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Inosine in the ischenic heart

44. Kugler G. Myocardial release of lactate, inosine and hypoxanthine during atrial pacing and exercise-induced angina. Circulation 197$59:43-g. 45. Aussedat J, Verdys M, Rossi A. Adenine nucleotide synthesis from inosine during normoxia and after ischaemia in the isolated perfused rat heart. Can J Physiol Pharmacol 1985;63: 1159-64. 46. Harmsen E, de Tombe PP, de Jong JW, Achterberg PW. Enhanced ATP and GTP synthesis from hypoxanthine or inosine after myocardial ischemia. Am J Physiol1984;246:H37-43. 47. Katz LA, Swain .JA. Portman MA, Balaban RS. Intracellular

pH and inorganic phosphate content of heart in vivo: a “‘P-NMR study. Am J Physiol 1988;255:H189-96. 48. Kentish JC. The effect of inorganic phosphate and creatine phosphate on force production in skinned muscle from rat ventricle. J Physiol (Land) 1989;370:585-604. 49. Ponce-Hornos JE, Langer GA. Effects of inorganic phosphate on ion exchange, energy state, and contraction in mammalian heart. Am J Physiol 1982;242:H79-88. 50. Lewandowski ED, Johnston DL, Roberts R. Effects of inosine on glycolysis and contracture during myocardial ischemia. Circ Res 1991;68:578-87.

Comparison of acute elastic recoil after directional coronary atherectomy versus standard balloon angioplasty We evaluated intraprocedural “elastic recoil” in 25 patients (22 men and 3 women) undergoing directional coronary atherectomy (DCA) of left anterior descending stenoses, and compared these with 25 temporally-matched (14 men and 11 women) patients having balloon angioplasties (PTCA). Quantitative arteriography was performed using the Coronary Measurement System (Leiden, The Netherlands), with “elastic recoil” defined as the difference in maximum device or balloon size minus residual minimum diameter. In addition, we determined the effects of relative device size, specific anatomic location (proximal/mid artery), lesion length, eccentricity (symmetry index), and dystrophic calcification on acute “recoil” severity after both procedures. Although initial coronary stenoses were similar (minimum stenotic diameter, DCA = 0.59 _+ 0.20 mm versus PTCA = 0.55 -t 0.23 mm, p = NS), less “elastic recoil” was observed after atherectomy (DCA = 0.83 t 0.57 mm versus PTCA = 1.26 + 0.56 mm, p < O.Ol), and this was confirmed by absolute recoil/maximum device size ratios (DCA = 23.5 +- 16.0% versus PTCA = 41.6 + 13.8%, p < 0.01). Acute “elastic recoil” was also influenced by maximum device size/“normal” coronary artery ratios [(ratio < 0.9, DCA = 0.26 f 0.10 mm versus PTCA = 0.84 r 0.13 mm, p < 0.01); (ratio 0.9 to 1.1, DCA = 0.69 k 0.41 mm versus PTCA 0.75 + 0.32 mm, p = NS); (ratio > 1.1, DCA = 1.09 + 0.64 mm versus PTCA = 1.59 r 0.48 mm, p < O.OS)]. Although anatomic features did not influence recoil severity after atherectomy, both lesion length (< 10 mm, 1.19 f 0.54 mm versus > 10 mm, 1.57 t 0.58 mm, p < 0.05) and eccentricity (symmetry index < 0.5, 1.45 _+ 0.43 mm versus symmetry index > 0.5, 1.21 + 0.59 mm, p < 0.05) adversely affected “recoil” after balloon angioplasty. Compared with standard balloon angioplasty, directional coronary atherectomy produces less “elastic recoil,” which although it is dependent on relative device size, is not influenced by stenosis morphology. (AM HEART J 1992;124:1459.)

Brian P. Kimball,

Sanh Bui, Eric A. Cohen, Ronald

G. Carere, and Allan G. Adelman

Toronto, Ontario, Canada

From the Cardiovascular Investigation Unit, Division of Cardiology, Department of Medicine, The Toronto and Mount Sinai Hospitals, and the University of Toronto. Received for publication Jan. 17, 1992; accepted June 18, 1992. Reprint requests: Brian P. Kimball, MD, The Toronto Hospital (General Division), 200 Elizabeth Street, EN 11-216, Toronto, Ontario, Canada M5G 2C4.

