Preserved autoregulation of coronary flow after off-pump coronary artery bypass grafting: retrospective assessment of intraoperative transit time flowmetry with and without intra-aortic balloon counterpulsation
Nakajima et al. Journal of Cardiothoracic Surgery
Preserved autoregulation of coronary flow after off-pump coronary artery bypass grafting: retrospective assessment of intraoperative transit time flowmetry with and without intra-aortic balloon counterpulsation
Background: Intra-aortic balloon pumping (IABP) markedly increases graft flow after coronary artery bypass grafting (CABG) with cardiopulmonary bypass. We sought to delineate the effects of IABP on graft flow after off-pump CABG (OPCAB). Methods: The clinical records of 32 patients (25 male, 7 female; mean age: 70 ± 9 years) who underwent OPCAB with IABP between January 2011 and May 2015 were retrospectively reviewed. Thirteen patients (41%) had a history of myocardial infarction, and 13 patients (41%) had a history of percutaneous coronary intervention. In total, there were 76 bypass grafts with 102 distal anastomoses. These included 50 in situ or pedicled grafts and 26 aortocoronary grafts. After completion of the anastomoses, the heart was positioned normally, and graft flow with IABP was measured using transit-time flowmetry under stable circulation. Then, IABP was turned off for 30 s to a few minutes, until graft flow was constant, for measurement of flow off IABP. Results: The angiographic patency rate was 100% (47/47). Overall, graft flow was 55 ± 36 ml/min on IABP and 53 ± 36 ml/min off IABP (p = 0.37). The pulsatility index was 4.1 ± 2.1 on IABP and 2.7 ± 1.5 off IABP (p < 0.001). There was no significant difference in graft flow between on and off IABP for aortocoronary bypass or in situ grafts. Graft flow was 57 ± 36 ml/min on IABP and 55 ± 37 ml/min off IABP (p = 0.41) in in situ grafts and 52 ± 34 ml/min on IABP and 49 ± 35 off IABP (p = 0.41) in aortocoronary grafts. Graft flow on IABP was more than 5 ml/min greater in 28 (37%) bypass grafts, and more than 5 ml/min lower in 20 (26%) bypass grafts. Conclusion: In contrast to previous reports for conventional CABG, graft flow after OPCAB was not necessarily increased by IABP, regardless of elevated diastolic arterial pressure. It is suggested that preserved autoregulation of coronary flow contributes to a lower impact on the heart and early functional recovery, and consequently, greater perioperative safety of OPCAB.
Off-pump; CABG; Surgery; Autoregulation; Graft flow
Off-pump coronary artery bypass grafting (OPCAB) is
beneficial for patients with systemic comorbidities, such as
renal or lung disease, or aortic calcification, or in patients
who are elderly. OPCAB was also reported to have less
impact than conventional on-pump coronary artery bypass
grafting (ONCAB) on cardiac function as determined by
cardiac enzyme release [1–3], and allowed earlier recovery
of the myocardium after surgery [4, 5]. In addition,
subendocardial myocardial damage was frequently detected by
magnetic resonance imaging after on-pump beating
coronary artery bypass graft (OBCAB) . However, the effects
of OPCAB on the myocardium or perioperative coronary
circulation have not yet been fully determined.
In the present study, we examined the effects of
intraaortic balloon pumping (IABP) on graft flow after
OPCAB, and compared the effects with those after
ONCAB to determine the influence of cardiopulmonary
bypass on flow regulation and the physiological nature
of the coronary circulation after OPCAB.
Clinical records and angiograms of 32 patients (25 male,
7 female; mean age: 70 ± 9 years) who underwent
OPCAB with IABP between January 2011 and May 2015
at our institution were retrospectively reviewed. This
study was approved by our institutional review board.
As shown in Table 1, 76 bypass grafts with 102 distal
anastomoses were created. Mean targets were 3.2 ± 0.8.
