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J Thorac Cardiovasc Surg 1997;114:100-108
© 1997 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

CONTINUOUS ANTEGRADE WARM BLOOD CARDIOPLEGIA ATTENUATES AUGMENTED CORONARY ENDOTHELIUM–DEPENDENT CONTRACTION AFTER CARDIAC GLOBAL ISCHEMIA AND REPERFUSION

Supported by grant CMRP 421 from the Chang Gung Memorial Hospital, Chang Gung Medical College, and in part by grant NSC85-2331-B-182-012 from the National Science Council, Executive Yuan, Taiwan, Republic of China.

Received for publication August 20, 1996. revisions requested Oct. 8, 1996; revisions received Nov. 13, 1996 accepted for publication Dec. 27, 1996. Address for reprints: Pyng Jing Lin, MD, Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, 199, Tun-Hwa North Rd., Taipei, Taiwan, Republic of China.

Abstract

Background: Experiments were designed to evaluate the effect of warm blood cardioplegia on endothelium-dependent contraction of the coronary endothelium after cardiac global ischemia and reperfusion. Method: Dogs (n = 12 in each group) were exposed to extracorporeal circulation with the body temperature at 37° C (group 1) or 28° C (groups 2 and 3). The ascending aorta was crossclamped for 120 minutes while continuous infusion of warm blood cardioplegec solution (group 1) or intermittent infusion of cold (4° C) crystalloid cardioplegic solution (group 2) was performed via the coronary arteries through the aortic root. Cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 minutes of reperfusion. Reperfused (groups 1, 2, and 3) and control (group 4) coronary arteries were then harvested for study. Results: Perfusate hypoxia caused endothelium-dependent contraction in the arteries of all four groups that could be attenuated by N^G-monomethyl-L-arginine (L-NMMA) or L-NMMA plus D-arginine, but not by L-NMMA plus L-arginine or endothelin receptor A and B antagonist PD 145065. The endothelium-dependent contraction results in groups 2 and 3 (75% ± 4% and 80% ± 5%, respectively) were significantly greater than those in groups 1 and 4 (15% ± 3% and 18% ± 5%, respectively). Scanning electron microscope studies showed that platelet adhesion and aggregation, areas of microthrombi, disruption of endothelial cells, and separation of the intercellular junction could be found in coronary segments from groups 2 and 3, but not in vessels from groups 1 and 4. Conclusion: These experiments suggest that global ischemia and reperfusion enhances hypoxia-mediated endothelium-dependent contraction of the coronary endothelium and damages the ultrastructure. These kinds of changes can be prevented by continuous antegrade infusion of warm blood cardioplegic solution during global ischemia

Warm blood cardioplegia has become popularized for myocardial protection in recent years. ^1-3 The potential advantages of continuous infusion of warm blood cardioplegic solution are appealing. The heart is aerobic, perfused, and rested while the cardioplegic solution is being infused. Warm blood cardioplegia can, therefore, be considered a tool of myocardial resuscitation. ³

The coronary endothelium regulates vasomotor tone and local tissue perfusion by producing endothelium-derived relaxing factors and endothelium-derived contracting factors that act on the underlying vascular smooth muscle. ^4,5 When exposed to hypoxia, when regenerated after mechanical injury, and after ischemia and reperfusion, the coronary endothelium exhibits augmented contraction. ^6-12 Augmented endothelium-dependent contraction after coronary ischemia and reperfusion appears to be an important factor in coronary vasospasm after ischemia and reperfusion of coronary arteries.

Several recent laboratory experiments have suggested that hyperkalemic crystalloid cardioplegic solutions per se augment endothelial cell production of endothelium-derived contracting factor. ^13-15 However, the effect of cardioplegia on coronary endothelium-dependent contraction after coronary ischemia and reperfusion has not been investigated clearly. The present study was designed to evaluate the effect of continuous warm blood cardioplegia on coronary endothelium-dependent contraction after global ischemia and reperfusion.

