RAPID ECTOPIC rhythms which remain

Transcription

1 Effect of Hypotherma on Expermentally Produced Arrhythmas By EZRA J. BEYDA, M.D., SOL ALVAREZ, M.D., OTTO F. MULLER, M.D., RAPID ECTOPIC rhythms whch reman refractory to the usual type of therapy wth antarrhythmc drugs are often encountered clncally. The effect of hypotherma as a possble method of treatment under these condtons s of consderable theoretcal and practcal sgnfcance, snce such a regmen mght help to tde the patent over a crtcal perod. In the presence of rapd ectopc rhythms, t s possble that hypotherma, by decreasng cardac exctablty and metabolc tssue demands, may be a lfe-savng procedure. The benefcal effects of hypotherma n certan clncal states n whch the reducton of metabolc demands and avodance of severe hypoxa are necessary, such as n overwhelmng sepss 1 or hemorrhagc shock, 2 "* have been reported. It s well known that durng total body coolng, as well as drect coolng of the heart, the cardac rate falls, 5 " 8 and wthn crtcal ranges a drect relatonshp between heart rate and temperature s found. 5 ' 7 ~ 9 Coolng of the snoatral node depresses ts actvty; 10 the refractory perod of the cardac muscle s prolonged; conducton s slowed; and exctablty of tssues s decreased by hypotherma. 5 - u - 12 The purpose of ths study was to determne the effect of hypotherma on acontne-produced rapd ectope rhythms n the dog. Methods Twenty-fve adult mongrel dogs, weghng 13 to 20 Kg., were used n ths study; two groups of experments were performed. From the Dvson of Cardology, Phladelpha General Hosptal, Phladelpha, Pennsylvana. Supported by a grant from the Heart Assocaton of Southeastern Pennsylvana, and Grant H 141 (C-9) from the U. S. Publc Health Servce. Receved for publcaton August 11, AND SAMUEL BELLET, M.D. Experments n the Anmal wth Open Chest (Sxteen Dogs) The anmals were anesthetzed by ntravenous admnstraton of pentobarbtal (30 mg./kg.) and artfcal respraton nsttuted through an endotraeheal tube connected to a postve-pressure apparatus set at 16 e.p.m. (cycles per mnute). A femoral artery was exposed and cannulated; the cannula was then connected to a Statham stran gauge and the blood pressure recorded on a Sanborn twnvso. Eleetrocardographc (lead II) and blood pressure recordngs were obtaned at varous ntervals durng the experment. The arrhythma was nduced by the applcaton of acontne, a method descrbed by Scherf 13 ' 14 and others. 15 The chest was opened through a rght thoraeotomy ncson at the fourth ntercostal space, and the surface of the rght atrum and atral appendage was exposed. A cotton pledget saturated wth a soluton of acontne (0.05 per cent n benzene) was appled to the surface of the atral appendage untl a rapd arrhythma was produced. Ths occurred wthn a perod of two to fve mnutes, and was known from prevous studes to contnue for several hours. As soon as the arrhythma was nduced, the dog was covered wth plastc bags flled wth ce. Body temperature readngs were made at frequent ntervals by means of a deeply nserted rectal thermometer. A temperature drop from a control of 99 to 104 F. to hypothermc levels of 78 to 92 F. was obtaned wthn a perod of 45 to 80 mnutes. In eght experments, after the above level of hypotherma and the desred effect on the ectopc rhythm were obtaned, rewarmng was effected. Ths was accomplshed by coverng the anmals wth hot-water bags. The temperature was brought up to ranges of 95 to 101 F. wthn a perod of 60 to 90 mnutes. The remanng anmals whch were not rewarmed were sacrfced at the end of the experment. Experments n the Anmal wth Closed Chest (Nne Dogs) The experment was performed n two phases. The dog was ntally prepared n the followng manner. Under pentobarbtal anesthesa and artfcal respraton, a rght thoraeotomy was made 120 Crculaton Research. Volume IX, January 1961

