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Ann Thorac Surg 1999;67:18-25
© 1999 The Society of Thoracic Surgeons

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Original Articles

Modulation of coronary perfusion pressure can reverse cardiac dysfunction after brain death

^a Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany

Address reprint requests to Dr Szabó, Department of Cardiac Surgery, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
e-mail: dzsi{at}hotmail.com

Presented at the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26–28, 1998.

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Background. Brain death results in a rapid decline in left ventricular function, which has clinical relevance for organ transplantation. The aim of the present study was to investigate coronary perfusion changes during brain death and their role in cardiac dysfunction.

Methods. In an in situ isolated canine heart model, brain death was induced by inflation of a subdural balloon catheter. The heart was perfused separately with the animal’s own blood by a pressure-controlled roller pump that was coupled to the measured aortic pressure. Myocardial contractility was estimated by the slope of the end-systolic pressure–volume relation.

Results. Induction of brain death resulted in a transient hyperdynamic response, followed by a significant decrease in systemic vascular resistance, coronary blood flow, and the end-systolic pressure–volume relation (p < 0.05). However, if coronary perfusion pressure was decoupled from aortic pressure and elevated to pre–brain death levels, coronary blood flow and the end-systolic pressure–volume relation were also restored to baseline levels.

Conclusion. Severe impairment of coronary blood flow may contribute to decreased contractility after brain death that can be reversed by modulation of coronary perfusion pressure.

	Introduction

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
During the past few years, an increasing number of patients with end-stage heart disease have been registered on the waiting lists for heart transplantation. Although in 1996 10% fewer transplantations could be performed worldwide [1], primarily because of a shortage of suitable donor organs, a considerable number of potential donor hearts must be rejected because of hemodynamic instability and poor cardiac function. Moreover, the major cause of early postoperative mortality and morbidity is graft failure. Many studies [2–6] describe a hemodynamic deterioration after brain death in potential donors, the exact mechanisms of which are yet not clearly understood. Several possible etiologies have been proposed, including direct cardiac myocyte injury, catecholamine-induced myocardial damage, and impairment of the ß-adrenoceptor–adenylyl cyclase system, as well as hormone depletion. In a recent study, there was no correlation between the occurrence of hemodynamic instability and severity of histologic changes after rapid induction of brain death [7]. Galinanes and associates [8] found no improvement in cardiac function in brain-dead animals if full blood replacement was performed with blood from non–brain-dead blood donors. Vice versa, if the blood of healthy animals was replaced by blood from brain-dead animals, cardiac function did not deteriorate. These data indicate that humoral and blood-borne factors, including hormone depletion after brain death, may have a less important effect on cardiac function than suggested in earlier studies.

The possible pathophysiologic link between altered loading conditions, organ perfusion with special reference to the heart, and cardiac function after brain death has not yet been investigated. Using the microsphere technique, Meyers and colleagues [4] and Herijgers and associates [9] showed a significant decrease in myocardial blood flow after brain death. However, in their studies, no conclusion could be made as to how far decreased myocardial blood flow contributes to decreased cardiac function. Therefore, the role of coronary perfusion changes in cardiac dysfunction after brain death was investigated in the present study. We used a modified model of the neurohumorally intact "in situ isolated heart" [10] with extracorporal circulation to analyze cardiac function independent of actual loading conditions. In this model, coronary perfusion could be examined as an independent determinant of left ventricular function.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Study animals
Twelve dogs (foxhounds) weighing 24 to 35 kg (mean, 27.4 ± 2.9 kg) were used in these experiments. All animals received humane care in compliance with the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research and the "Guide for the Care and the Use of Laboratory Animals" prepared by the National Academy of Sciences and published by the National Institutes of Health (NIH publication 86-23, revised 1985).

Brain death model
Experimental brain death was induced by creating intracranial hypertension [3]. A Foley catheter was introduced into the subdural space through a parietal burr hole in the skull. A rapid injection of 25 mL of saline inflated the balloon of the catheter, which caused an acute increase in intracranial pressure. Brain death occurred within few minutes in all dogs, and cerebellar herniation caused interruption of neurologic pathways between the midbrain and the spinal chord. Brain death was confirmed neuropathologically at the end of the experiments.

