© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
The effect of brain death on cardiovascular function in rats. Part I. Is the heart damaged?
aCentre for Experimental Surgery and Anaesthesiology, K.U. Leuven, Provisorium I, Minderbroedersstraat 17, B-3000 Leuven, Belgium
bJanssen Research Foundation, Beerse, Belgium
* Corresponding author. Tel.: +32 (16) 337298; Fax: +32 (16) 337855.
Received 4 August 1997; accepted 30 August 1997
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Abstract |
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 Top Abstract 1 Introduction2 Methods3 Results4 DiscussionReferences |
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Objective: Brain death induces important haemodynamic changes in rats, with a drop in arterial blood pressure, left ventricular developed pressure and dP/dtmax to less than 50% of its control value. Myocardial damage was reported to contribute to this paradigm. The role of potential underlying pathogenetic mechanisms, such as a circulating cardiodepressant factor, NO, endogenous opioid peptides, vagal or β-adrenergic activation, or hypophyseal dysfunction, were explored, but none of them could be demonstrated as the culprit. This study investigated whether functionally important intrinsic myocardial damage was induced by brain death in the rat, and whether coronary endothelial cell dysfunction, possibly causing multifocal ischaemia, contributed to this. Methods: Brain death was induced in rats by sudden inflation of an intracranial balloon. Extensive haemodynamic measurements, including heart rate, arterial blood pressure, central venous pressure, left ventricular pressure, and cardiac output, were performed. Hearts excised 1 and 4 h after brain death were examined histologically. The contractile reserve of these hearts was tested by administration of increasing doses of adrenaline (10–9 to 10–6 mol/l) in a Langendorff system. The coronary endothelium was tested with regard to its barrier function for macromolecules by determining the extravasation of injected Evans blue, and with regard to its vasoactive function by testing the effects of serotonin and nitroglycerin in a Langendorff system. Results: The haemodynamic measurements suggested that the cardiovascular collapse consisted mainly in alterations in afterload. Contractile reserve, as tested with increasing adrenaline doses, revealed a normal dose–response curve. No histological myocardial damage was found after brain death in rats. No abnormal extravasation of Evans blue was seen. Coronary vasoreactivity towards nitroglycerin and serotonin was normal. Conclusion: Myocardial damage, if present at all, contributes only minimally to the changes in haemodynamic profile seen after brain death in the rat, and the coronary endothelium appears to preserve its barrier and vasoactive function.
KEYWORDS Rat; Brain death; Myocardium; Contractile reserve; Coronary endothelium
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1 Introduction |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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Besides its fundamental interest, the study concerning the influence of brain death on the heart gained popularity in the era of heart transplantation. This is caused by the fact that a considerable part of the potential organ donors become haemodynamically unstable, precluding the use of the heart for transplantation [1]. Furthermore a small percentage of the transplanted hearts exhibit poor function, despite the fact that no immunological or surgical–technical reason is apparent [2].
Brain death induces a severe haemodynamic collapse in rats [3, 4], and myocardial damage was reported, proportional to the amount of catecholamines released at the moment of brain death [4]. Comparable phenomena were shown in many species, including baboons [5], pigs [6], and dogs [7]. This, however, does not necessarily mean that the catecholamine storm at the moment of brain death causes irreversible myocardial damage and that this myocardial damage, in turn, causes the haemodynamic collapse seen after brain death. Especially difficult to reconcile with this hypothesis is the fact that rat hearts explanted 60 min after brain death, when the haemodynamic collapse is already present in vivo for a considerable time, showed normal basal contractile function in a Langendorff system [3]. A possible explanation for the normal contractile function after explantation and a depressed myocardial function in vivo after brain death, could be a circulating or neurogenic cardiodepressive factor in vivo. Such a factor, however, is not present, as was elegantly demonstrated by Galiñanes and Hearse [8]. Another classical hypothesis to explain the brain death-induced cardiovascular collapse is thyroidal dysfunction caused by presumed hypophyseal inactivity, and its ensuing anaerobic cardiac metabolism. Changes in thyroid function were described after brain death. However, when hypothyroidism was experimentally induced by hypophysectomy in rats, cardiac dysfunction developed only slowly (days) and brain death induced after hypophysectomy resulted in comparable cardiac dysfunction as seen in rats that did not undergo hypophysectomy [9]. A number of alternative possible pathogenetic mechanisms (e.g. the influence of the β-adrenergic or vagal pathway, the effect of a chemical sympathectomy, the role of nitric oxide, the role of endogenous opioid peptides) explaining the cardiac dysfunction were explored without providing clear answers [8].
