European Heart Journal (1992) 13, 1109-1115

Myocardial protection during percutaneous transluminal coronary angioplasty: effects of trimetazidine* G. KOBER, T. BUCK, H. SIEVERT AND C. VALLBRACHT

Clinic Nordrhein, Ernst-Ludwig-Ring 2, D6350 Bad Nauheim, Germany KEY WORDS: Trimetazidine, PTCA, myocardial protection, effort angina. Trimetazidine (TMZ) has recently been shown to improve anginal symptoms without altering haemodynamic variables. A randomized, double-blind, placebo-controlled study was conducted in 20 patients to study the effects of TMZ on the severity of myocardial ischaemia during PTCA of the left anterior descending coronary artery. Five minutes after a first successful dilatation (Do), a control balloon inflation (Dt) was performed until onset of ischaemic signs on both the intracoronary (i.e.) andprecordial ECG. Two minutes later, patients received either TMZ6mg or placebo i.e. Another inflation (D2) was performed 5 min after Dr No differences were found between the two groups regarding responses in heart rate, systemic and i.e. pressures during the study. TMZ decreased the maximum ST-segment shift at D2 compared with D, (0-8 ±01\sl-4±0-3mV,P = 0-023) and delayed its onset (46±4\s36±5 s,P = 0-024). TMZ also decreased maximum T-wave changes (l-06±0-24 vs 219±0-3 mV, P = 0001), and significantly reduced the area under the curve (mv s~') of the i.e. ST-segment and T-wave changes during balloon inflation (P = 0-042 and P = 0-009 respectively). The placebo had no effect on these parameters. These results support the hypothesis that trimetazidine has a direct anti-ischaemic effect on human myocardial cells. Introduction The safety and the anti-anginal and anti-ischaemic efficacy of trimetazidine (TMZ) have been previously documented in the acute1'1 and chronic12'31 treatments of patients with coronary artery disease. These beneficial effects seem to be independent of the balance between oxygen supply and demand since neither systemic haemodynamics1'1 nor coronary bloodflow141were altered by the compound. These observations support the hypothesis • that trimetazidine has a direct cytoprotective effect on the ischaemic myocardium as suggested by numerous in-vitro experiments'31. The aim of this study was to determine whether TMZ protects the myocardium from ischaemia during percutaneous transluminal coronary angioplasty (PTCA). From a physiological point of view, this procedure provides a unique opportunity to study acute reversible ischaemia in man, and hence, test whether TMZ attenuates the ischaemic response at the regional level. Furthermore, interventions directed at protecting the myocardium are particularly necessary since they have the capability of improving the safety of PTCA161 and could enable more prolonged inflations to be performed, perhaps increasing the primary success rate of this procedure*71. Methods

evaluated between January and October 1989. All had incapacitating angina pectoris refractory to intensive medical therapy and gave written informed consent before the procedure. Angioplasty was performed entirely as clinically indicated and the study was approved by the ethical committee of the authors' Institution. Patients with angiographically circumscribed stenosis of the proximal LAD greater than 70%, who were aged less than 65 years, had an angiographic ejection fraction of more than 50% and had no contraindication to PTCA were eligible for the study. Patients with unstable angina, high-risk angioplasty (three-vessel disease, left main stenosis) or who had recently suffered an acute myocardial infarction were excluded. Beta-blocker therapy, calcium antagonists and/or long- and short-acting nitrates were stopped respectively 1 week, at least 48 h, and 2 h prior to the PTCA procedure. Among the 20 patients included, 10 had a history of myocardial infarction. Collateral vessels to the anterior wall were documented in two patients in the placebo group and three patients in the trimetazidine group. In the two groups, both the normal angiographic ejection fraction and the lack of left ventricular (LV) filling pressure elevation demonstrated the lack of alteration in LV function. Clinical characteristics of the patients are listed in Table 1.