Material and methods

Animal preparation.
Healthy mongrel dogs (25 to 30 kg) of either sex were anesthetized with sodium pentobarbital (30 mg/kg intravenous injection) and intubated with a cuffed endotracheal tube, and the lungs were ventilated with a respirator. The rectal temperature and arterial blood pressure were monitored. Next, a medial sternotomy was performed. Animals were heparinized (250 U/kg), and cardiopulmonary bypass (CPB) was instituted with cannulation of the ascending aorta and right atrium. The electrocardiogram was continuously monitored via limb leads. Deferoxamine (20 mg/kg) and methylprednisolone (20 mg/kg) were infused intravenously 30 minutes before the establishment of CPB. The dog was then placed on total CPB with a bubble oxygenator (C.R. Bard, Inc., Tewksbury, Mass.) at a flow rate of 50 ml/kg per minute. The myocardial temperature was continuously monitored via epicardial thermistor probes (Shiley, Inc., Irvine, Calif.). After the dog's condition stabilized the ascending aorta was crossclamped. A double-lumen aortic root cannula (DPL, Inc., Grand Rapids, Mich.) was inserted for delivery of cardioplegic solution and simultaneous measurement of infusion pressure. All infusions of cardioplegic solution were administered at 50 mm Hg pressure.

Animals were randomized into four groups with 12 dogs in each group. In dogs in group 1, the heart was protected by continuous warm blood cardioplegic (37° C) solution infused into the aortic root (antegrade infusion) with a rectal temperature of 37° C. Blood cardioplegic solution (Table I) was delivered as a mixture of four parts oxygenated blood to one part crystalloid solution with use of a Sarns MP4 cardioplegic solution delivery system (Sarns 3M Health Care Group, Ann Arbor, Mich.). Initial induction of cardiac arrest was accomplished with an induction solution with a potassium ion concentration of 20 mmol/L followed by continuous infusion of maintenance solution with a potassium ion concentration of 8 mmol/L. After 120 minutes of aortic crossclamping, the infusion of blood cardioplegic solution was stopped and the crossclamp was removed.

In group 3, the rectal temperature was kept at about 28° C. The cardioplegic solution was not used. After 120 minutes of aortic crossclamping, systemic rewarming to 37° C was achieved and the crossclamp was removed.

After declamping, the animals were weaned from CPB with a mean arterial pressure of 80 mm Hg. When ventricular fibrillation occurred, direct-current countershocks of 10 W were applied. Cardiotonic drugs and vasodilators were not used. The heart was maintained in the beating and working state for a total of 60 minutes. The heart was then excised.

An additional 12 dogs served as the control group (group 4). These dogs underwent induction of anesthesia, intubation, and median sternotomy, after which the heart was excised rapidly.

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 No. 85-23, revised 1985). The entire protocol was approved by the research committee of Chang Gung Memorial Hospital, which regulates all experiments involving animals.

Organ chamber studies.
The processes of organ chamber studies have been reported previously. ^6-8,12-18 The heart was quickly removed and immersed in cold oxygenated physiologic salt solution. The left anterior descending artery or left circumflex coronary artery, or both, were carefully dissected free and prepared as rings (4 mm in length).

In some rings, the endothelium was removed by gentle rubbing of the intimal surface with the tip of a pair of watchmaker's forceps. The rings were suspended in organ chambers (25 ml) filled with control solution (37° C; aerated with 95% O₂ and 5% CO₂; pH = 7.4) and connected to a strain gauge (Statham Gould UC2) for the measurement of isometric force. Rings were placed at the optimal point of their length-tension relationship by progressively stretching them at each level of distension until the contraction to KCl (20 mmol/L) was maximal.

Scanning electron microscope studies.
Hearts from eight dogs (2 dogs in each groups) were used for scanning electron microscope studies. The procedures have been reported previously by our group. ¹⁸ After ischemia and reperfusion, the coronary endothelium was fixed in situ at physiologic pressure with buffered physiologic solution for 5 minutes. This solution had the following composition (in millimoles per liter): KCl, 2.7; NaCl, 137.9; Na₂HPO4 · 7H₂O, 8.1; and KH₂PO₄, 1.1. Glutaraldehyde (1%) in buffered physiologic solution was then infused for 10 minutes. Segments (2 cm in length) of left anterior descending or left circumflex coronary artery, or both, were carefully harvested, kept in this iced perfusion-fixation solution, and sent for scanning electron microscopic processing.

