Effect of aerobic exercise training on estimated hepatic blood flow and plasma propranolol concentration after oral administration in young and elderly adults PDF
Preview Effect of aerobic exercise training on estimated hepatic blood flow and plasma propranolol concentration after oral administration in young and elderly adults
EFFECTOFAEROBICEXERCISETRAININGONESTIMATEDHEPATIC BLOODFLOWANDPLASMAPROPRANOLOLCONCENTRATIONAFTER ORALADMINISTRATIONINYOUNGANDELDERLYADULTS BY LYNNB.PANTON ADISSERTATIONPRESENTEDTOTHEGRADUATESCHOOL OFTHEUNIVERSITYOFFLORIDAINPARTIALFULFILLMENT OFTHEREQUIREMENTSFORTHEDEGREEOF DOCTOROFPHILOSOPHY UNIVERSITYOFFLORIDA 1993 Thisworkisdedicatedtomyfamilyforalltheirendlesspatience,loveand supportoverthelast5years. Thankyouforalwaysbeingthereforme. TABLEOFCONTENTS Page LISTOFTABLES vi LISTOFnCURES vii ABSTRACT ix CHAPTERS 1 INTRODUCTION 1 PurposeoftheStudy 6 ResearchHypothesis 6 Justification 6 Assumptions 7 Delimitations 7 Limitations 8 DefinitionofTerms 9 2 LITERATUREREVIEW 10 Liver Function 10 HepaticBloodFlow 13 Propranolol 17 ProteinBinding 19 EffectofAgingonPropranololConcentrations 20 Exercise,HepaticBloodFlow,andPropranolol 24 AcuteExerciseandPharmacokinetics 24 PhysicalFitnessandPharmacokinetics 25 GeneralTrainingAdaptationstoExerciseatRest 26 Summary 32 3 METHODOLOGY 33 Subjects 33 MethodsofDataCollection 37 BloodPressureMeasurements 37 BodyComposition 37 iii Plasma Volume Measurement 38 MaximalOxygenUptakeTest 39 HepaticBloodFlowandPropranololMeasurement 40 RandomizationofSubjects 44 Training 44 StatisticalAnalyses 45 4 RESULTS 47 SubjectCharacteristics 47 TrainingResponses 48 Training Stimulus 48 ParametersfromtheMaximalOxygenUptakeTest 48 RestingData 51 EstimatedHepaticBloodFlow 55 PropranololPharmacokineticsandProteinBindingAfter Oral Administration 58 PhysiologicalResponsestoOralPropranolol 64 5 DISCUSSIONANDCONCLUSIONS 74 TrainingResponses 74 MaximalOxygenUptake 74 RestingBloodPressureandHeartRate 75 RestingPlasmaVolume,BloodVolume,andHCT 76 EstimatedHepaticBloodFlow 77 PharmacokineticsofOralPropranolol 80 PhysiologicalResponsesofOralPropranolol 82 Conclusions 83 DirectionforFutureResearch 84 APPENDICES A INSTITUTIONALREVIEWBOARDAPPROVALLETTER 86 B DEMOGRAPHIC,MEDICAL,ANDACTIVITY QUESTIONNAIRES 88 C INFORMEDCONSENTTOPARHCIPATEINRESEARCH 99 D INSTRUCTIONSFORTESTINGDAYS 107 E 24HOURHISTORYQUESHONNAIRE 112 F DATACOLLECTIONFORMSFORESTIMATED HEPAHCBLOODFLOWANDORALPROPRANOLOL 114 IV LISTOFREFERENCES 115 BIOGRAPHICALSKETCH 128 V LISTOFTABLES Table Page 4-1 CharacteristicsofYoungandElderlySubjects 47 4-2 TrainingIntensityandPerceptionofEffortfortheYoungand ElderlySubjects 48 4-3 PhysiologicalParametersObtainedDuringInitialMaximal ExerciseTestintheYoungandElderlySubjects 49 4-4. MaximalTreadmillDataBefore(Tl)andAfter(T2)Training forYovmgandElderlySubjects 50 4-5 RestingBPandHRDataBefore(Tl)andAfter(T2)Training forYoimgandElderlySubjects 52 4-6 Evan'sBlueMeasurementsofRestingPlasmaandBlood VolumeDataBefore(Tl)andAfter(T2)TrainingforYoung andElderlySubjects 53 4-7 PhysiologicalParametersObtainedDuringInitialBaseline MeasurementofEstimatedHBFintheYoungand ElderlySubjects 55 4-8 EsimatedHBFDataBefore(Tl)andAfter(T2)Trainingfor YoungandElderlySubjects 56 4-9 PharmacokineticParametersObtainedDuringOral Administrationof80mgofPropranololPriortoTraining 58 4-10 PharmacokineticParametersObtainedDuringOral Administrationof80mgofPropranololDataBefore(Tl)and After(T2)TrainingforYoungandElderlySubjects(N=43) 59 4-11 ProteinBindingObtainedDuringOralAdministrationof 80mgofPropranololDataBefore(Tl)andAfter(T2) TrainingforYoungandElderlySubjects 63 VI USTOFFIGURES Figure Page 4-1 PercentchangesinrelativeV02maxforthecontroland training youngandelderlysubjects 51 4-2 Percentchangesinbloodvolumeforthecontroland traininggroupsofyovmgandelderlysubjects 54 4-3 ChangesinestimatedHBFbetweenthecontrolandtraining groupsofyoungandelderlysubjects 