In a previous study from our centre [7], it was shown that the myocardial histological and ultrastructural damage after brain death in dogs could not be distinguished from ischaemic damage. Necrosis is multifocal and takes place in clusters containing few cells. Shanlin et al. [4]reported that multifocal myocardial damage also occurred in rats after brain death. This group, moreover, described contraction bands in coronary smooth muscle cells and severe coronary spasms in coronary casts made with injected Microfil. The distribution of the lesions in the myocardium suggests mainly microvascular involvement, with endothelial derived substances as important regulators of microvascular tone. From these observations arose the hypothesis that brain death induces such a profound and long-lasting coronary vasoconstriction with a complete cessation of blood supply in certain topographical areas, that ischaemic myocardial damage occurs disseminated over the myocardium, possibly caused by coronary endothelial dysfunction.
The discrepancy between the normal basal cardiac function after brain death when the heart was tested in a Langendorff system and the cardiovascular collapse seen in vivo made us decide to carefully restudy the importance of intrinsic myocardial damage induced by brain death. The second aim of this study was to test coronary endothelial function after brain death, since deranged function could explain the topographical pattern of the myocardial damage described above.
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2 Methods |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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2.1 Surgical preparation
The investigation conforms with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1985). Male Wistar rats weighing approximately 350 g were anaesthetized with an intraperitoneal injection of a freshly prepared mixture of urethane (600 mg/kg) and
-chloralose (160 mg/kg; both from Sigma, St. Louis, MO, USA). A tracheostomy was performed and the rats were ventilated with a KTR4 small animal ventilator (Hugo Sachs, March-Hugstetten, Germany), with oxygen-enriched air, a stroke rate of 60/min, and a peak inspiratory pressure of 12–14 mmHg, with 40% inspiratory phase and 10% plateau, and 2 cmH2O of PEEP. The inspiratory pressure and air–oxygen mixture were adjusted every 15 min to keep the partial pressures of arterial blood gases within the physiological range. ECG lead II was continuously monitored. PE50 catheters (Intramedic, Clay Adams, NY, USA) were inserted in the left femoral artery and vein. Arterial blood pressure was continuously recorded. A 22-gauge intravenous catheter was inserted into the right jugular vein, to continuously monitor central venous pressure, kept constant at 4 mmHg by slowly injecting 0.25 ml of a 50/50 mixture of 0.9% NaCl and Geloplasma® (Institut Mérieux Benelux, Brussels, Belgium) as needed. A balloon catheter was placed subdurally (Fogarty 3F, Baxter, Irvine, CA, USA). Brain death was induced by sudden 300 µl inflation of the intracranial balloon. The balloon was kept inflated during the entire experiment. This method was shown to reliably stop all brain perfusion [10]and electrical activity in the brain [3].
2.2 Experimental protocols
2.2.1 Protocol 1: haemodynamic changes after brain death
A detailed study of the haemodynamic changes induced by brain death was performed. After surgery, as described above, and placement of the intracranial balloon catheter, a median sternotomy was performed. After opening the pericardium, a micromanometer tipped catheter (Millar Instruments, Houston, TX, USA) was inserted in the left ventricle (LV) through an apical stab opening. An ultrasonic transit-time volume flowprobe (Transonic Systems, Ithaca, NY, USA) was placed around the ascending aorta. After 30 min of stabilization, the intracranial balloon was inflated with 300 µl of saline in half of the rats (n=6), whereas the others were sham-operated non-brain-dead controls (n=6). ECG lead II, mean arterial blood pressure (MABP), central venous pressure (CVP), left ventricular pressure (LVP), first derivative of the left ventricular pressure (dP/dt), and aortic flow (CO) were continuously measured. The animals were followed for 60 min after brain death or time-matched in the sham-operated group. Preliminary experiments had shown that a stable haemodynamic situation is reached after 1 h and does not change for the following 3 h, so we decided to restrict the analysis to the first 60 min. Cardiac index (CI) was calculated as the aortic flow per 100 g body weight, systemic vascular resistance index was calculated as (MABP–CVP)/CI. Two additional parameters were calculated off-line and included in the analysis: (1) dP/dt at the common peak isovolumetric pressure (dP/dt at CPIP), as defined by Mason [11], was used as largely afterload-independent parameter for ventricular contractility; and (2) maximal dP/dt divided by the left ventricular pressure at that time ((dP/dtmax)/P), as less preload-dependent measure.
