HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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): Joseph Caspi John G. Coles Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Caspi, J. Articles by Wilson, G. J. Search for Related Content PubMed PubMed Citation Articles by Caspi, J. Articles by Wilson, G. J.

Ann Thorac Surg 1998;65:1730-1736
© 1998 The Society of Thoracic Surgeons

---

Original articles: cardiovascular

Brain Damage and Myocardial Dysfunction: Protective Effects of Magnesium in the Newborn Pig

^a Divisions of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
^b and Pediatric Cardiology The Hospital for Sick Children, Toronto, Ontario, Canada
^c Department of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada

Accepted for publication December 7, 1997.

Address reprint requests to Dr Caspi, Pediatric Cardiology, Children’s Hospital, 200 Henry Clay Ave, New Orleans, LA 70118

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Background. Brain damage is associated with myocardial dysfunction resulting from excessive release of endogenous catecholamines and Ca²⁺ overload. Magnesium ion, a natural Ca²⁺ blocker, has recently been recognized as a myoprotective agent.

Methods. Myocardial function was assessed in 3- to 7-day-old piglets from pressure–volume data (obtained by the conductance catheter/micromanometer technique) before and for 4 hours after ligation of the aortic arch vessels and was correlated with ultrastructural changes. Group a (n = 6) received MgSO₄ immediately after induction of brain damage for 4 hours, whereas group b (n = 6) did not receive MgSO₄ and served as control.

Results. In both groups after induction of brain damage, there was a significant (p < 0.05) increase in end-systolic elastance and preload-recruitable stroke work that persisted for 1 hour. However, after 2 and 4 hours, there was a significant (p < 0.05) reduction in both variables in group b (end-systolic elastance, 74% ± 5% and 59% ± 6%, respectively, and preload-recruitable stroke work, 77% ± 4% and 64% ± 3%, respectively, compared with baseline), and in group a, the values returned to baseline. The chamber stiffness index rose significantly (p < 0.05) in group b 15 minutes after induction of brain damage and remained significantly (p < 0.05) higher for 4 hours versus no significant change in group a. Plasma levels of epinephrine and norepinephrine were similar in the groups before and after brain damage. Electron microscopic study showed severe ultrastructural changes in group b and significantly milder changes in group a.

Conclusions. We conclude that MgSO₄ may protect the neonatal myocardium when administered immediately after brain damage.

	Introduction

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Patients who sustain traumatic brain damage are very often potential donors for heart transplantation. However, clinical and experimental studies have shown that brain damage can result in myocardial damage that occurs during the development of the brain death state and is not always detected at the time of harvest of the heart. Data from the International Heart Transplantation Registry [1] show that 25% of all recipient deaths after transplantation were due to myocardial dysfunction that was unrelated to acute rejection or infection. Electrocardiographic changes consistent with myocardial ischemia and atrial and ventricular arrhythmias observed after brain damage may reflect acute myocardial injury characterized by foci of myocardial necrosis, subendocardial hemorrhage, and contraction bands [2]. Toxic levels of circulating endogenous catecholamines have been found in patients and animal models after acute brain damage. These studies clearly indicate that the excessive sympathetic activity and the associated intracellular Ca²⁺ overload observed after brain injury is the primary mechanism of myocardial injury [3].

Previous studies concerned with the development of myocardial dysfunction after brain damage demonstrated that Ca²⁺ antagonists [4], ß-adrenergic blockade [5], surgical symphathectomy [6], and thyroid hormones [7] provide substantial protection against the development of myocardial damage. Magnesium has recently been recognized as a myoprotective agent during acute myocardial ischemia [8]. However, these studies were not performed in newborns. Therefore, this study was designed to examine the effects of the administration of magnesium on neonatal myocardial function after brain damage.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
The effects of the administration of MgSO₄ on myocardial function after brain damage were studied in newborn pigs 3 to 7 days old and weighing 1.9 to 2.8 kg. The animals were divided into two groups of 6 piglets each. Group a was given MgSO₄ for 4 hours immediately after induction of brain damage. Group b, receiving no MgSO₄, served as the control group. All animals received humane care in compliance with the "Guide for the Care and Use of Laboratory Animals" published by the National Institutes of Health (NIH publication 85-23, revised 1985).