Scanning electron microscope procedure.
The tissue processing of electron microscopic observation has been reported previously. ¹⁸ In brief, the specimens were fixed with iced 3% glutaraldehyde in 0.1 mol/L cacodylate buffer (pH 7.2 to 7.4) for 2 hours. Subsequently the specimens were rinsed with cold perfusion-fixation solution several times and post-fixed with 1% phosphate buffer osmium tetroxide (pH 7.2 to 7.4) for an additional 2 hours. For electroconduction and stabilization of the surface structure, the tissues were immersed in 1% tannic acid in distilled water for 30 minutes at 4° C and then transferred into 1% osmium tetroxide in distilled water for 30 minutes at 4° C, followed by a rinse with distilled water. The tissues were then dehydrated in graded concentrations of chilled ethanol. For scanning electron microscopy the tissue was subjected to critical-point drying. After drying, samples were mounted on specimen stubs and coated with platinum and palladium alloy to a 4 nm thickness. The specimens were examined with a Hitachi S-5000 scanning electron microscope operated at 3 kV.

Drugs.
The drugs acetylcholine chloride, potassium chloride, adenosine diphosphate, calcium ionophore A23187, (±)-isoproterenol hydrochloride, indomethacin, sodium fluoride, prostaglandin F₂, and sodium nitroprusside were obtained from Sigma Chemical Co. (St. Louis, Mo.) N^G-monomethyl-L-arginine (L-NMMA), L-arginine, and D-arginine were obtained from Calbiochem, La Jolla, Calif. Aluminum chloride was obtained from Aldrich Chemical (Milwaukee, Wis.). PD 145065 (C₅₂H₆₇N₇O₁₀) was obtained from Alexis Corp. (San Diego, Calif.). Indomethacin was dissolved in Na₂CO₃ (10^-5 mol/L). The calcium ionophore A23187 and PD 145065 were dissolved in dimethyl sulfoxide (Sigma) and diluted further in distilled water. The concentrations are expressed as final molar concentrations in the organ chambers.

Data analysis.
The data are expressed as means plus or minus the standard error of the mean. In all experiments, n refers to the number of animals from which blood vessels were taken. The responses gained from segments contracted with prostaglandin F₂ were expressed as percent changes from the contracted levels. With regard to relaxations, the negative logarithm of the effective concentration (in millimolars per liter) of agonist that caused 50% inhibition of the contraction to prostaglandin F₂ was calculated for concentration-response curves. For contractions, the maximal response (in grams of tension) and concentration of agonist inducing the half-maximal contraction were determined. The means of these values are presented. Statistical evaluation of data between groups was performed by analysis of variance.

Protocol of organ chamber studies.
Segments of coronary artery with and without endothelium from the same animal were placed in our eight-bath organ chamber system, studied, and compared. The following procedures were performed.

Studies of endothelium-dependent contraction to hypoxia.
The vascular segments with or without endothelium were contracted with prostaglandin F₂ (2 x 10^-6 mol/L) (initial tension) in an organ chamber gassed with 95% 0₂/5% CO₂ (oxygen tension [PO₂] 400 ± 10 mm Hg). When the contractile response to prostaglandin F₂ stablized, hypoxia was induced by aerating the organ bath with a mixture of 95% N₂ and 5% CO₂ for 20 minutes (pH = 7.4, PO₂ = 35 ± 7 mm Hg). ^7,12-15,18 After 20 minutes, oxygenation was reintroduced. Vascular segments were only exposed to one hypoxic period.

Studies of endothelium-independent relaxation.
To test the ability of the smooth muscle to relax, concentration-response curves to sodium nitroprusside (mediated by cyclic guanosine monophosphate, 10^-9 to 10^-4 mol/L) and isoproterenol (mediated by cyclic adenosine monophosphate, 10^-9 to 10^-4 mol/L) were obtained after the segments were contracted with prostaglandin F₂ (2 x 10^-6 mol/L).

Studies of endothelium-independent contraction.
To test the ability of the smooth muscle to contract, concentration-response curves to potassium ions (5 to 50 mmol/L, voltage dependent) and prostaglandin F₂ (10^-9 to 10^-4 mol/L, receptor dependent) were obtained.

