Russell D. Spruell

Tissue oxygenation with graded dissolved oxygen delivery during cardiopulmonary bypass

BACKGROUND Intravascular perfluorochemical emulsions together with a high oxygen tension may increase the delivery of dissolved oxygen to useful levels. The hypothesis of this study is that increasing the dissolved oxygen content of blood with incremental doses of a perfluorochemical emulsion improves tissue oxygenation during cardiopulmonary bypass in a dose-related fashion. METHODS AND RESULTS Oxygen utilization was studied in a profoundly anemic canine model of hypothermic cardiopulmonary bypass. Forty-two dogs underwent normovolemic hemodilution to a hematocrit of 15.8% +/- 0.6% (mean +/- standard error of the mean). Cardiopulmonary bypass was begun and resulted in a hematocrit of 9.4% +/- 0.6%. A standard priming solution was used in the control group (n = 12), and the test groups received 1.35 gm perfluorochemical.kg-1 (n = 10 dogs), 2.7 gm perfluorochemical.kg-1 (n = 10 dogs), or 5.4 gm perfluorochemical.kg-1 (n = 10 dogs) through the venous return cannula. Each animal underwent a series of randomized pump flows (0.25, 0.5, 1.0, 1.5, 2.0, and 3.0 L.min-1.m-2) at 32 degrees C. After the randomized flows were completed at 32 degrees C, the temperature was raised to 38 degrees C and cardiopulmonary bypass was discontinued. Mortality from cardiac failure on separation from cardiopulmonary bypass was 42% in the control group and 20% in perfluorochemical-treated groups. The mean perfluorochemical dose was higher in survivors than in nonsurvivors (2.9 +/- 0.4 versus 1.3 +/- 0.5 gm perfluorochemical.kg-1; p < 0.05). No differences in oxygen consumption or transbody lactate gradient were found between groups during cardiopulmonary bypass. Analysis of mixed venous oxygen tension (a surrogate measure for tissue oxygenation) as a function of cardiopulmonary bypass flow normalized to body surface area showed that the control group had significantly lower mixed venous oxygen tension (p < 0.05) than the perfluorochemical emulsion-treated groups. Furthermore, the differences were related to the perfluorochemical emulsion dose. These differences in mixed venous oxygen tension continued after termination of cardiopulmonary bypass. The coronary sinus oxygen tension and cardiac arterial-venous oxygen content differences during and after cardiopulmonary bypass were similar among the control and perfluorochemical emulsion-treated animals. Dissolved oxygen consumption during and after cardiopulmonary bypass was calculated. Dissolved oxygen consumption increased in the perfluorochemical-treated animals in a perfluorochemical dose-related manner and was significantly higher in perfluorochemical-treated animals than in the control animals (p < 0.05). CONCLUSIONS Graded increases in mixed venous oxygen tension during cardiopulmonary bypass were observed in response to graded increases in the dissolved oxygen delivery. These data suggest that enhancing oxygenation with perfluorochemical-dissolved oxygen is an effective temporary substitute for the use of hemoglobin-bound oxygen during cardiopulmonary bypass. Perfluorochemical-dissolved oxygen may be particularly beneficial in the setting of multiple hypoxic stresses.

Left atrial or ventricular cannulation beyond 30 days for a Thoratec ventricular assist device.

The authors used Thoratec left ventricular assist devices (VADs) for more than 30 days in eight patients. There were five left atrial (LA) (total, 513 days; range, 33-202 days) and three left ventricular (LV) cannulations (total, 484 days; range, 44-247 days). The flow provided by LA cannulation was less than that provided by LV cannulation. However, serial measurements of hematologic, renal, and hepatic function were similar for patients with LA and those with LV cannulation throughout support. Plasma free hemoglobin and lactate dehydrogenase (LDH) levels were similar for LA and LV patients. The five LA patients had one transient ischemic attack, one reversible ischemic neurologic deficit, and one stroke. The LV patients had no neurologic events (p = 0.20; LA versus LV total neurologic events). One LA patient and one LV patient died during support. Three LA patients underwent transplant, and one LA patient recovered native cardiac function. Two LV patients underwent transplant. In certain situations (e.g., recent anterior myocardial infarction; small left ventricular dimensions) LA cannulation may be advantageous. Neurologic events may be more common in LA patients, but in our small group this difference could be attributable to chance alone. LA or LV cannulation for a Thoratec VAD can provide adequate circulatory support for more than 30 days.