Surgical preparation and experimental design
The dogs were anesthetized with a bolus of pentobarbital (Nembutal; Abott) (12 mg/kg intravenously), paralyzed with pancuronium bromide (Pancuronium; Organon, Teknikka, Boxtel, the Netherlands) (0.1 mg/kg as a bolus, then 4 µg · kg^-1 · min^-1 intravenously), and endotracheally intubated. The level of anesthesia was maintained with the synthetic opiate piritramide (Dipidolor; Janssen-Cilag, Neuss, Germany) (1 mg/kg as a bolus and then 15 µg · kg^-1 · min^-1 intravenously). The dogs were ventilated with a mixture of nitrous oxide and oxygen (40%:60%) at a frequency of 12 to 15 breaths/min and a tidal volume starting at 15 mL · kg^-1 · min^-1. The settings were adjusted by maintaining arterial partial carbon dioxide pressure levels between 35 and 40 mm Hg. The left femoral artery and vein were cannulated to record aortic pressure, and blood samples were taken for analysis of blood gases, electrolytes, and pH. The animals received 500 U/kg of heparin.

Basic intravenous volume substitution was carried out with Ringer’s solution at a rate of 1 mL · kg^-1 · min^-1. If necessary, the rate of volume substitution was modified according to the continuously controlled input–output balance to maintain perfusion volumes at baseline levels. According to the values of K⁺, HCO₃^-, and base excess, substitution included administration of potassium chloride and sodium bicarbonate (8.4%). No catecholamines or other hormonal or pressor agents were administered. Rectal temperature and the standard peripheral electrocardiogram were monitored continuously.

The right femoral artery was prepared for arterial cannulation of the extracorporal circulation. After lateral thoracotomy in the fourth intercostal space, the pericardium was incised. The great vessels of the hearts were isolated. A 14F retroplegia balloon catheter with a second small lumen was introduced into the ascending aorta through the left subclavian artery. The left pulmonary artery was cannulated to collect coronary sinus effluent. The superior and inferior vena cavas were cannulated for the venous return of the extracorporal circulation, and the azygos vein was ligated. The extracorporal circuit consisted of a heat exchanger, a venous reservoir, a roller pump, and a membrane oxygenator.

Figure 1 shows the in situ isolated heart model. After cannulation of all vessels, extracorporal circulation was initiated. Arterial perfusion was performed through the right femoral artery and the retroplegia balloon catheter, which was placed in the ascending aorta. Perfusion volume was adjusted to achieve the same mean aortic pressure measured before extracorporal circulaton. Perfusion volume was within the range of 2.0 to 2.5 L/min. After a 5-minute equilibrium period, the balloon of the retroplegia catheter was inflated with 5 to 7 mL of fluid, which led to total occlusion of the aortic root. The hearts were perfused through the aortic root in a retrograde manner with the animal’s own blood by a second pressure-controlled roller pump separately from the organism. Through the small lumen of the catheter, coronary perfusion pressure was monitored continuously and kept at the same level as mean aortic pressure.

View larger version (26K): [in this window] [in a new window]   Fig 1. Experimental model (see Material and Methods). (A. = arteria; LV = left ventricular; V. = vena.)

Coronary artery and venous lactate concentrations and myocardial lactate contents were measured with standard photometric methods.

Perfusion–contractility matching/closed-loop analysis
We measured myocardial contractility (E_max) and coronary perfusion pressure independently of each other ("open-loop analysis"). Under physiologic conditions, the ventricle perfuses itself through the coronary circulation. In intact situations, the coupling between left ventricular and coronary perfusion pressures forms a feedback loop that can affect ventricular contractility. According to Sunagawa and colleagues [11], we constructed a so-called closed-loop analysis from the open-loop data in which feedback between left ventricular and coronary pressures was simulated. We used the corresponding left ventricular pressure points from the open-loop–estimated systolic pressure–volume relations at each coronary perfusion pressure assuming a coupling ratio of 1. That is, we selected the pressure–volume coordinates as follows: At a coronary perfusion pressure of 40 mm Hg, we used the left ventricular pressure–volume point where left ventricular pressure was equal to 40 mm Hg; at a coronary perfusion pressure of 50 mm Hg, we used the left ventricular pressure–volume point where left ventricular pressure was equal to 50 mm Hg; and so forth, up to 100 mm Hg of coronary perfusion pressure.