Twelve (38%) patients had diabetes mellitus, and 13
(41%) patients had a history of percutaneous coronary
Conduit types are listed in Table 2. There were 50 in
situ (pedicled) grafts, including 38 in situ internal
thoracic artery (ITA), 3 in situ gastroepiploic artery, and 9
Table 1 Baseline patients' characteristics
Renal dysfunction (Creatinin > 2.0)
History of percutaneous coronary intervention
History of myocardial infarction
Ejection fraction of left ventricle (%)
Ejection fraction of left ventricle < 40%
Table 2 Conduit types
In-situ (pedicled)graft In-situ ITA
in-situ ITA with free ITA
in-situ ITA with radial artery
GEA gastroepiploic artery, ITA internal thoracic artery
composite grafts, and 26 aortocoronary grafts, including
25 saphenous vein grafts and one free ITA. The
indication for IABP was unstable angina pectoris following
acute or recent myocardial infarction in 11, unstable angina
without myocardial infarction in 20. In one patient, acute
myocardial infarction was due to coronary dissection
during coronary intervention. Patients, who presented
cardiogenic shock, necessitated cardiopulmonary bypass were
excluded. In preoperative coronary angiography, TIMI
grade II antegrade or reduced collateral flow was found in 6
coronary vessels of 5 patients. Operation was emergent or
urgent in all but one patient, who had poor left ventricular
function resulting from an old myocardial infarction. No
patient had atrial fibrillation.
Details of the OPCAB procedure and routine flow
measurement have been reported previously . After
completion of the anastomoses, the position of the heart
was returned to normal. Flow measurement using
transit-time flowmetry (TTFM; Medi-stim, Oslo,
Norway) was started when the haemodynamics became
stable, which was usually at a systolic blood pressure
greater than 100 mmHg, usually with low dose of
noradrenaline and dopamine. First, graft flow under 1:1
IABP support was recorded. Then, IABP was turned off
for a period of 30 s to a few minutes. When graft flow
became constant, it was recorded. The measurement
usually took less than 5 min. The haemodynamic status,
such as blood pressure, heart rate, and dose of
catecholamine could not be strictly defined, but the
haemodynamic status and dose of catecholamine during flow
measurement on IABP and off IABP were comparable in
each patient. For sequential or composite bypass grafts,
graft flow was measured in the proximal graft. For
patients without renal dysfunction or other comorbidity,
such as severe calcification of the aorta or severe chronic
obstructive pulmonary disease, catheter or computed
tomography coronary angiography was performed about
2 weeks after surgery.
The continuous variables are expressed as mean ±
standard deviation and compared with the unpaired Student
t-test, using SPSS version 8.0 (SPSS Inc., Chicago, IL,
USA). Differences in outcomes were considered
statistically significant when at p < 0.05.
In postoperative angiography, the graft patency rate was
found to be 100% (47/47). Mean graft flow was 55 ±
36 ml/min on IABP and 53 ± 36 ml/min off IABP (Fig. 1).
Flow was 3.8% higher on IABP but the difference was
not statistically significant (p = 0.37). The pulsatility
index on IABP was 4.1 ± 2.1, and was significantly higher
than off IABP (2.7 ± 1.5; p < 0.001) (Fig. 2).
In situ grafts and aortocoronary bypass grafts were
analysed separately. There was no significant difference in
graft flow between on and off IABP for aortocoronary
bypass or in situ grafts. Mean graft flow was 57 ± 36 ml/
min on IABP and 55 ± 37 ml/min off IABP (p = 0.41) in in
situ grafts, and 52 ± 34 ml/min on IABP and 49 ± 35 ml/
min off IABP (p = 0.41) in aortocoronary grafts. The
pulsatility index was 3.8 ± 1.5 on IABP and 2.5 ± 1.0 off IABP
in in situ grafts (p < 0.001) and 4.6 ± 2.9 on IABP and 3.3
± 2.1 off IABP in aortocoronary bypass grafts (p < 0.001).
Compared with off IABP, mean graft flow on IABP
was greater in 42 (55%) bypass grafts, and lower in 32
(42%) bypass grafts. The changes in each patient are
shown in Fig. 3. Graft flow on IABP was more than
5 ml/min greater in 28 (37%) bypass grafts, and more
than 5 ml/min lower in 20 (26%) bypass grafts.