2 HYPOTHERMIA AND ARRHYTHMIAS 121 under aseptc condtons, and the rght atral appendage exposed. The termnal end of a polyethylene tuhe (#16-1S, 25 em. long) was sutured to the wall of the appendage and covered by a small pouch of the wall made wth a purse-strng suture. The chest was then closed, wth the dstal end of the polyethylene tube protrudng through the ncson and the anmal permtted to recover. Three to fve days followng the operaton the dog was agan anesthetzed and the experment carred out as n the frst group, except that the arrhythma was produced by njecton of the aeontne soluton through the polyethylene tube. A soluton of 0.1 per cent was used n these experments and njected nto the rght atral pouch onto the surface of the rght atrum, usng 0.5 ml. ncrements at 5- to 10-mnute ntervals untl the arrhythma was produced. The effectve dose of acontne vared from 1 to 5 mg. and the tme elapsed between the njecton and the appearance of the ectopc rhythm was 3 to 20 mnutes. Results Open-Chest Experments The results obtaned n ths group are summarzed n table 1. Effects of Hypotherma on the Heart Bate and Bhythm (Fgures 1, S, and S) Control electrocardograms after the chest was opened showed a snus rhythm n all anmals. The cardac rate ranged from 100 to 185 per mnute. Followng the applcaton of acontne to the rght atrum, a rapd arrhythma was produced n all nstances. Atral fbrllaton occurred n 11 cases, whle a more regular supraventrcular tachycarda appeared n the fve remanng cases. The ventrcular rate of the nduced arrhythma ranged from 170 to 300 per mnute. In all experments, hypotherma resulted n a marked slowng of the ventrcular rate. The rate decreased to a level of 60 to 165 per mnute. Wth an average drop of temperature of 13 P., the reducton n rate averaged 54 per cent. In nne nstances, normal snus rhythm was restored under hypotherma; n one other nstance, the rhythm changed from an atral flutter wth ventrcular rate of 250 to an A-V nodal rhythm of 110 per mnute (dog 14). Although the heart rate was slowed, the arrhythma was unaffected n the remanng sx anmals. Crculaton Research, Volume IX. January 1961 TEMPCF) 10* 1O0 10* 100 j ft fl* ' Comro1 flconmnt HwrtlBH-ma toaram. Fgure 1 Effect of hypotherma and subsequent recarmng on the heart rate and rhythm n aeontne-produced rapd arrhythmas. The ordnate represents the ventrcular rate; the abscssa, the varyng temperature levels durng normotherma, hypotherma, and rewarmng. Ths graph shores the effect observed n four representatve anmals. Note the producton of the arrhythma and the rapd ventrcular rate followng applcaton of acontne. Note also the rather rapd decrease n rate and the restoraton of snus actvty under hypotherma. On reoarmng, note the moderate ncrease n rate and persstence of snus rhythm. Effects of Hypotherma on the Blood Pressure (Fgures S, S, and 4) Pror to the nducton of tachycarda, the control blood pressure averaged 110/75 mm. Hg. Wth the occurrence of a rapd ectopc rhythm followng applcaton of acontne to the atrum, a fall n blood pressure was observed n 14 experments. Ths drop averaged 13 per cent for the systolc and 15 per cent for the dastolc pressures. In the remanng two cases, no sgnfcant change occurred. Durng hypotherma, the blood pressure n nne cases further decreased by 21 and 22 per cent, respectvely, for the systolc and dastolc components. In two other experments (nos. 4 and 10), the blood pressure rose under hypotherma, returnng toward the control fgures. In the remanng three cases, no sgnfcant change n pressure was noted. Effects of Bewarmng on the Heart Bate and Bhythm In eght experments, the effects of rewarmng of the anmal were studed. In ths group, the cardac rate ranged from 60 to

