The effect of burn injury on the heart in the whole body and on the extracorporeally perfused isolated heart

Burns, 9.53-61

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The effect of burn injury on the heart in the whole body and on the extracorporeally perfused isolated heart M. I. Kuzin, V. F. Portnoy, G. F. Dwortsin and A. V. Machulin A. V. Vishnevsky Institute of Surgery of the Academy of Medical Sciences of the USSR, Moscow, USSR

Summary

Cardiac performance during the initial stage of burn shock in dogs was studied in the whole body and compared with the function of the isolated hearts, perfused from donor animals similarly burned. Continuous recording of the functional indices using electromagnetic Aowmetry and ECG with on-line processing of the data enabled us to establish the following facts. Progressive decrease of cardiac output secondary to the depression of myocardial contractility against the background of stable inflow takes place as early as 2-5 minutes after massive burning in the whole body. No significant changes of the functional indices of the isolated hearts, perfused from the perfusion donors similarly burned, were observed in the second group of experiments. The underlying mechanisms of the above phenomena are discussed.

INTRODUCTION THE

decrease in cardiac output in burned patients was first established by Richards (1944). Since that time, this phenomenon has been repeatedly reproduced experimentally (Gilmore and Handford, 1956; Michie et al., 1963). The decrease in cardiac output is observed in the first few minutes after a massive burn and it reaches 50 per cent ofthe initial level after 5-10 minutes (Portnoy et al., 1982). The causes of such an abrupt decrease in cardiac output are not established as yet. It should be noted that the direct methods of myocardial contractility investigation have not been applied following bum injury in the whole body so far, and the majority of authors decide whether cardiac failure has taken place by the indirect data.

The study of the causes of low cardiac output in the whole body presents considerable problems, as several different factors are simultaneously involved in burn shock. Neural and humoral influences, disturbances of peripheral circulation-any of these factors may lead to the depression of myocardial contractility. Experimental models, which permit the study of one of the possible factors, might help to solve this question. It was shown, for example, that perfusion of isolated papillary muscles of the rabbit ventricle with the serum of burned rabbits had a negative inotropic effect (Hakim et al., 1973; Vomovitsky et al., 1979; Vasiletz, 1979). Our work was therefore designed to study cardiac performance in the initial stage of bum shock in the whole body and, using the same model, to compare it with that of the isolated heart, perfused from the burned dog. It was thought that this might help study the effect of humoral factors in bum injury on the dog myocardium at the organ level. MATERIALS

AND METHODS

Two groups of experiments adult mongrel dogs.

were carried out on

Group I

Nine experiments were carried out. Dogs weighing 7.5-18 kg were used. Premeditation comprised 2 per cent Promedol I5 mg/kg i.m. and general anaesthesia was induced using 3 per cent Nembutal 30 mg/kg i.v. and Succinilcholine

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1

DISPLAY

+JlP”TERI_

HR

Cl

SC0 SAP

sv SW

DA P dP/dt T P R -dvdy

A

e,

C

Fig. 1. Schematic presentation of the recording, processing and display of cardiac performance. A, The position of the probes, electrodes and catheters; B, the curves, being processed by the computer; C, the indices, calculated and displayed by the computer. I, A cuff EMF probe on the ascending aorta; 2, a catheter in the aorta; 3, a catheter in the LV cavity; 4, bipolar electrode for recording LVEG; 5, bipolar electrode for recording RAEG. RAEG, Right atrial electrogram; LVEG, left ventricular electrogram; AP, aortic pressure; LVP, left ventricular pressure; CO, cardiac output; HR, heart rate; SCO, specific cardiac output; dP/dt,,,, the maximum velocity of LVP increase; V-dP/dt,ex, the maximum velocity of LVP decrease; SAP, systolic arterial blood pressure; DAP, dyastolic arterial blood pressure; TPR, total periferal resistance; VcE, conractile element velocity; CI, contractility index; F,,,, the maximum volume blood flow velocity in the aorta; SV, stroke volume; SW, stroke work.)