2.2.2 Protocol 2: ex vivo myocardial contractility
After placing the intracranial balloon, and 30 min of stabilization, brain death was induced in half of the rats (n=2x6). Thirty minutes later, the rats were heparinized, and the hearts were rapidly excised via a bilateral anterior thoracotomy, and mounted on a modified Langendorff isolated heart perfusion system. The hearts were perfused at a perfusion pressure of 70 mmHg with a modified Krebs–Henseleit buffer, with final concentrations (in mmol/l): NaCl, 118.3; KCl, 4.7; MgSO4, 1.2; KH2PO4, 1.22; CaCl2, 1.3; NaHCO3, 25.0; glucose, 15.0. A fluid-filled latex balloon (Hugo Sachs, March-Hugstetten, Germany) was inserted through a pulmonary vein into the left ventricle. The balloon connected with a pressure transducer was used to continuously measure left ventricular diastolic and systolic pressure, and left ventricular dP/dt and heart rate were continuously derived. Coronary flow was measured with a 2N in-line flowprobe (Transonic, Ithaca, NY, USA) and also continuously recorded. After stabilization and recording of baseline values, cumulative doses of adrenaline were administered to the perfusion buffer, giving final concentrations of 10–9, 2x10–9, 5x10–9, 10–8, 2x10–8, 5x10–8, 10–7, 2x10–7, 5x10–7 and 10–6 mol/l. Every 90 s, the next higher concentration was started. To eliminate the chronotropic effect of adrenaline and its influence on myocardial contractility, isolated hearts were atrially paced at 420 beats/min in another series (n=2x6). The same dose–response curves were constructed.
2.2.3 Protocol 3: morphological alterations
One hour (n=6) and 4 h (n=4) after induction of brain death in rats, the hearts were excised and perfused with 2% glutaraldehyde in Sörensen's buffer at pH 7.4 for 5 min, further fixed by immersion for at least 2 h, rinsed in Sörensen's buffer overnight, postfixed in OsO4 2% for 1 h, and routinely embedded in Epon. Two-micrometer-thick transmural sections were cut, stained with Toluidine blue and examined with light microscopy. Ultrathin sections were stained with uranium acetate and lead citrate prior to examination in an electron microscope. Absence of structural damage was verified by examining transmural sections through the left ventricle at 5 different levels parallel to the apex, and confirmed by electron microscopy. Hallmark criteria were the absence of contraction band necrosis, subcellular oedema and swelling of mitochondria.
2.2.4 Protocol 4: endothelial barrier function
To test the integrity of the endothelial lining of the coronary arteries, Evans blue was injected in sham-operated rats, 30 s before the induction of brain death or 1 h after brain death (n=3x7). Ten minutes after the injection of Evans blue, the hearts were excised and from every series, 3 hearts were examined microscopically to examine Evans blue extravasation. For every time point, the 4 remaining hearts were flushed with the modified Krebs–Henseleit buffer as described above to rinse the coronary arteries from Evans blue. Afterwards, the left ventricle was divided into two parts, one of which was used to determine the wet weight to dry weight ratio, while the other was put in formamide (Sigma, St. Louis, MO, USA; 4 ml/g wet wt.) for 24 h at 20°C, for extraction of extravasated Evans blue, according to the methodology of Filep et al. [12]. The amount of extracted Evans blue was measured by spectrophotometry at 624 nm, and expressed as µg Evans blue per g dry weight of left ventricular tissue.
2.2.5 Protocol 5: endothelial function
As described in protocol 2, hearts were mounted on a Langendorff perfusion system (n=5x6). After stabilization, coronary vasomotor activity was tested by a 180-s infusion of serotonin (10–6 and 10–5 mol/l) and nitroglycerin (10–4 mol/l) in hearts from sham-operated and brain-dead rats. This was done in the presence or absence of L-NAME (10–4 mol/l) in the perfusion buffer. As fifth group, hearts were taken from non-brain-dead rats receiving 100 mg/kg of L-NAME i.v. 30 min before excision of the heart. Coronary flow was continuously measured with the 2N in-line flow probe. The percentage change in coronary flow was integrated during the last 120 s of the infusion of serotonin or nitroglycerin and taken as measure for the steady state effect of the vasoactive agents.