3 122 BEYDA, ALVAREZ, MULLER, BELLET Table 1 Summary of Experments n the Open-Chest Anmals Dog 1 o Control * 135/ / / / /50 115/75 120/ / / / XSR /75 XSR 100/80 After acontne / / Supraventrcular tachycarda / / /35 Supraventrcular tachvearda /60 Supraventrcular taclncarda / / / / / / /65 Effect of hypotherma (% decrease) 65 (72%) 100/ (66%) 90/ (66%) 100/ (45%) 110/ (45%) 78/ (51%) 55/40 86 (40%) 85/ (64%) 85/ (58%) 64/ (62%) 100/60 94 (60%) 40/ (47%) 85/50 62 (68%) 90/60 Coronary snus 110 (60%) 90/55 91 Effect of rewarrong ( % ncrease) 145 (123%) 90/ (107%) (200%) 90/60 96 Supraventrcular tachycarda 280 (62%) 45/40 (20%) 80/55 96 (36%) 80/55 97 Supraventrcular tachycarda 370 (147%) 100/ (30%) 100/80 Crculaton Research, Volume IX. January 1961

4 HYPOTHERMIA AND ARRHYTHMIAS 123 Table 1 (contnued) Summary of Experments n the Open-Chest Anmals Dog Control /65 'Normal snus rhvrhm. After acontne / /55 Effect of hypotherma (% decrease) 115 (42%) 80/ (20%) 70/40 90 Effect of rewarmng (% ncrease) 165 per mnute (average 108) at the hypothermc level. Increase of the temperature by an average of 11 F. (85 to 96 F.) produced an ncrease n rate to a level of 130 to 370 per mnute (average 199), an average rse of 84 per cent. In four nstances, the cardac rhythm, whch had been converted to a snus orgn under hypotherma, mantaned snus actvty wth rewarmng. In two others, the nduced arrhythma recurred at the hgher temperature; n the two remanng experments, the ectopc rhythm whch had perssted wth hypotherma contnued upon rewarmng. Effects of Rewarmng on the Blood Pressure In four anmals, the blood pressure, whch averaged 85/55 mm. Hg under hypotherma, rose by about 20 per cent upon rewarmng; n three others, a decrease n blood pressure of about 25 per cent was noted; n the remanng dog, no sgnfcant change occurred wth rewarmng. The blood pressure effects whch occurred after the ncrease n rate ncdent to the rewarmng dd not follow a constant pattern. The pressure was ether unchanged or only slghtly ncreased. Closed-Chest Experments Of the nne dogs n ths group, as a result of the aeontne njecton, three developed an ntal supraventrcular ectopc rhythm followed almost mmedately by ventrcular tachycarda and fbrllaton. The latter was most probably due to the spread of the acontne soluton over to the ventrcular Crculaton Research, Volume IX, January lge wall. The results obtaned n the remanng sx dogs are summarzed n table 2. Effect of Hypotherma on the Heart Bate, Cardac, and Blood Pressure The control rhythm was snus n all anmals, and the cardac rate ranged from 120 to 160 per mnute. Followng njecton of acontne, supraventrcular tachycarda was produced n four cases and atral fbrllaton n two others. The ventrcular rate ranged from 160 to 320 per mnute. Durng hypotherma the rate decreased to a level of 80 to 120 per mnute. An average reducton of temperature of 19 F. produced a decrease of the ventrcular rate averagng 59 per cent. In two nstances, normal snus rhythm was restored under hypotherma; n two others, supraventrcular ectopc rhythm perssted but was slow and regular (rates of 120 and 80 per mnute, respectvely); and n one experment, atral fbrllaton contnued, although wth a much slower ventrcular response (120 per mnute). In the remanng dog, after ntal converson of the arrhythma to a slow nodal rhythm was obtaned, sudden ventrcular fbrllaton and death of the anmal occurred. Systemc blood pressure was recorded n three of these experments. The control pressure averaged 155/95 mm. Hg, and wth the nducton of the rapd ectopc rhythm dropped by an average of 50 per cent. Under hypotherma a slght rse was observed n one ease and a slght addtonal drop n one other.

