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#- l HK0270092 36789 5 EFFECTS ON HEMOGLOBIN OXYGEN AFFINITY OF SMOKING IN RESIDENTS OF IN- TERMEDIATE ALTITUDE J LA~ CLIN MED 8/-I(2): 191-205J 1974 BREWER, G J/ SING, CF, EATON, JW, WEIL, JV, BREWER, IF, 6ROVER, RF PURPOSE: PRELIMINARY STUDIES IN LEAI)VILLE, COLO. (ALTITUDE 10,200 FT) SUGGEST THAT CIGARETTE SMOKING MAY PRODUCE "A SIGNIFICANT DECRE- MENT IN OXYGEN TRANSPORT, PARTICULARLY IN RESIDENTS AT INTERMEDIATE AND HIGH ALTITUDES." "IN AN EFFORT TO DOCUMENT THE WAYS IN WHICH CIGARETTE SMOKING MAY IN-' TERFERE WITH RESPIRATORY ADAPTATION TO ALTITUDEsn THE EFFECTS OF SMOKING ON HEMOGLOBIN OXYGEN AFFINITY AND RED CELL MASS WERE INVESTI-' GATED IN LEADVILLE RESIDENTS, AN ATTEMPT WAS ALSO MADE TO DETERMINE IF CIGARETTE SMOKING IS A CON- TRIBUTING FACTOR IN THE PRODUCTION OF EXCESSIVE POLYCYTHEMIA OF ALTI- TUDE (ABNORHALLY HIGH RED CELL COUNT), [~ETHODS: "CARBOXYHEMOGLOBIN (COHB) LEVELS, HEMOGLOBIN, RED CELL 2,3- DIPHOSPHOGLYCERATE (DPG), HEMATOCRIT, MEAN CELL HEMOGLOBIN CONCENTRA- TION AND ARTERIAL OXYGEN TENSION (PA02) WERE DETERMINED IN 15 NORMAL SMOKERS, 15 NONSMOKERS AND 20 POLYCYTHEMIC SMOKERS, ALL LONG-TERM ~LE RESIDENTS. PATH COEFFICIENT ANALYSIS WAS USED 1'O EVALUATE THE CONCOMITANT EFFECT OF THESE VARIABLES ON RED BLOOD CELL OXYGEN SA- TURATION. RESULTS: SMOKERS HAD GREATER OXYGEN AFFINITIES THAN NONSMOKERS, mPRESUMABLY" DUE TO COHB, CESSATION OF SMOKING FOR 2~ HOURS BY POLY- CYTHEMIC SUBJECTS RESULTED IN MARKED REDUCTION OF COHB LEVELS AND A DECREASE IN HEMOGLOBIN OXYGEN AFFINITY TO LESS THAN SEA LEVEL NORMAL, LONG-TERM EFFECTS COULD NOT BE ASSESSED BECAUSE ONLY FOUR SUBJECTS ILII-fR 98 Ct3HG 01039

BI HK0270093 36789 STOPPED SMOKING, HEHOGLOBIN, HEHATOCRIT AND DP6 VALUES iN SMOKERS WERE NOT SIGNIFI- CANTLY HIGHER THAN IN NONSHOKERS. OXYGEN SATURATION WAS MOST INFLUENCED BY PA02, FOLLOWED BY COHB (ESPECIALLY IN SHOKERS) AND DPG, IN POLYCYTHEHIC SMOKERS, RED CELL HASS HAS NOT SIGNIFICANTLY RELATED TO LEVELS OF DPG, COHs, ARTERIAL SATURATION AND ARTERIAL PH. RED CELL HASS WAS HIGHLY NEGATIVELY CORRELATED WITH PA0Z, D~scussJ.QN: =THE EXCESSIVE POLYCYTHEMIA OCCURRING AT HIGH ALTITUDE" PRESUHABLY ORIGINATES FROM MANY CAUSES. PROBABLY AN IMPORTANT FACTOR IS LUNG DISEASE, SUCH AS SILICOSIS FROM MINING, CHRONIC OBSTRUCTIVE LUNG DISEASE, AND CHRONIC BRONCHITIS;,..THE LIKELIHOOD OF A PRIHARY ROLE FOR PULHONARY ABNORMALITY OF SOME TYPE IN HANY OF THESE PATIENTS IS SUPPORTED BY THE PREVIOUS AND PRESENT OBSERVATIONS OF REDUCED