2.3 Data acquisition and management
All measured variables were continuously digitized at 1000 Hz (AT-MIO-16L9, National Instruments, Austin, TX, USA) and stored on a 486DX4/100 MHz personal computer, with a custom-made programme developed in Labview 3.0 (National Instruments, Austin, TX, USA).
Statistical analysis was performed with the statistical software package Statistica 4.5 (StatSoft, Tulsa, OK, USA). Data are expressed as means±s.e.m. For all tests used, the -level for statistical significance was set at 0.05. Repeated measurements ANOVA was used to test for significant differences in time for the haemodynamic variables. Two-way repeated measures ANOVA with group and dose and an interaction term between these two as independent factors was used for testing differences in the dose–response curves for adrenaline between the control and brain-death groups. ANOVA with post-hoc testing with the LSD test was used for testing differences in extravasation of Evans blue, and MANOVA for analysis of the fifth protocol. Changes in basal coronary flow before and after adding L-NAME were tested with a paired t-test.
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3 Results |
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3.1 Haemodynamic changes after brain death
Baseline values were taken after 30 min of stabilization, immediately before the intracranial balloon was inflated in the brain death group. In sham-operated animals, heart rate (HR), mean arterial blood pressure (MABP), left ventricular dP/dtmax (LV dP/dtmax), left ventricular dP/dtmin (LV dP/dtmin), left ventricular end-diastolic and peak systolic pressure, cardiac index (CI) and systemic vascular resistance index (SVRI) were stable throughout the entire measurement period. The effect of brain death induction on these parameters can be seen in Fig. 1. Heart rate was 422±12 min–1 in baseline conditions, and after a transient bradycardia and tachycardia immediately after brain death induction, continuously decreased to 350±8 min–1 1 h after brain death. Mean arterial blood pressure was 112±5 mmHg at baseline, rose to 184±10 mmHg 25 s after brain death and rapidly declined to 50±3 mmHg 210 s after brain death, with a stabilization afterwards. The same profile can be recognized in SVRI, LV peak systolic pressure, and dP/dtmax and dP/dtmin. A transient rise in LV end-diastolic pressure can be seen at the moment of brain death, accompanied also by a rise in CVP (not shown), suggestive of a central redistribution of the blood volume. The CI was 9.6±0.6 ml/min/100 g at baseline, decreased to 8.2±1.4 10 s after brain death, and afterwards increased to 12.0±0.9 1 h after brain death.
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In Fig. 2, the evolution in dP/dt at CPIP and (dP/dtmax)/P is shown. These parameters are expressed as percentage of the baseline value from the same experiment, since the differences in absolute values between the individual experiments were relatively large when compared with the evolution of the parameter in time. Most interesting was the comparison of dP/dt at CPIP before brain death with its final value, since dP/dt at CPIP did not correct for changes in preload that occurred early after brain death as evidenced by the changes in LV end-diastolic pressure and CVP. (dP/dtmax)/P, on the contrary, was significantly lower late after brain death than in control conditions. This parameter is known to be influenced by afterload, a parameter clearly influenced by brain death.
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3.2 Ex vivo myocardial contractility
Hearts excised 30 min after brain death or from sham-operated time-matched controls exhibited the same basal contractility when tested in a crystalloid perfused Langendorff system. No differences in dose–response curve for adrenaline (10–9 to 10–6 mol/l) could be found between the two groups for all parameters studied (peak systolic pressure, left ventricular dP/dt, heart rate, and coronary flow), and both in paced and unpaced conditions. The effect of adrenaline on left ventricular dP/dtmax and dP/dtmin when the hearts were paced at 420 min–1 is shown in Fig. 3 as example. It is evident that no significant differences exist between the control hearts and the hearts from brain-dead rats.
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3.3 Morphological alterations
No histological or ultrastructural damage could be detected in the hearts excised 1 or 4 h after brain death. At the light microscopic level, the hearts showed a regular pattern of structural organization that was identical to normal hearts. No signs of degeneration typical of acute ischaemia, such as the occurrence of contraction bands and cellular oedema, were seen (Fig. 4a). Electron microscopy revealed the presence of intact substructures. Mitochondria, which are the most sensitive subcellular organelles to ischaemia, were intact (Fig. 4b).