After OPCAB, patients have been reported to have less
myocardial injury as determined by biochemical
analyses. Koh and colleagues measured serial troponin T
release and reported less damage during OPCAB than
Fig. 1 Mean graft flow during on IABP (left) and off IABP (right).
There was no significant difference (p = 0.37)
Fig. 2 Pulsatility Index during on IABP (left) and off IABP (right). PI
on IABP was significantly higher than that during off IABP (p < .001)
ONCAB . Dijk and colleagues reported that creatine
kinase-MB release after OPCAB was reduced compared
with ONCAB . Although it is difficult to distinguish
myocardial stunning from irreversible injury even with
biochemical markers, electrocardiography, or functional
assessment , several studies confirmed that off-pump
surgery improved left ventricular contractility early after
surgery [4, 5]. In the late follow-up period, there was no
significant difference between ONCAB versus OPCAB
in the incidence or extent of irreversible myocardial
injury , or in left ventricular function at 6 months .
Cardiac magnetic resonance imaging is reported to be
reliable for detecting perioperative small myocardial necrosis
. Rahimi and colleagues reported that
revascularizationrelated hyper-enhancement was found in 32% of patients
and predicted an adverse cardiac event after percutaneous
coronary intervention or coronary artery bypass grafting
. Pegg and colleagues reported that the incidence of new
irreversible myocardial injury was significantly higher in
OBCAB than ONCAB under cardiac arrest .
It is generally accepted that IABP has a beneficial
effect in reducing cardiac work or myocardial afterload.
However, it is unclear whether there is an increase in
blood flow through stenotic coronary vessels or
increased collateral flow. Williams and colleagues reported
that, after IABP in patients who had unstable angina
with left anterior descending coronary artery stenosis,
O2 consumption was reduced, but great cardiac vein
flow was also reduced . Yoshitani and colleagues
reported that use of IABP decreased diastolic
intraluminal pressure distal to the stenosis, especially when the
stenosis was severe . In contrast, Takeuchi and
colleagues reported a significant increase in coronary flow
distal to the stenosis .
Several studies have reported that blood flow in bypass
grafts was markedly increased by IABP. In an animal
Fig. 3 Changes of mean graft flow during on IABP and off IABP. Graft flow on IABP was more than 5 ml/min greater in 28 (37%) bypass grafts
(left), and more than 5 ml/min lower in 20 (26%) bypass grafts (right), and the difference was less than 5 ml/min in 28 (37%) bypass grafts (middle)
model, IABP increased diastolic flow by 75% in
aortocoronary bypass grafts and by 38% in ITA grafts . In
that experimental study, graft flow was measured after
on-pump surgery and cardiac arrest. In a clinical study,
Onorati and colleagues found highly significant increases
of 50–90% in blood flow in all kinds of grafts . In
their report, 78% of patients underwent ONCAB. Rubino
and colleagues reported an increase in graft flow of 55–
95% with IABP in patients after ONCAB . Takami
and colleagues examined graft flow in 84 patients, 45%
of who had ONCAB, and reported that mean flow was
significantly increased by 23% . In general in these
previous studies, the mean increase in graft flow was
greater as the proportion of ONCAB increased.
Consequently, Onorati and colleagues concluded that a
combination of IABP and TTFM were useful for detecting
graft failure , such that no increase in flow with
IABP indicated a failed graft.
However, these results may be contradictory to the
concept of “autoregulation”, which is characterised by
the adaptability of vascular resistance to changes in
blood pressure over a wide range, and is essential for
maintaining appropriate flow distribution in different
regions and layers with variable vascular resistance, such
as the endocardial or epicardial myocardium . In
addition, in patients with multivessel disease, vascular
resistance in the area of the collateral receiving vessel
must be significantly lower than that in the area of the
collateral delivering vessel. According to a few papers
investigating the effects of IABP in normal coronary
arteries, there was an increase in coronary flow of only
1.1%  or 11% .
Balacumaraswami and colleagues investigated arterial
pressure and blood flow in bypass grafts and compared
ONCAB with OPCAB . After ONCAB, graft flow
was significantly higher for all grafts than after OPCAB,
and the flow/pressure ratio was greater for all grafts after
ONCAB . The study mentioned that reactive
hyperaemia resulting from cardiopulmonary bypass and
myocardial ischemia was the mechanism for increased graft
flow, in spite of lower arterial pressure.
