Ann Thorac Surg 1997;63:1303-1308
© 1997 The Society of Thoracic Surgeons
Original Article: Cardiovascular
Cardioplegia Preserves Hypoxic Response in Isolated Coronary Arteries but Not in Isolated Hearts
Christine C. Barbé, MS,
Frank F. Diemont, MD,
Pierre M. Bonnet, MD, PhD
UMR Centre National de la Recherche Scientifique 6542, Physiologie des Cellules Cardiaques et Vasculaires, Faculté des Sciences, Tours, France
Accepted for publication November 19, 1996.
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Abstract
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Background. Experiments were designed to determine whether hyperkalemic crystalloid cardioplegic solution alters the hypoxic response of isolated segments of rabbit coronary arteries.
Methods. Coronary arteries were suspended in organ chambers to measure isometric force. We measured the coronary perfusion pressure at a constant flow rate in isolated Langendorff-perfused hearts. Coronary arteries and hearts were preserved in warm (37°C) physiologic solution or in cold (10°C) crystalloid cardioplegic solution.
Results. In all groups of coronary arteries, the acetylcholine-induced relaxation before and after preservation was unchanged (n = 7). Hypoxia (15 mm Hg) caused an endothelium-dependent contraction, the amplitude of which did not change after cardioplegia. Conversely, in coronary arteries preserved in physiologic solution, hypoxic contraction amplitude decreased by 67% ± 17%. In isolated hearts, hypoxic perfusion (15 mm Hg) induced a vasodilation. In all groups, the second hypoxic vasodilation was significantly greater (group 1, first hypoxic perfusion 2.8% ± 2.8%, second hypoxic perfusion 18.2% ± 7.1%; group 2, first hypoxic perfusion 6.8% ± 1.5%, second hypoxic perfusion 29% ± 9%).
Conclusions. The crystalloid cardioplegic solution did not change the hypoxic response in isolated hearts and preserved the endothelium-dependent hypoxic contraction in coronary arteries.
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Introduction
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It is disputed whether the crystalloid preservation solutions used for cardiac operations could damage the endothelial cell layer of cardiac blood vessels [1–3]. It has been demonstrated that crystalloid cardioplegic solution enhanced the endothelium-dependent hypoxic contraction of canine isolated coronary artery [4]. Endothelium-dependent hypoxic contraction has been found in isolated coronary arteries of dogs [5–8], pigs [9], and sheep [8]. The mechanism of this reaction to hypoxia is unknown. Different suggestions include the release of endothelium-derived contracting factor [6, 9], the inhibition of endothelium-derived relaxing factor [10–12], and the synthesis or release of contractile superoxide anions [13, 14]. The physiologic role of the endothelium-dependent hypoxic contraction remains to be explained. It could be a major factor involved in the mechanism of the vasospasm [15, 16], which would then be favored during myocardial protection with crystalloid solutions. In isolated hearts hypoxia produces a vasodilation [17–19] that may be attributable to the role of adenosine [20–22], involve adenosine triphosphatase-sensitive potassium channels of vascular smooth muscle [17, 18], or the influence of endothelium-dependent mediators like nitric oxide [10, 23].
We studied the effects of cardioplegia solutions on the hypoxic response of isolated coronary arteries and compared them with hypoxic coronary vasodilation on the isolated heart. In particular, we tested the specific role of the endothelium in the modification of the hypoxic response induced by cardioplegia.
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Material and Methods
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Animal Preparation
ISOLATED CORONARY ARTERIES.
