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J Thorac Cardiovasc Surg 2002;123:53-62
© 2002 The American Association for Thoracic Surgery
Cardiopulmonary Support and Physiology |
From the Section of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, Ga.
Supported by the Carlyle Fraser Heart Center of Crawford Long Hospital, Emory University, and a Scientific Development Award (Z-QZ) and a Grant-in-Aid (JV-J) from the National American Heart Association.
Received for publication Dec 20, 2000. Revisions requested April 17, 2001; revisions received May 14, 2001. Accepted for publication June 15, 2001. Address for reprints: Jakob Vinten-Johansen, PhD, Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, 550 Peachtree Street NE, Atlanta, GA 30308-2225 (E-mail: jvinten{at}emory.edu).
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90% of left anterior descending diameter) and during active coronary perfusion with a constant flow pump. Measurements were made under normotension and hypotension produced by partial caval occlusion to reduce arterial pressure by 50%. |
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1,2 However, OPCAB usually requires a period of target coronary artery occlusion to achieve adequate visibility during distal anastomosis. This transient ischemic period may be superimposed on preexisting ischemia of varying degrees and may produce myocardial damage to the target segment. 3,4 In addition, retraction and stabilization maneuvers during OPCAB often cause hemodynamic instability and systemic hypotension, especially when the hearts are displaced vertically for exposure of lateral and posterior branches, 5,6 which may necessitate prompt conversion to conventional on-pump coronary artery bypass grafting. In this regard hemodynamic instability during displacement of the heart has been addressed with mechanical support systems for either the left 7 or right 8 ventricle. Several clinical studies have shown the effectiveness of intracoronary shunts to maintain myocardial perfusion to avoid ischemia of target vessels during routine OPCAB. 9-11 However, it is unclear how the adequacy of blood flow is affected by intracoronary shunts when systemic blood pressure, which drives coronary flow, is reduced by means of retraction and stabilization maneuvers during OPCAB.
In this regard we recently introduced the concept of perfusion-assisted direct coronary artery bypass (PADCAB), 12 a novel technique by which to perfuse grafted vessels directly during multivessel OPCAB by a computer-controlled blood-delivery system. This technique enables active perfusion of selected target myocardium independent of systemic blood pressure, which contrasts with passive blood flow provided by intraluminal shunts or mechanical ventricular support systems. PADACB has the potential to avoid ischemia and its physiologic consequences during OPCAB by maintaining adequate perfusion, even during systemic hypotension.
Accordingly, the present study tests the hypotheses that intracoronary shunts provide inadequate blood flow during target coronary occlusion, that this inadequate delivery of blood flow is exacerbated during hypotension, and that active perfusion maintains adequate blood-flow delivery during normal blood pressure and systemic hypotension.
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, A). The position of the transducer catheter did not interfere with LAD blood flow. A sampling catheter was introduced by means of direct puncture of the anterior interventricular vein (AIV) to sample venous blood draining exclusively from the region perfused by the LAD. The dogs were systemically heparinized with 300 U/kg heparin sodium supplemented with 300 U/kg every 90 minutes.
