Upsala J Med Sci 84: 181-187, 1979 Reaction to Cold of Patients with Coronary Insufficiency Christer Backman, Sonja Holm and H%kan Linderholm From the Department of Clinical Physiology, University of U m e d , U m e d , Sweden ABSTRACT Twenty s i x p a t i e n t s w i t h a n g i n a p e c t o r i s and coronary i n s u f f i c i e n c y a s judged by an e x e r c i s e E C G t e s t were examined. About h a l f of t h e p a t i e n t s had more pronounced ECG changes i n a c o l d room a t - 1 5 O C t h a n a t room t e m p e r a t u r e . They worked l e s s , t h e i r s u b j e c t i v e r a t i n g of e x e r t i o n d u r i n g e x e r c i s e was h i g h e r and t h e h e a r t performed l e s s work, e x p r e s s e d as t h e h e a r t r a t e b l o o d p r e s s u r e p r o d u c t . The o t h e r h a l f of t h e p a t i e n t s was n o t much i n f l u e n c e d by c o l d . During an e x e r c i s e t e s t i n t h e s u p i n e p o s i t i o n almost a l l p a t i e n t s g o t more pronounced ECG changes, worked l e s s and t h e h e a r t performed l e s s work t h a n i n t h e s i t t i n g p o s i t i o n . It i s s u g g e s t e d t h a t c o l d exposure as w e l l a s a supine body p o s i t i o n may t o a c o n s i d e r a b l e p a r t e x e r t t h e i r e f f e c t , i . e . lower t h e a n g i n a l t h r e s h o l d and i n c r e a s e ECG changes, by i n c r e a s i n g t h e c e n t r a l blood volume and t h e d i a s t o l i c volume of t h e l e f t h e a r t and t h u s c e t e r e s p a f i b u s sumption. t h e myocardial oxygen con- I N T R O D U C T I O N P a t i e n t s w i t h coronary h e a r t d i s e a s e o f t e n e x p e r i e n c e a d e t e r i o r a t i o n i n t h e i r c o n d i t i o n i n c o l d weather ( 4 , 5 ) . Many p a t i e n t s s t a t e t h a t t h e i r symptoms a r e provoked by a c o l d wind. Some p a t i e n t s observe t h a t an e x e r t i o n which can be maintained w i t h o u t d i f f i c u l t y i n warm weather may provoke an a t t a c k of an- g i n a p e c t o r i s i n t h e c o l d . Other p a t i e n t s may n o t be much i n f l u e n c e d by c o l d ( 5 , 1 3 ) . An examination of t h e way i n which p a t i e n t s w i t h coronary h e a r t d i s - e a s e r e a c t t o c o l d under s t a n d a r d i z e d c o n d i t i o n s i s t h e r e f o r e o f i n t e r e s t . I n t h i s way experiments may be performed t o e l u c i d a t e t h e mechanism of a c t i o n of c o l d i n t h e s e p a t i e n t s . 181 MATERIAL AND METHODS Twenty s i x p a t i e n t s from 41 t o 6 1 y e a r s of age (mean 50 y e a r s ) were exam- i n e d because of angina p e c t o r i s . They were chosen o u t of a l a r g e r number be- c a u s e t h e y showed ECG changes t y p i c a l of c o r o n a r y i n s u f f i c i e n c y d u r i n g and a f t e r an e x e r c i s e t e s t . They were n o t chosen because o f p a r t i c u l a r d i f f i - c u l t i e s i n c o l d weather. Most of them were under t r e a t m e n t w i t h beta-blocking drugs. The put,ieCC: performed two o r t h r e e e x e r c i s e t e s t s on a b i c y c l e ergometer under d i f f e r e n t c o n d i t i o n s . 1). Cycling i n t h e s i t t i n g p o s i t i o n i n a room a t a t e m p e r a t u r e of about +22OC. a t e m p e r a t u r e of about - 1 5 O C . I n t h e c o l d room t h e p a t i e n t s were d r e s s e d i n w a r m c l o t h e s , g l o v e s and a cap c o v e r i n g t h e head except f o r t h e f a c e . Before t h e c y c l i n g s t a r t e d t h e s u b j e c t s had s t a y e d for about two minutes i n t h e c o l d room. s u p i n e p o s i t i o n . 