Comparison between the Effects of Bretschneider’s HTK Solution and Cold Blood Cardioplegia on Systemic Endothelial Functions in Patients who Undergo Coronary Artery Bypass Surgery: a Prospective Randomized and Controlled Trial

Mercan, Ilker; Dereli, Yuksel; Topcu, Cemile; Tanyeli, Omer; Isik, Mehmet; Gormus, Niyazi; Ozturk, Elifnur Yildirim

doi:10.21470/1678-9741-2019-0327

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Brazilian Journal of Cardiovascular Surgery

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ORIGINAL ARTICLE • Braz. J. Cardiovasc. Surg. 35 (5) • Sep-Oct 2020 • https://doi.org/10.21470/1678-9741-2019-0327 copy

Comparison between the Effects of Bretschneider’s HTK Solution and Cold Blood Cardioplegia on Systemic Endothelial Functions in Patients who Undergo Coronary Artery Bypass Surgery: a Prospective Randomized and Controlled Trial

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

To investigate the effects of Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) solution and cold blood cardioplegia on systemic endothelial functions.

Methods:

A total of 50 patients who underwent isolated coronary artery bypass surgery between March 2018 and May 2018 were randomly divided into two groups - group 1 (Bretschneider’s HTK solution, n=25) and group 2 (cold blood cardioplegia, n=25). Data related to the indicators of endothelial dysfunction were recorded. Flow-mediated dilation was measured together with the assessment of the values of endothelin-1, von Willebrand factor, and asymmetric dimethylarginine to identify endothelial dysfunction. Then, the two groups were compared regarding these values.

Results:

The most significant result of our study was that the endothelin-1 level was significantly higher in group 2 than in group 1 (P<0.001). The value of flow-mediated dilation was found to increase to a lesser degree on the postoperative days compared to the value at the day of admission in group 1 (P=0.002 and P=0.030, respectively).

Conclusion:

Cardiopulmonary bypass leads to endothelial dysfunction. Our results revealed that Bretschneider’s HTK solution causes less severe endothelial injury than cold blood cardioplegia.

Keywords:
Bretschneider cardioplegic solution. Von Willebrand Factor. Histidine. Heart Arrest; Induced. Potassium Chloride. Coronary Artery Bypass

Abbreviations, acronyms & symbols
ACE ACT ADMA AF ANOVA BMI CABG CBC COPD CPB DM EDHF ELISA ET-1	= Angiotensin-converting enzyme = Activated clotting time = Asymmetric dimethylarginine = Atrial fibrillation = Analysis of variance = Body mass index = Coronary artery bypass grafting = Cold blood cardioplegia = Chronic obstructive pulmonary disease = Cardiopulmonary bypass = Diabetes mellitus = Endothelium-derived hyperpolarizing factor = Enzyme-linked immunosorbent assay = Endothelin-1		FMD HT HTK ICU IMA IU LAD LVEF NO PAD SD vWF WU	= Flow-mediated dilation = Arterial hypertension = Histidine-tryptophan-ketoglutarate = Intensive care unit = Internal mammary artery = International unit = Left anterior descending = Left ventricular ejection fraction = Nitric oxide = Peripheral arterial disease = Standard deviation = von Willebrand factor = Wisconsin University

Variables		Bretschneider's HTK	Cold blood cardioplegia	P-value
Age (mean ± SD)	(year)	60.1±7.8	62.7±9.4	0.183^* * Mann-Whitney U test
Sex, n (%)	Male	19 (76)	21 (84)	0.480^ Chi-square test
	Female	6 (24)	4 (16)
BMI (mean ± SD)	Kg/cm²	29.7±4.3	27.8±3.4	0.140^* * Mann-Whitney U test
LVEF (mean ± SD)	(%)	54.0±5.7	53.8±5.6	0.771^* * Mann-Whitney U test
Amount of cardioplegia (mean ± SD)^* * Mann-Whitney U test	(cc)	1285±196	1838±344	0.001^* * Mann-Whitney U test
Medical treatments	ACE inhibitor (+)	16 (64)	18 (72)	0.544^ Chi-square test
	Beta-blocker (+)	23 (92)	25 (100)	0.149^ Chi-square test
	Statin (+)	10 (40)	7 (28)	0.370^ Chi-square test
	Diuretic (+)	7 (28)	6 (24)	0.747^ Chi-square test
	Aspirin (+)	22 (88)	24 (96)	0.297^ Chi-square test
Comorbid diseases	Type 2 DM (+)	12 (48)	13 (52)	0.777^ Chi-square test
	HT (+)	17 (68)	12 (48)	0.152^ Chi-square test
	Hyperlipidemia (+)	9 (36)	12 (48)	0.390^ Chi-square test
	COPD (+)	3 (12)	3 (12)	1.000^ Chi-square test
	PAD (+)	0	0	1.000^ Chi-square test
Operative features	Dose of heparin (IU)	30.120±5.174	28.260±3.565	0.202^* * Mann-Whitney U test
	Dose of protamine (mg)	30.960±5.175	31.800±4.536	0.503^* * Mann-Whitney U test
	ACT (sec)	478±55	498±57	0.157^* * Mann-Whitney U test
	Pump output ACT value	114±6	112±12	0.259^* * Mann-Whitney U test
	Aortic clamp time (sec)	54.5±15.4	49.7±10.9	0.491^* * Mann-Whitney U test
	Cardiopulmonary bypass time (min)	94.2±23.7	93.3±21.1	0.719^* * Mann-Whitney U test
	Average heat CPB (ºC)	31.9±0.8	31.7±0.5	0.159^* * Mann-Whitney U test
	Side clamp time (min)	19.8±11.7	21.2±11.6	0.854^* * Mann-Whitney U test
	Heart re-beat type^* ***** Heart re-beat type: after removal of the cross-clamp, the patients who needed defibrillation were identified as fibrillated and the group of patients who did not require defibrillation were identified as spontaneously.			0,024^ Chi-square test
	Spontaneously	9 (36)	17 (68)
	Fibrillated	16 (64)	8 (32)
	Cardiac arrest time (sec)	38.3±10.4	39.9±18.4	0.961^* * Mann-Whitney U test
	Intraoperative urine amount (cc)	385±242	339±126	0.876^* * Mann-Whitney U test
	Intraoperative blood product use (+)	1 (4)	2 (8)	0.600^ Chi-square test
	Number of coronary lesions	3.0±0.7	3.1±0.7	0.734^* * Mann-Whitney U test
	Number of bypass	3.0±0.7	3.1±0.7	0.578^* * Mann-Whitney U test
	Use of IMA	25 (100)	25 (100)	1.000^ Chi-square test