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, B. Hemodynamic data and blood samples were obtained, and colored microspheres were injected at baseline. After reversible ligation of the LAD, an arteriotomy was performed distal to the occlusion through which either a 2-mm-diameter cannula (DLPlegia Highflow Vessel Cannulae; Medtronic DLP, Grand Rapids, Mich) or a 2.25-mm intraluminal shunt (FLOTHRU; Bio-Vascular, Inc, Saint Paul, Minn) was inserted. The outer diameter of the shunt was 90% of the LAD diameter at the point of insertion. For the intracoronary shunt series, 2 rubber snares were tightened around the proximal and distal ends of the shunt device after insertion into the arteriotomy. In the shunt series data were collected under normotensive conditions (Shunt-Normo group) and under systemic hypotension (Shunt-Hypo group) created by partial snaring of the inferior vena cava to 50% of baseline blood pressure. In the active-perfusion series the LAD cannula was attached to a delivery line from a constantvolume nonpulsatile pump (Myocardial Protection System cardioplegia and perfusion delivery system; Quest Medical Inc, Allen, Tex), and perfusion was immediately established with continuous withdrawal of femoral arterial blood(Fig 1, A). LAD systolic pressure was immediately matched to left ventricular systolic pressure by adjusting the flow rate, and the flow was considered to reach equilibration once the blood-flow rate and intracoronary pressure became stable. The compliance in the bladder-based perfusion system avoided the marked decrease in diastolic pressure observed with positive displacement perfusion systems. Thereafter, the flow was kept constant throughout the active-perfusion experiments. Data were again collected under normotensive (Perfusion-Normo group) and hypotensive (Perfusion-Hypo group) conditions. The dogs were allowed to stabilize for 20 to 30 minutes after each intervention. The order of shunt or active-perfusion series was randomized(Fig 1, B). During active perfusion, colored microspheres were injected into the proximal portion of the perfusion line and sampled distally at 3 mL/min to determine myocardial blood flow specifically in the area at risk to avoid loss of microspheres by adherence to pump components. The pump blood-flow rate was increased accordingly to compensate for reference-sample withdrawal from the catheter. Analysis of the perfusion tubing, shunts, and coronary catheters showed no adherent microspheres.
Data collection and analysis
Hemodynamic data, including left ventricular, systemic arterial (femoral arterial), and LAD pressures, and segmental length data were acquired during a 10-second period of respiratory apnea. The pressure-rate product was calculated from left ventricular systolic pressure multiplied by heart rate. The data from each channel were digitized and processed with computer algorithms by using an interactive videographics program (SPECTRUM; Wake Forest University, Winston-Salem, NC), as described previously. 14 Percentage of segmental shortening (SS%) and segmental stroke work (SW) were determined, as previously described.
Regional myocardial blood flow
Regional myocardial blood flow (RMBF) with 0.15 (in-line injection) to 2.0 (left atrial injection) million 15-µm color-labeled microspheres (Triton Technology, San Diego, Calif) was calculated by using the reference-sampling method, as previously described. Reference samples were withdrawn from the femoral artery or the perfusion line at a constant rate for 3 minutes. Postexperimental myocardial tissue and reference blood samples were analyzed with a spectrophotometer (DU7400; Beckman, Fullerton, Calif). Blood flow was calculated in the normal epicardium, normal endocardium, target epicardium, and target endocardium, as follows:
RMBF = (CTFR/CR)/WT,
where CT and CR are the absorbances from dispersed microspheres in the tissue and reference blood samples, respectively. FR is the reference flow rate, and WT is the total weight of the tissue sample in grams. Blood flow was also integrated over subepicardial and subendocardial regions to give transmural blood flow. Results are expressed as milliliters per minute per gram of tissue.
Regional oxygen and lactate extraction
Arterial and local coronary venous oxygen content and blood lactate concentration were measured with a blood gas and metabolite analyzer (Stat Profile M; Nova Biomedical, Waltham, Mass). The percentage of regional myocardial oxygen extraction was calculated from the arterial-AIV oxygen content difference divided by arterial oxygen content. Likewise, the percentage of regional transmyocardial lactate extraction was calculated from the arterial-AIV lactate difference divided by the arterial lactate concentration.
Regional oxygen consumption and delivery
Regional myocardial oxygen consumption (MVO2) of the LAD myocardium was calculated with the arterial-AIV oxygen content difference and the transmurally integrated myocardial blood flow from the target zone, as previously described, 13 and is expressed in milliliters of oxygen per minute per gram. Likewise, regional oxygen delivery (O2 delivery) was calculated with the arterial oxygen content and the transmurally integrated blood flow from the target zone. These measurements and calculations have been previously validated. 13 The regional oxygen supply/consumption ratio (O2S/MVO2) was also calculated. Under normal conditions, oxygen supply exceeds consumption (ratio >1), and a ratio approximating unity indicates a potential oxygen supply/consumption mismatch (consumption limited by supply).
