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nourished by collaterals develop markedly abnormal vascular reactivity such as by impaired endothelium-dependent vascular relaxations and enhanced constrictions to vasopressin.48 Possible mechanisms of this impaired microvascular endothelium-dependent relaxation in the collateral-dependent region may include changes in shear stress, pulsatile flow in the collateral-dependent microvasculature or intracellular calcium levels. Such changes may cause disturbance in microvascular tone during a disease state.18
It has been also found that treatment of collateral-dependent vessels with angiogenic growth factors may enhance endothelium-dependent relaxation, in addition to improving other aspects of cardiac performance. In patients suffering from disease not amenable to current intervention techniques (e.g. surgical coronary grafting or percutaneous techniques), direct treatment with angiogenic factors can theoretically be the basis for a clinical improvement. Several studies have demonstrated that therapeutic angiogenic interventions, in the setting of chronic ischemia, are associated with a marked improvement in myocardial function, myocardial perfusion and endothelial-dependent vasodilation within the area supplied by collaterals.65−67 These studies used growth factors such as VEGF, FGF-1 or FGF-2 placement in the perivascular area. Possible mechanisms through which these factors act include FGF-2- and VEGF-induced release of NO, which improves collateral perfusion and decreases tissue ischemia.68 In addition, it has also been shown that during periods of chronic ischemia there occurs an upregulation of FGF-2 and VEGF receptors. This finding is consistent with results showing that after administration of growth factors, endothelial-dependent relaxation occurs in the collateral-dependent region but not in the myocardium perfused via original vessels.69 Also, these growth factors may stimulate the release of bone marrow-derived EPCs which promote collateral growth and endothelial function at the treated sites.
6. The Coronary Microcirculation in Hypertophic States
Clinically, patients suffering from ventricular hypertrophy often complain of angina-like symptoms. Animal and human studies have
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demonstrated that cardiac hypertrophy causes a reduction in the maximal capacity of the coronary circulation to dilate in response to either reactive hyperemia or pharmacological stimuli.5,61,70 One possible cause for this abnormal response may be caused by a mismatch between the elevated myocardial mass and relatively reduced coronary microcirculation. Peak flow normalized to myocardial mass may be reduced because of this relative paucity of coronary arterioles — since as the myocardium hypertrophies, the coronary resistance circulation may not increase adequately to keep pace with the larger muscle mass (see Chapter 9). Another possible mechanism of impaired vasodilator responses may be explained by endothelial dysfunction since many of the diseases associated with myocardial hypertrophy are also associated with a loss of endothelial NO production.
In normal hearts there is a linear relationship between the diameter of an epicardial coronary artery and the mass of myocardium perfused. Interestingly, epicardial coronary arteries do not enlarge appropriately as the myocardium hypertrophies such that for any diameter coronary artery, the amount of myocardium perfused is increased up to twofold. This phenomenon is particularly relevant in the presence of a coronary stenosis where a small lesion that is otherwise considered minimal, becomes flow limiting in a hypertrophic state.
7. Summary
This chapter provided an overview of some of the newer concepts regarding physiological, pathophysiological, and pharmacological control of the coronary microcirculation. It also emphasized that the properties of peripheral vessels cannot be extrapolated to the coronary circulation. Similarly, properties of one size or class of coronary microvessel cannot be generalized. Clearly, there has been dramatic changes in the technology used during older studies compared to the more recent ones. While we attempted to present studies that have directly examined the coronary microvessels using some of the newer technology (in vitro preparations or in situ observations), it was also important to present classical studies of the intact coronary circulation performed in intact animals or isolated hearts. Newer research questions
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have necessitated the use of more basic techniques, including cell culture and molecular biological approaches. Recent development has been the ability to make many in vivo measurements of coronary hemodynamics in human subjects in the catheterization laboratory, thus obviating the need for large expenses for large animal flow studies. As the field of vascular biology continues to grow, it will remain necessary for us to validate the observations seen during basic studies in the intact circulation found in our patients so this can be translated to the clinical setting.
References
1.Furchgott RF, Zawadzki JV (1980). The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288: 373–376.
2.Komaru T, Kanatsuka H, Shirato K (2000). Coronary microcirculation: physiology and pharmacology. Pharmacol Ther 86: 217–261.
3.Feigl EO (1983). Coronary physiology. Physiol Rev 63: 1–205.