Rabbits weighing 1.5 to 2 kg were given heparin (3,500 IU) by intraperitoneal injection and sacrificed by cervical dislocation. After thoracotomy, the heart was quickly excised and placed in a cold (4°C) calcium-free physiologic saline solution with the following composition (mmol/L): NaCl, 138.6; KCl, 5.4; MgCl2, 1.2; NaH2PO4, 0.33; HEPES, 10; and glucose, 11. The pH was adjusted to 7.4 with NaOH. The coronary arteries were prepared as segments (4 to 5 mm in length and 500 to 1,000 µm in diameter) from the left circumflex coronary artery taking care not to damage the luminal surface. In some rings the endothelium was mechanically removed by rubbing the intima. The presence or absence of functional endothelium was tested by the response to increasing doses of acetylcholine in rings precontracted by histamine. Relaxation occurred only in preparations with intact endothelium [10]. Each segment was suspended by two stainless steel wires passed through its lumen. One wire was anchored to the bottom of the organ chamber and the other was connected to a force transducer (Kent TRN 001-220) for measurement of isometric force. Segments of coronary artery with or without endothelium from the same animal were suspended in four organ chambers (6 mL) containing normoxic physiologic saline solution (PSS) at 37°C with the following composition (mmol/L): NaCl 138.6; KCl 5.4; MgCl2 1.2; NaH2PO4 0.33; CaCl2 1.8; HEPES 10; glucose 11. The pH was adjusted to 7.4 with NaOH. Before experiments, rings were preloaded (2 g) and allowed to equilibrate for 120 minutes at their optimal resting tension. In preliminary experiments a solution containing 40 mmol/L extracellular potassium was found to provide a steady-state contraction under normoxia and the optimal reaction of isolated rings to hypoxia. Potassium solution composition was as follows (mmol/L): NaCl, 104; KCl, 40; MgCl2, 1.2; NaH2PO4, 0.33; CaCl2, 1.8; HEPES, 10; and glucose, 11. The pH was adjusted to 7.4 with NaOH. Normoxic solution was equilibrated with 20% O2–80% N2 (partial pressure of oxygen, 150 mm Hg). Hypoxia was induced by switching to a potassium solution equilibrated with 100% N2. The partial pressure of oxygen of the hypoxic solution measured with a Clark electrode was 15 mm Hg. Cardioplegic exposure was obtained by placing the rings in a crystalloid cardioplegic solution that contained the following (mmol/L): NaCl, 147; KCl, 20; trihydroxymethylaminomethan, 10; MgCl2, 16; CaCl2, 1.8; and procaine chlorhydrate, 0.001, and was maintained at 10° C.
ISOLATED HEART PREPARATION.
A rabbit weighing 1.5 to 2 kg was killed by cervical dislocation, the chest was opened, and 0.2 mL of heparin was injected into the right ventricle. The heart was quickly excised and immersed in a beaker containing PSS at room temperature. The heart was mounted through the ascending aorta onto a perfusion apparatus and submerged in a small temperature-controlled organ bath at 37°C. The heart beat spontaneously without electrical pacing. Using a peristaltic pump, the heart was perfused with nonrecirculating PSS preheated to 37°C, at a constant flow rate of 26 mL/min. The PSS was equilibrated with 20% O2–80% N2 (normoxic PSS, partial pressure of oxygen 150 mm Hg) in a reservoir. Coronary perfusion pressure (CPP) was measured continuously at a T junction of the glass cannula to which the heart was attached through the aorta. The CPP was measured with a transducer (Gould P 23 D) and calibrated for each experiment and recorded on a pen recorder (Beckman R 612). Hypoxia (partial pressure of oxygen, 15 mm Hg) was induced by switching the perfusion to an identical PSS solution that had been equilibrated with 100% N2 in a second reservoir. For "cardioplegia," hearts were cooled both by decreasing the organ bath temperature to 10°C and by perfusion of crystalloid cardioplegic solution at 10°C. The hearts were rewarmed by perfusion of PSS at 37°C and by increasing the organ bath temperature.
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).
Protocols
ISOLATED CORONARY ARTERIES.
After 120 minutes of equilibration, rings were superfused with hyperkalemic solution (40 mmol/L) for 15 minutes, then exposed to hypoxic potassic solution for 15 minutes followed by 15 minutes of normoxic solution. The four rings were removed and for 2 hours, two were kept in PSS at 37°C (group 1) and two were placed in crystalloid cardioplegia solution at 10°C (group 2). The rings were again suspended in the organ chambers and the same hypoxic protocol was repeated (Fig 1A
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Fig 1. . Schematic representation of the experimental protocols. (A) Experimental protocol of the effects of cardioplegia on hypoxic response of isolated coronary arteries. (B) Experimental protocol of the effects of cardioplegia on hypoxic response of isolated heart. (CARDIO = cardioplegia; HYPO = hypoxic condition; K = potassic solution; NOR = normoxic condition; PSS = physiologic saline solution; T°C = variation of temperature.)