1 m&kg before burning. Assisted ventilation was carried out with an RO-3 machine using 50 per cent 0,: 50 per cent room air mixture under control of gas composition and acid-base balance (ABB) of arterial blood. After median sternotomy, the pericardium was opened. The main pulmonary artery was separated from the ascending aorta, on which a cuff probe of the electromagnetic flowmeter Nycotron-376 was placed to measure cardiac output (Fig. 1). A catheter was inserted via the left subclavian artery to record aortic pressure (AP) and another one through the left ventricular apex to register left ventricular pressure (LVP). The catheters were connected to EMT-34 transducers. Bipolar electrodes were fixed on the right atria1 auricle and the left ventricular apex to register right atria1 (RAEG) and left ventricular electrograms (LVEG). Visual determinations of venous pressure (VP) were performed in the inferior vena cava using a catheter and water manometer. Then the chest cavity was tightly closed. The indices of haemodynamics and cardiac performance were recorded on the eight-channel Mingograf-800 (Elema-Schonander). The signals from the Mingograf-800 were passed

through an analog-to-digital converter and were processed by the M-220 computer. On-line calculations of the indices studied were performed using a specially developed program (Portnoy et al., 1979). Calculation and typing of 18 indices, characterizing contractility, pump function and compliance of the myocardium were performed according to the program. These included: systolic (SAP), diastolic (DAP) and mean AP, systolic LVP and left ventricular end diastolic pressure (LVEDP), dP/dt,,,, VCE, contractility index (CI) (Veragut and Krayenbiihl, 1965) - dP/dt,,, (Frederiksen et al., 1973) time from the maximum increase to the maximum decrease of LVP, l/2 RT (Parmley and Sonnenblick, 1969) TRT (Weisfeldt et al., 1974), dF/dt,,,, F,,,, HR, stroke volume (SV), specific cardiac output, TPR and stroke work (SW). The most informative and evidently changing indices were chosen for analysis to facilitate perception of the material. Thirty-forty per cent of the body surface area was burned with boiling water. The considered indices were recorded before and during burning (duration, 2 minutes) and for 1 hour post burn (continuously during the first 10 minutes, then

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Fig. 2. Schematic drawing of isolation (A) and perfusion (B) of the isolated heart. 1, lntubation tube; 2, the right lung; 3, a reservoir with autologous blood; 4, a catheter for AP recording; 5, a catheter for LVP recording; 6, a tube in the descending aorta; 7, a tube in the main pulmonary artery; 8, a tube in the RA; 9, a reservoir, controlling inflow velocity; 10, venous reservoir; I I, venous line to the donor; 12, cardiac output resistance regulator; 13, EMF probe; 14, blood overflow line from the pressure stabilizing vessel; 15, bubble trap, EMF probes and termistor; 16, arterial line lumen regulator; 17, heat exchanger.

every 5 minutes). Unpaired t test was used to assess the significance of the observed changes. The correlation coefficient (r) of dP/dt,,, with the principal haemodynamic indices and some parameters was calculated. Group II

Nine experiments were carried out. The weight of the donors ranged from 5.5 to 11.5 kg, that of the recipients from 19 to 29 kg. Anaesthesia was induced by the same method as in group I. After median stemotomy and administration of heparin (3 mg/kg), a cannula was inserted into the left subclavian artery. Following crossclamping of the ascending aorta and brachiocephalic artery, partial blood-letting was performed into the vessel, fixed 100 cm above the heart level. Heart-lung preparation was isolated under the steady blood pressure. The left lung was excised. Polyethylene tubes were inserted into the ascending aorta, main pulmonary artery and the left atrium (Fig. 2a). These tubes connected the heart to the perfusion system. Retrograde perfusion of the isolated heart was carried out for the first 10 minutes, during which time the right lung was excized. Thus, adequate blood supply of the isolated heart was preserved during its isolation. Then the heart was perfused for I

hour with blood, inflowing into the left atrium under constant pressure (Fig. 26), volumetric velocity of the inflow being 50-60 ml min-I kg-l of the heart donor body weight. Thirty-forty per cent of the dog-recipient body surface was burned with boiling water for 2 minutes. The dogs were observed for 1 hour post bum. Volume loading tests of the isolated heart were carried out at the fifth, fifteenth, thirtieth, fortyfifth and the sixtieth minute before and after burning as follows: the vessel, from which blood flowed into the left atrium was lifted for 20-30 seconds to elevate left ventricular end diastolic pressure from 0 to I O-l 5 mmHg. The following indices were determined in the perfusion donor: HR, AP, VP, ECG, linear velocity of blood flow (LFV) in the ascending aorta using a catheter-tip EMF probe (Nycotron-376). The following parameters were recorded on the isolated heart: RAEG, LVEG, AP, LVP, left atria1 inflow pressure (IP), visually: volume velocity of inflow into the LA (VW), cardiac output (CC)) and CBF (RV output) with the aid of cannulating EMF probes (Nycotron 372 and 376). RAEG, LVEG, AP, LVP, VVI, CO and CBF of the isolated heart, as well as ECG and LFV of the perfusion donor, were recorded on the eight channel Mingograf-800 (Elema-Sch6nander).

