William D. Montgomery

Effects of oxygen, positive end-expiratory pressure, and carbon dioxide on oxygen delivery in an animal model of the univentricular heart

OBJECTIVE Respiratory manipulations are a mainstay of therapy for infants with a univentricular heart, but until recently little experimental information has been available to guide their use. We used an animal model of a univentricular heart to characterize the physiologic effects of a number of commonly used ventilatory treatments, including altering inspired oxygen tension, adding positive end-expiratory pressure, and adding supplemental carbon dioxide to the ventilator circuit. RESULTS Lowering inspired oxygen tension decreased the ratio of pulmonary to systemic flow. This ratio was 1.29 +/- 0.08 at an inspired oxygen tension of 100%, 0.61 +/- 0.09 at an inspired oxygen tension of 21%, and 0.42 +/- 0.09 at an inspired oxygen tension of 15% (p < 0.05 compared with an inspired oxygen tension of 100% and a positive end-expiratory pressure of 0 cm H2O). High-concentration supplemental carbon dioxide (carbon dioxide tension of 80 to 90 mm Hg) added to the ventilator circuit decreased inspired oxygen tension from 1.29 +/- 0.11 to 0.42 +/- 0.12 (p < 0.05 compared with baseline). A mixture of 95% oxygen and 5% carbon dioxide (carbon dioxide tension of 50 to 60 mm Hg) did not decrease the pulmonary/systemic flow ratio significantly. All three types of interventions influenced systemic oxygen delivery, which was a function of the pulmonary/systemic flow ratio. As the pulmonary/systemic flow ratio decreased from initially high levels (greater than 1), oxygen delivery first increased and reached an optimum at a flow ratio slightly less than 1. As the pulmonary/systemic flow ratio decreased further, below 0.7, oxygen delivery decreased. The ability of systemic arterial and venous oxygen saturations to predict the pulmonary/systemic flow ratio was examined. Venous oxygen saturation correlated well with both pulmonary/systemic flow ratio and systemic oxygen delivery, whereas arterial oxygen saturation did not accurately predict either pulmonary/systemic flow ratio or oxygen delivery. CONCLUSION This model demonstrated the value of estimating the pulmonary/systemic flow ratio before initiating therapy. When the initial ratio was greater than about 0.7, interventions that decreased the ratio increased oxygen delivery and were beneficial. When the initial pulmonary/systemic flow ratio was below 0.7, interventions that decreased the ratio decreased oxygen delivery and were detrimental. We conclude by presenting a framework to guide therapy based on the combination of arterial and venous oxygen saturations and the estimate of the pulmonary/systemic flow ratio that they provide.

ITA versus SVG: a comparison of instantaneous pressure and flow dynamics during competitive flow.

OBJECTIVE Competitive flow from patent native coronary vessels is implicated in the failure of internal thoracic artery (ITA) grafts, but it is not thought to affect saphenous vein graft (SVG) patency. This study examines instantaneous pressure and flow dynamics in left ITA and SVG grafts in competition with a patent left anterior descending (LAD) artery. METHODS SVG (3.0-4.0 mm) and ITA (1.5-2.0 mm) to proximal LAD (2.5-3.0 mm) coronary bypass was performed in 10 mongrel dogs. Flow and pressure were measured in the occluded (No Competition) and opened (Competition) ITA, SVG and LAD. RESULTS The ITA and SVG, when each was the sole inflow to the LAD, provided similar flow as the native LAD. During competitive flow, total LAD flow was preserved and flow in the ITA and SVG were reduced (8.20 +/- 1.25 and 10.00 +/- 1.73 ml/min; P < 0.005). SVG diastolic flow was reduced to 11.52 +/- 2.17 ml min (55.5%); P < 0.003. Flow in the SVG remained predominantly antegrade. In contrast, ITA diastolic flow was reduced more drastically, to 5.37 +/- 1.25 ml/min (80.7%); P < 0.0001. When the ITA was the only inflow to the LAD, there was delay in the LAD pressure wave. This delay disappears during competition due to the large, systolic retrograde flow up the ITA. CONCLUSION The ITA, compared to the SVG, is a longer and narrower conduit with lower levels of flow during competition. Due to a delay in the pressure wave, the ITA flow is retrograde during early systole. Low levels of flow, with a markedly decreased diastolic phase, and the oscillating pattern in systole (retrograde/antegrade) may be poorly tolerated by the ITA endothelium and lead to graft deterioration.