Experimental protocol
After 10 minutes of equilibrium after the final preparation, baseline measurements were performed to obtain systolic and diastolic function and coronary perfusion variables and biochemical data. Then the dogs were divided into two groups. Six animals with sham operation served as the control group. In the other 6 animals, brain death was induced as previously described. After sham operation or induction of brain death, measurements were performed after 5, 15, 30, 60, and 120 minutes. Coronary perfusion pressure was kept at the same level as the actually measured mean aortic pressure. After 120 minutes, perfusion pressure was decoupled from aortic pressure and set at baseline levels, and after 5 minutes of equilibrium, all measurements were repeated.

Statistical analysis
Results are expressed as mean ± standard error of the mean. The paired t test was used to compare two mean values within the groups. An unpaired t test and one-way analysis of variance were used for between-group comparisons. A probability value less than 0.05 was considered statistically significant.

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Variables in the control animals remained stable during the entire observation period. Hemodynamic variables are shown in Table 1 and coronary circulation variables in Table 2. Because none of the variables assessed changed significantly during the 2-hour observation period, only the average of the entire observation period is shown.

View larger version (23K): [in this window] [in a new window]   Fig 2. Left ventricular systolic (LVSP) (left panel) and end-diastolic (LVEDP) (right panel) pressure–volume relations. Values shown are mean ± standard error of the mean. (BDb = baseline, induction of brain death; BDt5 and BDt120 = 5 and 120 minutes after induction of brain death; BDt120+ = after decoupling of coronary perfusion pressure from aortic pressure and elevation to pre–brain death levels; Co = control [average values for the 2-hour observation period]; LVV = left ventricular volume.)

View larger version (17K): [in this window] [in a new window]   Fig 3. Slope of the peak systolic pressure–volume relation (Emax). Values shown are mean ± standard error of the mean. (BDb = brain death; Co = control [average values for the 2-hour observation period]; t5 and t120 = 5 and 120 minutes after induction of brain death; t120+ = after decoupling of coronary perfusion pressure from aortic pressure and elevation to pre–brain death level; * = p < 0.05 versus baseline; = p < 0.05 versus control group.)

Coronary perfusion pressure–flow relations/perfusion–contractility matching
The coronary perfusion pressure–flow relations, determined from 40 to 100 mm Hg of perfusion pressure in 10-mm Hg steps, did not differ between the groups. Figure 4 depicts the matching of coronary perfusion pressure and contractility (E_max) at the end of the experiment. The relation between the relative changes in coronary perfusion pressure and E_max was nearly identical in control and brain-dead dogs. In both groups the relation could be described by a typical inverse J-shaped curve. For each animal a "critical coronary perfusion pressure" could be identified, which was between 60 and 80 mm Hg (75.0 ± 2.23 mm Hg in control and 73.3 ± 3.33 mm Hg in brain-dead animals; not significant). While above this critical pressure, a change in coronary perfusion pressure led to only a small change in E_max; below this critical pressure, a further decrease in coronary perfusion pressure led to a significant (p < 0.05) decrease in contractility. We did not find any difference between coronary perfusion pressure–flow relations and perfusion–contractility matching before and 120 minutes after brain death induction. End-diastolic pressure–volume relations remained unchanged.

View larger version (15K): [in this window] [in a new window]   Fig 4. Perfusion–contractility matching as relation between percentile changes in coronary perfusion pressure (CPP) and slope of the peak systolic pressure–volume relation (Emax). Values shown are mean ± standard error of the mean. (BD = brain death; Co = control.)

View larger version (21K): [in this window] [in a new window]   Fig 5. Representative "closed-loop" analysis of left ventricular systolic pressure (LVSP)–volume (LVV) relations in a brain-dead animal constructed according to Sunagawa and colleagues [10] from the left ventricular systolic pressure–volume relations (straight lines) obtained for each coronary perfusion pressure (CPP) by simulation of feedback between left ventricular and coronary pressure (see Material and Methods for details).

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

Potential pathologic mechanisms of brain death–related hemodynamic instability
The initial acute hyperdynamic response was supposed to cause a direct cardiomyocyte injury with subsequent hemodynamic deterioration [6]. However, the hyperdynamic cardiocirculatory reaction is only transient, with return of the elevated hemodynamic indices to the physiologic range within a few minutes, and is therefore unlikely to cause persistent myocardial dysfunction.

A correlation between extreme catecholamine release related to the Cushing reaction [2, 3, 6, 12] and histologic myocardial damage was reported by Shivalkar and colleagues [13]. In contrast, Bruinsma and associates [7] refuted a relation between acute increase in myocardial workload, occurrence of hemodynamic deterioration, and myocardial histologic changes after rapid induction of brain death. Baroldi and coworkers [14] demonstrated myocardial necrosis in all types of brain injury in a human pathomorphologic study, but always to a minimal extent, which should not jeopardize cardiac function after transplantation.