Results

Endothelium-dependent contraction to hypoxia.
Reperfused (groups 1, 2, and 3) and control (group 4) coronary arterial segments with and without endothelium exhibited comparable contractile responses to prostaglandin F₂ (2 x 10^-6 mol/L, initial tension, about 30% of the maximal tension) (Fig. 1 and Table II). On exposure to hypoxia, contracted reperfused and control coronary segments with endothelium exhibited comparable relaxations (hypoxic relaxation) (groups 1 through 4, 30% ± 3%, 35% ± 2%, 33% ± 4%, and 32% ± 5% of initial tension, respectively; p = 0.8101; Fig. 2). In vascular segments with endothelium from all four groups, hypoxia induced contractions (hypoxic contraction) that were significantly greater than contractions in segments without endothelium (Fig. 1). However, coronary segments with endothelium from groups 2 and 3 exhibited hypoxic contractions (75% ± 4% and 80% ± 5%, respectively, of the initial tension, p = 0.0000) that were significantly greater than those of group 1 and group 4 segments with endothelium (15% ± 3% and 18% ± 5%, respectively) (Figs. 1 and 2). This endothelium-dependent hypoxic contraction could be attenuated by pretreatment with L-NMMA (10^-5 mol/L, a nitric oxide synthase inhibitor) in segments from all four groups with endothelium (Fig. 3). The effect of L-NMMA could be blocked with L-arginine (precursor of nitric oxide, 10^-4 mol/L) but not by D-arginine (analog of L-arginine, 10^-4 mol/L) (Fig. 3). L-NMMA, L-arginine, and D-arginine had no effects on the hypoxic responses of reperfused and control segments without endothelium. L-NMMA also did not change the baseline tension (before contraction with prostaglandin F₂) of the reperfused and control segments with or without endothelium.

View larger version (22K): [in this window] [in a new window]   Fig. 1. Isometric tension recordings on endothelium-dependent responses to hypoxia in reperfused (groups 1, 2, and 3) and control (group 4) coronary arterial rings with and without endothelium (n = 12). The coronary rings were suspended in an organ chamber gassed with 95% O2/5% CO2 (PO2 400 ± 10 mm Hg) and contracted with prostaglandin F2 (PGF2 alpha, 2 x 10-6 mol/L). When the contractile response to prostaglandin F2 was stable, hypoxia was induced by changing to a 95% N2/5% CO2 (PO2 35 ± 7 mm Hg) gas mix. After 20 minutes, oxygenation was reintroduced.

View larger version (24K): [in this window] [in a new window]   Fig. 2. Effect of hypoxia (95% N2/5% CO2) on tension in contracted (by prostaglandin F2 2 x 10-6 mol/L) canine coronary arterial rings with endothelium in all four groups. Data are shown as means plus or minus the standard error of the mean and are expressed as percent change from the initial contraction to prostaglandin F2 (zero on y axis). *Significant difference from rings with endothelium among the control rings (group 4).

View larger version (28K): [in this window] [in a new window]   Fig. 3. Effect of hypoxia and drugs on tension in contracted (by prostaglandin F2 2 x 10-6 mol/L) canine coronary arterial rings with endothelium from all four groups. Data are shown as means plus or minus the standard error of the mean and expressed as a percent of the initial contraction to prostaglandin F2. L-Arg, L-Arginine; d-Arg, D-arginine. *Significant difference from control rings (group 4) with endothelium; #significant difference from untreated rings with endothelium in the same group.

Endothelium-independent relaxation.
Increasing concentrations (10^-9 to 10^-4 mol/L) of isoproterenol and sodium nitroprusside induced comparable concentration-dependent relaxation in coronary rings with and without endothelium from all four groups. In all groups, the maximal relaxation induced by isoproterenol or sodium nitroprusside was not altered in coronary artery segments without endothelium, nor did this induction change the sensitivity to relaxation of the vascular smooth muscle (Table III).

2

Scanning electron microscope studies.
In coronary arterial segments from group 1, scanning electron microscope observations showed that the endothelium was continuous and was maintained in an integrated form without significant alterations of surface morphologic features in all specimens examined (Fig. 4, A). The smooth surface of the endothelium was consistently covered with flat endothelial cells. The interendothelial junctions could not be readily delineated (Fig. 4, B). We rarely observed blood cells that adhered to the endothelial surface. These findings were insignificantly different from those in control vessels (group 4). In the scanning electron microscope studies of the vessels from groups 2 and 3, swelling and disruption of the endothelial cells with wide separation of intercellular junctions were frequently demonstrated (Fig. 5, A). Platelet adherence and aggregation on the endothelial surface were constant findings in every specimen investigated (Fig. 5, B and C). In some areas, platelet microthrombi were noted (Fig. 5, B and C). In some instances, extensive disruption of the endothelium was seen (Fig. 5, D). Those surface morphologic changes of the endothelium were consistently noted on vessels from groups 2 and 3.