PATIENTS

Twenty patients undergoing routine PTCA of the left anterior descending coronary artery (LAD) were Mnstitut dc Rcchcrchcs Internationales Servier, Courbevoie, France Submitted for publication 14 June 1991, and in revised form 29 November 1991. Correspondence' G. Kober, Clinic Nordrhein, Erait-Ludwig-Ring 2, D 6350 Bad Nauheim, Germany. 0195-668X/92/08I109 + 07 $03.00/0

ANGIOPLASTY PROCEDURE

All patients received 0-5 g. day"' of acetylsalicylic acid starting at least 1 day prior to the study, and 200 units. kg"' of heparin at the start of the catheterization. No sedatives or tranquillizers were given as premedication. Nitrates and calcium blockers were not administered © 1992 The European Society of Cardiology

1110 G. Koberelal.

Table I Clinical characteristics of the study group (mean ± SEM)ST-segment elevation was measured at the J-point. These

Age (years) Males/females Duration of symptoms (months) Prior myocardial infarction Anterior

Inferior Coronary artery stenosis of more than 70% LAD LCX RCA

Placebo N=10

Trimetazidine N=10

53±1

56±2

9/1

9/1

18±6

16±7

6 4 2

4 3 1

10

10

2

1

1

3

recordings provided measurements of (i) time (s) to development of maximum ST-segment elevation and Twave amplitude changes, (ii) regression time of ST- and T-changes to normal, (iii) the area under the curve of ST-segment changes, plotted as a function of time, during the inflation period (mV . s~'). Anginal symptoms during dilatations were classified as follows: grade 0 (no angina); grade 1 (slight angina); grade 2 (medium angina) and grade 3 (severe angina). A mean value of anginal score was calculated for both groups. STATISTICAL ANALYSIS

The homogeneity of baseline values, before the control dilatation, was tested using a one-way analysis of variance. For each parameter, the difference between values LA D = left anterior descending coronary artery; LCX = left circumbefore and after D, (Al) and D2 (A2) were measured. flex coronary artery; RCA =rightcoronary artery. Differences between Al and A2 in the trimetazidine group were compared to the placebo group using a two-way intracoronarily during the procedure. PTCA was per- analysis of variance with repeated time measurements. formed using the percutaneous transfemoral technique as Lastly, a two-way analysis of variance (time x subject) enabled the comparison of the ischaemia induced between previously described'8"101. Before introduction of the 8F-guiding catheter, a D, and D2 in each treatment group. The type 1 error for 12-lead ECG was recorded. Throughout the study period, these analyses was 5%. the following parameters were continuously recorded: precordial lead V5; intracoronary ECG (i.e. ECG) (derived directly via the 0014in intracoronary angio- Results plasty guide wire acting as an electrode obtaining an ECG There was no significant difference between the placebo directly from the myocardial area supplied by the vessel to and the trimetazidine group with regards to the severity of be dilated); systemic blood pressure (SBP); intracoronary LAD stenosis both before and after PTCA, and between blood pressure (IBP) (monitored distal to the balloon); both the duration and pressure of the occlusion (Table 2). heart rate (HR); subjective angina pectoris symptoms (Fig. l).The size of the inflated balloon (2-5, 30 or Similarly, there were no statistically significant differences 35 mm) was chosen according to the dimension of the between the two groups regarding central and intraprestenotic vessel diameter (shaft size 2-7 F; lumen size coronary haemodynamic parameters recorded 10 s before D, (Table 3). When the effects of D, and D2 on haemo0019 in). dynamic parameters were compared, no significant All patients underwent three balloon inflations (Fig. 1). difference was observed within the placebo and the TMZ During the first balloon inflation (D,,), signs of ischaemia group and there was no significant difference between the and the severity of the ischaemic reaction detected by the groups with regards to heart rate (Fig. 2) (/" = 0-091) ECG were used to determine the pressure and duration of systemic blood pressure (/) = 0-719) and intracoronary the two subsequent inflations (D, and D2), both of which blood pressure (occlusion pressure) variations (/* = 0-173) were to be carried out for the same period of time and at (Fig. 3). equal occlusion pressures. Do was followed by a 5-min recovery period before D,. Two minutes after D, patients received, according to randomization, a 1-5 ml bolus of EFFECTS OF REPETITIVE CORONARY OCCLUSION (D,, Dj) IN THE either placebo (group 1, N=10) or 6mg trimetazidine PLACEBO GROUP (group 2, N = 10). The bolus was injected into the coronary In the i.e. ECG, the amplitude of maximum STartery via the catheter tip which was positioned distal to segment shift was not altered (A2 = 0-98 ± 0-22 mV vs the stenosis. After a further 3 min, the third inflation (D2) Al = 116±018mV, /> = 0176) following placebo injecwas performed. The final study group consisted of 20 tion. The time to maximum ST-segment shift was patients who demonstrated ST-T elevation of 0-1 mV or unchanged (A2 = 39-3±6-8s vs Al =47-3±6-0s, P = more 80 ms after the J-point, during the control balloon 0-138). Similarly, there was no significant variation in occlusion (D,). peak T-wave amplitude (P = 0-486), or in the area under the curve of ST-segment and T-wave changes plotted as a DATA ANALYSIS function of time during balloon inflation (/J = 0-102 and Continuous recording of the parameters started during P = 0-207 respectively) (Figs 4 and 5). the last 10 s before D, and ended in the first 1-5 min after In lead V5, maximum ST-segment shift (P = 0-373) D2. Magnitude of ST- and T-elevation (mV) were and peak T-wave amplitude (/> = 0177) did not vary recorded every 10 s in both V5 and i.e. ECG leads. The significantly. Angiographic ejection fraction (%)