Brain death–related hormone depletion [2, 3, 6, 15], and especially loss of thyroid hormones, was assumed to play an essential role because of a direct effect on myocardial contractility and anaerobic conversion of myocardial metabolism. Administration of thyroid hormones was shown to reverse hemodynamic and metabolic consequences of experimental brain death by Novitzky and colleagues [15]; however, in other experimental [4] and clinical [16] studies, no benefit of such therapy could be documented. In the present study, no evidence of anaerobic conversion of myocardial metabolism was observed with respect to blood and myocardial lactate content, although the hearts were subjected to the brain death–associated neurohumoral response, including catecholamine storm and hormone depletion. At identical coronary perfusion pressures and loading conditions, no significant differences in left ventricular function were found between control and brain-dead animals as well as before and after induction of brain death. These findings suggest only a minor importance of neurohumoral changes in hemodynamic instability after brain death in the potential donor, which is in agreement with the previously mentioned study of Galinanes and colleagues [8]. Therefore, we hypothesized that mechanisms other than neurohumoral mechanisms must be at least partly responsible for the observed cardiac dysfunction.

Coronary perfusion and myocardial function after brain death
As described in previous reports [2, 3, 6] and observed in the present study, systemic vascular resistance showed a marked decrease after brain death as a consequence of the loss of sympathetic tone. The subsequent decrease in aortic and coronary perfusion pressure as well as coronary blood flow may have contributed to the decrease in myocardial performance. Using the microsphere technique, a significant decrease in myocardial blood flow was demonstrated in a porcine [4] and a rat [9] model of brain death. Both studies underlined an apparent correlation between the impairment of myocardial blood flow and the observed deterioration of left ventricular function. Although there was no histologic evidence for myocardial ischemia [4], the data obtained did not allow determination of whether the decreased coronary flow was still sufficient to fulfill the actual needs of the myocardium. In the present study, myocardial oxygen consumption and lactate production did not change after the acute phase of brain death, indicating that the decrease in contractility was unlikely to be caused by global ischemia of the myocardium.

Even if a decrease in coronary perfusion pressure and flow does not lead to major ischemia, it may have an impact on myocardial contractility. Sunagawa and associates [11] demonstrated in cross-circulated isovolumetrically working hearts that neither the slope nor the volume intercept of the end-systolic pressure–volume relation changed so long as coronary perfusion pressure was higher than a "critical perfusion pressure." However, ventricular function deteriorated below a mean pressure of 67.0 ± 22.1 mm Hg. In the present study a similar critical perfusion pressure was found. The finding that mean aortic and coupled coronary pressures in brain-dead animals were below this range suggests that hemodynamic instability in the potential donor may not reflect the direct cardiac effects of brain death; rather, it may reflect altered loading conditions and coronary perfusion. A further important finding is the reversibility of cardiac dysfunction after brain death when coronary perfusion pressure was elevated to pre–brain death levels.

A possible pathologic mechanism leading to decreased contractility may be the so-called garden hose effect, which postulates a relation between systolic function and coronary perfusion pressure based on solely mechanical effects [17, 18]. This concept could be supported by a histologic study demonstrating lengthened sarcomeres in isolated guinea pig hearts as a result of increasing coronary perfusion pressure [19]. In a range where coronary autoregulatory reserve is exhausted [11, 20, 21], the reduction of intravascular pressure decreases the stretching of the intramyocardial vessels and, in turn, the surrounding myocardium. Under these conditions, the lack of evidence of myocardial ischemia may not be surprising. The reduction in contractility as a consequence of decreased coronary perfusion pressure reduces myocardial oxygen demand and therefore myocardial oxygen consumption, and lactate production can remain unchanged even at a lower coronary perfusion pressure and flow.

The closed-loop analysis [11] may also explain why changes in coronary perfusion pressure could play a central role in donor heart dysfunction. In a model of the physiologic situation in which left ventricular and coronary perfusion pressures are coupled, we observed a curvilinear systolic pressure–volume relation with a negative slope in the lower pressure region. It can be assumed that in the potential donor, coronary perfusion pressure falls into the negative slope region of the systolic pressure–volume relation because of an excessive reduction in afterload (loss of the sympathetic vasomotor tone) and preload (diabetes insipidus) [2, 3, 6]. Then, the low coronary perfusion pressure reduces contractility, which tends to further lower coronary perfusion pressure in the setting of increasing end-systolic volume and decreasing ventricular pressure. Once this vicious cycle is triggered, the ventricle is unable to recover on its own.