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ISOLATED HEART.
Baseline tension was obtained by 30 minutes of PSS perfusion at 37°C. Two experimental groups were designated. In group 1, hearts were exposed to hypoxia, allowed to recover in normoxia, perfused with normoxic PSS at 37°C for 2 hours, and then reexposed to hypoxia. In group 2, successive exposures to hypoxia were separated by 2 hours in cardioplegia. For both groups exposure to hypoxia consisted of being perfused with hypoxic PSS at 37°C for 7 minutes followed by perfusion with normoxic PSS at 37°C for 15 minutes. Cardioplegia consisted of cooling the heart to 10°C and over a 2-hour period perfusing 50 mL of cold crystalloid cardioplegic solution for 2 minutes every 30 minutes. Between applications of cardioplegic solution the hearts were not perfused. At the end of 2 hours in cardioplegic solution the hearts were rewarmed for 15 minutes and to reestablish basal CPP, they were perfused for 30 minutes with normoxia PSS at 37°C.
Drugs
Acetylcholine and histamine were obtained from Sigma and the crystalloid cardioplegic solution came from the "Pharmacie Centrale des Hôpitaux de Paris," Paris, France.
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Statistical Analysis
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The variation of pressure during hypoxia was estimated as follows: % = (Diastolic pressure just before hypoxia - Minimal diastolic pressure during hypoxia)/Diastolic pressure just before hypoxia. Isolated coronary artery contraction and relaxation are expressed as percentage of potassium contraction in normoxia.
All values were expressed as mean ± standard error of the mean. Statistical evaluation of data in the same groups was performed by paired Student's t test analysis. Analysis of variance test was used to compare groups 1 and 2. Differences were considered significant when the p value was less than 0.05.
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Results
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Isolated Coronary Arteries
After equilibration, 11 rings perfused with normal PSS were superfused with hypoxic PSS during 15 minutes. Hypoxia did not affect the resting tone (Fig 2A). On the other hand, in rings that were contracted by superfusion with hyperpotassium solution (40 mmol/L K+o), hypoxia induced a further contraction that developed in about 2 minutes, reached a maximum in 5 minutes, and then decreased slightly. Sometimes, we could see a steady-state but often this hypoxic contraction declined to the level seen in normoxic potassic solution (Fig 2B). The hypoxic contraction was reversible. Exposed to three successive hypoxic periods separated by 10 minutes of normoxia, we never observed either potentiation or inhibition of the hypoxic responses of isolated coronary artery rings.
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Fig 2. . Isometric tension recording of isolated rabbit coronary artery rings. (A) The preparation was exposed to hypoxic physiologic saline solution (PSS). No effect was observed. (B) The preparation was contracted with 40 mmol/L hyperpotassium solution (K 40 mM). Hypoxic hyperpotassium solution induced a contraction of about 10 mN.
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The magnitude of potassic contraction in rings with or without endothelium (tested by the response to acetylcholine, see Material and Methods) was not significantly different (7.4 ± 2.1 mN and 7.8 ± 1.8 mN, respectively. We conclude that the mechanical removal of the endothelium did not damage the smooth muscle medial layer of the rings. Hypoxia induced a contraction of 34.8% ± 8.3% in rings with endothelium (n = 6), but a relaxation of 37% ± 4.3% in rings without endothelium (n = 6) (Fig 3). Similar results were obtained in rings precontracted by histamine (10-5 mol/L), with intact endothelium, hypoxia induced contraction of 48% ± 7% and a relaxation of 26% ± 5% without endothelium (n = 8). Indomethacin (10-5 mol/L) did not alter the hypoxic response in rings with or without endothelium (n = 4; data not shown). These results demonstrated that the hypoxic contraction is independent of the mechanism of precontraction (voltage activation with hyperpotassium and receptor stimulation with histamine) and also independent of prostaglandin metabolism. Moreover, they show that hypoxic contraction is dependent on an intact endothelium.
