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Hipertensión Arterial/Hypertension

The complex quantitative
assessment of preconditioning

Sidorenko G., Komissarova S.

National Center of Cardiology, Minsk, Belarus.

 

 

Aim was to determinate contractive, coronary and neurohumoral reserve of adaptation in patients with ischemic heart disease (IHD) and chronic heart failure before GABS.


Methods: 60 patients (mean age 56.7±4.5 years, M/W 24/10) with stable angina CCS class II – III, Q-MI > 6 months, NYHA class II – IV (EF LV 34.3±3.3%) had multyvessell coronary artery disease (3 and more) and waited for GABS. All patients were underwent short-term Holter-monitoring during repeated 6 minutes walking test (6 MWT). The heart rate variability (HRV) has been investigated in the course of spectral analysis and time-domain methods of 5-minute ECG recorder after each 6 MWT. Distance covered and walking time till time discrepancy between load and heart rate were determined (S-1). Also walking distance at maximal ST-segment displacement (S-2) was registered. We calculated the working capacity (A, J) by Cavagna formula (1976), the data of metabolic value (MV) using N.Valeur formula (2005) and adaptation index (AI=A 2 /A 1). The risk of postoperative complication group included 12 patients with non sustained ventricular tachycardia (8 pts) and fibrillation (2 pts), re-infarction (2 pts). Basic group (48 pts) was without the complications.

Results are indicated in the Table:

variables

Basis group (n=48)

Risk group (n=12)

I test

II test

I test

II test

Contractive

S- 1, ?

242,9±75,2

292,6±67,1

194,3±92,9

134,3±83,5

A -1, J

37732±11062

45299±10278**

30216±12227

20706±1327*

? V -1

7,98±3,3

8,26±4,2*

7,26±3,1

6,87±2,8*

? I -1

1,20 *

0,69 *

Coronary

S -2, ?

249,1±44,1

231,7±43,2

206,1±103,2

115,1±25,2

A-2

30595±12205

39593±16441*

27100±11557

17613±8800*

? V -2

8,54±4,4

8,77±4,5

8,2±3,9

4,9±1,1**

AI -2

1,29 *

0,65 **

Neurohumoral

SDNN, ? s

59,8±8,7

66,5±10,6 *

50,5±8,9

38,2±7,9 *

RRi , ??

835 ± 68,2

997,6 ± 91,5*

797,3 ± 49,6

693 ± 60,1*

HF, %

35,7±6,8

48,2±9,8 *

39,3±8,6

37,2±8,4

LF, %

37,2±6,4

41,5±9,5

37,1±7,9

32,9±8,6

p<0,01 versus tests I and II; ** p<0,001 versus tests I and II.
Conclusions: shot-term Holter-monitoring during repeated 6 MWT with 5-minute ECG recorder after each 6 MWT HRV detecting alloned to quantitative assess preconditioning (reserve of adaptation) in the patients with IHD before GABS.

 

 

INTRODUCTION
Efforts to prevent ischemic injury have focused on finding ways to block events associated with irreversible ischemic injury. In 1986, Murrey et al described a classic phenomenon termed ischemic preconditioning (IP) for the first time. It was originally thought that each ischemic episode caused cumulative ATP depletion while the intermittent reperfusion would wash out the ischemic catabolites. Surprisingly ATP levels were not depleted by subsequent ischemic challenges and no infarction occurred. This observation led the same group of scientists [1] to test a slowing of consumption during ischemia associated with a rapid and protective adaptation of the myocyte. They tested this hypothesis by subjecting the myocardium to a series of four 5-min coronary branch occlusions; each separated by 5 min of reperfusion. This rendered the myocardium more resistant to the subsequent sustained 40-min ischemic insult. The infarct size was reduced to 25% of that seen in control group. This phenomenon is called "preconditioning with ischemia". Evidence of adaptation or enhanced tolerance to ischemia has been described in at least 5 clinical settings: with repeated balloon inflations during coronary angioplasty; with repeated bouts of exercise (the "walk-through" or "warm-up" phenomenon); with preinfarct angina; and with brief ischemia intentionally imposed before coronary artery bypass grafting or before harvesting donor hearts destining for transplant [2, 3]. However, quantitative assessment of range of adaptation effect of preconditioning has not been carrying out. We offered variants of quantitative, noninvasive assessment of reserve of adaptation.

