 24 hours after the race finish showed no change from pre-race or finish echo and ECG recordings other than a persistent increase in heart rate and a further increase inCPK. CASE2

Over several years, this 45-yeaM>Id white man developed an idiopathic cardiomyopathy, and while pressor dependent, underwent cardiac transplantation. Previously inactive, be began exercise

training 10 to 15 hours per week and was studied nine months postoperatively during the United States Triathlon Series National Championship Race (1.5 k swim, 40 k bike and 10 k run). At that time, he was asymptomatic although he was taking prednisone, azathioprine, cyclosporine, persantine, and hydrochlorthiazide. Baseline physical examination was remarkable only for an s. and a brief systolic ejection murmur. Resting echocardiogram was normal (Table 1). Resting ECG showed a rightward axis, incomplete right bundle branch block, and inferior T wave abnormality. Selected serum chemistries are shown in Table 2. He successfully completed the triathlon in four hours and 12 minutes. At the finish, his physical exam result was unchanged; however, his echocardiogram showed a marked decrease in left ventricular cavity size without a change in fractional shortening. Left ventricular filling, on Doppler echo, showed a decrease in the early to late flow velocity ratio. These changes resolved after 24 hours of recovery, although systolic BP remained slightly elevated. The ECG showed no significant change. A Holter study obtained during the race showed sinus rhythm throughout with a mean heart rate of 144 bpm (range of 139 to 162 bpm). DISCUSSION

These cases document remarkable athletic achievement in two patients with different forms of heart disease. While necessarily anecdotal, they suggest that significant cardiac abnormalities do not preclude either the attainment of extreme fitness or the safe, successful completion of competitive endurance events. Exercise training of at least moderate intensity has been embraced for its ability to modify cardiac risk factors and to improve the quality of life. However, the achievement of cardiac conditioning is controversial in the coronary pa-

Table 2-Buultafrom Selected Blood Chemiatries PtNo

Na (mgldl)

1 (2.4 mi swim, 112 mi bike, 26.2 mi run) Pre-race 140 Finish 143 Recovery 2 (1.5k swim, 40k bike, 10k run) Pre-race 145 Finish 143 Recovery 142

898

K (mwdl)

CPK (UIL)

4.4 5.2

554

4.6 4.2 4.6

%MB

LDH (UIL)

%LD-1

207 318 257

25 20

936

3 3 2

92 156 213

1 3 <1

209 266 220

23

108

22

8

22

Endurance Exercise in Heart Disease (Douglas et a/)

tient,"" 10 and exercise training in patients with a denervated, transplanted heart appears to result in an increased peripheral oxygen consumption without an increase in cardiac output. 11 ' 14 Our first patient suggests that, under some circumstances, those with extensive coronary artery disease may display remarkable endurance exercise performance beyond the previously reported completion of marathon runs. 3•4 Of note, however, is the persistent elevation in heart rate at recovery, which suggests evidence of delayed cardiac fatigue or overwork. 15 Although both fractional shortening and blood pressure were slightly reduced at recovery, these differences are small and are most likely related to the decrease in left ventricular size rather than indicative of cardiac dysfunction. Other than these changes, the finish and recovery values for all parameters fall within the range of those previously published for other, similarly aged or even younger competitors, 16 suggesting that exercise effects in our patient were indeed similar to those in healthy normal subjects. In particular, the increases in CPK at finish and recovery are consistent with those seen in other athletes completing this amount of exercise,l1 and in the absence of elevation of %CPK-MB or LD-1 isoenzymes, do not suggest myocardial damage. Our second patient demonstrates that vigorous exercise training of the denervated heart is also possible. Kavanagh et al 14 have clearly demonstrated this in a longitudinal study of a large group of transplant recipients, including one who successfully completed a marathon run. 18 Several features are of note in our patient. The decrease in ventricular dimensions without change in shortening seen at race finish was resolved within 24 hours. While explainable by dehydration, vasodilation secondary to elevation in body temperature, and/or the decrease in diastolic filling time associated with an increased heart rate, others have reported a decline in LV volume at higher levels of exercise in transplanted hearts. 11 The altered left ventricular filling pattern is similar to transient changes we have previously observed in ultraendurance events and may represent a transient alteration in diastolic characteristics. 16 Finally, systolic blood pressure remained mildly elevated at recovery, perhaps because of adrenergic stimulation. It is important to state firmly that our findings do not imply that endurance exercise is safe or even possible for most cardiac patients. Indeed, several recent reports suggest that myocardial contractility may be transiently impaired at the end of a marathon run. 1,._21 Further, it must be remembered that those with underlying organic heart disease are susceptible to the common "side effects" of prolonged exercise, such as dehydration, hyperthermia, hyponatremia, and other electrolyte abnormalities, which might have more significant consequences in those with heart disease. Obviously, the cases presented are exceptionally motivated individuals, whose illnesses left them with adequate cardiac reserve. They demonstrate that, while not suitable for the vast majority of cardiac patients, vigorous exercise and the achievement of extreme levels of fitness are not necessarily precluded.