Anesthesia and monitoring
The animals were anesthetized with intravenous sodium pentobarbital (30 mg/kg) after administration of atropine sulfate (0.1 mg/kg). Sedation was maintained with continuous infusion of fentanyl, 10 to 20 µ · kg^-1 · h^-1. After endotracheal intubation, ventilation was maintained with a fixed-pressure respirator and inspired mixture of oxygen and room air (inspired oxygen fraction, 0.4). The hematocrit was maintained between 30% and 35%, pH between 7.35 and 7.45, partial oxygen tension between 150 and 250 mm Hg, and carbon dioxide tension between 35 and 45 mm Hg. Serial measurements of ionized Ca²⁺, K⁺, and glucose were performed every hour. Serum ionized Ca²⁺ concentration was maintained in the normal range with supplement of CaCl₂, as required. Administration of CaCl₂ did not coincide with measurement of left ventricular (LV) function. The temperature was maintained at 37°C during the course of the experiment.

A median sternotomy was performed and the pericardium, opened. The aortic arch and arch vessels were dissected free. Left ventricular pressure was monitored with a high-fidelity 5F transducer-tipped pressure catheter (PC-350; Millar Instruments, Houston, TX) that was introduced through the apex. A 5F multielectrode conductance catheter (Webster Labs, Baldwin Park, CA) was placed into the left ventricle through a stab wound and advanced so that its tip was positioned at the aortic root. Proper position of the conductance catheter was confirmed by palpation and at postmortem examination.

Left ventricular volume measurements
The conductance catheter was connected to a model Sigma-5 signal-conditioner processor (Leycom, Ocgstgeest, the Netherlands) for continuous, instantaneous LV volume measurements [9]. The Sigma 5 instantaneously calculates LV volume [V(t)] by the following equation:

where is an empirical slope constant for the V(t)-G(t) relation and assumed to be 1.0 in all experiments; L is the interelectrode distance, and is the resistivity of the blood measured by a cuvette attached to the Sigma 5 system; and Vc is the correction volume for the parallel conductance formed by tissue surrounding the LV cavity. To obtain V(t), Vc was determined by a rapid injection of hypertonic saline solution (1 mL) into the right atrium while ventilation was held at end-expiration and calculated from a least-square regression of the altered end-systolic and end-diastolic volumes. A signal-processing computer (NEC 486) and software designed in our laboratory were used to determine Vc when end-systolic volume was equal to end-diastolic volume.

Experimental protocol
After signal calibration, baseline pressure–volume (P–V) relation measurements were performed by transient inferior vena cava occlusion with an adjustable snare. The brachiocephalic trunk was clamped at its origin followed by ligation of the left subclavian artery. This method has previously been shown to result in irreversible brain injury in pigs within 120 minutes [10].

Administration of MgSO₄, 1 g/h (50% solution diluted with 5% dextrose in water) into the external jugular vein, was commenced (infusion pump model 921; Harvard Apparatus, Millis, MA) simultaneously with the induction of brain damage and continued for 4 hours. After stabilization for 15 minutes, the P–V relation was measured, and measurements were repeated every 60 minutes for 4 hours.

Data analysis
The electrocardiographic and LV pressure and volume data were recorded on -inch magnetic tape (PR 280; Ampex, Redwood City, CA) and simultaneously displayed on a precalibrated digital x-y oscilloscope (model 2090; Nicolet, Madison, WI). The three signals were digitized by an analog-digital convertor (DT 2621; Data Translator, MA) at a sample frequency of 333 Hz or every 3 ms through the cardiac cycle. The obtained P–V loops were analyzed including one or two steady-state beats and six to eight subsequent cycles in the first 3 seconds after inferior vena cava occlusion. End-systole was defined by the points of maximal pressure to absolute volume ratio for each cardiac cycle. The end-systolic P–V relation was generated from a least-square linear regression of these points with the expression [11]. To describe the position of the end-systolic P–V relationship, we calculated the volume when Pes = 100 mm Hg (V₁₀₀) [12].