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Fig 3. . Hypoxic contraction of isolated rabbit coronary artery rings with (A) or without (B) endothelium (n = 6). Data are shown as means ± standard error of the mean and expressed as percent change of an initial contraction evoked by 40 mmol/L potassium solution.
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EFFECTS OF 2 HOURS OF CARDIOPLEGIA ON ISOLATED RINGS.
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The effects of preservation for 2 hours in cardioplegic or normal PSS solutions were first tested on control parameters of isolated rings of coronary artery. The magnitude of the contraction evoked by histamine was not different before and after the preservation periods. No difference was observed in acetylcholine-induced relaxation of the histamine contraction whatever the preservation procedure (n = 7): the doses causing 50% relaxation were 1.7 x 10-6 ± 6 x 10-7 and 1.2 x 10-6 ± 1.4 x 10 -7 with PSS and 6.6 x 10-7 ± 7.9 x 10-8 and 1.6 x 10-6 ± 3.1 x 10 -7 with cardioplegia before and after 2 hours of preservation, respectively. The magnitude of the potassium-induced contractions before (8.1 ± 2 mN) and after (7.9 ± 1.8 mN) preservation was unchanged (n = 7).
The amplitude of hypoxia-induced contraction in rings precontracted in hyperpotassium solution was not significantly different after 2 hours of preservation in crystalloid cardioplegic solution (4.1 ± 0.3 mN before and 4.5 ± 0.3 mN after preservation) (Fig 4). On the other hand, after 2 hours of preservation in normal PSS, the amplitude of 2 hours of preservation in normal PSS, the amplitude of the contraction induced by hypoxia was decreased by 67% ± 17% (Fig 4). These results suggest that cardioplegia preserved the reaction of isolated rings of coronary artery to hypoxia.
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Fig 4. . Isometric tension recording of isolated rabbit coronary artery rings, exposed to 40 mmol/L potassium normoxic then hypoxic solution, before (A) and after (B) 2 hours of preservation in either saline solution (PSS) or crystalloid cardioplegic solution (Cardioplegia). Compared with the response before preservation (A), in both cases hypoxic contraction amplitude was less important after preservation (B). However, the decrease was more marked in the predominant ring kept in saline solution (upper traces) compared with that in crystalloid solution (lower traces).
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ISOLATED HEART.
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Exposed to hypoxia, CPP decreased in less than 1 minute. Because the coronary blood flow was maintained constant this decrease corresponded to a coronary vasodilation. In all experiments this vasodilation reversed in about 10 minutes with perfusion of normoxic solution (Fig 5).
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Fig 5. . Effects of hypoxia on rabbit coronary artery perfusion pressure before (A) and after (B) cardioplegia. The records were from the same heart. The thickness of traces was the result of the pressure variation between systole (upper limit of trace) and diastole (lower limit of trace), which cannot be seen on this compressed time scale. (A) We observed a slight reduction in coronary perfusion pressure (about 4 mm Hg), which represents a vasodilation. (B) The vasodilation was more important (about 16 mm Hg). There are clear differences between the traces shown in (A) and (B). In (A), before cardioplegia, it was homogeneous, whereas in (B), after cardioplegia, it was clearly irregular.
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In the control group (group 1), the second hypoxic vasodilation observed after 2 hours of preservation in PSS was significantly greater than the vasodilation attributable to the first hypoxic challenge (paired t test, p = 0.03) (Table 1). The basal pressure measured just before the hypoxic challenge remained constant during the experiments (paired t test, p = 0.2, not significant).
In the cardioplegic group (group 2), exposure to cardioplegic solution induced cardiac arrest. After cardioplegia, during the rewarming period, in about 40% of the hearts we observed abnormal beats and rarely ventricular fibrillation. In these cases the experiments were stopped (n = 7). In this group the basal pressure before and after 2 hours of cardioplegia had increased significantly (paired t test, p = 0.002). The second hypoxic vasodilation, observed after 2 hours in cardioplegia, was significantly greater (paired t test, p = 0.04) (see Table 1
). The kinetic of the vasodilation was different after cardioplegia (Fig 5B). Comparative analysis of hypoxic vasodilation recorded in groups 1 and 2 did not show a significant difference (analysis of variance test, p = 0.6).