Inotropes in the hypoplastic left heart syndrome: Effects in an animal model

BACKGROUND Despite substantial changes in the surgical treatment of children born with the hypoplastic left heart syndrome, overall mortality remains high. Although further improvements in outcomes appear to depend on more effective perioperative care, few experimental data exist to guide appropriate pharmacologic therapy in these infants. Because different inotropic agents may have different effects on the ratio of pulmonary to systemic flow (Qp/Qs), we hypothesize that they may not be equally effective at increasing oxygen delivery. METHODS In neonatal piglets (n = 6; 3.5 to 6.5 kg), we placed an innominate artery-to-pulmonary artery shunt, created an atrial septal defect, and then occluded right ventricular outflow. We examined the effects of a number of commonly used inotropic agents, administering high and low concentrations of dopamine (5 and 15 micrograms.kg-1 .min-1), dobutamine (5 and 15 micrograms.kg-1.min-1), and epinephrine (0.05 and 0.1 microgram /min). RESULTS Dobutamine at 15 micrograms.kg-1.min-1 increased the Qp/Qs ratio from 1.03 +/- 0.6 at baseline to 2.52 +/- 0.55 (p < 0.05) and decreased oxygen delivery from 50 +/- 4.3 to 36 +/- 1.7 mL/min (p < 0.1). The arterial-venous oxygen difference increased as oxygen delivery went down, going from 44% +/- 1% to 48% +/- 2% (p < 0.1). Epinephrine at 0.1 microgram.kg-1.min-1 decreased the Qp/Qs ratio from 1.23 +/- 0.21 to 0.82 +/- 0.08 (p < 0.05) and increased oxygen delivery from 40 +/- 9.7 to 56 +/- 1.7 mL/min (p < 0.05). Systemic venous oxygen saturation increased from 36% +/- 4.8% to 50% +/- 8.6% (p < 0.05). Although dopamine decreased the Qp/Qs ratio and increased oxygen delivery, these changes were not statistically significant. CONCLUSIONS Dopamine, dobutamine, and epinephrine all increased cardiac output but had substantially different effects on the Qp/Qs ratio and on oxygen delivery, possibly due to differential effects on systemic and pulmonary vascular resistances. This suggests that inotropic agents may not be equally beneficial in the clinical setting. Systemic venous oxygen saturation and the arteriovenous oxygen difference may help determine if a given inotrope improves oxygen delivery.

Clinical experience with the video-assisted saphenectomy procedure for coronary bypass operations

BACKGROUND Leg wound complications after saphenectomy are frequent after coronary bypass operations and have a detrimental effect on postoperative quality of life and treatment cost. To reduce morbidity, we evaluated a new technique of video-assisted vein harvest. METHODS Between March 1996 and October 1996, 50 patients had video-assisted saphenectomy (VAS) and 40 patients had the standard open technique (control group). An additional 13 patients had both procedures (hybrid group). Level of pain, edema, and wound complications were evaluated at discharge and at 2, 4, and 6 weeks postoperatively. RESULTS The mean operating time for VAS patients was slightly higher than for control (60.6+/-24.7 minutes versus 53.2+/-21.1 minutes; p > 0.05). The average incision length in VAS patients was 13.8+/-8.8 cm for an average of 3.3 grafts per patient. Three VAS procedures were aborted, two because of time constraints, and one because of bleeding, and a segment of vein was lost to injury. The VAS group had considerably less early postoperative pain than the control group (1.7+/-1.2 versus 4.1+/-1.4 [1 = mild, 10 = severe]; p < 0.005) and edema was similar for both groups. Patients in the hybrid group reported less pain in the VAS-operated leg. Serious wound infection occurred in 4 patients, with 2 patients in the control group requiring reoperation for drainage and flap reconstruction. CONCLUSIONS Based on this initial experience, VAS harvesting, although initially more time consuming, is a rapidly mastered technique, results in shorter overall incision length, and is associated with considerably less postoperative pain than the standard open technique.