View larger version (361K): [in this window] [in a new window]   Fig. 4. Scanning electron micrographs of coronary arteries of group 1 animals showing (A) intact surface morphologic features of endothelium and (B) that endothelium is continuous without interruption. White bar indicates length of 30.0 µm.

View larger version (743K): [in this window] [in a new window]   Fig. 5. Scanning electron micrographs of coronary arteries of group 2 and 3 animals. A, Swelling and disruption of the endothelial cells with wide separation of intercellular junctions were frequently demonstrated. B, Platelet adherence and aggregation on the endothelial surface were a constant finding. C, Platelet microthrombi were noted. D, Extensive disruption of the endothelium was seen. These surface morphologic changes of the endothelium were consistently noted on vessels from groups 2 and 3. Black bar indicates length of 30.0 µm.

The major findings of this study were that endothelium-dependent contraction to hypoxia was augmented and the ultrastructure of the coronary endothelium was significantly damaged after cardiac global ischemia and reperfusion (group 3). This augmented endothelium-dependent contraction and the morphologic changes could not be prevented by intermittent infusion of cold crystalloid cardioplegic solution (group 2), but could be prevented by continuous antegrade infusion of warm blood cardioplegic solution (group 1). In addition, smooth muscle contraction in response to potassium ions (voltage dependent) or prostaglandin F₂ (receptor dependent) and smooth muscle relaxation in response to isoproterenol (cyclic adenosine monophosphate–mediated) or sodium nitroprusside (cyclic guanosine monophosphate–mediated) were well preserved after ischemia and reperfusion with (groups 1 and 2) or without (group 3) cardioplegic solution infusion.

The coronary endothelium can produce contracting factor. Rubanyl, ⁹ De Mey, ²⁰ and Vanhoutte ²¹ and their coworkers have demonstrated that in canine coronary and femoral arteries, hypoxic augmentation of contraction was caused by a diffusible factor released by the endothelium, which they termed endothelium-derived contracting factor. We have described endothelium-dependent contraction caused by hypoxia in the human and canine internal thoracic arteries. ^7,12 L-NMMA ²² attenuated this hypoxia-induced endothelium-dependent contraction. ^6,7,12 Free radical scavengers, superoxide dismutase, catalase, or deferoxamine, did not inhibit this hypoxic contraction. ^7,12 However, we found that thromboxane A₂ may be one of the endothelium-derived contracting factors induced by human internal thoracic artery. ^12,23 We also found that this hypoxia-induced endothelium-dependent contraction was enhanced after coronary ischemia and reperfusion ^6,18 and after preservation with hyperkalemic cardioplegic solution. ^13-15 This endothelium-dependent hypoxic contraction was attenuated by L-NMMA, indicating that this hypoxic contraction was induced by an L-arginine–dependent pathway. ^6,7,12-15,18 In this study, we also demonstrated that endothelium-dependent contraction in canine coronary endothelium on exposure to hypoxia after cardiac global ischemia and reperfusion (groups 2 and 3) was augmented and could be attenuated by L-NMMA but not by PD 145065, an antagonist of endothelin receptor A and B. ¹⁹ Such a mechanism would be consistent with our previous findings and indicated that hypoxic endothelium-dependent contraction was induced by an L-arginine–dependent pathway, but not by endothelin, and was augmented after cardiac global ischemia and reperfusion. Augmented endothelium-dependent contraction after coronary ischemia and reperfusion appears to be an important factor in coronary vasospasm after ischemia and reperfusion of coronary arteries. ⁶ The exact roles of nitric oxide and L-arginine in endothelium-dependent hypoxic contraction are not clear. ^6,7,12,13 Further studies are necessary to clarify the underlying mechanism.