Use of Current Generation Perfluorocarbon Emulsions in Cardiac Surgery

The development of novel perfluorocarbon emulsions that contain higher concentrations of perfluorochemicals than previous emulsions has renewed interest in the use of this class of erythrocyte substitute in cardiopulmonary bypass (CPB). Perfluorocarbons have the potential to increase the oxygen content of the perfusate and thus increase the capacity of the heart-lung machine to deliver oxygen to the body during CPB. Increasing the capacity of the heart-lung machine to deliver oxygen to the body has important implications for the conduct of cardiac operations. For example, adding perfluorocarbons to the pump prime solution may allow larger volumes of blood to be withdrawn from the patient immediately prior to bypass for transfusion after bypass. Lowering the acceptable hematocrit during CPB with the use of perfluorocarbons may also decrease the need for homologous transfusions of erythrocytes in neonates or anemic adults who undergo CPB.

Perfluorocarbons Are Effective Oxygen Carriers in Cardiopulmonary Bypass

Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2) tension may increase the delivery of dissolved O2 to useful levels. A severely anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2 to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N = 42; hematocrit = 15.8 +/- 0.6% [mean +/- SEM] before CPB and 10.9 +/- 0.1% during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC.kg-1, 2.7 g PFC.kg-1, or 5.4 g PFC.kg-1 added via the venous return cannula. Pre-CPB and post-CPB cardiac function was measured by the first derivative of left ventricular pressure (dP/dtmax). The dP/dtmax on separation from CPB was: group 1, 619 +/- 96; group 2, 738 +/- 56; group 3, 782 +/- 101; and group 4, 828 +/- 100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour after separation from CPB was higher in group 1 than in PFCE treated dogs; however, this trend did not attain statistical significance (p < 0.065). The PFC dose was higher in survivors than in nonsurvivors (2.6 +/- 0.4 g PFC.kg-1 versus 1.2 +/- 0.5 g PFC.kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that they can be used as a temporary erythrocyte substitute to diminish the need for allogeneic transfusions during cardiac operations.

Arrest Duration Influences Postcardioplegia Electrophysiologic Recovery and Reperfusion Arrhythmias

BACKGROUND This study tests the hypothesis that postcardioplegia electrophysiologic recovery is influenced by the duration of cardioplegic arrest. METHODS Pigs were randomized to various durations of cardioplegic arrest (group I, 15 minutes; group II, 60 minutes; group III, 120 minutes). Electrophysiologic data included limb lead, atrial and ventricular epicardial, and ventricular endocardial electrocardiograms. Variables included times for earliest electrical activity and sinus rhythm; number of defibrillations; mechanism for reperfusion ventricular fibrillation; and time until last ventricular fibrillation. RESULTS Time to last ventricular fibrillation was 73+/-8, 134+/-23, and 238+/-23 seconds for groups I, II, and III (mean+/-standard error of the mean; p < 0.05 between group III versus groups I and II). The number of defibrillations was 1.0+/-0.3, 5.8+/-1.2, and 10.5+/-1.1 for groups I, II, and III (p < 0.05 between groups). The time to sinus rhythm was 66+/-8, 192+/-27, and 249+/-23 seconds for groups I, II, and III (p < 0.05 group I versus groups II and III). The most common mechanism for reperfusion arrhythmias was an accelerating ventricular tachycardia that initiated fibrillation (79 of 167 episodes). However, in many instances postdefibrillation amplifier saturation masked the initiation of reperfusion arrhythmias. CONCLUSIONS Electrophysiologic recovery after cardioplegic arrest is influenced by the duration of cardioplegic arrest.