Statistical analysis
Linear data were analyzed by means of 1-way analysis of variance for repeated measures to identify time-dependent (intervention) interactions. If significant interactions were found, then further pairwise analysis was performed by using post hoc analysis to locate the source of the differences. A P value of less than .05 was considered significant, and means ± SEM are reported.
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). However, systemic hypotension was associated with a 68.5% reduction in RMBF in the subepicardial region and a 77.4% reduction in RMBF in the subendocardial region relative to the previous normotensive state.
Segmental function
Segmental function in the target zone decreased with interposition of the shunt under normal blood pressure(Fig 3). SS% decreased more than SW because of a rightward shift in the systolic trajectory indicative of some degree of paradoxical bulging during systole followed by contraction. However, hypotension with the shunt in place was associated with approximately a 70% reduction in both SS% and SW(Fig 3). Active perfusion restored regional function to baseline values(Fig 3), although hypotension induced by partial caval occlusion was associated with a similar decrease in segmental function, as seen with the shunt. However, this was not coincident with a decrease in blood flow, as was observed with the shunt. Moreover, SS% in the noninvolved zone in the Shunt-Normo and Perfusion-Normo groups were similar to the baseline values(Fig 4). Hypotension induced by partial caval occlusion was equally associated with a decrease in SS% and segment work(Fig 4), suggesting that part of the decrease in function was caused by ventricular unloading.
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). However, the oxygen supply/consumption ratio (O2S/MVO2) averaged 2.7 ± 0.5, which was comparable with the baseline value(Table 3). Systemic hypotension with the shunt caused a further decrease in MVO2, and oxygen extraction increased nearly 2-fold(Table 3). The O2S/MVO2 ratio decreased to 1.3 ± 0.1, and transmyocardial lactate extraction converted to production(Table 3). In contrast, oxygen variables remained at or exceeded baseline values in the active-perfusion series during both normotensive and hypotensive conditions.
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Discussion |
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1,16 others have demonstrated myocardial damage of varying degrees during OPCAB. 3,4 Additionally, experimental studies have reported persistent contractile dysfunction, endothelial injury, and apoptosis as physiologic consequences of brief coronary occlusion. 17-19 These consequences have prompted the use of several strategies, such as a "proximal first" approach, intraluminal coronary shunts, and ischemic preconditioning of the target myocardium, especially in multivessel OPCAB, to reduce the duration and consequences of ischemia. 4,11,20,21 In this regard the PADCAB technique is one of the options to avoid ischemia induced by temporary coronary occlusion. 12 Although the technique was originally applied to graft conduits after the completion of the distal anastomosis, the target coronary artery can be perfused directly with the aid of an intraluminal device, as was applied in the present study.
In the present study we tested the potential benefits of active perfusion over passive coronary perfusion through an intracoronary shunt in a canine OPCAB model. The outer diameter of the shunt used in our study was 2.25 mm, which is commonly used for clinical cases and which was approximately 90% of the diameter of the native vessel. The myocardial blood flow during shunt interposition was significantly impeded; myocardial blood flow was further impaired by systemic hypotension, especially to the subendocardium. This maldistribution of blood flow with the shunt was associated with a significant decrease in O2 delivery, O2 consumption, and segmental function in the target myocardium. With normal blood pressure, O2 delivery and O2 consumption decreased by over 50% during interposition of the intracoronary shunt. However, the O2 supply/consumption ratio and O2 extraction were not altered, and there was no net change in lactate extraction that would indicate an ischemic condition. 22 With superimposed hypotension and shunting, O2 delivery was further decreased, and O2 extraction increased nearly 2-fold. The O2 supply/consumption ratio decreased to unity (1.3 ± 0.1), and transmyocardial lactate extraction converted to production without a change in the arterial lactate concentration. Therefore under normotensive conditions, the shunt reduced O2 delivery and contractile function in similar proportion without ischemia, whereas during hypotension, O2 delivery was reduced to the point of limiting O2 supply and consequently inducing ischemia. In contrast to the shunt series, oxygen variables remained or exceeded baseline conditions during active perfusion with normal blood pressure. Moreover, hypotension did not induce a decrease in O2 delivery (caused by maintained blood flow levels) or an increase in O2 extraction, and the O2 delivery/consumption ratio remained at the baseline level. Consequently, lactate extraction was maintained with active perfusion, even during hypotensive conditions.