Endothelium-dependent contraction to hypoxia was augmented if the coronary arterial segments were preserved continuously in crystalloid cardioplegic solutions with a potassium ion concentration of 16 mmol/L for 1 hour ¹³ or in University of Wisconsin solution with a potassium ion concentration of 125 mmol/L for 6 ¹⁴ or 24 ¹⁵ hours. However, the effect of cardioplegic solution on endothelium-dependent contraction of the coronary artery after cardiac global ischemia and reperfusion is not clear. In the present studies, the endothelium-dependent contraction to hypoxia was augmented after intermittent infusion of crystalloid cardioplegic solution (potassium ion concentration 16 mmol/L, group 2) into the coronary arteries during cardiac global ischemia. Nevertheless, in coronary arteries from group 1 animals, which were infused continuously with warm blood cardioplegic solution (with a potassium ion concentration of 20 mmol/L initially followed by 8 mmol/L), the endothelium-dependent contraction to hypoxia was not significantly different from that of the control group (group 4). Indeed, there was no ischemia, or reperfusion, of the coronary arteries with continuous infusion of warm blood cardioplegic solution into the aorta. In these studies, we demonstrate that continuous infusion of warm blood cardioplegic solution (with a low potassium ion concentration and provision of continuous oxygenation) has the benefit of preventing coronary endothelial dysfunction after ischemia and reperfusion injury.

The ultrastructural change to the endothelium after reperfusion injury is obvious. ^18,24 VanBenthuysen and coworkers ²⁴ demonstrated canine epicardial coronary endothelial ultrastructural injury after ischemia and reperfusion. Our previous study demonstrated injuries to the ultrastructure of endothelium of reperfused coronary arteries by scanning and transmission electron microscopy. ¹⁸ In the present studies, significant surface morphologic changes to the endothelium were found in coronary arteries from group 2 and 3 animals, but not in the coronary endothelium from group 1 arteries. This indicated that warm blood cardioplegia effectively protected the morphologic features of the coronary endothelium from ischemia and reperfusion injury.

Coronary arteries may be exposed to systemic hypoxia in the postoperative period after cardiac operation. ¹³ Coronary arteries may also be exposed to local hypoxia or ischemia as a result of impaired release of endothelium-derived relaxing factor from coronary endothelium after global or local ischemia and reperfusion. ^16,17,25,26 Endothelium-dependent contraction to hypoxia was enhanced after coronary ischemia and reperfusion. The morphologic changes induced platelet adhesion and aggregation, as well as platelet-induced vasoconstriction. A possible consequence of disruption of endothelial cell junctions is the loss of interendothelial transmission of hyperpolarization and, therefore, of a potential vasodilation. Impaired production of endothelium-derived relaxing factor, enhanced production of endothelium-derived contracting factor, and morphologic changes after coronary ischemia and reperfusion will put the coronary arteries at risk for ischemic events such as vasospasm and thrombosis.

In conclusion, cardiac global ischemia and reperfusion with or without protection with intermittent cold crystalloid cardioplegia enhances endothelium-dependent contraction and damages the structure of the coronary endothelium. These kinds of endothelial dysfunction and morphologic changes can be prevented by continuous antegrade infusion of warm blood cardioplegic solution.

Footnotes

From the Divisions of Thoracic and Cardiovascular Surgery,^a Plastic and Reconstructive Surgery,^b and Cardiology,^c Chang Gung Memorial Hospital, Chang Gung Medical College, Taipei, Taiwan, Republic of China.

References

1. Lichtenstein SV, Ashe KA, el Dalati H, Cusimano RJ, Panos A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg 1991;101:269-74.[Abstract]
   
2. Yau TM, Weisel RD, Mickle DAG, et al. Alternative techniques of cardioplegia. Circulation 1992;86(Suppl):II377-84.
   
3. Guyton RA. Warm blood cardioplegia: benefits and risks. Ann Thorac Surg 1993;55:1071-2.[Medline]
   
4. Vanhoutte PM. The endothelium: modulator of vascular smooth-muscle tone. N Engl J Med 1988;319:512-3.[Medline]
   
5. Bassenge E, Busse R. Endothelial modulation of coronary tone. Prog Cardiovasc Dis 1988;30:349-80.[Medline]
   
6. Pearson PJ, Lin PJ, Schaff HV. Production of endothelium-derived contracting factor is enhanced following coronary reperfusion. Ann Thorac Surg 1991;51:788-93.[Abstract]
   
7. Lin PJ, Pearson PJ, Schaff HV. Endothelium-dependent contraction and relaxation of the human and canine internal mammary artery: studies on bypass graft vasospasm. Surgery 1991;110:127-35.[Medline]
   