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Comment
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In isolated rabbit coronary artery we have shown that it is necessary to precontract the rings to observe a hypoxic contraction. Contraction, rather than relaxation, as a response to hypoxia was dependent on the presence of an intact endothelium, as has been show elsewhere [6, 8–10, 15, 16].
Two hours of preservation in cardioplegic solution did not modify the magnitude of the contractions evoked by potassium contraction, or histamine. The endothelium-dependent relaxation evoked by acetylcholine was also kept intact suggesting that cardioplegia did not impair liberation of the endothelium-dependent relaxing factor. These results are in agreement with Evora and colleagues [24] and confirm that potential endothelium damage observed by others [2, 3, 25, 26] could be attributable to a different mechanism than cardioplegia itself. We also show that after 2 hours of preservation, hypoxic contraction strongly decreased in PSS but it was not altered in cardioplegic solution. This suggests that either crystalloid solution or hypothermia prevented the time-dependent decline of the hypoxic response. Lin and co-workers [4] showed that cardioplegia increases hypoxic contraction. However, in their studies, the hypoxic contraction of vascular segments of the control group was realized immediately after the relaxing adaptation period and other rings were preserved for 60 minutes, before being submitted to hypoxia. The time-dependent decrease of the hypoxic contraction under control conditions did not seem to be taken into account in their studies.
We have to emphasize that large diameter rings obtained from the left circumflex coronary artery are representative of only part of the coronary arterial tree. The resistive coronary arterioles exclusively relax under hypoxia and this might counteract the hypoxic contraction observed in the larger conductive vessels.
In isolated perfused rabbit hearts hypoxia induced a coronary artery vasodilation. This phenomenon has been well described [25], but the mechanism is still being debated. The most interesting finding of our experiments was the potentiation of the hypoxic vasodilation after 2 hours of preservation. This was observed whether PSS or cardioplegic solution was used as preservation solution. These results suggest that it was the time period and not the solution that was responsible. The requirement for this delay is emphasized by the observation that exposure to three successive hypoxic periods, each separated by only 10 minutes of normoxia, never potentiated the hypoxic response (data not shown). We suggest that the first hypoxic exposure triggered a sort of vascular preconditioning that potentiated the second hypoxic response.
It has been suggested that hyperkalemic cardioplegia solutions impair production of endothelium-derived relaxing factor [2, 3]. Our results in the isolated heart showing the absence of any specific effect of hyperkalemic cardioplegic solution on hypoxic vasodilation might suggest that this hypoxic vasodilation was not dependent on endothelium-derived relaxing factor. However, in isolated arteries Evora and colleagues [24] demonstrated that cardioplegic solution or hypothermia did not impair the endothelium and demonstrated that endothelium-derived relaxing factor release evoked by acetylcholine was not changed by 2 hours of preservation.
A significant increase of the basal CPP was observed exclusively after crystalloid preservation. The high concentration of potassium ions in the cardioplegic solution could explain this observation. Potassium ions induce contraction of all muscular structures of the heart. Potassium-evoked vasoconstriction could be associated with vessel collapse caused by cardiomyocyte contraction, which would explain the observed CPP increase. In separate experiments cardiac wall tension was recorded using a transducer fixed on the apex of the heart. We found that cardioplegia and hypoxia induced an increase in wall tension (n = 3; data not shown). Froldi and colleagues [27], studying the effects of high extracellular potassium concentration on hypoxia-induced atrial activity and metabolic changes in isolated rat atria, also observed an increase of diastolic tension and a decrease of contractile function.
In our protocol cardiac arrest was observed and alternating periods of perfusion and nonperfusion were applied only when crystalloid solution was used for preservation. Previous investigations have already demonstrated injuries to the endothelium during surgical ischemia [1, 28]. The barotrauma or shear stress induced by the alternating perfusion and nonperfusion periods during cardioplegia (repeated perfusion every 30 minutes separated by cardiac arrest) might play a role. Nakanishi and associates [29] suggested that the endothelium dysfunction observed after reperfusion may be a specific event of reperfusion injuries [30, 31]. Sawatari and colleagues [32] also concluded that the high shear stress and pressure during reperfusion impaired the endothelial function by different mechanisms. Using NNA, a specific blocker of nitric oxide, Van Beckerath and colleagues [17] abolished the increase of CPP. These studies strongly suggest that flow variation or barotrauma might explain the basal increase of CPP observed after cardioplegia.
