© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
The effect of brain death on cardiovascular function in rats. Part II. The cause of the in vivo haemodynamic changes
Centre for Experimental Surgery and Anaesthesiology, K.U. Leuven, Provisorium I, Minderbroedersstraat 17, B-3000 Leuven, Belgium
* Corresponding author. Tel.: +32 (16) 337298; Fax: +32 (16) 337855.
Received 4 August 1997; accepted 30 October 1997
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Abstract |
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 Top Abstract 1 Introduction2 Methods3 Results4 DiscussionReferences |
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Objective: Brain death-induced haemodynamic collapse in rats is not caused by intrinsic myocardial damage as shown in the accompanying paper. We investigated whether this collapse could be caused by the withdrawal of the basal adrenergic tone. Methods: Heart rate and blood pressure variability was studied in rats before and after brain death. The effect of high doses of phentolamine, propranolol or their combination administered before or after brain death was assessed. Results: Heart rate variability in the respiratory frequency range significantly increased, whereas in the low-frequency range it tended to decrease after brain death. Systolic and diastolic blood pressure variability up to 0.18 Hz largely disappeared, but stayed unchanged in the respiratory frequency range. High-dose combined phentolamine and propranolol pretreatment induced a haemodynamic picture comparable to the situation seen after brain death without pharmacological intervention. Brain death did not further deteriorate the haemodynamic situation after combined pretreatment. On the other hand, once the haemodynamic collapse after brain death had settled, adrenergic blockade had no important influence any more. Conclusion: We conclude that the haemodynamic situation seen after brain death is one of profound sympathetic withdrawal.
KEYWORDS Rat; Brain death; Haemodynamic collapse; Adrenergic system; Autonomic nervous system; Heart rate variability
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1 Introduction |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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Since in the first part of this study [1], it became clear that no important intrinsic myocardial damage is caused by brain death in the rat, the tremendous haemodynamic alterations after brain death remain to be explained. It is clear from haemodynamic indices, especially left ventricular dP/dt at the common peak isovolumetric pressure, that afterload reduction greatly influences the final haemodynamic picture after brain death in the rat. Furthermore, a significant decrease in circulating noradrenaline is present late after brain death [2]. From these observations, we hypothesized that a withdrawal of the influence of the autonomic nervous system, and specifically, the sympathetic system, is responsible for the changes in the global haemodynamic situation. At first sight, this hypothesis already seems to have been tested and weakened by Galiñanes and Hearse [3]. They studied the effect of propranolol administration, bilateral vagotomy or chemical sympathectomy on brain death-induced haemodynamic changes and concluded that the autonomic nervous system cannot be held responsible. Some methodological problems exist, however, with this study. A major component of the autonomic, and specifically sympathetic nervous system, the
-adrenergic system, was not tested, although it is known that -adrenoreceptors are functionally active and are present in considerable density in rat myocardium [4]. Furthermore, the interaction between the peripheral circulation and cardiac contractile parameters is ignored, and, especially in the peripheral circulation, the effect of -adrenoreceptors is highly important. Thirdly, the chemical sympathectomy performed with 6-hydroxydopamine hydrobromide reduced the myocardial pool of catecholamines, but not the plasma concentrations. The myocardial pool mainly reflects the catecholamines contained in vesicles in nerve endings. Catecholamine concentrations at the neuroeffector junctions, however, are better reflected in changes in plasma concentrations since a constant gradient exists between the synaptic cleft and the vascular lumen [5]. Given the cited methodological questions, the absence of intrinsic myocardial damage as proved in the accompanying paper [1], the suggestive haemodynamic alterations and the decrease in circulating catecholamines after brain death [2], we decided to carefully restudy the importance of the changes in the