Upsala J Med Sci 95: 63-74 The Influence of Body Temperature on lkaumatic Vasospasm Jonas Wadstrom and Bengt Gerdin Department of Surgery, University Hospital, Uppsala, Sweden The effect of hypothda on traumatically induced sos spasm was studied in campression of a 3.2 rmn segment of the artery for 3 s. ?he internal diameter was continuously measured with the aid of an operating micrcscope during transillumination of the artery. Measurements were k q m before spasm induction and continued until the spasm was ocrmpletely resolved. spasm was first induced at nomthennia and then after reduction of the body tempera- ture by 1.0"C and 1.75"C. ?he spasm was evaluate3 in terms of its duration, intensity (% reduction of initial diameter) and severity (area under the curve where diameter was plotted against time). ?he results were ccrmpared with those in a control group which was kept nomthermic. Reduction of the body temperature caused a significant im=rease in the duration of the spasm andincreased its severity, but did not influ- its intensity. an in vivo model of the rabbit ear artery. spasm was induced by standanh 'zed Microvascular techniques are well established in several surgical disci- plines. These procedures can be attended with very specific complications. One of thm is a local increase in vascular tone, which frequently occur^ at the site of a microvascular anastonasis. This sos spasm is sometimes so severe that it can jeopardize the patency of such an anastomosis and the success of the p e e . The pathophysiology of vasospasm occurring after microvasailar procedures is not laxrwn. m e factor which has been suggested as a cause of aggravation of the spasm is local coolirg, this effect of local cooling has been used in an experimentdl model for investigation of vasospasm OcCuTring in connection with mirramscular surgery (10). The iqgrtance of maintaining a normal bcdy 63 temperature during micruvascular surgery in patients in order t o prevent vasospasm has been pointed out by several autho?s (13,16,7,1,2). 'lhis opinion is n o t , however, based on experimentdl o r clinical studies and to our knmledge the effect of general hypothermia on t r a m t i c t so spasm has not y e t been investigated. W e have therefore tested the hypothesis that a decrease in body temperature aggravates traumatically induced ~sospasn. Animals en adult long-eared loop rabbits of both sexes, with a body weight of 2.4- 4 . 4 kg, w e r e used. They w e r e housed under s- 'zed e n v i r o m t a l c o d - tions with free access t o w a t e r and focd for t w o w e e k s prior t o the expri- mts, in accordam=e w i t h the institution's guide for the care and use of laboratory animals. Animal metxiration The animals w e r e anesthetized with alphaxolone-alphadolone (AlthesM, Glaxo), 3 w/kg given intravenously and diazepam ( D i a z d s , Kabi V i t r u m , ) , 2 mg/kg intramuscularly ( i . m . ) . Ixlring this short-lasting anesthesia the sensow nerve running parallel t o the central ear artery w a s cut a t the base of the l e f t ear. ?his made it possible t o perform the rest of the e x p r k t s with only l i g h t sedation, proctuced by 0-2 further injections of 1 w/kg diazepam given intravenously. The rabbits w e r e kept in a specially designed open box. A w a t e r blanket (Aquamatic K-20-D, Hamilton, C i n c h a t t i , Ohio, USA) w a s l a i d over t h e i r backs and was set a t 37°C. The central body temperature was measured continuously with a rectal thenmneter. The expri- mtdl set-up is sham in Fig. 1. The skin w a s incised along the left e x artery and the w o a d edges w e r e everted with a continuous suture (Fig. 1; right inset). The wound w a s moistened w i t h Ringer-acetate and covered with p l a s t i c polyethylene f o i l (Glad PackR, Union Carbide) in order to maintain a constant environment in the wound. The preparation of the vessel caused an i n i t i a l , transient m s c q a m , which spontaneously resolved i n approxirrately 10 min. To allm the vessel to regain wmplete n o m l i t y a minimum of 30 m h was always a l l w e d to elapse between the i n i t i a l preparation and the conduction of the f i r s t experiment. 64 Fig. 1. An artist's view of the e x p e r b t a l set-up. Induction of sos spasm Vasospasm was induced w i t h a Wachenfeldt clipapply- forceps (Fig. 2; Stille-Werner, Stockholm, Sweden), w i t h an occlusion area of 3.2 x 1.4 rmn = 4.5 rmn2. A t rest it is cl& and exerts a standardized canpression force of 2.45 N a t an area of 4 . 