In conclusion, we show that cardioplegia did not change the hypoxic vasodilation of the coronary artery in the isolated heart but protected the isolated vessels' hypoxic contraction. Whatever is the explanation of this difference of hypoxic response between isolated heart and vessels, it has to be noted that cardioplegia only affects the hypoxic contraction of isolated vessels. This suggests that cardioplegia directly influences the endothelium-dependent hypoxic contraction mechanism. Because cardioplegia in isolated arteries did not change voltage, or receptor-dependent contraction, or the release of endothelium-derived relaxing factor, we suggest that the crystalloid solution used for cardioplegia does not favor vasospasm.
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Acknowledgments
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This study was supported by operating grants from the Fondation pour la Recherche Médicale. We thank Pr Didier Garnier, Dr Claire Malécot, and Christophe Vandier for helpful comments on the manuscript, and Dr Ian Findlay for language corrections.
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Footnotes
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Address reprint requests to Dr Bonnet, Laboratoire de Physiologie des Cellules Cardiaques et Vasculaires, UMR CNRS 6542, Faculté des Sciences, Parc de Grandmont 37200, Tours, France.
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References
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|---|
- Pearson PJ, Lin PJ, Schaff HV. Global myocardial ischemia and reperfusion impair endothelium-dependent relaxations to aggregating platelets in the canine coronary artery. J Thorac Cardiovasc Surg 1992;103:1147–54.[Abstract]
- Saldanha C, Hearse D. Coronary vascular responsiveness to 5-hydroxytryptamine before and after infusion of hyperkalemic crystalloid cardioplegic solution in the rat heart. J Thorac Cardiovasc Surg 1989;98:783–7.[Abstract]
- Mankad PS, Chester AH, Yacoub MH. Role of potassium concentration in cardioplegic solutions in mediating endothelial damage. Ann Thorac Surg 1991;51:89–93.[Abstract]
- Lin PJ, Chang CH, Yao PC, Liu HP, Hsieh HC, Tsai KT. Endothelium-dependent contraction of canine coronary is enhanced by crystalloid cardioplegic solution. J Thorac Cardiovasc Surg 1995;109:99–105.[Abstract/Free Full Text]
- Vanhoutte PM. The endothelium modulator of vascular smooth muscle tone. N Engl J Med 1988;319:512–13.[Medline]
- 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]
- Furchgott RF. Role of endothelium in responses of vascular smooth to drugs. Circ Res 1983;53:557–73.[Free Full Text]
- Borda LJ, Shuchleib R, Henry PD. Hypoxic contraction of isolated canine coronary artery. Mediation by potassium-dependent exocytosis of norepinephrine. Cir Res 1980;46:870–9.[Abstract/Free Full Text]
- Rubanyi GM, Vanhoutte PM. Hypoxia releases a vasoconstriction substance from the canine vascular endothelium. J Physiol 1985;364:45–56.[Abstract/Free Full Text]
- Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;299:373–6.