Left ventricular stroke work (SW) was calculated as the integral of LV pressure (P) and volume (V) over the entire cardiac cycle: . The stroke work–end-diastolic volume (EDV) relation was determined by least-square linear regression during caval occlusion with the expression . This relationship is defined as the preload-recruitable stroke work. End-diastole was defined as 40 ms before the peak first time derivative of LV pressure was reached during the cardiac cycle. The end-diastolic P–V relation points during caval occlusion were exponentially fitted by the equation [13].

Electron microscopic study
The effects of brain damage on myocardial ultrastructure were studied in both groups a and b and compared with normal neonatal myocardium. At the conclusion of each experiment, the left ventricle was excised, and a slice through the middle portion of the ventricle was immersed in ice-cold 2% glutaraldehyde and 2% paraformaldehyde in 0.1 mol/L phosphate buffer at pH 7.40. Cubes (0.5 to 1 mm³) were cut from this slice under fixative from the midzone of the septum and lateral wall and fixed for 2 hours. Subsequently, the samples were washed in buffer, postfixed in 1% osmium tetroxide, dehydrated in graded alcohols, and embedded in epoxy resin. Semithin sections were stained with toluidine blue for proper trimming and orientation to achieve longitudinally cut myocardial fibers. After the edges of the blocks were trimmed to eliminate areas of mechanical damage, thin sections were cut from the central face of the best-preserved two blocks, stained with lead citrate and uranyl acetate, and examined by electron microscopy.

Semiquantitative assessment of ultrastructural changes was performed in a blinded fashion by a single observer with a method described previously [14]. Mitochondrial structure change was assessed by assigning an ischemic damage grade of 0 to 4 to the 300 mitochondria in each micrograph from each heart [15]: 0 = normal ultrastructure; 1 = early swelling as manifested by clearing matrix density and separation of cristae; 2 = more marked swelling without disruption of cristae; 3 = massive swelling with disruption of cristae; and 4 = massive swelling with disruption of cristae and loss of integrity of the mitochondrial membrane. The mitochondrial score for each case was determined by averaging the grades of more than 300 mitochondria.

Plasma catecholamine measurements
Plasma levels of epinephrine and norepinephrine were measured from a peripheral vein before brain damage and 15 minutes, 2 hours, and 4 hours after brain damage. The blood samples were rapidly placed in chilled tubes containing EGTA (Egtazic acid) and centrifuged at 4°C for 15 minutes. Plasma was separated into collecting tubes and frozen at -70°C for subsequent assay [16].

Statistical analysis
All data are presented as the mean ± the standard error of the mean. To compare between groups and to test for the overall effect of Mg²⁺ on each hemodynamic variable, an analysis of covariance was performed using the SAS statistical package [17]. The level of significance was considered a p value of less than 0.05.

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
The mean hemodynamic variables obtained before brain damage and 15 minutes, 1 hour, 2 hours, and 4 hours after the induction of brain damage for each group are presented in Table 1. Baseline values were comparable between the two groups. There was a significant increase in LV end-systolic pressure, LV end-diastolic pressure, stroke work, heart rate, and cardiac output in both groups 15 minutes and 1 hour after induction of brain damage compared with baseline. After 2 and 4 hours, LV end-diastolic pressure remained significantly higher and at 4 hours LV end-systolic pressure, stroke work, and cardiac output were significantly lower in group b compared with baseline, whereas these variables returned to baseline in group a.

View larger version (23K): [in this window] [in a new window]   Fig 1. End-systolic elastance (Ees) before and 15 minutes, 1 hour, 2 hours, and 4 hours after brain damage in MgSO4–treated animals (group a) and controls (group b). (* = significant difference versus baseline; = significant intergroup difference.)

View larger version (40K): [in this window] [in a new window]   Fig 2. Preload-recruitable stroke work (Mw) before and 15 minutes, 1 hour, 2 hours, and 4 hours after brain damage in MgSO4–treated animals (group a) and controls (group b). (* = significant difference versus baseline.)