High flow demand on small arterial coronary bypass conduits promotes graft spasm

Despite the superior long-term patency of arterial grafts, surgeons are often reluctant to use arterial grafts on coronary vessels that supply large areas of myocardium because postoperative shock may occur. We hypothesized that supramaximal flow through small arterial conduits would decrease distal intraluminal pressure, thereby reducing afterload on the smooth muscle and rendering the arterial graft vulnerable to spasm. Fourteen internal thoracic and eight gastroepiploic arteries were harvested from adult pigs (220 to 250 pounds). Arteries were mounted on a computer-controlled perfusion system with inflow pressure at 80 mm Hg and outflow resistance adjusted to simulate normal (in situ) or supramaximal (coronary artery bypass graft) flow demands. Artery pressures and flow rates were measured at baseline and after norepinephrine was added to the system. Internal thoracic arteries had no hemodynamic response to norepinephrine at normal flow. Under supramaximal flow demands, large internal thoracic arteries (2.5 to 3.0 mm) had no hemodynamic response to norepinephrine. However, for small internal thoracic arteries (2.1 to 2.9 mm), norepinephrine reduced distal internal thoracic arterial pressure (63.2 +/- 2.2 to 27.0 +/- 1.9 mm Hg) and flow rate (99.4 +/- 5.0 to 45.4 +/- 2.7 ml/min, median effective dose = 9.12 x 10(-9) mol/L). Under normal flow demands, the flow rate in gastroepiploic arteries (1.0 to 2.0 mm diameter) decreased (14.1 +/- 0.5 to 4.8 +/- 0.8 ml/min, p < 0.05) only at high concentrations of norepinephrine (median effective dose = 1.26 x 10(-6) mol/L). Supramaximal flow demands reduced distal gastroepiploic arterial pressure (77.5 +/- 0.5 to 49.5 +/- 3.8 mm Hg, p < 0.05), which resulted in a greater decrease in flow rate (80.0 +/- 3.7 to 6.8 +/- 1.6 ml/min, p < 0.05) at lower concentrations of norepinephrine, (median effective dose = 3.24 x 10(-8) mol/L, p < 0.05). In four studies in internal thoracic arteries and eight in gastroepiploic arteries, arteries were cut in half, reattached, and reperfused. The proximal half of the internal thoracic artery did not respond to norepinephrine, but the distal half had a 53% +/- 7% decrease in flow. Both gastroepiploic artery halves reacted and flow rate decreased by 88% +/- 2% (proximal half) and 89% +/- 3% (distal half). In conclusion, small arterial conduits develop large transconduit pressure gradients under supramaximal flow demands. Under these conditions, arteries are very sensitive to vasoconstrictors and flow may cease with higher drug concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal model of the univentricular heart and single ventricular physiology.

The univentricular heart complexes are a fairly common and potentially lethal set of congenital cardiac anomalies. Progress in developing new therapeutics has been hampered by a lack of suitable animal models. The authors developed a stable, closed heart preparation to systematically examine potential interventions. Using neonatal piglets (3.5-6.0 kg), a 6-mm PTFE graft was anastomosed end to end to the innominate artery and end to side to the pulmonary artery. An atrial septostomy was made, using a Rashkind septostomy catheter passed transvenously. With the same catheter, the tricuspid valve was rendered incompetent. Occlusion of the right ventricular outflow tract completed a univentricular circuit. All cardiac output exited from the left ventricle, and pulmonary blood flow was maintained via the innominate artery-to-pulmonary artery shunt. Pressure transducers measured central venous (mid inferior vena cava), aortic, and pulmonary arterial pressures. Oximetric probes recorded systemic venous and arterial oxygen saturations. Transit-time flow probes measured total cardiac output and pulmonary flows. Systemic flow was calculated by subtracting pulmonary flow from total cardiac output. This model has been completed in 30 animals. Minimal pressure drops have been recorded across the innominate-to-pulmonary artery graft. Pulmonary flows up to 700 +/- 52 mL/min were seen. Total cardiac outputs are as high as 1370 +/- 88 mL/min. Mean ratios of pulmonary to systemic flow (Qp/Qs ratio) range from 1.29 +/- 0.08 to 0.41 +/- 0.09. The model allows for full continuous monitoring of systemic and pulmonary pressures and flows and for accurate characterization of the physiological effects of respiratory and pharmacological interventions. In addition, mechanical constriction of the graft may allow direct alteration of the Qp/Qs ratio, with determination of an optimum value for this ratio.

Evaluation of the long-term effectiveness of extraluminal and intraluminal vasodilators in an in vitro porcine model of arterial graft spasm.