sympathetic nervous system after brain death. Since reversal of the effects of brain death on the sympathetic nervous system is, of course, impossible, we had to use indirect approaches to corroborate the hypothesis of sympathetic denervation. First, we studied the effect of brain death on heart rate and blood pressure variability, two parameters known to be heavily influenced by the autonomic nervous system [6, 7]. Secondly, high doses of - and/or β-adrenergic receptor blockers were given before brain death, to induce a status with almost complete inhibition of the basal sympathetic tone and afterwards to study the effect of brain death in this situation. Thirdly, the same high doses of adrenergic blockers were given after brain death, to see if there was still an important sympathetic tone present after brain death. Since it was shown [3]that parasympathetic denervation by bilateral vagotomy did not significantly influence the basal haemodynamic status nor that it influenced the haemodynamic collapse after brain death, we did not thoroughly reinvestigate the parasympathetic system, even more so because our preliminary experiments gave identical results to those already published [3]. |
2 Methods |
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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 (HSE, March-Hugstetten, Germany), with oxygen-enriched air, at a stroke rate of 60/min, and a peak inspiratory pressure of 12–14 mmHg, with 40% inspiratory phase and 10% plateau. The inspiratory pressure and air–oxygen mixture were adjusted every 15 min to keep the 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. An intracranial balloon catheter was placed subdurally (Fogarty 3F, Baxter, Irvine, CA, USA). Brain death was induced by sudden inflation of the intracranial balloon with 300 µl of saline. The balloon was kept inflated during the entire experiment. This method has been shown to reliably inhibit all brain perfusion [2]and stop all brain electrical activity [8].
2.2 Experimental protocols
2.2.1 Protocol 1: heart rate and blood pressure variability
Since we observed, during our previous work, that the arterial pressure signal and the heart rate lost normal variability after brain death, blood pressure and heart rate variability were quantitatively studied (n=5). Blood pressure and ECG were digitized at 2000 Hz. Systolic and diastolic arterial blood pressure were determined from beat to beat, and the RR interval was derived from the ECG. After stabilization following the surgical procedure, arterial blood pressure and ECG were recorded 5 times for 420 s. Afterwards, brain death was induced and 30 min later, the same parameters were recorded for another 5 times 420 s. A normalized interval spectrum as described by DeBoer et al. [9]was calculated for systolic, diastolic and mean blood pressure and RR interval. For every 420 s, a spectral analysis was performed with the Time Series Analysis module of Statistica 4.5 (StatSoft, Tulsa, OK, USA) using the exact length of the data. Spectral density estimates were calculated with a Hamming window of width 5. The density in three different spectral frequency ranges of interest was calculated (low-frequency band, 0.04–0.10 Hz; mid-frequency band, 0.10–0.18 Hz; respiratory frequency band, 0.75–1.25 Hz, since the rats were mechanically ventilated at 1 Hz) [6]. The mean from the five measurements before and after brain death for every studied parameter was taken as the value used for the further statistical evaluation.
2.2.2 Protocol 2: effect of adrenergic blockade
Following 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 through an apical stab opening. A flowprobe (Transonic, Ithaca, NY, USA) was placed around the ascending aorta. ECG, arterial pressure, central venous pressure, left ventricular pressure, first derivative of the left ventricular pressure, and aortic flow were continuously measured. Brain death was induced after a stabilization period of 30 min. Fifteen min before (protocol 2a) or 30 min after (protocol 2b), inflation of the intracranial balloon, phentolamine (Phe; Regitine, Ciba-Geigy, Basel, Switzerland; 10 mg/kg i.v., followed by a continuous infusion of 10 mg/kg/h, protocol 2a1 and 2b1), or propranolol (Prop; Inderal, Zeneca, Destelbergen, Belgium; 1 mg/kg i.v., followed by 0.5 mg/kg/h, protocol 2a2 and 2b2), or a combination of both drugs (protocol 2a3 and 2b3) were administered. Two additional parameters were calculated off-line and included in the analysis. These were: (1) dP/dt at the common peak isovolumetric pressure (dP/dt at CPIP), as defined by Mason [10], 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.