Aim was to determinate contractive, coronary and neurohumoral reserve of adaptation in patients with ischemic heart disease (IHD) and chronic heart failure before GABS.

METHODS
60 patients (mean age 56.7±4.5 years, M/W 24/10) with stable angina CCS class II – III, Q-MI > 6 months, NYHA class II – IV (EF LV 34.3±3.3%) had multivessell coronary artery disease (3 and more) and waited for GABS. All patients were underwent short-term Holter-monitoring during repeated 6 minutes walking test (6 MWT). The heart rate variability (HRV) has been investigated in the course of spectral analysis and time-domain methods of 5-minute ECG recorder after each 6 MWT. Distance covered and walking time till time discrepancy between load and heart rate were determined-1). Also walking distance at maximal ST-segment displacement was registered.

We calculated the working capacity (A, J) by Cavagna formula (1976),

  1. A=m × ( 0,657×t+1,19×S) were: A-work (J), m-body weight (kg), S-distance (m) and t-time (s) till discrepancy between load and heart rate;
  2. Spend power (SP, W) by formula W=A/t were: W-power (watt), A-work value (J), t-time till discrepancy (s);
  3. The data of metabolic value (MV) using N.Valeur formula (2005) MET=(13 W/F+3,5), were: W-power (watt), F-weight (kg), MET-metabolic value index
  4. adaptation index (AI=A 2 /A 1).

Adaptation index (AI) parameters were determined on during the performance of first and second loads and they were expressed as second-to-first test ratio. If ratio value constituted more than 1, then, it was considered as adaptation reserve presence with its quantitative expression.

Risk group was singled out in order to check adaptation reserve determination effectiveness clinically

The risk of postoperative complication group included 12 patients with non sustained ventricular tachycardia (8 pts) and fibrillation (2 pts), re-infarction (2 pts), inotropic support (8 pts). Basic group (48 pts) was without the complications.

RESULTS
are indicated in the Table:

Comparison of investigation result with the use of 6 min walk test in the specified groups is listed in the table1:

The variables of two repeated modified 6MWT with detecting of working capacity till time discrepancy between load and HR in patients with stable angina and NYHA class II – IV.

Variables

Basic group ( n=22 )

Risk group (n=10)

I test

II test

I test

II test

Distance by 6 MWT, m

346,8±95,4

391,9±91,9 ^

302,1±108,6 **

286,1±136,9

Distance till discrepancy HR, m

242,9±75,2

292,6±67,1 ^^

194±92,9

134,3±83,5

Time till discrepancy HR, m

233,9±51,6 **

277,6±54,5 ^^

235,9±79,4 *

159,9±67,7

Working capacity, J

37732,3±11062 **

45299±10278 ^^

30216±12227 **

20706±13270

Spent power , W

159,1±32,7 ^

165,1±34,2 ^

135±37,6

126,5±24,3

Metabolic value

7,98±3,3 *

8,26±4,2 ^

7,26±3,1 *

6,87±2,8

Reserve of adaptation, AI

1, 2

0,68

Note: 1. versus test I and II: * – p<0,01; ** – p<0,001;
2. versus basic group and risk group: ^ – p<0,01; ^^ – p<0,001;

 

In second testing work performed increased in the main group (+20,1%; AI=1,2, p<0,01), but it decreased in the risk group (-31,5%; AI= 0,68, p<0,02). These data testify to high adaptation capability in the main group, which was evidenced by clinical observation in the postoperative period, which was evolving without complications and, on the contrary, the depletion of adaptation possibilities in the risk group was accompanied by such complications as the requirement for assisted blood circulation and inotropic support, life threatening rhythm disturbances.

Comparison for investigation result in two specified groups till ST-segments depression appearance during the load is listed in Table 2.