REFERENCES 1 Wenger NK. Rehabilitation after myocardial infarction. JAMA 1979; 242:2879-81 2 Coplan NL, Gleim GW, Nicholas JA. Principles of exercise prescription for patients with coronary artery disease. Am Heart J 1986; 112:145-49 3 Kavanagh T, Shephard RH, Pandit V. Marathon running after myocardial infarction. JAMA 1974; 229:1602-05 4 Hellerstein HK. Limitations of marathon running in the rehabilitation of coronary patients: anatomic and physiologic determinants. Ann Acad Sci 1977; 301:484--94 5 Maron BJ, W!sley YE, Arce J. Hypertrophic cardiomyopathy compatible with successful completion of the marathon. Am J Cardiol1984; 53:1470-71 6 Amsterdam EA, Laslett LJ, Dressendorfer RH, Mason DT. Exercise training in coronary heart disease: is there a cardiac effect? Am Heart J 1981; 101:870-73 7 Boone T. Exercise prescription for cardiac patients: reasons for concern. Sports Med 1986; 3:157-64 8 Paterson DH, Shephard RJ, Cunningham D, Jones NL, Andrew G. Effects of physical training on cardiovascular function following myocardial infarction. J Appl Physiol1979; 47:482-89 9 Hartung GH, Rangel R. Exercise training in postmyocardial infarction patients: comparison of results with high risk coronary and post-bypass patients. Arch Phys Med Rehabil1981; 62:14750 10 Ehsani AA, Martin WH, Heath GW, Coyle EF. Cardiac effects of prolonged and intense exercise training in patients with coronary artery disease. Am J Cardiol1982; 50:246-54 11 Savin WM, Haskell WL, Schroeder JS, Stinson EB. Cardiorespiratory responses of cardiac transplant patients to graded, symptom-limited exercise. Circulation 1980; 62:55-62 12 Pope SE, Stinson EB, Daughters GT, Schroeder JS, Ingels NB, Alderman EL. Exercise response of the denervated heart in long-term cardiac transplant recipients. Am J Cardiol 1980; 46:213-18 13 Schroeder JS. Hemodynamic performance of the human transplanted heart. Transplant Proc 1979; 11:304-08 14 Kavanagh T, Yacoub MH, Mertens OJ, Kennedy J, Campbell RB, Sawyer P. Cardiorespiratory responses to exercise training after orthotopic cardiac transplantation. Circulation 1987; 77:162-71 15 Dressendorfer RH, Wade CE, Scaff JH. Increased morning heart rate in runners: a valid sign of overtraining? Phys Sports Med 1985; 13:77-86 16 Douglas PS, OToole M, Hiller WDB, Hackney K, Reichek N. Cardiac fatigue after prolonged exercise. Circulation 1987; 76:1206-13 17 Palevsky H, Douglas PS, Hiller WD, Bogin K, Reichek N, OToole M. Muscle enzyme patterns before and after ultraendurance racing. Med Sci Sports Ex 1986; 18:60 18 Kavanagh T, Yacoub MH, Campbell R, Mertens D. Marathon running after cardiac transplantation: a case history. J Cardiopulmonary Rehab 1986; 6:16 19 Perrault H, Peronnet F, Lebeau R, Nadeau RA. Echocardiographic assessment of lett ventricular performance before and after marathon running. Am Heart J 1986; 112:1026-31 20 Chan W, Pipe A, Barrie M. Acute effect of marathon running on left ventricular function. (Abstract) Med Sci Sports Exerc 1987; 19(suppl2):83 21 Boynton M, Winslow E, Ling R, Mehlman D. Are echocardiographic estimates of left ventricular function altered by running a marathon? (Abstract) Med Sci Sports Exerc 1987; 19(suppl 2):84

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