View larger version (17K): [in this window] [in a new window]   Fig 3. Volume when end-systolic pressure is 100 mm Hg (V100) before and 15 minutes, 1 hour, 2 hours, and 4 hours after brain damage in MgSO4–treated animals (group a) and controls (group b). (* = significant difference versus baseline.)

View larger version (28K): [in this window] [in a new window]   Fig 4. Chamber constant (k) before and 15 minutes, 1 hour, 2 hours, and 4 hours after brain damage in MgSO4–treated animals (group a) and controls (group b). (* = significant difference versus baseline; = significant intergroup difference.)

View larger version (134K): [in this window] [in a new window]   Fig 5. Electron micrographs of myocardium from a piglet after brain damage showing (A) rupture of sarcolemma and (B) mitochondrial swelling and deposition of dense (calcium) granules with loss of internal architecture. (A, x7,000 before % reduction; B, x3,000 before % reduction.)

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

Numerous experimental brain-death models and clinical studies in humans have shown a direct relationship between brain death and major histopathologic and functional changes in the myocardium [18, 19]. In a clinical study [20] of 172 donor hearts, the mortality rate of patients receiving hearts with impaired myocardial function before transplantation was 44% compared with 6% for recipients of undamaged hearts. Most potential heart donors are brain-damaged patients, and in the majority of cases, the heart is excised only after a long period. Therefore, it may be subjected to ischemic damage that will affect its use. Data from the international heart transplantation registry [1] showed that 25% of all recipient deaths after transplantation were the result of "cardiac failure." In view of the scarcity of donor hearts, it is conceivable that methods to reduce myocardial damage occurring during the period from brain injury to harvest of the heart may contribute to better functional recovery after transplantation.

The release of endogenous catecholamines and the massive activation of ß-adrenergic receptors have been implicated as the primary mechanism in the pathogenesis of myocardial damage and the hemodynamic instability that occur after brain death [21]. Similar myocardial histopathologic changes have been shown in animals after infusion of epinephrine and norepinephrine [3]. A direct relationship has been found between the level of endogenous catecholamines, the extent of brain damage, and the severity of myocardial damage [22]. Postmortem studies [23] showed that patients who died of acute intracranial lesions associated with a sudden increase in intracranial pressure demonstrated transmural scattered foci of myocardial damage that were very typical with petechial hemorrhages in the subendocardium, contraction bands, and coagulative myocytolysis. The ultrastructural changes in our study involved scattered areas of myocardial damage consisting of ruptured sarcolemma, swelling of the mitochondria with calcium granule deposition, and, in the extreme forms, contraction bands. These changes in myocardial muscle are consistent with the changes observed with reperfusion injury after myocardial infarction [2].

The rise of endogenous catecholamines induces a mobilization of cellular Mg²⁺, particularly from the myocardium, and a massive Ca²⁺ influx through the cell membrane, which results in intracellular Ca²⁺ overload. This, in turn, promotes activation of the Ca²⁺–adenosine triphosphatase located at the inner surface of the sarcolemma, thus causing further depletion of adenosine triphosphate. Elevated cytosolic Ca²⁺ levels also trigger a cascade of destructive events including activation of proteases and phospholipases that results in loss of membrane integrity and alteration in the activity of the Na–Ca²⁺ exchange system in the sarcolemma and sarcoplasmic reticulum. This results in impaired ability of the cell to sequester efficiently the elevated levels of intracellular Ca²⁺.

Administration of MgSO₄ has been associated with enhanced myocardial protection, possibly through its Ca²⁺ antagonistic effect. Studies to date appear to indicate that within the muscle cell, Mg²⁺ blocks the influx of Ca²⁺ through the slow channels, inhibits release of Ca²⁺ from the sarcoplasmic reticulum in response to a sudden influx of extracellular Ca²⁺, which normally stimulates its release, and competes with Ca²⁺ over nonspecific binding sites on troponin-C and myosin, thus affecting the ability of Ca²⁺ to develop maximal tension at any given Ca²⁺ concentration. It also activates the Ca²⁺-adenosine triphosphatase of the sarcoplasmic reticulum, which, by removing Ca²⁺ from the cytosol, regulates the diastolic properties of the left ventricle [24].