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The PO, of inflowing and outflowing coronary blood, using an IL-213 gas analyser, and the temperature of inflowing blood (TT- 14M, Waters) were also measured. The following functional parameters of the isolated perfused heart were considered while processing the material: HR, SAP, DAP and perfusion blood pressure (PP = DAP + l/3 [SAP-DAP], LVP, LVEDP, dP/dt,,,, CI, - dP/dtmax, l/2 RT, TRT, SC0 (ml/min per 1 kg), SW (gem cycle-i), TPR (dines s-i cm-s). Investigations of gas composition and ABB of arterial and venous blood (IL-2 13) were carried out during perfusion of the isolated heart before and after burning. 0, consumption by the isolated heart was calculated using Fick formula. RESULTS Group I

The curves, recorded at different stages ofthe experiments are presented on Fig. 3. Considerable increase of SC0 was observed during burning (Fig. 4). It increased from 123 + 8.7 to 162 + 7.2 ml mini kg-i by the second minute. SC0 abruptly decreased at the first minute post burn. It decreased to 80 per cent of the initial level in 2 minutes and to 50 per cent in 5 minutes (63.2 f 10.6 ml min-i kg-i, P
1

(initial: 3 111 + 594, P >O.l). Depression of these indices continued during the next 15 minutes and became significant by the twentieth minute post bum. A significant decrease in dP/dt,,, (P < 0.02) and dF/dt,,, (P < 0.05) was noted by the thirtieth minute post bum. Decrease of F,,, in the early post bum period was significant by the tenth and twentieth minute. These indices remained decreased during a 1 hour follow-up period. Compliance index (- dP/dt,,,), increasing during the first 5 minutes post burn, did not differ from the initial level later on. As to the other contractility indices, which were calculated by the computer (VCE, CI), the dispersion of data obtained did not allow statistical processing. However, dynamic analysis of these indices in some experiments revealed the same trend: depression during the first 5 minutes post burn, maintained for 1 hour ofobservation. HR changes during the experiments were insignificant. Considerable increase of SAP from 121 + 5.9 to 170 k 11.1 and DAP from 86 _+ 5.5 to 137 k 7.9 mmHg was observed during burning (Fig. 5). Progressive decrease of AP was observed during the following hour, and by the thirtieth minute it dropped below the initial level (P <0.05), remaining then at that level. A sharp increase of VP from 44.7 + 10.9 to 93.9 + 12.5 cm H,O took place during burning. Then it also decreased gradually and, by the fifth minute post bum, its difference from the initial level became insignificant. During the observational hour, VP was close to the initial level. An increase in LVEDP from 2.5 I 1.0 to 7.2 + 1.6 mmHg (P ~0.05) took place by the second minute post burn. It remained elevated

Fig. 3. Cardiac function curves in massive bum trauma. A, Before burning; B, during burning; C, 5 minutes post bum; D, 30 minutes post burn; E, 60 minutes post burn. I, RAEG; 2, LVEG; 3, AP; 4, LVP; 5, dF!/dt,,,; 6, CO.

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0

7lz-Y

dV

‘tlH

03s

0

Kuzin et al.: Effect of Burn Injury on the Heart

during the entire follow-up period, though its difference became insignificant in 5 minutes. Progressive TPR increase in the post-burn period reached a significant level by the third minute, continued during the first 10 minutes and then decreased gradually, becoming insignificant after 20 minutes. A high correlation of the studied indices with dP/dt,,, was found. There was no correlation between HR changes and in this group (r = 0.28). dP/dt,,, Group II