4/l/41299

Balloon angioplasty is an effective revascularization strategy in selected patients with coronary artery disease.l Recent studies on atherosclerotic animal models, ex vivo necropsy specimens,2 and innovative in vivo imaging techniques, such as intravascular angioscopy3 and ultrasonography,4 have determined that this technique depends on plaque compression/ 1459

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fracture, medial dissection, and contralateral “normal” vessel wall expansion. The importance of reversible elastic deformation of the coronary artery was investigated by Jain et a1.,5 who studied acute intraprocedural pressure/volume patterns during balloon angioplasty. Although plaque “compaction” (27 5’;.) and acute disruption (“cracking”) (17 “; ) were seen, the most frequent pattern involved simple “stretching” (56%) withinelasticlimitations, thereby confirming previous angiographic studies suggesting significant “arterial recoil” after balloon deflation.emg Directional coronary atherectomy is an alternative techniquelO for the treatment of coronary stenoses, with potential advantages over standard balloon angioplasty such as primary plaque excision and the creation

of a smooth

propensity

endoluminal

for platelet/thrombi

surface,

aggregation.‘l

with

less

In ad-

dition to selective removal of atherosclerotic plaque, directional coronary atherectomy frequently pro-

duces pathologic

disruption

of the internal

elastic

lamina and subjacent coronary media.12 AIthough the precise mechanism of directional coronary

atherectomy changes

is a source of ongoing debate,13, l4 these

may

affect coronary artery decrease the magnitude of acute arterial recoil. This study directly cornpares immediate coronary artery “recoil” following

“compliance”

standard atherectomy

significantly

and potentially

balloon

angioplasty

in de novo

stenoses. In addition,

left

versus directional anterior

we evaluated

descending

the effect of rel-

ative device size (maximum device size/“normal” coronary dimension ratios), specific location (proximal/mid vessel), and stenosis morphology (lesion length, eccentricity, calcification) on “recoil” severity. METHODS Patient population. Twenty-five consecutive patients (22 men and 3 women) with an average age of 56 years (range 39 to 78 years) undergoing directional coronary atherectomy at The Toronto Hospital (General Division) between July 1990 and April 1991 were included in this study. Each patient was initially referred to the Interventional Cardiology Service for a percutaneous,transcatheter revascularization procedure, with selection of coronary atherectomy basedon predefinedanatomiccriteria.‘” These subjects were temporally matched bo 25 patients with “successful”standard balloon angioplasties(14 menand 11 women, average age63 years [range 40 to 81 years]) of the proximal/midleft anterior descendingartery. Angiographic successwasdefined by a minimum 20CCdiameter improvement and a residual stenosis diameter < 50% in the absenceof ischemic complications (acute occlusion, myocardial infarction, emergency bypass surgery). Exclusion from directional coronary atherectomy was basedon anatomic factors known to limit this technique, such as left

December 1992 Heart Journal

main stem disease,marked proximal arterial tortuosity, severecalcification, major side branch involvement (> 1..j mm diameter), or severedistal coronary artery disease. Quantitative coronary arteriography. Multiple projections were performed asclinically indicated to facilitate the angioplasty/atherectomy procedure. All subjectsreceived parenteral nitroglycerin, using an intravenous (120 to 200 pg) or intracoronary (80 to 120pg) route of administration. Individual cineangiographicserieswere chosenfor quantitative analysis based upon the exclusion of overlapping branch vesselsand the best delineation of stenoses’severity and overall length. Pre- and postprocedure cineangiograms were obtained using identical radiographic angulation, under similar magnification conditions, to permit direct comparisonof the final outcome. All coronary stenosisdata were generatedwith the Coronary Measurement System (CMS, Medical Imaging Systems, Nuenen, The Netherlands) asrecently developed by Dr. H. Reiber (Leiden, The Netherlands).i6-is Cineangiogramswere reviewed without knowledgeof the specific interventional procedure (directional coronary atherectomy IDCA] or percutaneoustransluminal coronary angioplasty [PTCA]) by a technician using an Elk CAP 35E tine projector (General Electric Canada,Inc, Mississauga,Ontario, Canada) and standard (525 interlaced) television monitor. A single, maximally opacified right anterior oblique (cranial/caudal angulation) angiographic frame was selected with minimal motion artifact (blurring) in cardiac diastasis (diastole). Original images were optically magnified (X 2.3), utilizing an optimally focusedarea of interest centered within the video screen.The nontapered section of the angiographic catheter (8F, PTCA or IlF, DCA) was usedfor absolutecalibration, with standardization of light intensity before frame digitization so that maximal light intensity at any point wasjust below saturation. Proximal and mid left anterior descending segments were defined according to standard American Heart Association criteria,lg while “normal” regionswere incorporated into the stenotic segment analysis. A preliminary coronary lumen was identified using an automated edge detection system based on cross-sectionaldensitometry (weighted first, second derivative method). A “secondpass,” high-density interrogation of closely adjacent regions and a “point-to-point” probability search enabled further refinement of the “true” luminal border, thus minimizing the necessity for manual correction. Normal coronary diameters represented interpolated values at. any given point based on an analysis of the entire anatomic segment.The program derives absoluteminimum stenotic diameter and estimated cross-sectional areas (circular cross-sectionalprofile), with relative percent diameter and area obstructions. Stenotic length was calculated using “curvature analysis” after achieving a minimum interpolated value (90c; to 100’; ), with the “symmetry index” determined by the ratio of plaque dimensions(in percent) at the site of minimum lumen diameter. For the purposesof this study, maximum “working” diameter of each device (atherotome or angioplasty balloon) was derived from manufacturer’s specifications, including