70±3

, 73±3

Effects of trimetazidine during P TCA

5min

2 rmn

111 I

3 mm

1

Injection i.e.

Placebo TMZ 6 mg

HR, SBP, IBP ECG (V5)

Recordings

ECG (ic ) Clinical symptoms

Figure I Study design: D = balloon inflation, HR = heart rate, SBP = systemic blood pressure, IBP = intracoronary blood pressure. The initial dilatation (Do) is not considered in the analysis because of possible additional ischaemia due to catheter positioning.

Table 2

Characteristics of the PTCA procedure (mean ± SEM)

Severity of LAD stenosis before PTCA (%) Severity of LAD stenosis after PTCA (%) Duration of occlusion (s) range (s) Balloon inflation pressure (bar) range (bar)

Placebo N=10

Trimetazidine N=10

77 ± 2

84 ± 2

33 ± 2 59±4 30-90 6-4±0-5 4-10

36 ± 2 61 ± 5 40-90 6-1 ±0-3 5-8

LAD = left anterior descending coronary artery.

EFFECTS OF REPETITIVE CORONARY OCCLUSION (D,, D2) IN THE TRIMETAZIDINE GROUP

In the trimetazidine group mean severity of angina decreased between D, (2-2 ± 10) and D2 (1-4 ±0-7) while in the placebo group this decrease was less marked (2-2 ± 0-6 at D, vs 1 -7 ± 0-7 at D2). However, the difference between the two groups was not statistically significant (/> = 0170). Discussion The results of the present study indicate that intracoronary administration of trimetazidine delays the development and reduces the magnitude of the ischaemic response in patients undergoing PTCA. These beneficial effects occurred without altering systemic haemodynamics such as heart rate and blood pressure and this, therefore, suggests a direct cytoprotective effect of TMZ on the myocardium, as previously hypothesized'4"121.