Unimpaired contractile function requires that oxygen availability equals or exceeds oxygen demand. A decrease in oxygen supply will downregulate contractile function to that level supported by the oxygen supply so that the oxygen supply/demand (consumption) ratio will be greater than or equal to 1.0. In our data, with interposition of the shunt, transmural blood flow decreased by 67% with a correspondingly equivalent decrease in contractile function, so the O2 supply/consumption ratio was not altered. The lack of ischemia was supported by an absence of lactate production by the target myocardium. Therefore a condition similar to hibernation was created by the shunt. 23,24 However, hypotension, which may also be encountered during vertical displacement of the heart to visualize posterior target vessels, 5,6,25 or during ventricular compression by stabilization devices, exacerbated the decrease in blood flow, with the greatest decrease being observed in the subendocardium (86% decrease from baseline). The subendocardium is particularly vulnerable to oxygen supply and demand imbalances. 27 Therefore the decrease in myocardial blood flow observed in the present study during hypotension with the shunt was likely sufficient to create myocardial ischemia, as evidenced by lactate production from the target myocardium, and an O2 supply/consumption ratio of approximately 1.0 indicates supply limitation. The additional decrease in target area contractile function may have been due to the combined effects of impaired oxygen delivery and ventricular unloading created by caval occlusion. In contrast, selective PADCAB perfusion maintained adequate myocardial blood flow and oxygen supply both under normotensive and hypotensive conditions and therefore effectively disconnected the blood supply from variations in passive perfusion pressure.
The present data from the noninvolved (LCx-perfused) zone demonstrated that there was no change in the RMBF or segmental function, regardless of the methods used to perfuse the LAD area under normotensive conditions. However, during hypotension induced by partial caval occlusion, segmental function decreased equally in both perfusion modalities. The decrease in function in the noninvolved segment during hypotension is likely caused by preload reduction and ventricular unloading. Hence part of the decrease in function in the target (LAD) myocardium is likely attributed to preload reduction, whereas a portion is due to insufficient blood flow to support function.
There is an apparent discrepancy between the oxygen consumption and the contractile work achieved in the target vessel during hypotension in the active perfusion set of data: the decrease in regional contractile function far exceeded the decrease in oxygen consumption. Relative to the preceding normotensive period, hypotension was associated with a 50% decrease in peak left ventricular systolic pressure and a 60% decrease in systolic shortening, and oxygen consumption decreased by only 25%. Accordingly, the oxygen supply/demand ratio was higher during hypotension than during normotension. However, the relatively small decrease in oxygen consumption during hypotension is consistent with a comparable decrease in pressure-rate product, which declined by 28% from the normotensive value. This index correlates well with myocardial oxygen consumption as long as there are no significant changes in inotropic state. 28 The increase in heart rate during hypotension counterbalanced the decrease in left ventricular pressure and mitigated the decrease in pressure-rate product. Although systolic shortening also decreased to a relatively large extent (approximately 50%), the degree of contractile shortening is a relatively minor determinant of overall myocardial oxygen demands. 29,30 Hence the oxygen consumption during hypotension was consistent with the combined pressure and heart-rate determinants of myocardial oxygen demands predicted by the pressure-rate product.