CORONARY VASCULAR REGULATION DURING POSTCARDIOPLEGIA REPERFUSION

BACKGROUND This study extends previous investigations of global and regional myocardial blood flow during early postcardioplegia reperfusion. The hypothesis tested is that coronary vascular regulation becomes abnormal within 3 minutes after the start of postcardioplegia reperfusion. METHODS Pigs (n = 40) were supported by cardiopulmonary bypass and 38 degrees C blood cardioplegic solution was infused. A control preischemic microsphere injection (No. 1) was given in asystolic hearts. Groups 1 to 3 had 1 hour of hypothermic cardioplegic arrest. Group 4 (control group) had 1 hour of perfusion without cardioplegia. A blood cardioplegic solution at 38 degrees C and 70 mm Hg pressure was infused to maintain asystole during the initial 7 to 10 minutes of reperfusion in all groups. Left ventricular intracavitary pressures were set at 0, 10, 20, or 0 mm Hg in groups 1, 2, 3, and 4 (n = 10 pigs per group), respectively, during the initial 7 minutes of reperfusion. The ventricle was then decompressed. At 30 seconds, 3 minutes, and 6 minutes after reperfusion, microsphere injections 2, 3, and 4 were given in asystolic hearts. Microsphere injection No. 5 was given 10 minutes after reperfusion in beating vented hearts. RESULTS (1) Left ventricular distention during the initial 7 minutes of reperfusion after hypothermic cardioplegic arrest attenuates postischemic hyperemia. (2) Left ventricular intracavitary pressure of 20 mm Hg during reperfusion causes a decrease in endocardial blood flow relative to epicardial blood flow at 6 minutes after reperfusion. (3) Global myocardial blood flow during postcardioplegia reperfusion falls significantly below preischemic control values despite the return of electromechanical activity. INFERENCE Coronary vascular regulation (i.e., coronary resistance and metabolic flow recruitment) becomes abnormal within 3 minutes after the start of reperfusion after hypothermic blood cardioplegic arrest.

Perfluorocarbon oxygen transport. A comparative study of four oxygenator designs.

Improvements made in current generation perfluorocarbon emulsions (PFCEs) warrant renewed interest in PFCEs as an oxygen (O2) carrying substance during cardiopulmonary bypass (CPB). Before embarking on in vivo studies of PFCEs during CPB, an in vitro study was designed to: 1) demonstrate increased O2 content attributable to PFCEs, and 2) compare O2 transfer to a PFCE crystalloid mixture by four oxygenator designs (one bubble oxygenator, two hollow fiber membrane oxygenators, and one silastic membrane oxygenator). A circuit was designed to circulate fluid between a deoxygenating device and a test oxygenator. In protocol I, either a crystalloid solution or a crystalloid PFCE mixture was circulated through bubble oxygenators at flows ranging from 0.5 to 3 l/min, and at temperatures of 4, 20, 30, or 40 degrees C. In protocol II, a crystalloid PFCE mixture was circulated at flows ranging from 0.5 to 6 l/min at temperatures of 4, 20, 30, or 40 degrees C. Four different oxygenator designs were compared using the in vitro test circuit. The comparison variables for protocols I and II were arterovenous oxygen (AVO2) difference and O2 transfer rate measured at each flow for each temperature. Protocol I showed that the AVO2 differences and O2 transfer rates were higher in the crystalloid PFCE mixture than in the crystalloid solution, although statistical comparison was precluded by the small sample size. In protocol II, the hollow fiber and silastic membrane oxygenators had higher (P < 0.05) AVO2 differences and oxygen transfer rates than the bubble oxygenators at all flows and temperatures tested. Future trials to evaluate PFCEs during cardiopulmonary bypass should use hollow fiber or silastic membrane oxygenators, rather than bubble oxygenators, to maximize transfer of O2 to the PFCE.

Measurement of percent oxyhemoglobin by optical densitometry in perfluorocarbon supplemented blood.