4.Hoffman JI (1987). Transmural myocardial perfusion. Prog Cardiovasc Dis 29: 429–464.
5.Marcus ML (1983). The Coronary Circulation in Health and Disease (McGraw-Hill, New York).
6.Schaper W (1979). The Pathophysiology of Myocardial Perfusion (Elsevier/NorthHolland Biomedical Press, Amsterdam/New York).
7.Nellis SH, Liedtke AJ, Whitesell L (1981). Small coronary vessel pressure and diameter in an intact beating rabbit heart using fixed-position and free-motion techniques. Circ Res 49: 342–353.
8.Chilian WM, Eastham CL, Marcus ML (1986). Microvascular distribution of coronary vascular resistance in beating left ventricle. Am J Physiol 251: H779–H788.
9.Chilian WM, Layne SM, Klausner EC, Eastham CL, Marcus ML (1989). Redistribution of coronary microvascular resistance produced by dipyridamole. Am J Physiol 256: H383–H390.
10.Chilian WM (1991). Microvascular pressures and resistances in the left ventricular subepicardium and subendocardium. Circ Res 69: 561–570.
11.Fujii M, Nuno DW, Lamping KG, Dellsperger KC, Eastham CL, Harrison DG (1992). Effect of hypertension and hypertrophy on coronary microvascular pressure. Circ Res 71: 120–126.
12.Jones CJ, Kuo L, Davis MJ, Chilian WM (1995). Regulation of coronary blood flow: coordination of heterogeneous control mechanisms in vascular microdomains. Cardiovasc Res 29: 585–596.
13.Murad F (1986). Cyclic guanosine monophosphate as a mediator of vasodilation.
J Clin Invest 78: 1–5.
308 B. Ramlawi et al.
14.Corson MA, James NL, Latta SE, Nerem RM, Berk BC, Harrison DG (1996). Phosphorylation of endothelial nitric oxide synthase in response to fluid shear stress. Circ Res 79: 984–991.
15.Venema RC, Sayegh HS, Arnal JF, Harrison DG (1995). Role of the enzyme calmodulin-binding domain in membrane association and phospholipid inhibition of endothelial nitric oxide synthase. J Biol Chem 270: 14705–14711.
16.Michel JB, Feron O, Sacks D, Michel T (1997). Reciprocal regulation of endothelial nitric-oxide synthase by Ca2+-calmodulin and caveolin. J Biol Chem 272: 15583–15586.
17.Myers PR, Minor RL, Jr, Guerra R, Jr, Bates JN, Harrison DG (1990) Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature 345: 161–163.
18.Uematsu M, Ohara Y, Navas JP, Nishida K, Murphy TJ, Alexander RW, Nerem RM, Harrison DG (1995). Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 269: C1371–C1378.
19.Arnal JF, Yamin J, Dockery S, Harrison DG (1994). Regulation of endothelial nitric oxide synthase mRNA, protein, and activity during cell growth. Am J Physiol 267: C1381–C1388.
20.McQuillan LP, Leung GK, Marsden PA, Kostyk SK, Kourembanas S (1994). Hypoxia inhibits expression of eNOS via transcriptional and posttranscriptional mechanisms. Am J Physiol 267: H1921–H1927.
21.Duncker DJ, van Zon NS, Ishibashi Y, Bache RJ (1996). Role of K+ ATP channels and adenosine in the regulation of coronary blood flow during exercise with normal and restricted coronary blood flow. J Clin Invest 97: 996–1009.
22.Boatwright RB, Downey HF, Bashour FA, Crystal GJ (1980). Transmural variation in autoregulation of coronary blood flow in hyperperfused canine myocardium. Circ Res 47: 599–609.
23.Pohl U, Holtz J, Busse R, Bassenge E (1986). Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 8: 37–44.
24.Drexler H, Zeiher AM, Wollschlager H, Meinertz T, Just H, Bonzel T. (1989). Flow-dependent coronary artery dilatation in humans. Circulation 80: 466–474.
25.Jimenez AH, Tanner MA, Caldwell WM, Myers PR (1996). Effects of oxygen tension on flow-induced vasodilation in porcine coronary resistance arterioles.
Microvasc Res 51: 365–377.