2 ) , Cycling i n t h e s i t t i n g p o s i t i o n i n a room a t 3 ) . Most of t h e p a t i e n t s a l s o worked on t h e b i c y c l e ergometer i n t h e During t h e e x e r c i s e t e s t ( 1 6 ~ 2 ) t h e work w a s i n c r e a s e d s t e p w i s e w i t h i n d i - v i d u a l l y chosen increments e v e r y s i x minutes u n t i l t h e p a t i e n t w a s unable t o c o n t i n u e o r t h e ECG change o r o t h e r signs l e d t o an i n t e r r u p t i o n of t h e t e s t . Heart r a t e , r e s p i r a t o r y frequency, blood p r e s s u r e , and t h e s u b j e c t i v e r a t i n g of e x e r t i o n ( 2 ) were r e c o r d e d a t t h e end of each work l o a d . The maximum work l o a d performed was t a k e n t o be t h e h e a v i e s t l o a d a t which t h e s u b j e c t worked f o r s i x minutes w i t h an increment p r o p o r t i o n a l t o t h e com- p l e t e d p e r i o d a t t h e n e x t h i g h e r l o a d (17). The t o t a l work performed w a s c a l - c u l a t e d a s t h e sum of work l o a d s m u l t i p l i e d by t i m e . The ( h e a r t r a t e ) ( s y s t o l - i c blood p r e s s u r e ) product was c a l c u l a t e d f o r t h e maximum work l o a d and used a s an e x p r e s s i o n of h e a r t work l o a d (14). F o r e a c h p a t i e n t e q u a l work l o a d s were used under t h e d i f f e r e n t c o n d i t i o n s of e x e r c i s e . A group o f 17 p a t i e n t s o f mean age 54 ( r a n g e 36-70) y e a r s w i t h a n g i n a pec- t o r i s and f a i r l y comparable w i t h t h e 26 p a t i e n t s d e s c r i b e d were used as con- t r o l s i n t h e room t e m p e r a t u r e - c o l d room s t u d y . They performed two e x e r c i s e t e s t s i n t h e s i t t i n g p o s i t i o n a t a room t e m p e r a t u r e o f about +22OC w i t h an i n t e r v a l of l e s s t h a n one month. A s c o n t r o l s i n t h e s i t t i n g - s u p i n e s t u d y 26 h e a l t h y s u b j e c t s of mean age 70 ( r a n g e 61-83) y e a r s (17) were used. RESULTS Fourteen of t h e 26 p a t i e n t s (group 1) g o t more pronounced ST d e p r e s s i o n s (0.5 - 1 mm) d u r i n g t h e e x e r c i s e t e s t i n t h e c o l d room compared w i t h t h e t e s t a t room t e m p e r a t u r e ( " c o l d r e s p o n d e r s " ) . The remaining 12 p a t i e n t s (group 2 ) d i d n o t g e t more ST d e p r e s s i o n s i n t h e c o l d room t h a n a t room t e m p e r a t u r e 182 on e q u a l work l o a d . F i g . 1 ( l e f t s i d e ) and Table 1 show r e s u l t s o f group 1 and group 2 as w e l l a s t h e whole group ( 1 + 2 ) a t room t e m p e r a t u r e and i n t h e c o l d room. The average of t h e maximum work l o a d performed, t h e maximum h e a r t r a t e r e a c h e d , t h e h e a r t r a t e s y s t o l i c b l o o d p r e s s u r e product as an e x p r e s s i o n of t h e h e a r t work a t maximum work l o a d , t h e t o t a l work performed d e c r e a s e d , and t h e r a t i n g of sub- j e c t i v e e x e r t i o n i n c r e a s e d s i g n i f i c a n t l y i n group 1 b u t n o t i n group 2 . The p e r c e n t a g e d i f f e r e n c e between t h e e x e r c i s e performance as w e l l as t h e s u b j e c - t i v e r a t i n g of e x e r t i o n o f t h