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consideration of maximum inflation pressureand known compliancefeatures. Absolute “recoil” was defined as the difI’erence between maximum device size and final minimum stenotic diameter, with relative “recoil” determined by the absolute recoil/maximum device size ratio (in percent). To further clarify the issueof “relative” device size, all procedureswere categorized accordingto maximum device/coronary artery size ratios, being described as “undersized” (ratio < 0.9), optimal (ratio 0.9 to l.l), or oversized (ratio > 1.1). Independent of appropriate device sizing issues, absolute “recoil” was evaluated by specific anatomic location (proximal/mid left anterior descending). In addition, the infIuence of certain morphologic features on recoil severity was determined, including lesion length (< 10 mm versus> IO mm), eccentricity (symmetry index < 0.5, versussymmetry index > 0.5), and tine-fluoroscopic dystrophic calcification (nil/mild versusmoderate/severe). Table I lists preprocedural data. Statistics. Quantitative arteriographic measurements are reported as group meansand standard deviations for both directional coronary atherectomy and standard balloon angioplasty. Statistical comparison of continuous variables usedStudent’s t tests,while categorical data were analyzed by chi square methodology, with statistical significance defined asp, < 0.05. RESULTS General

outcomes. Despite the temporal matching process, case selection bias resulted in smaller “normal” reference diameters in the PTCA subjects (PTCA, 2.84 + 0.54 mm versus DCA, 3.27 rt 0.77 mm, p < O.Ol), although both initial absolute minimum stenotic diameters (PTCA, 0.55 it 0.23 mm versus DCA, 0.59 -t 0.20 mm, p = NS), and relative percent diameter stenosis (PTCA, 79.9 ? 8.5:; versus DCA, 82.0 f 5.6rA, p = NS) were similar. As indicated in Fig. 1, postprocedure minimum stenotic diameters were substantially larger after directional coronary atherectomy (PTCA, 1.70 f 0.44 mm versusDCA, 2.75 & 0.55 mm, p < O.OOl), aswas residual percent diameter stenosis (PTCA, 34.4 +- 10.7’; versus DCA, 17.9 + 10.7!‘;, p < 0.001). Although on average the atherectomy device was significantly larger than calculated maximum inflated balloon diameters (PTCA, 2.97 _t 0.57 mm versus DCA, 3.54 + 0.14 mm, p < 0.05), relative to coronary artery size (maximum device size/reference coronary dimension) no significant differences were observed (PTCA, 1.17 h 0.25 versus DCA, 1.10 f 0.19, p = NS). As indicated in Fig. 2, absolute coronary artery “recoil” was significantly greater after PTCA (PTCA, 1.27 * 0.57 mm versus DCA, 0.83 ? 0.57 mm, p < 0.01). These observations were confirmed when expressed in relative terms as absolute recoil/maximum device size (PTCA, 41.6 + 13.8? versus DCA, 23.5 + 16.O@C,p < O.Ol), or ab-

Coronary recoil in DCA us PTCA Table

1461

I. Preprocedural data DCA

Reference “normal” diameter (mm) Minimum luminal diameter (mm) Relative diameter stenosis (T ) Lesion length (mm) Symmetry index Dystrophic calcification Nil/mild (no.) Moderate/severe (no.) LEA. Directional coronary coronary angioplasty. *p < 0.1. tp < 0.05.

atherectomy;