We did not observe any effects of coronary perfusion pressure on diastolic function and chamber stiffness, in agreement with the studies of Abel and colleagues [10] and Templeton and associates [22].

Direct effects of afterload on myocardial contractility
The possible direct participation of decreased afterload in the decline of cardiac contractility independent of coronary perfusion pressure remains to be clarified. Using brain death as a model for the totally denervated heart, Suga and colleagues [23] found increased left ventricular contractility by a separate increase in aortic pressure. In an in vivo canine model, Asanoi and associates [24] observed that under autonomic blockade, changes in afterload were followed by parallel changes in contractility. They postulated the existence of a control system that maintained optimal stroke work over a wide range of afterload conditions by mechanisms other than neural reflexes. According to this hypothesis, the reduced contractile state after brain death might also be seen as a response to decreased afterload for stroke work optimization.

Study limitations
To allow a separate analysis of coronary perfusion of the neurohumorally intact heart independent of the actual loading conditions, we had to use extracorporal circulation with isolated perfusion of the heart. In previous pilot experiments [25], extracorporal circulation was shown to cause coronary and peripheral vasodilation after 3 hours. Later, hemolysis and a decrease in hemoglobin concentrations could be observed. Moreover, extracorporal circulation can cause activation of cytokines, which may lead to deterioration of cardiac function. Therefore, in the present study we limited the observation period to 2 hours. During this time, the preparation remained stable, as shown in the control animals.

This short period of brain death, in contrast to significantly longer periods in the clinical situation and in other experimental studies [2, 4, 6–9, 12], might appear to be a limitation. However, because brain death–associated cardiac depression occurred within 2 hours in all reported studies without any further major hemodynamic changes thereafter, the 2-hour period of brain death in the present study seems to be sufficient to achieve potential cardiac effects. Furthermore, during longer observation periods, cardiac function may also be influenced in simple in situ preparations by an increasing number of factors that are not necessarily brain death related.

Conclusions
The present data show that the hemodynamic deterioration after brain death is closely related to the changes in coronary perfusion as a consequence of altered loading conditions. Furthermore, in our model, cardiac dysfunction after brain death could be reversed by elevation of coronary perfusion pressure to the physiologic range. The significance of these findings for the clinical management of potential donors needs to be confirmed by further studies.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
This study was supported by a grant ("Forschungschwerpunkt Transplantation") from the University of Heidelberg and by grant SFB 414/Q2 from the Deutsche Forschungsgemeinschaft. We thank Dr Susanne Bährle for critical review and recommendations; Lutz Hoffmann and Nicole Stumpf for technical assistance; and Karin Sonnenberg for biochemical measurements.