5 m2, i.e. a pressure of 5.45 x lo5 N/m2, between its claws. The ear artery was pinched w i t h the f o r c e p for 3 s. A f i r s t pinch was made on t h e d i s t a l part of the ear, and two further pinches w e r e made P roxiFal t o the f i r s t one. Measurement of the inner diamter !Ihe ear w a s fixed w i t h needles to a specially designed cork board which allowed t h e c e n t r a l ear artery to be transilluminated w i t h cold light abare w i t h an operat- microscope equipped w i t h a 25 X objective w i t h a focal distance of 100 rmn and a JVC video color camera. The inner diameter of the a r t e r y w a s measured directly on the video monitor. The resolution of the set-up w a s determined a f t e r calibration w i t h a L e i t z m i a x m e t e r ruler and found to be 0.01 rmn. 'Ihe f i r s t measuTement w a s made in the undistuked (Intralux-500, Volpi AG, Switzerland). The artery w a s then hspe&ed from vessel, whereafter spasn was induced and measuLpments w e r e r e p t e d every min 5-908571 65 u n t i l no visible spasm remained, i.e. when there was no narrowing of the traumatized segment compared with the neighbor- nontraumatizd vessel -t. Fig. 2. A schematic view of the Wachenfeldt clipapplying forceps. Experiments A. EXprimentdl Group: n=5. One episode of spasm was f i r s t induced a t no& body temperature. The core temperature w a s then lwerd by applying a p l a s t i c bag f i l l e d with ice cubes t o the back of the animal. T h i s 1cwe.mil the body temperature a t a rate of 1.8"C per hour, a t which rate the diameter of the artery m i n e d unchanged. When the core tenperahre had fallen by close t o 1.0 and by 1.75"C episodes of spasm were again induced. Blood smples for determination of serum cortisol w e r e taken before reduction of t h e body temperature and just before the f i r s t induction of spasm after the cooling. They were irmdiately centri- fuged, frozen to -70°C and l a t e r analyzed with an FUA method. B. Control Group: -5. These experiments w e r e performd as in the experimental group, but the animals w e r e kept nomthermic throughout the study period. 66 variables The fo1lawi.q variables w e r e measured or c a l d a k d and are depicted in Fig. 1. %: the initial inner diameter of the vessel. Q: the inner d i a m e t e r during IMximdl spasm. I+: the findl inner d i a m e t e r when the spasm was resolved and when the inner diameter of the t r a u m a t i z e d vessel segment w a s the same as that of the adjacent vessel segment. TO: the time of removdl of the forceps fm the traumatized vessel. %: the earliest time of maximdL spasm; Q. +: the duration of spasm; the time of Dp. The follawing four variables w e r e thereafter used in the descriptive and statistical andlysis of the vascqam. 1. !the initial ..- temperature. - I %I before and after reduction of the boay 2. !lk duratiopl of the spasn, Tp 3 . ‘Ihe intensity of the spasn, given i n percent and defined as ( b - 4 4 1 / 9 x 100 4. !the sxerity of the spasn, calculate3 as the area D x T, defined as the integrated decrease in d i a m e t e r f m To t o TF (shaded area in Fig. 3 ) . Diameter D I D M I I I I I I I I I I I I I T T O M Time T F D F Fig. 3 . A graph in w h i c h the diameter is plotted over time. The different variables are defined in the Materials and Methods section. 67 statistical evaluation m e difference between the first, controle spasm and each of the two experi- mental spasnrs w a s calculated for each animal, both in the experimental and the control group. The two groups w e r e then campared r q a r d i q these diffe- remes by Student’s two-sample t test. All data are given as mean ? SEM. A difference at the 5% level is regarded as significant and is indicaw by an asterisk in the figures. 39 - P t! 5 8 9 ) c 38- 9) 4 3 37- 0 PI 36 - the experiments the rabbits w e r e very calm and relaxed in their boxes and the e x p e r k t a l set-up did not appear to disturb the awake rabbit to any appreciable extent. ?he k d y temperatures of all animals at the different measurment times are shm in Fig. 4 . 6 A 1 I T I A 6 1 T 0 1 I I11 Experiments 0 cooled A control Fig. 4 . Body tenperatwe, in dqrees Celcius at the the of the experi- me.nts in the experimentdl and control groups. The temperature derreased by close to l.O(degrees Celcius) in the experiment 2 and 1.75(degrees Celcius) in experiment 3 . N=5 in a l l experi- ments. 68 At the first level there was a decrease in body tenperature varying from 0.8 to 1.1"C and at the second level the body temperature had dec=reased by 1.1- 2.0"C. ?he expcsed left centml ear a r t e r y d d be readily observed with the cold light transillumination. In the vessel the outer and inner diameters were very similar (Fig. 5 A), but after induction of t so spasm these diameters w e r e easily separable (Fig. 5 B). After a 3 s pinch with the forceps, the central artery reacted with vasospassn. Ime constricted sqmnt was limited to the pinched area. spasm w a s maximal within 1 min ard the inner d i a ~ t e r was decreased to approximately 15% of the original value. 