26.Kuo L, Chilian WM, Davis MJ (1991). Interaction of pressureand flowinduced responses in porcine coronary resistance vessels. Am J Physiol 261: H1706–H1715.
27.Young MA, Knight DR, Vatner SF (1987). Autonomic control of large coronary arteries and resistance vessels. Prog Cardiovasc Dis 30: 211–234.
28.Wang SY, Friedman M, Johnson RG, Weintraub RM, Sellke FW (1994). Adrenergic regulation of coronary microcirculation after extracorporeal circulation and crystalloid cardioplegia. Am J Physiol 267: H2462–H2470.
29.Lamping KG, Chilian WM, Eastham CL, Marcus ML (1992). Coronary microvascular response to exogenously administered and endogenously released acetylcholine. Microvasc Res 43: 294–307.
Regulation of Coronary Vascular Tone and Microvascular Physiology |
309 |
30.Hammarstrom AK, Parkington HC, Coleman HA (1995). Release of endothelium-derived hyperpolarizing factor (EDHF) by M3 receptor stimulation in guinea-pig coronary artery. Br J Pharmacol 115: 717–722.
31.Sellke FW, Dai HB (1993). Responses of porcine epicardial venules to neurohumoral substances. Cardiovasc Res 27: 1326–1332.
32.Van Winkle DM, Feigl EO (1989). Acetylcholine causes coronary vasodilation in dogs and baboons. Circ Res 65: 1580–1593.
33.Gu J, Polak JM, Adrian TE, Allen JM, Tatemoto K, Bloom SR (1983). Neuropeptide tyrosine (NPY) — a major cardiac neuropeptide. Lancet 1: 1008–1010.
34.Clarke JG, Davies GJ, Kerwin R, Hackett D, Larkin S, Dawbarn D, Lee Y, Bloom SR, Yacoub M, Maseri A (1987). Coronary artery infusion of neuropeptide Y in patients with angina pectoris. Lancet 1: 1057–1059.
35.Maturi MF, Greene R, Speir E, Burrus C, Dorsey LM, Markle DR, Maxwell M, Schmidt W, Goldstein SR, Patterson RE (1989). Neuropeptide-Y. A peptide found in human coronary arteries constricts primarily small coronary arteries to produce myocardial ischemia in dogs. J Clin Invest 83: 1217–1224.
36.Mione MC, Ralevic V, Burnstock G (1990). Peptides and vasomotor mechanisms.
Pharmacol Ther 46: 429–468.
37.Kuo L, Davis MJ, Chilian WM (1988). Myogenic activity in isolated subepicardial and subendocardial coronary arterioles. Am J Physiol 255: H1558–H1562.
38.Davis MJ (1988). Microvascular control of capillary pressure during increases in local arterial and venous pressure. Am J Physiol 254: H772–H784.
39.Kuo L, Chilian WM, Davis MJ (1990). Coronary arteriolar myogenic response is independent of endothelium. Circ Res 66: 860–866.
40.Narayanan J, Imig M, Roman RJ, Harder DR (1994). Pressurization of isolated renal arteries increases inositol trisphosphate and diacylglycerol. Am J Physiol 266: H1840–H1845.
41.Osol G, Laher I, Cipolla M (1991). Protein kinase C modulates basal myogenic tone in resistance arteries from the cerebral circulation. Circ Res 68: 359–567.
42.Miller FJ, Jr., Dellsperger KC, Gutterman DD (1997). Myogenic constriction of human coronary arterioles. Am J Physiol 273: H257–H264.
43.Conway RS, Kirk ES, Eng C (1988). Ventricular preload alters intravascular and extravascular resistances of coronary collaterals. Am J Physiol 254: H532–H541.
44.Bellamy RF (1978). Diastolic coronary artery pressure-flow relations in the dog. Circ Res 43: 92–101.
45.Eng C, Jentzer JH, Kirk ES (1982). The effects of the coronary capacitance on the interpretation of diastolic pressure-flow relationships. Circ Res 50: 334–341.
46.Kanatsuka H, Ashikawa K, Komaru T, Suzuki T, Takishima T (1990). Diameter change and pressure-red blood cell velocity relations in coronary microvessels during long diastoles in the canine left ventricle. Circ Res 66: 503–510.
47.Lamping KG, Kanatsuka H, Eastham CL, Chilian WM, Marcus ML (1989). Nonuniform vasomotor responses of the coronary microcirculation to serotonin and vasopressin. Circ Res 65: 343–351.