The strategy to induce systemic hypotension was designed to simulate the influence of vertical displacement of the beating heart, which is required for exposure of posterior LCx branches. Hemodynamic changes during vertical displacement of the beating heart occur by means of outflow tract obstruction, and compressive forces imposed by the tissue stabilizers have been previously investigated. 5,6 The observed decrease in coronary blood flow, stroke volume, and systemic pressure can be successfully reversed by augmented ventricular preloads. However, in broader terms the physiologic consequences of reduced coronary perfusion pressure observed with hypotension are also applicable to severe stenosis of the target vessel in which perfusion pressure and flow distal to the lesion are impeded. The hypotension maneuver used in the present study similarly caused a decrease in the myocardial blood flow, segmental work, and systemic pressure. We interpret the decrease in systolic shortening during hypotension to be due to the combined effects of preload reduction and inadequate blood flow. Inadequate blood flow (supply-demand mismatch) is suggested by lactate release from the myocardium served by the LAD coronary artery.
From the clinical point of view, the use of intracoronary shunts is better than simple occlusion during anastomosis in providing blood supply to avoid ischemia of the distal segments. The present study has demonstrated the possible advantage of selective active perfusion of target myocardium over the use of intracoronary shunts, especially when systemic hypotension is encountered in a planned or unplanned manner. Currently, the PADCAB technique has been reported for perfusion through the grafted vessels to eliminate the risk of ischemia or hypoperfusion of grafted segments during subsequent anastomosis. However, the target coronary artery, which is being anastomosed, could be perfused directly with the use of an intraluminal device. Although segmental function under systemic hypotension was due to a combination of preload reduction and limitation in oxygen delivery and was not maintained by selective perfusion, ischemia was avoided, and adequate perfusion was maintained.
The impaired delivery of blood through the shunt was observed in a model of unobstructed coronary artery blood flow. In coronary arteries with significant disease, the perfusion pressure distal to the stenotic lesion may be lower than that in the aorta or in the normal coronary artery. In this situation the impedance of blood flow by the shunt may be greater, thereby potentially creating ischemia rather than hibernation, especially during periods of hypotension. The additional impairment of blood flow by coronary lesions should be examined with models of stenosis of varying degrees. However, in chronically stenotic coronary arteries, the development of collateral blood supply occurring in chronic ischemia may offset the mismatch in oxygen supply versus demand observed in the present model of acute ischemia. Furthermore, the index of regional contractile function (systolic shortening) used in the present study is not load independent; that is, the percentage of systolic shortening will increase with afterload reduction or a decrease in heart rate or will decrease with preload reduction (as observed during the hypotension interval) independent of changes in contractility. We interpreted a decrease in systolic shortening fraction as dysfunction only when it was associated with localized lactate release. However, further studies should use load-independent indices to investigate the relationship between coronary blood flow, function, and metabolism during interposition of the shunt. Finally, the injection of microspheres into the perfusion line was made in the absence of a device to ensure adequate mixing with the blood. The possible axial streaming of the microspheres may have decreased the number of microspheres withdrawn from the side port of the perfusion line and thereby may have led to an overestimation of transmural blood flow. Second, axially streaming microspheres may have favored a greater distribution of microspheres to the subendocardial tissue.
In summary, the present study demonstrated that blood flow through an appropriately sized coronary shunt is inadequate to meet oxygen demands necessary to maintain regional contractile activity but causes hibernation rather than ischemia. However, ischemia is observed with the shunt during hypotension. The impaired delivery of myocardial blood flow caused by the intracoronary shunts and hypotension is overcome by means of selective and active perfusion of the target vessel with a bladder-based pump that makes perfusion independent of upstream blood pressure. This novel assist strategy for OPCAB grafting can be used in cases requiring prolonged periods of ischemia or ischemia in multiple target areas and for patients who are likely to experience systemic hypotension at some point during the surgical procedure. Further studies confirming the clinical benefits of this active-perfusion strategy and the length of time that a shunt can be used without producing unfavorable effects should be conducted before adoption in clinical practice.
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