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3.4 Endothelial barrier function
In none of the hearts examined histologically, could a significant amount of extravasated Evans blue be detected. In control animals, 11.06±1.19 µg extravasated Evans blue per gram dry weight could be extracted, as compared with 11.33±2.13 µg in the group with Evans blue injection immediately before induction of brain death, and 8.81±.58 µg in the group with Evans blue injection 1 h after brain death. No significant differences between the groups could be detected.
3.5 Endothelial function
The coronary vasoactive effects of the tested drugs are shown in Fig. 5. The vasoactive agents induced significantly different reactions, according to the group of hearts, as is shown by the overall significance of the interaction term drugxgroup when tested with MANOVA (P=0.003). The results of the post-hoc testing to see where exactly the differences lie, are also shown in Fig. 5. Important to notice is the fact that no significant differences exist between the brain death and its corresponding control group. Adding L-NAME to the perfusion buffer resulted in a significant decrease in basal coronary flow (from 15.3±1.0 to 11.9±1.1 ml/min, P<0.001). After L-NAME administration, a more pronounced vasodilation is caused by nitroglycerin infusion than with control buffer, but this just fails to reach the significance level required in most pairwise comparisons. Serotonin 10–6 mol/l also induced vasodilatation when L-NAME was present in the perfusion buffer, serotonin 10–5 mol/l sometimes induced vasoconstriction and sometimes vasodilatation resulting in a large variation, both in the brain death and control group. Remarkable was that only in vivo pretreatment with L-NAME was able to inhibit serotonin-induced coronary vasodilation, with a consistent vasoconstriction induced both by 10–6 and 10–5 mol/l serotonin administration.
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4 Discussion |
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With this comprehensive series of experiments concerning the effect of brain death in the rat and its consequences on myocardial function, we were able to clarify the apparent inconsistencies in published reports. On the one hand, a severe haemodynamic collapse has been reported in the rat after brain death and this collapse was attributed to myocardial damage; but, on the other hand, normal basal contractile function of hearts explanted 60 min after induction of brain death has also been reported [3]. No circulating or neurogenic cardiodepressant factor is present that could eventually reconcile both observations [8]. In the present study, brain death has a tremendous impact on the haemodynamic situation in the rat as already largely described in previous studies [3, 4, 10]. An important difference between the present study and the study of Galiñanes and Hearse [3], however, was that the cardiac output did not drop after brain death in the present study but, on the contrary, slightly increased. This led us to the hypothesis that the haemodynamic changes were not caused by intrinsic myocardial damage, but that these changes might largely be the consequence of afterload reduction. This was further corroborated by the stability after brain death of the afterload independent parameter of ventricular contractility dP/dt at CPIP [11]. The reason for the difference in the effect of brain death on cardiac output between our study and that of Galiñanes and Hearse [3]is not entirely clear, but differences in anaesthetic regimen undoubtedly play an important role. We have chosen the use of
-chloralose and urethane because they produce a long-lasting stable anaesthesia, without the need for additional doses of the drugs, and because this anaesthesia preserves vascular reactivity to phenylephrine and nitroglycerin [13], thus, probably, also preserving the vascular response to the intense sympathetic stimulation at the moment of brain death [10]. Furthermore, a comparable anaesthesia was used in the study of Shanlin et al. [4], a study that showed myocardial damage after brain death in rats. Interestingly, all haemodynamic parameters after brain death were similar in the study of Galiñanes and Hearse [3]and ours, despite the highly different starting conditions of cardiac index, stroke volume index, and systemic vascular resistance index, and, to a lesser extent, heart rate. These differences in starting value of the haemodynamic parameters, in which stroke volume plays an important role, can be explained by the known abdominal vasoconstrictive effects of urethane and chloralose [14]. Intrinsic myocardial contractility was, furthermore, studied in isolated Langendorff-perfused hearts. It was previously shown, in a paracorporeal blood-perfused system, that the basal, unstimulated contractility of hearts from brain-dead or control rats is equal [3]. In our set-up, not only basal contractility was equal, but also the inotropic response towards adrenaline was exactly the same. Galiñanes and Hearse [3]interpreted their results as the protective effect of explantation against the deleterious effects of the brain death status. This, however, seems unlikely since, in our experiments, the situation after brain death had already stabilized before the hearts were harvested, and from unpublished experiments, we know that this situation remains stable for at least 4 h. Since elegant studies of the same group [8]have ruled out a stable circulating cardiodepressant factor and found no evidence of a neurogenic cardiodepressant factor, no intrinsic myocardial contractile damage seems to be present. This interpretation is also compatible with our in vivo haemodynamic measurements, showing that the paramount difference is a strong decrease in afterload.