48.Sellke FW, Quillen JE, Brooks LA, Harrison DG (1990). Endothelial modulation of the coronary vasculature in vessels perfused via mature collaterals. Circulation 81: 1938–1947.
310 B. Ramlawi et al.
49.Klassen GA, Armour JA (1982). Epicardial coronary venous pressures: autonomic responses. Can J Physiol Pharmacol 60: 698–706.
50.Yuan Y, Mier RA, Chilian WM, Zawieja DC, Granger HJ (1995). Interaction of neutrophils and endothelium in isolated coronary venules and arterioles. Am J Physiol 268: H490–H498.
51.Lefer DJ, Nakanishi K, Vinten-Johansen J, Ma XL, Lefer AM (1992). Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs. Am J Physiol 263: H850–H856.
52.Piana RN, Wang SY, Friedman M, Sellke FW (1996). Angiotensin-converting enzyme inhibition preserves endothelium-dependent coronary microvascular responses during short-term ischemia-reperfusion. Circulation 93: 544–551.
53.Cayatte AJ, Palacino JJ, Horten K, Cohen RA (1994). Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb 14: 753–759.
54.von der Leyen HE, Gibbons GH, Morishita R, Lewis NP, Zhang L, Nakajima M, Kaneda Y, Cooke JP, Dzau VJ (1995). Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci U S A 92: 1137–1141.
55.Moroi M, Zhang L, Yasuda T, Virmani R, Gold HK, Fishman MC, Huang PL (1998). Interaction of genetic deficiency of endothelial nitric oxide, gender, and pregnancy in vascular response to injury in mice. J Clin Invest 101: 1225–1232.
56.Yu SM, Hung LM, Lin CC (1997). cGMP-elevating agents suppress proliferation of vascular smooth muscle cells by inhibiting the activation of epidermal growth factor signaling pathway. Circulation 95: 1269–1277.
57.Itoh H, Pratt RE, Ohno M, Dzau VJ (1992). Atrial natriuretic polypeptide as a novel antigrowth factor of endothelial cells. Hypertension 19: 758–761.
58.Sellke FW, Armstrong ML, Harrison DG (1990). Endothelium-dependent vascular relaxation is abnormal in the coronary microcirculation of atherosclerotic primates. Circulation 81: 1586–1593.
59.Chilian WM, Dellsperger KC, Layne SM, Eastham CL, Armstrong MA, Marcus ML, Heistad DD (1990). Effects of atherosclerosis on the coronary microcirculation. Am J Physiol 258: H529–H539.
60.Drexler H, Zeiher AM, Meinzer K, Just H (1991). Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolaemic patients by L- arginine. Lancet 338: 1546–1550.
61.Treasure CB, Klein JL, Vita JA, Manoukian SV, Renwick GH, Selwyn AP, Ganz P, Alexander RW (1993). Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels. Circulation 87: 86–93.
62.Quillen JE, Sellke FW, Brooks LA, Harrison DG (1990). Ischemia-reperfusion impairs endothelium-dependent relaxation of coronary microvessels but does not affect large arteries. Circulation 82: 586–594.
63.Matsunaga T, Okumura K, Ishizaka H, Tsunoda R, Tayama S, Tabuchi T, Yasue H (1996). Impairment of coronary blood flow regulation by endothelium-derived nitric oxide in dogs with alloxan-induced diabetes. J Cardiovasc Pharmacol 28: 60–67.
Regulation of Coronary Vascular Tone and Microvascular Physiology |
311 |
64.Sellke FW, Shafique T, Schoen FJ, Weintraub RM (1993). Impaired endotheliumdependent coronary microvascular relaxation after cold potassium cardioplegia and reperfusion. J Thorac Cardiovasc Surg 105: 52–58.
65.Bauters C, Asahara T, Zheng LP, Takeshita S, Bunting S, Ferrara N, Symes JF, Isner JM (1995). Recovery of disturbed endothelium-dependent flow in the collateral-perfused rabbit ischemic hindlimb after administration of vascular endothelial growth factor. Circulation 91: 2802–2809.
66.Harada K, Friedman M, Lopez JJ, Wang SY, Li J, Prasad PV, Pearlman JD, Edelman ER, Sellke FW, Simons M (1996). Vascular endothelial growth factor administration in chronic myocardial ischemia. Am J Physiol 270: H1791–H1802.