2.3 Data acquisition and management
All measured variables were continuously digitized at 2000 Hz for protocol 1 and at 1000 Hz for protocol 2 (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. Differences before and after brain death were tested with paired t-test for differences in heart rate and blood pressure variability, and with repeated measures ANOVA for differences in the variables studied in protocol 2. Differences between the different treatment groups were tested with two-way ANOVA.
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3 Results |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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3.1 Heart rate and blood pressure variability
RR interval variability in the low-frequency range is 0.002331±0.000857 vs. 0.000876±0.000303, and in the mid-frequency range 0.000746±0.000229 vs. 0.000323±0.000143 in control conditions and after brain death, respectively. Both decreases fail to reach statistical significance. The variability in RR interval in the high-frequency range is significantly higher after brain death than in control conditions (0.12935±0.002953 vs. 0.005340±0.002091, respectively, P=0.02).
Variability in systolic blood pressure significantly decreases after brain death in the low- and mid-frequency range (0.120521±0.16814 vs. 0.003625±0.000603, P=0.002; and 0.046774±0.007334 vs. 0.002932±0.000262, P=0.004, respectively). The spectral density of systolic blood pressure variability up to 0.5 HzEq of a representative individual experiment is shown in Fig. 1. As can be clearly seen, almost all variability is lost after brain death. In the respiratory frequency range, no significant differences can be seen in systolic blood pressure variability (1.108692±0.284410 vs. 1.156481±0.251072).
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Diastolic blood pressure variability follows the same pattern as systolic blood pressure variability with a significant decrease after brain death in the frequency range between 0.04 and 0.18 HzEq, without significant changes after brain death in the respiratory frequency band (0.269120±0.043606 vs. 0.014715±0.004109, P=0.003 in the low-frequency range; 0.129055±0.029571 vs. 0.012777±0.003992, P=0.02 in the mid-frequency range; and 1.152402±0.406541 vs. 0.690375±0.110767 in the respiratory frequency range). A graphical representation of these results is shown in Fig. 2.
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3.2 Effect of adrenergic blockade
3.2.1 Effect of administration of adrenergic blockers before brain death (protocol 2a)
The effect of administration of phentolamine, propranolol or the combination 15 min before brain death on heart rate, mean arterial blood pressure, left ventricular pressure, cardiac index, systemic vascular resistance index and left ventricular dP/dt is shown in Fig. 3. As control group, the brain death group without interventions as described in the accompanying paper [1]was used. The initial status was the same for all groups studied. Heart rate significantly dropped after the addition of propranolol, and even significantly more after the combination of phentolamine and propranolol, whereas phentolamine alone had no significant effect. The effect of brain death on heart rate was significantly less important when propranolol or the combination therapy was administered before brain death. Final heart rate was significantly slower with combined pretreatment than in all other groups. Addition of phentolamine, or the combination of phentolamine and propranolol, significantly reduced mean arterial blood pressure. The increase in blood pressure by brain death induction was significantly tempered by phentolamine or the combined pretreatment. The final blood pressure was slightly, but significantly, higher in the group pretreated with phentolamine vs. the propranolol treated group. No significant differences in cardiac index were caused by the administration of adrenergic blockers. Brain death induction, however, induced a transient decrease of the cardiac index (CI) in the group that received propranolol, and a transient increase in the phentolamine treated group. No significant differences were observed in the other two groups. No differences in the final CI were observed between the groups. The systemic vascular resistance index (SVRI) significantly decreased after administration of phentolamine or the combination. A significant rise in the SVRI was seen early after brain death in the control and propranolol treated group, whereas in the others it remained stable. The final situation of the SVRI was comparable in all groups. Propranolol significantly increased left ventricular end-diastolic pressure (LVEDP). Brain death induced a further significant increase up to 28.8±2.0 mmHg in the propranolol-treated group, but did not significantly influence LVEDP in the other groups. The final value of LVEDP was the same in all groups. Propranolol (vs. the phentolamine group), but especially the combined treatment (vs. all other groups), significantly decreased LV peak systolic pressure. The effect of brain death on LV peak systolic pressure was significantly less pronounced in all three treated groups than in the control group. LV peak systolic pressure stayed higher in the phentolamine treated group than in the propranolol treated group. The combined treatment significantly reduced dP/dtmax and dP/dtmin significantly vs. all other groups. Early after brain death, dP/dtmax and dP/dtmin rose significantly more in the control group than in the 3 other groups. Finally, the group with combined pretreatment had a slight, but significantly lower dP/dtmax and dP/dtmin than the control and phentolamine treated groups.