Cardiopulmonary bypass causes not only a systemic inflammatory
response and multiorgan dysfunction , but also a
cardiac hyperaemic state, resulting in impairment of
autoregulation. In addition, Ono and colleagues reported
that impaired autoregulation of cerebral blood flow by
cardiopulmonary bypass was detected in 20% of their
patients, and associated with perioperative stroke .
In the present study, there was no significant
difference in graft flow between on IABP and off IABP after
OPCAB, suggesting that OPCAB has specific
physiological characteristics. We suggest that autoregulation
may be preserved or minimally damaged by OPCAB as
there is only localized rather than global cardiac
ischemia. In addition, the increase in flow with IABP in
proportion to the increase in diastolic pressure in
previous studies may be attributable to a “hyperaemic state”
induced by cardiopulmonary bypass and cardiac arrest.
In the current study, graft flow on IABP was markedly
lower than flow without IABP in 26% of bypass grafts.
One reason for this is that reduced cardiac work and
oxygen demand with IABP could decrease coronary
flow, irrespective of higher diastolic pressure. Another
possibility is that there is decreased resistance through
the stenotic portion of the native coronary artery when
diastolic blood pressure increases . Thus, IABP may
increase blood flow through the native coronary artery
with severe stenosis or the collateral circulation, rather
than the bypass graft without stenosis. This would be
consistent with the absence of an increase in pressure
in the vessel distal to the severe stenosis, as reported by
Yoshitani and colleagues .
There are implications arising from this study. As
mentioned in previous papers, one explanation for
subendocardial damage in OBCAB may be inadequate
coronary perfusion to distal territories . We suggest,
first, that another possible explanation may be preserved
autoregulation after OPCAB, which would function to
protect from malperfusion even in coronary circulation
with variable vascular resistance. Second, TTFM during
OPCAB may reflect a more physiological and natural
coronary circulation compared with ONCAB. Therefore,
TTFM during OPCAB is considered reliable for
detecting not only technical failure, but also future graft
occlusion associated with poor graft flow resulting from
moderate native coronary stenosis or poor flow demand
. Third, even in our limited experience, the patency
of a graft is not correlated with an increase or decrease
in graft flow with IABP, in contrast to the effect of IABP
after ONCAB. Consequently, preserved autoregulation
would play a definitive role in the perioperative safety of
OPCAB. We suggest that autoregulation may be
associated with a lower risk of hypoperfusion syndrome as a
result of in situ ITA grafting, even after division of the
old saphenous vein graft in redo off-pump surgery.
Conversely, there may be a concern over increased risk of
coronary spasm during OPCAB because of the absence
of vasodilatation by induced hyperaemia.
This study has a few limitations. First, the number of
patients was limited. If a larger number of bypass grafts
were analysed, differences in graft flow between on IABP
and off IABP may have reached statistical significance.
However, we consider that any difference would never
be as great as those reported in previous ONCAB
studies. Second, selection bias might have been present, as
most of our patients had unstable angina and urgent or
emergency surgery was required. In such situations,
coronary flow could be impaired by the underlying
myocardial stunning. In addition, preoperative
angiography showed coronary flow of TIMI grade II in 5
patients, which might be associated with ischemic damage
on microvascular circulation. We presume that, however,
increased graft flow during IABP cessation, which was
seen in 26% of bypass grafts, could not be explained by
microvacular damage or myocardial stunning. These
were inevitable limitations of a retrospective
observational study in the clinical field. Taking these into
account, however, we believe that this study indicates that
there is regulation of coronary flow after OPCAB, in
contrast to the state after ONCAB.
In conclusion, graft flow after OPCAB is not necessarily
increased by IABP, probably because damage to coronary
autoregulation is minimal. In contrast to ONCAB, the
absence of an increase in mean flow with IABP was not
indicative of possible graft occlusion or the necessity for
anastomotic revision. Preserved autoregulation is a
possible mechanism and would be consistent with the less
invasive nature of OPCAB compared with ONCAB.