OBJECTIVE Postoperative graft spasm is a concern when arterial conduits are used because there may be insufficient arterial graft flow. Intraoperatively, vasodilators are used to increase flow and prevent spasm, but little is known about their duration of effectiveness. METHODS To examine this we attached porcine gastroepiploic and internal thoracic arteries (GEA, n = 48; ITA, n = 24, 10-12 cm long) to a computer-controlled perfusion system (constant inflow pressure 80 mm Hg) with a fixed outflow resistance. Norepinephrine (10(-9)-10(-5) M) was incrementally added to the perfusate at baseline (B), then immediately (h+0) and 2 h (h+2) after the vessels were treated with 30 min of extraluminal or intraluminal nitroglycerin, nitroprusside, verapamil or papaverine. RESULTS At (B), norepinephrine caused a dose-dependent decrease in flow in both the ITAs and GEAs. In the ITAs, at (h+0), both extraluminal and intraluminal papaverine and, to a lesser extent nitroprusside, increased initial flow and decreased graft sensitivity to norepinephrine. At (h+2), only extraluminal papaverine sustained this maximal effect (ED50 for extraluminal papaverine at (B) 2.6 E(-7) vs. (h+2) 1.3 E(-6), P = 0.01). For the GEAs, at (h+0), both extraluminal and intraluminal verapamil, papaverine, nitroprusside and nitroglycerin attenuated flow reduction due to norepinephrine. At (h+2), only extraluminal papaverine, extraluminal verapamil and intraluminal verapamil were effective in preventing norepinephrine-induced spasm (ED50 for extraluminal papaverine at (B) 1.0 E(-7) vs. (h+2) 6.4 E(-6) (P = 0.004); extraluminal verapamil at (B) 1.2 E(-7) vs. (h+2) 4.0 E(-6); intraluminal verapamil at (B) 5.8 E(-7) vs. (h+2) 5.7 E(-6), P = 0.005). CONCLUSION Verapamil-and papaverine-treated arteries have a greater duration of efficacy in resisting spasm than arteries treated with nitroglycerin and nitroprusside. In the ITA, extraluminal administration of papaverine is most efficacious, possibly due to the prolonged exposure afforded by this route of administration. The effects of verapamil and papaverine are more prolonged in the GEA when administered extraluminally, potentially due to absorption in the perivascular fat-pad and subsequent slow release. The results of this study suggest that extraluminally administered verapamil and papaverine appear to be the preferred vasodilators for preventing arterial graft spasm in the postoperative period. This may be especially important when multiple arterial grafts are used.

Arterial bypass graft spasm: an examination of the role of high flow demands and endothelial function in the porcine GEA

This study examined why an artery becomes vulnerable to spasm when used as a bypass graft. We hypothesized that high flow demands would decrease pressure distally in the conduit (afterload), thus increasing the sensitivity to vasoconstrictors. Furthermore, perioperative endothelial dysfunction would additionally sensitize the artery to constrictors. Six gastroepiploic arteries (GEA, 1.0-1.5 mm diameter, 11 cm length) were harvested from adult pigs (110-125 kg) and mounted on a computer-controlled perfusion system. The inflow pressure was set at 80 mmHg and outflow resistance was adjusted to simulate normal (in situ) or high (coronary bypass graft) flow demands. Gastroepiploic flow and distal pressures were measured at baseline [B] and after adding norepinephrine (NE, 10(-9) M to 10(-5) M). Under normal flow demand, a minimal pressure drop existed across the GEA and flow decreased only at high NE concentrations. High flow demand decreased distal GEA pressure and increased the sensitivity to NE. To block endothelial function N-Monomethyl-L-Arginine, Monoacetate (L-NMMA, 10(-5) M) was then added. Under high flow demand, blocking endothelial function resulted in an additional fivefold increase in sensitivity to NE (ED50 from 9.75 10(-8) M to 2.11 10(-8) M, P < 0.05). It was shown that in long narrow arterial grafts, high flow demands cause cumulative pressure losses. Even with normal endothelial function, these pressure losses render the artery responsive to vasoconstrictors. Endothelial dysfunction additionally increases the sensitivity of the artery. Anastomosis of a small arterial graft to a large myocardial perfusion bed may result in reduced distal conduit pressure and may predispose to the development of myocardial ischemia even when low doses of vasoconstrictors are used. Perioperative endothelial dysfunction may exacerbate this effect.