PAO2 IN HOST OF THEM AS HELL AS BY THE STRONG RELATIONSHIP BEI"~EEN PA02 AND RED CELL HASS. DECREASED HYPOXIC VENTILATORY DRIVE IS PROBABLY ANOTHER FACTOR CONTRIBUTING TO POLYCYTHEHIA AT HIGH ALTITUDE, "HORE THAN 80 PER CENT OF THE PATIENTS WITH POLYCYTHEHIA IN LEADVILLE ARE CIGARETTE SHOKERS, IT CAN BE THEORETICALLY CALCULATED (UNDER SEA LEVEL CONDITIONS) THAT 5 PER CENT C0-HB REDUCES OXYGEN TRANSPORT BY ABOUT 20 TO ~PER CENT UNDER CONDITIONS OF AVERAGE VENOUS DESATURA- TION OF 25 TO 30 PERCENT, IF OTHER CARDIOVASCULAR-RESPIRATORY FACTORS DO NOT COMPENSATE. (THIS EFFECT HAY BE DIMINISHED SOMEWHAT AT HIGH ALTITUDE BECAUSE THE LEFT-SHIFT OF THE OXYGEN DISSOCIATION CURVE INCREASES OXYGEN LOADING 1N THE LUNGS.) THE EFFECT OF C0 ON OXYGE~ TRANSPORT IS DUE PRIMARILY TO ITS EFFECT ON OXYGEN AFFINITY. THIS DEFICIT MUST EITHER BE MADE UP BY INCREASED CARDIAC OUTPUT, OR THE TISSUE P0z HUST FALL TO A CERTAIN EXTENT. ~E HAVE ALSO PREVIOUSLY SHOWN THAT CIGARETTE SHOKING CAUSES A REVERSIBLE REDUCTION IN PA02 AVERAGING ABOUT 5 HH, HG. THE SMOKING-INDUCED REDUCTION IN PA02 BAY ~TF~ 9B ~OH6 0104~.

HK0270094 36789 ]BE DUE TO C0 AND THE FORMATION OF C0- HB,.,."" ISLK/ U MICH MED SCH, ANN ARBOR, MICHI U MICH MED SCH, ANN ARBOR, MICN; U COL MED CENT, DENVER, COLO HEMATOLOGICAL STUDYa CLINICAL STUDY, PROSPECTIVE STU3Y, MALE DATA, HUNDRED, CIGARETTE SMOKING, NONSMOKERS, EXSMOKERS, ALTITUDE FACTORS, CARBOXYHEMOGLOBIN, HEMOGLOBIN OXYGEN AFFINITY INCREASE SMOKING ASSOC~ HEMOGLOBIN OXYGEN DISSOCIATION CHANGES SMOKING ASSOCs SMOKING PHYSIOLOGICAL EFFECTS, ARTERIAL OXYGEN SATURATION, HEMATOCRIT SMOKING NONASSOC, HEMOGLOBIN SMOKING NONASSOCa BLOOD 2 3 DIPHOSPHOGLYCERATE SMOKING NONASSOC/ BLOOD 2 3 DIPHOSPHOGLYCERATE INCREASE, HEMATOCRIT INCREASEs ERYTHROCYTE INCREASE, ERYTHROCYTOSIS, SMOKING AMOUNT', BLOOD CARBON MONOXIDE INCREASE SMOKING ASSOC, HEMOGLO31N CONCENTRATION, ARTERIAL OXYGEN TENSION DECREASE SMOKING ASSOC, MULTIPLE FACTORS INTERACTION, SMOKING ABSTINENCEs BLOOD CARBON MONOXIDE DECREASE SMOKING DISCONTINUATION ASSOC, SMOKING DISCONTINUATION DURATION, POPULATION SAMPLE SIZE CONCESSION, METHODOLOGY CONCESSION, POLYCYTHEMIA SMOKING CAUSATION 2/ STATISTICAL ANALYSIS, BLOOD COUNT, BLOOD GAS ANALYSIS, MULTIVARIATE ANALYSIS, CHRONIC OBSTRUCTIVE LUNG DISEASE, SILICOSIS, CHRONIC BRONCHITIS, HYPOXEMIA/ ENGLISH LANGUAGE, ANN ARBOR MICH RESIDENCE, USA RESIDENCE, DENVER COLO RESIDENCE, GRANTOR USPHS, GRANTOR USPHS REs CAREER DEVEL AWAR~., GRANTOR US NAVY, GRANTOR.US ARMY, LEAI)VILLE COLO E:TF~ 98 cor,IG o1o,.~-I