The conditions of perfusion and coronary haemodynamics of the isolated heart were characterized by stability and did not differ before and after burning of the perfusion donor. During all the follow-up period before and after burning, 0, consumption by the perfused heart remained constant, being 3 k 0.48 ml mini 100 g-r (Fig. 6). The analysis of functional indices of the isolated perfused heart before and after burning (Fig. 7) showed that HR, LVP and myocardial compliance indices (- dP/dt,,,, l/2 RT, TRT) did not change at different stages. Myocardial contractility indices (dP/dt,,,, CI) also did not change significantly, although an insignificant CI decrease was observed at almost all the lo-minute intervals. Significant SC0 decrease, beginning from the fortieth minute (P ~0.05) and continuing at 50 and 60 minutes (P ~0.01) was observed by the end of the first hour after buming against the background of LVEDP increase (P ~0.02). This resulted in a decrease of SC0 (P < 0.02) and SW (P ~0.05) by the sixtieth minute post burn. It was demonstrated during loading tests and stage-by-stage drawing of the LV functional curves of the isolated heart that burning did not cause myocardial depression, though 5 minutes after burning, the curve, reflecting interrelationships between dP/dt,,, and LVEDP shifted downward and to the right (Fig. 7). DISCUSSION

Analysing the results, one should take into account the specific aspects of our experimental model. The experiments were carried out on anesthetized animals. According to Cannon (I 9 15) changes occurring in the body during pain stimulation can be induced in the anaesthetized animal to a great extent, though the latter does not suffer from pain. TPR elevation is characteristic for profound Nembutal anaesthesia, which caused high initial TPR as well as slightly depressed myocardial contractility.

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However, judging by the initial contractility indices and by its increase during burning, Nembutal had an insignificant negative inotropic effect. In group I of the experimental model, burning was performed after thoracic operation. Though not accompanied by significant haemorrage, operational trauma might influence the degree of the body response to bum trauma. All these factors, however, did not obscure the principal responses to extensive bum trauma. The data obtained show that closely related significant changes in cardiac performance and haemodynamics took place at the earliest stage of bum trauma. Powerful stimulation from the skin receptors during burning induced acute activation of cardiac function. Then, during the first minutes post bum the maximum TPR increase and significant depression in cardiac output were observed. Different degrees of changes in cardiac output, observed by us and other authors, can be attributed to the differences of experimental animals, models, anaesthesia and severity of bum trauma. Depression in cardiac output during the first minutes post bum could be caused by functional overload of the myocardium (high systolic load) due to high AP. Actually, during that period, dP/dt,,,, as well as LVEDP, significantly exceeded the initial level, but cardiac output proved to be decreased. High TPR persisted during the following observational period. Against the background of low cardiac output, AP remained at a level close to the normal one. A distinct trend towards contractility depression was already observed by the fourth to fiRh minute post bum, the mean being 88 per cent of the initial level by dP/dt,,, the fourth minute, 78 per cent by the fifth and 67 per cent by the tenth minute. Mean dF/dt,,, was 77, 72 and 68 per cent correspondingly, dropped to 47 per cent of the initial dF/dt,,, level by the fortieth minute. A significant depression in myocardial contractility was observed IO-20 minutes post bum. Low cardiac output persisted throughout the follow-up period, in spite of high VP and LVEDP. Our experiments give evidence of the fact that such an early depression of pump function and contractility of the myocardium in massive burn trauma is not associated with deficient blood inflow. High VP and LVEDP at the same moment as a decrease in cardiac output was recorded testify to the above conclusion. LVEDP exceeded the initial level throughout the observational period. Therefore, the assumption arises that the low cardiac output syndrome at the beginning of

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burn shock is caused by primary cardiac failure. What is the nature of myocardial contractility depression induced by burn trauma? Which factors, humoral or neural, are responsible for the development of this phenomenon? The experimental model which we used in group II of the experiment made it possible to study the effect of humoral factors on the isolated dog hearts. This not only excluded the immediate influence of the extracardial nervous system on the heart but also created similar regimens of coronary haemodynamics and blood inflow into the left ventricle before and after burning. The data obtained show that no significant changes took place in the isolated heart during the follow-up period. Oxygen consumption, which reflects the intensity of myocardial metabolism, remained constant. There were no significant changes of the indices characterizing myocardial automatism, contractility, compliance and of stroke work of the heart. According to the conditions of the experiments, left ventricular inflow (as well as output) was two times lower than normal cardiac output in the whole body. Repeated load tests of combined volume-systolic character were carried out to discover left ventricular functional reserve. The peak load ventricular output exceeded its normal level. Myocardial failure was not observed in these experiments. No significant depression of myocardial contractility and pump function took place in the specific conditions of our experiments. These data disagree with the results of group I, in which a rapid and significant deterioration of myocardial function was observed. Therefore, it can be supposed that the nervous system of the burned animal exerts a direct negative inotropic effect on the heart. A detrimental haemodynamic effect in the whole body also cannot be excluded. Another possible explanation is the ‘unsensitivity’ of the isolated heart to humoral factors, which appear as a result of bum trauma. Taking into account the law of increased sensitivity of denervated structures (Rosenblueth and Cannon, 1949) one can assume that the direct depressive action of the blood-borne agents is overlapped by increased myocardial sensitivity to catecholamines. The same concentrations of catecholamines do not cause a significant increase of myocardial contractility in the whole body. This assumption is not confirmed by the direct evidence. However, recent experimental data show the direct depressive effect of burned rabbit sera on the contractility of papillary muscles (Hakim et al., 1973;