Further investigations are necessary to confirm these
IABP: Intraaortic balloon pumping; ITA: Internal thoracic artery; OBCAB:
Onpump beating coronary artery bypass grafting; ONCAB: On-pump
conventional coronary artery bypass grafting; OPCAB: Off-pump coronary
artery bypass grafting; PI: Pulsatility index; TTFM: Transit-time flowmetry
HNa carried out data analysis and writing manuscript. AI participated in the
design of study. MT supported writing manuscript. MK participated in
collection of data. KU participated in the design of the study and performed
the statistical analysis. MI carried out data collection. TA and HNi conceived
of the study, and participated in its design and coordination and helped to
draft the manuscript. All authors read and approved the final manuscript.
Ethics approval and consent to participate
This retrospective study was approved by institutional review board of
Saitama Medical University International Medical Center. For retrospective
observational study, written informed consent was waived. Approval
1. Koh TW , Carr-White GS , DeSouza AC , Ferdinand FD , Hooper J , Kemp M , Gibson DG , Pepper JR . Intraoperative cardiac troponin T release and lactate metabolism during coronary artery surgery: comparison of beating heart with conventional coronary artery surgery with cardiopulmonary bypass . Heart . 1999 ; 81 ( 5 ): 495 - 500 .
2. van Dijk D , Nierich AP , Jansen EW , Nathoe HM , Suyker WJ , Diephuis JC , van Boven WJ , Borst C , Buskens E , Grobbee DE , Robles De Medina EO , de Jaegere PP . Octopus Study Group. Early outcome after off-pump versus onpump coronary bypass surgery: results from a randomized study . Circulation . 2001 ; 104 ( 15 ): 1761 - 6 .
3. Taggart DP . Biochemical assessment of myocardial injury after cardiac surgery: effects of a platelet activating factor antagonist, bilateral internal thoracic artery grafts, and coronary endarterectomy . J Thorac Cardiovasc Surg . 2000 ; 120 ( 4 ): 651 - 9 .
4. Selvanayagam JB , Petersen SE , Francis JM , Robson MD , Kardos A , Neubauer S , Taggart DP. Effects of off-pump versus on-pump coronary surgery on reversible and irreversible myocardial injury: a randomized trial using cardiovascular magnetic resonance imaging and biochemical markers . Circulation . 2004 ; 109 ( 3 ): 345 - 50 .
5. Selvanayagam JB , Kardos A , Francis JM , Wiesmann F , Petersen SE , Taggart DP , Neubauer S. Value of delayed-enhancement cardiovascular magnetic resonance imaging in predicting myocardial viability after surgical revascularization . Circulation . 2004 ; 110 ( 12 ): 1535 - 41 .
6. Pegg TJ , Selvanayagam JB , Francis JM , Karamitsos TD , Maunsell Z , Yu LM , Neubauer S , Taggart DP. A randomized trial of on-pump beating heart and conventional cardioplegic arrest in coronary artery bypass surgery patients with impaired left ventricular function using cardiac magnetic resonance imaging and biochemical markers . Circulation . 2008 ; 118 : 2130 - 8 .
7. Takazawa A , Nakajima H , Iguchi A , Tabata M , Morita K , Koike H , Uwabe K , Asakura T , Niinami H. Impacts of intraoperative flow on graft patency of sequential and individual saphenous vein grafts . Innovations (Phila) . 2015 ; 10 ( 2 ): 85 - 9 .
8. Monte GU , Drager LF , Souza FS , Avila LF , Parga Filho JR , César LA , Izaki M , Meneghetti JC , Rochitte CE , Kalil FR . Magnetic resonance vs technetium99 m pyrophosphate scintigraphy in the detection of perioperative myocardial necrosis . Arq Bras Cardiol . 2008 ; 91 ( 2 ): 113 - 8 .
9. Rahimi K , Banning AP , Cheng AS , Pegg TJ , Karamitsos TD , Channon KM , Darby S , Taggart DP , Neubauer S , Selvanayagam JB. Prognostic value of coronary revascularisation-related myocardial injury: a cardiac magnetic resonance imaging study . Heart . 2009 ; 95 ( 23 ): 1937 - 43 .