It is also evident that Mg²⁺ plays a major role in regulating the diastolic properties of the left ventricle. The decrease in the slope constant of the end-diastolic P–V relationship indicates a greater chamber distensibility. We speculate that this phenomenon is attributable to the competing effect of Mg²⁺ with Ca²⁺ on the binding sites on the actin-myosin cross-bridges and the enhanced removal of Ca²⁺ from the cytosol.

Similar effects have been shown in other studies [4–7] concerned with myocardial dysfunction after brain damage with the use of ß blockers, calcium blockers, and thyroid hormones. Hearts from brain-dead rats that received triiodothyronine before transplantation showed improved postoperative function [7]. Although the mechanism of action may be different, magnesium, thyroid hormones, ß blockers, and calcium blockers share similar myoprotective effects after brain damage.

Myocardial performance was assessed by using a multielectrode conductance catheter providing continuous LV volume measurement. The end-systolic P–V relationship, the stroke work–end-diastolic volume relationship, and their slopes have been accepted as load-sensitive indices of ventricular contractility. The validity of this technique for assessment of cardiac contractility has previously been established in adult animals and has been adapted for analysis of newborn cardiac function by our group [9]. Applegate and associates [25] showed that the conductance catheter accurately measures absolute volumes at steady state but can underestimate the slope and position of the end-systolic P–V relation when it is determined by caval occlusion. However, the end-systolic P–V relationship accurately measures the direction and magnitude of change in LV systolic function. In addition, we used the volume axis value at P₁₀₀ (V₁₀₀) as a variable describing the position of the slope of the end-systolic P–V relation in the normal operating range of the left ventricle, thus avoiding the problems of interpretation of V₀ in a range where curvilinearity of the slope may occur [12].

The present study has four major findings: (1) Irreversible brain damage is associated with an immediate rise in the level of circulating endogenous catecholamines. (2) There is a reduction in systolic function and an alteration in the diastolic properties of the left ventricle after brain injury. (3) The myocardial functional changes correlate with severe ultrastructural changes. (4) Better recovery of LV systolic and diastolic function was observed in Mg²⁺-treated animals.

The major limitation of this study is that after 4 hours, the preparation became very unstable because of extreme edema, peripheral vasoconstriction, and acidosis. Therefore, it would be impossible to draw any firm conclusions regarding the potential recovery of the left ventricle on the basis of the hemodynamic data obtained after 4 hours. Right ventricular dysfunction after brain damage may also contribute to early recipient death; this warrants further investigation.

In conclusion, irreversible brain damage in the newborn pig resulted in myocardial functional and ultrastructural changes. These changes that occur within the first 4 hours after brain damage may contribute to the early failure of some transplanted hearts. Administration of magnesium to victims of head trauma who are potential heart donors may be beneficial because of its calcium antagonist effects.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Supported by grant T-1376 from the Ontario Heart Foundation.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