5 BEYDA, ALVAREZ, MULLER, BELLET 124 A) Control- k.c UUr looaltna ys^^^ o98of or j r [ vwj,! T, ' * ; I I? rr 1 '"'! \!!.!!! - I T! " 1 } ' *.... I j. j j j ] j j _ t.j,! -s A A A! A! -n\ ' rs^ V4J "H \*0- Fgure 2 Effect of hypotherma and subsequent rewarmng on acontne-produced arrhythma (dog 8). (a) Control tracng; chest opened, (b and c) After applcaton of acontne to the atral wall. Note the appearance of a rapd supraventrcular tachycarda and slght drop n blood pressure, (d, e, and f) Durng hypotherma, further converson to atral fbrllaton wth gradual slowng of the ventrcular rate s seen, and fnally restoraton of slow snus actvty. Note also the slght drop n blood pressure at the lower temperature, (g, h, and ) Tracng durng gradual rewarmng of the anmal; note the persstence of snus rhythm wth gradual ncrease of heart rate. The blood pressure ncreases wth the ncrease of temperature. The thrd anmal, as mentoned before, ded wth ventrcular fbrllaton durng the ncepton of hypotherma. Effect of Rewarmng on the Heart Mate, Cardac, and Blood Pressure Rewarmng was carred out n three anmals of ths seres. From an average of 93 per mnute at hypothermc levels, the heart rate rose to an average of 175 per mnute when the temperature was rased. Snus rhythm whch was restored by hypotherma n one case perssted when the anmal was rewarmed. In a second ease, atral fbrllaton whch had been converted to a slow regular rhythm by hypotherma reappeared upon rewarmng. In the thrd anmal, after snus rhythm was restored rewarmng produced a ventrcular tachycarda; however, the dog was recooled Crculaton Research, Volume IX, January 1961

6 125 HYPOTHEKMIA AXD ARRHYTHMIAS, Control 7 After! *! conltlm j.!.. 1! 97oF. Fgure 3 Effect of hypotherma and subsequent revarmng on acontne-produced arrhythma (dog 1.) (a) Control tracng; chest opened, (b) After applcaton of acontne to the atral vall. Note the appearance of a rapd atral fbrllaton and a sgnfcant drop n blood pressure, (c, d, e, and f) Tracngs durng hypotherma. Note the gradual slowng of the ventrcular rate and the restoraton of a slov snus rhythm. Note also the ntal fall of the blood pressure whch rses agan vth the re-establshment of snus actvty and sloung of the cardac rate, (g, h, and ) Tracngs durng gradual rewarmng of the anmal. Snus rhythm perssts and the heart rate gradually ncreases. A slght drop n blood pressure tvth the ncrease of rate s also seen. and the temperature lowered agan from 90 to 77 F., wth re-establshment of a slow snus rhythm. The blood pressure was recorded on rewarmng n two experments. There was a rse of approxmately 40 per cent n one nstance and a sharp drop n the other n the presence of ventrcular tachycarda. Dscusson There are numerous reports n the lterature Crculaton Research. Volume IX, January 1961 dealng wth the occurrence of arrhythmas durng hypotherma.16"10 However, lttle data are avalable concernng the effect of low body temperature on ectopc rhythms and most of those studes were performed n the solated heart. Ruskn and Decherd20 found that ventrcular tachycarda produced by varous methods n the solated rabbt heart could be rapdly stopped by mmerson of the ventrcles n ced water. Drken et al.,21