Double grafting of the left anterior descending artery: is the distance between the internal mammary artery and supplemental vein graft anastomoses relevant in graft survival?

INTRODUCTION Under certain conditions (small internal mammary artery (IMA) or large runoff), double grafting of the left anterior descending (LAD) artery system is necessary to avoid the ominous consequences of myocardial hypoperfusion. Previous studies have shown that a saphenous vein (SVG) adjacent to an IMA graft leads to failure of the IMA. This study compares IMA flow patterns when adjacent ( < 1 cm) and separated (3-4 cm) from a SVG placed on a proximally occluded LAD. METHODS A SVG and right IMA (PIMA) to proximal LAD (2.5-3 mm) coronary bypass were performed in 12 mongrel dogs. The left IMA (DIMA) was anastomosed to the distal LAD (1.5 mm). All anastomoses were carried out without cardiopulmonary bypass. The native LAD was occluded proximally to the PIMA anastomosis, and all graft flows were measured in competitive and non-competitive flow conditions. RESULTS Isolated graft to LAD flows were similar for the three conduits. There was a drop in flow in both the PIMA and DIMA when placed in competition with the SVG (10.1+/-3.0 vs. 19.1+/-4.6 ml/min; P < 0.05). The total drop in flow was significantly greater in the PIMA (67.6 vs. 39.9%; P < 0.05). Diastolic flow was better preserved in the distal IMA graft (19.6 + 5.6 vs. 10.2+/-3.0 ml/min; P < 0.05). The patterns of flow were much different during competition and there was significant retrograde systolic flow in all PIMA grafts while there was no (n = 5) or minimal retrograde flow (n = 7) in the DIMA grafts. CONCLUSION An IMA graft, when adjacent to a SVG, sustains a significant decrease in both total and diastolic flows and develops an oscillating pattern of flow in early systole (retrograde then antegrade). Placing the IMA more distally on the LAD improves flow and decreases retrograde flow. In clinical situations requiring double grafting on the LAD, distance between grafts may be an important factor in maintaining IMA patency.

What in-vitro method should surgeons use to evaluate the clinical behavior of arterial bypass conduits.

UNLABELLED Surgeons have traditionally relied on ring preparations to predict how arterial bypass conduits will behave in the postoperative circulation. OBJECTIVE This study compared pharmacologic [norepinephrine (NE) challenge] and physiologic [arterial preload] responses of gastroepiploic (GEA) and internal thoracic (ITA) arteries in a standard static ring preparation and a dynamic perfusion system. METHODS Six GEAs (1.0-1.5 mm dia.) and six ITAs (1.5-2.0 mm dia.) 11 cm long were harvested from adult pigs and mounted on a computer controlled perfusion system. Inflow pressure was set at 80 mmHg and outflow resistance was adjusted to simulate high (80-90 ml/min) and low (15-20 ml/min) flow demands. NE response (10(-9)-10(-5) M) was measured under low flow conditions and at high flow conditions when distal arterial pressure (load) was reduced. NE response (10(-9)-10(-5) M) was also evaluated in arterial rings (ITA N = 6, GEA N = 6) with tensions adjusted to simulate the loads occurring at low flow (80 mmHg) and high flow (60 mmHg) situations. RESULTS In the static ring preparation, NE response [ED50] was similar for both GEA and ITA and was not affected by load. The dynamic preparation demonstrated that the GEAs were significantly more responsive to NE than the ITAs [ED50 high flow ITA 6.1 +/- 0.3**, GEA 7.2 +/- 0.3***; *P < 0.05 versus baseline, **P < 0.05 versus low flow values, ***P < 0.05 versus ITA]. Furthermore, in the dynamic preparation, NE response was profoundly affected by reduced load which occurs under high flow conditions [7.18 +/- 0.3 versus 6.1 +/- 0.3 under high flow and 5.8 +/- 0.1 versus no response under low flow conditions]. CONCLUSION Static ring preparations do not discern differences between ITA and GEA susceptibility to spasm and fail to detect the effect of load. The dynamic preparation demonstrated significant differences between the GEA and ITA potential to spasm which is consistent with widespread clinical experience. Furthermore a dynamic preparation is highly sensitive to reduced load which occurs under high flow conditions. Although it is more demanding, the dynamic preparation provides superior information to the surgeon in predicting the behavior of arterial bypass grafts.