In the i.e. ECG, the amplitude of maximum ST- PROTECTION OF THE MYOCARDIUM DURING PTCA segment shift significantly decreased (A2 = 0-85 ± 0-13 mV Besides its therapeutic role in reducing coronary vs A1 = 1 -39 ± 0-30 mV, P = 0-023) following trimetazidine stenoses, PTCA has been widely used to evaluate the injection. Time to maximum ST segment shift significantly effectiveness of drug interventions directed at protecting increased (A2 = 46-3 ±3-9 svsAl = 36-1 ±4-7 s,/ 3 = 0024) the myocardium against ischaemia'9131. When adminis(Fig. 6). Trimetazidine administration significantly tered intravenously, pharmacological interventions decreased peak T-wave amplitude (/) = 0001) and signifi- appear to have a wide range of counteracting effects on cantly decreased the area under the curve of ST-segment the cardiac workload causing inconsistent or only modest and T-wave amplitude changes, plotted as a function of effects on the ischaemic response'14151. Often, these time during balloon inflation (f = 0-002 and />< 0-001 compounds alter systemic haemodynamics, such as respectively) (Figs 4 and 5). cardiac preload, peripheral arterial resistance, blood Conversely, in lead V5, maximum ST-segment shift pressure and heart rate, therefore making their potential did not significantly vary (P = 0-475) whereas trimetazi- direct cardiac effect more difficult to interpret. Even dine significantly decreased peak T-wave amplitude with intracoronary drug administration during coronary (7> = 0019). angiography, it is not usually possible to separate vascular COMPARISON BETWEEN TRIMETAZIDINE AND PLACEBO GROUPS

Compared with the placebo,-trimetazidine significantly increased the time to maximum ST-segment shift in i.e. ECG (/> = 0-009) (Fig. 6), and decreased the peak T-wave amplitude in i.e. ECG (/> = 0007) and the area under the curve of ST-segment and T-wave changes vs time during the balloon inflation period (P = 0-042 and /> = 0003 respectively) (Figs 4 and 5).

effects (on epicardial coronary arteries, resistance vessels, collaterals) and direct cellular effects. Direct myocardial effects can only be evaluated by regional (i.e. intracoronary) administration of drugs during PTCA in man, when haemodynamic changes and effects on collaterals can be excluded'131. The design of such studies, as used in the present investigation, involves multiple balloon inflations of short duration which induce repetitive episodes of brief ischaemia'8^101. This procedure has been demonstrated to

1112 G. Kober etal.

Table 3

Homogeneity before D, Trimetazidine (N = 10) Mean (SEM)

Placebo ( N = 10) Mean (SEM)

Parameter

Heart rate (beats. min~') Systemic blood pressure (mmHg) Intracoronary blood pressure (mmHg) STi.c. (mV) STV 3 (mV) Ti.c. (mV)

690 106-5 78-1 0-560 0020 0-770 0-205

TV,(mV)

71-4 (3-4) 115-7 (5-5) 67-4 (4-3) 0-475 (0-119) 0031 (0028) 1-445 (0-505) 0-400 (0-108)

(2-9) (5-2) (60) (0-266) (0017) (0-656) (0082)

Trlmttandino- group ( N =10 )

Placebo- group

20

_

1 |

20

10

10

0

0

0

0

-10

-10

1 1

1 1 — - ^

| 1

?n

i

010

1

i

10

1

i

1

1

50

30

i

1

i

1

90

70

i

1

130

110

i

-?n

i

O-IO

I 10

i

1 30

i

i 50

1

1 70

i

I

i

90

1 110

i

1 i 130

Tim* ( • )

Figure 2 Course of the change in mean heart rate (HR) during D2 (dotted lines) as compared to D, (solid lines) in the placebo and the trimetazidine group. The dotted vertical line represents the end of the inflation period (mean value). No significant difference between the two groups (/>=0-108) and between the pre- and post-drug dilatation within each group was observed.

Placebo group

Trimei02idine group

(N =10)

(/VxlO)

00

00 -

90 80

90 »

80

70

x E

60

Q. CD

40

x

50

/

— ^

70 60 50

30

-V \ 30

20 -

20

10 0

10

/

/^

40

1

O.IO 0

1

i

i

|_

|

1

1

I

1

1

1

1

1

0

1

1

1

1

1

1

1

1

1

1

1

1

1

1

10 20 30 4 0 50 60 70 8 0 9 0 100 110 120 130 WO 010 0 10 2 0 SO 4 0 50 60 70 80 9 0 100 NO 120130 140 Tint (>)

Figure 3 Evaluation of the mean post-stenotic intracoronary pressue (IBP) during D2 (dotted lines) as compared to D, (solid lines) in the placebo and the trimetazidine group. The dotted vertical line represents the end of the inflation period (mean value). No significant difference in the so-called occlusion pressure between the two groups (P= 1073) and between the preand post-drug dilatation, within each group was observed.