	References

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1. Hosenpud J.D., Bennett L.E., Keck B.M., Fiol B., Novick R.J. The registry report of the International Society for Heart and Lung Transplantation: Fourteenth official report—1997. J Heart Lung Transplant 1997;16:691-712.[Medline]
2. Novitzky D., Wicomb W.N., Cooper D.K.C., Rose A.G., Fraser R.C., Barnard C.N. Electrocardiographic, haemodynamic, and endocrine changes occurring during experimental brain death in the chacma baboon. Heart Transplant 1984;4:63-69.
3. Sebening C., Hagl C., Szabó G., et al. Cardiocirculatory effects of acutely increased intracranial pressure and subsequent brain death. Eur J Cardiothorac Surg 1995;9:360-372.[Abstract]
4. Meyers C.H., D’Amico T.A., Peterseim D.S., et al. Effects of triiodothyronine and vasopressin on cardiac function and myocardial blood flow after brain death. J Heart Lung Transplant 1993;12:68-80.[Medline]
5. Wicomb W.N., Cooper D.K.C., Lanza R.P., Novitzky D., Isaacs S. The effects of brain death and 24 hours storage by hypothermic perfusion on donor heart function in the pig. J Thorac Cardiovasc Surg 1986;91:896-909.[Abstract]
6. Bittner H.B., Kendall S.W.H., Campbell K.A., Montine T.J., Van Trigt P. A valid experimental brain death organ donor model. J Heart Lung Transplant 1995;14:308-317.[Medline]
7. Bruinsma G.J.B.B., Nederhoff M.G.J., Geertman H.J., et al. Acute increase of myocardial workload, hemodynamic instability and myocardial histologic changes induced by brain death in the cat. J Surg Res 1997;68:7-15.[Medline]
8. Galinanes M., Hearse D.J. Brain-death-induced cardiac contractile dysfunction: studies of possible neurohormonal and blood borne mediators. J Mol Cell Cardiol 1994;26:481-498.[Medline]
9. 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.[Medline]
10. Abel R.M., Reis R.L. Effects of coronary blood flow and perfusion pressure on left ventricular contractility in dogs. Circ Res 1970;27:961-971.[Abstract/Free Full Text]
11. Sunagawa K., Maughan W.L., Friesinger G., Guzman P., Chang M.S., Sagawa K. Effects of coronary arterial pressure on left ventricular end-systolic pressure-volume relation of isolated canine heart. Circ Res 1982;50:727-734.[Abstract/Free Full Text]
12. Soblosky J.S., Rogers N.L., Adams J.A., Farell J.B., Davidson J.F., Carey M.E. Central and peripheral biogenic amine effects of brain missile wounding and increased intracranial pressure. J Neurosurg 1992;76:119-126.[Medline]
13. Shivalkar B., Van Loon J., Wieland W., et al. Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function. Circulation 1993;87:230-239.[Abstract/Free Full Text]
14. Baroldi G., Di Pasquale G., Silver M.D., Pinelli G., Lusa A.M., Fineschi V. Type and extent of myocardial injury related to brain damage and its significance in heart transplantation: a morphometric study. J Heart Lung Transplant 1997;16:994-1000.[Medline]
15. Novitzky D., Cooper D.K.C., Morell D., Isaacs S. Change from aerobic to anaerobic metabolism after brain death and reversal following triiodothyronine therapy. Transplantation 1988;45:32-36.[Medline]
16. Randell T.T., Höckerstedt K.A.V. Triiodothyronine treatment is not indicated in brain dead multiorgan donors: a controlled study. Transplant Proc 1993;25:1552-1553.[Medline]
17. Arnold G., Kosche F., Miessner E., Neitzert A., Lochner W. The importance of the perfusion pressure in the coronary arteries for the contractility and the oxygen consumption of the heart. Pflügers Arch 1968;299:339-356.
18. Arnold G., Morgenstern C., Lochner W. The autoregulation of the heart work by the coronary perfusion pressure. Pflügers Arch 1970;321:34-55.[Medline]
19. Poche R., Arnold G., Gahlen D. Über den Einfluß des Perfusionsdruckes im stillgestellten aerob perfundierten, isolierten Meerschweinchenherzen auf Stoffwechsel und Feinstruktur des Herzmuskels. Virchows Arch 1971;8:252-266.
20. Downey J.M. Myocardial contractile force as a function of coronary blood flow. Am J Physiol 1976;230:1-6.[Abstract/Free Full Text]
21. Isoyama S., Maruyama Y., Koiwa Y., et al. Experimental study of afterload reducing therapy: the effects of reduction of systemic vascular resistance on cardiac output, aortic pressure and coronary circulation in isolated ejecting canine heart. Circulation 1981;64:490-499.[Abstract/Free Full Text]
22. Templeton G.H., Wildenthal K., Mitchell J.H. Influence of coronary blood flow on left ventricular contractility and stiffness. Am J Physiol 1972;223:1216-1220.[Free Full Text]
23. Suga H., Sagawa K., Kostiuk D.P. Controls of ventricular contractility assessed by pressure-volume ratio, E_max. Cardiovasc Res 1976;10:582-592.[Medline]
24. Asanoi H., Ishizaka S., Kameyama T., Sasayama S. Neural modulation of ventriculoarterial coupling in conscious dogs. Am J Physiol 1994;266:H741-H748.[Abstract/Free Full Text]
25. Hoffmann L., Wiedensohler H., Hackert T., et al. Experimenteller Einsatz der Herz-Lungen-Maschine: das in situ isoliert perfundierte Herz. Thorac Cardiovasc Surg 1997;45(Suppl):84.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Christian Sebening Christian Friedrich Vahl Siegfried Hagl Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Szabó, G. Articles by Hagl, S. Search for Related Content PubMed PubMed Citation Articles by Szabó, G. Articles by Hagl, S. Related Collections Related Article