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The evolution in (dP/dtmax)/P and dP/dt at CPIP is shown in Fig. 4. dP/dt at CPIP significantly decreased only after combined treatment with phentolamine and propranolol. Early after brain death, dP/dt at CPIP transiently decreased in the group pretreated with propranolol, and had a slight tendency to do so in the control group. No significant differences were seen 1 h after brain death between the treated and control group. The groups pretreated with phentolamine or the combination had a significantly lower dP/dt at CPIP at the end of the experiment compared with the group pretreated with propranolol. (dP/dtmax)/P significantly decreased in the group pretreated with propranolol and especially after combined treatment. After brain death, (dP/dtmax)/P transiently increased in the control group and decreased after propranolol administration. No significant differences could be found at the end of the observation period. A comparison of the studied haemodynamic parameters between the control group and the groups pretreated with propranolol, phentolamine, or the combination is made schematically in Table 1.
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3.2.2 Effect of administration of adrenergic blockers after brain death (protocol 2b)
Fig. 5 graphically presents the effect of adrenergic blockade installed after brain death. Heart rate significantly decreased when phentolamine, propranolol or the combination was administered 30 min after brain death. One hour after brain death, heart rate was significantly lower after administration of propranolol and phentolamine combined than in all other groups. Administration of phentolamine increased mean arterial blood pressure insignificantly. The final value in this group, however, was marginally significantly higher than in the group treated with phentolamine and propranolol combined. No significant changes were seen after administration of adrenergic blockers in cardiac index and systemic vascular resistance index. Apart from the short-lived increase in LV peak systolic pressure after administration of phentolamine, no changes in LVEDP or left ventricular peak systolic pressure (LVPSP) were induced by adrenergic blockade. The same holds true for dP/dtmax and dP/dtmin with a transient increase in both parameters after phentolamine administration.
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The evolution in (dP/dtmax)/P and dP/dt at CPIP is shown in Fig. 6. dP/dt at CPIP significantly decreased transiently only after combined treatment with phentolamine and propranolol. No significant differences are present at the end of the measurement period. A temporary increase in (dP/dtmax)/P is seen after phentolamine administration and a temporary decrease after combined administration. All effects, however, swiftly disappear. A schematic comparison of the final values of the studied haemodynamic parameters between the control group and the groups treated with propranolol, phentolamine, or the combination 30 min after brain death is presented in Table 2.
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4 Discussion |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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Brain death induces severe haemodynamic changes in rats, generally regarded as a ‘collapse’. In the accompanying paper, we demonstrated that no important intrinsic myocardial damage can be held responsible for this collapse [1]. Galiñanes and Hearse [3]convincingly demonstrated that no circulating cardiodepressant factor was present. The main change that was suggested by the careful monitoring of the haemodynamic effects of brain death induction in rats, was an important reduction in afterload. Blood pressure measured late after brain death reaches the same level as seen in pithed rats, completely denervated by a total destruction of the spinal medulla [11]. These observations made us hypothesize that the haemodynamic collapse was caused by the withdrawal of the sympathetic tone, thereby lowering the cardiac inotropic status, and causing generalized vasodilatation, with the heart unable to substantially increase cardiac output, since chronotropic and inotropic responses are abolished.