A new generation of perfluorocarbon emulsions is being clinically evaluated as erythrocyte substitutes. However, the effect of perfluorocarbon emulsions on optical densitometric measurements of percent oxyhemoglobin (%O2Hb) has not been fully characterized. The purpose of this study is to quantify the effect of blood perfluorochemical concentration and hematocrit (Hct) on %O2Hb measurements. The authors hypothesize that perfluorocarbon emulsions affect the accuracy of %O2Hb measurements, and that the effect of perfluorochemical concentration and Hct on these measurements can be mathematically described. Porcine blood was used in this experiment. Blood with a Hct of 18% or 9% was mixed with a perfluorocarbon emulsion (Oxygent [AF0142]; Alliance Pharmaceutical Corporation, San Diego, CA). The concentrations tested were 0 g (Group I; n = 69 measurements for a Hct of 18%, and n = 35 measurements for a Hct of 9%), 0.73 g (Group II; n = 47 at 18%, n = 33 at 9%), 1.45 g (Group III; n = 46 at 18%, n = 30 at 9%), and 2.90 g (Group IV; n = 45 at 18%, n = 31 at 9%) of perfluorochemical per deciliter of blood (g PFC/dl). A tonometer was used to establish a range of oxygen tensions within each group while maintaining physiologic pH and PCO2. Error in %O2Hb measurements increases with higher perfluorochemical concentrations and lower Hct values. These errors in %O2Hb measurements are predictable; as such, an equation for correcting %O2Hb measurements in perfluorocarbon supplemented blood can be generated.

Anatomic definition of a vulnerable extranodal site in AV node reentry

The success of methods that ablate atrioventricular (AV) node reentry demonstrates that extranodal tissue is part of the reentry circuit. The hypothesis of this study is that atrial tissue approaching the posterior AV node is part of the AV node reentry circuit and is especially suitable for complete division with sparing of AV conduction. This study measured AV node function after either an anterior or posterior perinodal incision. The only significant change noted in antegrade function was a lengthening of the Wenckebach point after the posterior incision. Retrograde AV conduction and ventricular echoes were abolished by the posterior incision, whereas the anterior incision had no discernible effect on retrograde AV node function. Anatomic analysis of the two incisions showed that the posterior incision completely interrupted the posterior atrial input to the AV node, whereas the anterior incision spared the medial input to the AV node. The atrial tissue posterior to the AV node is anatomically suited for complete interruption. Ablation of atrial tissue posterior to the AV node is proposed for abolishing AV node reentrant tachycardia.

Fluxo coronário desregulado durante reperfusão pós cardioplegia

Metabolic coronary blood flow recruitment and distribution were studied in the setting of ventricular fibrillation (VF) during post-cardioplegia reperfusion. Fifteen pigs were placed on cardiopulmonary bypass and subjected to one hour of intermittent cold blood antegrade cardioplegia, followed by controlled myocardial reperfusion. According to the electromechanical status during the first ten minutes of reperfusion, the animals were allocated into 3 groups (n=5). Whereas Group 1 remained asystolic, the other two groups developed short (Group 2) or long duration VF (Group 3). Myocardial oxygen consumption (MVO2), in m/O2 /min/g (mean ± standard error) during reperfusion was 1.325 ± 0.144 (Group 1); 2.472 ± 0.208 (Group 2) and, 2.469 ± 0.228 (Group 3). MVO2 difference between asystolic and both short and long duration VF hearts was significant (p<0.001). Groups 1.2 and 3 endo-epi ratio and global coronary blood flow rate (169.3 ± 11.7; 185.0 ± 15.7 and 179.9 ± 13.2 ml/min/100g; respectively) were similar. These results demonstrate that coronary blood flow autoregulation was impaired because there was no increase in myocardial perfusion in response to the increase oxygen consumption imposed by VF during the first ten minutes of post cryocardioplegia reperfusion. This finding is of great clinical importance because it suggests that VF can potentially aggravate reperfusion lesions in formerly compromised hearts, i.e., those with coronary artery obstruction, ventricular distension or ventricular hypertrophy.