Histologically or ultrastructurally, we could not find myocardial damage. On the one hand, this was not surprising given our results of in vivo haemodynamics and ex vivo contractility, but on the other hand, this is in contradiction with the study of Shanlin et al. [4], describing multifocal microscopical myocardial necrosis, myocardial contraction bands, and even smooth muscle contraction bands in the coronary arteries. In that study, increased intracranial pressure was maintained, however, for only 15 s, with an abrupt deflation of the intracranial balloon afterwards. Furthermore, histological examination was only performed in hearts, after Microfil injection through the brachial artery to produce coronary artery casts, and without rinsing the coronary arteries of blood. Fixation was with immersion and not with perfusion as in our experiments. These differences in methodology and tissue preparatory procedures may account for the histological damage observed in the latter study. The fact that the same kind of lesions, although to a lesser extent, were seen in control rats in the study of Shanlin et al. [4]makes methodological difficulties even more likely to be the cause of the difference. Although the myocardial damage seen after acute stroke, often termed myocytolysis, and its accompanying ECG changes [15]can be reproduced in rats [16, 17], this is not necessarily in contradiction with our results. In our model of brain death, the entire brain, including brainstem, stops inevitably functioning since very rapidly brain perfusion is abolished [10], whereas in the model of experimental stroke in rats by unilateral occlusion of the middle cerebral artery, the brainstem with the major cardiocirculatory regulatory centres remains intact, and even in the cerebral hemispheres, there is an asymmetry of sympathetic and ensuing cardiac consequences of experimental stroke [16].
Endothelial damage was hypothesized to be a possible underlying pathophysiological mechanism, able to induce the kind of myocardial damage described after brain death in dogs [7]and rats [4], although we were unable to demonstrate this damage in our experiments in rats. The first approach was to test the integrity of the coronary endothelial lining. No important extravasation of macromolecules was evident, a fact suggestive of intact endothelial lining, and also suggestive of normal endothelial NO production, since it is known that inhibiting NO synthase with L-NAME induces endothelial leakage of Evans blue [18]. There was even lower extravasation after brain death, probably related to the lower arterial blood pressure after brain death. Testing endothelium dependent coronary vasoreactivity by serotonin [19]did not show significant differences between the brain death and the control group. This implies that the overall endothelial NO production and vascular smooth muscle cell reactivity toward this compound remains intact. An interesting additional observation made in protocol 5 of this study was that only in vivo pretreatment with L-NAME, but not addition of this drug to the perfusion buffer, was able to prevent serotonin-induced coronary vasodilatation. Since basal coronary flow decreased significantly after the addition of L-NAME to the perfusion buffer, an effective concentration of this drug was used during these experiments. This suggests that: (1) L-NAME causes a specific endothelial and/or smooth muscle cell damage when administered in vivo (maybe induced by the pronounced long-lasting hypertension); or (2) that serotonin-induced coronary vasodilatation is not entirely dependent on NO production; or (3) that the involved enzyme cannot be blocked entirely by this concentration of L-NAME.
What are the implications of this study for the clinical cardiac transplantation programmes? It is clear that, contrary to what was found in this study, intrinsic myocardial damage caused by brain death is observed in human potential donor hearts [20]. This discrepancy can probably be explained by species differences in autonomic nervous system regulation, sensitivity of the coronary circulation or the myocardium for catecholamines, but also by the heterogeneity in patterns of intracranial pressure rise in clinical circumstances. The results of this study, however, caution against rashly turning down potential donor hearts from donors that became haemodynamically unstable. It is not justified to rely exclusively on standard haemodynamic parameters in this decision-making, since an apparent haemodynamic collapse per se is not necessarily indicative of intrinsic myocardial damage.
To conclude this study, we can state that intrinsic myocardial damage, if present at all, contributes only minimally to the haemodynamic changes seen after brain death in the rat. This, of course, raises the question of the exact pathophysiological mechanism of this so-called collapse.
Time for primary review 32 days.
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Acknowledgements |
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P.H. is an ‘Aspirant van het Fonds voor Wetenschappelijk Onderzoek, Vlaanderen, Belgium’. This work was supported in part by a grant from the ‘Fonds voor Wetenschappelijk Onderzoek, Vlaanderen, Belgium’.
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