		Bretschneider's HTK	Cold blood cardioplegia	F statistic	P-value^* * Two-way analysis of variance for mixed measured		F statistic	P-value^* * Two-way analysis of variance for mixed measured		F statistic	P-value^* * Two-way analysis of variance for mixed measured
ADMA (µmol/L)	T0	100±26	100±52	18.833	0.001	Group	2.59	0.115	ADMA group interaction	1.886	014
	T1	148±34	157±44
	T2	140±57	149±41
	T3	128±46	155±51
	T4	121±50	145±52
vWF (U/L)	T0	4.0±0.6	4.2±0.8	66.287	0.001	Group	0.019	0.892	vWF group interaction	2.79	0.043
	T1	5.9±1.2	6.3±1.2
	T2	5.6±1.2	5.5±1.3
	T3	5.1±1.1	4.7±1.0
	T4	4.7±0.7	4.6±0.7
ET-1 (pg/mL)	T0	38.7±12.5	36.6±5.2	99.115	0.001	Group	10.923	0.002	ET-1 group interaction	8.957	0.001
	T1	59.0±13.1	68.4±6.2
	T2	56.5±14.0	66.6±6.4
	T3	49.4±15.0	63.5±7.8
	T4	45.5±11.0	53.5±10.2
Lactate (mmol/L)	T0	1.4±0.4	1.4±0.4	25.32	0.001	Group	1.67	0.202	Lactate group interaction	1.23	0.301
	T1	2.5±0.5	2.1±1.1
	T2	1.9±0.6	1.8±0.6
	T3	1.7±0.5	1.4±0.4
	T4	1.5±0.4	1.5±0.5
FMD (%)	T0	6.20±0,92	6.10±1.14	46.083	0.001	Group	4.326	0.043	FMD group interaction	6.58	0.008
	T2	5.57±0.79	4.68±1.02
	T4	5.74±0.81	5.27±0.89

		Bretschneider's HTK	Cold blood cardioplegia	P-value
Total complications	n (%)	11 (44)	13 (52)	0.571
Pulmonary	n (%)	7 (28)	7 (28)	1.000
Antibiotic revision	n (%)	3 (12)	8 (32)	0.088
Arrhythmia	n (%)	2 (8)	5 (20)	0.221
Neurological	n (%)	2 (8)	2 (8)	1.000
Renal	n (%)	2 (8)	2 (8)	1.000
Gastrointestinal	n (%)	1 (4)	0	0.312

		Bretschneider's HTK	Cold blood cardioplegia	P-value
Amount of drainage	(cc)	1027±362	1123±450	0.600
Amount of blood used	unit	1.7±1.1	1.7±1.4	0.819
Inotropic need and dosage	mcg/kg/day	0.039±0.058	0.040±0.053	0.460
Extubation time	(hour)	9.6±2.7	10.8±4.2	0.335
ICU stay	(hour)	42.8±17.4	46.4±19.7	0.366

Authors' roles & responsibilities

IM
YD
CT
OT
MI
NG
EYO

Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published
Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published
Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; final approval of the version to be published
Drafting the work or revising it critically for important intellectual content; final approval of the version to be published
Final approval of the version to be published
Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; final approval of the version to be published
Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; final approval of the version to be published

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[1] Ilker Mercan Department of Cardiovascular Surgery, Konya Training and Research Hospital Hacı Şaban Mah. Yeni Meram Cad. Nº:97, Meram, Konya, Turkey. Zip Code: 42090 E-mail: drilkermercan@hotmail.com