10. Williams DO , Korr KS , Gewirtz H , Most AS . The effect of intraaortic balloon counterpulsation on regional myocardial blood flow and oxygen consumption in the presence of coronary artery stenosis in patients with unstable angina . Circulation . 1982 ; 66 ( 3 ): 593 - 7 .
11. Yoshitani H , Akasaka T , Kaji S , Kawamoto T , Kume T , Neishi Y , Koyama Y , Yoshida K. Effects of intra-aortic balloon counterpulsation on coronary pressure in patients with stenotic coronary arteries . Am Heart J . 2007 ; 154 ( 4 ): 725 - 31 .
12. Takeuchi M , Nohtomi Y , Yoshitani H , Miyazaki C , Sakamoto K , Yoshikawa J. Enhanced coronary flow velocity during intra-aortic balloon pumping assessed by transthoracic Doppler echocardiography . J Am Coll Cardiol . 2004 ; 43 ( 3 ): 368 - 76 .
13. Tedoriya T , Kawasuji M , Sakakibara N , Takemura H , Watanabe Y , Hetzer R. Coronary bypass flow during use of intraaortic balloon pumping and left ventricular assist device . Ann Thorac Surg . 1998 ; 66 ( 2 ): 477 - 81 .
14. Onorati F , Santarpino G , Rubino A , Cristodoro L , Scalas C , Renzulli A. Intraoperative bypass graft flow in intra-aortic balloon pump-supported patients: differences in arterial and venous sequential conduits . J Thorac Cardiovasc Surg . 2009 ; 138 ( 1 ): 54 - 61 .
15. Rubino AS , Onorati F , Scalas C , Serraino GF , Marsico R , Gelsomino S , Lorusso R , Renzulli A. Intra-aortic balloon pumping recruits graft flow reserve by lowering coronary resistances . Int J Cardiol . 2012 ; 154 ( 3 ): 293 - 8 . doi:10.1016/j. ijcard. 2010 .09.058. Epub 2010 Oct 25.
16. Takami Y , Masumoto H. Effects of intra-aortic balloon pumping on graft flow in coronary surgery: an intraoperative transit-time flowmetric study . Ann Thorac Surg . 2008 ; 86 ( 3 ): 823 - 7 .
17 Rouleau J , Boerboom LE , Surjadhana A , Hoffman JI . The role of autoregulation and tissue diastolic pressures in the transmural distribution of left ventricular blood flow in anesthetized dogs . Circ Res . 1979 ; 45 ( 6 ): 804 - 15 .
18 19 20 21 22 23 24 Anderson RD , Gurbel PA . The effect of intra-aortic balloon counterpulsation on coronary blood flow velocity distal to coronary artery stenoses .
Cardiology. 1996 ; 87 ( 4 ): 306 - 12 .
Kimura A , Toyota E , Lu S , Goto M , Yada T , Chiba Y , Ebata J , Tachibana H , Ogasawara Y , Tsujioka K , Kajiya F. Effects of intraaortic balloon pumping on septal arterial blood flow velocity waveform during severe left main coronary artery stenosis . J Am Coll Cardiol . 1996 ; 27 ( 4 ): 810 - 6 .
The effects of on-pump and off-pump coronary artery bypass grafting on intraoperative graft flow in arterial and venous conduits defined by a flow/ pressure ratio . J Thorac Cardiovasc Surg . 2008 ; 135 ( 3 ): 533 - 9 .
Inflammatory response after coronary revascularization with or without cardiopulmonary bypass . Ann Thorac Surg . 2000 ; 69 ( 4 ): 1198 - 204 .
Schwartz JS , Carlyle PF , Cohn JN . Effect of coronary arterial pressure on coronary stenosis resistance . Circulation . 1980 ; 61 ( 1 ): 70 - 6 .
Nakajima H , Iguchi A , Tabata M , Koike H , Morita K , Takahashi K , Asakura T , Nishimura S , Niinami H. Predictors and prevention of flow insufficiency due to limited flow demand . J Cardiothorac Surg . 2014 ; 9 : 188 .