e group 1 p a t i e n t s a t room t e m p e r a t u r e and i n t h e c o l d room w a s s t a t i s t i c a l l y s i g n i f i c a n t l y g r e r 5 e r t h a n t h e d i f f e r e n c e between t h e two work t e s t s , b o t h a t room t e m p e r a t u r e , i f t h e 17 p a t i e n t s of t h e con- t r o l group w i t h a n g i n a p e c t o r i s ( T a b l e 1). Max. work load 120 1 '00 c L--J performed, Max. heart rate, 140 1 100 - HRxSBP Beats. kPa 3 2 10-3, min *IT I Body position Sitt Sitt Temp. *22'C -15'C t - Sitt sup *22T F i g . 1 . R e s u l t s of t h e e x e r c i s e t e s t s a t room t e m p e r a t ~ r e , + 2 2 ~ C , and i n t h e c o l d room, -15OC, s i t t i n g on t h e b i c y c l e ergometer f o r angina p e c t o r i s pa- t i e n t s who responded w i t h i n c r e a s e d ECG changes i n t h e c o l d , group l(.) and f o r non-responders, group 2 ( = ) , l e f t s i d e of t h e f i g u r g . The r i g h t hand s i d e of t h e f i g u r e shows r e s u l t s from t e s t s performed a t +22 C i n t h e s i t t i n g and supine p o s i t i o n f o r group 1 + 2 ( A ) . The symbols i n d i c a t e means and v e r t i c a l b a r s s t a n d a r d e r r o r of t h e mean. 183 Table 1. Maximumwork l o a d performed, t o t a l work performed, maximum h e a r t r a t e , and r a t i n g of s u b j e c t i v e e x e r t i o n d u r i n g work on e q u a l l o a d i n t h e s i t t i n g po- s i t i o n a t room t e m p e r a t u r e , RT i n a c o l d room, and 1+2. The r e s u l t s of work t e s t I1 a r e g i v e n a s d i f f e r e n c e s between work t e s t I and I1 i n p e r c e n t of work t e s t I , i . e . 1 0 0 * ( I - I I ) / I . about +22OC i n t h e two work t e s t s . Mean and SEM a r e g i v e n . +22OC, (work t e s t I ) and d u r i n g a second t e s t CR - 1 5 O C , (work t e s t 11) f o r t h e angina p e c t o r i s group 1 , 2 The c o n t r o l group of a n g i n a p e c t o r i s p a t i e n t s e x e r c i s e d a t room t e m p e r a t u r e V a r i a b l e Group n Work t e s t I Work t e s t I1 ,% change from work t e s t I RT +22'C C R - 1 5 O C RT +22OC Maximum work l o a d , bJ Group 1 14 96 10 Group 2 1 2 96 ; 11 C o n t r o l group 17 78 - 8 Group 1 + 2 26 9 6 ; 7 2 1 7.6xx'0 1 ; 3 . 2 11 - 8.OX 0 +_ 3 . 9 T o t a l work performed Wxmin Group 1 1 4 1026 3 171 26 8.4xxy0 Group 2 1 2 9 4 1 ; 193 -4 ; 9 . 5 + Group 1+2 26 987 7 126 13 - 6 . 9 C o n t r o l group 1 7 800 - 130 -1 - 6 . 4 Max h e a r t r a t e s t r o k e /min Group 1 1 4 125 4 Group 1+2 26 125 7 4 C o n t r o l group 17 123 - 7 Group 2 1 2 126 8 R a t i n g o f e x e r t i o n Group 1 Group 2 Group 1+2 C o n t r o l group 14 15 a.7 1 2 16 ; 0 . 5 26 1 5 ; 0 . 4 17 ' 14 - 0.4 -16 ? 3.4xx300 - 5 ; 3 . 1 xx,oo -10 - 2 . 5 + 0 4 2.2 n = number of s u b j e c t s , x and o i n d i c a t e 0.05 >F 7 0 . 0 1 , xx and 0 0 i n d i c a t e 0.01>Pr0.001, x and xx i n d i c a t e t h e p r o b a b i l i t y t h a t t h e d i f f e r e n c e between work t e s t I and work t e s t I1 i s caused by random f a c t o r s . o and 00 i n d i c a t e t h e p r o b a b i l i t y t h a t t h e d i f f e r e n c e between t h e p e r c e n t a g e change between work t e s t I and work t e s t I1 of t h e p a t i e n t group and t h e c o r r e s p o n d i n g p e r c e n t a g e change between t h e two work t e s t s of t h e c o n t r o l group i s caused by random f a c t o r s . The s y s t o l i c blood p r e s s u r e d u r i n g m a x i