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The sleep electrocardiogram at extreme altitudes
how clearance is calculated for a drug following first-order kinetics. Third, we did not intend to mislead readers with the term “steady-state.” Based on the study by Gugler et aLs the phenytoin concentrations at the doses we administered should have been at steady state after 14 days of dosing. We do agree that amiodarone concentrations after 6 and one-half weeks (i.e., 45 to 46 days) of daily administration of amiodarone were probably not at steady state. However, if an average half-life of 25 days is assumed for amiodarone, then our subjects were approximately at 75% of steady state, assuming amiodarone follows first-order pharmacokinetics. In conclusion, we feel that a 25% reduction in the daily dose of phenytoin for patients receiving 3 to 4 mg/kg/day is a reasonable initial estimate when amiodarone is concurrently administered. We reiterate that changes in phenytoin dosage regimens during coadministration with amiodarone should ultimately be guided by a combination of the clinical condition of the patient and by the serum concentrations of phenytoin. Paul E. Nolan, Jr., P~MD Brian L. Ersbd, PIMSID Gifford L. Hoyer, MI Marla Bliss, 8s Kathleen Gear, es, RY Frank I. Marcus, MD
Tucson,Arizona 19 September 1990 1. Grech-Belanger0. Depressiveeffect of amicdaroneon hepatic drug metabolismin the rat. Res Commun Chem Pathol Phnrmacol 1984; 44: 1S-30.
2. Winter WE,Tozer TN. Phenytoin.In: Evans WE, Schentag JJ, Jusko WJ, eds. Applied Pharmacokinetics. Principles of Therapeutic Drug Monitoring. Spokane:Applied Therapeutics, 1986:493-558. 3. McGovern G, Geer VR, LaRaia PJ, Garan H, Ruskin JN. Possible interaction between amiodarone and phenytoin. Ann Intern Med 1984;101:650-651. 4. Cheng H, Jusko WJ. Mean residencetime concepts for pharmacokinetic systems with nonlinear drug elimination described by the Michaelis-Menten equation. Pharmacol Res 1988;5:156-1.64.
of any tachyarrhythmias (see our Figures 6 and 7L2 This case confirms comoletelv the data obtained by Malconian ei alin the hypobaric chamber.
with respiration, may yield important additional information in such patients,2 and should also have been measured in the patients presented by Vermilion et al. It is Giantanco Ruja, MD possible that large changes in diastolic Padova, Italy function occurred despite little change in 8 August 1990 A-wave velocity after balloon valvuloplas1. Malconian M, Hultgren H, Nitta M, An- ty. There are clearlv diastolic abnormalihelm J, HoustonC, Fails H. The sleeuelectro- ties in these patients with severe RV outcardiogram at extreme altitudes (Operation flow tract obstruction but the exact nature EverestII). Am J Cardiol 1990:65:1014-1020. of these abnormalities has yet to be deter2. Buja GF, Simini G, Miragiia G, Nava A. mined. Twenty-four-hours Holter monitoring in the Andrew N. Redington conquestof K2. J Sports Card 1985;2:43-49. Michael L. Rigby Alison Hayes Dan Penny
London, United Kingdom 10 August 1990
Right Ventricular Diastolic Function in Children Although we found the data presented by Vermilion et all interesting, we believe their approach to the analysisof right ventricular (RV) diastolic filline mav be oversimplistic and would advise caution in the interpretation of their data regarding the isolated analysis of tricuspid A-wave velocity and velocity integral in patients after relief of RV outflow tract obstruction. Indeed, these changes may be uninterpretable in the absence of a detailed analysis of the pattern of pulmonary artery flow. The accompanying figure shows the pulmonary artery flow pattern of 1 of 4 patients whom we studied after complete relief of RV outflow tract obstruction for pulmonary atresia with intact septum. Although there was a dominant A wave on the tricuspid inflow Doppler, it is almost wholly accounted for by forward flow into the pulmonary artery coincident with atria1 systole. Thus, late RV diastolic filling may be markedly restricted in the presence of a large A wave on the tricuspid inflow Doppler, the right ventricle acting as a conduit between the right atrium and the pulmonary artery in late diastole. E-wave deceleration time, and its change Y
.
1. Vermilion RP, Snider AR, MelionesJN, Peters J, Merida-AsmusL. PulsedDoppler evaluation of right ventricular diastolic fiiling in chil-
dren with pulmonary valve stenosis before and after balloonvalvuloplasty.Am J Cardiol 1990: 66179-84. 2. Appleton CP, Hatle LK, PoppRL. Demonstration of restrictive ventricular ohvsiologvbv Doppler echocardiography.J Am’&1 Caydid 1988;11:757-768. REPLY: The comments made by Redington and colleagues are intriguing but largely unrelated to our recent article on right ventricular (RV) diastolic filling in children with isolated pulmonary valve stenosis.’ We agree that an isolated analysis of tricuspid valve peak A velocity and A area fraction is inadequate to assessRV diastolic filling. For this reason, our study included measurements of indexes of early diastolic filling such as peak E velocity, first-third area fraction. E area fraction. and peak filling rate normalized for stroke volume. We disagree with Redington et al’s statement that RV diastolic function cannot be assessedin the absence of a detailed analysis of the pattern of pulmonary artery flow. In our experience, analysis of the pulmonary artery Doppler wave
ECG
5. Gugler R, Manion CV, Azarnoff DL. Phenytoin: pharmacokineticsandbioavailability. Clin Pharmacol Ther 1976;19:135-142.
The Sleep Electrocardiogram Extreme Altitudes
at
I found the article by Malconian et al’ to be informative and interesting and would like to add to their report my experience in this field. As reported,2 I had the opportunity to examine a Holter recording in a subject who climbed, in the summer of 1983, the northern face of K2. During this recording he spent a night at a bivouac at about 8,200 meters above sea level. I observed, while he slept at this altitude, sudden and cyclic variations of heart rate with periods characterized by junctional rhythm (45 beats/min) and sinus rhythm (65 beats/min) in the absence
PCG
THE AMERICAN JOURNAL OF CARDIOLOGY FEBRUARY 1, 1991
329
Tucson,Arizona 19 September 1990 1. Grech-Belanger0. Depressiveeffect of amicdaroneon hepatic drug metabolismin the rat. Res Commun Chem Pathol Phnrmacol 1984; 44: 1S-30.