8. Lin PJ, Pearson PJ, Carrier HV, Schaff HV. Superoxide anion mediates the endothelium-dependent contractions to serotonin by regenerated endothelium. J Thorac Cardiovasc Surg 1991;102:378-85.[Abstract]
   
9. Rubanyi GM, Vanhoutte PM. Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J Physiol 1985;364:45-56.[Abstract/Free Full Text]
   
10. Iqbal A, Vanhoutte PM. Flunarizine inhibits endothelium-dependent hypoxic facilitation in canine coronary arteries through an action on vascular smooth muscle. Br J Pharmacol 1988;95:789-94.[Medline]
    
11. Cartier R, Pearson PJ, Lin PJ, Schaff HV. Time course and extent of recovery of endothelium-dependent contractions and relaxations after direct arterial injury. J Thorac Cardiovasc Surg 1991;102:371-7.[Abstract]
    
12. Pearson PJ, Lin PJ, Evora PRB, Schaff HV. Endothelium-dependent response of human internal mammary artery to hypoxia. Am J Physiol 1993;264:H376-80.[Abstract/Free Full Text]
    
13. Lin PJ, Chang CH, Yao PC, Liu HP, Hsieh HC, Tsai KT. Endothelium-dependent contraction of canine coronary artery is enhanced by crystalloid cardioplegic solution. J Thorac Cardiovasc Surg 1995;109:99-105.[Abstract/Free Full Text]
    
14. Lin PJ, Chang CH, Yao PC, et al. Enhancement of endothelium-dependent contraction of the canine coronary artery by UW solution. Transplantation 1994;58:1323-8.[Medline]
    
15. Lin PJ, Tsai KT, Yao PC, Chang CH. Endothelium-dependent contraction of canine coronary artery is enhanced after 24 hours' preservation with University of Wisconsin solution. Transplant Proc 1995;27:791-2.[Medline]
    
16. Pearson PJ, Schaff HV, Vanhoutte PM. Acute impairment of endothelium-dependent relaxations to aggregating platelets following reperfusion injury in canine coronary arteries. Circ Res 1990;67:385-93.[Abstract/Free Full Text]
    
17. Pearson PJ, Schaff HV, Vanhoutte PM. Long term impairment of endothelium-dependent relaxations to aggregating platelets after reperfusion injury in canine coronary arteries. Circulation 1990;81:1921-7.[Abstract/Free Full Text]
    
18. Lin PJ, Chang CH, Lee YS, et al. Acute endothelial injury following coronary artery bypass grafting. Ann Thorac Surg 1994;58:782-8.[Abstract]
    
19. Wellings RP, Warner TD, Thiemermann C, Cristol JP, Corder R, Vane JR. Vasoconstriction in the rat kidney induced by endothelin-1 is blocked by PD 145065. J Cardiovasc Pharmacol 1993;22(Suppl):S103-6.
    
20. De Mey JG, Vanhoutte PM. Anoxia and endothelium-dependent reactivity of the canine femoral artery. J Physiol 1983;335:65-74.[Abstract/Free Full Text]
    
21. Vanhoutte PM, Auch-Schwelk W, Boulanger C, et al. Does endothelin-1 mediate endothelium-dependent contractions during anoxia? J Cardiovasc Pharmacol 1989;13(Suppl):S124-8.
    
22. Rees DD, Palmer RMJ, Hodson HF, Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol 1989;96:418-24.[Medline]
    
23. Lin PJ, Chang CH, Pearson PJ, et al. Thromboxane A₂ is one mediator of endothelium-dependent hypoxic vasoconstriction in human internal mammary arteries. Ann Thorac Surg 1993;56:97-100.[Abstract]
    
24. VanBenthuysen KM, McMurtry IF, Horwitz LD. Reperfusion after acute coronary occlusion in dogs impairs endothelium-dependent relaxation to acetylcholine and augments contractile reactivity in vitro. J Clin Invest 1987;79:265-74.
    
25. Pearson PJ, Lin PJ, Schaff HV. Global myocardial ischemia and reperfusion impair endothelium-dependent relaxations to aggregating platelets in the canine coronary artery: a possible cause of vasospasm after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1992;103:1147-54.[Abstract]
    
26. Evora PRB, Pearson PJ, Schaff HV. Impaired endothelium-dependent relaxation after coronary reperfusion injury: evidence for G-protein dysfunction. Ann Thorac Surg 1994;57:1550-6.[Abstract]
    

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