67.Sellke FW, Wang SY, Friedman M, Harada K, Edelman ER, Grossman W, Simons M (1994). Basic FGF enhances endothelium-dependent relaxation of the collateral-perfused coronary microcirculation. Am J Physiol 267: H1303–H1311.
68.Sellke FW, Wang SY, Stamler A, Lopez JJ, Li J, Simons M (1996). Enhanced microvascular relaxations to VEGF and bFGF in chronically ischemic porcine myocardium. Am J Physiol 271: H713–H720.
69.Rapps JA, Jones AW, Sturek M, Magliola L, Parker JL (1997). Mechanisms of altered contractile responses to vasopressin and endothelin in canine coronary collateral arteries. Circulation 95: 231–239.
70.Marcus ML, Harrison DG, Chilian WM, Koyanagi S, Inou T, Tomanek RJ, Martins JB, Eastham CL, Hiratzka LF (1987). Alterations in the coronary circulation in hypertrophied ventricles. Circulation 75: I19–I25.
71.Harrison DG, Doughan AR, Sellke FW (2005). Physiology of the coronary circulation. In: Sellke FW, Del Nido PJ, Swanson SJ (eds.), Sabiston and Spencer Surgery of the Chest, 7th edn. (Elsevier Inc., Philadelphia), pp. 753–766.
72.Gallery HF, Webster NR (2004). Physiology of the endothelium. Br J Anaesth 93(1): 105–113.
73.Vanhoutte PM, Boulanger CM, Vidal M, Mombouli JV (1993). Endotheliumderived mediators and the renin-angiotensin system. In: Robertson JIS, Nicholls ME (eds.), The Renin-Angiotensin System (Gower Medical Publishing, London).
74.Komaru T, Ashikawa K, Kanatsuka H, Sekiguchi N, Suzuki T, Takishima T (1990). Neuropeptide Y modulates vasoconstriction in coronary microvessels in the beating canine heart. Circ Res 67: 1142–1151.
75.Sekiguchi N, Kanatsuka H, Sato K, Wang Y, Akai K, Komaru T, Takishima T (1994). Effect of calcitonin gene-related peptide on coronary microvessels and its role in acute myocardial ischemia. Circulation 89: 366–374.
76.Kanatsuka H, Lamping KG, Eastham CL, Dellsperger KC, Marcus ML (1989). Comparison of the effects of increased myocardial oxygen consumption and adenosine on the coronary microvascular resistance. Circ Res 65: 1296–1305.
77.Lamping KG, Clothier JL, Eastham CL, Marcus ML (1992). Coronary microvascular response to endothelin is dependent on vessel diameter and route of administration. Am J Physiol 263(3 Pt 2): H703–H709.
78.Osborne JA, Siegman MJ, Sedar AW, Mooers SU, Lefer AM (1989). Lack of endothelium-dependent relaxation in coronary resistance arteries of cholesterolfed rabbits. Am J Physiol 256(3 Pt 1): C591–C597.
312 B. Ramlawi et al.
79.Quillen JE, Sellke FW, Armstrong ML, Harrison DG (1991). Long-term cholesterol feeding alters the reactivity of primate coronary microvessels to platelet products. Arterioscler Thromb 11: 639–644.
80.Kuo L, Davis MJ, Cannon MS, Chilian WM (1992). Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine. Circ Res 70: 465–476.
81.Lamping KG, Piegors DJ, Benzuly KH, Armstrong ML, Heistad DD (1994). Enhanced coronary vasoconstrictive response to serotonin subsides after removal of dietary cholesterol in atherosclerotic monkeys. Arterioscler Thromb 14: 951–957.
82.Hasdai D, Mathew V, Schwartz RS, Smith LA, Holmes DR Jr, Katusic ZS, Lerman A (1997). Enhanced endothelin-B-receptor-mediated vasoconstriction of small porcine coronary arteries in diet-induced hypercholesterolemia. Arterioscler Thromb Vasc Biol 17: 2737–2743.
83.Métais C, Li J, Li J, Simons M, Sellke FW (1998). Effects of coronary artery disease on expression and microvascular response to VEGF. Am J Physiol 275 (4 Pt 2): H1411–H1418.