CAPÍTULO 4: RESULTADOS
4.2. FORMAS DE RECONOCIMIENTOS DESEADAS EN LA ORGANIZACIÓN
[K+] produced by IRLA was less than the sum of the rise in [K+] produced by HMA and HRA.
By taking the magnitude of pH fall into consideration, four rabbits were eliminated from the analysis. In case of IRLA, the three observations used in this analysis might not have b e e n representative of the effects of IRLA on arterial [K+] and thus the contribution of exercise-induced K+ release to the rise in plasma K+ may not have been e x p r e s s e d in the r e s u l t s .
The hyperkalemic response observed during IRLA, HMA and HRA ma y have resulted from release of K+ not only from active muscles but also from other sources. Increased arterial [K+] from haemolyzis is improbable because there was no overt evidence of the presence of haemoglobin in blood samples and because measured arterial [K+] remained constant during the cont r o l experiments. Release of K+ from e r y t h r o c y t e s in response to changes in pH, Paco2 and Pao2 is also unlikely to have been responsible for hyperkalemic responses reported in this chapter. D u r i n g an acute r e s p i r a t o r y a c i d o s i s in humans, Kilburn (19 65) found that K+ content in erythrocytes remai n e d relatively constant. Rolett and colleagues (1990) m e a s u r i n g K+ content of erythrocytes, also, found that it remained constant during limb exercise.
In this thesis, cell damage as a result of surgery or IRL can be ruled out as a cause of the hyperkalemia. During the control periods, arterial [K+] remained fairly steady not c h a n g i n g by more than 0.1 mmol/1. Furthermore, increased a r t e r i a l [K+] o b s e r v e d duri n g IRLA, s h o u l d h a v e b e e n main t a i n e d following stopping inspiratory resistive loading b u t a r t e r i a l [K+] d e c r e a s e d to c o n t r o l l e v e l s a f t e r inspiratory resistive loaded breathing
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Undoubtedly, the liver could have contributed to the rise in arterial [K+] observed in IRLA and HRA. It has been shown that hypercapnia and asphyxia can induce release of K+ from this organ as a consequence of a c t i v a t i o n of sympathetic e f f e r e n t a n d i n c r e a s e d c a t e c h o l a m i n e o u t p u t from the adrenals (Fenn & Asano, 1956). Since the results presented in this chapter showed that HRA produced a rise in arterial [K+] by no more than 0.5 mmol/1, it could be argued that only a fifth of the total rise in arterial [K+] o b s e r v e d during IRLA, averaging 2.3 mmol/1, can be a t t ributed to K+ release from the liver.
On the basis of the discussion so far, the probable source of K+ release was the skeletal muscles w h i c h include the inspiratory muscles. For both HMA and HRA, the net efflux of K+ from these muscles cannot be attributed to contraction of m u s c l e s as all skeletal muscles w ere paralysed, and t h e r e f o r e c o u l d be a t t r i b u t e d to an e x c h a n g e of e x t r a c e l l u l a r H+ for intracellular K + . However, it is not t o t a l l y clear w h e t h e r the release of K+ f rom skele t a l mu s cles during IRLA occurred as result of an exchange of e x t r a c e l l u l a r H+ for i n t r a c e l l u l a r K+ or i n c r e a s e d neuromuscular activity.
Ba s e d on e x p e rimental evidence, it is c l ear that a net efflux of [K+] from exercising limb muscles is responsible for the rise in plasma [K+] during exercise (Hnik et al., 1976; Hirche et al., 1980; Linton et al, 1984, Sjogaard G, 1986, M e d b 0 & Sejersted, 1990). Two studies showed while e x e r c i s i n g leg released K + , the contralateral resting leg w o u l d take up K+ (Sj0gaard, 1986; Rolett et al., 1990). In v i e w of this observation, it could be argued that the only m u s c l e s that could have lost K+ d u ring I R L A e x p e r i m e n t s presented in this thesis were the loaded inspiratory muscles as all o t h e r m u s c l e groups were inactive. E l e c t r i c a l stimulation of phrenico-diaphragm preparation has been shown to induce a substantial movement of K+ out of the diaphragm (Lade & Brown, 1963). This indicates that, like o ther
s k e l e t a l muscles, the diaph r a g m may r e l e a s e K+ d u r i n g i n t e n s e d i a p h r a g m a c t i v i t y such as s e v e r e i n s p i r a t o r y resistive loading.
In conclusion, this chapter present evidence that indicates that hyperkalemia observed during IRLA may be due to the a d d i t i v e effect of an acute m e t a b o l i c a n d r e s p i r a t o r y a cid o s e s . A l t h o u g h the c o n t r i b u t i o n of the e x e r c i s i n g inspiratory muscles to the rise in arterial [K+] was not demonstrated, the possibility that exercising muscles did contribute cannot be ignored. The source of the increased pl asma [K+] cannot be identified with confidence. However, r e g a r d l e s s of the source of K+ release, the s t u d i e s p r e s e n t e d in the last three chapters have i n d i c a t e d that p o t a s s i u m and hydrogen ions could be potential stimuli of diaphragmatic chemoreceptors.
Potassium and hydrogen have been shown to activate group IV a f f e r e n t s in nerves arising from limb s k e l e t a l m u s c l e s
(Rybicki et al., 1985; Kaufman & Rybicki, 1987). Sjogaard (1990) has proposed that K+ release from exercising muscles m a y initiate reflexes that would control the p a t t e r n of contraction of the muscle. Since the diaphragm is a skeletal mu scle and plenty of small afferents arising from it, the i n c r e a s e d e x t r a c e l l u l a r K+ obser v e d d u r i n g i n s p i r a t o r y r e s i s t i v e l o a d i n g may h a v e e x c i t e d t y p e III a n d IV d i a p h r a g m a t i c r e c e p t o r s , i n i t i a t i n g a refl e x , w h i c h r e g u l a t e d the activity of the diaphragm, and in so doing i n f l u e n c e d v e n t i l a t i o n . This h y p o t h e s i s is t e s t e d in Chapters 9 and 10.