be safe as it induces only a minor prolongation of the duration of the PTCA intervention. The recovery periods between each dilatation allow any ischaemic parameters to normalize; thus, a cumulation of ischaemia from one inflation to another can be excluded'816-171. In the present study this was demonstrated by the fact that electro-

cardiographic signs of ischaemia resolved both rapidly and totally during reperfusion. To illustrate that multiple balloon inflations during PTCA have the potential to represent an accurate and reproducible model of acute regional myocardial ischaemia, recent studies have stressed various practical

Effects of trimetazidine during P TCA 1113

Placebo group

I

Trlmetazldine group

2-0

2-0

(/V=IO)

1-5

1-5

1.0

1-0

D,-0, P'0-OOZ 0-3

0-5

-Coronary occlusion I

-0-5

0-100

I

I

I

I

I

II

I

I

I

I

I

I

I

I

I

-0-5

10 20 30 40 50 6 0 70 8 0 9 0 100110 120 130WO

010 0

I

I

I

10 20 30 4 0 50 6 0 TO 80 9 0 100110120 130MO

Time (« )

Figure 4 Magnitude of the ST-segment shift (i.e. ECG) in the placebo group (P) and the trimetazidine group (TMZ) during inflations D, (solid lines) and D ; (dotted lines). There was no significant change following P, whereas with TMZ the area under the curve was significantly reduced at D2 (striped area) compared with that observed at D, (P=0-002). The group x time interaction: /* = 0-042.

Placebo group (/V=IO)

Trimetazidine group

2

Ai .,.....„.

1.3

1.5

;

I

D,-D, =NS

1 /

0-3

0-5 0 -0-5

-0-3

0-1

0-1

0-10 0

10 20 30 40 50 60 70 80 90 100 DO 120 130140

Coronary occlusion n i

0-10 0

1

1 1

I

1

li

1

I

I

I

I

I

I

I

10 20 30 40 50 60 70 80 90 100110 120 I30M0

Time (•)

Figure 5 Magnitude of T-wave amplitude (i.e. ECG) in the placebo group (P) and the trimetazidine group (TMZ) during inflations D, and D3. There was no significant change following P whereas, with TMZ, the area under the curve was significantly reduced at D2 (striped area) compared with that observed at D, (P < 0001). The group x time interaction: P •= 0003.

considerations that have to be taken into account117181. In this respect, the design of the protocol used here included intracoronary ECG (i.e. ECG) recordings to monitor ischaemia, and only the subsequent inflations after the primary dilatation were evaluated. In comparison to external leads, recording of the i.e. ECG reduces the distance between the ischaemic area and the electrode, making the recording more sensitive1'7"20'. When monitored via the tip of the angioplasty wire, positioned distal to the occluding balloon, potentials were directly derived from the ischaemic area improving the reliability of this ischaemia index. Because of methodological reasons, the first inflation period following balloon positioning is unreliable for the evaluation of therapeutic interventions"71. In the study, as in earlier trials'8'9' only subsequent dilatations were used for comparisons. During such brief coronary occlusion periods, changes in

coronary blood flow during inflation and during the subsequent reactive hyperaemia are paralleled by changes in myocardial metabolism'8''6"21'. In the present study, the reproducibility of balloon inflations was confirmed by the absence of electrical and haemodynamic differences between D2 and D, in the placebo group. MYOCARDIAL PROTECTION BY TRIMETAZIDINE

In a recent, double-blind, cross-over study, trimetazidine was shown to be as effective as nifedipine in patients with effort angina'31. The bicycle exercise test showed that the rate-pressure product for the same workload remained unchanged under trimetazidine, whereas it decreased under nifedipine'3'. Similarly, in the present study, haemodynamic parameters remained unaltered after intracoronary trimetazidine, confirming that trimetazidine exerts a cardio-protective anti-ischaemic effect,

1114 G. Kober eta\.

P- 0-024

40

T

30

This study was presented in part at the American Heart Association (63rd Scientific Sessions)—12-15 November 1990, Dallas, TX, U.S.A.; Circulation 1990; 82(4): direct anti-ischemic effect of trimetazidine during coronary angioplasty (PTCA).