- Muramatsu M, Iwama Y, Shimizu K, et al. Hypoxia-elicited contraction of aorta and coronary artery via removal of endothelium-derived nitric oxide. Am J Physiol 1992;263:H1339–47.[Abstract/Free Full Text]
- Yang XP, Wu ZJ, Xu YF, et al. Effects of inhibitor of endothelium-derived relaxing factor on hypoxic contraction of isolated pig coronary artery. Acta Pharmacologica Sinica 1994;15:323–6.[Medline]
- Pearson PJ, Lin PJ, Schaff HV. Production of endothelium-derived contracting factor is enhanced after coronary reperfusion. Ann Thorac Surg 1991;51:788–93.[Abstract]
- Lin PJ, Pearson PJ, Cartier R, Schaff HV. Superoxide anion mediates the endothelium-dependent contractions to serotonine by regenerated endothelium. J Thorac Cardiovasc Surg 1991;102:378–85.[Abstract]
- Rubanyi G, Paul RJ. Two distinct effects of oxygen on vascular tone in isolated porcine coronary arteries. Circ Res 1985;56:1–10.[Abstract/Free Full Text]
- Kwan YW, Wadsworth RM, Kane KA. Effects of hypoxia on the pharmacological responsiveness of isolated coronary rings from the sheep. Br J Pharmacol 1989;96:849–56.[Medline]
- Von Beckerath N, Cyrys S, Dischner A, Daut J. Hypoxic vasodilatation in isolated, perfused guinea-pig heart: an analysis of the underlying mechanisms. J Physiol 1991;442:297–319.[Abstract/Free Full Text]
- Daut J, Maier-Rudolph W, Von Beckerath N, Mehrke G, Gunther K, Goedel-Meinen L. Hypoxic dilatation of coronary arteries is mediated by ATP-sensitive potassium channels. Science 1990;247:1341–4.[Abstract/Free Full Text]
- Conway MA, Nelson MT, Brayden JE. 2-Deoxyglucose-induced vasodilation and hyperpolarization in the coronary artery are reversed by glibenclamide. Am J Physiol 1994;266:H1322–6.[Abstract/Free Full Text]
- Berne R. Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. Am J Physiol 1963;204:317–22.[Abstract/Free Full Text]
- Nakhostine N, Lamontagne D. Adenosine contributes to hypoxia-induced vasodilation through ATP-sensitive K+ channel activation. Am J Physiol 1993;265:H1289–93.[Abstract/Free Full Text]
- Wei HM, Kang YH, Merrill GF. Canine coronary vasodepressor to hypoxia are abolished by 8-phenyltheophylline. Am J Physiol 1989;257:H1043–8.[Abstract/Free Full Text]
- Gräser T, Vanhoutte PM. Hypoxic contraction of canine coronary arteries: role of endothelium and cGMP. Am J Physiol 1991;261:H1769–77.[Abstract/Free Full Text]
- Evora PRB, Pearson PJ, Schaff HV. Crystalloid cardioplegia and hypothermia do not impair endothelium-dependent relaxation or damage vascular smooth muscle of epicardial coronary arteries. J Thorac Cardiovasc Surg 1992;104:1365–74.[Abstract]
- Cartier R, Dagenais F, Hollmann C, Carrier M, Pelletier LC. The role of preservation solutions in coronary endothelial damage during cold storage. Transplant 1993;56:997–1000.[Medline]
- Chiavarelli R, Macchiarelli G, Familiari G, et al. Ultrastructural changes of coronary artery endothelium induced by cardioplegic solutions. J Thorac Cardiovasc Surg 1989;37:151–7.
- Froldi G, Pandolfo L, Chinellato A, Ragazzi E, Caparrotta L, Fassina G. Protection of atrial function in hypoxia by high potassium concentration. Gen Pharmacol 1994;25:401–7.[Medline]
- Nilsson FN, Miller VM, Vanhoutte PM, McGregor CGA. Methods of cardiac preservation alter the function of the endothelium in porcine coronary arteries. J Thorac Cardiovasc Surg 1991;102:923–30.[Abstract]
- Nakanishi K, Zhao ZQ, Vinten-Johansen J, Lewis JC, McGee S D, Hammon JH. Coronary artery endothelial dysfunction after global ischemia, blood cardioplegia, and reperfusion. Ann Thorac Surg 1994;58:191–9.[Abstract]
- Sellke FW, Shafique T, Schoen FJ, Weintraub RM. Impaired endothelium-dependent coronary microvascular relaxation after cold potassium cardioplegia and reperfusion. J Thorac Cardiovasc Surg 1993;105:52–8.[Abstract]
- Sellke FW, Shafique T, Johnson RG, et al. Blood and albumin cardioplegia preserve endothelium-dependent microvascular responses. J Thorac Cardiovasc Surg 1993;55:977–85.
- Sawatari K, Kadoba K, Bergner KA, Mayer JE. Influence of initial reperfusion pressure after hypothermic cardioplegic ischemia on endothelial modulation of coronary tone in neonatal lambs. J Thorac Cardiovasc Surg 1991;101:777–82.[Abstract]
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Abstract
Introduction