The variables of two repeated modified 6MWT choosing for analysis of ST-segment displacement in patients with stable angina CCS class II – III in basic and risk group

Variables

I test

II test

Basic group

( n=48)

Risk group

(n=12)

Basic group

( n=48)

Risk group

(n=12)

Distance till max ST-displacement, m

249,1±44,1

206,1±103,2 ^

231,7±43,2

115,1±25,2 *^

Time till max ST-displacement, s

263,1±46,6

175,1±17,1 ^^

239,0±42,1*

220,0±19,9 *

Working capacity, J

3 0 59 5 ±1 2205

27100±11557 ^^

3 9 59 3 ±1 6441 * *

17613±8800 **^^

Spent power , W

1 59 , 7 ±39,6

156,5±36,3** ^

1 65 , 1 ±42,3

80±11,3 ^^

Metabolic value

8,54±4,4

8,77±4,5*

8,2±3,9

4,96±1,1 ^

Reserve of adaptation (AI)

1,29

0,65

Note: 1. versus test I and II: * – p<0,01; ** – p<0,001;
2. versus basic group and risk group: ^ – p<0,01; ^^ – p<0,001;

 

Work performed and spent power in the basic group during second testing increased (22,7%, p<0,01, AI=1,29), as for risk group, the above –mentioned constituents decreased (-32,9%, AI=0,65, p<0,001). These data testify to increased tolerance to ischaemia during the second test and cardioprotective influence of first ischaemic episode on the subsequentone during this second test.

Comparison for dynamics change in adaptation reserve index depending on FC NYHA and for stable angina according to CCS. Significant increment for adaptation reserves in patients with FC II-III according to NYHA and III FC according to CCS and adaptation reserve depletion in patients with FC IV NYHA and stable angina FC according to CCS (p<0,001).

Figura 1: Adaptation index comparison depending upon FC according to NYHA and stable angina according to CCS.

Comparison between investigation results for 5 min recording and heart rhythm variability in two specified groups is listed in table 3.

The variables of heart rate variability choosing for analysis during two repeated modified 6MWT in patients with stable angina CCS class II – III in basic and risk group

Variables

Basic group (n=48)

Risk group (n=12)

I test

II test

I test

II test

SDNN, ms

59,8±8,7^

66,5±10,6^

50,5±8,9

38,2±7,9

RRi , ms

835 ±123 ,2 ^

9 9 7,6 ±91 ,5* *^

7 97 ,3 ±49 , 6^

693± 60,1* ^

rMSSD , ms

29,9 (16,4-44,4)^

25,9 (16,0-40,0)^

10,4 (5,4-17,8)

15,5 (7,3-32,4)

HF, %

35,7±6,8^

48,2±9,8

39,3±8,6

37,2±8,4*

LF, %

37,2±6,4

41,5±9,8

37,1±7,9

32,9±8,4

VLF, %

18,4±8,6^

21,6±9,1

23,3±6,9^

25,2±6,8^

Reserve of adaptation

1,11

0,75

Note: m±SD; * are indicated,*- mediians are listed 25 and 75 quartiles for index distribution
1) versus I group and II group: ** - p<0,01
2) versus basic and risk group: ^ - 0,01

 

In repeated testing, time and spectral indices were increasing in the basic group (AI>1), as for the risk groups, these indeces were decreasing (AI<1), which testifyies to high neurohumoral adaptation capability in the basic group, however, depletion of adaptation possibility was noted in the risk group.

CONCLUSION
The above – listed investigation results demonstrate the reality as for preconditioning phenomenon reproduction in clinical setting with quantitative assesment for its expressivity. While summing up the result obtained by us, it is easy to get, convinced that preconditioning effect is also observed at coronary blood circulation level, in myocardial contractile function, in heart rhythm variability which testifies to neurohumoral influences. The method described by us above is distinguished, first by its rapidity, second, provides quantitative characteristic for phenomenon expressivity. It allows to manage obtained for risk specification of surgical interventions and for objective solutions of labour examination problems.

 

BIBLIOGRAPHY

  1. Murray CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell in ischemic myocardium. Circulation 1986 ; 74: 1124-36.
  2. Przyklenk K., Kloner RA. Ishemic preconditioning: exploring the paradox. Prog Cardiovasc Dis 1998 ; 40:517-54
  3. Yellon DM, Dana A. The preconditioning phenomen: a tool for the scientist or a clinical rea

 

 

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