2. Winter WE,Tozer TN. Phenytoin.In: Evans WE, Schentag JJ, Jusko WJ, eds. Applied Pharmacokinetics. Principles of Therapeutic Drug Monitoring. Spokane:Applied Therapeutics, 1986:493-558. 3. McGovern G, Geer VR, LaRaia PJ, Garan H, Ruskin JN. Possible interaction between amiodarone and phenytoin. Ann Intern Med 1984;101:650-651. 4. Cheng H, Jusko WJ. Mean residencetime concepts for pharmacokinetic systems with nonlinear drug elimination described by the Michaelis-Menten equation. Pharmacol Res 1988;5:156-1.64.
of any tachyarrhythmias (see our Figures 6 and 7L2 This case confirms comoletelv the data obtained by Malconian ei alin the hypobaric chamber.
with respiration, may yield important additional information in such patients,2 and should also have been measured in the patients presented by Vermilion et al. It is Giantanco Ruja, MD possible that large changes in diastolic Padova, Italy function occurred despite little change in 8 August 1990 A-wave velocity after balloon valvuloplas1. Malconian M, Hultgren H, Nitta M, An- ty. There are clearlv diastolic abnormalihelm J, HoustonC, Fails H. The sleeuelectro- ties in these patients with severe RV outcardiogram at extreme altitudes (Operation flow tract obstruction but the exact nature EverestII). Am J Cardiol 1990:65:1014-1020. of these abnormalities has yet to be deter2. Buja GF, Simini G, Miragiia G, Nava A. mined. Twenty-four-hours Holter monitoring in the Andrew N. Redington conquestof K2. J Sports Card 1985;2:43-49. Michael L. Rigby Alison Hayes Dan Penny
London, United Kingdom 10 August 1990
Right Ventricular Diastolic Function in Children Although we found the data presented by Vermilion et all interesting, we believe their approach to the analysisof right ventricular (RV) diastolic filline mav be oversimplistic and would advise caution in the interpretation of their data regarding the isolated analysis of tricuspid A-wave velocity and velocity integral in patients after relief of RV outflow tract obstruction. Indeed, these changes may be uninterpretable in the absence of a detailed analysis of the pattern of pulmonary artery flow. The accompanying figure shows the pulmonary artery flow pattern of 1 of 4 patients whom we studied after complete relief of RV outflow tract obstruction for pulmonary atresia with intact septum. Although there was a dominant A wave on the tricuspid inflow Doppler, it is almost wholly accounted for by forward flow into the pulmonary artery coincident with atria1 systole. Thus, late RV diastolic filling may be markedly restricted in the presence of a large A wave on the tricuspid inflow Doppler, the right ventricle acting as a conduit between the right atrium and the pulmonary artery in late diastole. E-wave deceleration time, and its change Y
.
1. Vermilion RP, Snider AR, MelionesJN, Peters J, Merida-AsmusL. PulsedDoppler evaluation of right ventricular diastolic fiiling in chil-
dren with pulmonary valve stenosis before and after balloonvalvuloplasty.Am J Cardiol 1990: 66179-84. 2. Appleton CP, Hatle LK, PoppRL. Demonstration of restrictive ventricular ohvsiologvbv Doppler echocardiography.J Am’&1 Caydid 1988;11:757-768. REPLY: The comments made by Redington and colleagues are intriguing but largely unrelated to our recent article on right ventricular (RV) diastolic filling in children with isolated pulmonary valve stenosis.’ We agree that an isolated analysis of tricuspid valve peak A velocity and A area fraction is inadequate to assessRV diastolic filling. For this reason, our study included measurements of indexes of early diastolic filling such as peak E velocity, first-third area fraction. E area fraction. and peak filling rate normalized for stroke volume. We disagree with Redington et al’s statement that RV diastolic function cannot be assessedin the absence of a detailed analysis of the pattern of pulmonary artery flow. In our experience, analysis of the pulmonary artery Doppler wave
ECG
5. Gugler R, Manion CV, Azarnoff DL. Phenytoin: pharmacokineticsandbioavailability. Clin Pharmacol Ther 1976;19:135-142.
The Sleep Electrocardiogram Extreme Altitudes
at
I found the article by Malconian et al’ to be informative and interesting and would like to add to their report my experience in this field. As reported,2 I had the opportunity to examine a Holter recording in a subject who climbed, in the summer of 1983, the northern face of K2. During this recording he spent a night at a bivouac at about 8,200 meters above sea level. I observed, while he slept at this altitude, sudden and cyclic variations of heart rate with periods characterized by junctional rhythm (45 beats/min) and sinus rhythm (65 beats/min) in the absence
PCG
THE AMERICAN JOURNAL OF CARDIOLOGY FEBRUARY 1, 1991
329