3.27 0.59 82.03 11.40 0.60

t + j I +

PTCA 0.77 2.84 0.20 0.55 5.62 79.93 4.86 9.81 0.28 0.70

17 8 PTCA, percutaneous

+ f ik k

0.54f 0.23 8.52 3.45* 0.29

19 6 transluminal

solute recoil/reference coronary diameter (PTCA, 51 +- 26 Pi versus DCA, 28 + 25 @O , p < 0.01). Coronary “recoil” per maximum device size/reference coronary artery ratios. As depicted in Table II,

postprocedural acute coronary artery “recoil” was evaluated according to maximum device size/reference coronary artery ratios for both directional atherectomy and balloon angioplasty subjects, In general terms, as the device (atherotome or angioplasty balloon) exceeds “normal” reference coronary diameter, we observed greater absolute immediate “recoil” regardless of the specific interventional technique. For any given maximum device size/coronary artery ratio, acute “recoil” was consistently lessafter directional coronary atherectomy in comparison to standard balloon angioplasty. Similar conclusions were derived from analysis of relative “recoil” ratios, including absolute recoil/maximum device size [(ratio < 0.9, DCA 9.1 it 4.0% versus PTCA 29.5 k 11.1’:1, p < O.Ol), (ratio 0.9 to 1.1, DCA 20.8 -t 12.6”; versus PTCA 26.5 + 6.3’;. , p = NS), (ratio > 1.1, DCA 30.3 t 17.6% versus PTCA 47.7 + ll.O? , p < 0.05)], and absolute recoil/“normal” reference coronary size [(ratio 0.9, DCA 8.2 -t 3.7 !;# versus PTCA 24.4 + 9.1%, p < O.Ol), (ratio 0.9 to 1.1, DCA 20.7 F 12.6% versus PTCA 26.4 ? 6.3’C, p = NS), (ratio > 1.1, DCA 40.4 I 28.8% versus PTCA 63.8 i 21.8”;) p < 0.05)]. Stenotic morphology. As indicated in Fig. 3, acute arterial “recoil” was independent of specific anatomic location, following atherectomy (proximal, 0.79 f 0.60 mm versus mid, 0.96 ? 0.43 mm, p = NS), or balloon angioplasty (proximal, 1.34 -t 0.50 mm versus mid, 1.04 t- 0.70 mm, p = NS), although directional coronary atherectomy consistently produced less acute “recoil” in comparison to standard balloon angioplasty. These data were confirmed by analysis of relative recoil according to absolute recoil/maximum device size ratios [ (DCA,

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-

r ii!

p 10 mm 1.57 +_0.58 mm, p < 0.05), as depicted in Fig. 4. These data were confirmed by “relative” recoil ratios [(DCA, < 10 mm 23.2 2 16.4% versus > 10

mm 25.9 -+ 15.1%, p = NS) and (PTCA, < 10 mm 40.9 i 14.1% versus > 10 mm 44.8 + 12.0X, p < 0.05)], with consistently less “recoil” identified after directional atherectomy. As illustrated in Fig. 5, stenotic eccentricity, as defined by the “symmetry index,” failed to influence absolute “recoil” following atherectomy (index < 0.5, 0.85 -t 0.65 mm versus index > 0.5,0.82 t 0.51 mm, p = NS), although “recoil” was greater in asymmetric lesions after balloon angioplasty (index < 0.5, 1.45 & 0.43 mm versus index > 0.5, 1.21 i_-0.59 mm,

Coronary recoil in DCA usPTCA

17 DCA H PTCA

0 EI

1463

DCA PTCA

p 1.10

Abbreviations

(mm)

(n = 4) 0.26 k 0.10 (n = 12) 0.69 t 0.41 (n = 9) 1.09 ? 0.64

PTCA

(mm)

(n = 4) 0.84 + 0.13t (n = 6) 0.75 f 0.32 (n = 15) 1.59 t 0.48*

as in Table I.

*p < 0.05. tp < 0.01.

of the relatively bulky atherotome. Based on typical definitions (maximum device size - minimum stenotic diameter), these data indicate that acute “elastic recoil” is substantially lessafter directional coronary atherectomy when compared with standard balloon angioplasty. This single factor is largely responsible for the quantitative benefits of this technique, including larger postprocedural minimum stenotic diameters and less residual coronary stenosis.20q21Although acute recoil severity increases as the atherotome exceeds reference “normal” coronary artery dimensions, directional coronary atherectomy produces less acute “elastic recoil” than balloon angioplasty performed with similar size catheters. Beyond the obvious issuesof appropriate device size, neither directional atherectomy or balloon angioplasty “recoil” was influenced by the precise anatomic location of the stenosis (proximal/mid left anterior descend-

December

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et al

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3-

2-

0 0

p.co.05

DCA PTCA

p