The ideal approach to prove or refute this hypothesis is to directly measure the autonomic output before and after brain death, and if diminished after brain death, to stimulate the autonomic output in a physiological way. The first part is complicated by the problem to find representative sympathetic outflow circuits for the total outflow. This should at least consist of two parts, one of the sympathetic outflow to the heart and the other to the vasculature. Recently, it was shown in dogs that cardiac sympathetic efferent neuronal function is obtunded by acutely raising intracranial pressure [12]. No studies on outflow to the vasculature after brain death have been reported. The second part is clearly impossible with the present knowledge.
Another approach to study autonomic cardiovascular regulation is the study of heart period (RR interval) and blood pressure variability, a method also well validated in rats [6, 7, 13]. As is shown in Fig. 2, a tremendous decrease in blood pressure variability is evident in the frequency range of 40–180 mHz. Inhibition of the -adrenergic component of the sympathetic system by phentolamine is known to induce an important drop in blood pressure variability in that frequency range [6, 13]. RR variability in the low- and mid-frequency range decreases after brain death, although failing to reach significance. A decrease in this frequency range can be attributed to a diminished effect of the β-adrenergic component of the sympathetic system, or can be due to inhibition of the parasympathetic system. In the latter case, however, a severe decrease in RR variability in the respiratory frequency range would be expected [7], whereas the contrary is observed. It is interesting, in the light of this observation, that a slight non-significant increase in high-frequency RR variability was reported after administration of atenolol in rats [7]. These data suggest that as a consequence of brain death, the greatest changes in the autonomic nervous system concern the sympathetic part of it. This is not surprising, since the mechanism of this change probably is a withdrawal of a continuous, normally existing tone [12]that is mainly sympathetic in rats [6]. This withdrawal in sympathetic tone is, furthermore, demonstrated by the significant decrease in circulating noradrenaline after brain death [2].
In the second part of this study, we administered very high doses of - and/or β-adrenergic blockers before and after brain death. The global picture induced by the combined pretreatment is very comparable to what we see after brain death, whereas blocking only one of both systems is clearly insufficient. Brain death induced after this combined blockade does not further deteriorate the haemodynamic situation. On the other hand, administration of high doses of phentolamine, propranolol or their combination after the haemodynamic collapse induced by brain death had settled, barely had an influence on the haemodynamic situation. This implies that significant sympathetic tone is no longer present at the time of administration of the drugs.
Interestingly, combined adrenergic blockade before brain death importantly reduced heart rate without a concomitant decrease in the cardiac index, thereby implying a proportional increase in stroke volume, probably attributable, to a large extent, to a reduced afterload significantly facilitating ventricular ejection, as evidenced by the reduction in the SVRI. This, however, cannot explain the findings when this combined treatment was started 30 min after brain death, since at that moment, the SVRI remained stable. Another contributing factor is probably the increased diastolic filling of the ventricle by slowing of the heart rate. The negative chronotropic effect of phentolamine or even more the combination of propranolol and phentolamine is rather unexpected. Charocopos [14], however, had already observed that injection of phentolamine in propranolol-treated rats slowed heart rate by about 20%. In brain-dead rats, the decrease in heart rate seems to be even more pronounced, despite the fact that the sympathetic nervous system is probably at a low level of activity, as evidenced in the other haemodynamic parameters studied. These observations suggest that: (1) the formulations of propranolol and phentolamine used exert direct effects on the heart rate, independent from the sympathetic system; or (2) this effect is more pronounced at low levels of sympathetic tone.
Despite the fact that several significant differences in the final haemodynamic situation between the pretreated and treated groups are reported in the results section, it is important to bear the global picture in mind, with the differences between the groups much smaller than the effect of brain death on most parameters. Generally speaking, combined pretreatment with phentolamine and propranolol does induce a situation comparable to the one seen after brain death, with brain death causing no further deterioration in the haemodynamic situation. Furthermore, treatment with adrenergic receptor blockers does not importantly alter the haemodynamic status, once the brain death-induced haemodynamic collapse has been installed.