20 10 %

study, using the afore-mentioned model, demonstrate in man a direct anti-ischaemic effect of trimetazidine without haemodynamic changes.

0

References

-10 -20 -30

NS -40

Figure 6 Time to maximum ST-segment shift (i.e. ECG) during inflation D2 expressed as a percentage of that measured during D r Trimetazidine significantly delayed this onset (/> = 0024) whereas placebo had no significant effect (/>=0-138). The group x time interaction: /> = 0009.

presumably mediated by local cellular effects. Due to the study design, the involvement of an effect on large epicardial coronary arteries can be excluded. Recruitment of new collaterals or improvement of collateral flow in already-perfused vessels under TMZ can be excluded since the coronary occlusion pressure was not altered after TMZ compared with the pre-drug occlusion, and varied in both the TMZ and the placebo group in a similar manner. Although coronary blood flow was not directly measured it can be anticipated, from the unchanged systemic and coronary occlusion pressure, that coronary blood flow remained unaffected after TMZ-administration, as seen in animal experiments'4'. The suspected cellular metabolic effects by which TMZ displays its anti-ischaemic activity cannot be explained by the data presented in this paper. However, in numerous in-vitro and animal experiments a cardioprotective effect of TMZ on different parameters of cell metabolism has been documented'522"241. Reduction in cellular acidosis'22'23' and antioxidant activity1241 may partly explain the cardioprotective activity of this compound. Trimetazidine belongs to a class of new compounds that display their anti-ischaemic effect without inducing any haemodynamic effects'12'. Furthermore, this cardioprotective effect recently shown in three experimental models is as potent as nifedipine'"' and is not related to calcium entry blockade or a-adrenoreceptor antagonism. Similarly, trimetazidine improves effort angina to the same extent as nifedipine without modifying the ratepressure product during exercise. From' these studies it can also be confirmed that TMZ acts without altering haemodynamics. In conclusion, PTCA when a rigorous study design is used (i.e. double-blind vs placebo, ignoring the first dilatation) can be assumed to be a reproducible and reliable model for ischaemia. The results of the present