'Ihis intense constriction remained virtually stable for 5 mint whereafter it slowly resolved. Fig. 5. 'Ihe appearance of an u n d i s m (A) and a spastic (B) vessel SeFpnent. ?he arruws indicate the border of the tunica nwcularis. 69 The internal diameters before induction of sos spasm were similar in the two groups and at all tins (Fig. 6). Hypothennia caused a significant in the duration of spasm, whereas the duration was similar in the three' different experiments in the control group (Fig 7) . Furthermore, the severity of the spasm w a s also significantly bcreasd in the hypothennic animals ccwpared with the Controls (Fig 8 ) . The intensity of the spasm, i.e. the relative decrease in diameter, remained unchangd d u r i n g hypothda (83.8 +5.3% at -1.75"C) ccanpared with the value in the control group (85.8 f3.3%). The serum cortisol levels were not affected by the ice cooling of the animals( 282 f27 ml/l and 286 ? 29 ml/l after). l.ooo 1 0.800 n E! El 0.600 W k a 4 0.400 ;a A 0 T A 6' 1 0 cooled A control T T t 0 1 Normo- 0.000 J thermia - 1 .O"C - 1.75"C Fig. 6. The internal diameter before induction of spasm. The boay temperature in the cooled group w a s reduce3 by close to 1.0 and 1,75"C i n experiment 2 and 3, respectively. The control group was kept mnwthennic in all three experiments. N=5 in all experi- mts 70 35 30 25 20 15 10 5 0 Fig. 7. 20 15 10 5 0 Fig. 8. T 1 A O T T * 0 1 i T * 0 0 cooled A control A NOITX~O- - 1 .ooc - 1.75"C thermia ?he duration of spasm. The body temperature in the cooled group was reduced by close to 1.0 and 1.75-C in expriment 2 and 3, respectively. The control group was kept nomthermic in d l three experherb. N=5 in a l l e x p e x k t s . 0 cooled A control T * 0 1 A T * 0 1 A Normo- - 1 .ooc - 1.75OC thermia The severity of spasm. The boay temperature in the cooled group was reduced by close to 1.0 and 1.75"C in experiments 2 and 3, respectively. The control group was kept nomthermic in all three -bents. N=5 in all experiments. 71 DISCUSSION I n this study w e have shown that general h p t h d a aggravates t r a m a t i c vasospasm i n the central ear artery of the rabbit. It has been postulated on theoreticdl grounds that the rabbit ear is a specialized organ f o r tempera- ture control (15,14) . This has been studied specifically by H i l l et 61. (6) , who found, however, that a t l o w ambient temperatures there was a n e t heat loss, an3 that a t high temperatures there w a s a n e t heat influx, demon- strating that the rabbit ear is not a special organ for temperature control. we therefore believe that the results of our studies on the rabbit ear artery can be generalized to most vascular beds. There are several possible ways i n w h i c h the body temperature might influence t h e duration and s e v e r i t y of vasospasm. V e s s e l contraction induced by reduction of the core and local temperature is known t o be under sympathetic c o n t r o l ( 4 , 1 2 , 1 7 , 9 ) . Themdyrmu ' c studies of the noradrenaline receptor binding have sham a higher a f f i n i t y for the receptor a t lower temperatures (11) and that the maximal response to adrenaline and noradrenaline in the rabbit ear artery occurs a t a temperature close t o 25°C ( 8 ) . There is also an increase i n the myqenic tone, w h i c h is temperature4eperdent. This l a t t e r increase seem t o be independent of the adrenergic response but is Ca2+ dependent (5,3). These and other mechanisms may contribute t o the aggravated response of traumatically induced vasospasm observed i n the present study. Since the i n i t i a l diameters of the vessels w e r e similar a t norm1 and reduced core temperature and since the serum cortisol levels remained unchanged, activation of the sympathetic response is probably not sufficient to explain the results. It is therefore possible that the myqenic temperature depen- dence is an important mechanism underlying the aggravation. 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F u h u a publishing Company, Inc., 1987, p. 39 73 17. Walther, 0. E., Iriki, M. & Simon, E.: Antagonistic changes of blood flm and sympathetic activity in different Mscular beds following central thenml s t h u l a t i o n . Pf1uger-s A r c h . 319:162, 1970 Address for reprints: Jonas WadstrCm, MD Urnversity H o s p i t a l 5-75185 -la, Sweden -t of surgery Telephone +46-18-663000 Fax +46-18-693606 74