As a conclusion of the two parts of the study concerning the effect of brain death on cardiovascular function in the rat, we can state that no important intrinsic myocardial damage is caused by brain death induction, and that the severe haemodynamic changes are mainly caused by sympathetic withdrawal.
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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References |
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TopAbstract1 Introduction2 Methods3 Results4 DiscussionReferences |
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- Herijgers P, Borgers M, Flameng W. The effect of brain death on cardiovascular function in rats. Part I. Is the heart damaged? Cardiovasc Res (1998) 38:98–106.
[Abstract/Free Full Text] - Herijgers P, Leunens V, Tjandra-Maga T.B, Mubagwa K, Flameng W. Changes in organ perfusion after brain death in the rat and its relation to circulating catecholamines. Transplantation (1996) 62:330–335.[CrossRef][Web of Science][Medline]
- Galiñanes M, Hearse D.J. Brain-death-induced cardiac contractile function: studies of possible neurohormonal and blood-borne mediators. J. Mol. Cell. Cardiol. (1994) 26:481–498.[CrossRef][Web of Science][Medline]
- Mukherjee A, Haghani Z, Brady J, et al. Differences in myocardial - and β-adrenergic receptor numbers in different species. Am. J. Physiol. (1983) 245:H957–H961.[Web of Science][Medline]
- Kopin I.J, Zukowska-Grojec Z, Bayorh M.A, Goldstein D.S. Estimation of intrasynaptic norepinephrine concentrations at vascular neuroeffector junctions in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. (1984) 325:298–305.[CrossRef][Web of Science][Medline]
- Akselrod S, Elish S, Oz O, Cohen S. Haemodynamic regulation in SHR: investigation by spectral analysis. Am. J. Physiol. (1987) 253:H176–H183.[Web of Science][Medline]
- Japundzic N, Grichois M.-L, Zitoun P, Laude D, Elghozi J-L. Spectral analysis of blood pressure and heart rate in conscious rats: effects of autonomic blockers. J. Auton. Nerv. Syst. (1990) 30:91–100.[CrossRef][Web of Science][Medline]
- Galiñanes M, Hearse D.J. Brain death-induced impairment of cardiac contractile performance can be reversed by explantation and may not preclude the use of hearts for transplantation. Circ. Res. (1992) 71:1213–1219.
[Abstract/Free Full Text] - DeBoer R.W, Karemaker J.M, Strackee J. Comparing spectra of a series of point events particularly for heart rate variability data. IEEE Trans. Biomed. Eng. (1984) 31:384–387.[Web of Science][Medline]
- Mason D.T. Usefulness and limitations of the rate of rise of intraventricular pressure (dp/dt) in the evaluation of myocardial contractility in man. Am. J. Cardiol. (1969) 23:516–527.[CrossRef][Web of Science][Medline]
- Gillespie J.S, Muir T.C. A method of stimulating the complete sympathetic outflow from the spinal cord to blood vessels in the pithed rat. Br. J. Pharmacol. Chemother. (1967) 30:78–87.
- Murphy D.A, O'Blenes S, Nassar B.A, Armour J.A. Effects of acutely raising intracranial pressure on cardiac sympathetic efferent neuron function. Cardiovasc. Res. (1995) 30:716–724.
[Abstract/Free Full Text] - Murphy C.A, Sloan R.P, Myers M.M. Pharmacologic responses and spectral analyses of spontaneous fluctuations in heart rate and blood pressure in SHR rats. J. Auton. Nerv. Syst. (1991) 36:237–250.[CrossRef][Web of Science][Medline]
- Charocopos F. The mechanism of beta-adrenergic receptor blockade-induced elevation of arterial blood pressure in rats. Arch. Intern. Physiol. Biochem. (1982) 90:173–178.[CrossRef]
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