[1] Sellier P, Audouin P, Payen B, Corona P, Duong TG, Ourbak P. Acute effects of trimetazidine evaluated by exercise-testing. Eur J Clin Pharmacol 1987; 33: 205-7. [2] Sellier P. Effets de la trimetazidine sur les.paramitres ergometnques dans l'angor d'effort. Etude multicentrique controlee a double insu contre placebo. Arch Mai Coeur 1986; 9: 1331-6. [3] Dalla-Volta S, Maraglino G, Della-Valentina P, Viena P, Desideri A. Comparison of trimetazidine with nifedipine in effort angina: a double-blind, crossover study. Cardiovasc Drugs Ther 1990; 4: 853-60. [4] Timour Q, Goupit P, Lang J, Durr F, Faucon G. Antianginal effects of trimetazidine: mechanisms. Xth International Congress of Pharmacology, Sydney, Australia, August 23-28, 1987; 648 (Abstr). [5] Harpey C, Clauser P, Labrid C, Freyria JL, Poiner JP. Tnmetazidine, a cellular anti-ischemic agent. Cardiovasc Drug Rev 1989; 6: 292-312. [6] McDonald FM, Fuchs M, Kreuzer J el al. Haemodynamic and antiarrhythmic effects of intracoronary perfusion during percutaneous transluminal coronary angioplasty. Eur Heart J 1985; 6: 549-56. [7] Kaltenbach M, Beyer J, Walker S, Klepzig H, Schmidts L. Prolonged application of pressure in transluminal coronary angioplasty. Cathet Cardiovasc Diagn 1984; 10: 213-9. [8] Kober G, Scherer D, Hopf R, Petri A, Seifert U, Kaltenbach M. Myokardmetabolismus bei der transluminalen Angioplastie. Z Kardiol 1983; 72: 65 (Abstr). [9] Kober G, Kastner R, Hopf R, Kaltenbach M. Die direkte myokardiale antiischamische Wirkung von Diltiazem beim Menschen. Z Kardiol 1986; 75: 386-93. [10] Sievert H, Friedmann A, Schrader R, Kaltenbach M, Kober G. Untersuchungen zum EinfluB des Kalziumantagonisten Nisoldipin auf den koronaren BlutfluB und die Myokardischamie bei temporarer Koronarokklusion. Z Kardiol 1992 (in press). [11] Hugtenburg JG, Jap JW, Mathy MJ, Van Heiningen PNM, Bohnenn VA, Heijnis JB, Boddeke HWG, van Zwieten PA. Cardioprotective effect of trimetazidine and nifedipine in guinea-pig hearts subjected to ischemia. Arch Int Pharmacodyn Ther 1989; 300: 186-208. [12] Boddeke E, Hugtenburg J, Jap W, Heynij J, van Zwieten P. New anti-ischaemic drugs: cytoprotective action with no primary haemodynamic effects. TiPS 1989; 10: 397-400. [13] Zalewski A, Savage M, Goldberg S. Protection of the ischemic myocardium during percutaneous transluminal coronary angioplasty Am J Cardiol 1988; 61: 54G-60G. [14] Doorey AJ, Mehmel HC, Schwartz FX, Kubler W. Amelioration by nitroglycerin of left ventricular ischemia induced by percutaneous transluminal coronary angioplasty: assessment by hemodynamic variables and left ventriculography. J Am Coll Cardiol 1985; 6: 267-74. [15] Feldman RL, Joyal M, Conti R, Pepine CJ. Effect of nitroglycerine on coronary collateral flow and pressure during acute coronary occlusion. Am J Cardiol 1984; 54: 958-63. [16] Serruys PW, Wijns W, van der Brand M el al. Left ventricular performance, regional blood flow, wall motion, and lactate metabolism during transluminal angioplasty. Circulation 1984; 70: 25-36. [17] Perry RA, Seth A, Hunt A el al. Balloon occlusion during coronary angioplasty as a model of myocardial ischaemia: reproducibility of sequential inflations. Eur Heart J 1989; 10: 791-800.

Effects of trimetazidine during PTC A 1115

[18] Friedman PL, Shook TL, Kirshenbaum JM, Selwyn AP, Ganz P. Value of the intracoronary electrocardiogram to monitor myocardial ischemia during percutaneous translumina! coronary angioplasty. Circulation, 1986; 74: 330-9. [ 19] Spach M J, Barr RC, Lanning CF, Tucek PC. Origin of the body surface QRS and T wave potential from epicardial potential distributions in the intact chimpanzee. Circulation 1976; 55: 268-78. [20] Zalewski A, Goldberg S, Dervan JP, Slysh S, Maroko PR. Myocardial protection during transient coronary artery occlusion in man: beneficial effects of regional beta-adrenergic blockade. Circulation 1986; 73: 734-9.

[21] Rothman MT, Bairn DS, Simpson JB, Harrison DC. Coronary hemodynamics during percutaneous transluminal coronary angioplasty. Am J Cardiol 1982; 49: 1615-22. [22] Lavanchy N, Martin J, Rossi A. Anti-ischaemic effects of trimetazidine: 3I P-NMR spectroscopy in the isolated rat heart. Arch Int Pharmacodyn 1987; 289: 97-110. [23] Renaud JF. Internal pH, Na + and Ca 2+ regulation by trimetazidine during cardiac cell acidosis. Cardiovasc Drugs Ther 1988; 1:677-86. [24] Mandonneau-Parini I, Harpey C. Effects of trimetazidine on membrane damage induced by oxygen free radicals in human cells. BrJClin Pharmacol 1985; 20: 148-51.

Myocardial protection during percutaneous transluminal coronary angioplasty: effects of trimetazidine.

Trimetazidine (TMZ) has recently been shown to improve anginal symptoms without altering haemodynamic variables. A randomized, double-blind, placebo-c...
489KB Sizes 0 Downloads 0 Views