57 4-4 ConcentrationofpropranololatT1acrosstimefortheyoungand elderlysubjects 60 4-5 Concentrationofpropranololacrosstimefortheelderly subjectsinthecontrolandtraininggroupspre(Tl)and post(T2)testing 61 4-6 Concentrationofpropranololacrosstimefortheyoung subjectsinthecontrolandtraininggroupspre(Tl)and post(T2)testing 62 4-7 MeanresponsesofsystolicBPintheyoungandelderlyafter administrationof80mgoforalpropranolol 65 4-8 MeanresponsesofsystolicBPfortheelderlysubjectsinthe controlandtraininggroupspre(Tl)andpost(T2)testingafter administrationof80mgoforalpropranolol 66 4-9 MeanresponsesofsystolicBPfortheyoungsubjectsinthe controlandtraininggroupspre(Tl)andpost(T2)testingafter administrationof80mgoforalpropranolol 67 4-10 MeanresponsesofdiastolicBPintheyoungandelderlyafter administrationof80mgoforalpropranolol 68 4-11 MeanresponsesofdiastolicBPfortheelderlysubjectsinthe controlandtraininggroupspre(Tl)andpost(T2)testingafter administrationof80mgoforalpropranolol 69 4-12 MeanresponsesofdiastolicBPfortheyoungsubjectsinthe controlandtraininggroupspre(Tl)andpost(T2)testingafter administrationof80mgoforalpropranolol 70 4-13 MeanresponsesofHRintheyoimgandelderlyafter administrationof80mgoforalpropranolol 71 4-14 MeanresponsesofHRfortheelderlysubjectsinthecontrol andtraininggroupspre(Tl)andpost(T2)testingafter administrationof80mgoforalpropranolol 72 4-15 MeanresponsesofHRfortheyoungsubjectsinthecontrol andtraininggroupspre(Tl)andpost(T2)testingafter administrationof80mgoforalpropranolol 73 viii AbstractofDissertationPresentedtotheGraduateSchool oftheUniversityofFloridainPartialFulfillmentofthe RequirementsfortheDegreeofDoctorofPhilosophy EFFECTOFAEROBICEXERCISETRAININGONESTIMATEDHEPATIC BLOODFLOWANDPLASMAPROPRANOLOLCONCENTRATIONAFTER ORALADMINISTRATIONINYOUNGANDELDERLYADULTS By LynnB.Panton August,1993 Chairman: JamesE.Graves MajorDepartment: ExerciseandSportSciences Toevaluatetheeffectof4monthsofendurancetrainingonestimated hepaticbloodflow(EHBF)andoralpropranololpharmacokinetics,23young (Y)(30±5years)and20elderly(E)(67±5years)adultswererandomlyassigned toendurancetraining(Y:n=12;E:n=10)ornonexercisingcontrol(Y:n=ll;E: n=10)groups. Trainingconsistedoftreadmillwalkingand/orstairclimbing3 timesperweek. EHBFandplasmapropranololconcentrationsfollowinga singledoseof80mgoforalpropranololweremeasured,beforeandafter4 monthsoftraining,basedonbloodsamplestakensequentiallyduringsupine rest. BloodsampleswerequantifiedusingindocyaninegreenandHPLC technology,respectively. IX Trainingincreasedmaximaloxygenuptake(V02max) (Y:12.5±3.6%; E:13.6±5.5%)andplasmavolume(PV)(Y:15.2±1.6%;E:12.6±2.2%)inboththe youngandelderlyexercisers,relativetocontrols. Relativeincreasesin V02maxandPVfortheyoungandelderlyexercisersdidnotdiffer. Initial valuesofEHBF(Y:1306+378ml/min;E:1073±354ml/min)andthearea underthecurvetohour10fororalpropranololconcentrations(Y:558+214 ng/ml;E:658±369ng/ml)werenotdifferentbetweentheyoungandelderly. Afterthe4monthsa2x2factorialanalysisofcovariance(ANCOVA)founda significantinteractionbetweenageandtreatmentinEHBF. Post-hocanalysis showedthatEHBFwasnotdifferentbetweentheelderlycontrolandtraining groups. However,adjustedposttrainingmeansfortheyoimgcontrol(1126 ml/min)andtraining(1338ml/min)groupsweresignificantlydifferent. However,differenceswereduetothecontrolgroupdecreasingandthe traininggroupnotchanging. Nodifferenceswerefoundinthe pharmacokineticsoforalpropranololafter4monthsoftrainingineither group. Theresultsshowthat1)youngandelderlyadultsincreaseV02max andPVtothesamerelativeextentwhengivenasimilartrainingstimulus;2) atbaseline,healthyelderlyadultsdonotdifferinEHBFororalpropranolol pharmacokineticswhencomparedtotheyoung;3)4monthsofexercise trainingdoesnotincreaseEHBFinyoungorelderlyadults;and4)4months ofexercisetrainingdoesnotchangethepharmacokineticsoforalpropranolol inyoungorelderlyadults.
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