7 126 BBYDA, ALVAREZ, MULLER, BELLET T HP( f) O0 100! JJ/tar Control j flcomunc Fgure 4 Effect of hypotherma and subsequent rewarmng on the blood pressure. The ordnate represents the systolc blood pressure levels; the abscssa, the varyng temperature durng normotherma, hypotherma, and rewarmng. The effect observed n four representatve anmals s shown on ths graph. Note the sharp drop n pressure followng applcaton of acontne and producton of the rapd ectopc rhythm. Under hypotherma, an ntal further drop n pressure occurs and later, as the temperature s decreased and the heart rate slowed, the pressure rses agan. Further rse n blood pressure s seen durng rewarmng. Table 2 Summary of Experments n the Closed-Chest Anmals DOK Control * 160/ / /75 98 After acontne /45 Supra ventrcular tachycarda 320 Supraventreular tachycarda /85 Nodal tachycarda Supraventreular tachycarda /25 Burn and Goodford 22 stated that n the solated heart, producton of ventrcular fbrllaton by stmulaton was easer at hgher temperatures. Beaulnes and Day 23 studed the effect of temperature on electrcally produced arrhythmas n the solated rabbt atra. They found that "on lowerng the temperature the arrhythma dmnshed n -ate and often ceased altogether." Hgher temperatures were found to favor the producton of these arrhythmas. More recently, Sommervlle 24 reported brefly on the effect of hypotherma on establshed atral fbrllaton n 15 patents undergong surgery for the repar of atral septal defect. Durng early coolng, marked slowng of the ventrcular rate was observed and n half the patents "the rhythm became precsely regular when the temperature had fallen 1 to 2 C." No statement s avalable relatve to the effect of rewarmng on these arrhythmas. Induced rapd ectopc rhythms were slowed by hypotherma n all the anmals, and n the Effect of hypotherma (% decrease) A-V nodal 120 (54%) 75/ (75%) (50%) /80 78 A-V nodal 80 (56%) (61%) 78 Intal slowng to A-V nodal rhythm then ventrcular fbrllaton Effect of rewarmng (% ncrease) 215 (78%) 130/ (118%) 89 Ventrcular tachycarda t U0 (75%) 75/50 90' Normal snus rhythm. tn ths experment, ventrcular tachycarda appeared durng rewarmng. The anmal was then recooled from 90 to 77 T., and normal snus rhythm at a rate of 80 per mnute was obtaned; the blood pressure rose to 100/50 mm. Hg. Crculaton Research, Volume IX, January 1961

8 HYPOTHERMIA AND ARRHYTHMIAS 127 majorty of cases, normal snus rhythm was restored. A benefcal cardac effect had, therefore, resulted n all cases. Durng hypotherma the systemc blood pressure s reported to show a gradual fall. 8 Such a fall occurred n about half of our experments. In the remander, the blood pressure ether dd not change or rose wth the drop n temperature. Slowng of the cardac rate and, therefore, better dastolc fllng of the heart mght explan the fndng. The effect of coolng on ectopc rhythms durng hypotherma s very lkely medated by changes n the followng m3 r oeardal propertes decreased exctablty, ncreased refractory perod, ncreased conducton tme, and ncreased duraton of acton potental. 5 " 7 ' 9 " 12 ' 20, T] ese actons, n many respects, are smlar to the mechansms by whch antarrhythmc drugs (qundne and procane) act n controllng rapd ectopc rhythms. The decrease n cardac work durng hypotherma s an addtonal benefcal factor. The aforementoned experments suggest that the use of hypotherma represents an added therapeutc measure n the treatment of rapd ectopc rhythms whch may be worthwhle explorng n patents who are refractory to the usual methods of therapy. Summary The effect of hypotherma on expermentally produced rapd arrhythmas n the dog was studed. Rapd eetopc rhythms were produced n open-chest and "ntact" anmals by applcaton of acontne soluton to the rght atral wall. In all experments, a benefcal cardac effect was obtaned marked slowng of the ventrcular rate occurred n all cases, and n approxmately half of the cases snus rhythm was restored. On rewarmng, although the heart rate ncreased, the snus rhythm acqured durng hypotherma perssted n most nstances. The blood pressure fell when a rapd arrhythma was produced. A further drop was observed n