m u m work l o a d was n o t s i g n d i f f e r e n t between t h e groups o r t h e d i f f e r e n t c o n d i t i o n s of e x e r c i s e 184 f i c a n t l y The mean s y s t o l i c p r e s s u r e s were s l i g h t l y h i g h e r d u r i n g t h e e x e r c i s e i n t h e c o l d room. Angina p e c t o r i s was r e c o r d e d e a r l i e r i n t h e c o l d room t h a n a t room tempera- t u r e i n 11 of 1 4 s u b j e c t s of group 1 and i n 6 of 1 2 s u b j e c t s of group 2 . A l - though s u g g e s t i v e t h i s d i f f e r e n c e i s n o t s t a t i s t i c a l l y s i g n i f i c a n t . S e v e r a l of t h e p a t i e n t s i n b o t h groups performed a n e x e r c i s e t e s t i n t h e s u p i n e p o s i t i o n . There was no s i g n i f i c a n t d i f f e r e n c e between t h e s u b j e c t s from group L and group 2 and t h e r e f o r e t h e r e s u l t s a r e g i v e n f o r a l l t h e s e p a t i e n t s t o g e t h e r on t h e r i g h t hand s i d e o f F i g . 1 , cf a l s o Table 2 . Table 2 . R e s u l t s from e x e r c i s e t e s t s performed a t room t e m p e r a t u r e , +22OC, s i t t i n g (work t e s t I ) and s u p i n e (work t e s t 11) f o r t h e a n g i n a p e c t o r i s pa- t i e n t s of groups 1 , 2 , 1 + 2 and a c o n t r o l group of h e a l t h y males ( 1 7 ) V a r i a b l e Group n Work t e s t I Work t e s t I1 % change from work t e s t I S i t t i n g Supine Maximum work l o a d , Y Group 1 9 88 1 1 . 5 Group 1 + 2 1 9 93 ; 8.4 C o n t r o l group 26 136 - 5 . 4 Group 2 1 0 97 1 2 . 6 37 1 0 .2xx 33 ; 5 . 5 30 7 6.ixXx 18 - 2.0n xx T o t a l work performed Wxmin Group 1 7 964 263 45 I 1 0 . g X X Group 2 7 864 ; 185 52 7 1 0 . g n Group 1+2 1 4 914 y 158 48 < 7.3= C o n t r o l group 26 1 5 9 1 - 107 28 - l.Oxx Max h e a r t r a t e s t r o k e / m i n Group 1 11 123 1 1 . 7 17 I 2 . 9 r Group 2 1 0 126 ; 9 . 1 8 7 1.9 Group 1+2 21 125 ; 5 . 0 1 2 7 2.0- C o n t r o l group 26 153 - 3 . 4 9 - 3.9= Symbols a s i n Table 1 The maximum work l o a d performed, t h e t o t a l work performed, t h e maximum h e a r t r a t e and t h e h e a r t work l o a d , c a l c u l a t e d as t h e h e a r t r a t e s y s t o l i c blood p r e s s u r e p r o d u c t , were a l l lower i n t h e supine p o s i t i o n . The impairment of e x e r c i s e performance i n t h e s u p i n e p o s i t i o n , e x p r e s s e d a s t h e p e r c e n t a g e of t h e r e s u l t i n t h e s i t t i n g p o s i t i o n , f o r t h e a n g i n a P e e t o r i s 185 p a t i e n t s was n o t s t a t i s t i c a l l y s i g n i f i c a n t l y g r e a t e r t h a n t h a t found i n t h e c o n t r o l group of 26 h e a l t h y o l d s u b j e c t s , s e e Table 2. There was no s i g n i f i c a n t d i f f e r e n c e between s y s t o l i c blood p r e s s u r e d u r i n g maximum e x e r c i s e l o a d i n t h e s i t t i n g and s u p i n e p o s i t i o n s . ST d e p r e s s i o n s were i n a l l c a s e s b u t t h r e e more pronounced i n t h e s u p i n e t h a n i n t h e s i t t i n g po- s i t i o n . I n a few c a s e s t h e e x e r c i s e t e s t i n t h e c o l d room was of s i g n i f i c a n c e f o r t h e d i a g n o s i s of coronary i n s u f f i c i e n c y , as t h e r e were no s i g n i f i c a n t E C G changes a t room t e m p e r a t u r e , while ECG changes t y p i c a l of coronary i n s u f f i c i e n - cy appeared d u r i n g and a f t e r t h e e x e r c i