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Vasiletz, 1979; Vomovitsky, 1979). This may seem to contradict the theory of the ‘unsensitivity’ of the isolated heart to bum myocardial depressants. However, there is no information on the similarity of denervation law in the whole organ with a completely preserved intracardiac nervous system, which provides the heart with autoregulation (Kositsky, Chervova, 1968), and in the tissue strip. It is also not known whether the experimental results are species-dependent. Our data give evidence of the absence of depression of contractility and pump function of the isolated heart as compared with the heart in the whole body, though in both cases the heart is perfused with blood of similar composition. We explain this by the influence of extracardiac nervous system. However, further investigations will be needed to specify the nature of low cardiac output in the initial stage of bum shock.

REFERENCES

Cannon W. B. Bodily changes in pain. Boston. Fear and Page. Frederiksen J., Mesfeldt M. L., Scully H. E. et al. (1973) Hemodynamic determinants of maximum left ventricular relaxation rate. Fed. Proc. Abstr. 32, 658. Gilmore J. P. and Handford S. W. (1956) Hemodynamics response of the dog to thermal radiation. J. Appl. Physiol. 8,293-298.

Hakim A. A., Sladek C. D. and Rosenthal S. R. (1973) Thermal injury: actions of acute burn serum on rat heart. Proc. Sot. Exp. Biol. Med. 144,359-363. Kositsky G. I. and Chervova I. A. (1968) The heart as the self-regulating system. Moscow, Nauka-Publishers. Michie D. D., Goldsmith R. S. and Mason A. D. (1963) Effects of hydralasine and high molecular weight dextran upon the circulatory response to severe thermal bums. Circ. Res. 13,468-473. Parmlev W. W. and Sonnenblick E. H. (1969) Relation between mechanics of contraction and relaxation in mammalian cardiac muscle. Am. J. Physiol. 216, 1084.

Portnoy V. F., Dwortsin G. F. and A. V. Machulin (1982) Cardiac performance at the initial stage of burn shock. Pathol. Physiol. Exp. Ther. 1, IO. Portnoy V. F., Nidekker I. G., Dwortsin G. F. et al. (1979) An automatic system for intraoperational assessment of cardiac function. Anesteziol. Reanimatel. 3,28-32.

Richards D. W. (1944) The circulation in traumatic shock in man. Harvey Lect. 39, 2 17-253. Rosenblueth A. and Cannon W. B. (1949) Supersensitivity ofthe denervated structures. New York.

Kuzin et al.: Effect of Burn Injury on the Heart

L. A. (1979) Study of the effect of burn serum on electrical activity and contractility of the homoiothermal myocardium. Bull. Exp. Biol. Med. 8, 710. Veragut U. P. and Krayenbiihl H. P. (1965) Estimation and quantification of Myocardial contractility in the closed-chest dog. Curdiol. Pm. 47, 96-112. Vasiletz

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Vornovitsky E. G., Lenykova N. A. and Vasiletz L. A. (1979) Changes of contractility of the rabbit heart myocardium during bum shock. Bull. EXD. Biol. Mid. 1, 6-8. Weisfeldt M. L., Armstrong P., Scully H. E. et al. (I 974) Incomplete relaxation between beats after myocardial hypoxia and ischemia. J. C&Z. Invert. 53, 1626-1636. Paper accepted I I November

Cmw\pond~wce .d~ould hi addrcwed IO: Professor M. Kuzin, Moscow. USSR.

Vishnevsky

Institute

198 I

of Surgery. B. Serpuchovskaya

27. M-93.