approxmately half the eases durng hypotherma. In the remanng cases no change, or a slght rse n blood pressure, occurred durng coolng. The results obtaned n the expermental anmal would Crculaton Research. Volume IX, January 1981 appear to have a bearng on the therapy of certan refractory arrhythmas n the human subject. References 1. LEWIS, F. J., RING, D. M., AND ALDEN, J. F. Technque for total body coolng of febrle, gravely ll patents. Surgery , PRANK, H. A., SELIGMAN, A. M., AND FIXE, J. Traumatc shock X. Treatment of hemorrhagc shock rreversble to replacement of blood volume defcency. J. Cln. Invest , OVERTON, E. C, AND DEBAKEY, M. E. Expermental observatons on the nfluence of hypotherma and automatc blockng agents on hemorrhagc shock. Ann. Surg , POSTEL, A. H., EEID, L. C, AND HINTON, J. "W. Therapeutc effect of hypotherma n expermental hemorrhagc shock. Ann. Surg , BROOKS, C. MCC, HOFFMAN, B. P., SUCKLING, E. E., AND ORIAS, 0. Exctablty of the Heart. New York, Grune & Stratton, CARDI, L. Functonal changes of heart durng hypotherma. Angology 7 2, HEGNAUER, A. H., SCHRIBER, W. J., AND MATERIUS, H. O. Cardovascular response of the dog to mmerson hypotherma. Am. J. Physol , HOOK, W. E., AND STORJIONT, B. T. Effect of lowered temperature on heart rate, blood pressure and electrocardogram. Am. J. Physol , BADEER, H. Influence of temperature on S-A rate of dog's heart n denervated heart-lung preparaton. Am. J. Physol , EYSTER, J. A., AND MEEK, W. J. Orgn and conducton of the heart. Physol. Rev. 1 1, CORABOEUF, E., AND WEIDIIANN, S. Temperature effects on the electrcal actvty of Purknje fbers. Helvet. physol. et pharmacol. acta 12 32, PINKSTON, J. O., KAO, F. F., AND BROOKS, C. McC. Studes on the exctablty of the heart as tested by chroncally mplanted electrodes and the effects of temperature thereon. Abstr. 19th Internat. Physol. Congress, Montreal, 1953, p SCHERF, D. Studes on aurcular tachycarda caused by acontne. Proc. Soc. Exper. Bol. & Med , SCHERF, D. Methods of nducng atral arrhythmas n ntact dogs II.. J. Pharmacol. & Exper. Therap , PRrNZMETAL, M., CORDAT, B., BRILL, I. C, OBLATH, R. W., AND KEUOER, H. E. The Aurcular Arrhythmas. Sprngfeld, 111., Charles C Thomas, 1952.

9 BADEER, H. Ventrcular fbrllaton n hypotherma. J. Thoracc Surg , COVINO, B. G., CHAELESON, D., AND B'AMATO, H. E. Ventrcular fbrllaton n hypotherme dogs. Am. J. Physol , HOFF, H. E., AND STANSFIELD, H. Ventrcular fbrllaton nduced by cold. Am. Heart J , SENNING, A., ABO, J. C, AND MELINA, D. Ventrcular fbrllaton n atral nterventons under hypotherma. Mn. Cardoangol. Eur , RUSKIN, A., AND DECHERD, 6. M.. Temperature change, conducton and electrcal systole of the solated rabbt heart. Am. J. Physol , lT DIEKEN, M. N. I., GEVEES, F., HEEMSTBA, H., AND HUIZINQ, E. F. Study of defbrllatng agents on perfused rabbt hearts. Crculaton Research 3 24, BEYDA, ALVAREZ, MULLER, BELLET 22. BUBN, H. H., AND GOODFORD, P. J. Effect Of lack of glucose and lack of oxygen on ventrcular fbrllaton. J. Physol , BEATTLNES, A., AND DAY, M. Effect of temperature on arrhythmas n solated rabbt hearts. J. Physol , SOMSIERVILLE, W. Effect of hypotherma on atral fbrllaton. Brt. Heart J , OSBORN, J. J. Expermental hypotherma Respratory and blood ph changes n relaton to cardac functon. Am. J. Physol , SWAN, H., ZEAVIN, I., HOLMER, J. H., AND MONTGOMERY, V. Cessaton of crculaton n general hypotherma I. Physologcal changes and ther control. Ann. Surg , HOLLANDER, P. B., AND WEBB, J. L. Cellular membrane potental and contractlty of normal rat atrum and the effect of temperature tenson and stmulus frequency. Crculaton Research 3 604, Crculaton Research, Volume IX, January 1961