s e t e s t i n t h e cold room. E x e r c i s e i n t h e s u p i n e p o s i t i o n w a s even more e f f e c t i v e i n t h i s r e s p e c t . DISCUSSION S e v e r a l p a t i e n t s i n group 1 were v e r y i n c a p a c i t a t e d d u r i n g t h e w i n t e r and i n t h e s e p a t i e n t s t h e examination of t h e r e a c t i o n t o an e x e r c i s e t e s t i n t h e c o l d room was of i n t e r e s t f o r t h e e v a l u a t i o n of t h e i r degree of i n c a p a c i t y . P a t i e n t s o f group 2 demonstrated a low s e n s i t i v i t y t o c o l d . It i s p o s s i b l e t h a t t h e i r r e a c t i o n t o c o l d i s t h e r e s u l t of an a d a p t a t i o n t o c o l d (1). About h a l f of t h e a n g i n a p e c t o r i s p a t i e n t s r e a c t e d t o c o l d exposure or approximately t h e same p r o p o r t i o n as t h a t r e p o r t e d by o t h e r a u t h o r s ( 5 , 1 3 ) . S e v e r a l mechanisms have been d i s c u s s e d a s an e x p l a n a t i o n f o r t h e e f f e c t of c o l d i n p a t i e n t s w i t h coronary i n s u f f i c i e n c y , such as r e f l e x c o n t r a c t i o n of coronary a r t e r i e s a s r e s u l t of t h e cold s t i m u l u s t o t h e s k i n (5,ll,l2) i n - c r e a s e d v a s c u l a r r e s i s t a n c e and i n c r e a s e d blood p r e s s u r e ( 4 , 7 ) and t h e r e f o r e i n c r e a s e d work f o r t h e h e a r t ( 9 ) . Another e x p l a n a t i o n ( 1 0 ) might be t h a t c o l d r e s u l t s i n a g e n e r a l vasocon- s t r i c t i o n of cutaneous v e s s e l s and consequent r e d i s t r i b u t i o n o f t h e blood v o l - ume , w i t h an i n c r e a s e i n t h e c e n t r a l blood volume ( 6 ) and probably i n c r e a s e i n c e n t r a l venous p r e s s u r e s , a t l e a s t i n i t i a l l y . I n t h i s way an e f f e c t i s o b t a i n - e d which may be similar t o t h a t o b t a i n e d by changing from an u p r i g h t t o a su- p i n e body p o s i t i o n ( 3 ) o r by t h e i n t r a v e n o u s a d m i n i s t r a t i o n of d e x t r a n ( 8 ) . The s i m i l a r i t i e s between t h e changes o b t a i n e d i n c o l d and i n t h e s u p i n e p o s i - t i o n axe s u g g e s t i v e . It i s l i k e l y t h a t c o l d as w e l l a s t h e supine p o s i t i o n r e - s u l t s i n some i n c r e a s e i n t h e d i a s t o l i c volume of t h e l e f t h e a r t . Changes i n v e n t r i c u l a r volume a r e of c r i t i c a l importance i n d e t e r m i n a t i n g myocardial oxy- gen consumption, s i n c e an i n c r e a s e means t h a t an augmented w a l l t e n s i o n w i l l be r e q u i r e d by t h e h e a r t f o r t h e same e x t e r n a l work (15 ) . 186 REFERENCES 1. Le B l a n c , J . , Dulac,S., Cot6,J., and Girard,B.: Autonomic nervous system and a d a p t a t i o n t o c o l d i n man. J Appl P h y s i o l 39:181-186, 1975. 2. Borg,G. and Linderholm,H.: E x e r c i s e performance and p e r c e i v e d e x e r t i o n i n p a t i e n t s w i t h coronary i n s u f f i c i e n c y , a r t e r i a l h y p e r t e n s i o n and vasoregu- l a t o r y a s t h e n i a . A c t a Med Scand 187: 17-26,1970. h o l d d u r i n g l e g e x e r c i s e . 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Received A p r i l 2 , 1 9 7 9 Address f o r r e p r i n t s : P r o f e s s o r Hzkan Linderholm Department of C l i n i c a l Physiology U n i v e r s i t y of UmeH S-901 85 UmeH,Sweden 187