1. Fragomeni L.S., Kaye M.P. The Registry of the International Society for Heart Transplantation: fifth official report. J Heart Transplant 1988;7:249-253.[Medline]
2. Kolin W., Norris J.W. Myocardial damage from acute cerebral lesions. Stroke 1984;15:990-993.[Abstract/Free Full Text]
3. Rona G. Editorial review: catecholamine cardiotoxicity. J Mol Cell Cardiol 1985;17:291-306.[Medline]
4. Novitzky D., Cooper D.K.C., Rose A.G., Reichart B. Prevention of myocardial injury by pretreatment with verapamil hydrochloride prior to experimental brain death. Am J Emerg Med 1987;5:11-18.[Medline]
5. Kolin A., Brezina A., Kellen J.A., Lewis A.J., Norris J.W. Reversible myocardial damage in gerbil brain ischemia and its prevention by beta-adrenergic blockage. Br J Exp Pathol 1988;69:621-630.[Medline]
6. Novitzky D., Wicomb W.N., Cooper D.K.C., Rose A.G., Reichart B. Prevention of myocardial injury during brain death by total cardiac sympathectomy in the Chacma baboon. Ann Thorac Surg 1986;41:520-524.[Abstract]
7. Votapka T.V., Canvasser D.A., Pennington D.G., Koga M., Swartz M.T. Effects of triiodothyronine on graft function in a model of heart transplantation. Ann Thorac Surg 1996;62:78-82.[Abstract/Free Full Text]
8. Antman E.M. Magnesium in acute MI [Editorial]. Circulation 1995;92:2367-2372.[Free Full Text]
9. Kass D.A., Midie M., Graves W., Brinker J.A., Maughan W.L. Use of a conductance (volume) catheter and transient inferior vena cava occlusion for rapid determination of pressure–volume relationship in man. Cathet Cardiovasc Diagn 1988;15:192-202.[Medline]
10. 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]
11. Kass D.A., Yamazaki T., Burkhoff D., Maugham W.L.M., Sagawa K. Determination of left ventricular end-systolic pressure–volume relationship by the conductance (volume) catheter technique. Circulation 1986;73:586-595.[Abstract/Free Full Text]
12. Little WC, Cheng CP, Peterson T, Vinten-Johansen J. Response of the left ventricular end-systolic pressure–volume relation in conscious dogs to a wide range of contractile states. Circulation 1988;78:736–45. [Published erratum appears in Circulation 1989;79:205.]
13. Gaasch W.H., Battle W.E., Oboler A.A. Left ventricular stress and compliance in man: with special reference to normalized ventricular function curves. Circulation 1972;45:746-762.[Abstract/Free Full Text]
14. Warner K.G., Khuri S.F., Kloner R.A. Structural and metabolic correlates of cell injury in the hypertrophied myocardium during valve replacement. J Thorac Cardiovasc Surg 1987;93:741-754.[Abstract]
15. Sawa Y., Matsuda H., Shimazaki Y. Ultrastructural assessment of the infant myocardium receiving crystalloid cardioplegia. Circulation 1989;76(Suppl 5):141-145.
16. Foti A., Kimura S., DeQuattro V., Lee D. Liquid-chromatographic measurement of catecholamines and metabolites in plasma and urine. Clin Chem 1987;33:2209-2213.[Abstract/Free Full Text]
17. SAS user’s guide. Version 5. Cary, NC: SAS Institute, 1985:1–596.
18. Bittner H.B., Kendall S.W.H., Chen E.P., Davis R.D., Van Trigt P., III Myocardial performance after graft preservation and subsequent cardiac transplantation from brain-dead donors. Ann Thorac Surg 1995;60:47-54.[Abstract/Free Full Text]
19. 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;3:308-317.
20. Darracott-Cankovic S., Stovin P.G.I., Wheeldon D., Wallwork J., Wells F., English T.A.H. Effect of donor heart damage on survival after transplantation. Eur J Cardiothorac Surg 1989;3:525-532.[Abstract]
21. Shivalkar B., Van Lon J., Weiland 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]
22. Todd G.L., Baroldi G., Pieper G.M., Clayton F.C., Eliot R.S. Experimental catecholamine-induced myocardial necrosis. I. Morphology, quantification and regional distribution of acute contraction band lesions. J Mol Cell Cardiol 1985;17:317-338.[Medline]
23. Greenhoot J.H., Reichenbach D.D. Cardiac injury and subarachnoid hemorrage: a clinical, pathological, and physiological correlation. J Neurosurg 1969;30:521-531.[Medline]
24. Hasselbach W., Fassold E., Migala A., Rauch B. Magnesium dependence of sarcoplasmic reticulum calcium transport. Fed Proc 1981;40:2657-2661.[Medline]
25. Applegate R.J., Cheng C.P., Little W.C. Simultaneous conductance catheter and dimension assessment of left ventricle volume in the intact animal. Circulation 1990;81:638-648.[Abstract/Free Full Text]

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): Joseph Caspi John G. Coles Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Caspi, J. Articles by Wilson, G. J. Search for Related Content PubMed PubMed Citation Articles by Caspi, J. Articles by Wilson, G. J.